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Question 1

Which cancers are associated with the following chemicals?
1. aromatic amines
2. benzene
3. wood dust
4. vinyl chloride

Answer 1

1. bladder cancer
2. leukaemia
3. nasal adenocarcinoma
4. angiosarcomas

Question 2

How does radiation increase the risk of cancer?

Answer 2

by increasing DNA damage leading to the accumulation of mutations in tumour-supressor genes and oncogenes

Question 3

which carcinoma are low fibre diets in the West associated with? why does the diet lead to carcinomas?

Answer 3

associated with colorectal carcinoma
low fibre diets lead to an increased transit time through the bowel, thereby increasing exposure to carcinogenic substances

Question 4

which carcinoma is associated with smoked food in Japan?

Answer 4

gastric carcinoma

Question 5

characteristic translocations can be induced by which cytotoxic drugs, and what cancer can they lead to?

Answer 5

may be induced by topoisomerase inhibitors and lead to an acute leukaemia

Question 6

How does HPV cause cancer? Which cancers does it cause?

Answer 6

the E6 protein produced by HPV16 binds to and inactivates the p53 protein
this leads to dysregulation of the cell cycle and apoptotic pathways and subsequent malignant transformation of epithelial cells infected
it causes cervical and anal cancers - associated with sexual transmission of HPV

Question 7

infection of epstein barr virus is associate with which cancers?

Answer 7

associated with non-Hodgkin’s lymphoma and other lymphomas

Question 8

what is the most common genetic abnormality of epstein barr virus?

Answer 8

caused by epstein barr nuclear antigens (EBNA), an 8:14 translocation in which the proto-oncogene of c-myc on chromosome 8 becomes transcriptionally controlled by the conrol elements of immunoglobulin genes on chromosome 14

Question 9

which cancers are associated with hepatitis B virus?

Answer 9

hepatocellular cancer, and leads to a greater than 100-fold increased risk

Question 10

how do retrovirus infections cause cancers?

Answer 10

by integration into the cellular retroviruses can cause abnormal overexpression of oncogenes. Retroviral infection has been implicated in numerous animal tumours

Question 11

in humans, the HTLV1 retrovirus infection is associated with which cancer?

Answer 11

T-cell lymphomas

Question 12

which cancer is helicobacter pylori associated with?

Answer 12

causative factor in malignancy, particularly mucosal associated lymphoid tissue (MALT) tumours

Question 13

what symptoms do cancer patients usually present with?

Answer 13

lumps - breast lumps, change in moles, nodes, nodules and MSK lumps
bleeding - haemoptysis, rectal bleeding, haematuria, post-menopausal or irregular menstrual bleeding
pain - chest or abdo pain, headache
change in function - change in bowel habit, new cough, dyspnoea, weight loss, fever, acute confusional state

Question 14

what do these stages of T (primary tumour) of the TNM mean?
Tx
T0
Tis
T1, 2, 3, 4

Answer 14

Tx = primary tumour cannot be assessed
T0 = no evidence of primary tumour
Tis = carcinoma in situ
T1, 2, 3, 4 = increasing size and/or local extent of the primary tumour

Question 15

what do these stages of N (regional lymph nodes) of TNM mean?
Nx
N0
N1, 2, 3

Answer 15

Nx = regional lymph nodes cannot be assessed
N0 = no regional lymph node metastasis
N1, 2, 3 = increasing involvement of regional lymph nodes

Question 16

what do these stages of M (distant/organ metastasis) of TNM mean?
Mx
M0
M1

Answer 16

presence of distant metastasis cannot be assessed
no distant metastasis
distant metastasis

Question 17

what does the grade of a tumour mean?

Answer 17

refers to the extent the tumour resembles normal tissue or has a bizarre appearance

Question 18

what do the following grades mean?
GX
G1
G2
G3

Answer 18

GX = grade of differentiation cannot be assessed
G1 = well-differentiated: similarities remain to normal tissue of the organ of origin
G2 = moderately differentiated
G3 = poorly differentiated: bizarre cells

Question 19

for which parts of the body is CT and PET-CT used?

Answer 19

evaluation of chest and abdominal malignancies

Question 20

for which parts of the body is MRI used?

Answer 20

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

in the RECIST system for comparing clinical trials, what do the following terms mean?
complete response (CR)
partial response (PR)
stable disease (SD)
progressive disease (PD)

Answer 21

CR = no disease detectable radiologically
PR = all lesions have shrunk by at least 30% but disease still present
SD = less than 20% increase in size or less than 30% decrease in size
PD = new lesions or lesions that have increased in size by more than 20%

Question 22

what is the rate of additional cancers for each CT scan?

Answer 22

one additional cancer per 1000-2000 scans

Question 23

which tumours are MRIs the gold standard for imaging?

Answer 23

neurospinal, rectal, prostate and MSK tumours, and staging for subtypes of head and neck cancer

Question 24

which devices are vulnerable to the effects of MRIs?

Answer 24

most pacemakers and implantable cardiac defibrillators
metallic foreign bodies eg vascular clips, surgical staples

Question 25

what is the principal investigation for detection of skeletal metastases?

Answer 25

bone scintography (bone scan)

Question 26

how does PET scanning work?

Answer 26

positron emission tomography detects high-energy emitted by short-lived radioisotopes, which can be chemically tethered to molecules such as glucose or somatostatin to form a trace eg fluorine 18 deoxyglucose (SDG-18), a radioactive form of glucose

Question 27

what does the sensitivity and specificity of a tumour marker mean?

Answer 27

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, sensitivity is 0.95
specificity describes its ability to accurately define those who are disease free. If in 100 disease-free people the marker is negative in only 90 (ie there are 10 false positives) the specificity of the test is 0.9

Question 28

which tumour markers should a young male with disseminated bone metastases be tested for?

Answer 28

serum LDH, aFP, and BHCG (pregnancy test) to diagnose chemo sensitive and potentially curable germ cell tumours

Question 29

which tumour markers are used in testicular teratoma?

Answer 29

HCG and aFP

Question 30

when is CEA high?

Answer 30

in the setting of colorectal carcinoma
also more common in people who smoke, or have IBD, hepatitis, pancreatitis or gastritis

Question 31

when are CA125 levels elevated?

Answer 31

mainly used as a tumour marker in ovarian carcinoma
also elevated in pancreatic, lung, colorectal and breast cancer; usually where these are disseminated to the abdominal cavity

Question 32

what is alpha fetoprotein (aFP) and when is it elevated? when is it undetectable?

Answer 32

it is a glycoprotein produced by the normal foetal yolk sac, liver and intestines
levels are moderately elevated in hepatitis, but high levels are also produced by hepatocellular carcinoma and cancers containing yolk sac elements eg teratoma
it is undetectable in normal individuals after the first year of life

Question 33

what is human chorionic gonadotrophin (HCG) and when is it elevated?

Answer 33

it is a glycoprotein consisting of two subunits
HCG is elevated in patients with gestational trophoblastic disease (hydatiform mole, choriosarcoma)
there is also a specific elevation of the B-subunit with non-seminomatous testicular cancers and some with seminoma
It is also raised in pregnancy!

Question 34

what is prostate specific antigen (PSA) and when is it elevated?

Answer 34

it is a protein produced by prostatic cells
levels are raised in prostate cancers but also with benign hypertrophy of the prostate - a near ubiquitous phenomenon as men age
may also be elevated by rectal exam, in prostatitis and UTI

Question 35

when are immunoglobulins used as tumour markers? how are they measured?

Answer 35

can be a measure of the paraproteinaemias eg myeloma and Waldenstrom’s macroglobulinaemia, and occasionally non-Hodgkin’s lymphoma
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 36

what are the different types of biopsies?

Answer 36

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 37

what is neoadjuvant chemotherapy? what are the aims? for which cancers is it used?

Answer 37

pre-operative treatment of an operable tumour before definitive surgical intervention
aims are to make the tumour smaller, to allow less radical surgery, while at the same time treating occult micro metastases
established for osteosarcoma, and is being tested in clinical trials for other malignancies such as breast cancer

Question 38

what is primary chemotherapy and when is it used?

Answer 38

initial chemotherapy for a tumour that is inoperable or of uncertain operability, where a reduction in the tumour bulk in a pre-defined manner may make surgery with curative intent feasible

Question 39

what is adjuvant chemotherapy?

Answer 39

it is the use of chemotherapy following a complete macroscopic clearance at surgery
chemotherapy in this setting treats the occult microscopic metastases which we know usually lead to relapse after surgery for lymph node positive disease eg breast cancer and colorectal cancer.

Question 40

when is tamoxifen used as a hormonal treatment for cancer?

Answer 40

used for in-situ breast cancer before invasive carcinoma is recognised (ie before overt malignancy appears)

Question 41

which cells are usually affected by chemotherapy?

Answer 41

haematopoietic stem cells and the lining of the GI tract, producing low blood counts (myelosuppression) and mucositis

Question 42

what is the usual schedule of cycles and for how long?

Answer 42

treatment every 3-4 weeks, and maximally effective after a 6 month course

Question 43

which chemotherapy drugs are available orally?

Answer 43

cyclophosphamide, etoposide, capecitabine and tamoxifen

Question 44

what is the route of most chemotherapy?

Answer 44

given IV as bolus injection or short infusion

Question 45

when is chemotherapy given intravesical? what is the advantage of this?

Answer 45

chemotherapy is routinely given this way in the management of superficial bladder cancer
has the advantage of producing high doses at the site of the tumour, with negligible systemic absorption and hence minimal systemic toxicity

Question 46

when is chemotherapy given intraperitoneal?

Answer 46

can be administered directly into the peritoneal cavity in the context of tumours that spread trans-coelomically (eg ovarian cancer)

Question 47

when is chemotherapy given intra-arterial? what is the advantage?

Answer 47

any tumour that has a well-defined blood supply is potentially suitable eg hepatic artery infusion for liver metastases
this allows higher doses to be delivered to the involved site and reduces systemic toxicity

Question 48

how are routine cytotoxic chemotherapy doses calculated?

Answer 48

according to the patient’s body surface area - most commonly used formula is that of DuBois and DuBois

Question 49

which is the only chemotherapy drug to have its own dose calculation?

Answer 49

carboplatin - has its own dose calculated according to renal function

Question 50

how does nausea arise as a side effect of chemotherapy? what can be used to control this?

Answer 50

nausea arises from a combination of direct simulation of the vomiting centre, peripheral stimulation and anticipatory causes
the use of 5-HT antagonist drugs like ondansetron can help with this

Question 51

how is myelosuppression caused by chemotherapy? what is the lowest point of the drop known as? what is the neutrophil count? how long does it take to recover?

Answer 51

chemotherapy causes bone marrow suppression by killing haematopoietic progenitor cells
this leads to a leucopenia and thrombocytopenia generally after 10-14 days from the beginning of each cycle
the lowest point of this drop is known as the NADIR!
a neutrophil cunt greater than 1x10^9/1 is rarely associated with a clinical infection. However, a risk of infection with a count less than 0.5 x 10^9/1 is significant
haematopoietic recovery usually occurs after 3-4 weeks, enabling further cycles of chemotherapy to be given

Question 52

what is oral mucositis indicating?

Answer 52

may reflect more general damage to the whole GI epithelium, a rapidly dividing cell population susceptible to cytotoxic chemotherapy

Question 53

why does diarrhoea occur as a side effect of chemotherapy?

Answer 53

due to colitis or small bowel mucosal inflammation

Question 54

why is constipation a side effect of chemotherapy?

Answer 54

constipation is usually due to dehydration with reduced oral intake due to nausea, and to adverse effects of other meds being taken eg opiate analgesics or 5-HT antagonists

Question 55

what can be used to control the side effect alopecia?

Answer 55

can be controlled by the use of a cold cap which reduces the blood flow to the scalp

Question 56

when does peripheral neuropathy occur as a side effect? how long does it take to recover from it?

Answer 56

these occur with the platinum drugs (particularly cisplatin), taxanes, and vinca alkaloids
neuropathy, principally affecting sensory nerves, may recover partially over a period of months, but patients are usually left with a residual deficit

Question 57

which drugs are related to central neurological toxicity?

