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Cancer Flashcards

1
Q

Benefits of mammography screening

A 
Reduction in breast cancer mortality
Detects cancer earlier
Can find smaller cancers 
- Decreases extensiveness of treatment required
- Allows for breast conserving surgery
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2
Q

Limitations of mammography screening

A 
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
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3
Q

Epidemiology of breast cancer

A 
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
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4
Q

Signs and symptoms of breast cancer

A 
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
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5
Q

Breast lump - indications of malignancy

A 
Hard
Painless
Irregular margins
Fixation to skin or chest wall
Skin dimpling
Discharge that is unilateral and bloody
Nipple retraction
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6
Q

Breast lump - indications it’s benign

A 
Firm or rubbery
Often painful
Regular or smooth margins
Mobile
No skin changes
If discharge bilateral, no blood
No nipple changes
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7
Q

Gene associated with breast cancer

A

BRCA1 or 2

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8
Q

Most common breast cancer type

A

Almost all are from glandular epithelium lining lactiferous ducts - adenocarcinomas

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9
Q

Investigations for breast cancer

A

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

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10
Q

Triple assessment for breast cancer

A

Imaging - US or mammography

Clinical examination

FNA or core biopsy

Need all 3 negative to exclude carcinoma

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11
Q

Tumour marker in breast cancer

A

CA 15-3

Can be used for prognosis

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12
Q

Hisological markers in breast cancer

A

Oestrogen and progesterone receptor status

HER2 - human epidermal growth factor 2

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13
Q

Likely met sites for breast cancer

A

Bone
Brain
Lung
Liver

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14
Q

Staging of breast cancer

A 
0 - in situ
1 - up to 2cm
2 - 2-5cm or nodes on same side
3 - over 5cm of adherent nodes
4 - mets
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15
Q

Management of breast cancer

A

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)

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16
Q

Types of breast cancers

A 
Invasive ductal (90%)
Invasive lobular (8%)
Mucinous or tubular = rare
DCIS = pre invasive
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17
Q

Prognosis of breast cancer

A

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

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18
Q

Complications of breast cancer

A

Psychological implications
- Can be reduced with less destructive surgery, counselling, nipple preservation, reconstructive surgery
Post op complications
Lymphoedema of the arm

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19
Q

Risk factors for lymphoedema

A

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

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20
Q

Treatments for lymphoedema

A 
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
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21
Q

Pathogenesis of cancer mets

A 
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
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22
Q

Lab pathway of tissue sample

A
  1. Sample collected and placed in formalin
  2. Transferred to lab - delay from porter
  3. Allowed to fix overnight - time delay
  4. Placed in cassette
  5. Processed to wax overnight - time delay
  6. Sectioned and stained
  7. Added to pile of slides for pathologist - time delay with staffing levels
  8. Reported by pathologist
  9. Written report typed - time delay by secretary staffing
  10. Report checked and signed by pathologist
  11. Report sent to requesting physician
  12. Report received by requesting clinician
  13. Read
  14. Report acted on

Minimum of 2-3 days,

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23
Q

Describe bronchoscopy process

A

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

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24
Q

Role of coroner

A

Independent official with legal responsibilities for the medical legal investigation of certain deaths: sudden, unexplained, unnatural or violent in nature

