Cancer Flashcards
Benefits of mammography screening
Reduction in breast cancer mortality Detects cancer earlier Can find smaller cancers - Decreases extensiveness of treatment required - Allows for breast conserving surgery
Limitations of mammography screening
Not 100% accurate False negatives - miss 20% of cancers False positives - cause anxiety and result in extra testing Overdiagnosis leading to over treatment Pain Anxiety Radiation risk
Epidemiology of breast cancer
Most common female cancer in the UK Most common cancer (15%) Increases with age More common in females Highest in Caucasians (Western Europe) FHx - yes especially BRCA1 or 2 gene
Alcohol COCP HRT ionising radiation Raised BMI Smoking Hodgkin's lymphoma Digoxin Diabetes Decreased parity Increased age at giving birth Increased age of menopause Decreased age at menarche
Signs and symptoms of breast cancer
Breast mass - hard, immobile, attached to chest wall Discharge - unilateral, bloody Skin changes - dimpling, peau d'orange Inverted nipple Lump under arm Lymphadenopathy mets may cause symptoms
Breast lump - indications of malignancy
Hard Painless Irregular margins Fixation to skin or chest wall Skin dimpling Discharge that is unilateral and bloody Nipple retraction
Breast lump - indications it’s benign
Firm or rubbery Often painful Regular or smooth margins Mobile No skin changes If discharge bilateral, no blood No nipple changes
Gene associated with breast cancer
BRCA1 or 2
Most common breast cancer type
Almost all are from glandular epithelium lining lactiferous ducts - adenocarcinomas
Investigations for breast cancer
Routine bloods (LFTs for ?mets)
Mammography
- Superior in elderly and in lower density breasts
- Over 40
- On everyone with proven malignancy
US
- More effective in younger patients
- Done in pregnancy or lactation or under 40s
MRI
- In difficult cases: breast implants, BRCA mutation, suspected tumour with multiple foci
If mass found non-palpable
- Core needle biopsy
- Open biopsy
If palpable
- FNA (not ideal if lesion <1cm)
- Core needle biopsy (also provided pathological result)
- Excision biopsy or incisional biopsy
CXR
CT if mets suggested
Can do sentinel node biopsy
Triple assessment for breast cancer
Imaging - US or mammography
Clinical examination
FNA or core biopsy
Need all 3 negative to exclude carcinoma
Tumour marker in breast cancer
CA 15-3
Can be used for prognosis
Hisological markers in breast cancer
Oestrogen and progesterone receptor status
HER2 - human epidermal growth factor 2
Likely met sites for breast cancer
Bone
Brain
Lung
Liver
Staging of breast cancer
0 - in situ 1 - up to 2cm 2 - 2-5cm or nodes on same side 3 - over 5cm of adherent nodes 4 - mets
Management of breast cancer
Surgery, chemotherapy, radiotherapy
<4cm or DCIS then conservative surgery + whole breast ratiotherapy
> 4cm or multifocal then mastectomy and chest wall radiation if high risk
If Node involvement = node resection then radiotherapy + chemotherapy
Hormonal therapy
- Oestrogen receptor POSITIVE - aromatase inhibitor (anastrazole) if post menopausal. Tamoxifen if pre-menopauseal
Biological
- HER2 positive = trastuzumab (Herceptin)
Types of breast cancers
Invasive ductal (90%) Invasive lobular (8%) Mucinous or tubular = rare DCIS = pre invasive
Prognosis of breast cancer
Depends on biological characteristics and therapy given
Increased risk of recurrence if node positive or oestrogen receptor negative
Nottingham Prognostic index
Recurrence 2-5% at 5-20 years
Complications of breast cancer
Psychological implications
- Can be reduced with less destructive surgery, counselling, nipple preservation, reconstructive surgery
Post op complications
Lymphoedema of the arm
Risk factors for lymphoedema