Answer 57

eg ifosfamide-induced encephalopathy and 5-FU induced cerebellar toxicity

Question 58

how does cisplatin cause ototoxicity?

Answer 58

cochlear damage rather than auditory nerve damage is believed to be responsible for the high tone hearing loss associated with cisplatin
the effect is permanent
pre-existing high-tone hearing damage precludes the use of cisplatin

Question 59

when does nephrotoxicity occur as a side effect of chemotherapy?

Answer 59

this occurs with platinum agents, principally cisplatin, and with the alkylating agent ifosfamide
renal excretion of many cytotoxics means that adequate renal function is required to reduce overall toxicity

Question 60

which drugs cause bladder toxicity? give an example of an antidote

Answer 60

cyclophosphamide and ifosfamide cause haemorrhagic cystitis in a dose-dependent manner
antidotes exist such as Mesna

Question 61

which chemotherapy drugs are associated with cardiac side effects?

Answer 61

doxorubicin and paclitaxel are both associated with acute arrhythmias
5-FU (and related drugs such as capecitabine) may cause coronary artery spasm and therefore induce cardiac ischaemia

Question 62

when does extravasation occur as a side effect of chemotherapy?

Answer 62

some cytotoxic drugs are highly vesicant and cause tissue damage on extravasation. they are administered through fast-running drips under direct observation, to dilute any vesicant action and to make nurses administering treatment aware immediately if extravasation occurs

Question 63

what is hand-foot syndrome? how is it resolved?

Answer 63

ie palmar plantar erythema
erythema of the palms of the hands and soles of the feet is frequently seen with 5-FU, capecitabine and some of the targeted agents eg sunitinib, erlotinib
side effect usually responds to drug withdrawal and emollients but patients will need to be reviewed for other drug side effects eg bowel toxicity in the case of 5-FU

Question 64

which drugs cause photosensitivity?

Answer 64

some drugs such as 5-FU cause photosensitivity
patients should be advised regarding the use of high-factor sun blocks

Question 65

which drugs cause pigmentation as a side effect?

Answer 65

bleomycin leads to skin and nail pigmentation
it occurs in combination with pulmonary fibrosis and a common pathogenic process is thought to be responsible

Question 66

which drug causes myalgia and arthralgia as a side effect?

Answer 66

with use of paclitaxel and are usually well controlled with non-steroidal analgesia

Question 67

which drugs are associated with frequent hypersensitivity reactions on administration?

Answer 67

both paclitaxel and docetaxel cause allergic reactions

Question 68

how do chemotherapy drugs cause second malignancies? what is the most carcinogenic of the anti-cancer drugs?

Answer 68

some cause sub-lethal DNA damage that may eventually lead to the genetic changes require to induce a second malignancy
the most carcinogenic anti-cancer drugs are alkylating agents and procarbazine

Question 69

which chemotherapy drugs cause infertility?

Answer 69

most drugs are associated with a reduction in fertility
some drugs, notably alkylating agents, render patients infertile at standard doses
most patients who have high-dose treatments become infertile

Question 70

which chemotherapy drugs cause long term pulmonary damage?

Answer 70

may result from fibrosis induced by drugs such as bleomycin and busulphan
high-dose or prolonged administration of most alkylating agents is associated with pulmonary fibrosis or pneumonitis

Question 71

which cancers can cause bone marrow replacement by malignant infiltration and produce pancytopenia?

Answer 71

more common in haematological malignancies and certain solid cancers eg breast, lung and prostate cancer

Question 72

what is the type of anaemia usually cause by repeated chemotherapy?

Answer 72

often macrocytic but not megaloblastic

Question 73

what are the investigations for myelosuppression?

Answer 73

a transient nadir in blood counts following chemotherapy can be observed
full evaluation (to check for bone marrow infiltration) includes a blood film, measurement of haematinics, bone marrow aspirate and trephine

Question 74

what is the treatment for anaemia in myelosuppression?

Answer 74

heamoglobin less than 10 g/dl - may benefit from blood transfusion
use of recombinant erythropoetin in preventing symptomatic anaemia can be benficial and reduce risks of transfusion reactions and viral transmission

Question 75

what are the clinical signs of significant thrombocytopenia?

Answer 75

petechial haemorrhage
spontaneous nose bleeds
corneal haemorrhage
haematuria

Question 76

at what level would you give a patient a platelet transfusion due to thrombocytopenia?

Answer 76

platelet count less than 20 x 10^9/L

Question 77

what are the potential consequences of neutropenia in chemo patients? when should patients seek help?

Answer 77

may quickly lead to multi-organ failure associated with septic shock - should seek immediate attention from the unit delivering their radiotherapy if they develop a fever

Question 78

when does a patient require Abx in neutropenic sepsis?

Answer 78

total white counts less than 1 x 10^9/L with an associated fever require immediate in-patient management with broad spectrum antibiotics

Question 79

why should rectal and vaginal examinations not be performed in suspected neutropenic sepsis?

Answer 79

due to the risk of causing bacteraemia if the mucosa is breached

Question 80

which investigations are carried out for neutropenic sepsis?

Answer 80

extensive cultures of blood, urine, sputum, throat etc and a chest X-ray

Question 81

when would a change in IV Abx occur with neutropenic sepsis? what would you give if the patient has a persistent fever despite appropriate antibiotic treatment?

Answer 81

failure to respond to initial antibiotics within approximately 48 hours requires a change to second-line broad-spectrum antibiotics
give patient additional antifungal or antiviral agents

Question 82

when would prophylactic antibiotics be administered for neutropenic sepsis?

Answer 82

should be considered in the presence of chronic obstructive airways disease and the use of co-trimoxazole in patients with lymphoma at risk of pneumocystis pneumonia

Question 83

what are the current targets of immunotherapy in cancer?

Answer 83

Cytotoxic T Lymphocyte Antigen 4 (CTLA4) expressed on T lymphocytes
Programmed cell death protein 1 (PD1) more broadly expressed across a range of immune cells including B cells and antigen-presenting cells, and its ligand
Programmed death Ligand 1 (PDL1) expressed on a broad range of both immune andcancer cells

Question 84

how do long-acting monoclonal antibodies work?

Answer 84

they act via immune checkpoint blockage to release anti-tumour immunity
some may also act against cancer cells through complement pathways and antibody-dependent cytotoxicity

Question 85

how are immunotherapy drugs administered and how are the doses calculated? give some examples

Answer 85

all are delivered intravenously and dosing is either calculated by weight or flat dosing based on idealised body weight
examples: ipilimumab, nivolumab, pembrolizumab and atezolizumab

Question 86

is immunotherapy curative or palliative?

Answer 86

most treatment is palliative, for patients with advanced disease

Question 87

what are the unusual features of cancer immune checkpoint inhibitor side effects?

Answer 87

1. first side effects can occur any time from the start of first infusion until many months after the drug has been withdrawn
2. many side effects do not wax and wane with the cycle of treatment (in contrast to chemo)
3. peak incidence of new immune mediated side effects is 6-8 weeks after first treatment but the range is very wide

Question 88

what are the types of rashes that can occur as a side effect of immunotherapy?

Answer 88

typically patients present with a maculopapular eczema type rash on the trunk. other patterns have been described including psoriatic plaques, angioedema and vitiligo > these will respond to topical emollients and steroid cream
rare but serious include steven johnson syndrome > these patients require high dose IV steroids and specialist referral

Question 89

what are the symptoms of pneumonitis from immunotherapy?

Answer 89

can present with often dry cough, SOB, reduced exercise tolerance and fatigue
symptoms may develop rapidly over a few days or more slowly over several weeks
median time to onset after single agent nivolumab is 3-4 months and symptoms usually take 4-6 weeks to improve

Question 90

what are the investigations and treatment of penumonitis?

Answer 90

initial: obs, FBC, CRP and CXR. full biochem screen can pick up other side effects and sputum, and screening for viral, opportunistic and bacterial chest infections is of benefit
most patients will benefit form oral steroids though some eg with pyrexia, high neutrophil and CRP, will require treatment for infection first

Question 91

What does pneumonitis look like on Chest X-ray?

Answer 91

can look like infection
CXR shows consolidation and haziness

Question 92

at what stage will diarrhoea be a side effect of immunotherapy?

Answer 92

within the first 2 months

Question 93

what are. the features of concern with diarrhoea/colitis?

Answer 93

frequency >6 times a day
associated abdo pain
bloody diarrhoea
nausea
nocturnal diarrhoea

Question 94

What are the initial assessments for diarrhoea/colitis as a side effect in immunotherapy? what investigation is useful in treatment later?

Answer 94

include obs, fluid balance, FBC, CRP, stool sample (for MCS & C.difficile toxin) and AXR. Flexible sigmoidoscopy is useful in guiding later treatment

Question 95

what are the initial assessments for hepatitis as a side effect on immunotherapy?

Answer 95

should include a med review (consider recent statins and Abx), alcohol history, hepatitis blood screen (inc. viral hepatitis and iron studies) and imaging (usually USS) to investigate thrombosis and possible metastases

Question 96

how are mild and serious cases of hepatitis treated as a side effect of immunotherapy managed?

Answer 96

mild: withhold cancer immunotherapy treatment and frequent biochemical re-assessment
serious: require immunosuppression with high dose steroids and specialist referral

Question 97

how common is nephritis in cancer immunotherapy? what are the symptoms?

Answer 97

less common occurring in 1-4% of patients
consider if patients present with AKI
nephritis can be asymptomatic at first or present with symptoms of uraemia: weakness, fatigue, anorexia, malaise, thirst and reduced urine output

Question 98

what are the initial assessments for nephritis caused by cancer immunotherapy?

Answer 98

include a careful history, focus on meds and infection and/or lower urinary tract symptoms
next evaluate fluid balance and perform biochemistry, urine dipstick (send for MCS to microbiology if appropriate) and urine protein/creatinine ratio

Question 99

what are the differentials of nephritis caused by cancer immunotherapy?

Answer 99

dehydration , recent IV contrast, infection, meds, hypotension, obstructive uropathy

Question 100

what is the management of serious cases of nephritis caused by cancer immunotherapy?

Answer 100

require immunosuppression with high dose steroids and specialist referral

Question 101

what is the commonest pattern of nephritis in cancer immunotherapy-caused nephritis?

Answer 101

acute tubulo-interstitial nephritis with lymphocytic infiltration

Question 102

what is the difference between myalgia and arthralgia? which is more common?

Answer 102

myalgia is muscle pain
arthralgia is joint pain without swelling
myalgia is more common than arthralgia

Question 103

what are some more serious rheumatological complications of cancer immunotherapy?

Answer 103

acute myositis, polymyalgia rheumatica and arthritis

Question 104

what are the initial assessments for myalgia/arthralgia as a side effect of cancer immunotherapy?

Answer 104

rheumatological history, exam of skin and joints and use of plain x-rays to exclude bone metastases

Question 105

what is the management of myalgia/arthralgia as a side effect of cancer immunotherapy?

Answer 105

mild cases: manage symptomatically eg paracetamol and or ibuprofen
moderate or severe cases (ie patients with significant pain or swelling affecting function esp activities of daily living) benefit from specialist referral and oral or intra-articular steroids

Question 106

what are the symptoms of endocrinopathies caused by cancer immunotherapy?

Answer 106

often present with non-specific symptoms such as fatigue, mild headache, mood change, malaise, thirst, weight change or feeling generally unwell

Question 107

what are the standard safety bloods for patients on cancer immunotherapy? what are the assessments for toxicity?

Answer 107

should include regular assessment of thyroid function (T4, TSH) and cortisol (unless on systemic steroids)
acute assessment of toxicity may require a wider panel of hormone bloods along with simple obs (BP critical) and biochemistry (look for low sodium in adrenal insufficiency)

Question 108

what is a common endocrine disorder caused by cancer immunotherapy?

