Cancer care Flashcards
What is the assessment for breast cancer
Triple assessment: clinical exam, USS/mammo, histology/cytology - FNA/core biopsy
USS or mammo for breast cancer
USS if <35, both if >35
What is sentinel node biopsy
Blue dye or radiocolloid into tumour area, probe/see sentinel node, biopsy and send for histology/immunohistochemistry
Predicting prognosis for breast cancer
Nottingham prognostic index = size + histological grade + nodal status
Also ER/PR status and vascular invasion
What is pre menstrual breast change
Nodularity and pain in upper outer quadrant with fibrosis, adenosis, cysts, epitheliosis, papillomatosis = benign mammary dysplasia
When are breast cysts common
Perimenopause
Common benign breast lumps
Fibroadenoma - collagenous mesenchyme, firm, smooth, mobile, multiple. Regress, stay same or get bigger (1/3 each)
Fibroadenosis - focal or diffuse nodularity
Infective mastitis?
Usually staph a, coamox/Flucloxacillin /incise, drain
Physiological nipple discharge/?
Duct ectasia - dilatation with age = green, brown, bloody discharge
Fat necrosis in breast?
Fibrosis and calcification after trauma = mass
Nodal status for breast cancer
1 = ipsilateral and mobile, 2 = fixed
Premalignant breast diseases?
Non invasive dcis = microcalcification on mammo, unifocal or widespread, 30-50% progress
Non invasive lcis = multifocal, rarer, higher risk of progression
Most common breast cancers
Invasive ductal carcinoma (70%)
Invasive lobular carcinoma
Medullary - younger patients
RF for breast cancer
FHx, age, uninterrupted oestrogen exposure - nulliparity, first pregnancy >30y/o, early menarche and late meno Not breast feeding HRT Obesity BRCA
Stages of breast cancer
1 = confined to breast and mobile 2 = + node in ipsilateralaxilla 3 = fixed to muscle but not chest wall, ipsilateral axilla node matted and may be fixed, skin involvement 4 = fixed to chest wall, distant mets
TNM for breast
T: 1 = <2, 2 = 3-5, 3= >5, 4 = fixed to chest wall or peau d’orange
N: 1 = mobile ipsilateral, 2 = fixed
Treat stage 1-2 breast cancer
Surgery - wide local excision or mastectomy axillary node sample/clearance
Radiotherapy - prevent local recurrence after surgery, and nodes if positive and not completely cleared
Chemo - improve survival esp if young and node pos, or neoadjuvant
Endocrine therapy
Types of hormone therapy for breast cancer
Tamoxifen oestrogen blocker
Aromatase inhibitor targets oestrogen synthesis, better tolerated, for post-meno
GnRH analogues or ovarian ablation if pre-meno and ER pos
ADRs of radiotherapy for breast
Pneumonitis, pericarditis
Rib fractures
Lymphoedema
Brachial plexopathy
Treat stage 3-4 breast cancer
Bisphosphonates for painful bony lesions to decrease pain and fracture risk
Tamoxifen, chemo
Investigations for stage 3-4 breast cancer
LFT, calcium, cxr, skeletal survey, bone scan, CT/MRI or PET/CT, liver us
Causes of nipple discharge
Intraductal papilloma - bloody or clear
Duct ectasia - yellow/green
RF for colorectal cancer
Neoplastic polyps UC, Crohn’s FAP HNPCC Low fibre diet Previous cancer Smoking Genetics
Sx of colorectal cancer
Left = bleeding/mucus, altered bowel habit, tenesmus, mass Right = weigh loss, Hb low, abdo pain Both = abdo mass, perforation, haemorrhage, fistula
Use of CEA in colorectal cancer
Monitor disease and effectiveness of treatment
Tests for colorectal cancer
FBC - microcytic anaemia Faecal occult blood Sigmoidoscopy Barium enema or colonoscopy / CT DNA if familial polyposis once >15y
What is anterior resection for
Low sigmoid or high rectum tumour - anastamosis
What is APR and what is it for
Low rectal tumour (=<8cm from anus), permanent colostomy and remove anus and rectum
What is hartmann’’s procedure
Emergency obstruction or palliation
Proctosigmoidectomy and close rectal stump
Colorectal Surgery if not fit?
Transanal endoscopic microsurgery for local excision through wide proctoscope
endoscopic stenting
Chemo in colorectal cancer?
Reduce mortality for Duke C
Palliation for mets
Sx of anastomotic leak after colectomy
Raised temperature
Abdo pain
Peritonism
What are polyps and what 3 types are in GIT?
Lumps above the mucosa
Inflammatory - IBD, lymphoid hyperplasia
Hamartomatous - juvenile, Peutz-Jeghers syndrome
Neoplastic - adenomas with malignant potential
Sx of polyps in GIT
Blood/mucus
Most common site of colorectal carcinomas
Rectum = 45%, sigmoid = 25%
Duke’’s classification
Stage A - beneath muscularis mucosa
B - through muscularis mucosa
C - regional lymph nodes
D - distant mets
Potential screening programs for colorectal cancer and flaws
Now = FOB home test every 2y from 60-69y, but high false pos
Sigmoidoscopy for left sided, high sens and spec but expensive and not accepted
Colonoscopy - perforation rate higher than sigmoidoscopy, cost, sedation, not accepted
Chemo for colorectal cancer?
Adjuvant, including biologics for VEGF/EGFR
Who gets regular colonoscopy?
