Palliative / Oncology / Haematology Flashcards
1
Q
Classical Side Effects of Chemotherapeutics?
A
Anthracyclines (doxorubicin, daunorubicin) and anti-HER-2 monoclonal antibodies (e.g. Herceptin) cause cardiomyopathy.
Platinum agents (cisplatin, carboplatin) cause peripheral neuropathy and sensorineural hearing loss.
Cyclophosphamides lead to haemmorhagic cystitis and transitional cell carcinoma of the bladder.
Tamoxifen increases the risk of endometrial cancer (both an oestrogen agonist and antagonist (i.e SERM) - antagonist in breast tissue/ agonist in endometrial and bone tissue - prevents osteoporosis).
Bleomycin can cause lung fibrosis and Gemcitabine - pneumonitis
Cisplatin has a risk of ototoxicity and nephrotoxicity
Cytarabine can cause ataxia
5-FU Palmar erythema (hand and foot) and coronary vasospasm
2
Q
_____ is associated with peripheral neuropathy and is a common therapeutic agent in non-Hodgkin’s lymphoma.
A
Vincristine
Vincristine is a chemotherapy drug that belongs to a group of drugs called vinca alkaloids. Vincristine works by stopping the cancer cells from separating into 2 new cells. So, it stops the growth of the cance
3
Q
Lung cancers can be divided into small-cell and non-small cell tumours. The most common histological type of tumour is ____ , followed by _____ cancer.
A
adenocarcinoma
squamous cell
4
Q
Hypertrophic pulmonary osteoarthropathy (HPOA) is a syndrome characterized by the triad of ____, _____ and _____ of the large joints, especially involving the lower limbs.
A
periostitis
digital clubbing
painful arthropathy
HPOA (Hypertrophic pulmonary osteoarthropathy) this occurs in 3% of cases. There will be joint stiffness, and severe pain in the wrists and ankles, sometimes also gynaecomastia.
On x-ray there will be proliferative periostitis at the ends of the long bones, which have an ‘onion skin’ appearance. This is also associated with finger clubbing where cancer is the cause. It is thought to be caused by a blood borne factor released by the tumour – when patients have the primary tumour removed, the pain goes away!
5
Q
Paraneoplastic syndromes of lung cancer: Cushing’s syndrome, SIADH, and Lambert-Eaton syndrome suggest _____, whilst hyperparathyroidism suggests ____.
A
small-cell lung cancer
squamous cell cancer (Often causes hypercalcaemia – by bone destruction or production of PTH analogues (PTHrp).
6
Q
Important features of small cell lung cancer.
Arise from ____ cells aka _____ cells. These are APUD cells, and as a result, these tumours will secrete many poly-peptides mainly ACTH.
A
Endocrine AKA Kulchitsky or Argentaffin (Stain) cells (Arise from the bronchus)
The _endocrine cells_ of the gastrointestinal tract are APUD cells. This acronym stands for amine precursor uptake and decarboxylation, after the classical function of the cells, which may relate to their role in hormone synthesis.
They can also cause various presentations such as Addison’s and Cushing’s disease.
Small cell carcinoma spreads very early and is almost always inoperable at presentation.
These tumours do respond to chemotherapy, but the prognosis is generally poor.
**Carcinoid syndrome is the collection of symptoms some people with a neuroendocrine tumour may have**
7
Q
Lung cancer commonly metastasises to the___ , ___, ___ and ____.
The most likely mechanism by which brain metastases spread is via the bloodstream.
A
brain
breast
adrenals
bone
8
Q
_____ is the correct antibiotic regimen for neutropenic sepsis.
A
IV Tazocin (piperacillin and tazobactam)
(often presents post chemotherapy in a neutropenic or immunosuppressed patient)
Remember if patient is admitted for IV antibiotics and sepsis always stop chemotherapy tablet that they are on!
9
Q
Clinical features of Immunotherapy toxicity?
A
Think inflammation
- Dermatological manifestations such as a pruritic maculopapular rash
- Immune colitis resulting in diarrhoea (ex. nivolumab)
- Endocrinopathies such as hypophysitis, adrenal insufficiency, and hypothyroidism.
- Hepatitis
20-60% of people get these reactions
It is important to be able to recognise the clinical features of immunotherapy toxicity in cancer patients, as these agents now form the first line medical management for many cancers, notably metastatic melanoma and colorectal cancer.
Notably, immunotherapy toxicity is often delayed, and can occur even months after the last cycle of immunotherapy has been administered.
High dose steroids form the mainstay of management for these autoimmune events, although discussion with the oncology team would be necessary as steroids hamper treatment efficacy.
10
Q
Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) of small cell lung cancer shows cells with _____.
A
dense neurosecretory granules
11
Q
_____ is the preferred contraceptive option in women and girls with PCOS
A
COCP
*It helps control period regularity, as well as other manifestations of the condition like acne*
12
Q
What is the initial most effective initial dosing regimen of opioid analgesia in a cancer patient with persistent/worsening/severe pain?
A
A total daily oral Morphine dose of 30mg.
NICE recommends that a dose of 20-30 mg oral Morphine is safe and effective for opiate naïve patients initially commenced on opioid analgesia.
Though dependent on patient choice, immediate release oral morphine solution given four-hourly (i.e as 5 mg immecdiate release formulation that over 24 hrs adds up to 20-30mg - also known as Oramorph) is the recommended formulation used to initially determine a patient’s pain control requirements.
The total daily oral Morphine dose can later be converted to twice daily modified release Morphine sulphate tablets, also known as MST Continus tablets.
13
Q
Most common microorganism cause of neutropenic sepsis evolving from an indwelling peripheral line?
A
Staphylococcus Epidermitis
This is a coagulase-negative staph, and is a common cause of line infections (particularly in neutropenic patients, from which they can develop neutropenic sepsis)
14
Q
______ cancer commonly presents in elderly patients, particular women, with signs of airway compromise (stridor) and dysphagia. It is a rare but aggressive tumour
A
Anaplastic thyroid carcinoma
15
Q
Morphine prescribed for breakthrough pain is stipulated as ____ of the total oral Morphine dose, and prescribed as instant release oral Morphine such as “Oramorph” solution.
A
1/6
For example the dose required for breakthrough pain for this patient is (30x2)/6 = 10mg.
*Oral Codeine is 1/10 the strength of oral Morphine*
16
Q
Side Effects of Radiotherapy:
Early side effects ______
Late side effects ______
A
The side effects of radiotherapy are cumulative and thus occur mostly towards the end of the treatment course. Normal treatment course would be 5 days/wk for 1-10 weeks.
Early side effects
- Tiredness
- Fatigue
- Skin erythema
- Alopecia
- Mucositis (diarrhoea, dysuria) -
E.g - A common side effect of radiotherapy to the prostate region would be mucositis in the rectum called proctitis. This can lead to diarrhoea and the presence of blood in the stool.
Late side effects
- Skin pigmentation changes
- Pulmonary fibrosis
- Infertility
- Secondary cancers
- Constrictive Pericarditis -
Delayed constrictive pericarditis after radiotherapy for thoracic malignancies is well described, secondary to radiation-induced fibrosis of the pericardium. Constrictive pericarditis initially presents with features of right heart failure (such as a raised jugular venous pressure) as the right ventricle is less muscular and is first affected. A pericardial rub may be present as a result of the myocardium coming up against the edges of a tightened pericardium.
Radiotherapy is an important form of therapy for cancer and accounts for 50% of all treatment regimens. There are many side effects of radiotherapy and they are best characterised into early and late onset side effects
17
Q
Squamous cell carcinoma often causes _____ as it secretes _____ not parathyroid hormone.
A
Hypercalcaemia
Parathryoid related peptide (PTHrp)
18
Q
______ form the first-line combination chemotherapy regimen for Hodgkin’s lymphoma.
A
Doxorubicin, Bleomycin, Vinblastine and Dacarbazine (abbreviated as ABVD)
19
Q
The most effective treatment for SVCO is _____ .