Increased number of lymph nodes removed
Axillary lymph node dissection
Multiple surgery to chest or more extensive surgery - increased chance of disruption
Radiation therapy
Chemotherapy - causes weight gain which is a RF
Breaks in skin
being overweight or obese
Infection or injury on the same side - leads to inflammation and causes increased work on the lymph system
Treatments for lymphoedema
Elastic sleeve or elastic vest (breast swelling) Compression bandaging Manual lymphatic drainage (massage) Combined physical therapy Exercises Compression pumps Weight loss Kinesio taping methods Low level laser therapy
Pathogenesis of cancer mets
Transformation Angiogenesis Motility and invasion (capillaries, venules and lymphatics) Embolism and circulation Transport Arrest in capillary beds Adherence Extravasation into organ parenchyma Response to micro environment Tumour cell proliferation and angiogenesis mets
Lab pathway of tissue sample
- Sample collected and placed in formalin
- Transferred to lab - delay from porter
- Allowed to fix overnight - time delay
- Placed in cassette
- Processed to wax overnight - time delay
- Sectioned and stained
- Added to pile of slides for pathologist - time delay with staffing levels
- Reported by pathologist
- Written report typed - time delay by secretary staffing
- Report checked and signed by pathologist
- Report sent to requesting physician
- Report received by requesting clinician
- Read
- Report acted on
Minimum of 2-3 days,
Describe bronchoscopy process
Fibre optic bronchoscope in thickness of pencil
Usually done as outpatient or day case
- Numb inside of nose and back of throat with a spray
- Sedative to relax
- May be given additional oxygen
- Tube passed through nose or mouth down to trachea and bronchi
- May cause cough
- 20-30 minutes
- Can do biopsies or bronchial lavage
Role of coroner
Independent official with legal responsibilities for the medical legal investigation of certain deaths: sudden, unexplained, unnatural or violent in nature
Deaths reportable to coroner
Sudden deaths from unknown causes
Cause of death unknown
Any vehicle, aeroplane, train or boat accident
Suspicious circumstances
Suicide
Not been seen by doctor in last 28 days
? due to negligence, misconduct or malpractice
Any death within 24 hours of admission
Any death caused by a treatment or anaesthesia
Any infant death or still birth
Reasons for retaining tissue from a post mortem
Microscopic examination
Complex abnormality requiring detailed examination
Sample may need to undergo prep before examination
Prep may take several weeks
Benefits of a post-mortem
Provides valuable info on cause of death
Provides information for future treatment or research
Gives relatives information which could impact on their health
Data can improve and assess medical care and research causes and prevention
Assists education of doctors
Provides accurate mortality and morbidity stats to improve mental health
Epidemiology of lung cancer
3rd most common cancer in the UK 2nd most common in men and women Increases with age More common in men (slightly) Increased in Caucasians FHx - yes
RFs
- Smoking
- Asbestos exposure
- Past cancer
- Radon
- COPD
- TB
- Pneumonia
- Silicosis
- Ionising radiation
- Coal dust
Small cell lung cancer
15% of lung cancers
WORST PROGNOSIS
Also called oat-cell carcinoma Arises from Kulchintsky cells Cells often act as hormones or neurotransmitters Grow rapidly Highly malignant Metastasise early Normally inoperable at presentation Respond to chemo but poor prognosis
Types of non-small cell lung cancers
Squamous (42%) Adenocarcinoma (40%) Large cell (8%) Carcinoid tumours (6%) Bronchoalveolar cell (4%)
Squamous cell lung cancer
