Medicine D Flashcards

Question

Summarise carcinoid tumours

Answer 1

Carcinoid tumours arise from argentaffin cells located in the foregut, midgut and hindgut. These can be found in the bronchi, stomach, small intestine, appendix and rectum. They secrete serotonin and have also been found to secrete ACTH, histamine, dopamine, substance P, neurotensis, prostaglandins, and kallikrein. Possible features include episodic flushing, wheezing, diarrhoea, and right sided heart valve disease. Carcinoid tumour markers include 24hr urine 5HIAA as levels are not elevated with other types of tumours. 5HIAA is produced as a breakdown product of serotonin. Sensitivity is 73% and specificity of 100%. However, the level of 5HIAA only becomes elevated when carcinoid tumours have metastasised to the liver, making the potential for a cure unrealistic. 5HIAA testing is useful to estimate the extent of disease and prognosis. There may be a false positive test with foods rich in serotonin such as bananas, walnuts, plantains, pineapple, pecans, Kiwi and avocados. Drugs such as acetaminophen, aspirin (salicylates), guaifenesin and L-dopa can also interfere. Chromogranin A is considered as the best test for detecting carcinoid tumours, and for monitoring their activity. Elevated levels of CgA are found in 80-100% of patients with carcinoid tumours and used in diagnosis, assessment of treatment and evaluation of recurrence. A positive test result does not always indicate carcinoid tumours are present, because CgA levels can also be increased by neuroendocrine tumours (phaeochromocytoma).

Answer 2

Parathyroid, pancreatic islet cells, and pituitary tumours. Biochemical tests include fasting gut hormones (including gastrin), insulin/glucose, and pituitary hormones. There is a MEN1 gene

Answer 3

Medullary thyroid carcinoma, phaeochromocytoma, and hyperparathyroidism. The genes involved are RET proto-oncogenes. Possible biochemical tests include calcitonin (in known disease), CEA (staging), metadrenalines (plasma and urine), calcium, and PTH.

Answer 4

Medullary thyroid carcinoma, phaeochromocytoma, and marfanoid. The genes involved are RET proto-oncogene. Possible biochemical tests include calcitonin (in known disease), CEA (staging), and metadrenalines (plasma/urine).

Answer 5

A normal blood smear will contain normal neutrophils, lymphocytes, and RBCs. A bone marrow biopsy may be needed to confirm leukaemia. This may be a bone marrow aspirate which is smeared and stained, this can also be genetically tested, and antibody tested. The other option is bone marrow trephine which is where a sample of core is decalcified, sliced, and looked at histologically. In haematological malignancy the abnormal cells proliferate in the bone marrow and/or other organs to replace normal cells and reduce elements of the bone marrow which causes abnormal blood counts.

Answer 6

1. Leukaemia can be acute or chronic 2. Lymphoma: Hodgkin lymphoma, high grade non-Hodgkin lymphoma and low-grade non-Hodgkin lymphoma 3. Myeloma 4. Myeloproliferative neoplasms 5. Myelodysplastic syndromes

Answer 7

1. Acute myeloid leukaemia (AML) 2. Acute lymphoblastic leukaemia (ALL) Clinical features include fatigue, infection, bruising, bleeding, high white cell count, low Hb (anaemia), thrombocytopenia (low platelets) and low neutrophils (neutropenia). Pathophysiologically there is an accumulation of blasts at the expense of normal haemopoiesis.

Answer 8

Acute myeloid leukaemia has an incidence of 3/100000 and occurs mainly in the over 65s. It is associated with radiation, previous chemotherapy, congenital syndromes, and previous myelodysplastic syndrome. Features include tiredness, infection, and bleeding. Treatment is with 3-4 cycles of combination chemotherapy or haemopoietic stem cell transplants for some patients. There is an over 50% long term survival rate in fit patients and 1-20% in less fit patients.

Answer 9

Acute lymphoblastic leukaemia (ALL): This accounts for 30% of childhood cancers (600 cases per year in the UK) and 20% of adult acute leukaemia. Symptoms and signs include tiredness, bruising, bleeding, thrombocytopenia, weight loss, abdominal pain, lymphadenopathy, and splenomegaly. Treatment is with induction and consolidation therapy. HSCT or 2 years of maintenance therapy. There must be some CNS prophylaxis throughout as this can progress to the brain or relapse in the brain and spinal cord so intrathecal chemotherapy and possibly radiotherapy to the brain and spinal cord should be considered. There is a 90% 5 year survival rate in children and 40% in adults.

Answer 10

This is a complication of prolonged neutropenia and is life threatening.

Answer 11

This is the most common leukaemia in the western world. There is a slow accumulation of CLL cells in the blood, bone marrow, lymph nodes, liver, and spleen. There is a failure of the normal immune system and thus abnormal immune reactions as low antibody levels. CLL usually responds to treatment, but relapse is inevitable and subsequent treatments are less effective. CLL is the most common leukaemia at 1/10,000. Clinically a immunophenotyping blood test is used for diagnosis, and there should be careful monitoring in case of transformation into a high grade lymphoma. It can be asymptomatic or cause weight loss, night sweats, temperature, itching, bruising, abdominal pain, enlarged lymph nodes, and an enlarged spleen. The majority of patients are over 60. Therapy is with chemotherapy and targeted therapies. 70% of patients will require treatment for their disease. Novel treatments include ibrutinib and venetoclax which blocks thyrosine kinase and BCL2 respectively to prevent lymphocyte proliferation. Asymptomatic CLL does not require treatment.

Answer 12

CML is commonly associated with the Philadelphia chromosome (95%) which is a translocation between chromosome 9 and 22. T(9;22)(q34;q11). Incidence is 1/100,000. 20-50% are asymptomatic and found incidentally on FBC but signs and symptoms can include splenomegaly and bony pain. Treatment is with Imatinib or other tyrosine kinase inhibitors. There is an over 90% 7-year survival rate. Some patients can present in a blast crisis which is transformation to acute leukaemia (ALL or AML).

Answer 13

This is the over-production of mature blood cells. This can be the overproduction of neutrophils (CML), RBCs (polycythaemia vera) or platelets (essential thrombocytosis). Idiopathic myelofibrosis results in low blood counts due to replacement of bone marrow with collagen so there is extramedullary haematopoiesis and hepatosplenomegaly. Treatment is with gentle chemotherapy and venesection.

Answer 14

This occurs when there is ineffective clonal haematopoiesis. This causes abnormal blood counts (anaemia) and should be considered in patients with abnormal blood counts with no obvious explanation (macrocytic anaemia with normal haematinics). The RBCs will have a dysplastic morphology. There is a wide spectrum of severity, and treatment varies depending on this. It almost exclusively occurs in patients over 60.

Answer 15

Clinical features include anaemia and pancytopenia (caused by accumulation of malignant plasma cells in bone marrow – b-cell derived antibody producing cells), lytic bone lesions (pathological fractures and hypercalcaemia), monoclonal paraprotein (hyper viscosity and renal failure) through IgG or IgA or free light chains. Mnemonic CRAB: Calcium, Renal, Anaemia and Bone Treatment is with induction combination chemotherapy and autologous stem-cell transplants in the first remission. The disease follows a chronic relapsing course with may be treated with immunomodulatory drugs and monoclonal antibodies.

Answer 16

Hodgkin Lymphoma: 3/100,000 per annum. Classical HL present with asymptomatic lumps and incidence spikes between ages 15-30 and 65+. 25% will have systemic symptoms. Lymphopenia and anaemia are often present in advanced disease. Symptoms of pruritis and intermittent fevers are associated with night sweats. B symptoms are drenching night sweats and weight loss of more than 10% in 6 months.