HNPCC, FAP
Stomach cancer pathology
Mostly adenocarcinoma - diffuse (more common, worseprognosis) or intestinal (better prognosis) Borrmann classification: 1) polypoid/fungating 2) excavating 3) ulceration and raised 4) linitis plastica
Symptoms of stomach cancer
Non-specific Dyspepsia (inv if >1m and >50y) Weight loss, anorexia, early satiety, vomiting Dysphagia and odynophagia if junctional Anaemia
bad signs on exam for stomach cancer
Epigastric mass Hepatomegaly, jaundice, ascites Virchow node = Troisier’s sign Acanthosis nigricans Succussion splash (outlet obstruction)
What is Krukenberg tumour
Stomach tumour spread to ovary
Imaging gastric cancer
Gastroscopy and multiple ulcer edge biopsy
Endoscopic US
CT/MRI for staging
Staging laparoscopy if locally advanced and no mets
Treat gastric cancer
Curative laparotomy
Subtotal gastrectomy
Lymphadenectomy
Neoadjuvant CRT
Endoscopic laser to decrease bleeding
Combination chemo if advanced - for QoL and survival
Endoscopic mucosal resection for early tumours confined to mucosa
5y survival for gastric cancer
<10%
Risk factors for oesophageal cancer
Obesity Smoking Alcohol, radiotherapy, caustic = SCC Achalasia Reflux oesophagitis +- Barrett’s oesophagus, hiatus hernia, antacids = adeno Man (5x woman)
Where and type of oesophageal cancer
50% middle, 30% bottom, 20% upper
2/3 Squamous 1/3 adeno
Sx of oesophageal cancer
Dysphagia, weight loss, retrosternal chest pain, lymphadenopathy
Hoarse, cough (paroxysmal if aspiration pneumonia) if upper
Tests for oesophageal cancer
Barium swallow CXR Oesophagoscopy with biopsy/EUS CT/MRI Staing laparoscopy if infra-diaphragmatic
staging for oesophageal cancer
TNM T1 = lamina propria/submucosa T2 = muscularis propria T3 = adventitia T4 = adjacent structures N1 = regional node mets M1 = distant mets
Treatment for oesophageal cancer
Radical oesophagectomy if localised T1/2 = transhiatal or transthoracic
Neoadjuvant chemo
CRT if no surgery
Palliative = CRT, stent, laser
Causes of oesophageal rupture
Iatrogenic Trauma Carcinoma Boerhaave syndrome corrosive ingestion
Sx of oesophageal rupture
Odynophagia Tachypnoea, dyspnoea Fever Shock Surgical emphysema
Manage oesophageal rupture
NGT, Abx, PPI
Antifungals, surgery, oesogo-cutanesous fistula
When to order urgent endoscopy for stomach cancer
> 55 with dyspepsia
<55 with dyspepsia and one of: weight loss, anorexia, vomit, dysphagia, sx of bleeding
Causes of lung nodules on cxr
Malignancy Abscess Granuloma Carcinoid tumour Pulmonary hamartoma AV malformation Encysted effusion Cyst Foreign body Skin tumour
Common types of lung tumour
Squamous 35%
Adenocarcinoma 25%
Small cell 20%
Large cell 10%
Signs and symptoms of lung cancer
Cough, haemoptysis, dyspnoea, chest pain, slow resolving pneumonia
Cachexia, anaemia, clubbing (nsclc), hypertrophic pulmonary osteoarthropathy = wrist pain, supraclavicular or axillary nodes
Chest - consolidation, collapse, pleural effusion
Signs of mets from lung cancer
Bone tenderness
Hepatometaly
Confusion, fits, focal CNS signs, cerebellar syndrome
Proximal myopathy, peripheral neuropathy, Lambert Eaton myasthenic syndrome
Local complications of lung cancer
Local - recurrent laryngeal nerve palsy, phrenic nerve palsy, SVC obstruction, Horner’s syndrome (pancoast), rib erosion, pericarditis, AF
Metastatic complicatiotns fo lung cancer
Brain
Bone - pain, anaemia, raised calcium by squamous tumours
Liver
Adrenals - Addison’s
Endocrine complicatiotns fo lunc cancer
Small cell. = SIADH (low sodium high ADH), ACTH (cushings’)
Squamous = PTH (high calcium)
Tests for lung cancer
Sputum and pleural fluid cytology
CXR - nodule, hilar enlargement, consolidatoin, collapse, effusion, bony secondaries
Percutaneous FNA or biopsy if peripheral/superficial
Bronchoscopy for histology and operability
CT for staging
Treatment for lung cancer
Non small cell - excision if peripheral and no spread (stage 1-2)
- Curative RT if resp reserve poor
- CRT if advanced
Small cell nearly always disseminated but may respond to chemo +-RT
Palliation for lung cancer
RT for obstruction, SVC, haemoptysis, bone pain, cerebral mets
SVC obstruction - stent, RT, dexamethasone
Tracheal stent
Pleural drainage for effusions
Prognosis of lung cancer
Non small cell = 50% 2y
Small cell - 3m median survival if untreated
Staging for lung cancer
T1 <3cm in lobar or distal
T2 >3cm and >2cm distal to carina or any size + pleural involvement or obstructive pneumonitis
T3 involves chest wall, diaphragm, mediastinal pleura, pericardium
T4 involves mediastinum, heart, great vessels, trachea, oesophagus, vertebral body or malignant effusion
N1 - peribronchial or ipsilateral hilum
N2 - ipsilateral mediastinum or subcarinal
N3 - contralateral mediastinum or hilum or supraclavicular
Features of different lung cancers
Scc - bronchiobstruction causes infection - cavitation on cxr, slow grow, local spread
Adenocarcinoma - peripheral, scar tissue, bronchial mucous glands, effusion from mets to mediastinal node and pleura
Large cell - neurosecretory, poorly differentiated, grown and met early
Small cell - central, present with systemic disease, neurosecretory granules
Complications of surgery and CRT for oesophageal cancer
Surgery = anatamotic leak, stricture, reflux, motility problems CRT = perforation, stricture, pneumonitis, pulmonary fibrosis
Most common renal cancer
Renal cell carcinoma= 90% - proximal renal tubular epithelium
Sx of renal cell carcinoma
50% incidental finding
Haematuria, loin pain, abdo mass, anorexia, malaise, weight loss, PUO
Varicocoele from invasion of left renal vein obstruction
Initial test findings for renal cell carcinoma
BP high from renin secretion
FBC - polycythaemia from epo
ALP - high if bony mets
Urine for RBC and cytology
Imaging for renal cell carcinoma
US CT/MRI IV urogram Renal angiography CXR - cannonball mets
Treatment for renal cell carcinoma
Radical nephrectomy
Angiogenesis inhibitors
Staging for renal cell carcinoma
Robson: 1 - in kidney 2 - perinephric fat 3 - renal vein 4 - adjacent/distant organs
Where is transitional cell carcinoma