42% of non-small cell Present as obstructive lesions of the BRONCHUS Can lead to infection Local spread common Mets occur late
Adenocarinoma of the lung
40% Arises from the mucus cells most common in NON SMOKERS associated with ASBESTOS Invasion of the pleura and mediastinal lymph nodes common Often mets to brain and bone
Large cell carcinoma of lung
8%
Less differentiated forms of adenocarcinoma and squamous cell carcinoma
Mets early
Signs and symptoms of lung cancer
Cough haemoptysis weight loss SOB Chest pain Clubbing Fever Weakness Dysphagia
SVC obstruction
Hoarseness
Horner’s syndrome
Investigations for lung cancer
FBC - Raised WCC, CRP, low Hb
U&Es
LFTs
CXR - urgent if 3 weeks of one of: cough, chest pain, dyspnoea, weight loss, hoarseness, clubbing, lymphadenopathy or chest signs
Contrast CT for staging - done before bronch and biopsy
PET/CT is offered to all potentially curable patients
Bronchoscopy - histological diagnosis and to assess operability
Neck US - for visualising lymph nodes
Percutaneous transthoracic needle biopsy - for superficial lymph nodes and peripheral lesions
Biopsy (surgical) if not possible in other methods
Cytology of sputum or pleural fluid
Histological testing for EGFR-TK mutation as may change treatment
- Epidermal growth factor receptor tyrosine kinase
Management of non-small cell lung cancer
Smoking cessation
Lung function tests on all prior to surgery
Surgical resection - if stage 1 or 2 with hilar lymph node sampling
- If complete resection then adjuvant chemo
- If partial resection then radiotherapy
Radiotherapy - stage 1-3 not suitable for surgery. Can do radical radiotherapy if good performance status
Chemotherapy - offered to all
- In stages 3&4 can increase survival and quality of life
- If EGFR-TK positive ERLOTINIB
Cisplatin most commonly used
Management of small cell lung cancer
Smoking cessation
Multi-drug regimen
In limited stage: 4-6 cycles of cisplatin combination chemo with thoracic irradiation
If there is a good response then prophylactic cranial irradiation
In extensive disease
- Maximum 6 cycles
- Supportive and palliative care
Supportive and palliative care in lung cancer
Breathlessness: strong opiate, psychological support + breathing control
Bronchial obstruction - radiotherapy or debulking bronchoscopy
Pleural effusions: aspiration or drainage. Talc pleurdiesis
Haemoptysis: radiotherapy or debulking bronch
Cough: opioids, radiotherapy
Hoarseness: refer to ENT
Chest pain: radiotherapy
SVC: chemo and radiotherapy. stent insertion.
Cerebral mets: corticosteroids + radiotherapy
Complications of lung cancer
Recurrent laryngeal nerve palsy phrenic nerve palsy horner's syndrome pancoast's syndrome SVC obstruction pericarditis Rib erosion AF
SVC obstruction
Can be due to external pressure, involvement of the vessel by tumour tissue or clot obstructing the lumen
SVC extends from innominate veins to RA, early compressed due to thin walls.
4 collateral routes in SVC obstruction
Azygous system
Internal mammary system
Long thoracic venous system
Femoral and vertebral veins
Epidemiology of SVC obstruction
Most common in men
85% of cases are linked to lung cancer
30-40 more likely to be benign
40-60 years more likely to be malignant
Symptoms of SVC obstruction
dyspnoea cough Chest pain Neck and face swelling Arm swelling Dizziness Nausea Headache Disturbed vision Nasal stuffiness Stupor Syncope Can be gradual or acute
Aggravated by bending or lying down
Signs to SVC obstruction
More pronounced when arms lifted
Dilated veins over arms, neck and anterior chest wall
oedema of upper body, extremities and face
Severe respiratory distress
Cyanosis
Engorged conjunctiva
Convulsions and coma
Link between tobacco and lung disease
DOSE RESPONSE RELATIONSHIP
- Causes many lung disease
- Worsens chronic lung disease