Answer 108

thyroid disorders - in many cases acute thyroiditis cause hyperthyroidism (high T4 low TSH) followed after a delay of some weeks by hypothyroidism (low T4 high TSH)

Question 109

what should you always check for and treat before starting thyroid replacement in cancer immunotherapy?

Answer 109

always check and treat any abnormality of adrenal function

Question 110

acute pituitary inflammation (hypophysitis), caused by cancer immunotherapy, presents in which way and causes what? what are the tests for it? what is the management?

Answer 110

can cause headache, visual disturbance and a wide range of hormone abnormalities inc. adrenal insufficiency and secondary hypothyroidism (low T4 low TSH)
blood cortisol levels vary across the day (9am sample is most useful) and formal assessment of adrenal function with a short Synacthen test is ideal
patients with proven adrenal insufficiency or high clinical index of suspicion should start hydrocortisone replacement with adive about sick day rules (double dose), back up IM injection if vomiting and specialist referral

Question 111

what is a short Synacthen test?

Answer 111

it is based on measurement of serum cortisol before and after an injection of synthetic ACTH - it assesses adrenal function

Question 112

what are the side effects of steroids? what are the long term issues?

Answer 112

sleep disturbance, mood change, indigestion (+/- gastrointestinal bleeding), weight gain, high BP and increased risk of infection
long term: diabetes, osteopenia/osteoporosis, and proximal myopathy

Question 113

what does it mean when cancers are hormone-dependent?

Answer 113

their rate of growth is influenced by levekls of hormones, and interfering with those hormones in one way or another may lead to growth arrest or tumour regression.

Question 114

which cancers are most commonly hormone sensitive?

Answer 114

those arising within tissues under hormonal control of normal cellular proliferation or survival
including: prostate, breast and endometrium (sex hormones), lymphocytic malignancies such as lymphoma, leukaemia, and myeloma (corticosteroids)

Question 115

at which stages are hormonal treatments used in cancer treatment?

Answer 115

neo-adjuvant or instead of surgery (primary medical therapy)
adjuvant therapy
to shrink established metastases and improve quality and duration of life (palliative therapy)

Question 116

what receptors can be used in tumour cells to predict hormone sensitivity? give an example

Answer 116

the presence of cytoplasmic steroid receptors
eg oestrogen receptor (ER) in breast cancer

Question 117

what is a medicinal way of inducing reversible “medical castration” in both men and women? how do they work? for which people is this unsuitable and why?

Answer 117

long-acting LHRH analogues eg goserelin, leuprorelin
by receptor down-regulation in the pituitary, block LH and FSH production and, in turn, gonadal hormone output
unsuitable for postmenopausal women for whom sex hormone production is mainly extra-gonadal, in fat and adrenal glands

Question 118

The rate-limiting step in oestrogen synthesis is the conversion of androstenedione to oestrone by the enzyme aromatase. In postmenopausal women, andostenedione is secreted by what? why is this an important step?

Answer 118

it is secreted by the adrenal and aromatized in other tissues including fat and liver. This step is the target for aromatase inhibitors

Question 119

what is aminoglutethimide and what does it need alongside it?

Answer 119

it was the first aromatase inhibitor and is non-specifc
as it also blocks an earlier stage in steroid synthesis, corticosteroid supplementation is required

Question 120

what kind of drug is tamoxifen?

Answer 120

hormone inhibitor and acts as an anti-oestrogen

Question 121

what are the 2 types of anti-androgen? how do they work?

Answer 121

1. steroidal anti-androgens eg cyproterone acetate - have a dual action. in tumour cells they inhibit the androgen receptor, but in the hypothalamus they substitute for testosterone, so stimulate negative feedback inhibition with subsequent decrease in LHRH release
2. non-steroidal anti-androgens eg bicalutamide - inhibit testosterone in both tumour cells and hypothalamus, so feedback inhibition is lost and serum testosterone levels rise

Question 122

what is the “maximum androgen blockade”?

Answer 122

describes the combination of a non-steroidal anti androgen with an LHRH analogue to prevent the effect of non-steroidals, where they increase the serum testosterone levels, and is used as a therapeutic strategy in prostate cancer

Question 123

how are glucocorticoids useful in cancer hormonal treatment?

Answer 123

glucocorticoids in high concentration induce apoptosis in some malignant lymphoid cells and form an important component of treatments for lymphoid leukaemias, lymphomas, myeloma and Hodgkin’s disease

Question 124

what is the aim of using hormone supplementation in certain sex-hormone sensitive cancers?

Answer 124

to induce negative feedback loops eg oestrogen to down-regulate hypothalamic LHRH in prostate cancer, or tachyphylaxis (down-regulation) of receptors eg high-dose oestrogens in breast cancer

Question 125

how do progestogens work? why are they widely used in palliative medicine?

Answer 125

may give direct inhibition of tumour growth via acting as an agonist of the progesterone receptor, but also produce negative feedback on the pituitary/gonadal axis
these drugs may also stimulate the appetite and are widely used in palliative medicine for that reason

Question 126

what are the ways radiotherapy is delivered and what is the most common form in the UK?

Answer 126

using photons/x-rays electrons, radio-isotopes or protons
external beam radiotherapy using photons/x-rays is the most common form in the UK

Question 127

how does radiotherapy work?

Answer 127

X-rays penetrate deep into body tissue whilst sparing the over-lying skin, where they produce secondary electrons and free radicals which cause DNA damage to both cancer cells and normal cells - this is the ‘skin-sparing’ effect

Question 128

how is it that normal cells can repair after radiotherapy but cancer cells can not?

Answer 128

Normal cells can often repair the DNA damage and therefore survive. Conversely, cancer cells commonly have defective DNA repair pathways and are unable to repair radiotherapy induced DNA damage, with cancer cells subsequently undergoing cell death at the time of cell division (mitotic cell death) or apoptotic cell death

Question 129

what does Gy mean?

Answer 129

the dose of radiation delivered to body tissue is expressed in the unit Gray (Gy)

Question 130

what is a fraction?

Answer 130

radiotherapy is commonly delivered as a series of small doses called fractions rather than as a single large dose

Question 131

what is a typical schedule for a head and neck cancer patient?

Answer 131

70Gy in 35 fractions over 7 weeks

Question 132

what are commonly used palliative schedules for radiotherapy?

Answer 132

8Gy in 1 fraction
20Gy in 5 fractions
30Gy in 10 fractions

Question 133

which cancers are highly radiosensitive and which do not respond well to radiotherapy?

Answer 133

seminoma and Hodgkin’s disease are highly radiosensitive and respond well to low doses of radiation whereas cancers such as a glioblastoma multiforme are relatively radio-resistant to even high doses of radiotherapy

Question 134

what is the therapeutic index with regards to radiotherapy?

Answer 134

the balance between tumour control and the side effects of radiotherapy

Question 135

what is concurrent chemotherapy?

Answer 135

chemotherapy given to patients during their radiotherapy treatment - it is thought to act as a radiosensitiser, increasing the sensitivity of the cells to radiation

Question 136

what is the most common external beam radiotherapy used in the UK?

Answer 136

3D-conformal radiotherapy

Question 137

what is the gross tumour volume, clinical target volume and planning target volume?

Answer 137

GTV: tumour is delineated on each CT slice it appears on
CTV: margin is then added for microscopic disease spread, which may include adjacent nodal groups
PTV: finally a further margin is added to allow for minor daily variations in patient and tumour position

Question 138

what is the multi-leaf collimator?

Answer 138

MLC: part of the head of the radiotherapy machine and helps to shape the beam of radiation

Question 139

does radiotherapy hurt?

Answer 139

radiotherapy treatment itself is painless and the patient neither sees nor fells anything as it is being delivered

Question 140

what are the 2 main types of side effects for radiotherapy and give examples for each?

Answer 140

1. acute: usually after first 5-10 fractions. side effects tend to increase during treatment and often hit a peak in the first few weeks following the end of treatment eg localised skin reaction, oral mucositis and diarrhoea
2. late: develop at least 3 months after radiotherapy and sometimes manifest years later. long-term toxicity occurs as some of the damage to normal cells cannot be repaired and partly due to the development of fibrosis and blood vessel damage within the irradiated tissue eg lung fibrosis, skin atrophy and infertility

Question 141

does having radiotherapy increase your chances of getting cancer?

Answer 141

yes - radiotherapy itself is a carcinogenic and there is a risk of a second malignancy developing as a result of treatment

Question 142

should you give radiotherapy to pregnant women?

Answer 142

radiotherapy is a teratogenic and therefore must be avoided in any woman who is pregnant

Question 143

what is brachytherapy?

Answer 143

a form of radiation treatment where radiation sources are placed within or close to the tumour
it allows the delivery of a localised high radiation dose to a small tumour volume, increasing the chance of tumour control whilst minimising the dose to surrounding normal tissue

Question 144

which cancers commonly have brachytherapy?

Answer 144

prostate, gynaecological, oesophageal and head and neck cancers

Question 145

what are the two main types of brachytherapy?

Answer 145

intracavity: the radioactive material is placed inside a body cavity such as the uterus and cervix
interstitial: where the material is put into the target such as the prostate

Question 146

what is important to notify a patient after brachytherapy?

Answer 146

Radiation protection is of particular importance in brachytherapy. Whilst a radioactive source is in situ the patient will be radioactive. Before discharge a patient will be advised about their on-going radiation risk to others.

Question 147

what is a radio-isotope? what is the most commonly used form and when is it used?

Answer 147

an unstable form of a chemical element which emits radiation when it decays and is another method of radiation delivery
The most commonly used form is radioactive iodine, I-131, which is used in the management of the most common forms of thyroid cancer

Question 148

how does iodine work as a radioisotope?

Answer 148

the iodine is preferentially taken up by and concentrated in any remaining thyroid tissue, normal or malignant, where it emits radiation as it undergoes radioactive decay, ablating the thyroid cells
few other tissues in the body take up iodine, and so it is selectively delivered radiation

Question 149

how long does it take for a patient to have radiation low enough to be safe to others after receiving iodine radioisotope therapy?

Answer 149

The patient will need to remain in the lead lined room until the level of radiation they are emitting is low enough to be safe to others, which is usually around four days

Question 150

what is stereotactic radiotherapy? why is it useful and when is it used?

Answer 150

when a tumour deposit is well defined and small eg brain metastases or lung primary, can deliver large dose of radiotherapy to target with a very small margin. Th biological dose (a concept that quantifies the chance of cell death within the target) can be increased by giving a small number of large fractions
used to treat oligometastatic disease since they generally have minimal side effects and yet produce high levels of local control
also possible in patients unfit for surgery

Question 151

what is arc therapy? what is the advantage?

Answer 151

allow the treatment unit to deliver treatment continuously as it moves through an arc around the patient
the MLC leaves can also be moved throughout this process
advantages: treatment delivery can be very fast (so more patients treated per day on individual machine), dose can effectively be ‘painted’ onto the target volume with much greater accuracy and with sparing of surrounding tissue

Question 152

what is intensity modulation?

Answer 152

refers to the moving of the MLC leaves during treatment delivery to build up dose in different parts of the treated volume - in Leeds volumetric modulated arc therapy is a type of intensity modulated radiotherapy used

Question 153

what is phase 1 of clinical trials?

Answer 153

aim is to determine toxicity (previously tested in vitro and in animals) and establish maximum tolerated dose (MTD)
drugs with no clinical activity seen are NOT rejected at this phase
dose escalation is performed, commencing at 10% of the dose /kg that is lethal in 10% of mice (‘LD10’). in general, 3 patients are treated at each dose level until side effects are seen and then 6 patients per group until maximum tolerated dose is reached
it is performed on patients with any tumour, in whom no conventional therapy is appropriate
patients must remain generally fit and have near-normal renal and hepatic function
trials are not randomized or comparative

Question 154

what is phase 2 of clinical trials?

Answer 154

once drug doses and scheduling have been defined from phase 1 trials, aim of phase 2 is to assess the particular anti-tumour activity of a new treatment in a range of different cancers
the radiological tumour shrinkage (‘response rate’) is the primary outcome measure for most phase 2 trials
it is not necessary to have a control arm and random allocation of treatment in all phase 2 trials, but can be useful

Question 155

what is phase 3 of clinical trials?