Answer 17

High grade b cell non-Hodgkin’s lymphoma affects all ages and usually presents with systemic symptoms and large masses/features of organ infiltration. Low grade b cell non-Hodgkin’s lymphoma usually occurs in the over 50s and the presentation is usually painless widespread low-volume lymphadenopathy. Splenomegaly is common in advanced disease and asymmetry, or bulk disease may signify high-grade transformation.

Answer 18

Investigations should include a biopsy of a representative node/organ involved and HIV serology for HL or high-grade NHL. These tests are diagnostic. Staging is with CT neck/chest/abdomen/pelvis and a PET-CT for HL/high grade NHL The staging system is called Ann Arbor system.

Answer 19

HL: Combination chemotherapy +/- radiotherapy High grade NHL: Combination chemotherapy +/- radiotherapy Low-grade NHL: Guided by symptoms/disease extent Stem cell transplantation can be autologous (patient’s own cells) or allogenic (donor). Autologous can be curative (HL) or to extend remission in myeloma whereas allogenic is always done for curative intent and most commonly used in acute leukaemia. Mortality is between 10-40% depending on the clinical situation.

Answer 20

Important aspects are low Hb (anaemia), high HCT +/- Hb (primary/secondary polycythaemia) and low Hb in context of pancytopenia or high WBC (malignancy). Anaemia in infants (>150) and 6 months (>114) have different limits. MCV is used to investigate the type of anaemia and a low MCH may indicate IDA or thalassaemia. MCHC is only important if considered hereditary spherocytosis.

Answer 21

The normal range is between 80-100 fL unless pregnant (>85) or an infant (74-84). Generally microcytic is <80, normocytic 80-100 and macrocytic is >100. Microcytic anaemia is caused by IDA, thalassemia trait, anaemia of chronic disease (usually normocytic), lead poisoning, and sideroblastic anaemia. Normocytic anaemia is caused by anaemia of chronic disease, renal failure (low EPO), acute bleeding, mixed deficiency, MDS, leukaemia, and sickle cell disease. Macrocytic anaemia is caused by B12/folate deficiency, liver/alcohol, MDS (myelodysplastic syndrome), haemolysis, hypothyroidism, and some medications. Pernicious anaemia is an autoimmune condition affecting B12 absorption and thus macrocytic. Ferritin is used to diagnose IDA and should be above 20. Older patients with an IDA should be referred under 2ww for bowel cancer. Microcytic anaemia in pregnancy is usually IDA or thalassaemia trait. If thalassemia trait, then the partners DNA becomes very important. This is more common in patients from a Mediterranean background.

Answer 22

Haemolysis will present with macrocytic anaemia, abnormal bilirubin but normal LFTs. A Haptoglobin should be done to confirm as part of the haemolytic screen. This is an emergency and requires admission and steroids.

Answer 23

Macrocytosis should be investigated with B12/folate/LFTs/ GGT/TFTs/LDH/Haptoglobin/retics and direct antiglobin tests. There should also be a comprehensive drug history taken. If B12 deficient (due to malabsorption such as PA or pancytopenia) then give IM folic acid. If there is evidence of haemolysis start folic acid and call haematology and if above is normal then consider MDS and refer to haematology.

Answer 24

Myeloma may present with a normocytic anaemia, hypercalcaemia, and raised total protein. Anti-paraprotein should be considered abnormal.

Answer 25

This is defined as persistently raised Haematocrit (HCT). In women this is >0.48 and in males >0.52. This is almost always secondary to another condition such as reduced plasma volume (dehydration and diuretics) and increased red cell mass (hypoxia increasing EPO as seen in smoking, apnoea and altitude or ectopic sources of EPO such as renal or cerebral malignancy). Primary polycythaemia is diagnosed when secondary causes are excluded. This is an acquired genetic mutation seen in JAK2 mutation (95% of patients) It is normally associated with raised platelets and WBCs and there is a risk of arterial and venous clots. Acute treatment (especially if there is a clot) is venesection aiming for HCT <0.45. There is a small risk of transformation into acute leukaemia or myelofibrosis. The EPO is often suppressed as the bone marrow is producing inappropriate amounts of RBCs.

Answer 26

Elevated platelet count in which the majority are transient and the rest reactive. There should be an urgent referral to haematology of the platelet count is greater than 1000 or platelets between 600-1000 in association with thrombotic events, vascular compromise, or neurological symptoms. There is an increased risk of thrombosis in primary thrombocythemia. Secondary causes include infection, bleeding, IDA, inflammation, and cancer.

Answer 27

Thrombocytopaenia (low platelet count) is asymptomatic if platelets less than 50 but there is a risk of spontaneous haemorrhage when platelets less than 20. You must always question whether the case is isolated or part of pancytopenia. Causes include spurious (sample problems), reduced production (drugs, B12/folate, viral infection, aplastic anaemia, malignant marrow infiltration, leukaemia, MDS, and HIV infection), or increased destruction (ITP, hypersplenism, DIC, TTP, HUS or SLE). Other causes include drugs such as Alcohol, Thiazides, Quinine, heparin, valproate, phenytoin, carbamazepine, and gold. Acute or chronic infections which can cause it include TB, EBV, VZV, HIV, Strep, Mycoplasma and Hep C. Pregnancy can cause it if there is gestational thrombocytopaenia or HELLP syndrome.

Answer 28

1. Neutrophils: Differentials can include infection, inflammation, and cancer (Haem and non-haem) 2. Lymphocytes: If chronic this is normally in keeping with CLL 3. Blast cells: Think Acute leukaemia if the patient is not severely unwell such as sepsis where bone marrow dysfunction may be expected. If an elevated WCC also presents with anaemia or thrombocytopaenia then think leukaemia or bone marrow infiltration.

Answer 29

Neutropenia is commonly due to transient viral infection, benign ethnic neutropenia (Afro-Caribbean), autoimmune disease, splenomegaly, drug induced, B12/folate, MDS, lymphoma, leukaemia, and myeloma if there are low platelets. Drug causes include carbimazole, septrin, sulfasalazine and psychotropic drugs). Mild = 1-1.5, moderate 0.5-1 and severe is less than 0.5. Investigations should include FBC, film, B12/folate, autoimmune screen, and viral screen.

Answer 30

Lymphopenia can be seen in old age, infection, Drugs (steroids and other immunosuppression), alcohol excess, autoimmune disease, and systemic illness. Less common causes include immunodeficiency, and lymphoproliferative disorders. Investigations should include an FBC, film, repeat FBC in 6 weeks, HIV, Hep B and C, autoimmune screen, and immunoglobulins.

Answer 31

Eosinophilia should be a concern if it is chronic or progressive (not intermittent). Majority of the causes are secondary such as parasites, inflammatory disease, or malignancy. Primary disease is a diagnosis of exclusion and should have an urgent haematology referral if there are cytopenia, rapid rising count or evidence of end organ damage.

Answer 32

Common side effects of cancer treatment include myelosuppression (neutrophils/platelets/ reduced Hb), GI toxicity (nausea/vomiting/diarrhoea and oral mucositis), alopecia (is especially caused by alkylating agents, anthracyclines, Taxanes, and etoposide), infertility (alkylating agents can cause spermatogenesis and thus men more than women), and teratogenicity.

Answer 33

Specific toxicities include: Cardiomyopathy (Anthracyclines such as doxorubicin and epirubucin) Nephrotoxicity (cisplatin may be irreversible damage) Ototoxicity as seen in Cisplatin where high pitch hearing loss is most common. Pulmonary fibrosis is seen in bleomycin, busuphan and carmistine. Neurotoxicity (peripheral neuropathy) is caused by Vincristine, Taxanes and Cisplantin. Haemorrhagic cystitis is caused by cyclophosphamide and Ifosfamide. Secondary malignancies are more common with alkylating agents (AML) and Etoposide (AML).

Answer 34

Financial: Cancer survivors are 37% more likely to be unemployed than others. Quality of life is often understood via the metrics of mobility, self-care, usual activities, pain, and anxiety/depression. This is the EQ5D score.