- Increases risk of resp infections
- Acute respiratory illness
- Impaired lung growth in childhood and adolescents
- Early onset and accelerated decline in age related lung function and respiratory symptoms
- Asthma
- Poor asthma control
- COPD morbidity and mortality
- Decreased lung function in infants with maternal smokers
- Increase risk of lung cancer (80% of cases are attributable)
Contents of cigarette smoke
Acrolein - cilia tonic, impairs lung defence Formaldehyde - irritant and cilia toxic Nitrogen oxides - oxidant activity Cadmium - oxidative injury Hydrogen cyanide - oxidative
Free radicals cause oxidative stress which results in DNA damage
Links between cocaine and lung disease
Depends on route of entry, dose and freq
Increases risk of
- acute respiratory symptoms
- Increased infection and aspiration pneumonia
- Increased barotrauma and pneumothorax due to inhalation
- Airway injury - nasal wall, septum
- Asthma: precipitates bronchospasm and wheeze
- Haemoptysis due to capillary damage
- Crack lung: 2y to prolonged inflammation associated with fever, hypoxia, haemoptysis, resp failure and diffuse eosinophilia alveolar infiltrates
- Emphysema
Links between cannabis and lung disease
Greater exposure to smoke as long inhalation time Increased resp symptoms Increased COPD Injuries to bronchial mucosa Decreased cilia Increased lung cancer Increased pneumothorax
Side effects of chemotherapy
Myelosuppression: anaemia, low WCC Alopecia Nausea and vomiting Infertility Fatigue Impaired wound healing Mouth ulcers Teratogenicity Menopausal symptoms Decreased libido Extravasation
Types of radiation therapy in lung cancer
External beam radiation therapy - focused beam from outside the body
- intensity modulated
- Stereotactic
brachytherapy
- Internal radiation therapy
- Shrinks tumours in airway to relieve symptoms
- Done through surgery or bronchoscope
Complications of radiotherapy - ACUTE
General fatigue Erythema Desquamation Skin tanning Hair loss GI: decreased taste, oral mucositis, D&V, N&V Immunosuppression Pneumonitis
Complications of radiotherapy for lung cancer - CHRONIC
Neck fibrosis Jaw muscle fibrosis Lymphoedema Infertility Delayed healing Telangiectasia Salivary dysfunction Transverse myelitis Increased CV risk Hypothyroidism Hearing loss Cataracts or retinitis
Increased risk of secondary cancer
Aims of TNM staging
Aid clinician in planning of treatment
To give indication of prognosis
To assist evaluation of results of treatment
To facilitate the exchange of information between treatment centres
To contribute towards the continuation of investigation into human cancer
TNM staging
T - size of the primary tumour and degree of local spread /4
N - size, location and number of lymph nodes affected /3
M - mets present or not /1
Cancer staging never changes
If there is any doubt, use the lower level. All cases should be confirmed microscopically
Epidemiology of colon cancer
3rd most common cancer cause 2nd most common cause of cancer death 47 per 100,000 Increased in males Increased with age
RFs
- FHx under 60
- Past history of colorectal cancer
- Polyposis syndromes: HNPCC, FAP, Turcot’s syndrome, Peutz-Jegher’s syndrome, juvenile polyposis syndrome)
- UC/Crohn’s
- Pelvic radiotherapy
- Obesity
- Sedentary lifestyle
- Diet high in meat and fat
- Increased alcohol
- Diabetes
- Cholecystectomy
Symptoms of colon cancer
Dependent on site
left sided - early obstruction, fresh rectal bleeding, tenesmus, mucus, early change in bowel habit, mass in LIF
right sided - anaemia from occult bleeding, altered bowel habit, weight loss, anaemia. More advanced at presentation
Can have symptoms of obstruction of perforation
hepatomegaly from mets
Abdominal distension