Answer 155

randomised trials comparing new with established treatments
primary endpoints assessed are usually length of life whatever the cause of death (overall survival), or length of life until the cancer grows (progression-free survival)
radiological shrinkage (response rate) and QOL are often secondary
if benefit of a new treatment is thought to be small, a large sample size will be required to achieve statistical significance
for this reason most of these trials are run in multiple centres and countries

Question 156

which criteria is used to define tumour responses radiologically? which definitions are used after treatment for target lesions?

Answer 156

RECIST (response evaluation criteria in solid tumours)
definitions:
complete response (disappearance of all target lesions)
partial response (at least a 30% decrease in the sum of longest diameters of target lesions taking as reference the baseline LD sum)
progression disease (at least a 20% increase in sum of LD of target lesions taking as reference the smallest sum LD recorded since treatment started or the appearance of one or more new lesions)
stable disease (neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD, taking as references the smallest sum LD since the treatment started

Question 157

what do the following terms mean?
overall survival
disease free survival
progression free survival

Answer 157

overall survival: the length of time between entry to the trial and death from whatever causes
disease free survival: the time between entry into the trial and recurrence of the tumour or death from other causes
progression free survival: time between entry into the trial and disease progression or recurrence

Question 158

which toxicity in clinical trials, on the scale 1 to 4, which is most toxic?

Answer 158

grade 1 = least toxic
grade 4 = most toxic

Question 159

what do the following trials involve?
basket trials
umbrella trials
platform trials

Answer 159

“Basket trials” - where tumours harbouring a particular genetic mutation (of whatever primary site) are tested with a new drug that targets that mutation.
“Umbrella trials” - where patients with a particular type of cancer (e.g. non-small cell lung cancer) are all tested to establish the genetics of their tumours and then offered different experimental treatments depending on the results.
“Platform trials” - where multiple experimental arms are compared with a single control arm to reduce costs and increase the number of patients able to receive novel therapies.

Question 160

What would you prescribe for a 73 y.o. man with advanced renal cancer and multiple lung metastases who is complaining of progressive breathlessness?

Answer 160

oramorph PO

Question 161

what do the different scores for performance status mean?

Answer 161

0 = normal
1 = symptomatic and ambulatory cares for self
2 = ambulatory >50% time
3 = ambulatory <50% time nursing care required
4 = bedridden

Question 162

A 66 y.o. man presented with a change in bowel habit. Subsequent investigations show a right-sided colonic mass but no metastatic disease. He undergoes a colectomy and histology confirms a Duke’s C adenocarcinoma (indicates LN involvement). What treatment should he be offered next?
Adjuvant chemotherapy
Radical radiotherapy
Surgical excision
Surveillance
Systemic hormone therapy

Answer 162

adjuvant chemotherapy

Question 163

A 77 y.o. lady presents to her GP with hip pain. X-ray shows mixed sclerotic/lytic lesion in the iliac blade and subsequent imaging and biopsy confirm small primary HER2- ER+ breast cancer. Which is the most appropriate initial treatment approach?
Palliative chemotherapy
Palliative radiotherapy
Palliative systemic hormone treatment
Surgical excision
Symptom management alone

Answer 163

Palliative systemic hormone treatment
Hormone therapy appropriate - chemo may be considered if liver involvement. Bisphosphonates may be added for prevention of skeletal related events

Question 164

A 64 y.o. woman with hyperthyroidism and alcohol dependence complains of episodes of palpitations associated with breathlessness. She is a non-smoker and is otherwise well. On examination her pulse is 88bpm and regular, heart sounds normal, chest clear and no ankle oedema.
Which is the most appropriate diagnosis?
Anaemia
Anxiety
COPD
Heart failure
Paroxysmal AF

Answer 164

Paroxysmal AF
Thyrotoxicosis and alcohol are RFs for AF. The episodic nature of her symptoms suggests paroxysmal AF depsite a normal HR on exam

Question 165

What is the first line treatment for animal bites?

Answer 165

Co-amoxiclav

Question 166

What is the 2nd line treatment of skin infections given to patients who are allergic to penicillin?

Answer 166

erythromycin

Question 167

A 69 y.o. man with myeloma is admitted to the oncology ward with constant nausea. He has vomited small amounts of bile stained fluid for the last 3 days and feels thirsty.
Which anti-emetic do you prescribe?

Answer 167

Haloperidol
The patient most likely has a chemical or ‘ toxic’ cause for his vomiting (stimulation of the chemoreceptor trigger zone) probably hypercalcaemia and therefore the most suitable FIRST line antiemetic would be haloperidol
Haloperidol is usually drug of choice in renal impairment (likely with this story)

Question 168

A 71 y.o. woman with advanced lung cancer complains of passing hard stool. She is opening her bowels once a day as previously but this is now painful. What is the most suitable laxative to prescribe?
Bisacodyl suppositories
Co-danthramer suspension
Docusate capsules
Fybogel sachets
Senna tablets

Answer 168

Docusate capsules
The patient is having difficulty passing hard stool but has no change in the frequency of opening her bowels. She therefore needs a laxative that will soften the stool. Docusate is the only laxative in the list with only softening action

Question 169

A 63 y.o. man undergoing treatment for prostate cancer complains his left leg ‘gave way’ yesterday and feels odd. He denies any back pain. Which is the most appropriate investigation?
CT scan brain
Isotope bone scan
MRI spine
PSA
X-ray thoracic spine

Answer 169

MRI spine
symptoms are highly suggestive of a neurological problem. Spinal cord compression is an oncological emergency and is best excluded or characterised if present by MRI, which can also determine whether surgery, radiotherapy or supportive care are best management. It is possible to have cord compression without back pain, Brain mets are very uncommon in prostate cancer

Question 170

An 81 y.o. woman presents to her GP with gradual onset of breathlessness on exertion. She has a history of angina and hypertension. On exam, she has a systolic murmur, fine crackles at both lung bases and pitting oedema of the ankles. Her ECG shows left ventricular hypertrophy. What are the most appropriate investigations to perform?
CXR and coronary angiogram
CXR, Echo and bloods for BNP
Exercise tolerance test
Spirometry and bloods for FBC, U&E
24 hour ECG and echocardiogram

Answer 170

CXR, Echo and bloods for BNP
The patients appears to have heart failure as a result of ischaemic heart disease and hypertension. Her ECG shows LVH and she may also have some valvular disease. NICE guidelines for Heart Failure 2010 suggest BNP and Echo in all patients suspected of having heart failure. A CXR would also be helpful.

Question 171

A 41 y.o. woman presents to her GP with 3 weeks history of dysphagia. She has no weight loss or abdominal pain but has vomited on several occasions. She is HIV positive and is on antiretroviral treatment but has no other recent medical history. Which is the most appropriate investigation to arrange?
Urgent bloods for FBC, HIV viral and CD4 count
Urgent CXR
Urgent direct access CT scan
Urgent direct access US
Urgent direct access upper GI endoscopy

Answer 171

Urgent direct access upper GI endoscopy
NICE guidance offer urgent direct access upper GI endoscopy (to be performed within 2 weeks) to access for oesophageal cancer or stomach cancer in people:
with dysphagia
55 and over with weight loss and upper abdominal pain
or reflux or dyspepsia
The HIV is a red herring - it should not change your investigation

Question 172

A 69 y.o. man with metastatic mesothelioma was dying at home but had a fall and the paramedic ambulance brought him to the Emergency Department. He did not sustain any injuries but died on the ward the following day. What is the most appropriate cause of death to write on the medical cause of death certificate?
1a fall
1a metastatic mesothelioma
1a fall, 2 metastatic mesothelioma
1a fall 1b frailty 1c metastatic mesothelioma
Do not issue a certificate and refer to HM coroner

Answer 172

Patient had an occupational-related illness therefore must be discussed with HM coroner who may give permission for death certificate to be issued (as per D)

Question 173

A 60 y.o. man visits the practice nurse to discuss lifestyle modification after a friend died of cancer. The patient’s BMI is 35. Which cancer is a man who is obese at more risk of?
Bladder
Colon
Lung
Melanoma
Prostate

Answer 173

Colon cancer
Cancer Research Uk estimates obesity is one of the most important causes of colon cancer and accounts for 11-14% of cases

Question 174

You see a 65 y.o. woman in the surgery, on examining her pulse you notice she is in AF at a rate of 110bpm she is asymptomatic, you arrange an ECG which confirms AF. She has an active lifestyle but has asthma for which she takes salbutamol and an inhaled corticosteroid/long acting beta agonist. She takes no other medications and has no other PMH. You calculate her CHAD2DS2VASc score as 2. Which is the most appropriate management?
Beta blocker and aspirin
Calcium channel blocker
Calcium channel blocker and oral anticoagulant
Digoxin
Refer for cardioversion

Answer 174

Calcium channel blocker and anticoagulant
Beta blockers are contraindicated in patients with asthma
NICE no longer recommend aspirin monotherapy for stroke prevention in AF
Rhythm control not appropriate as you don’t know how long she has had AF and there is no known underlying cause

Question 175

A 70 y.o. woman complains that soon after waking she had a fleeting loss of vision in her left eye followed by a change in sensation affecting the right side of her body. Neurological exam later that day shows no abnormalities. Which is the most likely diagnosis?
Acute anxiety
Bell’s palsy
Migraine
Multiple sclerosis
Transient ischaemic attack

Answer 175

Transient ischaemic attack
sudden onset of symptoms. Amaurosis fugax and sensory change which lasts less than 24 hours

Question 176

A 73 y.o. man with prostate cancer and multiple bone and lymph node metastases is admitted to MAU with increasing fatigue and swollen ankles. He is currently taking paracetamol 1mg QDS, oxycodone 20mg BD and dexamethasone 0.5mg daily.
His blood tests on admission show: sodium 141 (137-144), potassium 5.9 (3.5-4.9), urea 25 (2.5-7) and creatinine 487 (60-110)
What is the most likely cause of his renal failure?
dehydration
hypercalcaemia
medication
obstructive uropathy
polycystic kidney disease

Answer 176

Obstructive uropathy
In dehydration urea and sodium likely to be higher and clinical story to match
hypercalcaemia unusual in prostate cancer (sclerotic not lytic mets) and creatinine usually rises to est 200 only
medication only likely if on ACE/NSAIDs/diuretics
Obstructive uropathy very common in prostate cancer: prostate and retroperitoneal LN obstruct ureters

Question 177

A 10 y.o. boy with asthma comes to surgery for his routine review. He is using his salbutamol inhaler every day about 2 or 3 times but more when he is playing football. He wakes up coughing most nights and occasionally has to sit out of PE due to wheezing. Which is the most appropriate additional treatment?
Antimuscarinic eg ipratropium bromide
Leukotriene receptor antagonist eg montelukast
Oral theophylline
Regular long-acting beta2 agonist eg salmeterol
Regular standard dose inhaled corticosteroid eg beclometasone

Answer 177

Regular standard dose inhaled corticosteroid
the patient is not controlled on step 1 of the BTS (british thoracic society) guidelines so must move up to step 2 which involves adding a regular steroid inhaler
Long acting beta 2 agonists are step 3 and should only be started in patients already on regular inhaled steroid preventer therapy. What would you add next? NICE = leukotriene receptor antagonist LTRA eg montelukast (cheaper but less effective) SIGN/BTS = long acting B2 agonist inhaler LABA eg salmeterol

Question 178

An 81 y.o. lady has her annual review for hypertension. Her BP is 100/60 and U&Es show the following: sodium 128 (NR 135-145), potassium 4.5 (NR 3.5-5), urea 7.0 (NR 3.0-8.3), creatinine (NR 44-133). Which of her medications would you stop?
Amlodipine
Atenolol
Bendroflumethiazide
Paracetamol
Ramipril

Answer 178

Bendroflumethiazide
thiazide diuretics are a common cause of hyponatraemia in the elderly

Question 179

What is a normal spirometry?