Answer 35

Rare: Severe symptoms caused by damage to the brachial plexus from an obsolete form of radiotherapy for breast cancer Intermediate: Faecal incontinence, urinary incontinence, and sexual difficulties from radiotherapy or surgery for pelvic cancers Common: Risk of cardiovascular disease, fatigue, and osteoporosis caused by chemotherapy or hormone treatments for breast and prostate cancer.

Answer 36

Improving outcomes can be achieved by using appropriate doses of drugs for therapeutic index and thus reduced damage to normal tissues. Recognising toxicity earlier will also help reduce the long-term impact. At the end of therapy all patients should have a holistic needs assessment to anticipate problems and get ahead of them. Utilise charities and support systems.

Answer 37

This is a type of treatment using ionization radiation to control or kill the cancer cells. Radiotherapy is used for 60-70% of all patients diagnosed with cancer. Types of radiotherapy include external beam radiotherapy/Teletherapy, Brachytherapy and radionucleotide therapy. Treatment should be delivered so that the tumour will receive the maximal possible dose whilst the normal tissue receives a dose within tolerance limits.

Answer 38

External beam radiation therapy can be 2- or 3-dimensional, intensity modulated, image guided, intraoperative, stereotactic or particle beam/proton radiotherapy. Conventional 2d radiotherapy uses X-rays to localise the tumour whereas 3D uses CT/PET/MRI scans to create a 3D picture of the tumour and the surrounding anatomy. 3D has an improved precision accuracy and thus decreased normal tissue damage.

Answer 39

Intensity modulated radiation therapy (IMRT) is a 3D method whereby radiation is shaped to fit the exact shape of the tumour. The radiation is broken into beamlets of which the intensity can be subsequently adjusted. IMRT allows higher doses of radiation to be delivered to the tumour whilst preserving tissue around the tumour. For patients treated with 3D or IMRT there will need to be frequent imaging of the tumour, bony anatomy, and implanted fiducial markers for daily set-up accuracy. This also allows the movement of tumours to be tracked.

Answer 40

Stereotactic radiotherapy (SBRT) and stereotactic radiotherapy (SRS0) refers to stereotactic radiation treatments in 1-5 fractions on specialised linear accelerators. This uses sophisticated imaging; treatment planning and immobilisation techniques and respiratory gating may be necessary for motions management in lung tumours (inspiration and expiration). SBRT is used for the spine, lung, liver, brain, adrenals, and pancreas.

Answer 41

Proton beam therapy is where protons deposit most of their energy at a given depth, minimizing risk to tissues beyond that point. This allows for highly specific targeting of tumours located near critical structures. It is most commonly used in paediatrics, CNS and intraocular malignancies.

Answer 42

Intra-operative radiation therapy (IORT) is delivers a concentrated dose of radiation therapy to a tumour bed during surgery. Advantages include decreased volume of tissue to pass through, increase of the effective dose, and it has been proven to be good for breast cancer.

Answer 43

Brachytherapy is where radioactive sources are implanted into the tumour or surrounding tissue such as 125I, 103Pd, 192Ir or 137Cs. The purpose is to deliver high doses of radiation to the desired target whilst minimising the dose to the surrounding tissue. Types ca be intracavitary implants, interstitial implants, or intra-operative implants.

Answer 44

Systemic Radiation Therapy uses radiopharmaceuticals, given by injection or IV, that collect where the cancer is and deliver their radiation there to kill the cancer cells. There is highly specific targeting of radiation with radionucleotides that decay within the body in specific locations. This is seen in iodine-131 for thyroid tumours, radium-223 for bone metastases and radioactive beads used for liver cancer.

Answer 45

Generally, radiation therapy works by damaging the DNA of cells and destroys their ability to reproduce. Both normal and cancer cells are affected by radiation, but cancer cells have generally impaired ability to repair their damage which leads to cell death. All tissues have a tolerance level, or maximum dose, beyond which irreparable damage may occur. Fractionation, or dividing the total dose into small daily fractions over several weeks which takes advantage of differential repair abilities of normal and malignant tissues. Fractionation spares normal tissue through repair and repopulation while increasing damage to tumour cells through redistribution and reoxygenation.

Answer 46

Factors which affect radio-sensitivity include physical (LET and dose rate), chemical (increased oxygen, cytotoxic drugs, and sulfhydryl compounds), and biological status such as stage of mitosis.

Answer 47

The absorbed dose is the quantity of radiation absorbed per unit mass of absorbing material. The RAD (Radiation absorbed dose) is the traditional basic unit. The modern unit is the Gray (Gy or cGy), and is defined as 1 J absorbed/Kg.

Answer 48

The radiation oncology team include a clinical oncologist, medical physicist, planning radiographers and treatment radiographers. Radiotherapy may be used as a neoadjuvant, adjuvant or palliative measure.

Answer 49

Radiation therapy is used for adjuvant/neoadjuvant therapy in breast, prostate, lung, ano-rectal, oesophagus, head/neck, brain, skin, gynaecological, lymphomas, bladder, and sarcoma. Most side effects occur at the end of a treatment course. Treatment course usually run over 5 days a week for up to 10 weeks. Palliative radiotherapy is useful for spinal cord compression, vascular compression (superior vena cava syndrome), bronchial obstruction, GI bleeding, gynaecological bleeding, oesophageal obstruction, and bone pain.

Answer 50

Radiation side effects include breast swelling and skin erythema, nausea, vomiting, diarrhoea, cough, SOB, oesophageal irritation, taste alternation, dry mouth, mucositis, skin redness, hair loss, scalp redness, urinary frequency, vaginal irritation, impotence, and fatigue but all these symptoms are dependent on the site which is being radiated.

Answer 51

This works on the principles of inducing cell death but is only effective on proliferating cells. The faster the tumour is dividing; the better chemotherapy is. Chemotherapy can be cell cycle specific or non-specific. Combinations of chemotherapies should be one cell cycle specific and non-specific so that there are multiple attacks on the tumour and a lower toxicity : Benefit ratio.

Answer 52

1. Antimetabolites: These prevent DNA synthesis (Capecitabine is a pro-drug requiring liver activation. 2. Alkylating Agents: Prevent uncoiling of DNA for replication which can either be done by topoisomerase inhibitors to prevent uncoiling or non-classical alkylating agents which lock the DNA crosslinks in place so they do not unravel. 3. Vinca Alkaloids: These cause cell cycle arrest by preventing microtubule formation 4. Antimitotic antibiotics: These prevent the synthesis of mitosis by intercalating to inhibit synthesis, membrane binding to increase permeability or free radical formation to disrupt the DNA chain and prevent mitosis alkylation. 5. Taxanes: Spindle fibre inhibition

Answer 53

Methotrexate, 5-FU, and Capecitabine

Answer 54

Etoposide and ifosphamide

Answer 55

Cisplatin, carboplatin, and oxaliplatin

Answer 56

Vincristine and vinblastine

Answer 57

Doxorubicin and epirubicin

Answer 58

Paclitaxel and docetaxel

Answer 59

GI tumours tend to respond to 5-FU type based regimes

Answer 60

- Complete response: Disappearance of all measurable disease - Partial: 30% decrease from baseline - Minimal response: Decrease in measurable lesion; no new lesions - Stable disease: Neither partial or progressive decrease criteria have been met (Palliative goal) - Progressive disease: 20% increase in one or more lesions

Answer 61

A cycle is defined as a dose of oncology therapy (sometimes multiple drugs in combination) A course is a number of cycles given as a block. With chemotherapy this s often 4-6 whereas targeted therapy or immunotherapy is often given continuously. A line is a number of different treatment types. 1st line is not the 1st treatment. 3rd line would mean two previous failed oncological therapies. Response to treatment is measured with the RESIST criteria or CR/PR/SD/PD ORR/RR = Response rate, PFS = progression free survival (time from starting treatment to PD), OS = overall survival (starting treatment until death) and TTNT = Time To Next Therapy. Toxicity is severity graded – CTCAE v.5

Answer 62

All paediatric cancers, some lymphomas, Germ cell testicular tumours, AML, choriocarcinoma, Ewing’s sarcoma, Embryonal rhabdosarcoma and Wilm’s tumour. For the majority of cancers chemotherapy will only form part of the overall treatment. Chemotherapy may be used for curative treatment (neo-adjuvant or adjuvant) or for palliative treatment.