A
Systemic treatment with chemotherapy
*The effects of this are most rapid in small cell lung cancers and lymphomas, which are highly chemo-sensitive tumours*
Percutaneous transcatheter insertion of a central venous stent - SVC stenting would be strongly considered in the palliative management of a patient with SVCO.
20
Q
Evidence of SVCO can be elicited by _____ - where lifting the arms over the head for more than 1 minute will precipitate facial plethora (Swelling and redness) and cyanosis.
A
Pemberton’s test
21
Q
Causes of raised AFP
A
Hepatocellular carcinoma
Liver metastasis
Neural tube defects
Germ cell tumours (e.g non-seminoma testicular tumour)
22
Q
Cancers most likely to metastasise to the liver include ______, _____ and ____.
A
Colorectal (via the portal circulation which drains the gut)
breast
lung
23
Q
_____ classification can be used to stage colorectal cancer:
A
Duke’s
A: limited to the bowel wall (i.e. not beyond the muscularis).
B: extending through the bowel wall (i.e. beyond the muscularis).
C: regional lymph node involvement.
D: distant metastases.
It is important to learn the Duke’s staging for examinations.
24
Q
Patients with _____ in colon cancer benefit from ____ adjuvant chemotherapy.
A
Lymph node involvement (i.e TNM stage 3 or C stage in Duke’s)
post-operative
25
Current NHS screening programmes for colon cancer iinclude:
**Faecal immunochemical test (FIT) every 2 years for men and women age 60-74.**
If positive patients are referred for colonoscopy - this reduces the chances of death by 16%.
One of flexible sigmoidoscopy has now been discontinued.
26
\_\_\_\_\_ is not used as a diagnostic tool in colon cancer but can be used to monitor therapeutic response to interventions.
**Carcinoembryonic antigen** (CEA)
\*however it is not always raised in patients and thus is not a reliable tool\*
NOT used for diagnosis
27
For stage IV colon cancer disease (metastases): _____ chemotherapy may also be performed.
pre-operative
The staged colectomy and resection of metastatic disease is performed after pre-operative chemotherapy.
28
Peutz-Jeghers syndrome predisposes to colon cancer and is caused by a mutation in the ____ gene and has an _____ inheritance pattern.
STK11
autosomal dominant
Patients typically present in their teens with mucocutaneous pigmentaiton and hamartomatous polyps.
Note that the risk of neoplastic transformation of hamartomatous polyps is low, but many polyps are present so patients are at increased risk of developing colorectal cancer. They are managed with regular endoscopic surveillance.
29
Opiate naïve patients who are commenced on strong opioids such as Morphine will invariably experience nausea and constipation. They must therefore be started on \_\_\_\_\_\_.
**Regular Senna** and **as-required Cyclizine**
Although nausea is often transient, constipation persists due to reduced intestinal peristalsis. Therefore regular pro-kinetic laxatives such as Senna should be prescribed, whereas Cyclizine should be prescribed on an as-required basis.
30
Which opiate can be prescribed in patients with renal failure who cannot take morphine?
**Alfentanyl**
31
What type of cancer is the most common cause of death in the male population?
Lung cancer
Lung cancer is most common cause of cancer deaths in the male population account for 23%. However, it is the second most common form of cancer overall, accounting for 14% of all cancer cases in 2014.
32
\_\_\_\_\_ is the opiate of choice for patients with renal impairment, and therefore the most appropriate for this patient due to their significant diabetic nephropathy.
Oxycodone
According to NICE, a total daily dose of **20-30 mg of oral Morphine is** safe and effective.
**Oxycodone is approximately 1.5 times stronger than Morphine.** Hence this regimen represents about 23 mg of oral Morphine, which is likely to be safe and effective.
It would also be necessary to prescribe as-required immediate release Oxycodone for any breakthrough pain (pain not controlled by regular opioids). This is stipulated as 1/6th the total daily opioid dose. In this case, 2.5 mg of Oxycodone is the right dose to prescribe for breakthrough pain.
33
What is the most important initial pharmacotherapy for patients suffering with symptoms of SVCO?
**IV Dexamethasone (8mg BD)**
- can be administered to reduce swelling and therefore the pressure on the SVC.
34
There is a diverse range of causes for confusion in oncology patients:
**Metabolic disturbance** (hypoglycaemia, hypercalcaemia)
**Infection** (pneumonia, UTI)
**Metastatic** spread to the brain
**Anaemia**
**Intense pain**
**Side effects of pain medication**
35
Common clinical features of head and neck cancers include:
Dysphagia
Odynophagia
Dysphonia
ALARM symptoms (tiredness, unexplained weight loss, loss of appetite)
Lymphadenopathy
Airway compromise (stridor)
Bad breath (halitosis)
Focal neurology (VII cranial nerve palsy)
36
In anybody that is immunosuppressed (e.g. taking azathioprine for Crohn's or rheumatoid arthritis, recent chemotherapy or acute leukaemia), if they present with a sore throat, _____ must be excluded using an \_\_\_\_. This is true even if examination is normal.
**neutropenia**
**urgent full blood count (FBC)**
37
Morphine administered subcutaneously is _____ of oral Morphine
twice the strength
38
Signs of Hypercalcaemia in malignancy:
**polyuria**
**polydipsia**
**constipation**
**confusion**
**Squamous cell carcinoma** is the most likely malignancy as this is associated with **paraneoplastic hyperparathyroidism** (PTHrP). Additionally, **squamous cell cancer is also associated with HPOA affecting the hands and feet**.
\*Important to remember though that HPOA can be caused by ALL types of lung cancer\*
39
The WHO performance status classification categorises patients as:
0: able to carry out all normal activity without restriction
1: restricted in strenuous activity but ambulatory and able to carry out light work
2: ambulatory and capable of all self-care but unable to carry out any work activities; **up and about more than 50% of waking hours**
3: symptomatic and **in a chair or in bed for greater than 50%** of the day but not bedridden
4: completely disabled; cannot carry out any self-care; totally confined to bed or chair.
40
Medications for respiratory tract secretions in palliative patients
**Hyoscine hydrobromide** - Crosses BBB and thus can cause sedation but also act as an anti-emetic.
**Hyoscine butylbromide** - does not cross BBB
**Glycopyrronium**
41
General Side Effects of Chemotherapy?
**Bone Marrow Suppression**
**Teratogenicity**
**GIT epithelium damage**
**Constipation**
**Hair loss** (alopecia)
**Fertility** damage
**Extravasation**
**Anaphylaxis**
42
Drugs that cause specific side effects in chemotherapy?
**Peripheral neuropathy** (Platinum agents - Cisplatin/Carboplatin)
**Cardiomyopathy** (Anthracyclines - Doxrubicin/Daunorubicin / Herceptin)
**Haemorrhagic cystitis** - Cyclophosphamide
**Endometrial Cancer** - Tamoxifen
**Lung Fibrosis (pneumonitis/ILD)** - Bleomycin
**Ototoxicity** - Cisplatin
43
In a patient in which you suspect cancer, which blood result could would be a red flag?
Thrombocytosis (increased platelet count)
\*remember cancer is pro-thrombotic\*
44
What is the difference between acute and chronic leukaemia?
**Acute:** abnormal *_differentiation_* of bone marrow precursor cells
vs.
**Chronic:** Abnormal *_proliferation_* of mature malignant cells (for example - mitosis of monocytes becomes out of control)
45
What is the difference between myeloid and lymphocytic leukaemia?
Myeloid is a cancer of the myeloid progenitor cell which goes on to form cells such as erythrocytes/neutrophils etc.
vs.
Lymphocytic affects the lymphoid progenitor cell and thus cells such as B/T/NK cells (i.e the adaptive immune response)
46
What is the most commone leukaemia in adults?
Acute myeloid leukaemia - AML
\*It is associated with myelodysplastic syndromes\*
47
Clinical Presentation of AML?
It typically presents with symptoms of _bone marrow failure_:
**Anaemia**
**Bleeding**
**Infections**
and signs of infiltration, including:
**hepatomegaly**
**splenomegaly**
**gum hypertrophy**
48
How do you make a diagnosis of AML?
Blood tests commonly show **Leukocytosis** (raised WBCs) but white cells *can sometimes be normal or low*.