Answer 179

FEV1 and FVC greater than 80% of predicted and FEV1/FVC greater than 70% indicate normal spirometry
restrictive = FVC reduced, FEV1 reduced <80%, ratio normal
Obstructive = FVC normal, FEV1 reduced <80%, ratio reduced

Question 180

what are the side effects and signs of opioid toxicity?

Answer 180

side effects: constipation, nausea and vomiting, drowsiness (usually subsides after 48-72 hours)
toxicity: confusion, hallucinations, myoclonus, pupillary constriction, respiratory depression in overdose

Question 181

what is the conversion of oral morphine to the following?
subcutaneous morphine
oral oxycodone
oral codeine
subcutaneous diamorphine

Answer 181

subcutaneous morphine: divide by 2
oral oxycodone: divide by 2
oral codeine: x10
subcutaneous diamorphine: divide by 3

Question 182

what characteristics of tumours is needed for screening?

Answer 182

tumours should ideally:
be curable when detected early in the majority of the patients
be relatively common
have a ling pre-invasive or non-metastatic stage
be able to be detected by relatively simple tests
be distinct from benign lesions

Question 183

what are the ideal characteristics of a screening test?

Answer 183

tests should ideally:
be able to detect cancer at an early enough stage to implement effective treatment
be sensitive (ie be able to distinguish tumours clearly and give a low false negative value) - not miss actual cases
be specific (ie would not give false positive results)
be well tolerated hence improving compliance
be easy to administer or perform
be inexpensive
be well publicised in order to ensure high uptake amongst the target population

Question 184

what are the potential advantages and disadvantages of screeening?

Answer 184

advantages:
reduction of mortality by detecting early disease that is curable
less radical treatment hence reducing morbidity
saving on health service resources by increased cure rates
reassurance given by a negative tes

disadvantages:
increased length of anxiety and morbidity if no effective intervention is possible
the over-investigation of false positive cases with associated morbidity
over-treatment of borderline cases that do not require treatment
false reassurance from a false negative result
possible harmful effects of the screening test
cost of screening a large population

Question 185

what are the screening programmes in the UK?

Answer 185

cervical cancer
breast cancer
colorectal cancer

Question 186

what are the ages at which the following are screened?
cervical cancer
breast cancer
colorectal cancer

Answer 186

cervical: all women aged between 25 and 64; women aged 25-49 invited for cervical smears every 3 years, after that invited every 5 years
breast: regular mammography offered to all women between ages of 50 and 70 every 3 years
colorectal: men and women offered bowel screening using faecal occult blood every 2 years from 60 to 69 - this is being extended to 74

Question 187

What is advanced care planning?

Answer 187

a voluntary process of discussion and review to help an individual who has capacity to anticipate how their condition may affect them in the future and, if they wish, set on record choices about their care and treatment
outcomes include:
advance statement of wishes to inform subsequent best interest judgements
advance decisions to refuse treatment which are legally binding if valid and applicable
appointment of lasting powers of attorney for health and welfare and/or property and affairs

Question 188

what are the 3 causes of pain in cancer patients?

Answer 188

the disease itself eg bone invasion
the treatment eg radiotherapy induced oesophagitis
a concurrent disease eg osteoarthritis

Question 189

what are the features of bone pain in cancer patients and what is the treatment?

Answer 189

features: either a dull ache over a large area or well localised tenderness over the bone. Often worse on weight bearing or with movement
treatment: NSAIDs eg diclofenac 50mg tds, radiotherapy and bisphosphonates eg pamidronate infusion

Question 190

what are the features and treatment of visceral pain in cancer patients?

Answer 190

features: dull, deep-seated, poorly localised pain. There may be tenderness over a particular organ eg liver. Some visceral pain is spasmodic such as bladder spasm or bowel colic.
treatment: for constant dull visceral pains follow the analgesic ladder. Pain caused by visceral stretch such as liver capsule pain can be treated by NSAIDs or corticosteroids to reduce inflammation. Colic pain responds to anticholinergic drugs such as subcutaneous hyoscine butylbromide for bowel colic and oral oxybutynin for bladder spasm

Question 191

what are the features and treatment of headache due to raised in cancer patients?

Answer 191

features: dull, oppressive pain usually worse on waking, coughing, sneezing and may be associated with nausea and vomiting
treatment: corticosteroids to reduce oedema eg 16mg po dexamethasone daily, reduce to lowest effective dose, NSAIDs and paracetamol

Question 192

what are the features and treatment of neuropathic pain in cancer patients?

Answer 192

features: pain in an area of abnormal sensation. It may be localised to specific dermatomes or over a wider, less defined area. There may be altered sensation in the area such as numbness or hyperaesthesia and autonomic changes such as pallor or sweating. the patient may describe the pain as ‘pins and needles’ or burning
treatment: antidepressants (amitriptyline 10-75mg nocte) and anticonvulsants (gabapentin 100-1200mg tds, pregabalin 25-300mg bd). Compression of a nerve may be helped by corticosteroids

Question 193

what are the 3 stages of the analgesic ladder?

Answer 193

step 1: paracetamol
step 2: weak opioid eg codeine plus paracetamol eg co-codamol
step 3: strong opioids eg morphine, diamorphine
NSAIDs may be used at any step; other adjuvant drugs include antiepileptics, antidepressants, corticosteroids

Question 194

what are the 3 strengths of co-codamol? what should the dose be for progressing from step 1 of the analgesic ladder?

Answer 194

co-codamol come as either 8mg codeine and 500mg paracetamol (weak), 15mg codeine and 500mg paracetamol, or 30mg codeine and 500mg paracetamol (strong)
generally when progressing from step 1 the preparation with codeine 30mg should be prescribed

Question 195

what are the side effects of strong opioids?

Answer 195

constipation - always prescribe a laxative eg co-danthramer
N&V (usually settles within a few days) - prescribe a prn antiemetic eg haloperidol, and consider a regular antiemetic if patient is already nauseates or has had sickness in the past
drowsiness when starting or changing dose (usually improves within 48 hours)
confusion and visual hallucinations are rare if correct dose given - check dose and renal function and consider an alternative option if confusion persists
respiratory depression is rare
psychological dependence and addiction are common fears among patients but are rarely a problem in clinic practice

Question 196

what is the usual starting dose of MST after co-codamol?

Answer 196

if patient has been on max strength of co-codamol then MST 20mg bd is usually appropriate

Question 197

how long do fentanyl transdermal patches last?

Answer 197

duration of action of 72 hours

Question 198

which patients are suitable to have fentanyl transdermal patches?

Answer 198

mainly suitable for patients with severe chronic pain already stabilised on other opioids

Question 199

what is xerostomia?

Answer 199

dry mouth

Question 200

what is the treatment of oral thrush (candidiasis)?

Answer 200

treat with systemic antifungals - fluconazole 50mg od 7 days - or topical agents - nystatin 1ml qds 7 days

Question 201

what are the features and treatment of gastric stasis/irritation caused N&V?

Answer 201

features: early satiety, epigastric fullness, hiccups, heartburn, often minimal nausea between vomits. May be caused by tumour, hepatomegaly, ascites (‘squashed stomach’) and dysmotility (drugs, autonomic failure)
treatment: metoclopramide 10-20mg po/sc 30 mins before meals or 30-60mg sc over 24 hours. Stop any causative drugs if possible, consider PPI if gastric irritation

Question 202

what are the features and treatment of toxic causes of N&V?

Answer 202

features: persistent or intermittent nausea, small vomits, ‘possets’, and retching. May be caused by drugs (opioids, digoxin, antiepileptics), hypercalcaemi, uraemia and infections (UTI, pneumonia)
treatment: haloperidol 1.5-5mg po/sc nocte

Question 203

what are the features and treatment of cerebral causes of N&V?

Answer 203

features: early morning headache, vomiting, may be little nausea. Associated neurological symptoms/signs
treatment: dexamethasone 8-16mg po od (reduced if possible) plus cyclizine 50mg tds po/sc or 150mg sc/24 hours

Question 204

what are the features and treatment of anxiety/anticipatory N&V?

Answer 204

features: may have specific precipitants such as certain situations, overly anxious or depressed
treatment: benzodiazepines, CBT, complementary therapies

Question 205

what is the treatment of indeterminate N&V?

Answer 205

levopromazine 6.25-12.5mg nocte po/sc

Question 206

what are the features and treatment of vestibular causes of N&V?

Answer 206

features: may be associated with movement, hearing loss, vertigo or tinnitus
treatment: consider cyclizine, hyoscine or cinnarizine

Question 207

what are the 3 classes of laxatives? give examples

Answer 207

bulk forming - fybogel (rarely appropriate in palliative care)
stool softeners - lactulose and sodium docusate, movicol (predominantly a softener but may also stimulate bowel motions, eac sachet requires 125mls of liquid to be swallowed)
stimulants - senna and dantron - avoid if patient has colic

Question 208

what is a down-side to lactulose?

Answer 208

may cause significant bloating and flatulence

Question 209

what are the laxatives of choice for opioid induced constipation?

Answer 209

co-danthrusate
co-danthramer
movicol

Question 210

what should you do if you have given laxatives but the patient still hasn’t passed bowels in 3 days?

Answer 210

consider rectal exam and the use of suppositories and enemas

Question 211

which cancers usually get intestinal obstruction?

Answer 211

ovarian and bowel cancer

Question 212

what are the symptoms of intestinal obstruction in cancer patients?

Answer 212

N&V
colicky pain
abdo distension
dull aching pain
diarrhoea and/or constipation

Question 213

which medication are given to cancer patients who have intestinal obstruction?

Answer 213

combination of antiemetics, analgesics, antisposmodics
if colic is a feature, stimulant laxatives and prokinetic drugs (metoclopramide) should be stopped and antispasmodics prescribes (hyoscine butylbromide)
dexamethasone and octreotide may also be used

Question 214

what are 3 possible causes of dyspnoae in cancer patients? give treatment for each

Answer 214

1. asthma - bronchodilators
2. pulmonary oedema - diuretics, diamorphine
3. pulmonary embolism - anticoagulants eg tinzaparin

Question 215

what are 4 possible causes of dyspnoea arising over several days in cancer patients? give treatments for each

Answer 215

1. exacerbation of COPD - antibiotics, bronchodilators
2. pneumonia - antibiotics, physiotherapy
3. bronchial obstruction by tumour - dexamethasone, stents or laser
4. superior vena cava obstruction - dexamethasone, urgent stenting

Question 216

what are 5 possible causes of more gradual onset of dyspnoea? give treatments for each

Answer 216

1. congestive cardiac failure - diuretics, digoxin, ACE inhibitors
2. anaemia - tranfusion?
3. pleural effusion - pleural aspiration/pleurodesis
4. ascites - paracentesis if appropriate
5. lymphangitis carcinomatosis - trial dexamethasone

Question 217

what is the non-pharmacological treatment of dyspnoea (if cause cannot be reversed or is inadequately reversed)?

Answer 217

discussion of fears and explanation with patient, family and staff
modification of lifestyle, breathing retraining and relaxation
oxygen may help acute dyspnoea, but palliative patients will not benefit from ocygen therapy. A fan directed onto the face often helps

Question 218

what are the pharmacological treatments of dyspnoea (if cause cannot be reversed or is inadequately reversed)?

Answer 218

opioids: decrease resipratory effort and therefore breathlessness eg oramorph 2.5mg four hourly if opioid naive - gradually titrate up the dose
benzodiazepines: lorazepam (0.5mg-1mg sub-lingual) may help anxiety associated breathlessness or give relief during panic attacks
midazolam (2.5mg-5mg subcut) may benefit patients who cannot tolerate oral/sub-lingual route

Question 219

what is the management of cough in cancer patients?

Answer 219

if patient having difficulty expectorating, a trial of saline nebulisers may be helpful
if cough is dry and irritating then simple linctus may help
alternatively opioids are cough suppressants eg codeine linctus, normal release oral morphine

Question 220

which cancers commonly cause metastatic spinal cord compression?

Answer 220

breast, bronchus and prostate

Question 221

what is the pathophysiology of metastatic spinal cord compression?