Answer 63

Adjuvant treatment is used to reduce the risk of tumour recurrence or spread and kill micro metastases (patients who die of metastatic disease yet had an operable tumour must have had micro metastases). Adjuvant treatment is used in breast cancer, colorectal cancer, lung cancer and early-stage ovarian cancer. It should be considered on a case-by-case basis. Risk of recurrence may be impacted by the histological subtype, size, grade, nodal involvement, residual tumour/margins, vascular invasion and ER/PR/HER2. Computer modelling is used to predict future outcomes and individual molecular markers may also be used for monitoring. Rarely multiple gene expression assays are used by they are very expensive.

Answer 64

Neoadjuvant treatment is where treatment is given before definitive local treatment (surgery). This is usually chemotherapy but can involve endocrine or targeted treatments. The aims include shrinking cancer prior to surgery for cosmetic or margins to be improved and to reduce the risk of tumour recurrence and spread. Neoadjuvant therapy can be beneficial because if allows less radical surgery, be used to see if chemotherapy is effective and make adjustments and is useful for drug development and research. Disadvantages include less prognostic information, potential for over-treatment and psychological damage as it takes a long time.

Answer 65

Palliative treatments aim to improve symptoms, maintain quality of life and prolong survival.

Answer 66

This is protocol based and the name of the chemotherapy regimen is commonly an acronym. Prescription should include drug names, protocol doses and calculated total doses, route, and method of administration (PICC/Hickman, ports for swimming, intra-arterial or intrathecal which is uncommon and used in lymphoma or breast cancer), infusion time and anti-emetics. Always consider pre-medications for taxanes and MAbs, hydration regimes (especially cisplatin and ifosfamide which are hard to excrete), supportive therapy (anti-emetics/growth factors), allergy status and dose modifications. It is important to understand the maximum cumulative doses: 1. Anthracyclines such as Epirubicin (900mg/m2), Doxorubicin (550mg/m2) and life time accumulative dose. 2. Bleomycin should be used with caution if over 40000 i.u. accumulative total dose. Signs of renal impairment should be monitored with baseline U&Es and the Cockcroft & Gault formula to estimate GFR. This should be done for platinums, capecitabine, ifosfamide and methotrexate. Liver impairment can be caused by Etoposide, Taxanes, and Anthracyclines. There should be baseline LFTs, monitoring LFTs, and dose adjustment accordingly. If a patient is obese then a BSA (Dubois & Dubois formula) should be calculated on mg/kg. Obesity may change ways drugs are metabolised such as increased blood volume (decreased steady state concentration), increased lean body mass and increased organ size. Further, the increased adipose tissue mass means that lipophilic drugs will have increased volume of distribution. There can also be fatty infiltration of the liver, increased GFR and altered hepatic blood flow. In obesity dosing done according to the BSA using the actual body weight may risk toxicity but ideal body weight may cause under dosing. The solution is to dose reduce according to toxicity and limit the BSA to 2-2.2m

Answer 67

Chemotherapy side effects (CTCAE criteria) include neutropenic sepsis, N&V, hair loss, bone marrow suppression, mucositis, diarrhoea, and fatigue. Systemic symptoms may occur with tumour necrosis, low Hb, low electrolytes, dehydration, morphine, and steroids. Antracyclines can cause cardiac myopathy. Gemcitabine can cause pneumonitis and bleomycin can cause pulmonary fibrosis. Specific side effects can include renal toxicity, hearing loss (cisplantin), neuropathy (taxanes), palmer erythema and nail cracking (5-FU), coronary vasospasm (5-FU), constipation, anaphylaxis, and extravasation (cannula fails and chemotherapy spreads into underlying tissues causing necrosis of the skin). Extravasation would require ice/warm hand, steroids cream, review by plastics and referral to a burns unit if needed. Personalised medicine in oncology can include the use UGT1A1 typing in irinotecan dosing. DPD deficiency in 5-FU toxicity is now routinely screened for because this can cause diarrhoea, mucositis, dehydration, and extreme fatigue causing ITU admission.

Answer 68

Biological therapies have been developed in response to the hallmarks of cancer as the big impacts of chemotherapy had been exhausted. All malignant cells exhibit the hallmarks of cancer which are resisting cell death, sustaining proliferative signalling, evading growth suppressors, activating invasion and metastasis, enabling replicative immortality and inducing angiogenesis. Further hallmarks have been added such as avoiding immune destruction, promoting inflammation, de-regulating cellular energetics and genome instability leading to mutation.

Answer 69

The EGFR pathway is associated with cell survival and proliferation. The mediators of this pathway can be mutated, some examples include RAS, BRAF, and PI3K. The EGFR receptor itself can also be susceptible to mutations.

Answer 70

- Endocrine/hormonal therapies: SERMs and aromatase inhibitors - Monoclonal antibodies: VEGF (bevacizumab), EGFR (Cetuximab) and HER2 (trastuzamab) - Tyrosine Kinase Inhibitors: EGFR (Erlotinib/Gefitinib), VEGFR (Sunitinib), and cKIT/bcr-abl (Imatinib) - Small molecule inhibitors: bRAF (Dabrafenib), MEK (trametinib), and mTOR (everolimus) - PARP inhibitors: Olaraparib - Immunotherapies (all monoclonal antibodies): CTLA4 (ipilimumab) and PD1/PD-L1 (Nivolumab and pembrolizumab) - Bisphosphonates

Answer 71

Biologics are monoclonal antibodies are active on the outside of target cells. Other targeted agents such as small molecule tyrosine kinase inhibitors are functionally active on the inside of target cells.

Answer 72

EGFR mutations, ALK mutations, and PDL1 positive

Answer 73

HER2, ER and PR receptor mutations and somatic mutations are BRCA 1+2

Answer 74

For a targeted therapy to work the target must not be mutated as this would inhibit its effect. The drug must target a protein further down the cascade than the mutation to prevent the pathway from working. The protein which is mutated must be identified before starting a targeted therapy.

Answer 75

Cetuximab is the treatment for colorectal cancer but a mutation will result in loss of drug function. People with a colorectal cancer with a RAS mutation will not respond to treatment.

Answer 76

Erlotinib (Tarceva) is the treatment for non-small cell lung cancer requires an EGFR mutation to work (EGFR-TK). Atezolizumab (Tcentric) for non-small cell lung cancer is an open label phase 3 drug which can be used generally. Performance status is a scoring system used to decide how fit a patient is and how likely they are to get benefits from treatment and withstand the side effects.

Answer 77

BRCA mutations respond well to carboplatin. A serious side effect of carboplatin is myelosuppression. Olaparib (PARP inhibitor) can be used because BRCA patients have defective homologous recombination DNA repair. There is the potential to encourage cell death via apoptosis by targeting more than one area of DNA repair at the same time. This overwhelms cellular acceptance of DNA damage and pushes the cell into apoptosis via synthetic lethality. PARP inhibitors also prevent DNA repair thus induced synthetic lethality. NICE approval for second line therapy as maintenance until progression following a platinum agent.

Answer 78

Trastuzamab (Herceptin) can be used as an adjuvant and is effective for metastatic disease as a first line treatment. Herceptin works by binding to HER2 receptors and blocking them which prevents ongoing signalling.