For this reason, **diagnosis is dependent on bone marrow biopsy**, as well as other molecular analyses.
Characteristic biopsy findings include **Auer rods**
49
Bone marrow biopsy of a patient suffering from AML will show which characterisitc finding?
Auer Rods
\*Auer rods are red needlelike crystals that contain peroxidase (arrows) and are an occasional but highly specific finding for a myeloid neoplastic disorder\*
50
The picture attached below indicates a cytoplasmic characteristic that indicates which cancer?
Auer Rods
Acute Myeloid Leukaemia
51
AML is usually treated with which two modalities?
Chemotherapy
Bone Marrow Transplantation
52
Prognosis of AML?
Without treatment: **2 months**
With treatment: **20% 3-year survival rate**
53
What is the most common cancer of childhood?
Acute Lymphocytic Leukaemia (ALL)
54
Clinical Presentation of ALL?
Common presentations include symptoms caused by _marrow failure_:
symptoms of **anaemia** including fatigue
**abnormal bleeding/bruising** caused by low platelets
**infections** caused by **low white cells**.
Symptoms may also be caused by _organ infiltration_:
**Bone pain**
**Hepatosplenomegaly**
_Clinical Signs_ include:
**Painless lymphadenopathy**
**Hepatosplenomegaly**
**CNS involvement** (e.g. cranial nerve palsies, meningism)
**Testicular infiltration** (resulting in painless unilateral testicular enlargement).
55
How is a diagnosis of ALL made?
Blood results show leukocytosis and **blast cells** (too many lymphocytic progenitor cells - blast cells refer to any type of progenitor stem cell) on blood film and bone marrow analysis
56
Management of ALL?
Chemotherapy
57
Prognosis of ALL?
Children have a **cure rate** of about **70-90%**
58
CML is most common in ____ patients, with males slightly more affected.
It is classically associated with the _____ chromosome.
**Middle-aged** (think ryan **m**urphy - male middle aged)
## Footnote
**Philadelphia**
59
CML usually presents with \_\_\_\_\_.
**Weight loss**
**Tiredness**
**Fever**
**Sweating**
_Common signs include:_
**Massive splenomegaly** (\>75%)
**Bleeding** (due to thrombocytopenia)
**Gout**
60
How do you make a diagnosis of CML?
Blood tests commonly show leukocytosis, in particular raised myeloid cells which include: **neutrophils, monocytes, basophils, and eosinophils.** Bone marrow analysis shows similar findings
61
Management of CML?
**Chemotherapy**
62
Prognosis of CML?
Median survival is **5-6 years.**
63
CLL is most common in ____ patients over the age of ___ . It is caused by the proliferation of functionally incompetent malignant ____ cells.
**Male**
**60**
**B-cells**
64
Clinical features of CLL?
CLL typically presents **asymptomatically**.
However, patients may present with:
**Non-tender lymphadenopathy**
**Hepatosplenomegaly**
**B-symptoms** (weight loss, night sweats, and fever).
Features of marrow failure (infection, anaemia, and bleeding) are _less common_ than in the acute leukaemias.
65
Diagnosis of CLL?
The most common initial blood result is an incidental lymphocytosis.
Subsequent **blood film** shows ***smudge cells***, which are cells damaged as they lack a cytoskeletal protein.
*Flow cytometry is then used to measure particular markers expressed by the malignant cells.* Other tests include immunophenotyping bone marrow biopsy.
66
A blood film of a patient suffering with CLL will show ____ cells.
Smudge Cells
- which are cells damaged as they lack a cytoskeletal protein.
67
Management of CLL?
Chemotherapy
68
Prognosis of CLL?
Rule of 1/3's:
**1/3 regress** (dont progress)
**1/3 progrees slowly**
**1/3 progress rapidly**
69
A _____ test detects antibodies or complement proteins that are attached to red blood cells and is used to detect haemolytic anaemias.
**Direct Coombs Test**
70
G6PD is an ______ red-cell enzyme disorder which may present in the neonatal period with jaundice, or later in life with episodic intravascular haemolysis following exposure to oxidative stressors.
X-linked recessive
71
The blood film of a G6PD patient typically shows ____ and _____ , and the diagnostic test is a _____ assay.
**Heinz bodies** (think glucose in heinz ketchup)
**bite cells** (heinz makes you wanna bite)
G6PD enzyme
72
Medications for restlessness and confusion
**Haloperidol**
**Levomepromazine** (broad spectrum but can cause tiredness)
**Midazolam**
73
**Medications for nausea and vomiting in palliative**
**Levomepromazine**
**Cyclizine**
**Haloperidol**
**Metoclopramide**
74
**Medications for breathlessness in palliative patients**
**May be a result of disease process (e.g. lung cancer, anaemia)**
**Therapeutic oxygen**
**Morphine**
**Midazolam (syringe driver)** or **Lorazepam (oral)**
75
**Medications for pain in palliative**
**Morphine**
First line for pain management
Good for all types of pain
Monitor for constipation
Monitor for unwanted sedation
**Diamorphine**
**Oxycodone** and **Alfentanyl (needs specialist palliative input)** - both useful for patients with _renal failure_ who cannot take morphine
\*Conversion of patient's usual daily dose of opiate analgesia to a 24 hour dose for use via a syringe pump, with 1/6-1/10 of the daily dose prescribed as 'breakthrough' analgesia. Should be reviewed every 24 hours.
76
What four items may you wish to discuss during an advanced care planning (ACP) meeting with a patient and family?
77
Carcinoid syndrome is the collection of symptoms some people with a ______ tumour may have.
It is more common when the tumour has spread to the ____ and releases hormones such as serotonin into the bloodstream.
Neuroendocrine
Liver
78
Tumour lysis syndrome is a common oncological emergency. It is associated with rapid cell death on starting chemotherapy and is common in tumours which are rapidly proliferating. These are classically haematological malignancies such as leukaemia and lymphoma.
**Clinical features**
It results in an increase in serum \_\_\_\_\_, \_\_\_\_, _____ precipitating renal failure.
Common symptoms include nausea, vomiting and muscle pain.
**Management**
Management focuses on preventing this from occurring through giving prophylactic _____ and in some cases a recombinant urate oxidase, rasburicase. Good hydration should be maintained.
*UPP*
**urate**
**potassium**
**phosphate**
\*and hypocalcaemia - n+v and muscle cramps i.e tetany\*
Deposition of uric acid and calcium phosphate crystals in the renal tubules may lead to an **AKI/acute renal failure**, which is often exacerbated by concomitant intravascular volume depletion due to the shift of potassium/phosphate and nuclei acids into the extracellular space - overwhelming normal homeostatic mechanisms.
**allopurinol**
79
Patient with clinical features suggestive of (malignant) spinal cord compression or cauda equina syndrome should have an urgent WHOLE spine MRI, with an aim (in appropriate cases) to surgically decompress within ____ hours.
In patients where malignancy is demonstrated on MRI, or in patients where clinical suspicion is high, administration of ____ mg daily in divided doses (with PPI cover) is indicated.
48
dexamethasone 16mg
80
\_\_\_\_\_ is the most frequently agent in chemotherapy to treat nausea and vomiting
Ondansetron
81
Tumour lysis syndrome occurs ___ days after chemotherapy whereas neutropenic sepsis is more likely to occur ___ days after chemotherapy.
A few days (around 3)
10 or more days
Tunour lysis syndrome is a condition which typically presents a few days after chemotherapy and is common for haematological malignancies, particularly **non-Hodgkin lymphomas**. The administration of chemotherapy can cause **significant cell death** in mitotically active tumours, resulting in the **extravasation** of intracellular contents such as **nucleic acids into the circulation.** These are then broken down into **uric acid and phosphate**. Uric acid can precipitate in renal tubules leading to an **acute kidney injury**, which may cause the anuria as reported by this patient. **Raised phosphate levels sequester free Ca2+ ions in the bloodstream, leading to hypocalcaemia and its characteristic symptoms, such as tetany (cramps) and vomiting**.
This man has significant risk factors for tumour lysis syndrome and combined with anuria means that he may have an acute kidney injury. The most appropriate management for this should be fluid resuscitation in the first instance, particularly given his hypotension.
