What increases the risk of breast cancer?
Nulliparous Earlier menarche Late menopause Interrupted pregnancy Obesity First degree relative
What decreases the risk of breast cancer?
Breastfeeding Late menarche Early menopause Normal BMI Childbirth Oopherectomy
What are the issues with breast cancer surgical management?
Mastectomy - emotional wellbeing of patient, reconstructive surgery option Lymph node clearance - risk of lymphedema, pain, loss of function and Oopherectomy - egg conservation, early menopause
What are the options for adjuvant systemic therapy for breast cancer?
Chemotherapy - tumours >1cm, ER -ve OR pre surgery to shrink tumour Endocrine - tamoxifen (ER/PR), herceptin (HER2 +ve), aromatase inhibitor (block androgen conversion to oestrogen) Radiotherapy - tumour >5cm, lymph node involvement, adjuvant to breast conservation surgery, risk of burns, secondary cancer, toxicity
What are the fertility issues in a premenopausal woman undergoing cancer treatment?
Chemotherapy can cause premature ovarian failure or amennorhea Consider fertility preservation on diagnosis of breast cancer
What lifestyle factors may have altered the natural history of breast cancer?
Alcohol - 2-5 alcoholic drinks per day increases risk of breast cancer 150% Overweight/obese - increased oestrogen release from adipose tissue Lack of physical activity Less children and lower breastfeeding duration OCP Depo injections HRT Older population Later pregnancy (> 30) Smoking More radiation exposure (CT)
When is a breast cancer relapse more common?
Within 5 years of diagnosis ER +ve cancer
What is this and what are the risk factors for formation?
Solar/Actinic keratosis - sun exposure, age, albinism, male, light skin, HPV, immunocompromised
p53 mutation leads to damaged keratinocytes that cannot undergo apoptosis
What are some features on history of solar keratosis and how is it diagnosed?
Pruritis, bleeding, hx of sun damage
Diagnose via dermatoscopy and skin biopsy
What is the treatment for solar keratosis?
Sun protection (future, and reduce progression to SCC)
What is this and what are the risk factors for development?
Squamous Cell Carcinoma - sun damage, previous skin cancer, ionising radiation, burns, arsenic, tar, HPV, immunocompromised, age, fair skin
What is evident on history of an SCC and how is it diagnosed?
Bleeding, crusting, pruritis, poor lesion healing, tender, skin mobile over other structures
Diagnose via biopsy (risk of invasion and metastases)
What is the treatment for SCC?
Bowens (SCC in situ) - cryotherapy, photohterapy, curretage, fluorouracil (topical), Mohs, radiotherapy
Invasive - surgical excision, Mohs (high risk on face - need 6mm margins)
What is this condition and what are the risk factors for development?
Basal Cell Carcinoma
Risks - UV exposure, radiation, arsenic, transplant history, +40
What are the features of a history of BCC and how is it diagnosed?
History - pearly nodular lesion, bleeding, ulcerated, telangiectasia, crusts and non-healing wounds
Diagnosis - biopsy and dermatoscopy (often diagnosable by appearance and hx)
What is the treatment for BCC?
Vismodegib (reduces tumour load)
Curettage and cautery
What is this condition and what are the risk factors for development?
Risks - sun exposure, age, fair skin, family history
What is the history of seborrheic keratoses and how is it diagnosed?
Stuck on lesion, wart like, raised, painless, itchy
Diagnosis with dermoscopy and biopsy ( may progress to Bowen's and SCC)
What is the treatment for seborrheic keratoses?
Curettage or cautery
What is this condition and what are the risk factors?
Overgrowth of hair cells and melanocytes - often congenital - round or oval shaped pigment patches, may have excess hair growth, rough surface, often become darker and more hairy in puberty
What is the treatment for melanocytic naevi and what is the risk of no treatment?
No Treatment - risk is development to malignant melanoma (mainly related to size of naevi)
What is this and what are the risk factors for development?
Risks: UV exposure, > 100 naevi, > 5 dysplastic naevi, previous extreme sun burn, fair skinned (fitzpatrick I or II), blue eyes, red hair, immunosuppression, hx of skin cancer, xeroderma pigmentosum
What are the features on history that make melanoma likely and how is it diagnosed?
ABCDE - asymetrical, irregular borders, multiple colours, diameter >6mm, evolving lesion
Spontaneous bleeding or ulceration
Bluish veil - dermal fibrosis
Diagnosed via biopsy and dermatoscopy
How is melanoma staged and how does this affect prognosis?
Stage 0 (in-situ melanoma): >98%
Stage I (Breslow's depth <1 mm and no nodal or metastatic disease): 90% to 95%
Stage II (localised disease, intermediate to thick depth): 45% to 78% (78% for non-ulcerated melanoma of depth 1 to 4 mm; 45% for an ulcerated melanoma >4 mm depth)
Stage III (nodal metastases): 69% (non-ulcerated melanoma of any depth with a single positive node) to 26% (ulcerated melanoma of any depth with 4 or more positive nodes)
Stage IV (metastatic): without treatment, overall prognosis is bleak, ranging from 3% to 10% depending on the extent and sites of metastasis. New drugs are changing this, with 20% having long-term survival with ipilimumab, and newer drugs await long-term follow-up data.