Lymphadenopathy
Locations of colon cancer
45% is rectosigmoid
30% ascending
15% descending
10% transverse colon
Common met sites for colon cancer
Liver
Lung
Bone
Pathophysiology of colon cancer
Malignant transformation of benign adenomatous polyp
Accumulation of multiple genetic mutations
APC gene - progession of early adenoma development
K-Ras gene - failure leads to cell proliferation
p53 gene - cell proliferation and impaired apoptosis
Investigations for colon cancer
FBC (anaemia)
Raised CRP
LFTs - normal unless mets
U&E - normal unless ureter compression
Colonoscopy - gold standard + biopsy for histological analysis
Double contrast barium enema - apple coring or mass (used if colonoscopy can’t be tolerated)
CT colonography but will need colonoscopy for biopsy
Once diagnosed CT TAP for mets
Liver US
CEA - carcinoembryonic antigen - not used for screening but can be used to predict relapse
Causes of raised CEA
Bowel cancer breast cancer Lung cancer Cancer of: Stomach Oesophagus Pancreas mesothelioma Medullary thyroid cancer
Management of rectal cancer
Determine risk of local recurrence
LOW - No lymph nodes T<3
MODERATE - T>3 or lymph
HIGH - <1mm resection margin, encroaching on local structures
Low = surgery
Moderate - pre-op radiotherapy then surgery
High = pre-op chemo, time to shrink, surgery
MDT
May need MRI to determine capsular involvement
Management of colon cancer
Stage 1 - resection II, low risk = resection II, high risk = adjuvant chemo III - adjuvant chemotherapy IV - symptom control, consider resection, MDT for management decision
FBC findings in iron deficiency anaeamia
Low Hb Low serum ferritin Hypochromic cells (Low MCH) Low MCV (microcytic) Low Iron
Causes of iron deficiency anaemia
Occult GI blood loss
- Aspirin/NSAID
- Colon/oesophageal/gastric cancer
- Benign gastric ulceration
- Angiodysplasia
- Oesophagitis
Malabsorption
- Coeliac disease
- Gastrectomy
- H. pyori infection
- less common: gut resection or bacterial overgrowth
Non GI blood loss
- menstruation
- blood donation
Management of iron deficiency anaemia
If anaemic:
- Check coeliac serology
- If positive: small bowel biopsy
- If negative and post-menopsaual then colonoscopy & OGD
If premenopausal, coeliac negative and anaemia
- If upper GI symptoms = OGD
- If FHx of colorectal cancer or lower GI symptoms = colonscopy
- If no GI symptoms = iron replacement and investigate further if becomes transfusion dependent
If no anaemia and under 50 then iron placement
- If no anaemia develops then no further investigation required
- If over 50 precede as if anaemic
Locations for gastric cancer
50% pylorus
25% lesser curve
10% cardia
8% lymphomas
Epidemiology of gastric cacncer
Increases with age (95% are over 55)
More common in men
8th most common cancer worldwide, 13th UK
Increased in Japan, China, South America
FHx - yes (2-3x increase if 1st degree family member)
RFs
- H. pylori infection
- Diet high in salt, preserved food, decreased fruit and veg
- Poor socioeconomic status
- Smoking
- Alcohol
- Atrophic gastritis
- Post-gastrectomy
- Blood group A
- meniere’s
Histological types of gastric cancer
Type 1 - intestinal - well formed glandular structures. Differentiated, more common in distal stomach. Strong environmental association
Type 2 - diffuse - poorly cohesive cells, particularly in cardia. Poorer prognosis. Loss of expression of cell adhesion moleucule E-Cadherin. Occurs in the younger population
Pathophysiology of gastric cancer
Correa’s cascade
- Chronic non atrophic gastritis
- Atrophic gastritis
- Intestinal metaplasia
- Dysplasia
- Cancer
90-95% adenocarcinoma
1-5% lymphomas
2% GI stromal tumours
Symptoms of gastric cancer
Early satiety Weight loss Dysphagia Epigastric pain Dyspepsia Nausea or vomiting Decreased appetite Haematemesis or melena