Answer 79

Vemurafenib is a BRAF inhibitor used for melanoma. Common side effects include skin rashes and lethargy. Ipilimumab can cause transient thyroiditis. Pembrolizumab (immunotherapy) can be used as alternative and will also cause thyroid toxicity.

Answer 80

NSCLC which is EGFR mutation positive and PDL1 expressive can be treated with chemotherapy alone or treated with a targeted therapy such as Gefitinib. This can cause skin reactions. NSCLC which has been treated with a platinum chemotherapy and an EGFR inhibitor can then be treated with an immunotherapy such as pembrolizumab. These do not work in all patients, have side effects and toxicity but there is a durable benefit from treatment. Cancer is still likely to win out eventually.

Answer 81

Immunotherapy treatments are a group of 6 drugs used to optimise and activate an immune system against a malignancy with both an immediate and durable response. It is defined as the prevention or treatment of disease with substances that stimulate an immune response. JAK point protein inhibitors are the current group of immunotherapies. They work by binding to the checkpoint proteins on cancer cells that allow the cancer to hide from the immune system, inactivate them and make them visible to CD8 cells which detect the cells and cause cell death. This then stimulates a b cell response and thus a memory response against the tumour.

Answer 82

Immunotherapies are used for upper GI, NSCLC, SCC, renal cell, urothelial, head and neck, Hodgkin lymphoma, Merkel cell carcinoma, and triple negative breast cancer. Challenges include the practicalities of the drugs and the high toxicity. They can cause immune-related adverse events due to widespread inflammation which commonly manifests as endocrinopathies, dermatitis, colitis and hepatitis. This is not seen in chemotherapies. 20-60% of patients will have a reaction severe enough that they require hospital admission. It is important that side effects are recognised as there is a significant mortality associated. Toxicity always requires active intervention even if just a biochemical disturbance. Mild immune related adverse event should be monitored, moderate should be given oral steroids, investigated and the drug omitted whereas severe should be admitted, given IV steroids, investigated, specialist referral and omit the drug.

Answer 83

A voluntary process of discussion and review about future care and treatment n the event of loss of capacity. This can be verbal but it is better if it is documented and shared. Advance statements set out general preferences to inform best decisions and if they refuse treatment then they are legally binding. A legal proxy should be assigned through lasting power of attorney for health and welfare. In clinical terms this include a DNACPR and clinical management plan. It is important the ACP is voluntary, and the patient is aware of the benefits. The outcome should be focussed on offering a conversation about future care and not completing the forms.

Answer 84

A patient’s desire for food decreases as death approaches and they may benefit from smaller meals, supplements, appetite stimulants (dexamethasone) and reassurance that decreased appetite is normal. In the active dying phase the patient is semi-comatosed and will be unable to take food. A patient’s desire for fluid decreases as death approaches. They will hopefully still be able to take fluid by mouth and there should be a focus on good oral hygiene and mouth care. Artificial hydration may be required in some circumstances such as bowel obstruction. In the active dying phase, the patient may still be able to take sips of fluid and mouth care should continue. There should be a review of the appropriateness of artificial hydration on a day-by-day basis. Appropriate palliative care will involve consideration of the option of artificial hydration, where dehydration results from a potential correctable cause (diuretics, sedation, vomiting, diarrhoea, or hypercalcaemia). Studies suggest that artificial hydration in the imminently dying neither improves survival or symptom control and thus would be an unnecessary intrusion. Generally, good mouth care and reassessment of medication are the most appropriate interventions. Clinicians must not subordinate the interests of the patient for the anxieties of relatives about fluid intake but should stive to address those anxieties nonetheless.

Answer 85

Euthanasia is ‘a good death’. This can be active where there is an intentional bringing about of the death of a patient on the request of the person. Passive euthanasia is selective non treatment of a patient such as withdrawing or withholding treatment.

Answer 86

Suicide is an intentional act of self-destruction. It was decriminalised in the 20th century but assisting suicide is still an offence which carries a 14-year prison sentence. This should be considered in the context of physician assisted suicide. Physician assisted suicide is suicide by a patient facilitated by means (prescription) or information (what dose would be lethal) provided by a physician aware of the patient’s intent.

Answer 87

Histopathology specimens are obtained, placed in a 10% neutral buffered formalin, and transported to the lab. Formalin is a fixative agent so it links protein molecules together to make tissues rigid and prevent decay. It also kills pathogens to make the tissue biologically inert. This is then embedded in a wax block, section, mounted on a glass slide and finally stained.

Answer 88

H&E: Haematoxylin (purple) & Eosin (pink) Histochemical stains: Used for Mucin Immunohistochemistry: Means of detecting characteristics of a cell/tissue using an antibody/antigen reaction

Answer 89

Approaching an undifferentiated malignant neoplasm in pathology. Pathology aims to answer the following questions: 1. Is this a carcinoma? 2. What sort of carcinoma is it? 3. Where was the primary site of origin? 4. Which therapy will it respond to? H&E stain, immunochemistry, discuss clinical correlation in MDT, specialist review, more immunochemistry and then do specific tests for most likely site such as a ALK analysis for lung carcinomas. Molecular tests are often very expensive and not routinely used in the UK and not recommended by NICE.

Answer 90

1. Carcinoma: Cytokeratin such as AE1/3, Cam5.2, and MNF116 2. Lymphoma: CD45, CD3 (T cells), and CD20 (B cells) 3. Melanoma: Melan A, HMB-45, and S100 4. Germ cell tumours: None 5. Sarcoma: None 6. Mesothelioma: Calretinin, CK5/6, and WT1

Answer 91

A basic panel would consist of MNF-116, AE1/3, CD45, Melan A, and HMB45 or S100. If a lymphoma is expected, then add CD3 or CD20. If none of these are positive then think again or repeat. On a immunochemistry stain blue is negative and brown is positive. Mucin staining is very good for detecting adenocarcinoma.

Answer 92

Once a carcinoma has been identified it can be subclassified based on its morphology, mitotic count, location, and immunohistochemical profile. Subclassifications: - Squamous Cell: p63 or CK5/6, there may be histological keratinisation and bridge formation - Adenocarcinoma: CK7, CK20, or other site specific markers. Histologically they show gland formation and mucin production. - Neuroendocrine carcinoma: Synaptopysin, chromogranin A or Ki-67 (proliferation index)

Answer 93

CK7+/CK20- : Lung, breast, oesophageal, and female genital tract CK7-/CK20+ : Colorectal and Merkel cell CK7+/CK20+ : Small bowel, transitional cell carcinoma, and mucinous ovarian (stomach) CK7-/CK20- : Hepatocellular, renal cell, and prostate

Answer 94

Patients with a known or suggested primary site of origin do better than those without, possibly due to the use of targeted therapies.

Answer 95

1. ER/PR/Her2 – Breast cancer 2. Oncotype Dx – 21 gene signature in breast cancer 3. Her2 – Gastric cancer 4. KRAS/NRAS/BRAF/MMR – colorectal cancer 5. EGFR/ALK/PDL-1/ROS-1 – Lung cancer 6. BRAF – Melanoma 7. KIT/PDGFRA mutations – GIST

Answer 96

1. Denial 2. Anger 3. Bargaining 4. Depression 5. Acceptance

Answer 97

Occurs when there is pathological vertebral body collapse or direct tumour growth causing compression of the cauda equina which may result in irreversible neurological damage and paralysis. Impending spinal cord compression should be treated in the same way. This is an oncological emergency. Metastases to the spine occurs in 3-5% of all patients with cancer and is most common in breast, lung, and prostate cancer. The ability to walk at time of diagnosis is a significant predictor of survival. Once paraplegia develops it is usually reversible. Pathophysiology: Haematogenous spread through the vertebral spine causing collapse and compression is responsible for 85% of cases. Other methods are direct tumour extention, direct deposition of tumour cells, direct compression causing oedema, venous congestion and demyelination. Gradual effects are often reversible but prolonged compression leads to vascular infarction of the spinal cord.