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25
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
26
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
27
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
28
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
29
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 ```
30
Types of non-small cell lung cancers
``` Squamous (42%) Adenocarcinoma (40%) Large cell (8%) Carcinoid tumours (6%) Bronchoalveolar cell (4%) ```
31
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 ```
32
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 ```
33
Large cell carcinoma of lung
8% Less differentiated forms of adenocarcinoma and squamous cell carcinoma Mets early
34
Signs and symptoms of lung cancer
``` Cough haemoptysis weight loss SOB Chest pain Clubbing Fever Weakness Dysphagia ``` SVC obstruction Hoarseness Horner's syndrome
35
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
36
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
37
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
38
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
39
Complications of lung cancer
``` Recurrent laryngeal nerve palsy phrenic nerve palsy horner's syndrome pancoast's syndrome SVC obstruction pericarditis Rib erosion AF ```
40
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.
41
4 collateral routes in SVC obstruction
Azygous system Internal mammary system Long thoracic venous system Femoral and vertebral veins
42
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
43
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
44
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
45
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)
46
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
47
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
48
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 ```
49
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 ```
50
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
51
Complications of radiotherapy - ACUTE
``` General fatigue Erythema Desquamation Skin tanning Hair loss GI: decreased taste, oral mucositis, D&V, N&V Immunosuppression Pneumonitis ```
52
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
53
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
54
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
55
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
56
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
57
Locations of colon cancer
45% is rectosigmoid 30% ascending 15% descending 10% transverse colon
58
Common met sites for colon cancer
Liver Lung Bone
59
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
60
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
61
Causes of raised CEA
``` Bowel cancer breast cancer Lung cancer Cancer of: Stomach Oesophagus Pancreas mesothelioma Medullary thyroid cancer ```
62
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
63
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 ```
64
FBC findings in iron deficiency anaeamia
``` Low Hb Low serum ferritin Hypochromic cells (Low MCH) Low MCV (microcytic) Low Iron ```
65
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
66
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
67
Locations for gastric cancer
50% pylorus 25% lesser curve 10% cardia 8% lymphomas
68
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
69
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
70
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
71
Symptoms of gastric cancer
``` Early satiety Weight loss Dysphagia Epigastric pain Dyspepsia Nausea or vomiting Decreased appetite Haematemesis or melena ```
72
Signs of gastric cancer
``` Palpable enlarged stomach Succession splash Hepatomegaly Periumbilical masses Enlarged Virchow's node Anaemia ```
73
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
74
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
75
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 ```
76
Role of TP53
Induces apoptosis when there is cell damage | If mutation or loss of TP53 then cancer
77
Interpreting the FBC | Hb
Haemoglobin Shows the CONCENTRATION of Hb in blood If low = anaemia
78
Interpreting the FBC | MCV
Mean cell volume Low = microcytic Normal = normocytic High = macrocytic
79
Interpreting the FBC | Reticulocyte count
Concentraiton of immature red cells | Increased in blood loss and haemolytic anaemia
80
What goes Hct or PVC show on FBC
Haematocrit or packed cell volume | Shows the % of red blood cells in the blood
81
Causes of microcytic anaemia
Iron deficiency Haemoglobinopathies Sideroblastic Myelodysplastic syndrome
82
Causes of normocytic anaemia
Anaemia of chronic disease Acute blood loss Haemolytic anaemia Sickle cell
83
Causes of macrocytic anaemia
``` Alcoholism B12 and folate deficiency Reticulocytosis Liver disease Oestrogens Methotrexate Hypothyroidism Bone marrow failure Pregnancy ```
84
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
85
Causes of B12 deficiency
Pernicious anaemia | Malabsorption (gastrectomy/ ileum resection)
86
Causes of folate deficient
Dietary (alcoholism, neglect) Increased requirements (pregnancy, haematopoiesis) Malabsorption (coeliac, pancreatic insufficiency, gastrectomy, Crohn's) Drugs (phenytoin, methotrexate, trimethoprim)
87
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
88
Causes of polycythaemia
Relative: - Acute dehydration - Obesity - HTN - Alcohol - Smoking Absolute - Ruba vera - Raised EPO - Hypoxia e.g. COPD
89
Causes of raised neutrophils
``` Bacterial infection Inflammation Necrosis Corticosteroids Malignancy Myeloproliferative disorder Stress ```
90
Causes of low neutrophils
``` post-chemotherapy agranulocytosis from drugs Viral infection Hypersplenism Bone marrow failure e.g. leukaemia Felty's syndrome ```
91
Drugs that cause agranulocytosis
Carbamazepine Clozapine Colchicine Carbimazole
92
Causes of raised eosinophils
``` Allergy Eczema Parasite infection (Leishmaniasis) Drug reactions Hypereosinophilic syndrome Hodgkin's disease ```
93
Features of Felty's syndrome
RA Leukopaenia Hypersplenism
94
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
95
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
96
Epidemiology of megaloblastic anaemia
More common in women peak age = 60 FHx
97
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
98
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 ```
99
Presentation of megaloblastic anaemia
SOB on exertion Fatigue Palpitations Exacerbations of angina
100
Conditions associated with pernicious anaemia
``` Vitiligo Primary hypothyroidism Hashimoto's disease Addison's disease Diabetes Hypoparathyroidism ```
101
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)
102
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 ```
103
management of megaloblastic anaemia
A cause must be found - not a final diagnosis - Correct defieicny - Treat underlying condition
104
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
105
WHO pain ladder
1. non-opioid including NSAIDs and Paracetamol +/- adjuvant analgesia (including steroids and antidepressants) 2. Opioid for mild-moderate pain +/- non opioid agent +/- adjuvant analgesia 3. opioid for moderate severe pain + 1 + 2
106
Management of mild to moderate pain
1. Paracetamol max dose 2. Substitute Paracetamol for NSAID (ibuprofen) 3. Add Paracetamol to 2 3. Paracetamol + naproxen 5. Full therapeutic dose of weak opioid (codeine)
107
Drugs used for neuropathic pain
Amitriptyline Gabapentin Pregabalin Duloxetine Tramadol only as acute rescue therapy
108
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)
109
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
110
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
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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 ```
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Courvosier's sign
palpable gall bladder, painless jaundice | Pancreatic cancer
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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 ```
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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
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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
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Prognosis of pancreatic cancer
Very poor Stage 1 A has medial survival or 24 months Stage 4 - 4 months
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Primary liver cancers
90% are hepatocellular carcinoma Other - hepatoblastoma (more common in children) - cholangiocarcinoma
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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 ```
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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
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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
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Aflatoxins
Mycotoxin produced from Aspergillus Found in contaminated soya beans
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Symptoms of liver cancer
``` Pruritus Confusion (hepatic encephalopathy) Weight loss Abdominal distension (ascites) Jaundice RUQ pain ```
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Signs of liver cancer
``` Splenomegaly Jaundice Hepatomegaly Bleeding oesophageal varices Palmar erythema Early satiety Ascites Spider naevi Peripheral oedema Anaemia Asterixis Periumbilical collateral veins ```
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Investigations for liver cancer
FBC - microcytic anaemia, thrombocytopaenia CRP - may be raised U&Es - hyponatraemia, raised urea LFTs - deranged - high IR or PT. Low albumin AFP - tumour marker for HCC Liver US - mass over 2cm + raised AFP is diagnostic FNA +/- biopsy Staging CT TAP
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Screening for liver cancer
HBV carriers High HBV DNA Hep C Alcoholic cirrhosis Surveillance = 6-12 monthly US and AFP
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Management of liver cancer
Liver transplant - minority are suitable. Solitary tumour under 5cm Tumour resection - Preferred choice if no cirrhosis - Higher recurrence rate than transplant - Only if no extrahepatic spread and adequate liver function Ablative therapy - Alcohol/ethanol injection - Radiofrequency ablation: high frequency US produces tumour necrosis,. Useful if resection not possible. - Microwave ablation: destroys tumour cells with heat and induces tissue necrosis - Chemoembolistion: high concentration chemo via hepatic artery - Systemic chemotherapy in advanced disease (HCC is relatively chemo resistant) - Selective internal radiation therapy