Signs of gastric cancer
Palpable enlarged stomach Succession splash Hepatomegaly Periumbilical masses Enlarged Virchow's node Anaemia
Investigations for gastric cancer
Urgent 2 week referral if
- Dyspepsia + one of: anaemia, dysphagia, weight loss, persistent vomiting, epigastric mass
- 55 with new onset dyspepsia
- dysphagia, obstructive jaundice, unexplained upper abdo pain, weight loss
Bloods - FBC (anaemia), LFTs
Endoscopy + biopsy (antisecretory therapy should be withheld until after endoscopy
Endoscopic US for local staging and depth of penetration
CT TAP for staging or PET/CT
Management of gastric cancer
Operable - preferred: pre-op chemo - surgery Distal cancer = sub total, proximal = total gastrectomy If curable remove D2 lymph nodes - post op chemo - consider adjuvant chemoradiation
Inoperable
- palliative chemotherapy
- HER2 negative then platinum based chemotherapy
- HER2 positive then trastuzumab
Blood transfusion for symptomatic anaemia
Corticosteroids for anorexia
Coeliac plexus nerve block for pain
Hallmarks of cancer
Genome instability and mutation Resisting cell death Sustaining proliferative signalling Evading growth suppressors Enabling replicative immortality Inducing angiogenesis Activating invasion and mets Reprogramming energy metabolism Tumour promoting inflammation Evading immune destruction
Role of TP53
Induces apoptosis when there is cell damage
If mutation or loss of TP53 then cancer
Interpreting the FBC
Hb
Haemoglobin
Shows the CONCENTRATION of Hb in blood
If low = anaemia
Interpreting the FBC
MCV
Mean cell volume
Low = microcytic
Normal = normocytic
High = macrocytic
Interpreting the FBC
Reticulocyte count
Concentraiton of immature red cells
Increased in blood loss and haemolytic anaemia
What goes Hct or PVC show on FBC
Haematocrit or packed cell volume
Shows the % of red blood cells in the blood
Causes of microcytic anaemia
Iron deficiency
Haemoglobinopathies
Sideroblastic
Myelodysplastic syndrome
Causes of normocytic anaemia
Anaemia of chronic disease
Acute blood loss
Haemolytic anaemia
Sickle cell
Causes of macrocytic anaemia
Alcoholism B12 and folate deficiency Reticulocytosis Liver disease Oestrogens Methotrexate Hypothyroidism Bone marrow failure Pregnancy
Blood tests for suspected anaemia
FBC
Haemotinics - B12, folate, ferritin
Iron studies
TFTs
Blood film +/- marrow biopsy if relevant (if ?bone marrow/haemolytic/sideroblastic)
Hb electrophoresis (if ?thalassaemia or sickle cell)
Bilirubin in haemolysis
Causes of B12 deficiency
Pernicious anaemia
Malabsorption (gastrectomy/ ileum resection)
Causes of folate deficient
Dietary (alcoholism, neglect)
Increased requirements (pregnancy, haematopoiesis)
Malabsorption (coeliac, pancreatic insufficiency, gastrectomy, Crohn’s)
Drugs (phenytoin, methotrexate, trimethoprim)
Causes of haemolytic anaemia
Inherited
- Sickle cell
- Thalassaemia
- Hereditary spherocytosis
- Elliptocytosis
- G6PD deficiency
- Pyruvate kinase deficiency
Acquired
- Autoimmune
- Drug induced
- DIC
- TTP
- Toxins (lead, uraemia, drugs)
- Malaria
- Paroxysmal nocturnal haemoglobinuria
Causes of polycythaemia
Relative:
- Acute dehydration
- Obesity
- HTN
- Alcohol
- Smoking
Absolute
- Ruba vera
- Raised EPO
- Hypoxia e.g. COPD
Causes of raised neutrophils
Bacterial infection Inflammation Necrosis Corticosteroids Malignancy Myeloproliferative disorder Stress
Causes of low neutrophils
post-chemotherapy agranulocytosis from drugs Viral infection Hypersplenism Bone marrow failure e.g. leukaemia Felty's syndrome
Drugs that cause agranulocytosis
Carbamazepine
Clozapine
Colchicine
Carbimazole
Causes of raised eosinophils
Allergy Eczema Parasite infection (Leishmaniasis) Drug reactions Hypereosinophilic syndrome Hodgkin's disease