Answer 98

Back pain (95%) which can be localised in the spine or neurogenic radicular pain, limb weakness (85%), sensory disturbance (52%), and autonomic dysfunction. Red flags are pain in the thoracic or cervical spine, spinal pain aggravated by straining, localised spinal tenderness, nocturnal pain, motor dysfunction, sensory dysfunction, and autonomic dysfunction.

Answer 99

Immediate management: Call MSCC co-ordinator and complete referral, lie patient flat with neutral spine if possible, log roll if spinal instability is suspected, MRI whole spine (T1/2), CT spine with contrast, and CT CAP and contrast. Prescribe Dexamethasone 16 MG stat then OD, PPI, stop NSAIDs and aspirin, monitor for hyperglycaemia and candida, LMWH, and WHO ladder for analgesia. Other investigations: FBC/INR/LFTs/U&Es/eGFR, bone profile, glucose, consider LDG, unknown primary and myeloma screen, and bladder scan. Treatment: Consider surgery in those with spinal metastases and structural instability, mechanical pain and paralysis and those with severe mechanical pain that may benefit from external spinal support. Radiotherapy as external beam may be effective in treating pain for up to 12 months. It may help to control pain if there is vertebral involvement but does not reduce mechanical pain. Bisphosphonates: If conventional analgesia fails, then can be used to treat spinal pain in patients with vertebral involvement from myeloma, breast cancer, or prostate cancer. Rarely epidural and intra-thecal analgesia are used. Best supportive care should be given to those with suspected MSCC with paralysis who are unfit for surgery.

Answer 100

Survival after diagnosis is 2-3 months, haematological primary has the longest survival. Lung cancer has the shortest survival. Surgically treated patients are more likely to survive one year.

Answer 101

Signs include myoclonus, extreme drowsiness, and pinpoint pupils.

Answer 102

To titrate the opiate and calculate a breakthrough PRN dose the total dose of PRN opiate required during the day (12 mg), divide by 2 (6 mg), and add this to the current dose. Nearest formula is 5 mg so overall dose should be 10 mg. The PRN dose should be between 6-10% of the total dose of morphine (morphine I/R liquid 3-4 mg PRN).

Answer 103

Side effects of opiates include constipation, nausea, vomiting, drowsiness, delirium, xerostomia, pruritis, hyperanalgesia, allodynia, and opioid toxicity (drowsiness, hallucinations, confusion, vomiting, myoclonus, pinpoint pupils and respiratory depression).

Answer 104

If you suspect opiate toxicity then management options should include a full assessment of the history and examination, dose reduction, check renal and liver function, assess for hypercalcaemia/sepsis/opioid sparing, and then switch opiates such as to fentanyl in renal failure. This patient should be switched to oxycodone.

Answer 105

Continuous infusion should be used when there is a poor swallow and the patient is unable to tolerate essential medications like analgesia and anti-seizure medications. It may also be required if there is a reduced consciousness, more than 2 doses of injectable medication are required within 24 hours, if patient is vomiting or there is bowel obstruction preventing oral absorption.

Answer 106

Physiological causes include constipation, gastric statis/outlet obstruction, raised intracranial pressure, bowel obstruction, hepatomegaly, and cough. Treatment causes include chemotherapy, radiotherapy to the brain or GI, opioids, NSAIDs, and antibiotics. Metabolic causes are hypercalcaemia, hyponatraemia, liver failure, uraemia, hyperkalaemia, and infection. Psychological causes: Anticipatory, anxiety, fear, and fatigue

Answer 107

Conservative management: Dietary alterations, hypnosis, acupressure, relaxation, and reflexology. Medical management: Vomiting centre: Cyclizine works on acetycholine, histamine H1, and serotonin 5HT2 receptors Chemoreceptor trigger zone: Haloperidol and Ondansetron: Work on dopamine D2 and serotonin 5HT3 receptors GI tract: Ondansetron also works on the GI tract via serotonin 5HT3 receptors. Vestibular apparatus: Cyclizine also works on histamine H1 and acetylcholine Prokinetics: Metaclopramide and domperidone Broad spectrum antiemetics: Levomepromazine

Answer 108

General causes: Fibre, reduced dietary intake, reduced mobility, hypokalaemia, opiates, iron, paracetamol, antihistamines, antiemetics, octreotide, dehydration, diuretics, weakness, and environmental causes. Cancer related: Bowel obstruction, spinal cord compression, and hypercalcaemia.

Answer 109

This should be tailored to any reversible causes including diet, fluid intake, and mobility, discuss environmental causes, privacy and dignity, changes to person’s care should be avoided to minimise triggers, maintain regular schedule for toileting, review medications, and help with dehydration and reduced mobility.

Answer 110

1. Lactulose or senna 2. Lactulose and senna 3. If opiate induced add naloxagol or methynaltrexone 4. If not opiate-induced consider an alternative macrogol, co-danthramer or hydrogen hydroxide 5. Rectal intervention

Answer 111

IV and SC fluids, use of NG tubes, or percutaneous gastrostomy, or total parenteral nutrition. This is considered a medical treatment, but Cochrane review found no significant benefit. This can be declined by a competent patient.

Answer 112

There are reversible causes of lack of appetite as well as causes of nausea, constipation, sore mouth, or entering the last few days of his life. Interventions which may improve his appetite could include a trial of steroids, management of a sore mouth such as candida or recognising he is dying and supporting his needs. Nausea should be managed with investigations of the cause of the nausea such as blood and infection screen if appropriate and then consider antiemetics.

Answer 113

This should be suspected when there is reduced food and fluid intake, reduced interest in surroundings and lack of interaction, increased fatigue, dysphagia, fluctuating consciousness and assessment of their medical conditions.

Answer 114

There are 4 drugs used: Morphine, oxycodone, diamorphine or alfentanil (renal dysfunction).

Answer 115

Cyclizine 50 mg TDS/PRN, Haloperidol 0.5-1 mg PRN, Metoclopramide 10 mg TDS, and Levomepromazine 6.25 mg PRN.

Answer 116

Glycopyrronium 200 micrograms PRN or Hyoscine hydrobromide 400 micrograms PRN.

Answer 117

Midazolam 2.5-5 mg PRN (useful for seizures and myoclonus), remember paradoxical agitation, and Levomepromazine 6.25-12.5 mg PRN.

Answer 118

Referral should be made to the coroner when there is an unknown cause of death, industrial illness, post-operative death, death related to an accident, death in custody, and any suspicious circumstances of the death. The medical examiner ensures transparency and scrutiny around the cause of death. These require senior review and discussion before signing the medical certificate of cause of death (MCCD).

Answer 119

Signs and symptoms which suggest imminent end of life include overwhelming fatigue, reduction in oral intake, progressive weight loss, deteriorating mobility, dysphagia, fluctuating consciousness, confusion/delirium, reduced communication, reduced social interaction, and the patient has come to terms with death. Late signs include mottled skin, cool extremities, irregular respiration, Cheyne-Stokes breathing, and respiratory secretions. In the dying phase the patient may experience pain, distressing breathlessness, agitation, delirium, nausea, vomiting, and respiratory tract secretions.

Answer 120

An individualised plan of care should be developed for the care of a patient likely to be dying and those important to them. This should include a preferred place of death, current and anticipated needs, symptom management preferences, anticipatory medications, care needs after death, religious needs, personal goals, resuscitation status, review long term medications, physical needs, hydration status, eating and drinking, and concerns regarding significant others.

Answer 121

Verification of death requires no visible respiratory effort, no palpable large pulses, no response to painful stimuli, pupils fixed and dilated, and no audible heart or breath sounds.