Bladder, ureter, renal pelvis
Sx of transitional cell carcinoma
Painless haematuria, frequency, urgency, dysuria, urinary tract obstruction
Investigate transitional cell carcinoma
Urine cytology
IV urogram
Cystoscopy and biopsy
CT/MRI
Main abdominal malignancy in children and sx
Nephroblastoma - Wilm’s tumour
Abdo mass and haematuria
Where and histology of prostate cancer
Adenocarcinoma in peripheral prostate
Where does prostate cancer spread
Seminal vesicles, bladder, rectum
Haematoenous to bone
Sx of prostate cancer
Nocturia, hesitancy, poor stream, terminal dribble, obstruction
Weight loss and bone pain = mets
Inv for prostate cancer
DRE PSA Transrectal USS and biopsy Bone X-ray, bone scan CT/MRI for staging
Treat prostate cancer
Local - radical prostatectomy or radiotherapy and hormonal therapy
Mets - hormonal drugs, GnRH analogues - stimulate then inhibit pituitary gonadotropin
Adjuncts - analgesia, treat hypercalcaemia, radiotherapy for bone mets/spinal cord compression
Prognostic factors in prostate cancer
Age
Pre treatment PSA level
Tumour stage
Tumour Gleason grade
How is Gleason grade calculated and what does it mean for treatment
Histology from 2 areas and add them, 2-10. High score = aggressive treatment
Pros and cons of PSA for asymptomatic. Men
May not die from it
False positive leads to invasive investigation
1/3 with high psa actually have cancer
Unnecessary treatment with ADRs
Risk factors for prostate cancer
Age - 80% of >80s
High testosterone
Family history
Risk and preventative factors for penile cancer
Very rare if circumcised
Chronic irritation, viruses, smema
Presentation of penile cancer
Fungating ulcer, bloody/purulent discharge
50% spread to lymph at presentation
What is balanitis
Balanitis - staph and strep in foreskin and glans
Common in diabetes, children with tight foreskin
Treat with abx, circumcision and hygiene advice
What is phimosis
Foreskin occludes meatus causing recurrent balanitis and ballooning
Cause painful sex, infection, ulceration and balanitis xerotica obliterans in adults
What is paraphimosis
Tight foreskin retracted and irreplaceable, including after catheterisation, preventing venous return so oedema and ischaemia of glans
Treat by squeezing glans, may need dextrose swab, aspiration, circumcision
What is prostatitis
Acute or chronic, >35y
S faecalis and E. coli
UTI, retention, pain, haematospermia, swollen/boggy prostate
Treat with analgesia and levofloxacin for 28d
Grading bladder tumours
Grade 1 = differentiated
2 = intermediate
3 = poorly differentiated
Common bladder cancers
Transitional cell
Rare = adenocarcinoma and scc
Risk factor for bladder cancer
Male (x4) Schistosomiasis = scc Smoking Aromatic amines - rubber industry Chronic cystitis Pelvic irradiation
Presentation of bladder cancer
Painless haematuria, recurrent UTI, voiding irritability
Tests for bladder cancer
Urine - microscopy and cytology - sterile pyuria
IVU - filling defect, ureteric involvement
Cystoscopy and biopsy = diagnostic
Bimanual EUA for spread
CT/MRI or lymphangiography for pelvic nodes
Staging bladder cancer
Tis = in situ Ta = epithelium T1 = lamina propria T2 = superficial muscle = rubbery thickening on EUA T3 = deep muscle = mobile mass on EUA T4 = beyond bladder = fixed mass on EUA
Treat bladder tcc
Tis, Ta, T1 = watch and wait, or TURBT - diathermy via transurethral cystoscopy. + intravesicular chemo or BCG (non specific inflammatory response) if high grade or many small
T2-3 = radical cystectomy +- adjuvant chemo
T4 = palliative CRT + catheterisation and diversions for pain
Follow up for bladder tcc
Regular cystoscopy - every 3m for 2y then every 6m if high risk
After 9m then yearly if low risk
Spread of bladder tcc
Local - pelvic
Lymphatic - iliac and paraaortic nodes
Haematogenous - liver and lung
Prognosis if node involvement of bladder tcc
6% if unilateral at 5y
0% if bilateral or para aortic
Complications of bladder tcc treatment
Sexual and urinary malfunction if cystectomy
Massive bladder haemorrhage
Ileal conduit - urine toxic to skin, ureters may stenose
Cause of raised PSA
Big prostate Infection uti Inflammation - catheter BPH cancer prostate
Bone scan findings with CaP
Sclerotic lesions, other cancers normally lytic
ADR of radical prostatetomy
Erectile dysfunction, retrograde ejactulation, urinary damage - incontinence
ADR of radiotherapy and different types of RT for prostate cancer
External beam or low does brachytherapy
Causes bowel symptoms ie diarrhoea
Hormonal treatment for CaP
Castration - surgical orchidectomy or medical LHRH agonist - neg feedback so suppresses T production from leydig cells. Cover with antiandrogen for first month to prevent LH surge causing growth of spinal mets
Screening issues with PSA
Lead time bias and length time bias
Origin of most bladder cancers
Papillomata, 80% confined to mucosa
Causes of pancytopoenia
Increaed peripheral destruction - hypersplenism
Decreased marrow production - aplastic anaemia, megaloblastic anaemia, myelofibrosis, marrow infiltration
Types of marrow infiltration causing pancytopoenia
Neoplasm - myeloma, lymphoma, acute leukaemia, solid tumours
TB, myelodysplasia
Causes of aplastic anaemia
AI - drugs, viruses (hepatitis, parvo), irradiation
Inherited - Fanconi anaemia
Treat aplastic anaemia
Asymptomatic - supportive
Immunosuppression
Curative - allogenic marrow transplant from HLA matched sibling
Support blood count with RBC, platelets and WBC
What is agranulocytosis
No production of wBC with granules: BEN (Basophils, Eosinophils, Neuttrophils)
What to safety net for agranulocytosis
Sore throat or fever
Treat agraanulocytosis
G-CSF
Neutropoenia regimen
Abx and cotrimoxaxole for PCP
ADR cotrimoxazole
Rash
What is neutropoenia regimen
If neutrophils <0.5x10^9/l Barrier nursing No IM injections or DRE Chlorhexidine on moist skin Oral hygiene Swab infection sites - mouth, axilla, perineum, IVI Culture blood x3, sputum, urine, stool if diarrhoea FBC, Plt, inr, U&E, ,LFT CXR
When to irradiate platelets
Immunosuppression or marrow transplant to prevent graft vs host
When to give platelets