Features of Felty’s syndrome
RA
Leukopaenia
Hypersplenism
Causes of thrombocytopaenia
Low platelets
Decreased production
- Bone marrow failure
- Aplastic anaemia
- megaloblastic anaemia
- myelosuppression
increased destruction or consumption
- DIC
- Thrombotic thrombocytopenic purpura
- Haemolytic uraemic syndrome
- Sequestration
- SLE
- CLL
Define megaloblastic anaemia
Abnormality of erythoblasts in bone marrow in which maturation of the nucleus is delayed relative to the cytoplasm
Results from defective DNA synthesis
Large immature RBCs (megaloblasts) and hypersegmented neutrophils are in circulation
Epidemiology of megaloblastic anaemia
More common in women
peak age = 60
FHx
Aetiology of megaloblastic anaemia
B12 or folate deficiency
- 80% is pernicious anaemia
B12 deficiency
- Gastrectomy, gastric resection, gastritis, H. pylori, congenital intrinsic factor deficiency
- Inadequate dietary intake
- Malabsorption, ileal resection, Crohn’s of ileum, chronic tropical sprue, HIV
- Drugs: colchicine, neomycin, metformin
- Long term PPI
B12 deficiency takes 4-5 years due to abundant liver stores
Folate def
- Dietary deficiency
- Malabsorption
- increased demand: haemolysis, leukaemia, pregnancy
- Increased urinary excretion: HF, acute hepatitis, dialysis
- Drug induced: alcohol, methotrexate, anticonvulsants, sulfasalazine, trimethoprim
Causes of non-megaloblastic macrocytosis
(not B12 or folate deficiency)
Alcohol abuse Liver disease Severe hypothyroidism Reticulocytosis Aplastic anaemia Red cell aplasia Myelodysplastic syndromes Myeloid leukaemia Azathioprine
Presentation of megaloblastic anaemia
SOB on exertion
Fatigue
Palpitations
Exacerbations of angina
Conditions associated with pernicious anaemia
Vitiligo Primary hypothyroidism Hashimoto's disease Addison's disease Diabetes Hypoparathyroidism
Investigations for megaloblastic anaemia
FBC (raised MCV, low Hb, raised reticulocytes)
Blood film (macrocytic red cells, neutrophils with hypersegmented nuclei, Howell-Jolly bodies)
Serum folate
Serum B12
LFTs - raised unconjugated bilirubin if increased breakdown of RBC precursors
Urinalysis
Coomb’s test for haemolytic anaemia
Bone marrow exam only if ? haematological malignancy
Autoantibody screen: intrinsic factor antibodies (only found in 27% of pernicious anaemia, but are 100% diagnostic)
Gastric parietal antibodies (more sensitive but less specific)
Schilling’s test - measures absorption of B12 by measuring radioactivity after oral B12 radioisotope (rarely used)
When are Howell-Jolly bodies seem
Asplenia
- Hereditary spherocytosis
- Trauma
- Autosplenectomy (sickle cell)
Radiation therapy e.g. Hodgkin's lymphoma Amyloidosis Severe haemolytic anaemia Megaloblastic anaemia Hereditary spherocytosis Myelodysplastic syndrome
management of megaloblastic anaemia
A cause must be found - not a final diagnosis
- Correct defieicny
- Treat underlying condition
Management of pernicious anaemia
6 injections of hydroxycobalamin every 2-4 days
Then every 3 months
If neurological involvement then every other day then every 2 months
If both B12 and folate deficient - treat the B12 first or it can precipitate subacute degeneration of the spinal cord
WHO pain ladder
- non-opioid including NSAIDs and Paracetamol
+/- adjuvant analgesia (including steroids and antidepressants) - Opioid for mild-moderate pain
+/- non opioid agent
+/- adjuvant analgesia - opioid for moderate severe pain + 1 + 2
Management of mild to moderate pain
- Paracetamol max dose
- Substitute Paracetamol for NSAID (ibuprofen)
- Add Paracetamol to 2
- Paracetamol + naproxen
- Full therapeutic dose of weak opioid (codeine)
Drugs used for neuropathic pain
Amitriptyline
Gabapentin
Pregabalin