Answer 122

Malignant neoplasm of the lymphatic system derived from germinal centre B cells. The presence of Reed-Sternberg cell and Hodgkin cells defines Hodgkin lymphoma. Malignant cells are mixed with non-neoplastic inflammatory infiltrate. Divided into Hodgkin’s lymphoma and NLPHL.

Answer 123

2.4/100000 per year with a mortality of 0.4/100000 in the UK. It mainly affects young adults and is the 3rd most common malignancy in 15-29s. Presentation is slow and variable. Symptoms often begin weeks to months before patient is evaluated and often presents with lymph node enlargement. More than 60% present with cervical or SC LAP. B symptoms are present in 40% such as fever, night sweats, fatigue and weight loss.

Answer 124

Incidence is influenced by infections of EBV and HIV, socioeconomic status, geography, and family history. EBV is nearly always positive in HIV associated HL and is independent of CD4 cell count. Obesity, diet, cigarette smoking, immunosuppression, presence of autoimmunity and genetic factors influence the incidence of HL.

Answer 125

FBC/U&Es/LFTs/CRP/ESR/LDH/Autoimmune screen/serum protein electrophoresis/ virology screen/HIV status/EBV/CMV/Hepatitis B and C/ haematinics if the patient is anaemic. Imaging depends on the area of involvement and manner of presentation. USG, CT or PET CT may be needed to guide biopsy decision.

Answer 126

Tissue biopsy is required to diagnose HL and its subtype. This can be CT or USG core biopsy of accessible lymph nodes. If core biopsy is non-diagnostic then excision biopsy is required. On histology there will be RS and HRS cells and lacunar cells in the presence of variable inflammatory infiltrate. Immuno-histochemistry can show CD30 (100%) and CD15 (75%). There are typically negative B and T cell markers on HRS cells. Histological subtypes of HL include classical and nodular lymphocyte predominant HL.

Answer 127

1. Involvement of a single lymph node region or of a single extra lymphatic organ or site 2. Involvement of two or more lymph node regions on the same side of the diaphragm or localised involvement of an extra lymphatic organ or site 3. Involvement of lymph node regions or structures on both sides of the diaphragm 4. Diffuse or disseminated involvement of one or more extra lymphatic organs or either isolated extra lymphatic organ involvement without adjacent regional lymph node involvement with disease in distant sites or involvement of the liver, bone marrow, pleura or CSF.

Answer 128

- Limited stage disease: Favourable or unfavourable depends on presence of MMR, ESR, and symptomatology - Advanced stage disease: The Hasenclever index includes age 45+, stage IV disease, male, WBC >15, lymphocytes <0.6, albumin <40 g/l and Hb <105 g/l.

Answer 129

The mainstay is chemotherapy +/- IFRT which is used in both limited stage and advanced stage disease. Main chemotherapies are ABVD and BEACOPP. PET adapted treatment strategy is used. Early-stage disease patient receive two courses of 4-6 cycles of ABVD along with INFR. There is a higher risk of relapse when IFRT is omitted. Advanced stage disease is treated with ABVD and BEACOPP. After 2 cycles of ABVD, PET positivity leads to escalation of treatment. PET negative patients de-escalate treatment to AVD to prevent toxicity. Salvage chemotherapies (IGEV, DHAP, and ICE) are used in relapse settings. These are followed by BEAM chemotherapy and stem cell transplants. Chemo-immunotherapy include anti-CD30 drug conjugates (Brentuximab Vedotin or Bleomycin), check point inhibitors, or 2 PD-1 inhibitors are in use such as nivolumab and pembrolizumab.

Answer 130

Patients are monitored regularly during and after completion of treatment with the main aim of identifying acute and late complications. Mortality associated with late complications is higher than deaths from relapsed disease 8 years later. Late complications include secondary malignancies, CVS events, pulmonary problems, endocrine dysfunction, infertility, and psychological issues.

Answer 131

Congenital benign: Branchial cysts, laryngocele, thyroglossal cyst, dermoid cyst and teratomas Acquired benign: infectious inflammatory, non-infectious inflammatory and non-inflammatory. Inflammatory lymphadenopathy can be viral (glandular fever, HIV, rhinovirus, or adenovirus), bacterial (staphylococcus, streptococcus, brucella, actinomycosis, and mycobacterium, syphilis, or cat-scratch disease), and parasites (toxoplasma). Non-infectious inflammatory and non-inflammatory disorder differentials could include sarcoidosis, autoimmune disorders (SLE), lipoma, or paragangliomas. Malignant causes include metastatic head and neck cancers, lymphomas, thyroid nodules, salivary gland tumours and schwannomas.

Answer 132

The HRS cells/HS cells are pathognomonic of Hodgkin lymphoma. They have bi-lobed kidney-shaped nuclei with prominent eosinophilic nucleoli. These cells have rearranged 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 a loss of expression of B-cell genes. Genetic lesions in HRS cells involve two main signalling pathways, including the JAK-STAT pathway and the NF-kB pathway. The HRS cells secrete various cytokines and chemokines, which are responsible for the presence of inflammatory infiltrate around HRS cells. The precise aetiological agent has not been identified, but there is a pathognomonic role of EBV in 40% of classical Hodgkin lymphoma. EBV nuclei acids and proteins have been detected in these cases. Immunosuppression is associated with an increased risk of HL, particularly in HIV patients, and is not dependent on CD4 count.

Answer 133

Acute: Neuropathy, constipation (vinblastine), pulmonary toxicity (bleomycin), acute allergic and anaphylactic reactions (immunotherapy and chemo-immunotherapy), liver toxicity, and renal toxicity. Cytopenia during treatment does require blood and platelet support. Patients with HL require irradiated blood to prevent GVHD. Regular surveillance and screening are required in long-term survivors of HL. The aim is early detection through screening and risk reduction measures of some late effects and lessen their impact on HL survivors. Late complications include secondary malignancies (breast, lung and colon are the most common whilst AML and other haematological malignancies can occur), coronary artery disease, valvular disease, arrhythmias, cardiomyopathies, peripheral vascular disease, pulmonary fibrosis, bronchiectasis, recurrent chest infections, hypothyroidism, diabetes, gonadal dysfunction (alkylating agents and radiotherapy to the pelvis), neuropathy, muscular atrophy, and psychological issues.

Answer 134

Neoadjuvant: If the tumour is too large to perform breast-preserving surgery or is inoperable. As a result of being locally advanced, treatment to shrink the tumour prior to surgery may be needed. In triple negative breast cancer (TNBC) survival is greater if NACT produces a complete response than if the patient has ACT. Adjuvant: Breast cancer can be removed by surgery and treatment can be given after surgery. Chemotherapy: Aims of treatment are to increase both progression free and overall survival, by reducing the risk of recurrence systemically. Chemotherapy regimens vary but generally include an anthracycline and a taxane. Chemotherapy is given in cycles, every 2/3 weeks +/- supported with G-CSF to prevent neutropenic sepsis and delay of subsequent cycles. Chemotherapy is offered to those patients who are assessed to be likely to benefit from it either according to their Oncotype DX score (a molecular diagnostic test that assesses risk of recurrence) or their Predict score where this is not available (a statistical package that calculates risk of recurrence). Radiotherapy: This is given to the breast or chest wall, +/- local node groups to reduce the risk of local recurrence, by up to 70%. It is given in daily fractions, which cause cell death by damaging DNA. Patients attend on weekdays for 1-3 weeks. Hormone therapy: This is given to those patients whose tumour cells show oestrogen/progestogen receptors (This is around 80%/65% of the total, and is more common in older women). This is in the form of tamoxifen (a selective oestrogen receptor modulator, SERM) or 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. These are given for 5-10 years and improve overall survival by suppression of recurrence of breast cancer systemically. Trastuzumab: Commonly called by the trade name Herceptin, this is a monoclonal antibody that acts against cells that display HER-2. It is given 3 weekly for 18 cycles and is positive in around 20% of patients with breast cancer. Palliative: If metastases are found on the CT or bone scan, rendering the tumour incurable. These options would range from palliative chemotherapy, to attempt to control the disease throughout the body, or for those who are not fit enough, radiotherapy and hormone therapy can provide good symptomatic control. Immunotherapy may also play a role – with checkpoint inhibitors eg atezolizumab in metastatic TNBC and the CK 4/6 inhibitor palbociclib which is used first line in ER+ HER2 –ve metastatic breast cancer.