If <10x10^9/l
Haemorrhage
Before procedure if <50x10^9/l
Survival of different blood products
RBC 120d
Platelets 7d
WBC 1-2c
How to do bone marrow biopspy
Posterior iliac crest Aspirate to film for microscopy Trephine bone core for cellularity, architecture and infiltration (neoplasm) Cytogenetics Flow cytometry
What is amyloidosis
Extracellular deposits of protein with abnormal fibrilar form, resistant to degradation
3 causes of amyloidosis
Plasma cell clonal proliferation - myeloma, lymphoma, MGUS, Waldenstrom’s
Serum amyloid A (acute phase protein) in chronic inflammation - RA, IBD, chronic infection (TB, bronchiectasis)
Familial amyloidosis - autosomal dominant
Sx of plasma cell proliferation causing amyloidosis
Kidneys - proteinuria, nephrotic syndrome
Heart - restrictive cardiomyopathy, angina, arrhythmia
GI - macroglossia, malabsorption, obstruction, hepatomegaly
Neuro - peripheral and autonomic neuropathy, carpal tunnel
Vascular - periorbital purpura
Sx of serum amyloid A from chronic inflammation
Kidneys. - nephrotic syndrome
Hepatomegaly
Sx of familial amyloidosis
Sensory/autonomic neuropathy
Renal/cardiac involvement
Treat familial amyloidosis
Liver transplant
Diagnosis of amyloidosis
Biopsy of rectum or sc fat as non invasive
What affects plasma viscosity
Concentration of large plasma proteins, chronic inflammation >24h - not acute:
RBC raised in polycythaemia rubra vera
WBC raised in leukaemia
Plasma components raised in myeloma and Waldenstrom’ss Macroglobulinaemia (IgM)
Treat raised plasma components
Plasmapheresis - remove plasma and discard, return RBC in more suitable medium
Sx of increased plasma viscosity
Decreased vision
Amaurosis fugax
Retinopathy - haemorrhage, exudates, blurred disc
CNS - disturbance, reduced cognition, falls
Chest and abdo pain
Spontaneous GI/Gu bleeding
What is ESR
How far RBC fall through anticoagulated blood column in 1h
What changes ESR
Proteins as make RBC stick together
- inflammation from infection, malignancy, rheumatoid arthritis, MI; anaemia; macrocytosis
Investigate raised ESR
History and exam FBC, U&E PSA Plasma electrophoresis CXR, AXR (AAA) Marrow or temporal artery biopsy
Calculate ESR
Male = age/2 Female = age+10 /2
Associations with ALL
Genetic susceptibility
Environmental ie radiation in pregnancy
Down’s syndrome
Ways of classifying ALL
Morphological - FAB
Cytogenetic - chromosomal abnormalities
Immunological - precursor B, B or T
Sx of ALL
Marrow failure - anaemia, infection, bleeding
Organ infiltration - hepatosplenomegaly, lymphadenopathy including parotid and mediastinal, orchidomegaly, CNS - cranial nerve palsy, meningism
Common infections in ALL
Chest, mouth, perianal, skin Bacterial septicaemia cmv, zoster, measles pneumocystis pneumoniae candidiasis
Investigations for ALL
Blast cells characteristic on film
CXR for mediastinal and abdominal lymphadenopathy
LP for CNS involvement
Treatment for ALL
Educate and motivate
Support - blood/platelet transfusion, IV fluids, allopurinol for tumour lysis prophylaxis, Hickman line
Chemotherapy - trials of remission/consolidation/CNS prophylaxis/maintenance ie monoclonal antibodies, cytokines, T cell infusions
Neutropoenia - abx, antifungals, antivirals
Matched related allogenic marrow transplant
Prognosis of ALL and bad prognostic signs
70-90% in children, 40% in adults Bad factors: Adult, male Philadelphia chromosome CNS signs on presentation Low haemoglobin WCC >100 B cell ALL
What gene is related to ALL
Philadelphia chromosome - BCR-ABL gene fusion from translocation of chromosomes 9 and 22
How common is AML, what’s the prognosis and what is it associated with
Most common leukaemia of adults, 2m prognosis if untreated
RF: Chemo for lymphoma, myelodysplasia, radiation, syndromes ie downs
Classification of AML
WHO classification
Sx of AML
Marrow failure - anaemia, infection, bleeding
DIC in some
Hepatosplenomegaly, gum hypertrophy, skin involvement
Inv AML
WCC may be high, normal or low Marrow biopsy Microscopy = Auer rods Immunophenotyping Cytogenetic analysis guides treatment
Complications of AML
Infection
Fever without infection
Tumour lysis causing plasma urate levels to rise
Leukostasis
Treatment of AML
Supportive
Chemo causing marrow suppression
Bone marrow transplant - pluripotent haematopoetic stem cells, using ciclosporin and methotrexate to prevent graft vs host
Complication of AML treatment
Graft vs host disease Leukaemia Opportunistic infections Infertility Relapse
What are myelodysplastic syndromes
MDS, myelodysplasia
Marrow failure
Most Primary, or secondary to CRT. 30% become acute leukaemia
Tests for myelodysplastic syndromes
Pancytopoenia, reduced reticulocytes
Marrow cellularity increased due to ineffective haematopoeisis
Ring sideroblasts in marrow
Treatment for myelodysplastic syndromes
Multiple RBC and platelet transfusions
Epo and G-CSF lowers transfusion requiremen
Immunosuppressants ie cyclosporin
Curative allogenic stem cell transplant - only if younger
Thalidomide analogues
When is CML mostly found
40-60y, slight male predominance
Chromosome associated with CML and what does it mean
Philadelphia chromosome in 80%, has tyrosine kinase activity
Without ph have worse prognosis
Sx of CML
Insidious - weight loss, tired, fever, sweats
Gout from purine breakdown
Bleeding
Abdo discomfort - splenic enlargment
Massive splenomegaly, hepatomegaly, anaemia, bruising
Inv CML
WBC >100 with whole spectrum of myeloid cells - myelocytes, neutrophils, basophils, eosinophils Hb low or normal urate and b12 high Marrow - hypercellular Ph on blood or marrow cytogenetics
Stages of CML
Chronic - months/years with few sx
Accelerated - Increasing symptoms, spleen size and counts
Blast transformation - features of acute leukaemia and death
Treatment for CML and side effects
Imatinib - BCL/ABL tyrosine kinase inhibitor
SE = nausea, cramps, oedema, rash, headache, arthralgia, myelosuppressiosn
+- a interferon
Stem cell transplant but high mortality and morbidity
What is CLL
Accumulation of mature B cells that have undergone cell cycle arrest in G0/1 phase
Commonest leukaemia?