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Prognosis of liver cancer
Depends on extent of underlying cirrhosis median survival 6 months. Liver failure can occur with death due to: - Cachexia - Variceal bleeding - Tumour rupture with peritoneal bleeding
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Types of ovarian cancers
Epithelial tumours (85-90%) - Arise from epithelial cells - Serous (40-50%) in 40-60 years - Endometroid (10-20%) in 50-70 years - Clear cell (5-6%) in 40-80 year associated with endometriosis - Mucinous (10%) Germ cell tumours (2-10%) - Derived from primitive germ cells of gonas - Women under 35 - Curable with high survival rates - Rapidly enlarging abdominal mass with pain Sex cord-stromal tumours <5% - from connective tissue cells - fibroma/fibrosarcoma/granulosa cell Borderline tumours - Low malignant potential - Do not respond well to chemo
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Epidemiology of ovarian cancer
``` 5th most common cancer in women 2% lifetime risk Increases with age, peak at 70 Increased in Caucasians Fhx yes - BRCA1/2 ``` ``` RFs Smoking Obesity Nulliparous Decreased exercise Early menarche Late menopause Asbestos Endometriosis HT Hx of infertility or infertility treatments e.g. clomifene ```
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Protective factors for ovarian cancer
COCP Child bearing Breast feeding Early menopause
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Met sites for ovarian cancer
Pelvic and peri-aortic lymph nodes Over abdominal peritoneum Bowel mesentery Liver capsule Peritoneal cavity
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Presentation of ovarian cancer
75% present with stage 3 or 4. Insidious onset ``` Abdominal discomfort Abdominal distension Bloating Urinary frequency Dyspepsia Weight loss Fatigue Anorexia Depression Pelvic or abdominal mass Abnormal uterine bleeding Ascites or pleural effusion Abdominal, pelvic or back pain is a later sign ```
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Investigations for ovarian cancer
``` Organise CA125 If raised - pelvic and abdo US If both raised = suspicious CT abdo pelvis for assessment Use Risk Malignancy Index 1 to assess likelihood of malignancy. Refer if >250 ``` Alpha fetoprotein can be used to exclude endodermal sinus tumours Beta hCG can be used for dysgerminomas, embryal carcinomas or choriocarcinomas Tissue sampling and histopathology
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Management of ovarian cancer
Exploratory laparotomy with standard TAH + BSO + lymph node biopsy Surgery, usually with adjuvant chemotherapy - Conservative if young and still want children Chemotherapy for all those stage 2 and above. Paclitaxel and carboplatin Can use intraperitoneal chemo Radiotherapy only in early disease CA125 can be used for monitoring efficacy and recurrence
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Cancers curable with chemotherapy
``` Teratoma Seminoma High grade Hodgkin's lymphoma Wilm's Myeloma ```
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Cancers with no gain for chemotherapy
Melanoma Renal Cholangiocarcinoma
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MOA of cytotoxics
Antimetabolites: 5FU, gemcitabine, capectiabine Alkylating agents - cyclophosphamide, cisplatin, carboplastin Mitotic spindle poison - vincristine Taxanes - paclitaxel, docetaxel Modify tertiary structure of DNS - etoposide
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Short term side effects of chemotherapy
``` Nausea and vomiting Anorexia Weight loss Alopecia Bone marrow suppression - neutropaenia, anaemia, thrombocytopaenia Infective symptoms Fatigue Liver and renal toxicity Mucositis peripheral sensory neuropathy Ototoxcity Acute cardiomyopathy ```
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Long term side effects of chemotherapy
``` Cardiomyopathy Pulmonary fibrosis Increased risk of secondary cancers, particularly Hodgkin's, acute leukaemia, testicular cancer Subfertility/infertility Renal insufficiency ```
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Why are brain tumours hard to treat with chemotherapy
Chemotherapy is a large molecular with low solubility BBB is lipid soluble and small molecules Can't cross the BBB to treat Brain tumours also poorly irrigated
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When chemotherapy can be given?
Primary chemotherapy - sole anti cancer treatment if highly sensitive tumour types Adjuvant - given after surgery to mop up microscopic disease Neo-adjuvant - given pre-surgery to shrink the tumour Concurrent - given with radiation
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Hormonal chemotherapy therapies
Usually reserved for breast and prostate cancer. Highly effective and relatively non-toxic Breast cancer - If oestrogen receptor positive, oestrogen binds to cells to increase growth - Tamoxifen (SERM) competes for this binding to stop growth - Aromatase inhibitors prevent precursors being converted into oestrogen Prostate cancer - androgens are a critical growth factor for prostate cancer - Goserelin - LHRH agonist - reduces pituitary production of LH and FSH - Flutamide anti-androgen, competitive androgen receptor inhibitor Resistance will eventually develop
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Biological chemotherapy agents
Work differently depending on the target cell Recognise and attach to specific proteins produced by cells - Breast cancer: Trastuzumab (Herceptin) if HER2 + - Lymphoma: Rituximab (anti CD20) - Colorectal cancer: Cetuximab (EGF receptor) - Colorectal, lung and breast: bevactzumab (VEGF) - CLL: Alemtuzumab (CD52) - Lung cancer: Erlotinib (EGFR-TK mutation)
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Normal bone marrow
Contains a matrix of sinusoids lined with epithelial cells interspaced with islands of erythropoeitic cells encapsulated by reticulin cells Composed of red marrow and inactive adipose tissue (yellow marrow) Found in pelvic, ribs and end of axial long bones At birth 100% red marrow, decreases with age
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Causes of bone marrow failure
Haemopoietic cell damage causing hypo/aplastic anaemia - Congenital: Fanconi's anaemia, Diamond Blackfan anaemia - Acquired: Hep B, EBV, parvovirus 19, autoimmunity, radiation, drugs, poisons (benzene), paroxysmal nocturnal haemaglobinuria - Abnormal or hostile marrow microenvironment - Immunological suppression of haematopoesis Maturation defects - B12 or folate deficiency Differentiation defects - myelodysplasia Bone marrow infiltration - Lymphoma - Myeloma - Carcinoma - Hairy cell leukaemia
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Fanconi's anaemia
``` Autosomal recessive Causes bone marrow failure by 40 Significant risk of AML Increased in Jewish population Genetic defect resulting in failure of DNA repair ``` ``` Short stature Café au lait spots petechial, bruises Fatigue Pale ```
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Presentation of bone marrow failure
Anaemia - fatigue, weakness, pallor, SOB, tachycardia Neutropaenia - recurrent or severe bacterial infections. sepsis. pneumonia. cellulitis Thrombocytopaenia - easy bruising, petechiae, bleeding from nose/gums, heavy periods, melaena, haematuria, haematemesis, severe headaches, dizziness If hepatomegaly, splenomegaly or lymphadenopathy - suggests leukaemia
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Investigations for bone marrow failure
FBC - normocytic normochromic anaemia, low reticulocyte count. Agranulocytosis, thrombocytopaenia Ham test / sucrose haemolysis test - Positive in paroxysmal nocturnal haemoglobinuria Falconi anaemia screening - in all children with aplastic anaemia Bone marrow biopsy and aspiration - histology may provide cause of the failure - Marrow replaced with fat cells - Very few haematopoietic cells - Hypoplastic in non-leukaemic causes Imaging - PET or MRI
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Paroxysmal nocturnal haemoglobinuria
Rare acquired, life threatening disease Destruction of red blood cells by the complement system Only ACQUIRED haemolytic anaemia - Defect in cell membrane (glycophosphatidylinositol) Haematuria- more noticeable in the morning
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Management of bone marrow failure
Transfusions of RBCs and platelets as required Severe cases - bone marrow transplant - only if under 55, with severe disease and a match If transplant not an option - intensive immunosuppressive therapy with haematopoietic growth factors: ciclosporin White blood cell stimulating agents: filgrastrim EPO
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Subtypes of nausea associated with chemotherapy
Acute - within 24 hours of chemo Delayed - between 24 hours and 5 days Breakthrough - occurs despite prophylactic treatment Anticipatory - triggered by surroundings or anxiety for chemotherapy Refractory - occurs with failed antiemetic use
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Chemotherapy that has high chance of nausea and vomiting
Cisplatin Dacarbazine Doxorubicin Cyclophosphamide Carboplatin Irinotecan Oxaloplatin
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Risk factors for N&V with chemotherapy
``` Female Under 55 N&V during pregnancy Hx of motion sickness Anxiety or depression ```
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Management of nausea and vomiting in chemotherapy
Acute - Dexamethasone - Add 5HT3 if severe Delayed - Domperidone - Add dexamethasone if severe
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Managing alopecia with chemotherapy
``` Always reversible Can be reduced by scalp cooling during chemotherapy Cut hair short. Wigs Wear sun cream ```
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Neuropathy and chemotherapy
More common with paclitaxel and docetaxel Can start anytime after treatment and worsens as treatment continues Starts in toes - Protect feet from injury - Use walking aids - Check water temperature
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MOA of radiotherapy