82
\_\_\_\_ is a centrally-acting histamine H1 receptor antagonist and is the anti-emetic of choice in bowel obstruction
Cyclizine
83
Radiotherapy for breast cancer does increase the risk of future ____ cancer. It is important to consider the delayed side effects of radiotherapy.
**Lung**
84
The classic symptoms of hypercalcaemia can be remembered with the mnemonic \_\_\_\_
"stones, bones, groans, thrones, psychiatric overtones".
"Stones" refers to kidney stones, nephrocalcinosis, and diabetes insipidus (polyuria and polydipsia). These can ultimately lead to kidney failure.
"Bones" refers to bone-related complications. The classic bone disease in hyperparathyroidism is osteitis fibrosa cystica, which results in pain and sometimes pathological fractures. Other bone diseases associated with hyperparathyroidism are osteoporosis, osteomalacia, and arthritis.
"Abdominal groans" refers to gastrointestinal symptoms of constipation, indigestion, nausea and vomiting. Hypercalcemia can lead to peptic ulcers and acute pancreatitis. The peptic ulcers can be an effect of increased gastric acid secretion by hypercalcemia.
"Thrones" refers to polyuria and constipation
"Psychiatric overtones" refers to effects on the central nervous system. Symptoms include lethargy, fatigue, depression, memory loss, psychosis, ataxia, delirium, and coma.
85
In non smokers which is the most likely lung cancer to get?
adenocarcinoma (most common lung cancer full stop)
86
Studies have shown CXR will pick up ___ % lung cancers and miss \_\_\_\_% (false negatives)
Thus what do you need to do in a patient where you highly suspect lung cancer?
80
20
Review patient, consider referral 2ww- especially higher risk patients with normal CXR
Risk factors: smoking, \>75, occupational exposures, DXT to chest, Immunosuppression
87
Common classes of chemotherapeutics and their mechanism of action.
**Anti-metabolites** (ex. Methotrexate/ Gemcitabine)
* Inhibit DNA synthesis
**Alkylating Agents** (ex. Etoposide)
* Prevent uncoiling of DNA (ex. topoisomerase inhibitors)
* Non-classical alkylating agents (ex. cisplatin/carboplatin) interfere with DNA cross linking.
**Vinca Alkaloids** (ex. vincristine/vinblastine)
* Cell arrest by preventing microtubule formation
**Anti-mitotic antibiotics** (ex. non-anthracyline - Bleomycin)
* _Intercalation_ - inhibiting DNA synthesis
* _Membrane binding_ - Increased permeability and destruction
* _Free radical formation_ - disruption of the DNA chain nd prevening mitosis alkylation - blocking DNA replication
**Taxanes**
* Spindle cell inhibition
88
\_\_\_ can be given in patients suffering from neutropenic sepsis to stumulate bone marrow production of white blood cells.
**_G-CSF_** - **Granulocyte Colony Stimulating Factor**
89
A partial response to chemotherapy is denoted by a \_\_\_\_% decrease in disease from baseline.
30
90
Progressive disease is denoted as a \_\_\_% increase in one or more lesions.
20
91
The criteria used to measure response to chemotherapy is called ____ criteria.
**RESIST**
92
Toxicity of chemotherapeutics is measured in severity by using the \_\_\_\_\_\_
Common Terminology Criteria for Adverse Events (CTCAE)
Grade 1 - mild symptoms from adverse event
to
Grade 5 - death from adverse event
93
Which chemotherapeutics require renal function monitoring?
"CIMP"
**Platinum agents** (ex. cisplatin)
**Methotrexate**
**Ifosphamide** (alkylating agent)
**Capecitabine** (pro-5U drug)
94
Which chemotherapeutics require more stringent liver function monitoring?
\*TEA\* - "llyods liver"
**Taxanes**
**Etoposide (alkaloid)**
**Anthracyclines**
95
Personalised Medicine in Oncology now can prevent serious adverse events occurring based on the patients genotype
* _____ typing in irinotecan dosing
* _____ deficiency in 5-FU toxicity –this is now done routinuely
People with these genes are not given these drugs as they will develop an extremely toxic reaction - mucocitis/diarrhoea/dehydration/ICU.
**UGT1A1**
**DPD**
96
In oregan and switzerland ___ is illegal but ____ is legal.
Active euthanasia - illegal
Physician assisted suicide (PAS) - legal
97
Cell Cycle independent Chemotherapeutics?
Platinum agents (cisplatin/carboplatin)
Alkylating agents (ex. doxorubecin)
\*think metals\*
98
Febrile Neutropenia can be defined as a temp \> ____ and a neutrophil count \< \_\_\_\_
38 degrees
0.5 ×109/L
99
A ____ score is used to determine risk of febrile neutropenia in cance patients.
A score of \> ___ is considered low risk
**MASCC** (Multinational Association for Supportive Care in Cancer)
**\> 21**
\***YOU WANT A HIGH SCORE**\*
100
\_\_\_\_ % of patients with a known malignancy develop hypercalcaemia.
30%
101
Management of Hypercalcaemia in cancer patients.
* **Vigorous fluid rehydration** (4L in 24hrs unless elderly and frail)
- Monitor for signs of fluid overload and electrolytes
- Recheck serum calcium before bisphosphonates
* Give **bisphosphonates** _after 24 hrs of fluid rehydration_:
1st line : **Zoledronic acid** (4mg IV)
*_Wait at least 5 days_* before further treatment as bisphosphonate action takes time.
2nd line: **Pamidronate**
* **Haloperidol** is anti-emetic of choice in hypercalcaemia
\**Bisphosphonates inhibit osteoclast activity reducing calcium release*\* - importantly they may prevent a recurrence unlike fluid rehydration
* Use of **_RANK ligand inhibitors_** (**Denosumab**)
102
Hypercalcaemia is defined as correct calcium \>\_\_\_\_ mmol/L.
2.65 mmol/L
103
Management of metastatic spinal cord compression (MSCC):
Emergency management:
**Urgent MRI** (\<24hrs)
Steroids: **Dexamethasone** 8mg BD PO (early in day as possible to help sleep) + PPI - to prevent gastric bleed
**Pain Management** (WHO pain ladder)
**Catheterisation/Laxatives**
Definitive management:
**Surgery** or **radiotherapy** (palliative)
Surgery only indicated if prognosis is \> 6 months and/or singular lesion
Offer patients with vertebral involvement from **myeloma or breast cancer bisphosphonates** to reduce pain and the risk of vertebral fracture/collapse.
104
\_\_\_\_ can be used temporarily in palliative patients to stimulate appetite.
Dexamethasone
105
The EGFR cell signalling pathway is a target of many immunotherapies as it is involved in _____ and \_\_\_\_\_\_.
Cell proliferation
Inhibition of apoptosis and cell survival
106
Monoclonal antibodies work on the outside of the cell whereas Tyrosin Kinase inhibitors work on the \_\_\_\_.
Inside of the cell with various protein targets.
107
Patients with a ____ mutation will not respond to cituximab treatment for colorectal cancer.
KRAS
108
Patients with a _____ mutation will respond _much better_ to treatment with Erlotinib in the treatment of NSCLC.
EGFR
\*becomes 1st line if patient has EGFR mutation\*
109
Olarparib is a ____ inhibitor used in the treatment of ____ positive ____ cancer. It is used primarily as a maintenance therapy following a platinum chemotherapy agent (ex. carboplatin)
PARP - inhibit DNA repair mechanisms
BRCA
Ovarian
PARP - _poly adenosine diphosphate-ribose polymerase_, a type of enzyme that helps repair DNA damage in cells
110
Patients with metastatic breast cancer confined to the bone can often have quite a good prognosis with _____ (herceptin)
Trastuzumab
\*useful in adjuvant and metastatic breast cancer\*
\*important to remember this is a mab and not a chemotherapeutic agent and thus you do not get the same degreeof immunosuppressive side effects as chemo\*
111
\_\_\_\_ is a downstream cell signalling protein in the EGFR cascade that can be targeted in melanoma treatment. This treatment can be enhanced by dual immunotherapy by combining with a ____ inhibitor.