CLL
What can trigger CLL
Pneumonia
Sx of CLL
Often incidentally found on FBC Anaemia/infections Weight loss, sweats, anorexia Enlarged rubbery non tender nodes Hepatosplenomegaly
Inv CLL
High lymphocytes
Then AI haemolysis, marrow infiltration - low Hb, neutrophils and platelets
Complicatiosn of CLL
AI haemolysis
Infection from hypogammaglobulinaemia (reduced IgG) - esp herpes zoster
Marrow failure
Progression of CLL
Nodes slowly enlarge and can cause lymphatic compression
Infections cause death
Transform to aggressive lymphoma - Richter’s transformation
1/3 don’t progress, 1/3 will progress, 1/3 actively progressing
Infections found in CLL that can cause death
Haemophilus Pneumococcus Aspergillosis Meningococcus Candida
Treat CLL
Chemo if symptomatic, or depending on genes
Steroids for AI haemolysis
RT for lymphadenopathy and splenomegaly
Supportive - transfusions, IV human Ig if recurrent infection, prophylactic azithromycin acyclovir (+cotrimoxazole nebs for PCP)
Stem cell transplant
Staging CLL
Rai stages: 1 - lymphocytosis 2 - with lymphadenopathy 3 - with spleno/hepatomegaly 4 - with anaemia 5 - with platelets <100
Differentiate between AML and ALL
More hepatosplenomegaly, testicular infiltration and CNS involvement in ALL. Mediastinal/thymic mass in ALL
Bone and skin involvement in AML
Gum hypertrophy in AML
Prophylaxis for PCP
Cotrimoxazole neb
CNS prophylaxis for ALL
Intrathecal or high dose IV methotrexate +- CNS irradiation
What is ALL remission defined as?
No evidence of leukaemia in blood or normal/recovering FBC
And <5% blasts in normal regenerating marrow
Can detect minimal residual disease with PCR
FAB stages of ALL
L1 = children, good prognosis L2 = adults, intermediate prognosis L3 = Burkitt’s lymphoma, adults, poor prognosis
Infection difficulties with leukaemia
Rare organisms
Common organisms present differently
Fever from AML
Fewer antibodies
Basis of definitive treatment in AML
Destroy marrow with cyclophosphamide and total body irradiation then repopulate with IVIg
Advantage of autologous instead of allogenic bone marrow transplant
Faster haematopoetic recovery and lower morbidity
Signs of Richter’s transformation for CLL
Systemic - night sweats and fever
Increased spleen and nodes (tonsils = breathing problems, sore throat)
Cytopoenias
WCC >200
Causes of lymphadenopathy
Infection - bacteria (TB = matted), viral (EBC, HIV), Protozoa (toxoplamosis)
Malignancy - primary (leukaemia, lymphoma), secondary (mets, neuroblastoma, virchow’s node)
AI - RA, SLE
Drugs
Classify lymphadenopathy
Size - >10mm, long and short axes
Extent - localised to infection, localisation not region ie mediastinum, generalised
Investigate lymphadenopathy
CXR if supraclavicular or cervical Infection swabs for culture and sensitivity FBC, blood film, ESR/plasma viscosity LFTs, LDH (released by cell turnover) Urate, calcium Lymph node excision biopsy Body CT/MRI Marrow biopsy - aspirate, trephine, cytogenetic, flow cytometry LP for cytology if CNS signs Effusion cytology
Findings on flow cytometry of bone marrow in lymphoma
Non-hodgkin’s = B cellswith abnormal kappa:lambda ratio Hodgkin’s = Reed-Sternberg cells
Causes of massive splenomegaly
3Ms:
Myelofibrosis
cMl
Malaria
Cause of splenomegaly
Increased function
Abnormal flow - organ, vascular or infection
Infiltration - metabolic or benign/malignant
Cause of increased spleen function
Immune hyperplasia - infection or AI
Extramedullary haematopoesis - marrow infiltration or destruction (toxins, radiation)
Defective RBCs - sickle cell, thalassaemia
Cause of abnormal flow through spleen
Organ - liver cirrhosis (portal hypertension - caput medusae?)
Vascular - hepatic/portal/splenic vein obstruction, Budd-Chiari
Infection - hepatic schistosomiasis
Types of spleen infiltration
Metabolic - amyloidosis Benign/malignant: leukaemia, lymphoma, myeloproliferative disorder - Eosinophilic granulomas - Metastatic tumour ie melanoma - Hamartoma
When is splenectomy indicated
Trauma
Hypersplenism
AI haemolysis (ITP, congenital haemolytic anaemia, warm AI haemolytic anaemia)
Risk in splenectomy or hyposplenism and why
Infection as spleen contains macrophages which phagocytise bacteria
Encapsulated organisms - strep pn, H influenza, neisseria meningitidis
2 causes of hyposplenism
Sickle cell
Coeliac
Management of hyposplenism or splenectomy
Advice:
Mobilise asap as transient increase in platelets can cause thrombi
Medical alert bracelet
Safety net for infection
Mediation:
Malaria prophylaxis if abroad
Immunisations - pneumococcal, meningococcal C, H influenzae B, annual influenzae
Prophylactic abx lifelong - phenoxymethylpenicillin or erythromycin
When to have/not have pneumococcal vaccine if splenectomy/hyposplenism
Every 5-10y
2w pre-op
Not if pregnant
What is lymphoma
Malignant proliferation of lymphocytes in lymphadenopathy, blood and organ infiltration
Sx for lymphoma
Anaemia, thrombocytopoenia x
B sx - fever, night sweats
Hyperviscosity - headache, blurred vision
Infections
PMH relevant to lymphoma
Diabetes, hypertension, kidney disease as most treatment includes steroids which can affect these
Drug history relevant tolymphoma
Azathioprine or methotrexate can cause macrocytosis
Previous chemo can. Cause myelodysplasia
Who gets Hodgkin’s lymphoma?
