Miscellaneous Flashcards
Name 5 risk factors for breast cancer
- Nulliparity
- 1st pregnancy >30 y/o
- Early menarche
- Late menopause
- HRT, OCP
- Obesity
- BRCA genes
- Not breastfeeding
- Past breast cancer
Why do BRCA genes increase the likelihood of getting breast cancer?
They are tumour suppressor genes
5-10% of breast cancer are due to mutations in BRCA1 or BRCA2
What is the most common form of breast cancer?
Invasive ductal carcinoma = 70%
Name 4 types of breast cancer
- Non-invasive ductal carcinoma in situ (DCIS) = premalignant
- Non-invasive lobular carcinoma in situ
- Invasive ductal carcinoma (70%)
- Invasive lobular carcinoma (10-15%)
- Medullary cancers (5% - effects younger patients)
- Colloid/mucoid cancer (2% - effects elderly)
Is there are better prognosis with breast cancers that are oestrogen receptor positive?
YES = better prognosis
60-70% breast cancers are oestrogen receptor positive
Is there are better prognosis with breast cancers that are HER2 positive?
HER2 - growth factor receptor gene
If positive = over expression = more aggressive disease with poorer prognosis
Give 4 signs of breast cancer
- Painless, increasing mass
- Nipple discharge
- Inversion of nipple
- Skin tethering
- Ulceration
- Oedema/erythema
Give 3 differential diagnosis’s of breast cancer
- Fibroadenoma
- Benign breast cysts
- Intraductal papilloma
Define fibroadenoma
Benign overgrowth of collagenous mesenchyme of one breast lobule
What is a benign Breast cyst?
Palpable, benign, fluid-filled rounded lumps that are not fixed to surrounding tissue
Define intraductal papilloma
Benign, warty lesion usually located just behind the aerola
How are breast lumps assessed?
Triple assessment
- Clinical examination
- Histology/cytology = fine needle aspiration (cystic lump) or core biopsy (residual mass or solid lump)
- Mammography/USS
What else should be checked if you suspect a patient has breast cancer?
Oestrogen receptor, progesterone receptor and human epidermal growth factor (HER2) status
What investigations are done in order to stage breast cancer?
CXR
Bone scan
Liver USS
CT/MRI or PET-CT
Describe the staging of breast cancer
Stage 1 = Confined to breast, mobile
Stage 2 = Growth confined to breast, mobile, ipsilateral lymph nodes
Stage 3 = Tumour fixed to muscle, ipsilateral lymph nodes matted/fixed, skin involvement larger than tumour
Stage 4 = Complete fixation of tumour to chest wall, distant metastases
Describe the TNM staging of breast cancer
T1<2cm, T2 = 2-5cm, T3 >5cm, T4 = fixed to chest wall
N1 = mobile ipsilateral nodes, N2 = fixed nodes
M1 = distant metastases
What is the treatment for stage 1-2 breast cancer?
- Wide local excision or mastectomy +/- breast reconstruction + axillary node sample/surgical clearance
- Radiotherapy after WLE
- Adjuvant chemotherapy (epirubicin + CMF - cyclophosphamide, methotrexate + fluorouracil)
What medication can be used in oestrogen and progesterone receptor positive breast cancer?
Endocrine agents to decrease oestrogen activity
Post menopausal = tamoxifen (ER blocker) or anastrozole (aromatase inhibitor)
Pre-menopausal = ovarian ablation or GnRH analogues (goserelin)
What is the management for stage 3-4 breast cancer?
Radiotherapy for painful bony lesion (+/- bisphosphonates - alendronate)
Tamoxifen for ER +ve
Trastuzumab for HER2 +ve tumour with chemo
Describer the screening programme for breast cancer
Biplanar digital mammography every 3 years in women ages 50-70 years old
Define lymphoedema
Chronic non-pitting oedema due to lymphatic insufficiency
Name the types of lymphoedema
- Primary = presents early in life due to inherited deficiency of lymphatic vessels
- Secondary = due to obstruction of lymphatic vessels
Give an example of primary lymphoedema
Milroy disease
- autosomal dominat
- primary congenital lymphoedema so lower leg swelling from brith
- treatment = compression sticking/bandage and encourage exercise
Give 2 examples of secondary lymphoedema
- Malignant disease
- Post-irradiation therapy
- Filarial infection
- transmitted by mosquito and caused by worms
- acute infection = fever, lymphadenopathy, chyluria
- causes elephantiasis
- treatment = diethylcarbamaxine
Define sarcoma
Cancer arising from cells of mesenchymal origin
Malignant tumours of cancellous bone, cartilage, fat, muscle, vascular or haematopoietic tissue
Give 3 examples of soft tissue sarcomas
Leiomyosarcoma
GI stromal tumours
Angiosarcoma
Liposarcoma
Describe the epidemiology of soft tissue sarcomas
80% of sarcomas
1500/year in UK
Give 2 risk factors for soft tissue sarcomas
- Neurofibromatosis type 1
2. Previous radiotherapy
Give 2 symptoms of soft tissue sarcomas
- Painless enlarging mass
2. Pain as lump grows
What is the most common initial place of metastases for a sarcoma?