Answer 135

Sensitivity: True positives/(true positives + false negatives) This is the chance that someone with the disease will be identified by the test Specificity: True negatives /(True negatives + False positives) So this is the chance that the test will only test positive with the disease Positive predictive value: TPs/ TP + FP So the percentage of true positives out of all the positive tests Negative predictive value: TNs/ TN + FN So the percentage of true negatives in all the negative tests Symptoms that can be referred under the 2WW rule have a 3% positive predictive value for the disease.

Answer 136

Occult malignancy is a term used for when routine testing or other tests find results which indicate cancer and can be used to expediate treatment. This might include VTE in absence of risk factors, unexplained pallor, lymphadenopathy, acanthosis nigricans or widespread pruritis without a skin condition (leukaemia and lymphoma).

Answer 137

0: Fully active and able to carry on all pre-disease performance 1: Restricted in physically 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 3: Capable of only limited self-care and confined to bed or chair more than 50% of waking hours 4: Completely disabled and cannot carry on any self-care

Answer 138

T: Size of primary tumour N: Prescence of lymph node metastases M: Presence of distant metastases T1: Tumour invades submucosa T2: Tumour invades muscularis propria T3: Tumour invades through the muscularis propria into the subserosa or into non-peritonealized pericolic or perirectal tissues T4: Tumour perforates visceral peritoneum or directly invades other organs or structures N1: Metastases in 1-3 regional lymph nodes N2: Metastases into 4 or more regional lymph nodes M0: No metastases M1: Distant metastases

Answer 139

Inflammation and redness of the skin, hair loss over treatment area, diarrhoea, nausea, infertility, soreness and dryness of the mouth, painful swallowing, irritative cough, tenesmus, cystitis, and bowel cramps. Early side effects are caused by the effect of radiotherapy on rapidly dividing cells. They peak 2 weeks after treatment and are usually transient.

Answer 140

These can be caused by inability to repair following severe acute side effects (rare) or caused by fibrosis and small vessel injury with endothelial damage in affected area (common). These are cells which divide more slowly so present later. These include strictures (oesophagus and small bowel), fistulae (vesicovaginal/rectovaginal), skin changes (telangiectasia and pigment changes), osteoradionecrosis (jaw), dry mouth, lung fibrosis, and cardiomyopathy. At radical doses radiotherapy may cause secondary malignancy in 15 years’ time.

Answer 141

Smoking increases hypoxic damage, radiosensitising medication (chemotherapy such as methotrexate for RA), older radiotherapy techniques, recent surgery, poor dental care for head and neck, genetic factors, extremes of age, and retreatment.

Answer 142

Palliative Chemotherapy: This is given with the intention to relieve symptoms. It is shown to improve symptoms in lung cancer, breast cancer, and colorectal cancer. There is also a small increase in survival. Palliative Radiotherapy: This is given with the intention to relieve symptoms and is shown to be effective for SOB, bleeding, dysphagia, headache, confusion, reducing tumour growth and preventing oncological emergencies. Is it shown to significantly reduce pain from bone metastases with 50% experiencing total pain relief. There is also a small increase in survival and progression free survival.

Answer 143

This is the presence of an abnormal monoclonal antibody in the blood. This occurs as a result of the development of a clonal population of plasma cells or lymphocytes. This is seen in lymphomas and CLL but the majority occur in plasma cell dyscrasias.

Answer 144

This is a family of disorders caused by clonal proliferation of plasma cells. There is a spectrum from more common, benign MGUS through to less common cancers such as plasma cell myeloma. Rare causes include amyloidosis in which the abnormal proteins can form large fibrils deposited in tissues causing organ dysfunction (nephrotic syndrome or heart failure).

Answer 145

MGUS (monoclonal gammopathy of undetermined significance): Small paraprotein (<30g/L) and no end organ damage (CRAB) Myeloma: Suspect with any size paraprotein if there is end-organ damage (CRAB) and can be confirmed with bone marrow biopsy (more 10% plasma cells needed). Plasma cell myeloma is managed with supportive care (radiotherapy, analgesia, spinal review, bisphosphonates, and fluids) and chemotherapy (including autologous stem cell transplant). Prognosis: Incurable but improving survival.

Answer 146

Indications are screening, diagnosis, prognosis and monitoring of prostate cancer. It should be considered alongside DRE in men with LUTS or erectile dysfunction. Men with a PSA above their age specific range should be referred under the 2WW. PSA can also be elevated in prostatitis, BPH, and after DRE.

Answer 147

Indications are prognosis and monitoring of stomach, colorectal and pancreatic cancer. It can be elevated in gastritis, IBD, pancreatitis, hepatitis, cirrhosis, and in smokers. It is often used to monitor relapse after curative surgery. Not used in primary care.

Answer 148

Indications are prognosis and monitoring of stomach, colorectal, and pancreatic cancer. Not used in primary care.

Answer 149

Indications are diagnosis, monitoring, and recurrence of ovarian cancer. All women should be offered a CA125 if there is persistent abdominal distention, early satiety, pelvic or abdominal pian, or increased urinary urgency/frequency.

Answer 150

Indications are screening, diagnosis, prognosis, and monitoring of hepatoma or germ cell tumours. It can be elevated by pregnancy, viral hepatitis, IBD, and Liver injury.

Answer 151

The acute leukaemia features of anaemia, thrombocytopenia (low Plts), and neutropenia (low neutrophils) are caused by failure of the normal bone marrow. Symptoms, as a result, are tiredness, bruising, and infection.

Answer 152

1. Supportive care of red cell transfusion, platelet transfusions, antibiotics, and haemopoietic growth factors 2. Intensive chemotherapy or palliative chemotherapy for less fit patients 3. Bone marrow transplantation (definitive management is with allotransplantation) 4. Bispecific monoclonal antibodies or Chimeric antigen receptor T cells (CAR-T) for ALL

Answer 153

Patient with low neutrophil count develops a fever treat with broad spectrum antibiotics immediately. This is an oncological emergency.

Answer 154

1. Neutrophils: Chronic Myeloid Leukeamia 2. Red Cells: Polycythaemia Rubra Vera 3. Platelets: Essential thrombocytosis 4. Idiopathic myelofibrosis (fibroblasts stimulated by growth factors released by proliferating platelet precursors (megakaryocytes) and results in low blood counts due to replacement of bone marrow with collagen)

Answer 155

Hepatosplenomegaly as the bone marrow is not working so the liver and spleen compensate. Myeloproliferative neoplasms have a long natural history which culminated in acute leukaemia.

Answer 156

This is essentially a liquid lymphoma. There is slow accumulation of CLL cells in the blood, BM, lymph nodes, liver, and spleen. Eventually there is failure of the bone marrow.

Answer 157

This is imaged with FDG-PET because the tumours are more metabolically active than normal tissue so can be visualised on PET scan.

Answer 158

Forms discrete lumps that grow in the MB and erode the bone which compromises the integrity of the bone and thus pathological fractures. Often present with back pain. The monoclonal paraprotein causes hypervsicosity and renal failure (IgG or IgA).

Answer 159

Platinum’s have a particular role in SCCs and are radiotherapy sensitising so good for patients with concurrent radiotherapy.

Answer 160

Breast cancer responds to anthracycline based regimes and taxanes are good for many malignancies but need to be combined with other drugs to be most effective.

Medicine D Flashcards

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