What is the treatment for melanoma?
Imiquimod topical treatment
Sentinel node biopsy
Ipilimumab - stage III melanoma
What is present on hx and examination of multiple myeloma?
Anaemia - SOB, pallor, syncope, fatigue
Bone pain (often back)
What are some investigations and their findings in multiple myeloma?
Urine electrophoresis - hypogammaglobinemia, albuminuria
Skeletal assessment - osteopenia
Bone marrow aspirate - plasma cell infiltration
Serum calcium - hypercalcaemia
FBE - anaemia
What are some differential diagnoses of monoclonal gammopathy?
What is smouldering myeloma?
Early asymptomatic face of myeloma - evidene on bone marrow biopsy - doesn't require active treatment straigh away
What are some complications of myeloma?
Thrombocytopenia (linked to - tumour infiltration of bone marrow, renal impairment and myelosuppressive effects of chemotherapy)
What are some treatment options for multiple myeloma?
Dexamethasone pre transplant
DVT prophylaxis (aspirin, enoxaparin)
Stem cell collection
Transplant - autologous or allogenic
Bisphosphonates and analgesics for bone disease
What are the 3 broad cell lineages of lymphoma?
What is non-hodgkin lymphoma?
Heterogeneous group of malignancies in the lymph system - B and T cell lymphomas. Cancer arising when B and T lymphocytes undergo a malignant change and multiply in an uncontrolled way - form tumours in lymph nodes and around the body. Majority are B lymphocyte derived
What are some risk factros for hodkin lymphoma?
Young adult from higher SES
How is hodgkin lymphoma staged?
What are the treatment options for Hodgkins lymphoma and the complications?
- Radiotherapy thyroid abnormalities (hypothyroid, Graves, thyroid cancer)
- Radiation and chemotherapy secondary malignancies, heart disease, pulmonary toxicity, ovarian dysfunction, testicular dysfunction, impaired immunity
What are the signs and symptoms of diffuse large B cell lymphoma?
Painless swelling in the neck, armpit or groin (caused by lymphadenopathy)
Extra nodal lymphadenopathy causing abdo pain, diarrhoea or bleeding
What are the prognostic factors for diffuse large B cell lymphoma?
ECOG Status: 0 - no symptoms, 1 - symptoms but ambulatory, 2 - bedridden for less than half the day, 3 - bedridden half the day or longer, 4 - chronically bedridden and needs ADL assistance
What is the treatment for diffuse large B cell lymphoma?
Stem cell transplant
Methotrexate chemotherapy if cancer has infiltrated spinal cord
What are INR/PT and APTT tests used for?
INR/PT - test of extrinsic clotting, used to measure warfarin effect levels, normal level is between 0.8-1.2 and with warfarin is 2-3, mechanical valve 2.5-3.5
APTT - characterises blood coagulation/clotting, measure of intrinsic clotting time
What are the features of vWF disease?
Most common inherited bleeding disorder
vWF is important for platelet adhesion and factor VIII transport
Autosomal dominant - decreased concentration of vWF
If severe there may be mucosal bleeding
Blood often normal except for reduction in platelets and APTT prolonged
Diagnosis via immunoassay
Treat with tranexamic acid, infusion or nasal spray to release stored vWF
What are the features of immune thrombocytopenia?
Low platelets not associated with systemic disease
Chronic in adults but usually self limiting and acute in children
Spleen size normal
Treatment - corticosteroids, splenectomy, immunosuppression, thrombopoietin receptor agonist drugs
Signs & Symptoms - petechiae, purpura, mucosal bleeding
Diagnosis - FBE with platelets elevated
What are the features of haemophilia A?
X-linked recessive condition, deficiency of factor VIII
Low factor VIII levels predispose to bleeding
Bleeds into joints (haemarthroses) cause chronic deformity, swelling and pain
Increase in haematuria and intracranial haemorrhage
Investigations - prolonged APTT, factor VIII assay
Contraindication for IM injections, use of NSAIDs
What are the features of haemophilia B?
X-linked recessive condition - deficiency of factor IX
Severely affected patients develop haemarthroses
Recombinant factor IX for treatment
Prophylactic treatment can be given once or twice weekly
What are some risks for prostate cancer development?
High fat diet
Black men have highest incidence
Age > 50
What is the clinical presentation of prostate cancer?
Abnormal DRE - asymmetrical nodular prostate
What are the differentials of a raised PSA?
Benign prostatic hyperplasia
What are the roles of biopsy and DRE in prostate cancer diagnosis?
Biopsy is required to see if prostate cancer is present and to give an idea of how aggressive the cancer is, PSA alone is not diagnostic of prostate cancer
DRE - can be used to distinguish between prostate cancer and BPH, but is not recommended as a standard test for patients who have no symptoms of prostate cancer (may lead to unnecessary prostate biopsy)
What are the treatment options for localised prostate cancer?