X-rays Collide with orbiting electrons in tissues to eject fast electrons - damages DNA through direct action More commonly collides with water producing hydroxyl radicals that damage DNA through indirect action (2/3)
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When is radiotherapy given in cancer?
Radically +/- chemotherapy as a curative treatment Adjuvant with surgery In palliation - to increase survival and increase quality of life
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What causes increase cell sensitivity to radiotherapy?
``` Cells in G2 or M Increased cell oxygenation Highly active metabolically Well nourished and rapidly dividing Lymphocytes and oocytes ```
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Immediate effects of radiotherapy
Depends on site ``` Lethargy Skin redness Local discomfort Nausea Mucositis, diarrhoea hair loss Decrease taste Blood changes Flu like symptoms Decreased libido Sore throat ```
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Long term effects of radiotherapy
``` Change in skin colour Fibrosis Delayed wound healing Breathing problems Impotence Dry mouth Infertility bowel changes - diarrhoea 2y cancer from radiation long term pain Lung classically has delayed response - pneumonitis ```
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Types of radiotherapy
External beam radiation therapy - 3D conformal radiation therapy - Intensity modulated radiation therapy - collimators, allows different areas to get different doses - Image guided: repeat scans during treatemtn to detect change in tumour and alter raditation - Steterotactic radiotherapy - high dose radiation to small tumour, extremely accurate and image guided - Proton therapy Internal radiation therapy - Brachytherapy - radiation delivered from sources placed inside the body Systemic - patient swallows or is injected with radioactive substance that can be bound to monoclonal antibodies - 131 I used in thyroid
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Congenital breast disease
1-5% of the population have accessory nipples (less common = accessory breast) Usually develops along the milk line Most common site for extra nipple is below the breast Most common site for extra breast in in axilla Treatment only for cosmetic purposes Subject to the same disease as normal breast tissue
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Cystic breast mass
MOST COMMON - Common cause of dominant breast mass - May occur at any age - Uncommon in post-menopausal - Fluctuates with menstrual cycle - Firm and mobile - Well demarcated from surrounding tissue - Not as smooth and mobile as fibroadenoma - Difficult to distinguish from solid mass Treatment = aspiration
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Fibroadenoma
2nd most common - Benign solid tumours containing glandular and fibrous tissue - Well defined, mobile mass - Breast mouse - Women between 15 and 35 - Cause unknown - Needs core biopsy - Increases in size with pregnancy or oestrogen therapy - Excise if >3cm, rapidly enlarging or patients wishes - Giant = 10cm
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Phylloides tumour
``` Rapidly growing 25% malignant 10% metastasise Bulky tumours that distort the breast May ulcerate through the skin due to pressure necrosis Treatment = wide excision ```
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Fat necrosis
Rare Secondary to trauma, often not remembered Tender Ill defined mass Occasional skin retraction Biopsy and clinical follow up to ensure decreasing size Can mimic cancer
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Galactocoele
Milk filled cyst from over distension of lactiferous duct Firm, non-tender mass in breast Common in upper quadrants, beyond areola Diagnostic aspiration is usually curative
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Duct ectasia
Usually in older women Dilation of subareolar ducts can occur Palpable retroareolar mass Nipple discharge or retraction Treatment = biopsy or excision
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Gynaecomastia
Benign growth of glandular tissue of the male breast Due to imbalance of oestrogen and androgens Unilateral or bilateral Physiological and common in infancy, adolescence and adults Causes: testicular tumours, drugs (cannabis, steroids, spironolactone), idiopathic, chronic disease No treatment
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Paget's disease of the breast
``` Cancerous Appearance of eczema Skin changes involving the nipple of the breast 2% of all breast cancers Areolar itchy and inflamed Skin may become flaky Discharge: straw coloured or bloody Burning sensation inverted nipple No lump as such ```
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Nipple discharge
Majority of cases are benign Most common cause is lactational Other causes: over stimulation, prolactin secreting tumours, hypothyroidism, drugs Unilateral spontaneous bloody discharge is suspicious
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Mastitis
Most common in lactating female Dry cracked fissured areola or nipple is portal for infection Usually caused by Staph or Strep Treat with HEAT, continued breast feeding and antibiotics Rule out malignancy
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Breast abscess
May present with breast swelling, tenderness and fever Breast tender, warm and fluctuant May also have purulent discharge and/or systemic symptoms Treated by US guided aspiration and Abx Surgical drainage only is skin necrosis
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Normal range of blood calcium
2.25-2.5mmol/L
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Blood calcium circulation
Calcium is protein bound Must take consideration of albumin levels to interpret blood calcium In hypercalcaemia, over half of circulating calcium is protein bound Levels from labs can be corrected or uncorrected (allowing for albumin) Only the unbound ionised calcium is physiologically important
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Aetiology of hypercalcaemia
90% of cases: 1. Primary hyperparathyroidism 2. Malignancy - Primary malignancy - Metastasis - Myeloma Others: - Granulomatous conditions: sarcoidosis, TB - Renal failure - Endocrine: thyrotoxicosis, phaechromocytoma, primary adrenal insufficiency - Drugs: thiazide diuretics, vitamin D and A - Familial hypocalciuric hypercalcaemia - Prolonged immbolisation - Calcium alkali syndrome - AIDS - Paget's disease
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Presentation of hypercalcaemia
2. 5-2.8 - Polyuria and polydipsia - Dyspepsia - Depression - mild cognitive impairment ``` 2.8-3.5 + muscle weakness + constipation + anorexia + fatigue ``` ``` >3.5 + abdominal pain + vomiting + lethargy + shortened QT interval + coma + pancreatitis ``` stones, bones, thrones, abdominal moans, and psychic overtones - Renal or biliary stones - Bone pain - Abdominal pain and nausea and vomiting - Thrones : polyuria - depression/cognitive dysfunction/coma
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Investigations for hypercalcaemia
Calcium levels Hypercalcaemia PLUS - Raised albumin and raised urea = dehydration - Normal ALP = myeloma, calcium alkali syndrome, thyrotoxicosis, sarcoidosis - Raised ALP - bony mets, sarcoidosis, thyrotoxicosis - Raised calcitonin = B cell lymphoma PTH levels ALP Phosphate X-rays US for stones CT for bony abnormality
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Pathophysiology of hypercalcaemia
Causes dehydration by inducing renal resistance to vasopressin - nephrogenic diabetes insipidus Dehydration leads to further increase in calcium Damages excitable membranes leading to muscle fatigue Raised calcium exceeds capacity for renal absorption and so it enters urine = stones
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Acute Management of hypercalcaemia
Increased fluids - 0.9% NaCl (increases urine output and decreases calcium) Loop diuretic (furosemide) IV bisphosphonates (after hydration) to decrease bone turnover Glucocorticoids - if vitamin D toxicity, lymphoma or sarcoidosis Iv gadolinium - if not responding to bisphosphates Denosumab - RANKL inhibitor to prevent calcium removal from bones in reponse to PTH stimulation If severe or renal failure then haemodialysis
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Management of chronic hypercalcaemia
Regular monitoring Decreased dietary calcium - dairy and leafy green veg Mobilisation
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Important side effect of bisphosphonates
Osteonecrosis of the jaw Also, oesophagitis if not taken correctly
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Define cauda equina syndrome
Cauda equina is formed by nerve roots caudal to the level of the spinal cord termination The syndrome is caused by compression of these nerves Medical emergency
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Causes of cauda equina
``` Herniation of intervertebral disc (usually lumbar) Tumours, mets, lymphomas, spinal tumours Trauma Infection Congenital spinal stenosis Spina bifida Spondylolisthesis Late stage anklylosing spondylitis Post-op haematoma Sarcoidosis ```
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Presentation of cauda equina syndrome
Low back pain, pain into legs Lower limb weakness and sensory deficit Bowel dysfunction: faecal incontinence, constipation, loss of anal tone and sensation Bladder dysfunction: urinary retention, difficulty starting or stopping stream, overflow incontinence, decreased urethral and bladder sensation Saddle and perineal anaesthesia Sexual dysfunction Decreased reflexes below the level (LMN)
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Presentation of spinal cord compression
``` Neurological symptoms - Abnormal gait, clumsy or weak limbs Loss of sexual, bladder and bowel function Sensory changes variable Reflexes are - increased below the level of the compression - Absent at the level of compression - Normal above compression ```
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Symptoms of spinal mets in a cancer patient
``` Pain in thoracic or cervical spine Progressive lumbar spinal pain Severe unremitting lower spinal pain Spinal pain aggravated by straining (stool, cough, sneeze) Localised spinal tenderness Noctural spinal pain preventing sleep ```
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Investigations in suspected cauda equina