**BRAF**
**MEK**
\*Takes cancer longer to overcome both cell signalling protein inhibtion\*
112
What is the difference between immunotherapies and targeted therapies?
**Targeted approaches** aim to **inhibit molecular pathways** that are critical to tumor growth and maintenance, whereas **immunotherapy** **stimulates a host response** that effectuates long-lived tumor destruction.
113
Anti-\_\_\_\_ and anti-\_\_\_\_ antibodies target so called "immune checkpoint" proteins, thereby activating the immune system to recognise and destroy cancer cells. In the process, the immune system becomes less discriminate at targeting healthy cells within the body, leading to various autoimmune sequelae.
**• CTLA4 - ipilimumab**
**• PD1/PD-L1 –nivolumab, pembrolizumab**
**https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/immunotherapy/types/checkpoint-inhibitors**
114
\_\_\_\_ trial is a type of clinical trial that tests how well a new drug or other substance works in patients who have different types of cancer that all have the **same mutation or biomarker**. Patients all receive the same treatment that targets the specific mutation or biomarker found in their cancer.
Basket trial
115
3 main types of radiotherapy:
* **External Beam Radiotherapy** or **Teletherapy (ex. stereotactic)**
* **Brachytherapy** (radioisotope is delivered directly to the tumour site itself via catheter etc) - "inside out radiotherapy"
* **Targeted Radionucleotide therapy** / systemic radiotherapy (ex. injected into bloodstream and finds tumour. Endocytosed and then emits gamma ray - iodine for thyroid tumours)
https://www.youtube.com/watch?v=6lqnMIwplcE
116
\_\_\_\_ takes advantage of the differential DNA repair mechanisms between Normal and tumour cells to deliver staggered radiotherapy to tissues.
Fractionation
Hyperfractionation means more number of doses
Hypofractionation means less regular doses but of a higher intensity
117
Radiotherapy like chemotherapy is most effective in the ___ and ___ phases of the cells cycle
G2 (growth) and particularly M phase (dividing)
118
The _____ (RAD) is the traditional unit of radiotherapy and corresponds to the amount of radiation absorbed per unit mass of tissue
This _modern_ unit is known as the _____ and corresponds to Joules absorbed per kg of tissue mass (J/kg).
**Radiation absorbed dose**
**Gray unit** (Gy)
119
Stages of grief
1. **Denial**
2. **Anger**
3. **Bargaining**
4. **Depression**
5. **Acceptance**
\*Of course this varies greatly between patients\*
120
Immunohistochemistry indicators of primary source of malignancy?
1st line screen:
Carcinoma - **Cytokeratin (e.g AE 1/3 / Cam 5.2 / MNF116)**
Lymphoma - **CD45** / **CD3**(_T-cells_)/ **CD20**(_B-cells_)
Melanoma - **Melan A** / **HMB45** / **S100**
If none of these 2nd line screen:
Germ cell tumour
Sarcoma
Mesothelioma - **Calretinin/ CK5/6 /WT1**
121
IHC can be used to establish subclassification of carcinoma.
Squamous markers - \_\_\_\_\_\_
Adenocarcinoma markers - \_\_\_\_\_\_
Neuroendocrine - \_\_\_\_\_\_
Squamous cell:
**P63** and **CK5/6**
Adenocarcinoma:
**CK7** and **CK20**
Neuroendocrine:
**Synapto****_phys_**in/ Chromogranin A / Ki-67
122
Routine tests done for molecular analysis of tumours.
_Breast cancer_ **- ER** /**PR**/ **HER-2** / **Oncotype Dx**
_Gastric Cancer_ - **HER-2**
_Colorectal Cancer_ - **KRAS**/ **NRAS** / **BRAF**/ **MMR**
_Lung Cancer_ - **EGFR** / **ALK/** **PDL-1**/ **ROS-1**
_Melanoma_ - **BRAF**
_GIST_ - **KIT** / **PGDFRA**
123
General Biochemical effects of Cancer
124
\_\_\_\_\_ effect in biochemistry is when the tumour marker level is so high it can actually swamp the detection system and so it is not present at the concentration you would expect.
Hook
125
\_\_\_\_\_ can be used by specialists as a tumour marker for late stage or metastasized breast cancer.
**CA15.3**
126
\_\_\_\_ is a tumour marker that can be used to monitor therapeutic response in pancreatic cancer but is generally not used for diagnosis due to it's low specificity and sensitivity.
It is also known as ____ antigen (protein on surface of RBC) and 10% of the caucasian population will not express it, it is thus not very reliable.
Ca19-9
Lewis Antigen
127
PSA can help to establish a diagnosis of Prostate cancer.
Malignant prostate cells tend to produce more ____ PSA whereas BPH/Prostatitis/normal prostate produces more ___ PSA.
Malignancy - Lots of Bound PSA
Benign - Lots of free PSA
128
Tumour Markers:
\_\_\_\_\_ (thyroid cancer)
\_\_\_\_\_ (medullary thyroid cancer)
\_\_\_\_\_\_ (Multiple myeloma and Waldenström macroglobulinemia)
\_\_\_\_\_\_ (Multiple myeloma, chronic lymphocytic leukemia, and some lymphomas)
\_\_\_\_\_ (leukaemia)
**Thyroglobulin**
**Calcitonin**
**Immunoglobulins** (SERUM AND URINE)
**β2 Microglobulin**
**JAK2 gene mutation**
129
Carcinoid tumours arise from the ____ cells of the foregut/midgut/hindgut.
They primarily secrete \_\_\_
They can be tested in the lab by looking at a 24hr urine \_\_\_\_.
However the best test for identifying carcinoid tumours is \_\_\_\_
**Argentaffin**
**Serotonin**
**5HIAA** (breakdown product of serotonin)
**Chromagranin - A**
\*note can also be raised in pheaochromocytoma\*
130
\_\_\_ gene is affected in MEN1, whereas the ____ gene is affected in MEN2 (A+B)
**MEN1 gene**
**RET Proto-oncogene**
131
\_\_\_\_ cells with their optically clear nuclei are pathognomonic of **_papillary_** thyroid cancers
**Orphan-Annie**
Papillary thyroid carcinoma findings are Orphan Annie Eye nuclei and papillae often associated with Psammoma bodies
132
Small cell lung cancers are commonly located in the \_\_\_\_.
**bronchus**
133
What are the red flags for metastatic spinal cord compression back pain?
SUMMARY: (**Pain / Motor dysfunction / Sensory dysfunction / bladder and bowel
dysfunction.**)
**1. Severe unremitting spinal pain**
**2. Spinal pain aggravated by straining** (opening bowels, coughing, sneezing)
**3. Nocturnal spinal pain preventing sleep**
**4. Sensory loss / disturbance like numbness, pins and needles sensation or
paraesthesia**(50% of patients have sensory loss)
**5. Localised _central_ spinal tenderness**
**6. Limb weakness (**75% patients**), mobility deterioration and sphincter disturbance** (at a later
stage)
\*if patient does not have back pain it is unlikely to be spinal cord compression - 90-95% patients will have back pain\*
134
WHO pain ladder and examples
135
Management of a patient presenting with acute MSSC?
1) Thorough **history and examination** (including neurological and PR exam) to
identify neurological deficits.
2) Referral for **imaging**: **whole spine MRI** scan is the _gold standard_ for suspected
metastatic spinal cord compression.
3) If spinal cord compression is suspected - **commence high dose
Dexamethasone 16 mg stat then 8 mg BD** _until_ imaging complete.
Follow local policy for urgent investigation and a **protein pump inhibitor** (e.g.
Omeprazole or Lansoprazole) if needed.
4) If _pain is not controlled_ by step 2 of analgesics, we would **escalate to step 3 (strong opioids + non opioids).** This means commencing the patient on an opioid preparation (preferably on M/R (modified release) opiate, given he was taking step 2
analgesia) and stopping codeine PRN.