Surveillance - 3monthly PSA, 6monthly DRE
How would disease recurrence post radical treatment for localised prostate cancer be picked up?
Rise in PSA (but slight rise is also seen with cessation of neoadjuvant treatment)
Gleason score > 8
What are the salvage options post radical treatment for localised prostate cancer?
Prostatectomy - good level of control but higher risk of incontinence, impotence and rectal damage
High intensity focused US
Adjuvant hormonal therapy
What are the treatment options for metastatic prostate cancer?
- External beam radiotherapy - high energy x-ray beams directed at prostate
- Brachytherapy - radioactive material inserted into prostate
- Androgen deprivation therapy (5 alpha reductase inhibitor)
- LH receptor agonist injections (block testosterone synthesis)
What are the causes of diarrhoea?
Secretory - secretion of chloride and water
- Increased electrolyte secretion
- Pancreatic cholera
- Villous adenoma
Osmotic - increased amounts of poorly absorbable osmotically active solutes in the gut lumen
- Disaccharidase deficiency
- Lactose intolerance
Exudative - due to exudation of mucous, blood and protein from site of active inflammation into bowel lumen
- IBD - Ulcerative colitis
- Entamoeba histolytica
Motility Disorder - abnormal intestinal motility with decreased contact b/w luminal contents and mucosal surfaces
What are the differences b/w small and large bowel diarrhoea?
- Increased frequency of defecation
- Small quantities
- Urgency and tenesmus (needing to go again soon after defecation)
- Red blood may be present
- Weight loss rare
- Left iliac fossa pain
- Normal or slightly increased frequency
- Large quantity of bulky or watery faeces
- No urgency or tenesmus
- Dark black melena with bleeding
- Weight loss may be present
- Central abdominal pain
What is the pathology of ulcerative colitis?
Continuous inflammation, worse distally and rectum is almost always involved - inflammation in mucosa and submucosa
Inflammation leads to excess mucous production and triggers diarrhoea
What is the clinical presentation of ulcerative colitis?
Mucous and pus in stool
Tenesmus (with rectal involvement)
Malaise and anorexia
Erythema nodosum - painful itchy raised lumps in skin (legs most common)
Pyoderma gangrenosum - pussy dead tissue, black necrotising mass, most common on legs or around a stoma
Primary sclerosing cholangitis
What are the complications of ulcerative colitis?
Toxic Megacolon - deeper layer of bowel becomes affected and colon enlarges and may perforate - colon diameter > 6cm
Acute attack - tachycardia, heavy bleeding, pyrexia
Dysplasia - two sites is reason for surgery to avoid malignancy
What is the treatment for ulcerative colitis?
Corticosteroids - hydrocortisone, prednisolone, dexamethasone (many side effects so not used for long term management - good for inducing remission but not for maintaining)
Amino-salicylate - help to maintain remission (5-ASA), may be nephrotoxic, thought to work by trapping ROS to reduce inflammation
Immunosuppressant's (azathioprine, cyclosporin) - may be used in severe cases of UC that don't respond to other treatments
- Restorative proctocolectomy - total removal of colon and rectum but preservation of anus for anastomosis (usually anastomosis occurs later to reduce morbidity and mortality)
- Complete proctocolectomy and permanent ileostomy - generally in elderly patients
What is the epidemiology of Chron's?
Peaks in 20s and 70s
Genetics, dietary factors and immune response play a role
What is the pathology of Chrons?
Causes skip lesions where part of bowel sit unaffected between affected sections
Most commonly ileocaecal
Often causes malabsorption due to stricturing and fibrosis of the small intestine (leads to shortening)
What is the clinical presentation of chrons?
Fissures and abscesses
Large joint arthritis
What are the complications of chrons?
Increased risk of GI malignancy - adenocarcinoma arising in distal ileum with poor prognosis
What are the management options for chrons?
Low residue diet
Low fat diet
Treatment of vitamin deficiencies
What is the action of aspirin?
Aspirin moves into the stomach and moves through the endothelium (endothelium produces prostacyclin) then the aspirin moves into the platelets in the gastric blood supply and permanently binds to COX – preventing thromboxane production (thromboxane vascoconstricts). Platelets don’t have a nucleus so they cannot resynthesise COX therefore cant form thromboxane, endothelial cells have a nucleus so they can produce more COX – leading to normal prostacyclin (vasodilator and platelet inhibitor) production – shifting the system towards vasodilation and anti coronary heart disease (less platelet activation for clotting and increased vessel diameter). This only happens for low dose of aspirin, because at a low dose the platelets can take up all of the aspirin from the stomach, but in a high dose aspirin would move to other cells.
What is the action of warfarin?
Vitamin K reductase inhibitor - prevents reduction of vitamin K, and therefore prevents activation of factors 2, 7, 9 and 10 - to reduce coagulation
Reversed by vitamin K
Increased by vitamin K deficiency or aspirin addition
What is the action of heparin?
Binds to antithrombin leading to reduced thrombin and factor 8a activation