EMERGENCY | MRI of whole spine ASAP
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Treatment of spinal metastases
Analgesia as required Bisphosphonates if breast cancer or myeloma to decrease pain and risk of metastatic spinal cord compression (MSCC) Radiotherapy - palliative for pain Consider vertebroplasty if mechanical pain or vertebral body collapse Consider surgery to stabilise the spine and prevent MSCC If MSCC and pain and not suitable for surgery offer halo vest or external orthosis Denosumab to prevent MSCC
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Treatment of threatened spinal cord in metastatic spinal cord compression
Nurrse flat with neural spine and slowly progress to gradual movements Loading dose dexamethasone ASAP (16mg) Start treatment within 24 hours Stage tumour and establish primary histology If surgery - spinal cord decompression and spinal column stabilisation Only offered in para/tetra plegic after 24 hours if for pain Radiotherapy if not surgery within 24 hours unless, >24 hours with permanent disability and pain free or overall prognosis too poor.
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Supportive therapy for spinal cord compression post event
``` Thromboprophylaxis Regular turning to decrease pressure sores Urinary catheter Faecal incontinence Rehab Social support ```
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Methods of treating cancer bone pain
Depends on the type of cancer and patients wishes - Radiotherapy - MOST COMMON, can relieve pain and swelling. Generally external - Hormonal therapy - Chemotherapy - Targeted therapies - Surgery Remove affected area, replace with prosthesis Bone support if weak and open to fracture Joint replacement Cementoplasty Analgesics Bisphosphonates if breast or myeloma Massage Heat
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Aetiology of haemolytic anaemia
Genetic - Red cell membrane abnormalities: hereditary spherocytosis, elliptocytosis - Haemoglobin abnormality: sickle cell, thalassaemia - Enzyme deficit: G6PD deficiency, pyruvate kinase deficiency Acquired - Immune: haemolytic disease of the newborn, blood transfusion reaction - Autoimmune WARM - + Coomb's - idiopathic, SLE, lymphoma, CLL, Evan's syndrome COLD - cold haemogluttin disease, paroxysmal cold haemoglobinuria, mycoplasma pneumonia, lymphoma, infectious mononucleosis Non-immune - Trauma: cardiac haemolysis, haemolytic uraemic syndrome, thrombocytic thrombocytopaenia purpura - Infection: malaria, sepsis, leishmaniasis - hypersplenism - paroxysmal nocturnal haemoglobinuria - liver disease
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Hereditary spherocytosis
Autosomal dominant Abnormality of erythrocytes Sphere shaped RBCs More prone to rupture, less flexible to travel through arteries ``` Anaemia Jaundice Splenomegaly Fatigue Howell-Jolly bodies ``` Blood smear: red blood cells appear small and lack central pale area Elevated reticulocytes Increased mean cell haemoglobin concentration
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G6PD deficiency
Glucose 6 phosphate dehydrogenase deficiency X linked recessive inborn error of metabolism Predisposes to haemolysis and jaundice after a number of triggers. - Illness, especially infection - Drugs (quinine) - Foods (fava beans/ broad beans) - Certain chemicals Can present with DKA, haemolytic crisis, prolonged jaundice in neonate, AKI Increased in Mediterranean and African Most common human enzyme condition, Heinz bodies are present Coomb's test negative (not immune mediated) Beulter fluorescent spot test - positive
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Pyruvate kinase deficiency
Inherited metabolic disorder of the enzyme pyruvate kinase which affects survival of red blood cells autosomal recessive - Symptoms most severe in childhood - Haemolytic anaemia - Cholecystolithiasis - Gallstones - Tachycardia - haemochromatosis - Splenomegaly - Jaundice
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Haemolytic disease of the newborn
Alloimmune condition that develops in a foetus when IgG produced by the mother pass through placenta. Some attack antigens on RBCs in foetal circulation causing haemolysis Develops reticulocytosis and anaemia Positive Coomb's test Elevated cord bilirubin Haemolytic anaemia Jaundice Causes: - foetal maternal haemorrhage - ABO incompatibility in transfusion - ABO haemolytic disease of the newborn - Rhesus D haemolytic disease of newborn
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Pathophysiology of haemolytic anaemia
Normal RBC has lifespan of 120 days Shorted in haemolytic anaemia It can occur by 2 mechanisms: - Intravascular: RBC destroyed in circulation due to complement fixation, trauma or other intrinsic factors: Raised Hb, haemosidinuria, decrease haptoglobulins, positive Schumm's test - Extravascular - most common RBC removed from circulation of mononuclear phagocytic system as they are intrinsically defective or have immunoglobulins on their surface
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Signs and symptoms of haemolytic anaemia
Can be caused by anaemia and underlying disease - Severe anaemia: tachycardia, SOB, angina - Gallstones (raised bilirubin) - Haemoglobinuria (in intravascular) - Pallor, pale conjunctiva - Hypotension (if severe) - Mild jaundice - Splenomegaly (CLL, SLE, lymphoma, hereditary spherocytosis) - leg ulcers (sickle cell) - Bleeding and petechiae - Evan's syndrome or TTP
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Investigations for haemolytic anaemia
FBC - Low Hb - Usually normal MCV or MCH - Platelets normal (high in CLL, SLE or haemolytic uraemic syndrome) - Coomb's test (positive if immune mediated) - Cold agglutinins High anti-I antibody = infectious mononucleosis, mycoplasma High anti-p antibody = paroxysmal cold haemoglobinuria US for spleen size
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Blood tests in haemolytic anaemia due to increased RBC breakdown
``` Low Hb High bilirubin High urobilinogen Raised LDH Decreased haptoglobin Positive urinary haemosiderin ```
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Causes of positive Coomb's test
Drugs: methyldopa, quinine, NSAIDs, interferon, ribavirin Autoimmune: - Haemolytic disease of newborn - Transfusion reaction - SLE - Evan's syndrome - Waldenstrom's - Infectious mononucleosis - Paroxysmal cold haemoglobinuria
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Causes of spherocytes on blood film with negative Coomb's test
Hereditary spherocytosis | Malaria
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Causes of bite cells, blister cells of Heinz bodies on blood smear
G6PD deficiency Pyruvate kinase deficiency Pyrimide 5' nucleotidase deficiency
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Causes of fragmentation on blood smear
Microangiopathic haemolytic anaemia - Eclampsia - Haemolytic uraemic syndrome - DIC - TTP
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Haemolytic uraemic syndrome
TRIAD - Haemolytic anaemia - AKI (uraemia) - Thrombocytopaenia In children Generally preceded by E. Coli O157 - Schisocytes - Anaemia - Elevated LDH - Low platelets - Confusion - Fatigue, - Oedema
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Management of haemolytic anaemia
``` Mainly supportive Folic acid as haemolysis can cause folate deficiency Discontinue any aggravating medications Avoids transfusions unless necessary Corticosteroids Splenectomy Rituximab (anti CD20) ```
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Beta thalassaemia
Normally haemoglobin in 2 alpha and 2 beta chains In beta thalassaemia - either none or reduced beta chains formed. Increased alpha chains precipitate causing ineffective erythropoiesis and haemolysis Increase HbA2 (alpha 2 delta 2) Increased HbF (alpha 2, gamma 2) - Major require regular transfusions. Severe. - Minor (trait) asymptomatic
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Alpha thalassaemia
Caused by gene deletions 4 deletions = Bart's (not compatible with life) no alpha, Hb gamma 4 3 = HbH (beta 4) severe anaemia 2 = HbA, some HbH 1 = HbA
211
Sickle cell pathology
HbS results from a single base mutation of adenine to thymine which changes glutamic acid to valine on the beta chain. HbSS - sickle cell (both genes abnormal) HbAS - sickle trait It does not manifest until HbF decreases to adult levels at 3-6 months Increased prevalence in African populations. Deoxygenated HbS is insoluble and polymerises Decreased flexibility, rigid and sickle. After time does not return to normal when oxygenated. Sickling produces - Decreased RBC survival - Impaired passage of cells through microcirculation - Obstruction and infarction - Precipitated by: infection, dehydration, cold, acidosis, hypoxia HbS releases oxygen more readily than HbA so feel well despite the anaemia
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Presentation of sickle cell anaemia
``` Anaemia Jaundice Pallor Lethargy Growth restriction Weakness ``` Veno-occulsive crisis - Acute severe bone/hand/feet pain due to occlusion of small vessels - Fever accompanies pain Pulmonary hypertension (increased free Hb, decrease NO, endothelial dysfunction) Acute chest syndrome - 30%. Chronic lung disease and pulmonary hypertension is most common cause of death in sickle cell - Caused by infection, fat embolism from necrotic bone marrow, pulmonary infarction from sequestration - SOB, chest pain, consolidation of chest Anaemia (60-60) Splenic sequestration - splenomegaly. Splenic pooling of RBCs and hypovolaemia can cause shock Bone marrow aplasia (after erythrovirus B19)
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Long term problems associated with sickle cell disease
Abnormal growth and development - Delayed sexual maturation, decreased weight, normal height by adulthood - Compression and shortening of bones from vaso occlusion - Increased osteomyelitis - Increased infections: especially bones, kidneys and lungs - Leg ulcers over malleoli - Cardiac issues: cardiomegaly, arrhythmia - Neuro: TIA, seizure, stroke, coma - Gall stones, hepatomegaly, priaprism, retinopathy, spontaneous abortion
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Investigations in sickle cell
FBC - Hb 60-80, high reticulocytes Blood film: sickling Sickle solubility test Hb electrophoresis - no HbA, 90% HBSS, 10% HbF
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General management of sickle cell