**Consider co-prescription of a laxative and / or an antiemetic.**
Additional Screen:
- FBC (rule out infection and neutropenia)
- U+E's and LFT's before opiate
- Bone Scan
- Myeloma Screen
(Discussion points: timescale for requesting urgent imaging, within a week vs within
24 hours - depending on clinical scenario i.e Bladder/Bowel dysfunction)
138
Other than an MRI scan what investigations would be useful in a patient presenting with suspected MSCC?
1) **FBC, INR, LFTs and renal profile ? eGFR for scanning**
2) **Bone profile**? hypercalcaemia
3) **Glucose** - high dose steroids precipitate hyperglycaemia
4) **Consider LDH** - associated with poor prognosis
5) **Unknown primary** - consider a myeloma screen
6) **Bladder scan**
139
Side Effects of Opiates?
1) **Constipation**
2) **Nausea and Vomiting**
3) **Drowsiness**
4) **Delirium**
5) **Xerostomia**
6) **Pruritus**
7) **Rarely: hyperanalgesia, allodynia** (pain on touch)
8) **Opioid toxicity**: drowsiness, hallucinations, confusion, vomiting, myoclonus,
pinpoint pupils and respiratory depression (if severe).
140
Presentation of Opiate Toxicity?
**Drowsiness**
**Hallucinations**
**Confusion**
**Vomiting**
**Myoclonus**
Pinpoint pupils and respiratory depression (if severe).
141
What are the indications for using a continuous subcutaneous infusion?
**Poor swallow and unable to tolerate essential medications** like analgesia and
anti-seizure medication.
**Reduced consciousness** and requiring essential medications like analgesia
and anti-seizure medication.
If requiring **more than two doses of an injectable medication within 24 hours**.
**Vomiting and nausea**.
If **absorption via the oral route is impaired,** for example bowel obstruction.
142
A patient who is thought to be dying should have an individualised
care plan reflecting their unique needs. What should be
considered within this plan?
- An individualised plan of care should be developed for the care ofa patient likely to be dying and those important to them including:
**- Preferred place of care and death.**
**- Current and anticipated needs, including preferences for
symptom management, including anticipatory medications.**
**- Any care needs after death.**
**- Religious / spiritual needs.**
**- Personal goals and wishes.**
**- Resuscitation status.**
**- Review of long-term medications.**
**- Physical needs.**
**- Eating and drinking, including hydration status.**
**- Concerns regarding their significant carers.**
143
Hodgkin Reed Sternburg cells express ___ in virtually all cells and ____ in the majority of Hodgkin lymphomas.
Remember Reed Sternburg cells can exist in other lymphomas and this is why they are now referred to as Hodgkin Reed Sternburg (HRS) cells solely when they are seen in Hidgkin's lymphoma
**CD 30**
**CD15**
**CD30**, also known as TNFRSF8, is a cell membrane protein of the **tumor necrosis factor receptor** family and tumor marker
144
Which patients should be discussed with the Coroner?
**- unknown cause of death**
**- death following an accident – road, work, inpatient**
**- not seen within the last 28 days by a clinician (COVID changes),
may return to pre COVID of 14 days**
**- post operative death**
**- any suggestion of neglect, poor care**
**- death in detention – custody, prison, section**
**- industrial illness eg. mesothelioma**
**- suicide**
145
The presence of ____ and ____ cells (\< ___ % of cells in involved
nodes) defines the Hodgkin lymphoma.
Remember Reed Sternburg cells can exist in other lymphomas and this is why they are now referred to as Hodgkin Reed Sternburg (HRS) cells solely when they are seen in Hidgkin's lymphoma.
Reed-Sternberg cells and Hodgkin
\<1%
147
Hodgkin lymphomas are divided into classic Hodgkin lymphoma and _____ Hodgkin lymphoma (WHO).
The classic Hodgkin
lymphomas (95% of cases) are further subtyped into:
\_\_\_\_\_ (constitutes 60 - 80%), characterised by dense \_\_\_\_
bands dividing lymph nodes into nodules.
\_\_\_\_\_ (20% cases) and has prominent ____ infiltrate.
Lymphocyte- ____ .
Lymphocyte-rich.
The last two subtypes are rare.
**Nodular lymphocyte predominant**
Nodular sclerosis - collagenous bands dividing lymphocytes into nodules
Mixed cellularity - eosinophilic infiltrate
Lymphocyte - depleted
Lymphocyte-rich
148
The ____ Cells are pathognomonic of Hodgkin lymphoma. They have _____ nuclei with prominent _____ nucleoli.
These cells haverearranged and somatically mutated immunoglobulin VH genes.
These cells are B-cell in origin but show global loss of B-cell phenotype. This is due to loss of expression of B-cell genes.
Genetic lesions in HRS cells involve two main signalling
pathways, including the ____ pathway and the ____ pathway.
**Reed-Sternburg**
**bi-lobed kidney-shaped**
**eosinophilic**
**JAK-STAT**
**NF-kB**
*The HRS cells secrete various cytokines and chemokines, which are responsiblefor the presence of inflammatory infiltrate around HRS cells.*
149
The precise aetiological agent has not been identified, but there is a pathognomonic role of ____ in ~ 40% of classical Hodgkin lymphoma.
**EBV**
EBV nucleic
acids and proteins have been detected in these cases.
150
Any new lump in adults should be investigated as ____ until proven otherwise.
**malignancy**
151
Hodgkin lymphoma most commonly presents with ___ enlargement of lymph nodes in the ___ or the ____ area.
60% of cases present with
involvement of the mediastinum. One quarter of cases show retroperitoneal LAP.
Mediastinal mass detected either incidentally or for the investigation of respiratory symptoms (cough, SOB or chest pain / discomfort) is also common.
Pain at the site of involved lymph nodes with ____ is unusual but characteristic finding.
**painless**
**neck** or **supraclavicular**
**alcohol intake**
152
\_\_\_\_ fever (high fevers for one to two weeks alternating with afebrile period of around one week) is almost diagnostic for ____ .
Cytopenia related to bone marrow infiltration, cholestasis related to hepatic involvement and autoimmune presentations, like AIHA, ITP or neutropenia, are rare
forms of presentation.
The frequency of splenic involvement is ~ ___ % and is most common in the MC and
LD subtype
**Pel-Ebstein**
Hodgkin's lymphoma
Splenic involvement is around **35%** and most common in **Mixed cellularity** and **Lymphocyte dense** subtype
153
The diagnosis of Hodgkin's Lymphoma is only confirmed by ____ investigations.
The biopsy of involved node should be done immediately. The excision biopsy is ideal but a quick way is to request core biopsy under radiological guidance.
\_\_\_\_ , ____ and on ____ cells are diagnostic. The cell markers may vary in different subtypes of Hodgkin lymphomas.
**Histological**
**CD30+, CD15+ CD20-**
**HRS** (Hodgkin's and Reed Sternburg cells)
There are no diagnostic laboratory features of Hodgkin lymphoma.
FBC may show anaemia (AOCD, AIHA), thrombocytopenia (marrow involvement with Hodgkin lymphoma, ITP or splenomegaly), neutropenia, lymphopenia or
eosinophilia.
**LDH** is raised in 35% cases and raised **beta 2-microglobulin** levels (normal renal function) _represents the burden of disease._
* *Hypercalcaemia** is _unusual_ in Hodgkin lymphoma (vitamin D secretion by HRS
cells) .
154
What radiological modalities can be used in the diagnosis and
management of Hodgkin lymphoma, and describe their clinical significance?
**1. X-ray**: can be used for symptoms of SOB, chest pains and cough. Shows a widened mediastinum in the presence of mediastinal LAP (lymphadenopathy).
**2. USG**: ultrasound is used as an initial investigation for assessment of cervical or supraclavicular lymph nodes. Ultrasound can be used for guiding core biopsies and
to assess the spleen size.
**3 CT staging**: CT scanning is used in guiding biopsy and in the staging of Hodgkin
lymphoma.
**4. PET scan:** useful in assessing the accurate staging of Hodgkin lymphoma. PET- adapted treatment of Hodgkin lymphoma has become a standard of care, though is still a bit controversial. Patients are assessed with a PET CT after two cycles of
chemotherapy and help decide to escalate or de-escalate the treatment to prevent long-term toxicity. PET CT can be used to determine whether IFRT (involved field
radiotherapy) is needed in individual patients with early stage disease.