Answer 221

it is caused by tumour or metastass in the vertebral body or paraspinal region pressing on the spinal cord. 2/3 occur in the thoracic region and the remainder in the cervical or lumbar sppine

Question 222

what are the complications of metastatic spinal cord compression?

Answer 222

can even lead to paraparesis, paraplegia and incontinence

Question 223

what are the symptoms of metastatic spinal cord compression?

Answer 223

back pain or nerve root pain - either unilateral or bilateral, which may be aggravated by movement, coughing or lying flat. Pain may precede other symptoms or may be absent in some patients
motor weakness - may be rapid or slow in onset, and can be subtle in the early stages; descriptions of perceived changes in strength are important
subjective sensory disturbance - often precedes objective physical signs eg ‘it feels like I am walking on cotton wool’
bladder/bowel dysfunction - generally occurs late, urinary retention often develops insidiously

Question 224

what are the signs of metastatic spinal cord compression?

Answer 224

weakness/paraparesis/paraplegia
changes in sensation occur below the level of compression; may be asymmetrical and may not necessarily be complete
reflexes are usually increased below the level of the lesion
clonus and painless bladder distension may be present

Question 225

what are the investigations of metastatic spinal cord compression?

Answer 225

whole spine MRI!

Question 226

what is the management of metastatic spinal cord compression?

Answer 226

corticosteroids (dexamethasone 16mg) should be commenced if there is a clinical suspicion of cord compression, pending definitive investigations. Subsequent treatment may involve surgery, radiotherapy or chemotherapy, either alone or in combination.
Surgery is usually favoured in situations of mechanical collapse of a vertebral body (where radiotherapy will rarely reverse the situation) but is less likely to be used if there is extensive disease elsewhere.
Management is usually coordinated by the on call oncology service, who will liaise with the neurosurgeons as required.
Management is time critical. Outcomes correlate with the level of function at the time of treatment. Complete paralysis, that has been present for several days, is almost never reversible.

Question 227

what is superior vena cava obstruction?

Answer 227

an extrinsic compression, thrombosis, or invasion of the wall of the superior vena cava

Question 228

what commonly causes superior vena cava obstruction?

Answer 228

most commonly caused by extensive lymphadenopathy in the upper mediastinum (often in patients with lung cancer or lymphoma), but can occur with any solid tumour
rarer causes include germ cell, breast or oesophageal cancer

Question 229

how is superior vena cava obstruction diagnosed and is it serious?

Answer 229

essentially a clinical diagnosis
should be regarded as an emergency since the patient’s condition may deteriorate rapidly

Question 230

what are the symptoms of superior vena cava obstruction?

Answer 230

• Headache or a “feeling of fullness” in the head
• Facial swelling
• Dyspnoea (often worse on lying flat)
• Cough
• Hoarse voice

Question 231

what are the signs of superior vena cava obstruction?

Answer 231

• Facial / upper limb oedema
• Prominent blood vessels on the neck, trunk and arms
• Cyanosis

Question 232

what is the management of superior vena cava obstructin?

Answer 232

commence on corticosteroids (dexamethasone 16mg daily) which can sometimes produce short-term relief of symptoms
urgent vascular stenting is the usual treatment of choice - often followed by radiotherapy or chemotherapy depending on the primary tumour type

Question 233

what investigations are important if a patient presented with superior vena cava obstruction as a first sign of caancer?

Answer 233

biopsy is important
if a germ cell tumour is possible then tumour markers may be useful eg AFP, BhCG, LDH

Question 234

when is hypercalcaemia commonly seen in cancer patients?

Answer 234

commonly seen in breast cancer, lung cancer, squamous cell carcinomas and myeloma

Question 235

what are the symptoms of hypercalcaemia?

Answer 235

symptoms may develop insidiously and hypercalcaemia may be missed as a cause of some commonly occurring symptoms
early: lethargy, malaise, anorexia, polyuria, thirst, nausea, vomiting, constipation
late: confusion, drowsiness, fits, coma

Question 236

what is the investigation of hypercalcaemia in cancer patients?

Answer 236

serum calcium corrected for serum albumin

Question 237

what is the management of hypercalcaemia?

Answer 237

rehydration using normal saline followed by IV bisphosphonates such as pamidronate or zoledronic acid
about 70% of patients respond
maximum response is seen after 6-11 days with an average duration of response of 3-4 weeks

Question 238

which cancers usually cause major haemorrhage?

Answer 238

eg a head and neck cancer eroding into a major vessel

Question 239

what is the management of major haemorrhage in cancer patients?

Answer 239

keep green towels close by to absorb and reduce the visual impact of blood loss
if time allows, IM into the deltoid muscle or SC midazolam as a sedative and amnesic can be given

Question 240

which symptoms and signs may indicate that a palliative patient has a short prognosis?

Answer 240

profound weakness
confined to bed for most of the day
drowsy for extended periods
disorientated
severely limited attention span
losing interest in food and drink
too weak to swallow medication

Question 241

what are the nursing needs of palliative patients?

Answer 241

treat dry mouth with good regular mouth care
assess immobility and pressure areas - special beds or mattresses may be needed
consider catheter, convene, or pads for incontinence
consider bowel care only if constipation is causing discomfort or agitation
fast track/continuing care funding will enable patients. to die at home or in a care home

Question 242

what are the possible benefits of withdrawing artificial hydration/nutrition in a palliative person at the end of their life?

Answer 242

less vomiting and incontinence
reduction in barriers between patient and family/carers
prevention of painful venepuncture

Question 243

which medications are commonly stopped when a palliative patient is no longer able to swallow?

Answer 243

vitamins/iron
hormones
anticoagulants
corticosteroids
antibiotics
antidepressants
cardiovascular drugs
anticonvulsants used for pain

Question 244

what are the 4 medications that patients should be prescribed when in the end of their life?

Answer 244

analgesic, antiemetic, anti-secretory and anxiolytic

Question 245

what is the ‘death rattle’ and how is it treated?

Answer 245

this is rattling noise produced by the movement of secretions in the upper airways, generally in patients who are too weak to expectorate effectively
patients are generally not distressed by the noise but relatives and carers may find this distressing
treatment: reposition the patient, antisecretory drugs eg hyoscine butylbromide (buscopan) or hyoscine hydrobromide (which may cause paradoxical agitation) may be needed

Question 246

what is the most commonly used syringe driver?

Answer 246

the McKinley T34

Question 247

what are the indications for a syringe driver?

Answer 247

• Inability to swallow drugs due to reduced conscious level, often in the last few days of life
• Persistent nausea and vomiting
• Intestinal obstruction
• Malabsorption of drugs
• Dysphagia

Question 248

is inadequate pain control an indication for syringe driver use?

Answer 248

it is not an indication unless there is reason to believe oral analgesics are not being absorbed

Question 249

what is a side effect of cyclizine in a syringe driver?

Answer 249

may cause skin irritation

Question 250

why is hyoscine butylbromide preferred over hyoscine hydrobromide as an antisecretory and antispasmodic?

Answer 250

hyoscine butylbromide (buscopan) does NOT cross the blood brain barrier
hyoscine hydrobromide may cause sedation or agitation

Question 251

which drugs are unsuitable for SC administration?

Answer 251

as they are too irritant:
diazepam, chlorpromazine, prochlorperazine

Question 252

which are the big 4 cancers?

Answer 252

breast, lung, prostate and colorectal

Question 253

what is the incidence of breast cancer in the UK?

Answer 253

the most common cancer in women, accounting for 15% of all new cases of female cancer
in UK: 55000 new cases diagnosed each year; approx 11000 women die from the disease
in UK: 1 in 8 women and 1 in 870 men will develop breast cancer

Question 254

what are the risk factors of breast cancer?

Answer 254

increasing age
increasing periods of oestrogen exposure: late childbearing, nulliparity, early menarche, late menopause, obesity
COCP and some types of HRT
obesity, alcohol
ionising radiation
FHx (first degree relative, particularly premenopausal)
genetics: BRCA1 gene (breast and ovarian cancer), BRCA2 gene (linked to early onset breast cancer and male breast cancer, but not with ovarian cancer)

Question 255

what is the histology of breast cancer?

Answer 255

Infiltrating or invasive ductal carcinoma is the most common cell type, comprising 70-80% of all cases. Lobular carcinoma, comprising approximately 10% of cases, is characterized by a higher incidence of multicentric tumours within the same or opposite breast. Other less common histological types include medullary, colloid, comedo and papillary.
Tumours are graded according to differentiation with grade 1 lesions being well differentiated and grade 3 lesions being poorly differentiated.

Question 256

what is the presentation of breast cancer?

Answer 256

most patients present with a breast mass
less common presentations include nipple discharge, regional lymphadenopathy (axillary or supraclavicular nodes) or symptoms of metastatic disease

Question 257

how are patients diagnosed with breast cancer?

Answer 257

referred to breast clinic either by GP (2ww) or through NHS breast screening programme
triple assessment:
1. clinical assessment (exam and history)
2. bilateral mammography - to detect multicentric tumours or synchronous primaries in the opposite breast
3. targeted US and biopsy of symptomatic breast area or area of mammographic abnormality. patients will also have. anUS of axillae with/without biopsy of suspicious nodes
cytological diagnosis should be confirmed by fine needle aspiration cytology (FNAC), needle biopsy, incisional or excisional biopsy

Question 258

when is MRI performed in breast cancer?

Answer 258

if there is discrepancy between clinical exam, mammogram and US findings, if breast density preludes accurate mammogram assessment and if the histology is lobular (as there is a higher frequency of multicentric disease)

Question 259

what do the following staging of breast cancer mean?
T0, Tis, T1, T2, T3, T4

Answer 259

T0 = no primary tumour
Tis = in situ disease, non-invasive
T1 = invasive tumour less than 2cm
T2 = primary tumour between 2 and 5cm
T3 = primary tumour greater than 5cm
T4 = skin involvement

Question 260

what do the following staging of breast cancer mean?
N0, N1, N2, N3
M0, M1

Answer 260

N0 = no lymph nodes
N1 = mobile axillary nodes
N2 = fixed axillary nodes
N3 = internal mammary nodes
M0 = no metastases
M1 = distant metastases

Question 261

what is the stage of the following breast cancers?
1. T or N > stage II, M0
2. Tis, N0, M0
3. T1, N0, M0
4. Any T, Any N, M1
5. T2/3, N0, M0 or T0/1/2, N1, M0

Answer 261

1. stage 4
2. stage 0
3. stage 1
4. stage 5
5. stage 2

Question 262

what is the management of localised breast cancer?

Answer 262

Each patient’s management plan should be discussed at a multidisciplinary meeting (MDT).
The standard treatment would be surgery first. However for a certain subset of patients neoadjuvant chemotherapy is considered (chemotherapy before surgery) such as when
* Initial surgery is not possible due to the size of the tumour
* To allow for breast conservation
* Her2 positive or triple negative breast cancer (ER, PR and Her 2 negative) as high response rates are possible

Question 263

what are the surgical options in breast cancer?

Answer 263

mastectomy or conservative surgery eg wide local excision, with postoperative radiotherapy

Question 264

how does the assessment of axillary lymph nodes. inbreast cancer determine the management?

Answer 264

If the initial assessment shows evidence of metastatic involvement of the lymph nodes then patients will have an axillary clearance.
If there is no evidence of metastatic involvement of the lymph nodes, patients will have a sentinel node biopsy (SNB). The sentinel nodes are the first few lymph nodes into which a tumour drains. Sentinel node biopsy involves injecting a tracer material that helps the surgeon locate the sentinel nodes during surgery. The sentinel nodes are removed and analyzed in a laboratory. If they are positive then patients will go on to have an axillary clearance or radiotherapy to the axillae.

Question 265

which factors determine whether breast cancer patients receive adjuvant systemic therapy with endocrine treatment or with cytotoxic chemotherapy?

Answer 265

• Hormone receptor status [oestrogen receptor (ER) status]
• HER-2 receptor status
• Menopausal status
• Tumour size and grade
• Nodal involvement
• Performance status

Question 266

what is trastuzamab and when is it used?