Prophylactic 500mg penicillin daily Pneumococcal and annual influenza vaccine Folic acid of haemolysis Blood transfusions if required Hydroxycarbamide - increased HbF concentration to decreased crises Stem cell transplant Counselling Stroke prevention Contraception - not IUDs as infection risk
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Management of acute painful sickle crisis
Avoid exposure to cold and dehydration Morphine IV/SC until pain controlled (PCA) Adjuvant oral analgesia - Paracetamol + ibuprofen/diclofenac Laxatives Antipruritics, antiemetics, anxiolytic as required.
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Prognosis of sickle cell
Median life expectancy 40-60 Most common cause of death in first 2 years = infection In adults = cerebrovascular disease, sepsis, acute chest syndrome or pulmonary hypertension
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4 main subtypes of leukaemia
Acute Myeloid Leukaemia (AML) Acute lymphoblastic leukaemia (ALL) Chronic Myeloid Leukaemia (CML) Chronic Lymphocytic Leukaemia (CLL)
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AML
Acute myeloid leukaemia Malignant disease of bone marrow in which precursors of blood cells are arrested in an early stage of development - Most AML shows > 30% blasts of myeloid lineage - Maturational arrest of bone marrow cells in 1st stage of development - Activation of abnormal genes through chromosomal translocation - Decreased number of blood cells - Failures of apoptosis leads to increased accumulation in liver and spleen
220
Types of AML
AML with characteristic gene abnormalities - better prognosis AML with multilineage dysplasia - prior MDS or myeloproliferative disease AML therapy related - post chemo or radiotherapy AML otherwise not characterised
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Epidemiology of AML
5 per 100,00 Most common acute leukaemia in adults Incidence increases with age - median age 67 RFs - Predisposing haematological disorders: MDS, aplastic anaemia, myelofibrosis, paroxysmal nocturnal haemoglobinuria, polycythaemia, ruba vera - Radiation - Congenital disorders: Bloom's syndrome, Down's, congenital neutropaenia, Fanconi's anaemia, neurofibromatosis - Autosomal DOMINANT - presents in 60s - Previous cancer chemotherapy
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Symptoms of AML
Children - acute symptoms over days to weeks Adults - fatigue over weeks to months ``` Dizziness SOB on exertion MI or angina Fever (high WBC, low neutrophils) Easy bleeding or bruising Haemorrhage in lungs, GI tract or CNS Fullness in LUQ and early satiety Leukostasis with respiratory distress and altered mental status Bone pain ```
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Signs of AML
``` Hepatomegaly Splenomegaly Lymphadenopathy Testicular enlargement Mediastinal mass SVCO Pallor Signs of infection Leukostasis - hypoxia, low GCS, retinal vein dilation, papilloedema, fundal haemorrhage Petechiae, purpura, ecchymoses Gingivitis ```
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Investigations for AML
FBC - Thrombocytopaenia - Anaemia (macrocytic) - WCC can be high, low or normal - Low neutrophils - Raised blast cells Clotting - DIC is common, raised PT, low fibrinogen LFTs and U&Es High LDH High lactic acid Both from increased cell turnover Peripheral blood film - blast cells Bone marrow aspiration - DIAGNOSTIC - Hypercellular with replacement of normal elements with blast cells - AUER rods - HLA typing and family for stem cell transplant Cytochemical stains for classification If child chromosomal analysis Check heart function as treatment cardio toxic
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Management of AML
Criteria of response = Blast cell clearance in bone marrow <5% of all nucleated cells, normal haematopoiesis and normal blood counts. Treatment given in 2 phases: - Induction (to achieve remission): cytarabine and daunorubicin. Severe bone marrow hypoplasia - Post remission consolidation: only if remission achieved. - Can use stem cell transplant in moderate to high risk (not low) - Blood product replacement - Antibiotics for infection ? potential antibiotic prophylaxis - Aciclovir for reactivation of herpes simplex or zoster - Allopurinol to lower uric acid levels
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Prognosis of AML
13% will get 2y malignancy In children 80% achieve remission Adults: - Young patients 80% remission, 5 year survival = 40% - Older patients: 60% remission, median survival 5-10 months Poor prognosis: failure to respond to 1 or 2 induction rounds, previous MDS or chemo, co-morbidities, increasing age
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ALL
Acute lymphoblastic leukaemia Malignant transformation of a clone cell from lymphoid progenitor cells. The majority are B cell in origin but some are from T cell precursors. - Lymphoid precursors proliferate and replace normal cells of the bone marrow. Blast cells spill into peripheral circulation - Immunophenotyping distinguished from other lymphoid malignancies
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Epidemiology of ALL
``` Most common cancer in children 3 per 100,000 12% leukaemias but 80% in children Peak incidence 2-4 years Smaller peak in 50s ``` RFs - Genetic (25% twin concordance) - Trisomy 21 - Fragile chromosomes: Fanconi's anaemia - Increased radiation dose - Smoking, alcohol, pesticides, illicit drug use (all weak associations)
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Symptoms of ALL
Fatigue, dizziness, palpitations Sever or unusual bone or joint pain Recurrent and severe infections Fever without obvious infection LUQ fullness and early satiety (splenomegaly) SOB Headache, irritability, altered mental status Haemorrhagic or thrombotic complications - DIC Bone pain
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Sanctuary sites for ALL
Testicles | Meningeal
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Signs of ALL
``` Pallor Non specific signs of infection Tachycardia Flow murmur Petechiae -> purpura -> echymoses Hepato and splenomegaly Lymphadenopathy Testicular enlargement Gum hypertrophy Cranial nerve palsy 3,4,6,8 Renal stones, AKI (raised uric acid) ```
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Investigations of ALL
FBC - Anaemia - Thrombocytopaenia - WCC high, low or normal - Neutropaenia (usually) - Will not always be abnormal if no bone marrow suppression yet Blood film - Blast cells (may be absent if just confined to marrow) Clotting - DIC can occur, raised PT, low fibrinogen Raised LDH and raised uric acid Check LFTs and U&Es prior to treatment CXR - lytic bone lesions or mediastinal mass ECG or echo due to cardio toxic drugs Bone marrow biopsy > 20% blasts in marrow or peripheral blood Flow cytometric demonstration of lymphoid antigens to confirm lymphoid and not myeloid Cytogenetics - Philidelphia chromosome Negative MYELOPEROXIDASE screen is diagnostic
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Classifications of ALL
B cell ALL - Early pre-B ALL - 10% - Common ALL - 50% - Pre -B ALL - 10% - Mature B ALL (Burkitt's) - 4% T cells ALL - Pre-T cell ALL - 5-10% - Mature T ALL - 15-20%
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Management of ALL
Mature B cell ALL get short term intensive chemo (30-40% remission rate) Others: - Remission induction - Consolidation/intensification - Maintenance Remission induction - Eliminates 90% of leukaemic cells to restore haemtopoeisis - Remission rate in children 98%, adults 85% - Quadruple therapy for 4-6 weeks: prednisolone, vincristine, anthracyclines, crisantaspase Consolidation - Starts once normal haematopoiesis - Methotrexate + mercaptopurine or aspraginase - Done if high or very high risk of relapse Maintenance - For 2 years - weekly methotrexate + daily mercaptopurine General supportive - Replacement blood products - Growth factors can alleviate myelosuppression (GCSF) - Antibiotics and antifungals for opportunistic infection - Allopurinol for high uric acid levels - Hickman line CNS prophylaxis - ALL patients often have meningeal leukaemia at relapse - Intrathecal and high dose chemotherapy Stem cell transplant allows intensification of chemo and radiotherapy by replacing damaged stem cells Relapse has very poor prognosis
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Complications of ALL
Susceptible to pneucystis jirovecii Impaired growth Secondary malignancy Cardiac or pulmonary disease Most complications are iatrogenic - Haemorrhage, anaemia infection - Hair loss, rash - N&V. Diarrhoea. Constipation - Mucositis - Electrolyte disturbance - Nephro and hepatotoxicity - Peripheral neuropathy - Stroke - Graft vs host disease - Tumour lysis syndrome
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Tumour lysis syndrome
Most commonly after treatment for leukaemias and lymphomas due to increased cell lysis. ``` Raised uric acid Raised phosphate Raised potassium Low calcium Raised blood urea nitrogen ```
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Prognosis of ALL
Better in children than adults 85% long term survival rate in children Adults have more cytogenic abnormalities and less likely to tolerate treatment Poor prognosis with: <12 months, > 10 years, male, adverse cytogenetics, CNS involvement, very high leukocyte count at presentation,
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Define CML
Myeloproliferative disorder of pluripotent haematopoietic stem cells affecting one or all cell lines - erythroid - platelet - myeloid Over time the leukaemic cells proliferate due to stepped up production and failed apoptosis
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Stages of CML
3 stages CHRONIC - Immune system is competent and patients are asymptomatic for prolonged periods - 4-5 years - More than 90% are diagnosed in chronic phase ACCELERATED PHASE - Defined by 15-30% blasts in the blood or bone marrow OR, >20% basophils in blood, thrombocytosis, thrombocytopaenia - In 2/3 chronic transforms into accelerated - Increased blasts, low Hb, Low platelets - Progressive maturation arrest - Increased symptoms, splenomegaly BLAST CRISIS - 1/3 straight from chronic to blast - >30% blasts in blood or bone marrow or extramedually blastic infiltration - Severe symptoms due to tumour burden: weight loss, fever, night sweats, bone pain, bleeding, infection - Aggressive acute leukaemia with marrow exhaustion is rapidly fatal and refractory to chemotherapy