Young people and elderly - 2 peaks
Risk factors for hodgkin’s lymphoma
Sibling Westernisation Obese EBV SLE Post-transplant
Causes of non-hodgkin’s lymphoma
Congenital immunodeficiency Acquired immunodeficiency AIDS - high grade lymphoma Infection - HTLV1, EBV, h. Pylori Environmental toxins
Histology for Hodgkin’s and non-hodgkin’s lymphoma
Hodgkin’s = Reed-Sternberg cells - mirror image nuclei Non-hodgkin’s = no reed-sternberg, mostly B cell lines, extranodal sites ie MALT
Association of H pylori and lymphoma
Causes MALT - extranodal Non-hodgkin’s
Regresses if treated
Classification of Hodgkin’s (4)
- Nodular sclerosing - indolent B cell lymphoma
- Mixed cellularity - higher incidence and worse prognosis if HIV
- Lymphocyte rich
- Lymphocyte depleted - poor prognosis
Classification of Non-Hodgkin’s (grades) and implication and 2-3 examples of each
WHO classification -
Low grade = indolent,incurable, widely disseminated at presentation - follicular and marginal zone (MALT) and lymphocytic lymphoma
High grade = more aggressive ,more curable long term, short hx of rapid node enlargement and systemic sx - Burkitt’s, lymphoblastic lymphoma
Burkitt’s lymphoma associations
Kids
Jaw lymphadenopathy
High grade non-hodggkin’s lymphoma
Staging of lymphoma
Ann Arbor - uses CXR, CTCAP, marrow biopsy if b sx or stage 3-4
1 - one node
2 - 2+ nodal areas on 1 side of diaphragm
3 - nodes on both sides of diaphragm
4 - spread beyond nodes ie liver or marrow
+ a = no systemic sx except pruritis
+ b = B sx ie weight loss unexplained fever, night sweats
+ E = localised extranodal extension
Sx of lymphoma
Nodes - enlarged, painless, rubbery, superficial, mostly cervical (some axillary or inguinal), alcohol-induced node pain, may change size +- matting
Systemic - fever >38, weight loss >10% in m, pruritis, lethargy
Mass effect (mediastinal) - SVC/bronchial obstruction, pleural effusion
Signs - anaemia, cachexia, hepatosplenomegaly
Treatment of Hodgkin’s lymphoma
Chemo, radio or both
+- stem cells - autologous or allogenic
ADR of chemo and radiotherapy for Hodgkin’s lymphoma
Chemo - nausea, allopecia, myelosuppression, infection
Radiotherapy - solid tumour, IHD, hypothyroid, lung fibrosis
AML, non-hodgkin’s lymphoma, infertility
Prognosis of Hodgkin’s lymphoma
40-95%
Sx of SVC obstruction - 5
Raised JVP Sensation of fullness in head Black outs Dyspnoea Facial oedema
Treatment of non-hodgkin’s lymphoma
Low grade and asymptomatic - none, localised = radiotherapy 9curative))
High grade - chemotherapy (CHOP)
Neutropoenia - G-CSF
Prognostic factors of non-hodgkin’s lymphoma and prognosis
> 60y, systemic, disseminated, bulky mass, raised LDH
Low grade = 50% 5y survival,
High grade = 30%
Causes of spinal cord compression
Extradural metastases
Extension of tumour from vertebral body
Crush fracture
Sx of spinal cord compression
Backpain, disturbing sleep , worse lying down or coughing
Weakness
Sensory loss with root distribution or sensory level
Bowel and bladder dysfunction
Determination of reflexes and neuro signs depending on level of spinal cord compression?
Above L1 = umn signs in legs
Below L1 = lmn signs in legs
Sensation reduced at level of lesion
Investigate spinal cord compression
Urgent MRI of whole spine
Manage cord compression
Dexamethasone IV then PO
Urgent RT
Vertebral body reinforcement for pain,or spinal reconstruction
Laminectomy if isolated tumour
Cause of SVCO
Normally lung cancer, also mediastinal enlargement from germ cell tumour or lymphadenopathy from lymphoma
Test for SVCO
Pemberton’s test - lift arms above head for 1m, makes facial plethora/cyanosis, raised jvp, inspiratory stridor
Inv svco
CXR, CT, venography, sputum cytology
Manage svco
Dexamethasone PO
Balloon venoplasty and SVC stenting
Radical or palliative C/RT
Causes of hypercalcaemia in cancer
10-20% in cancer patients
40% in myeloma
Lytic bone mets
Osteoclast activating factor or PTH like hormones from tumour
Sx of hypercalcaemia in cancer
Lethargy, anorexia, nausea Confusion Polydipsia, polyuria Constipation Dehydration
Treat hypercalcaemia in cancer
Manage underlying malignancy
Bisphosphonates IV or PO
Calcitonin if resistant
Manage RICP in cancer
Dexamethasone, RT, surgery
Mannitol for cerebral oedema
What is tumour lysis syndrome and complication?
Rapid cell death from starting chemo for rapidly proliferating leukaemia, lymphoma,, myeloma, some germ cell tumours
Rise in serum urate, K and phosphate, can cause renal failure
Prevent tumour lysis syndrome
Hydrate and allopurinol 24h before chemo
Treat tumour lysis syndrome
Dialysis
Rasburicase IVI - recombinant urate oxidase
ADR rasburicase
Fever, D&V, headache
Bronchospasm
Haemolysis
Rash
Medication for neutropoenia
Abx - aminoglycoside (gentamicin) and ceftazidime
G-CSF
Cotrimoxazole for pneumocystis
Risk factors for tumour lysis synddrome
High LDH
High creatinine or urate
WCC >25x10^9
Dangers of leukaemia
Tumour lysis
Neutropoenia
Hyperviscosity - WBC thrombi if WCC >100, in brain/lung/heart = leukostasis
DIC
Test findings for DIC
Plt low APTT and PT high Fibrinogen low Fibrin degradation products D dimers very high Schistocytes on film
Treat DIC
Treat cause Platelets if <50 Cryoprecipitate to replace fibrinogen FFP to replace coag factors Activated protein c reduces mortality
Types of chemo drugs
Alkylating agents - cyclophosphamide
Antimetabolites - methotrexate, 5-fluorouracil
Vinca alkaloids - vincristine
Antitumour antibiotics - actinomycin D, doxorubicin
Monoclonal antibodies ie against EGFR receptors
When does neutropoenia normally happen after chemo
10-14d
Manage extravasation of chemo agent
Stop infusion, attempt to aspirate blood from cannula then remove
Steroids and antidotes
Elevate arm
Steroid cream
How does radiotherapy work?
Ionising radiation makes free radicals which damage DNA
Normal cells repair better than cancer cells so recover before the next dose
When can radiotherapy be used for palliation?