Lung
Name 4 red flags of soft tissue sarcomas
- > 5cm
- Increasing in size
- Deep to the deep fascia
- Painful
What investigations might you do in someone you suspect to have a soft tissue sarcoma?
MRI followed by a needle biopsy
CT thorax for lung metastases
What is the treatment for a soft tissue sarcoma?
Excision with wide margin
+ Radiotherapy
Give 3 examples of bony sarcomas
- Osteosarcoma
- Ewing’s sarcoma
- Chondrosarcoma
Name 3 bone sarcoma red flags
- Non mechanical bone pain
- Night pain
- Palpable bone mass
Name 3 symptoms of a bony sarcoma
- Non mechanical bone pain
- Swelling
- Tiredness
- Pyrexia
- Weight loss
What investigations might you do in someone you suspect to have a bone sarcoma?
XR = bone destruction, new bone formation, periosteal swelling and soft tissue swelling
CT/MRI
Bone scans and biopsy
What is the treatment for a bony sarcoma?
Wide surgical excision and reconstruction
Chemotherapy +/- radiotherapy
Define amyloidosis
Group of disorders characterised by extracellular deposits of an abnormal fibrillar protein (amyloid) that is resistant to degradation
How are is amyloidosis classified?
- AL amyloidosis (primary amyloidosis)
- AA amyloidosis (secondary amyloidosis)
- Familial amyloidosis (ATTR)
Describe the pathophysiology of AL amyloidosis
Clonal proliferation of plasma cells –> amyloidogenic light chain protein production and deposition
Name 3 conditions AL amyloidosis is associated with
- Myeloma
- Waldenstroms
- Non-hodgkin’s lymphoma
Give 2 kidney features of AL amyloidosis
- Proteinuria
2. Nephrotic syndrome
Give 3 heart features of AL amyloidosis
- Restrictive cardiomyopathy
- Arrhythmias
- Angina
Give 3 nerve features of AL amyloidosis
- Peripheral neuropathy
- Autonomic neuropathy
- Carpal tunnel syndrome
Give 2 gut features of AL amyloidosis
- Macroglossia
- Malabsorption/weight loss
- Perforation
- Haemorrhage
- Obstruction
- Hepatomegaly
Give a vascular feature of AL amyloidosis
Periorbital purpura = characteristic feature
What is the treatment for AL amyloidosis?
Oral melphalan + prednisolone
OR high dose IV melphalan + autologous peripheral blood stem cell transplant
How does melphalan work?
Damage DNA within plasma cells –> prevents cell division –> reducing amyloid deposition
Describe the pathophysiology of AA amyloidosis
Amyloid is derived from serum amyloid A = acute phase protein
What conditions does the inflammation of AA amyloidosis reflect?
Chronic inflammation
- RA
- UC/Crohn’s
- Chronic infections - TB, bronchiectasis
How can AA amyloidosis present?
Affect kidney, liver + spleen
Proteinuria
Nephrotic syndrome
Hepatosplenomegaly
What is the treatment for AA amyloidosis?
Treat underlying condition
Describe the pathophysiology of familial amyloidosis
Autosomal dominant disease caused by mutations in transthyretin (transport protein produced by liver)
Mutant protein forms amyloid fibrils
How does familial amyloidosis present?
- Sensory or autonomic neuropathy
- Cardiomyopathy
- Renal involvement
What is the treatment for familial amyloidosis?
Liver transplant = cure
Where is a biopsy taken from when diagnosing amyloidosis?
Rectum or subcutaneous fat = relatively non-invasive
How is the diagnosis of amyloidosis confirmed?
Positive Congo Red staining with red-green birefringence under polarised light microscopy
What type of virus is HIV?
A RNA retrovirus
HIV1 responsible for most HIV
What genus does HIV belong to and what is the significance of this?
Lentivirus genus
Characterised by having long incubation periods
Briefly describe the mechanism of HIV replication
- GP120 binds to CD4 receptors
- Viral cashed, enzymes and nucleic acids are uncoated and released into the cell
- RNA is converted into DNA using reverse transcriptase
- Viral DNA is integrated into cellular DNA by integrase
- Viral DNA is transcribed into viral proteins
- Splicing
- New HIV cells ‘bud’ from CD4
Name 4 enzymes involved in HIV replications
- Reverse transcriptase
- Integrase
- RNA polymerase
- Proteases
Describe what happens when someone is initially infected with HIV
HIV enters via mucosa
Macrophages ingest HIV and presents an epitope of HIV to a T-cell
HIV then infects the T cell
Infection spills into the bloodstream = viraemia
What cells act as ‘host cells’ for HIV?