155
Please describe the various treatment modalities used for Hodgkin
Lymphoma?
**Radiotherapy**
IFRT (Involved-field radiation therapy i.e localised) is used to treat early stage disease along with chemotherapy. Localised residual disease can be treated with radiotherapy. SVC obstruction at the time of presentation may require radiotherapy.
**Chemotherapy**
The choice of chemotherapy is decided by the patient’s performance status, age and stage of the disease. The standard of care in fitter patients is _ABVD chemotherapy._ The BEACOPP, or escalated BEACOPP, are used in younger patients who are still PET positive after two cycles of ABVD.
**Chemo-immunotherapy** (brentuximab vedotin)
This agent is used in patients who are _resistant to initial chemotherapy or relapse after first-line treatment_. This can be
used as a bridge to an autologous stem cell transplant.
**Immunotherapy**
Immune check point inhibitors (PD-1 / PDL-1 inhibitors). These
include *nivolumab* and *pembrolizumab*.
**High-dose chemotherapy and autologous stem cell transplant**.
**Allogenic bone marrow transplant.**
156
Following a triple screen for breast cancer (i.e FNAC or core biopsy/Mammogram/Ultrasound/examination) what further investigations would you like?
Summary:
**Grade**
**Stage**
**Receptor status**: _oestrogen_ receptor, _progesterone_ receptor and _HER2_.
**Bone Scan**
**ECG**
**Echocardiogram**
**FBC/U+E's/LFT's**
Details
Staging CT scan and a bone scan.
ECG and a cardiac echocardiogram.
**Grading** in breast cancer is determined by the pathologist –
1= low grade,
well differentiated cancer cells
2= moderate
3 = high grade, poorly
differentiated cancer cells.
**Staging** in breast cancer follows the TNM system:
* *T**: is carcinoma in situ
* *1:** \<2cm
* *2:** 2-5cm
* *3:** \>5cm
**4:**
a) Invading chest wall
b) Invading skin
c) Invading skin and chest wall
d) Inflammatory Breast Cancer
**N**: may be assessed _clinically,_ where usually
cN1 = mobile axillary nodes
cN2 = fixed axillary node
cN3 = nodes beyond the axilla
Or _post-op/pathologically_, where
**pN1** = 1-3 axillary or internal mammary nodes
**pN2** = 4-9 axillary/ internal mammary nodes
**pN3**= 10+ axillary/ internal mammary
nodes or infra/supra clavicular nodes.
**M**: 0 = no metastases, 1 = metastases, most commonly bone, liver, lungs, brain.
157
What are the treatment options for breast cancer?
**Neoadjuvant Chemotherapy**
shrinks tumour before surgery
**Adjuvant chemotherapy**
aims to reduced recurrence systemically - Oncology Dx score used to determine if patient is likely to benefit for this treatment i.e are they likely to have a recurrence - delivered every 2/3 weeks
**Radiotherapy**
targeted therapy to chest wall to prevent local lymph node recurrence - given week days for 1-3 weeks.
**Hormone therapy**
tamoxifen SERM / an aromatase inhibitor (AI, for eg. letrozole, anastrazole, exemestane. The latter are only effective in post-menopausal women, whose main oestrogen supply comes from the
aromatisation of testosterone in their adipose cells.
**Immunotherapy**
Ex. Trastuzumab is used to target the HER2 receptor in 20% of cancers.
**Palliative**
Chemotherapy and Immunotherapy can also be used in metastatic disease for symptom control (ex. Checkpoint inhibitors atezolizumab in metastatic TNBC and the CK 4/6 inhibitor palbociclib which is
used first line in ER+ HER2 –ve metastatic breast cancer.
158
What other patient factors need to be considered to provode holistic care in Breast Cancer?
The need for referral for **genetic counselling and testing** for germ line mutations for pathogenic mutations in **BRCA1 and BRCA2**.
The possible effect of treatment on **reproductive function** / **fertility** and possible **early menopause**.
To provide holistic care need to consider:
- **Psychological** issues / needs
- **Social** issues
- **Spiritual** issues
159
Name the common causes of microcytic/normocytic/macrocytic anaemia?
160
The most common genetic mutation causing primary polycythaemia is a mutation in the ____ gene.
JAK2
161
The clinical features of multiple myeloma can be remembered by the mnemonic CRAB HAI:
Hyper(**C**)alcaemia: this arises primarily due to increased osteoclast-mediated bone resorption.
(**R**)enal impairment: this occurs due to multiple factors e.g. light chain deposition in the kidneys and hypercalcaemia.
(**A**)naemia: note that due to marrow infiltration by the tumour other cytopenias can occur (e.g. thrombocytopenia and leukopenia).
**(B**)one pathology: osteolytic lesions are common. This can lead to pathological fractures and vertebral compression fractures.
(**H**)yperviscosity: this can present with headache, visual disturbances, and thrombosis.
(**A**)myloidosis (AL): this has multiple sequelae including e.g. cardiac failure and neuropathies.
(**I**)nfection: recurrent infection occurs secondary to leukopenia and immunoparesis (there is low levels of functional IgG).
Paraprotein = abnormal antibodies produced by the immune system (ex. usually abnormal IgG or IgA or free light chains antibodies) - **accumulate in the blood or bone marrow or both**
162
\*Beware ____ infection (pneumonia) in patients with febrile neutropenia as can be life threatening.
Invasive Aspergillosis
163
Most common leukaemia is \_\_\_\_
CLL
164
Myeloproliferative Disorders are caused by \_\_\_\_
Overproduction of _mature_ cells in the bone marrow - known as a disorder of _high blood counts_
165
Multiple myeloma can be defined as the malignant accumulation of _____ cells in the bone marrow
Plasma cells (B-Cells that make antibodies)
166
In multiple myeloma multiple lytic lesions in the skull is often referred to as "\_\_\_\_\_ skull"
Pepper Pot
167
\_\_\_\_\_ lymphoma is can be high grade (usually fast growing) or low grade Non Hodgkin's Lymphoma.
Burkitts (this is how you spell it)
168
How would you investigate and diagnose hodgkin's lymphoma?
Surgical or radiological biopsy
Remember staging using **Ann Arbor system**
169
Lymphoma is staged using the ___ system.
**Ann Arbor (CT and PET)**
**Stage 1:** Single site
**Stage 2:** One side of the diaphragm
**Stage 3:** Both sides of the diaphragm
**Stage 4:** Outside lymph nodes (i.e bone marrow)
170
Lymphoma management comprises of _____ .
Chemotherapy +/- Radiotherapy
171
What are the causes of nausea and vomiting in palliative patients?
**TREATMENT**
• Chemotherapy
• Radiotherapy especially brain and
GIT
• Opioids
• NSAIDs
• Antibiotics
**• PHYSIOLOGICAL**
• Constipation
• Gastric stasis/outlet obstruction
• Raised intra cranial pressure
• Bowel obstruction
• Hepatomegaly
• Cough
**• METABOLIC**
• Hypercalcaemia
• Hyponatraemia
• Liver failure
• Uraemia
• Hyperkalaemia
• Infection
* **PSYCHOLOGICAL**
* Anticipatory
* Anxiety
* Fear
* Fatigue
172
Metaclopramide and Domperidone should be avoided in ____ and ____ because they are prokinetic and \_\_\_\_
**Mechanical Bowel Obstruction**
**CVD**
**Prolong the QT interval**
\*remember domperidone does not cross BBB and so has less extrapyramidal side effects and is safe to use in parkinsons patient\*
173
Important receptor targets in Nausea and Vomiting (palliative)
Vomiting Centre \_\_\_\_\_
Chemoceptor Trigger Zone \_\_\_\_\_\_
GIT \_\_\_\_\_
Vestibular Apparatus \_\_\_\_\_
Vomiting Centre - Cyclizine
Chemoreceptor Trigger Zone - Haloperidol and Ondansetron
GIT - Ondansetron
Vestibular apparatus - Cyclizine
174
Causes of Constipation
175
Management of Constipation
**Non-Pharmacological**
* Tailored to any reversible causes.