Haemoptysis, cough, SOB
Bone pain
Bleeding
Early reactions to RT
Tired Skin - erythema, desqamation, ulceration Mucositis - avoid spicy food, smoking and alcohol if head and neck RT, oral thrush Nausea and vomiting if stomach, liver or brain Diarrhoea if abdo/pelvis Dysphagia if thoracic Cystitis if pelvic Bone marrow suppression if large areas
Manage oral thrush, diarrhoea, n&v, pelvic cystitis, from RT
Thrush - oral solution nystatin +- fluconazole
Diarrhoea - loperamide, not high fibre bulking agents
N&V - metaclopramide (dopamine antagonist) or domperidone (blocks chemoreceptor trigger zone), then ondansetron (serotonin antagonist)
Cystitis - fluids, NSAIDs (diclofenac)
Late CNS reactions to RT and management
CNS - somnolence, spinal cord myelopathy (progressive weakness), brachial plexopathy (numb, weak, painful arm), reduced IQ if <6yo
MRI to exclude cord compression
Steroids for somnolence
Late lung effects of RT
Pneumonitis - dry cough, SOB
Give prednisolone and reduce over 6w
Late GI effects of RT
Xerostomia - give pilocarpine or artificial saliva with meals
Reduced healing - care with dental care
Benign strictures of oesophagus or bowel - dilatation
Fistulae - surgery
Radiation proctitis from prostate irradiation
Late GU effects of RT
Urinary frequency from small fibrosis bladder
Fertility - ova/sperm storage
Premature menopause or reduced testosterone - hormones
Vaginal stenosis and dyspareunia
Erectile dysfunction - can happen after several years
Late complications of RT
CNS Lung GI - mouth and intestines GU - urinary and repro Panhypopituitarism - consider growth hormones in children Hypothyroid Secondary cancers - sarcomas - often 10+y after Cataracts
Considerations of fertility in CRT
Damage germ cell spermatogonia
- impaired spermatogenesis or male sterility
- hastened oocyte depletion - premature menopause
GnRH agonists for women during chemo can help
Semen or embryo cryopreservation or ovarian tissue banking before treatment, the outcome depends on uterus integrity after treatment
Causes of n&v in palliative care
Chemo Constipation GI obstruction Drugs Pain Cough Squashed stomach Oral thrush Infection Uraemia
Basis for n&v treatment
Cause - analgesia, antibiotics, laxatives, fluconazole, drug management including route
Base drug on mechanism and site of action
Give regularly, not prn
Action of cyclizine
Antihistamine, central action, most causes
Action of domperidone
Blocks central chemoreceptor trigger zone - for younger patients who won’t have acute dystonic SE
Action of metaclopramide
Central antidopaminergic and peripheral proketic - good for gut stasis
Action of haloperidol
Dopamine antagonist, for drug or metabolic induced nausea
Action of Ondansetron
Serotonin antagonist, second line
Action of Levomepromazine
Morphine induced nausea, broad spectrum, can cause sedation
Prevent and treatment constipation in cancer treatment
From opiates, give bisacodyl or stimulant with softener
Movicol useful if resistant
Glycerol suppositories or arachis oil enema if oral therapy fails
Manage breathlessness in palliative care
Morphine - reduces respiratory drive and sensation of breathlessness
Relaxation techniques and bzds
Check for pleural or pericardial effusion
Thoracocentesis +- pleurodesis for significant pleural effusion
Pericardiocentesis or external beam radiotherapy for malignant pericardial effusion
Manage coated/dry mouth
Treat candida - fluconazole
Ice chips, pineapple chunks, gum
Chlorhexidine, saliva substitutes
Problems with venepuncture in palliative care
Extravasation, phlebitis
Infection, blockage - give saline or heparin, thrombosis/obstruction
Manage agitation, nightmares, hallucinations, vomiting in palliation
Haloperidol
What’s hyoscine for in palliative care
Vomiting from upper GI obstruction or noisy bronchial rattles
Manage ascites in palliative care
Spironolactone and bumetanide
What are syringe drivers and what drugs are they for in palliative care?
Sc continuous infusion of fluids and drugs to avoid cannulation repeatedly
1) Glycopyrronium or hyoscine hydrobromide for terminal secretions
2) Diamorphine for pain - better than morphine due to greater solubility reducing risk of precipitation at high doses
3) Midazolam for agitation and seizure control
4) Cyclizine or haloperidol for nausea
5) Hyoscine butylbromide for bowel colic
Work out dose for morphine
Start at 5-10mg/4h orally
Then add total over 24h and divide by 2 for 12h release, with 1/6 daily dose for breakthrough
ADR of morphine
Drowsy, n&v, constipation, dry mouth
Signs of morphine toxicity
Hallucinations and myoclonic jerks
What if morphine oral isn’t working
Diamorphine IV/SC
Oxycodone PO/IV/SC/syringe driver/PR has fewer side effects and more potent
Fentanyl transdermal patch
Morphine resistant pain?
Methadone or ketamine
Adjuvants - NSAIDs, steroids, muscle relaxants, anxiolytics
Neuropathic - amitriptylline or gabapentin
SSRI if depression
WHO analgesia ladder
1 - non opioid - aspirin, paracetamol, NSAID
2 - weak opioid - codeine, dihydrocodeine, tramadol
3 - strong opioid - morphine, diamorphine, hydromorphine, oxycodone, fentanyl
Tumour markers
Alpha-fetoprotein - germ cell tumour, hepatocellular carcinoma
CA125 - ovary, uterus, breast, hepatocellular carcinoma
CA19-9 - pancreas or colorectal carcinoma or cholestasis
Carcino-embryonic antigen - GI carcinoma especially colorectal cancer
Human epidermal growth factor receptor 2 - Overexpression of HER2 in breast cancer carries a worse prognosis - target with herceptin/trastuzumab, also ovarian, stomach, uterine
B-HCG - pregnancy and germ cell tumours
Causes of polycythaemia
Relative - reduced plasma volume - acute from dehydration or chronic from obesity, hypertension, alcohol, tobacco
Absolute - increased RBC mass - primary from rubra vera or secondary from hypoxia (chronic lung disease, cyanotic CHD, high altitude) or increased epo (renal carcinoma, hepatocellular carcinoma)
Polycythaemia rubra vera?