Answer 266

Therapy with Trastuzamab (Herceptin®) is effective in metastatic and localised disease where the cancer over-expresses the target epithelial growth factor receptor (HER-2) eg breast cancer. In the adjuvant setting it is given for 12 months. It can affect cardiac function and therefore patients will need to have regular cardiac monitoring (normally with a MUGA scan).

Question 267

which endocrine therapy is used in breast cancer?

Answer 267

tamoxifen - normally prescribed for premenopausal women who have tumours that are ER/PR positive (if no contraindications); 20mg/day reduces risk of recurrence and death in the adjuvant setting; increased thrombotic complications are reported and increased risk of endometrial cancer > normally given. for5 years
Aromatase Inhibitors. e.g. anastrazole, letrozole are demonstrated to have superior efficacy to tamoxifen in post-menopausal women with breast cancer. They have a different side effect profile including fewer vascular and malignant events, but more problems with osteoporosis.

Question 268

what do all breast cancer patients require following conservative surgery?

Answer 268

all patients require radiotherapy to the residual breast tissue to reduce chances of locoregional cancer recurrence
standard treatment is daily, monday to friday, for 3 weeks

Question 269

when can endocrine treatment be given as primary treatment in breast cancer?

Answer 269

can be used in ER/PR positive disease in slowly progressive disease, especially where there is no visceral involvement and the patient has minimal symptoms
median duration of response to a single endocrine therapy is 1-2 years

Question 270

higher response rate to endocrine therapy can be related to which factors in breast cancer?

Answer 270

• The dominant site of disease (highest in women with disease in soft tissue, less in those with bone metastases and less again in those with visceral metastases). This may simply reflect ER status
• An objective response to prior endocrine treatment.
• Greater duration of previous disease free interval.

Question 271

when is ovarian ablation used in breast cancer?

Answer 271

in premenopausal women, endogenous ovarian oestrogen production may be stopped by ovarian ablation (surgically or radiotherapy induced) or by the use of luteinizing hormone releasing hormone (LHRH) agonists

Question 272

what is the 5 year survival of the following stages of breast cancer?
stage 1
stage 2
stage 3
stage 4

Answer 272

stage 1 = 95%
stage 2 = 80%
stage 3 = 60%
stage 4 = 25%

Question 273

what is the epidemiology of lung cancer in the UK?

Answer 273

• Lung cancer is the 3rd most common cancer in the UK.
• 1 in every 13 men and 1 in every 15 women are diagnosed with lung cancer in their lifetime
• Lung cancer accounts for 22% of cancer related deaths in the UK
• Only 10% of patients who are diagnosed with lung cancer live for 5 years or more.

Question 274

what are the risk factors of lung cancer?

Answer 274

genetics
smoking
increasing age
history of COPD
industrial exposure to asbestos, chromium, arsenic and iron oxide
exposure to radiation

Question 275

where do lung tumours usually arise from histologically?

Answer 275

Tumours usually arise from the epithelium of the large and medium sized bronchi (only rarely from the lung parenchyma itself).

Question 276

how much do small cell lung cancers make up lung cancers? what are the features of them? what are they associates with?

Answer 276

15%
These are highly aggressive tumours which grow rapidly. They have usually metastasised and become inoperable prior to diagnosis. They can be very responsive to chemotherapy initially, but often relapse quickly. Overall, prognosis is generally poor.
They can also be associated with paraneoplastic syndromes - most commonly causing SIADH, Cushing’s syndrome or Lambert Eaton Myesthaenic syndrome (LEMS).

Question 277

what percentage of lung cancer is non-small cell?

Answer 277

85%

Question 278

what are the types of non-small cell lunger cancer? give features for each

Answer 278

squamous cell carcinoma (42%): often found centrally close to the bronchi; can present with bronchial obstruction; closely linked to cigarette smoking; squamous cell cancers can also secrete PTH relate peptide (PTHrp) which can lead to malignancy-related hypercalcaemia
adenocarcinoma (39%): often peripheral, more frequent in women, non-smokers and patients with previous asbestos exposure; more commonly associated with activating mutations. in EGFR and ALK
large cell carcinomas (8%): less differentiated than other NSCLCs and tend to metastasise early
other types = carcinoid, mesothelioma, sarcoma and lymphoma

Question 279

what are the clinical features of lung cancer?

Answer 279

majority present with non-specific symptoms of the primary tumour eg cough, dyspnoea, haemoptysis, chest pain, or recurrent chest infections
lat presentation is frequent as most of these symptoms are common in smokers
Occasionally, tumours are identified incidentally on x-rays or scans performed for some other reason.

Question 280

how do the following lung cancers present?
apical tumours
medistinal disease

Answer 280

apical tumours may invade the brachial plexus or sympathetic chain producing Horner’s syndrome or pain in the distribution of the nerve routes involved (Pancoast’s syndrome). Recurrent laryngeal nerve palsy and superior vena cava obstruction may be associated with mediastinal disease

Question 281

which lung cancer more commonly presents with clubbing, and which is more commonly presents with sputum production?

Answer 281

clubbing is more frequent with squamous cell carcinoma. Sputum production may be excessive in bronchio-alveolar carcinoma

Question 282

what are the investigations of lung cancer?

Answer 282

CXR
CT chest and upper abdomen
PET scan - used in patients who are thought to have operable disease to check for distant metastases which may not be picked up on CT.
bronchoscopy
Trans-thoracic biopsy under radiological guidance is sometimes required for the biopsy of peripheral lung tumours, or distant metastatic disease e.g. liver metastases.
tumour markers - neuron specific enolase and lactate dehydrogenase (not routinely used)
pulmonary function tests
cardiopulmonary exercise testing - important for patients who are being considered for surgical resection to ensure they are fit enough to undergo an operation

Question 283

what is the management of small cell lung cancer?

Answer 283

SCLC is generally considered a systemic disease at presentation. As such, the vast majority of patients will receive palliative chemotherapy.
If the disease appears “limited stage” at diagnosis (i.e. encompassable within a high dose radiotherapy field) then radical radiotherapy may be given (either alongside or following) the chemotherapy.
If the disease is more extensive at presentation, then chemotherapy is the mainstay of treatment although consolidation thoracic radiotherapy may also be used in patients who have a good response to chemotherapy.
Prophylactic cranial irradiation (see below) is also used in patients with limited disease and in those with extensive disease who respond to chemotherapy.

Question 284

what is the difference in management between complications of small cell and non-small cell lung cancer?

Answer 284

SCLC is one of the most chemo-sensitive solid tumours. Chemotherapy is therefore the mainstay of SCLC management with responses occurring within days. Complications such as superior vena cava obstruction or spinal cord compression can be treated with chemotherapy rather than radiotherapy. This is in contrast to NSCLC.

Question 285

what are the 2 indications for radiotherapy in the management of small cell lung cancer?

Answer 285

1. treatment of primary tumour
2. prophylactic cranial irradiation - brain mets frequent in SCLC; can have significant toxicities eg memory impairment, functional deficit and dementia
3. palliative

Question 286

is surgery appropriate for small cell lung cancer?

Answer 286

The early dissemination of SCLC means it should be considered a systemic disease at presentation. Surgical intervention is therefore inappropriate for the majority of cases.

Question 287

what is the prognosis of small cell lung cancer? what are the prognostic factors?

Answer 287

without treatment: poor, median survival of 2-4 months
treatment with systemic chemo: median survival 6-12 months
prognostic factors: extent of disease at presentation, number of metastatic sites, performance status, degree of weight loss and biochemical abnormalities (elevated LDH or low sodium or albumin)

Question 288

when is surgery used in non-small cell lung cancer? what is a definite contraindication?

Answer 288

stage 1 and 2 - surgical resection has a good prognosis and possible cure
mediastinal involvement is considered a contraindication to surgery

Question 289

when is radiotherapy used in non-small cell lung cancer?

Answer 289

In patients with early stage disease, who are not suitable for surgery, radical radiotherapy has often been used and produces 20% 5-year survival for patients with stage 1 or 2 disease. Continuous, hyperfractionated accelerated radiotherapy (CHART) is radiotherapy which is given three times a day for 12 consecutive days, and compared with conventional radiotherapy (often 20 to 30 once daily treatments), results in improved survival.
Giving radiotherapy at the same time as chemotherapy (concurrent chemo-radiotherapy) may also improve outcomes compared to giving chemotherapy first followed by radiotherapy (sequential chemo-radiotherapy). This is usually used in patients with Stage II-III dise
early NSCLC located more peripherally in the lungs is treated by stereotactic ablative body radiotherapy (SABR). This delivers a small number (≤5) of very large doses of radiotherapy to a small, highly conformal volume around the lung tumour.
Palliative radiotherapy is used frequently for symptomatic disease such as spinal cord compression, painful bone metastases or significant chest symptoms due to central disease (e.g. haemoptysis, cough).

Question 290

what are some examples of chemotherapy used in non-small cell lung cancer?

Answer 290

combination regimens are used, either Carboplatin and Gemcitabine or Carboplatin/Cisplatin and Pemetrexed. Docetaxel can be used as a 2nd line option

Question 291

when is targeted chemotherapy used in non-small cell lung cancer?

Answer 291

beneficial in some patients with advanced non-small cell lung cancer. Patients with adenocarcinoma are tested for mutations in EGFR and ALK at the time of diagnosis. If these are positive, tyrosine kinase inhibitors (TKIs) can be used (e.g Afatinib/Erlotinib/Gefitinib for EGFR mutations and Crizotinib for ALK mutations). The proportion of patients suitable for these treatments is < 10% overall but is higher in some ethnic groups and non-smokers. Patients on these targeted therapies can be treated with second line targeted therapies (Osimertinib/Ceritinib) rather than the standard chemotherapy described above.

Question 292

when is immunotherapy (pembrolizumab) used in non-small cell lung cancer?

Answer 292

recently been approved for patients with advanced NSCLC in patients with high PDL1 expression (a molecule involved in controlling the normal immune response). This can be used either before or after chemotherapy and a small percentage of patients can have a prolonged benefit with this.

Question 293

what is the prognosis and prognostic factors of non-ssmall cell lung cancer?

Answer 293

Without treatment, prognosis is likely to be short, and is usually measured between 3-6 months. Provided patients are fit enough to tolerate chemotherapy, this can extend average life expectancy by a number of months, possibly to just over a year. If patients are suitable for targeted treatment or immunotherapy, this can be substantially longer and prognosis may be around 2 years in some cases.

Question 294

what is the most common cancer in males?

Answer 294

prostate cancer

Question 295

what is the epidemiology of prostate cancer?

Answer 295

Prostate cancer is the commonest cancer in males, with more than 47000 new cases diagnosed in the UK in 2015. It is predominantly a disease of older men, with more than 50% occurring over the age of 75.

Question 296

what are risk factors for prostate cancer?

Answer 296

increasing age
higher in men from African and Afro-Caribbean backgrounds
Fhx, and men whose mothers were diagnosed with breast cancer
BRCA2 and pTEN gene mutations

Question 297

what is the histology of prostate cancer?

Answer 297

over 95% are adenocarcinomas, developing in glandular tissue in posterior or peripheral parts of the prostate
(benign prostatic hyperplasia more commonly arises in centre of gland)
histology defined by Gleason system

Question 298

what is the presentation of prostate cancer?

Answer 298

may be asymptomatic and diagnosed with rectal exam or PSA blood test
may present with lower urinary tract symptoms: poor stream, nocturia, dribbling and increased frequency, impotence is common
1 in 5 patients present with metastatic prostate cancer and may have bone complications such as anaemia, pain, pathological fracture, or spinal cord compression.
Typical rectal examination findings would include an enlarged, hard, craggy gland (or nodule). Ultimately there is obliteration of the median sulcus.

Question 299

what are the investigations of prostate cancer?