* Diet, fluid intake and mobility.
* Environmental factors should also be discussed e.g. correct posture; suitable and accessible toilet facilities (e.g. toilet seat raisers); allowing adequate time.
* Privacy and dignity.
* Changes to a persons’ care and regimen should be minimised in order to avoid constipation.
* Secondary to spinal cord compression: maintain a regular schedule for toileting. E.g. alternative day suppositories.
* Medications should be reviewed regularly to minimise constipation
* Related factors such as reduced mobility, reduced food intake, weakness and dehydration should be addressed where practical and appropriate.
176
How does a rectal exam help you decide on suppositories to give in constipation?
How to choose a laxative ?
Rectal – quicker result.
Oral – usually patient preference.
_Stimulant_ – if _reduced frequency_ of stool. (ex. domperidone / metaclopramide)
Softener – if hard stools.
Mixed – if both.
Trial and error, often patients describe a mixed picture.
177
Important Receptors in N+V
Cyclizine acts at \_\_\_\_
Domperidone and Metoclopramide \_\_\_\_\_
Haloperidol \_\_\_\_\_
Prochloperazine \_\_\_\_
Ondansetron \_\_\_\_
Levomepromazine \_\_\_\_
**Cyclizine** - Anti-histamine/ Anti-cholinergic
**Domperidone** / **Metoclopramide /Haloperidol**- Dopamine receptor antagonists - CTZ
**Prochloperazine -** mainly Dopamine antagonist but also acts at histamine and 5HT - Mainly Vestibular apparatus
**Ondansetron** - 5HT3 antagonist - Cerebral Cortex / CTZ / GIT
**Levomepromazine** - Most receptors (histamine 5HT dopamine etc)
\*Domperidone doesn't cross BBB and so doesn't cause extrapyramidal side effects\*
Remember: Vomiting centre is located in the medulla and so lies outside BBB, whereas CTZ is inside.
178
Non-pharmacological management of Nausea and Vomting
179
**Cyclizine**
Action:
Good for:
Side effects:
**Anti-histamine Anti-muscarinic** (Acts at all vomiting centres)
Central, Vestibular, Bowel Obstruction
Side effect - **Urinary retention** (thus not good in renal failure either) - antimuscurinic
180
**Ondansetron**
Action:
Good for:
Side effects:
**5HT antagonist** - GIT, Cerebral cortex, CTZ
Immediate chemo/radio therapy induced N+V
Gut irritation
**_Constipation_**
\*slows colonic transit so not good for hypomotility\*
181
**Haloperidol**
Action:
Side effects:
Good for:
**Dopamine receptor antagonist - CTZ**
**Extrapyramidal**
**Renal Failure** and **chemical toxicity (drugs, metabolic such as hypercalcaemia etc)**
182
**Hyoscine**
Action:
Side effects:
Good for:
183
**Levomepromazine**
Action:
Side effects:
Good for:
Sedating and anxiolytic
184
**Prochlorperazine**
Action:
Side effects:
Good for:
185
In Nausea and Vomiting which medications can be used for:
Chemical Toxicity (i.e metabolic - hypercalcaemia) and drugs \_\_\_\_\_\_
Motility Disorders \_\_\_\_
Bowel Obstruction \_\_\_\_\_
Raised ICP \_\_\_\_\_
Movement related vestibular \_\_\_\_
Post-op \_\_\_\_
Unknown\_\_\_\_
**Chemical Toxicity** (i.e metabolic - hypercalcaemia) and drugs
Dopamine antagonists (i.e _Haloperidol_, _Domperidone_, _Metoclopramide_)
**Motility Disorders** (i.e gastric stasis)
prokinetics - _Domperidone_ and _Metoclopramide_
**Bowel Obstruction**
_Anticholinergic_ (ex. Hyoscine/Cyclizine) - NB avoid prokinetics!
**Raised ICP**
_Cyclizine_ and _Steroid_
**Movement related/vestibular**
Anticholinergic or antihistamine - _Cyclizine_, _Hyoscine_, _Prochlorperazine_
**Post-op**
_Ondansetron_ (5HT3 antagonist)
**Unknown**
_Levomepromazine_ (though cyclizine often given in 'just in case' pack)
186
Opiates that can be used in renal compromise?
**Oxycodone** (Aim to avoid in SEVERE renal failure)
**Fentanyl** (useful for those with stable pain requiring strong opiates)
**Alfentanil** (if patient requires _syringe driver_ as fentanyl is transdermal) - thus can be used to titrate to patients pain quickly unlike fentanyl.
187
Anti-epileptic of choice in brain metastases is \_\_\_\_
Levetiracetam
188
The most common haematological malignancy?
**Non-Hodgkins Lymphoma**
2nd most common: Multiple myeloma
189
Which mnemonic can be used to break bad news to a patient?
SPIKE
## Footnote
**S** stands for **setting the scene.** This first part may be difficult to show in an OSCE situation. On the wards, doctors need to make sure that the setting is appropriately private. This means that bad news should preferably not be made behind a paper curtain, as this does not constitute real privacy. The doctor should also make sure that there are no disturbances: they should turn off their phone and hand their bleep to the nurse-in-charge if at all possible.
**P** stands for **perception**. This means that the candidate should make an obvious attempt early in the consultation to try and check the patient's understanding about what has happened so far. In this case, the patient has a very poor insight into the situation, which is not his fault. This makes the task much more difficult. It also highlights the importance of always making it clear, why certain investigations are being performed. If one doctor decides not to fully explain the situation, like the GP in this case, they will make the task much more difficult for the next clinician. If doctors are doing investigations to look for the possibility of cancer, the patient should be informed.
**I** stands for **invitation**. This is an invitation that the candidate gives to the patient - they will ask whether the patient wishes to know the results of the tests. It may be appropriate at this point to fire a "warning shot" so that they are aware that the news is not going to be good. Excellent candidates may also ask whether they would like to continue the conversation now or whether they would like someone with them. This signposts to the patient (and the examiner) that you are about to break bad news and you are being sympathetic to the patient's needs.
**K** stands for **knowledge**. This represents the need to actually convey the bad news to the patient. This needs to be done in an unambiguous, clear way. On the wards, patients often take in very little of what is said to them in these circumstances, therefore, it is a real test of the candidate’s communication skills. Excellent candidates will check understanding, allow the patient to ask questions and relay information in non-medical, universal terms.
**E** stands for **empathy**. This is self-explanatory. Despite what may be assumed, empathy can be learned and practiced. The more candidates practice these types of conversations, the better they will become at them. Stressed candidates are less likely to display empathy. Communication skills such as these are seen on the wards to different degrees. Excellent candidates will learn from what the good examples that they see on placement.
**S** stands for **strategy and summary.** This is the final stage of the conversation. Candidates should try and come up with a joint plan with the patient. They will also summarise the case and check understanding.
This station has the added complication that the patient is already upset with the health service in general. It is not uncommon for patients to have hidden agendas when coming into a consultation. Excellent candidates will be able to discuss the patient's concerns in a non-confrontational manner.
Excellent candidates will behave in a calm and considered manner, even if patients have insulted them or their profession. Candidates are likely to become frustrated with patients who behave in this way, however, they must remember that often there are very valid reasons. Doctors should always consult in a non-judgemental manner.
Although there is still some doubt in this case, as a histological diagnosis has not been made, candidates should not be overly optimistic or try and appease a distressed patient. This will only cause more pain in the long run as there is enough evidence to support the diagnosis of metastatic bowel cancer which has a poor prognosis.
Candidates should not guess about the prognosis if they do not know. It is impossible to answer the question "how long do I have left" with a precise length of time. Candidates should not attempt this. Excellent candidates will be honest and try to explain in an empathetic manner that they cannot answer such a question. They will reassure the patient that the whole multidisciplinary team will work hard to help the patient in every way possible.
190
"Breaking bad news" can be tackled using the "SPIKES" approach:
S: Setting
P: Perception
I: Invitation
K: Knowledge
E: Emotions and empathy
S: Strategy and summary