Duloxetine
Tramadol only as acute rescue therapy
Epidemiology of pancreatic cancer
Age: peaks in 70s and 80s Increased in men 2% of all cancers Very poor prognosis Fhx - 5-10% have inherited component
RFs Smoking Hereditary cancer syndromes Hereditary pancreatitis Chronic sporadic pancreatitis Diabetes mellitus Obesity Dietary factors (high red meat) IBD, peptic ulcer disease
- Peutz-Jeghers syndrome
- BRCA1 or 2
- HNPCC (Lynch’s syndrome)
Pathophysiology of pancreatic cancer
Linear progression from 3 precursor lesions to invasive ductal adenocarcinoma
Accumulation of multiple genetic alterations
65% head of pancreas
15% body
10% tail
10% multifocal
Spread to liver, lung, skin, brain
Symptoms of pancreatic cancer
Painless, progressive, obstructive jaundice
- Pale stools, dark urine
Abdominal pain - epigastric, radiating to the back, worse when supine, eased sitting forward
Non-specific upper abdominal pain or discomfort
Weight loss
Anorexia
Steatorrhoea
Thirst, polyuria, nocturia
Nausea and vomiting
Bruising
Haematemesis, melena
Signs of pancreatic cancer
Epigastric mass Iron deficiency anaemia (pallor) Enlarged supraclavicular node Petechia, purpura Jaundice Courvoiser's sign POSITIVE - palpable gall bladder, painless Trousseau's sign Hepatomegaly
Courvosier’s sign
palpable gall bladder, painless jaundice
Pancreatic cancer
Trousseau’s sign
HYPOCALCAEMIA BP cuff around the arm. Leave in place for 3 minutes Spasms of the hand and forearm indicate hypocalcaemia Flexion of wrist, MCP joints Extension of DIP and PIP
Investigations for pancreatic cancer
FBC - normocytic normochromic anaemia
LFTs - raised bilirubin, raised ALP and GGT
Hyperglycaemia
Tumour marker - CA19-9
US liver, bile duct and pancreas
Abdominal CT for staging
Endoscopic US for tumour biopsy and histological analysis
MRA - MR angiography - delineates tumour and vascular supply
Management of pancreatic cancer
10% resectable
- proximal pancreatic duodenectomy + antrectomy (Whipple’s procedure)
- adjuvant chemotherapy with GEMCITABINE
90% unresectable
- Stenting of bile duct or duodenum to relieve itch and jaundice
- Palliative chemotherapy if reasonable performance status
- Pain relief
- Coeliac plexus block
- Chemoraditation for severe pain
- Pancreatic enzyme supplements for weight maintenance
Prognosis of pancreatic cancer
Very poor
Stage 1 A has medial survival or 24 months
Stage 4 - 4 months
Primary liver cancers
90% are hepatocellular carcinoma
Other
- hepatoblastoma (more common in children)
- cholangiocarcinoma
Epidemiology of liver cancers
Prevalence follows rates of Hep B and C infection
Highest in Asia and Sub-Saharan Africa
Onset generally 20-30 years after insult
Risk increases with age
More common in men (4-8x)
FHx YES
RFs Alcohol Cirrhosis NAFLD Metabolic syndrome Primary sclerosing cholangitis Cholecystectomy Smoking Hep B and C COCP Diabetes HIB Alpha 1 antitrypsin deficiency High BMI Primary biliary cirrhosis SLE Parasitic flat worm infection Aflatoxins
Aetiology of hepatocellular carcinoma
Patients with cirrhosis have the highest risk of developing HCC
90-95% have underlying cirrhosis
Causes of cirrhosis
- Hep B or Hep C
- alcoholism
- Genetic haemachromatosis
- Primary biliary cirrhosis
- Aflatoxins (myotoxins produced by Aspergillus)
- Metabolic syndrome, diabetes, smoking
Pathophysiology of hepatocellular carcinoma
Acquisition of Hpe B in early life can cause chronic inflammation and cirrhosis
Hep B is a direct carcinogen and causes methylation of p16 gene causing HCC
Chronic Hep B, Hep C and metabolic disorder can lead to p53 damage
Aflatoxins from aspergillus (found in contaminated soya beans) causes mutations in p53
HCC from the development of dysplastic nodules
Spreads to lymph, bone and lungs