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Epidemiology of CML
1 per 100,000 15% of adult leukaemias Median age 60-65 Can be caused by PHILADEPHIA CHROMOSOME Translocation 9 to 22 places ABL from long arm of 9 to long arm of 22 in BCR region BCR-ABL encodes fro a protein with strong tyrosine kinase activity and results in CML
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Presentation of CML - Symptoms
``` Can be insidious in onset Fatigue Weight loss Night sweats Abdo fullness/ abdominal distension LUQ pain if splenic infarction ```
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Signs of CML
``` Splenomegaly hepatomegaly Lymphadenopathy Anaemia Easy bruising Fever Gout due to rapid cell turnover Hyperviscosity syndrome ```
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Hyperviscosity syndrome
Due to leucocytosis - Visual disturbance (papilloedema, venous obstruction, retinal haemorrhage) - Priaprism - Cerebrovascular event - Confusion Treat with leukocytophoresis, prednisolone, chemotherapy and allopurinol Avoid blood transfusions as can worsen
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Investigations for CML
FBC - normochromic normocytic anaemia - Leukocytosis - Granulocytes at all development stages - Increased eosinophils and basophils - Platelets: high low or normal Peripheral blood smear - All stages of maturation seen - Often resembles a bone marrow aspiration U&E - Normal - can have high LDH and urate Bone marrow aspiration - Quantify % blast cells and basophils - Assess degree of fibrosis and obtain material for cytogenetics Cytogenetics - FISH or PCR for Philadelphia chromosome HLA typing if considering transplantation
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Management of CML
Aim: - haematological remission (normal FBC and exam) - Cytogenetic remission (no Philadelphia chromosome) - Molecular remission (no BCR-ABL) - Tyrosine kinase inhibitor (IMATINIB) - 70% have cytogenetic response in 12 months Transplant - Most common indication for transplant - Should be done in chronic phase - Preferable if HLA matched sibling
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Risks of bone marrow transplant
``` Graft vs host disease Veno occlusive disease Life threatening infections Risk of 2y malignancies Decreased QoL ```
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Prognosis of CML
Increasing survival | Estimated 90% survival at 5 years
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Define chronic lymphoid leukaemia
CLL Malignant monoclonal expansion of B lymphocytes Accumulation of abnormal lymphocytes in blood, bone marrow, spleen, liver and lymph nodes Normal appearance but are immature and non-reactive resulting in immunological compromise 25% of all leukaemias Disease of the elderly
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Diagnostic criteria for CLL
Presence in peripheral blood of > 5000 B lymphocytes for over 3 months Leukaemic cells in blood smear - small mature lymphocytes, narrow border of cytoplasm, dense nuclei, no nucleoli and partially aggregated chromatin.
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Epidemiology of CLL
``` Most common leukaemia (25%) Increases with age 4.2 per 100,000 Increase in males FHx rare ```
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Symptoms of CLL
Insidious onset 90% are asymptomatic at diagnosis - detected on routine blood tests - Susceptibility to infection (zoster/simplex/pneumonia) - Symmetrically enlarged lymph nodes - Abdominal discomfort from enlarged spleen - bleeding / petechiae from skin/mucus membrane - Fatigue
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Signs of CLL
``` Lymphadenopathy Splenomegaly Heptatomegaly Petechiae Tonsillar enlargement pallor (rare = skin infiltration or involvement of lacrimal glands or salivary glands) ```
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Investigations in CLL
FBC - Normocytic normochromic anaemia - Clonal B cell lymphocytosis Blood film - Lymphocytosis and SMUDGE cells Coomb's test - before any treatment to determine if there is any autoimmune haemolytic anaemia Bone marrow aspirate - Lymphocytic replacement of normal marrow elements Lymph node biopsy - If lymph nodes enlarge rapidly then can transform into high grade lymphoma - If transformation = Richter's syndrome Immunophenotyping - peripheral blood flow cytometry confirms CLL and shows clonal B lymphocytes expressing CD5, CD19, CD20 and CD23
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Richter's syndrome
Transformation of CLL to high grade lymphoma + fever + weight loss + pain
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Staging of CLL
Binet system A, Hb>10, Platelets > 100, < 3 lymph nodes involved B Hb and platelets as A but with 3+ lymph nodes involved C - Hb< 10, platelets less 100 or both
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Management of CLL
``` No curative treatments Current treatments do not prolong survival If early disease = watch and wait - blood counts every 3- 12 months Chemotherapy only with active symptoms - Weight loss > 10% - Fatigue - Fever - Night sweats - Autoimmune haemolytic anaemia - Lymphadenopathy - Splenomegaly ``` Typically cyclophosphamide in combinations Rituximab (anti CD20) Steroids for autoimmune complications Stem cell transplant is only curative treatment but most paitents are elderly with increased morbidity and mortality so rarely justified Splenectomy Palliative radiotherapy for large spleen/lymph nodes
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Complications of CLL
Susceptible to infection - Antibiotic prophylaxis - Up to date with immunisations Autoimmune cytopaenia AUTOIMMUEN HAEMOLYTIC ANAEMIA (common) Hyperviscosity syndrome due to raised WCC Lymphatomous transformation - Richter's syndrome in 5% increased risk of 2y malignancy
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Types of lymphoma
Hodgkin's | Non-Hodgkin's
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Define Hodgkin's lymphoma
Uncommon haematological malignancy arising from MATURE B CELLS Characterised by presence of REED-STERNBREG CELLS
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Epidemiology of Hodgkin's lymphoma
3 per 100,000 2 age peaks - young adult 20-25 and 50-60 Nodular sclerosis type increased in young females (better prognosis) Increased in Caucasians Overall no gender difference RFs 5% familial Past EBV/infectious mononucleosis Higher socio-economic class
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Aetiology of Hodgkin's lymphoma & pathophysiology
Unknown Probably multi factorial Could be infectious as EBV is often harboured in Reed-Sternberg cells Unknown pathophysiology Immunoglobulin expression in ABSENT
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Classification of Hodgkin's lymphoma
Nodular sclerosis 70% Mixed cellularity 25% Lymphocyte rich 5% Lymphocyte depleted <1%
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Presentation of Hodgkin's lymphoma
Painless lymphadenopathy - usually in the head, neck, mediastinum Itching Eosinophilia ``` Unexplained fever Night sweats Weight loss Cough Dyspnoea Chest pain SVCO Abdominal pain Tonsillar enlargement Hepatomegaly Splenomegaly ```
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Investigations for Hodgkin's lymphoma
FBC - Low Hb - normochromic normocytic anaemia - Low platelets - Increased/decreased/normal WCC - EOSINOPHILIA Raised CRP/ ESR and LDH CXR: mediastinal mass, large mediastinal adenopathy PET/CT for staging - can use full body CT Excisional lymph node biopsy - REED-STERNBERG CELLS Immunohistochemical studies - *CD30*, CD15, CD20 Bone marrow biopsy TFTs can become abnormal after neck radiation
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Staging in Hodgkin's lymphoma
Ann Arbour system I - single lymph node area II - 2+ lymph node regions on same side of diaphragm III - Involvement on both sides of diaphragm IV - Involvement of extranodal sites A - no systemic symptoms B - symptoms (>10% weight loss, sweats, fever) Letter and number!
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Management of Hodgkin's lymphoma
If stage I then radiotherapy and chemotherapy ABVD - Doxorubicin, bleomycin, vinblastine and dacarbasine Staging PET pre chemo and after 2 cycles Response PET predicts overall survival - 95% of Hodgkin's is PET active Chemo treatment = cardiac and respiratory toxic to test first If the disease relapses then autologous transplant (stem cells)
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Prognosis of Hodgkin's lymphoma
90% of early stage achieve remission In advanced 50-70% can be cured Hasenclever prognostic index Predicts 5 year freedom from progressive and 5y survival
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Autologous stem cell transplant
Used in relapsed lymphomas and myelomas Always remove cells peripherally To gather cells - One round of chemo, GCSF given during chemo recovery. Chemo helps to release stem cells to peripheral blood Allows for stronger chemotherapy treatment that would otherwise wipe out the bone marrow Give own cells back to repopulate the bone marrow and allow recovery
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Define Non-Hodgkin's lymphoma
Group of lymphoproliferative malignancies with differing patterns of behaviour and response Greater tendency to disseminate to extranodal sites Low grade - not curable in advanced stages. Not responsive to treatment. low proliferation rate High grade - rapid proliferative rate. More responsive the intensive chemotherapy
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Classification of Non-Hodgkin's lymphoma
Can transform from low to high - Precursor B cell lymphoma ``` Mature B cell High grade - Diffuse large B cell lymphoma (DLBCL) 30-60% - Burkitt's lymphoma - Mediastinal large B cell Low grade - Follicular (20-25%) - marginal zone/Waldenstrom's - MALT lymphoma - Mantle cell (poor prognosis) ``` Precursor T cell lymphoma Mature T cell neoplasms
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Mature B cell Non-Hodgkin's lymphomas
High grade * Diffuse large B cell lymphoma (DLBCL) - Burkitt's - Mediastinal large B cell Low grade * Follicular - Marginal zone/Waldenstrom's - MALT lymphoma - Mantle cell
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Epidemiology of Non-Hodgkin's lymphoma