CD4+ cells
Macrophages and dendritic cells
HIV leads to immune dysfunction, how are the immune system cells affected?
- CD4 cells are excessively and inappropriately activated
- Impaired IL-2 production
- Decrease in number and function of CD4 cells
- B cells produce fewer specific antibodies
- Fewer NK cells, neutrophils and macrophages
Name 4 sanctuary sites for HIV
- Genital tract
- GI tract
- CNS
- Bone marrow
- Macrophages and microglia
Name 4 groups of people who are at high risk of HIV infection
- Men who have sex with men
- Heterosexual women
- IVDU
- Sex workers
- Truck drivers
How can HIV be transmitted?
- Sexual transmission
- Vertical transmission
- Contaminated blood, blood producers or organ donation
- Contaminated needles
What are the 4 main phases in the natural history of HIV?
- acute primary infection (seroconversion)
- Asymptomatic phase
- Early symptomatic HIV
- AIDS
What happens in the acute primary infection phase of HIV?
Transient fall in CD4 count followed by a gradual rise
Occurs 2-6 weeks after exposure
What signs and symptoms might you see when someone is in the acute primary infection phase of HIV?
Abrupt onset of non-specific symptoms
Fever, rash, weight loss, myalgia, lethargy, macuopapular rash (rarely meningoencephalitis)
What happens in the asymptomatic phase of HIV?
= Clinical latency phase
Progressive loss of CD4 T cells
What might happen in the asymptomatic phase of HIV?
30% show persistent generalised lymphadenopathy
= nodes >1cm diameter, >2 extra-inguinal sites and >3 months
What happens in the early symptomatic phase?
Manifestation of clinical features
How does the early symptomatic phase present?
Fever night sweats, diarrhoea, weight loss
+/- opportunistic infection (oral candida, herpes zoster, recurrent herpes simplex, seborrhoea dermatitis, tinea = AIDS related complex)
What is the CD4+ count when some is diagnosed with having AIDS?
< 200
Name 3 types of people who are likely to rapidly progress and develop AIDS?
- Elderly people
- Children
- People with a high viral load
Name 2 markers that are used for HIV monitoring?
- CD4+ count
2. Viral load (RNA concentration)
How can HIV be diagnosed?
Serum/salivary HIV-Ab by ELISA
Western blot
If a HIV test comes back as negative in a high risk individual why should second HIV test be done?
As their is a window period = time between potential exposure to HIV infection and point where test will give an accurate result
Test again at 6 weeks and 3 months
How can HIV be prevented?
- Education on transmission
- Increase use of contraception
- Disposable equipment
- Antenatal antiretroviral if HIV +ve
- Pre/post exposure prophylaxis
What does HAART stand for?
High active anti-retroviral treatment
What is HAART and what is its aim?
3 drugs are taken together
Aim is reduce viral load and increase CD4+ count
Good compliance = good prognosis
What drugs are used in HAART?
2 nucleoside reverse transcriptase inhibitors
AND 1 non-nucleoside reverse transcriptase inhibitor OR 1 protease inhibitor
Name a nucleoside reverse transcriptase inhibitor
Abacavir, didanosine, Emtricitabine
Name a non-nucleoside reverse transcriptase inhibitor
Efavirenz, etravirine
Name a protease inhibitor
Atazanavir, darunavir
Name 2 other possible drugs that can be used in the treatment of HIV
- Fusion inhibitors - enfuvirtide
2. Integrase stand transferase inhibitors - raltegravir
What are 4 main problems that surround HIV treatment?
- Mainly transmitted by sexual intercourse and so people don’t like to talk about it - taboo
- Period of latency means someone may infect others unwittingly
- HIV leads to a weakened immune system and so there is increased risk of infection
- HIV mutates a lot and so drug treatment is difficult
How would you define a ‘late diagnosis’ of HIV?
CD4+ count < 350
Name 3 AIDS defining respiratory diseases
- Pneumocystis pneumonia (PCP)
- Bacterial pneumonia
- TB
- Fungal infections
What are the symptoms of Pneumocystis pneumonia (PCP)?
Fever, SOB, dry cough, pleuritic chest pain, exertion drop in O2 sats
How do you treatment Pneumocystis pneumonia (PCP)?
Co-trimoxazole
Name 3 AIDS defining CNS diseases
- CNS lesions = cerebral toxoplasmosis, tuberculoma
- Ophthalmic lesions = Cytomegalovirus (CMV), choroidal tuberculosis, toxoplasmosis
- Meningitis = pneumococcal, cryptococcal
Name 3 AIDS defining neoplasms
- Lymphoma - non-hodgkin’s or primary CNS
- Kaposi’s sarcoma = low grade vascular tumour
- Cervical neoplasia