Answer 299

initial: DRE and serum PSA
if radical treatment appropriate then an MRI scan can visualise the prostate well and delineate any extra-capsular spread
if metastatic disease concerns then isotope radionucleotide bone scan
most patients will have US guided transrectal biopsy to confirm the diagnosis but where clinical suspicion is very high (e.g. PSA >100 with positive bone scan) this is not required

Question 300

What do the following stages of prostate cancer mean?
TX
T0
T1
T2
T3
T3a
T3b
T4

Answer 300

TX = primary tumour cannot be assessed
T0 = no evidence of primary tumour
T1 = clinically unapparent tumour not palpable nor visible by imaging
T2 = tumour confined within prostate
T3 = tumour extends through the prostate capsule
T3a = extracapsular extension (unilateral or bilateral)
T3b = tumour invades seminal vesicles
T4 = Tumour is fixed or invades adjacent structures other than seminal vesicles: bladder neck, external sphincter, rectum, levator muscles, and/or pelvic wall

Question 301

what do the following stage of prostate cancer mean?
N0
N1
M0
M1
M1a
M1b
M1c

Answer 301

N0 = no regional lymph node involvement
N1 = regional lymph node involvement
M0 = no distant metastases
M1 = distant metastases
M1a = non-regional lymph nodes(s)
M1b = bone(s)
M1c = other or multiple site(s) with or without bone disease

Question 302

what is the grading system of prostate cancer?

Answer 302

Gleason system scores tumours from 2 to 10 on the basis of histological patterns in the 2 most dominant areas of the tumour eg Gleason 4 + 3 means main area is 4 with the second area 3

Question 303

what is the general management of prostate cancer?

Answer 303

PSA, histological grade and stage can be used to stratify patients with local prostate cancer into risk groups and to counsel patients on management options. Treatment of locally advanced and metastatic patients is broadly palliative but can lead to durable symptomatic benefit and many patients live with their disease for years. . The most appropriate options are influenced by the patient’s age, fitness, existing medical issues and preferences

Question 304

when may observation be appropriate as management of prostate cancer?

Answer 304

In patients with asymptomatic disease, confined to the prostate, observation rather than active treatment may be appropriate, particularly where other conditions limit the length of survival that is expected. Radical treatment is unlikely to benefit men with life expectancy of less than ten years, some of whom will not require on-going surveillance. The optimum management of patients with an elevated PSA but no clinical evidence of prostate cancer is unknown

Question 305

when is surgery an appropriate management of prostate cancer?

Answer 305

Patients with localised disease (T2 disease or less) can be treated by radical prostatectomy with curative intent and this can be performed by perineal or retroperineal routes. Robotic laparoscopic surgery leads to reduced operating times, less blood loss and shorter hospital stays but, though mortality is low, prostatectomy can lead to temporary or lasting impotence and incontinence.
Palliative surgical techniques such as trans-urethral resections may be used to relieve prostatic symptoms or urinary obstruction in some men.

Question 306

when is radiotherapy used in the management of prostate cancer?

Answer 306

Radical radiotherapy may be used as an alternative to surgery in T1 and T2 tumours, where PSA is low, suggesting no occult metastases. It is also more appropriate for the control of more advanced local disease. Adjuvant radiotherapy may also be given following radical surgery if there is concern for residual disease.
Definitive radiotherapy should be delayed until at least six weeks following trans-urethral resection to prevent stricture formation.
Radiotherapy may be performed by external beam irradiation, by the interstitial implantation of radioisotopes (brachytherapy) or by a combination of these.
Side effects can include dysuria, rectal bleeding, diarrhoea, impotence and incontinence.
Palliative radiotherapy is used to palliate the primary tumour and/or to treat metastatic complications e.g. recurrent haematuria due to bleeding from prostate bed, bone pain from metastatic disease.

Question 307

how do LHRH agonists act as hormonal therapy for prostate cancer? give examples and what are the side effects?

Answer 307

eg leuprorelin, goserelin
Luteinizing-hormone releasing hormone (LHRH) interferes with the normal release of gonadotropins from the pituitary. This reduces the level of circulating testosterone to those following castration. LHRH agonists are given by monthly or 3 monthly subcutaneous or intra-muscular depot injections. Side effects include impotence, loss of libido and tumour flare. Tumour flare occurs on initiation of treatment (prior to the down regulation of gonadotropin) and is avoided by short-term concomitant anti-androgen therapy. Long-term consequences of medical castration include increased cardiac risk and osteoporosis.

Question 308

how do gonadortophin-releasing hormone antagonist act as hormone therapy for prostate cancer? give examples

Answer 308

leads to castrate levels of testosterone in 96% of patients within 3 days (without risk of tumour flare). Given by monthly subcutaneous injection it is indicated when tumour flare may lead to significant symptoms e.g. a patient presenting with metastatic spinal cord compression.

Question 309

how does oestrogen therapy treat prostate cancer? what are the side effects?

Answer 309

Oestrogens inhibit LHRH production from the hypothalamus but are rarely the best option due to side effects: impotence, loss of libido, gynaecomastia, myocardial infarction, stroke and pulmonary emboli.

Question 310

how do anti-androgens treat prostate cancer? give examples

Answer 310

e.g. bicalutamide, enzalutamide) compete with androgens for sites on the androgen receptor. Enzalutamide shows progression and survival benefit when combined with LHRH therapy in advanced prostate cancer.

Question 311

how is chemotherapy used to treat prostate cancer? give examples

Answer 311

Cytotoxic treatment with docetaxel (in combination with prednisolone) and cabazitaxel has been shown to improve quality of life and overall survival in patients with castrate-refractory metastatic disease. Recent data supports use of early docetaxel chemotherapy (+/- prednisolone) around the time of diagnosis of metastatic prostate cancer: six cycles of chemotherapy in fit men prolongs survival (median 60 months, ie an extra 15 months, HR 0.76, p=0.005) and has led to a change in practice.

Question 312

what is the prognosis of prostate cancer?

Answer 312

Survival is related to the extent of the disease.
Prostate cancer survival of men with low risk localised prostate cancer is excellent (99%) at 10 years whether they choose active surveillance, radiotherapy or surgery.
Prostate cancer 10 year survival (all UK patients) is around 84%.
Patients with metastatic disease have a median survival of 3.5 years. Pattern of disease (bone metastases), aggressive pathology and younger age are associated with a poorer prognosis.

Question 313

what is the epidemiology of colorectal cancer?

Answer 313

41000 new cases diagnosed every year in UK
4th most common malignancy after lung cancer - 10-15% of all malignancies, causes 16000 deaths each year
cancer. ofcolon is 1.5 times more common than rectal carcinoma

Question 314

what are the risk factors for colorectal cancer?

Answer 314

diet - rich in animal fats and meat and poor in fibre; common in Western countries
IBD - association with ulcerative colitis which is related to the extent of the bowel involvement and duration of inflammation
familial association - hereditary non-polyposis colon cancer (HNPCC), familial adenomatous polyposis (FAP) and Gardner’s syndrome; mutation sin APC gene (5q21-22 for FAP coli) and mutations in DNA mismatch repair genes (HNPCC)

Question 315

what is the stepwise process of progression from benign to invasive carcinoma in colorectal cancer? what is the pathophysiology?

Answer 315

APC mutations are associated with the development of benign adenomas whereas the progression to invasive carcinoma requires further mutations eg p53, DCC and RAS
these mutations may be caused by carcinogens present in faeces
in principle diets low in fibre prolong transit time and may prolong exposure to carcinogens
bile salts may act as carcinogens both directly and when degraded by bacteria present in the faeces

Question 316

what is the histology of colorectal cancer? where are they most commonly found?

Answer 316

40% of large bowel cancers occur in the rectum, 20% in the sigmoid colon, 6% in the caecum and the rest in the remaining colon
the histological types of cancer that occur are:
- epithelial: 90-95% adenocarcinoma (mucinous or signet ring). Rare others include squamous cell carcinoma and adenosquamous carcinoma.
- carcinoid
- gastrointestinal stromal tumour
- primary malignant lymphoma
colorectal cancer normally spreads by local invasion, lymphatic, venous and trans-coelomic spread within the peritoneal cavity

Question 317

what is the usual presentation of colorectal cancer?

Answer 317

presentation can be with classical features of altered bowel habit, weight loss, rectal bleeding and vague abdominal pain, although clinical features vary according to the site of the primary tumour and degree of spread
more occult tumours, typically of the right side of the colon and the caecum, can present with iron deficiency anaemia

Question 318

what are the investigations of colorectal cancer?

Answer 318

RECTAL EXAM IS ESSENTIAL
direct visualisation of the bowel with rigid sigmoidoscopy, flexible sigmooidoscopy and colonoscopy allows biopsy of suspicious lesions
double contrast barium enema is less useful as no histology is provided
CT provides staging and a useful evaluation of the bowel in some cases
CT colonoscopy combines CT scanning with insufflation of the whole colon with gas - this can help identify synchronous polyps within the bowel where colonoscopy is not possible, however it does not facilitate biopsy
other: tumour marker CEA (carcino-embryonic antigen) - although elevation of this protein is not diagnostic it can be useful to monitor

Question 319

what do the following stages of colorectal cancer mean?
TX
T0
T1
T2
T3
T4

Answer 319

TX - primary tumour cannot be assessed
T0 - no evidence of primary tumour
T1 - tumour invades submucosa
T2 - tumour invades muscularis propria
T3 - tumour extends through muscularis propria into peri-colic tissues
T4 - tumour invades visceral peritoneum or invades / adheres to adjacent organ or structure

Question 320

what do the following stages of colorectal cancer mean?
N0
N1
N2
MX
M0
M1
M1a
M1b
M1c

Answer 320

N0 - no regional lymph node involvement
N1 - involvement of 1-3 lymph nodes
N2 - involvement of 4 or more lymph nodes
MX - distant metastasis cannot be assessed (not evaluated by any modality)
M0 - no distant metastasis
M1 - distant metastasis
M1a - confined to one organ or site eg liver or lung, but not peritoneum
M1b - 2 or more sites (but not peritoneum)
M1c - peritoneal spread

Question 321

what is Duke’s staging used for and what do the stages A-D represent each?

Answer 321

A invasion into but not through the bowel wall
B invasion through the bowel wall but not into nodes
C lymph node involvement
D distant metastases

Question 322

when is surgery used as management for colorectal cancer?

Answer 322

Radical resection is the standard treatment for primary colorectal carcinoma because of the risk of unsuspected nodal metastases. Patients with early stage colorectal carcinoma are usually cured by surgical resection alone. The long-term results with rectal carcinoma are related to the initial surgical resection.
Surgery may also be indicated in patients with advanced disease. Resection of liver metastases in addition to the primary may be beneficial. Further resection of a local recurrence is associated with improved long-term survival.
Surgery or colonic stenting may be used in the palliative setting to manage or prevent an obstructing lesion.

Question 323

when is radiotherapy used as management for colorectal cancer?

Answer 323

predominantly used in treatment of rectal carcinomas
not commonly used in management of colon cancers due to the potential toxicity to adjacent organs and mobility of tumours
pre-operative (or rarely adjuvant) radiotherapy is indicated in high risk rectal carcinomas before (or rarely following) total resection
cases are selected on the basis of pelvic MRI staging scans
local recurrences can be palliated with radiotherapy
metastatic disease may also respond to palliative radiotherapy

Question 324

when is chemotherapy used as management for colorectal cancer?

Answer 324

adjuvant chemo for high-risk colorectal cancer eg Duke’s C carcinoma
5-FU is the most active agent in colorectal carcinoma with a response rate of approximately 25% - newer drugs such as Oxaliplatin and Irinotecan are now also in standard use

Question 325

what is the prognosis for each stage of Duke’s for colorectal cancer? also for age

Answer 325

5 year survival:
A - 80%
B - 50%
C - 15-40%
D - 5%
age below 40 is an adverse prognostic factor reflecting a biologically more aggressive tumour

Question 326

what is the screening for colorectal cancer?

Answer 326

faecal occult blood testing of average-risk populations (with follow up colonoscopy for positive cases)
given to people aged 60-74 every 2 years

Question 327

What is the difference between using the CHADVASC score and ORBIT score?

Answer 327

CHADVASC is used for the stroke risk of AF patients
ORBIT is used as a screening tool for the bleeding risk of AF patients and the need for anticoagulation