``` 5x more common than Hodgkin's Increased in Caucasian 12 per 100,000 Increased with age 60-70 Slightly more common in men Low grade are very rare in children ``` 2 most common; DLBCL and follicular RFs - EBV (Burkitt's) - Autoimmune disorders (Sjorgens, Hashimoto's) - H.pylori for GI lymphoma - Hep B and HIV for Karposi's sarcoma
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Presentation of Non-Hodgkin's lymphoma
Depends on stage and subtype Can occur anywhere Gives site specific symptoms LYMPHADENOPATHY B symptoms: lethargy, fevers, night sweats, weight loss, loss of appetite Systemic: GI tract, skin, bone marrow, sinus, GU tract, thyroid, CNS Tumour lysis syndrome is common with chemo - occurs in Burkitt's without treatment
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Tumour lysis syndrome
Raised uric acid Raised phosphate Raised K+ Hypocalcaemia Due to high cell lysis after treatment of lymphoma and leukaemia Causes: - Nausea and vomiting - Acute uric acid nephropathy - AKI - Seizures - Arrhythmias - Death Treat with allopurinol
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Investigations for Non-Hodgkin's lymphoma
FBC - Anaemia (marrow failure of autoimmune haemolytic anaemia) - Thrombocytopaenia /cytosis - High or low neutrophils U&Es for nephropathy or hypercalcaemia Uric acid CXR - mediastinal adenopathy, pleural or cardiac effusions PET/CT Biopsy of lymph node/ mass Bone marrow biopsy CT TAP for lymph nodes
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Staging of Non-Hodgkin's lymphoma
Ann Arbour system I - single lymph node area II - 2+ lymph node regions on same side of diaphragm III - Involvement on both sides of diaphragm IV - Involvement of extranodal sites A - no systemic symptoms B - symptoms (>10% weight loss, sweats, fever) Letter and number!
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Management of Non-Hodgkin's lymphoma
All have steroids during treatment LOW GRADE - Asymptomatic may not require therapy - Treat with marked systemic symptoms, lymphadenopathy causing disfigurement, bone marrow failure, compression syndrome - Low intensity chemo - Rituximab often used HIGH GRADE - Treat at presentation - RCHOP - Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone - If relapse the autologous stem cell transplant
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Complications of Non-Hodgkin's lymphoma
``` Pancytopaenia (due to marrow infiltration) Depends on location - SVCO - Spinal compression - GI obstruction ``` Tumour lysis syndrome
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Prognosis of Non-Hodgkin's lymphoma
Low grade = better prognosis but not curable Transformed has worse prognosis most relapse in the first 2 years High grade = aggressive but responds to chemo
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Define myeloma
Malignancy of memory B cells (PLASMA CELLS) | When they are healthy they should only be found in the bone marrow
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Epidemiology of myeloma
2nd most common haematological cancer 15-20% of haematological cancer deaths 4 per 100,000 Increases with age - median = 70 Increased in Blacks Increased in men
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Aetiology and pathophysiology of myeloma
Malignant proliferation of plasma cells (memory B cells) They accumulation in the bone marrow and produce monoclonal protein that causes organ and tissue impairment. It arises from genetic changes during terminal differentiation of B cell lymphocytes to plasma cells In half of cases: chromosomal translocation of oncogene onto chromosome 14 Imbalanced bone remodelling = increased osteoclasts Causing unopposed osteolysis and hypercalcaemia Plasma cells produce variable amounts of monoclonal free light chains when in urine = Bence Jones proteins When light chain load > absorptive capacity they precipitate as casts in the distal tubule Causes tubular obstruction, tubulointerstiial inflammation and AKI
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Presentation of myeloma
It can present with a wide variety of symptoms including those due to hypercalcaemia, anaemia, renal impairment and osteolysis - Bone pain (especially back pain) - Pathological fractures - Spinal cord compression - Lethargy - Anorexia - Dehydration (due to proximal tubule dysfunction_ - Recurrent bacterial infection) - Bruising or bleeding - Features of amyloidosis - cardiac failure, nephrotic syndrome - Features of hypercalcaemia - thirst, polyuria, constipation, nausea, confusion - Hyperviscosity - dizziness, confusion, blurred vision, headache, epistaxis, stroke
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Investigations for myeloma
FBC - normocytic normochromic anaemia - Leukopaenia - Thrombocytopaenia - High plasma viscosity U&E - Hypercalcaemia - Decreased renal function Raised CRP and ESR Raised uric acid Urine protein electrophoresis - Bence Jones Proteins Bone marrow aspirate and plasma cell phenotype Immunofixation of the paraprotein Skeletal survey - plan x-ray of long bones (humerus and femur), pelvis, spine and skull If an abnormality is found then spinal MRI Bone scan will be negative as it looks for active disease
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Diagnostic criteria for myeloma
SYMPTOMATIC All 3 1. Monoclonal plasma cells in marrow > 10% 2. Monoclonal paraprotein in serum or urine 3. Evidence of myeloma related organ or tissue impairement - Hypercalcaemia - Decreased renal function - Anaemia - Lytic bone lesions - Osteoporosis - Pathological fracture ASYMPTOMATIC 1 or 2 only
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Early stage myeloma
Monoclonal gammopathy of undetermined significance
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Management of myeloma
Currently incurable It is chronic, relapsing and remitting Only treat if symptomatic Elderly - Thalidomide + alkylating agent + corticosteroid Younger - Induction + high dose chemo + autologous stem cell transplant Treatment of relapsed or refractory disease depends on age, performance status, co-morbidities and tolerance of past treatments Pain control - Analgesia - Amitriptyline, carbamazepine, gabapentin - Corticosteroids - Radiotherapy - Surgery to stabilise # - Chemotherapy as treatment
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Complications of myeloma and their treatment
Hypercalcaemia - Rehydration, IV fluids, bisphosphonates Renal impairment - caused by light chain damage to proximal tubules - increased fluids, avoid nephrotoxins Anaemia - consider EPO if symptomatic - red cell transfusion risks worsening hyperviscosity Infection - treat any fever with broad spec abx - prophylactic trimethoprim during chemo - vaccinations up to date Cord compression - Dexamethasone and local radiotherapy Hyperviscosity -plasma exchange, venesection, chemotherapy
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Prognosis of myeloma
5 year survival average | If presents as an emergency = poor prognosis
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Epidemiology of testicular cancer
Relatively rare cancer 1 in 200 lifetime risk Most common between 15 and 40 Testicular cancer is the most common cancer between 20 and 35 RFs - Cryptochidism or testicular maldescent - Klinefelter's syndrome - FHx - Male infertility (x3) - Infantile hernia - Taller men (germ cell tumours - Testicular microlithiasis (small calcifications) Seminoma is the most common testicular tumour in over 60s, rare in under 10s
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Classification of testicular tumours
95% of them arise from germ cells Germ cell tumours - 50% Seminoma - 50 % Non-seminomas - Seminomas - Teratomas - Yolk sac tumours (also known as endodermal sinus tumours) Most common prepubertal Aggressive natural but overall prognosis excellent
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Genes involved in testicular cancer
Testicular germ cell tumour on X chromosome Virtually all testicular tumours show an abnormality on chromosome 12
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Symptoms of testicular cacer
95% present with a lump Painless Testicular pain and/or abdominal pain can be present Dragging sensation Recent history of trauma- may then examine self (not a cause) Hydrocoele Gynaecomastia (raised B-hCG)
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Metastasise sites of testicular cancer
Seminoma --> para-aortic nodes & back pain Teratoma --> blood born spread to liver, lung, bone and brain
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Investigations for testicular cancer
Diagnosis usually confirmed by US Tumour markers - AFP in yolk sac tumours (endodermal sinus tumours) - Beta hCG raised in teratoma and *seminoma* Tissue histology post orchidectomy Staging with CT thorax and abdomen
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Staging of testicular cancer
``` Royal Marsden Staging 1 - no disease outside testes 2 - Infradiaphragmatic nodal involvement 3 - supradiaphragmatic nodal involvement 4 - mets ```
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Management of testicular cancer
90% achieve remission Radical orchidectomy - offer testicular prosthesis to all If appropriate offer sperm storage if chemotherapy or radiotherapy Chemotherapy if required
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Epidemiology of bladder cancer
``` 7th most common cancer in the UK (4th most common in men, 11th in women) 11 per 100,000 Most patients are over 60 Increased in men (3:1) Women have a poorer prognosis ``` RF - 50% due to SMOKING - Aromatic amines, hydrocarbons (industrial plant chemicals) - Radiation to pelvis - Cyclophosphamide - Squamous can follow stones - In developing countries Schistosomiasis
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Bladder cancer types
90% are Transitional cell carcinomas 10% Squamous cells Transitional from mucosal urothelium may present as non-invasive papillary tumour or as a solid tumour that invades bladder wall and metastasises.
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Presentation of bladder cancer
Painless GROSS haematuria in 90% - Painless haematuria must be treated as malignancy of urinary tract until proven otherwise No abnormality on physical examination Advanced disease can cause - Voiding symptoms Only 5% have mets at presentation - Goes to lung, lymph, liver, bone and CNS

Year 3 (6 decks)

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