Malignant proliferation of a clone from one pluripotent marrow stem cell
JAK2 mutation
Excessive RBC, WBC and platelets - can cause hyperviscosity and thrombosis
Sx of polycythaemia rubra vera
Symptoms of hyperviscosity - headache, dizzy, tinnitus, visua disturbance
Itch after hot bath
Erythromelalgia - burnings in fingers and toes
Facial plethora
Splenomegaly
Gout from increased urate in increased RBC turnover
Arterial or venous thrombosis
Signs of arterial and venous thrombosis in polycythaemia rubra vera
Arterial - cardiac, cerebral, peripheral
Venous - DVT, cerebral, hepatic
Inv for polycythaemia rubra vera and findings
FBC - raised RBC, Hb, HCT, PCV, often raised WBC and platelets
B12 high
Marrow - hypercellular with erythroid hyperplasia
Neutrophil alkaline phosphatase high
Serum epo low
Treat polycythaemia rubra vera
Monitor HCT to decrease thrombosis risk
Venesection in young and low risk
If old and high risk (previous thrombosis), give hydroxycarbamide or a-interferon if pregnant
Low dose aspirin
Complications of polycythaemia rubra vera
thrombosis and haemorrhage (defectives platelets)
Transition to myelofibrosis or acute leukaemia
What is increased platelets and sx?
Essential thrombocytopoenia from clonal proliferation of megakaryocytes
Abnormal function - bleeding, or arterial/venous thrombosis, or microvascular occlusion = headache, chest pain, light headed, erythromelalgia
Treat essential thrombocythaemia
Exclude other causes of thrombocytosis
Aspirin low dose daily
Hydroxycarbamide to lower platelets if >60 or previous thrombosis
Result of myeloproliferative disorders
Myelofibrosis - hyperplasia of megakaryocytes produces platelet derived growth factor, leads to
- intense marrow fibrosis and
- myeloid metaplasia (haemopoesis in spleen and liver) causing massive hepatosplenomegaly
Presentation of myelofibrosis
Hypermetabolic syndrome - night sweats, fever, weight loss, abdo discomfort from splenomegaly
Bone marrow failure
Inv findings for myelofibrosis
Blood film - leukoerythroblastic cells (nucleated RBC)
Characteristic teardrop RBC
Hb low
Trephine for diagnosis
Manage myelofibrosis
Marrow support
Allogenic stem cell transplant - curative in young , but mortality high
Causes of thrombocytosis
Reactive = Bleeding Infection Chronic inflammation Malignancy Trauma Post-surgery Iron deficiency Essential thrombocythaemia
Causes of marrow fibrosis
Myelofibrosis Myeloproliferative disorder Lymphoma, leukaemia Secondary carcinoma TB Irradiation
What is myeloma?
Malignant clonal proliferation of B-lymphocyte derived plasma cells
Normally different plasma cells produce different Ig = polyclonal, but here get single clone of plasma cells = monoclonal band or paraprotein on serum or urine electrophoresis
Classify myeloma
On Ig product - 2/3 = IgG, 1/3 = IgA
Findings of myeloma investigations
Monoclonal band in serum or urine electrophoresis
Other Ig low - infection risk
Urine has Bence-Jones protein (free Ig light chains of kappa or lambda) filtered by kidney
Peak age of myeloma
70yo
Sx of myeloma
Osteolytic bone lesions due to increased osteoclast activation from myeloma cell signalling = back ache, pathological fracture in long bones/ribs, vertebral collapse
Hypercalcaemia sx
Anaemia, neutropoenia, thrombocytopoenia
recurrent bacterial infections - immunoparesis and neutropoenia
Renal impairment from light chain deposition - distal loop of henle and changes in glomeruli, can be deposited in form of AL-amyloid which causes nephrosis
Test findings for myeloma
FBC - normocytic normochromic anaemia - raised ESR - raised urea and creatinine - raised calcium - ALP normally normal Film = rouleaux formation Serum and urine electrophoresis for bence-jones and monoclonal bands X-ray = lytic lesions ie pepper pot skull and vertebral collapse, or osteoporosis
Treat myeloma
Supportive
- analgesia but avoid nsaid as renal impairment
- Bisphosphonates to reduce fracture rate and bone pain
- Local rt for focal disease
- Vertebroplasty if vertebral collapse
- Correct anaemia with transfusion or epo
- Renal failure - hydrate, dialysis if acute
- Infection - abx, regular IVIg if recurrent
Chemo - including prednisolone, reduces paraprotein levels and bone lesions
Stem cell transplant
Prognosis for myeloma
3-4y, worse if raised B2 microglobulin
Death from infection or renal failure
3 myeloma diagnostic criteria
Monoclonal protein band in serum or urine electrophoresis
Increaed plasma cells on BM biopsy
Evidence of end organ damage from myeloma - hypercalcaemia, renal failure, anaemia, or bone lesions (skeletal survey)
Causes of bone pain
V - osteonecrosis from microemboli
I - osteomyelitis, osteosclerosis from hep c
T - trauma/fractures
A - renal osteodystrophy, CREST
M - paget’s, sickle cell anaemia, hyperparathyroid
N - myeloma or primary malignancies, secondaries (breast, lung, prostate), hydatid cyst
Complications of myeloma and treatment
Hypercalcaemia - at presentation or relapse, rehydrate with saline, IV Bisphosphonates (zolendronate or pamidronate)
Spinal cord compression - urgent mri and dexamethasone 8-16mg OD PO, local radiotherapy
Hyperviscosity - reduced cognition, disturbed vision, bleeding - plasmapheresis
Acute renal failure - rehydration, dialysis
What is paraproteinaemia
Immunoglobulins from single clone of plasma cells - monoclonal band on serum electrophoresis
Categories of paraproteinaemia
Multiple myeloma
Waldenstrom’s macrolobulinaemia
Primary amyloidosis
MGUS - low concentration of paraprotein but no myeloma, amyloid, macroclobulinaemia orlymphoma, no bone lesions or bence-jones
Paraproteinaemia in lymphoma or leukaemia
Heavy chain disease - neoplastic cells produce free Ig heavy chains
What is Waldenstrom’s macroglobulinaemia, sx and treatment
Lymphoplasmacytoid lymphoma producing monoclonal IgM paraprotein
Causes hyperviscosity with CNS and ocular symptoms, lymphadenopathy, splenomegaly, increased ESR
Only treat if symptomatic - with chemo or plasmaphoresis for hyperviscosity
Inherited causes of thrombophilia - 4
Factor V Leiden = activated protein C (apc) resistance
Prothrombin gene mutation - downregulation of fibrinolysis
Protein c and s deficiency
Antithrombin deficiency
What is antiphosopholipid sydrome
Lupus anticoagulant and anticardiolipin antibodies = antiphospholipid antibodies
Risk of venous and arterial thrombosis, thrombocytopoenia and recurrent foetal loss in pregnancy
Normally primary disease but can be in SLE
Tests for thrombophilia
FBC, film, clotting, INR, PT
APC resistance test
Fibrinogen concentration
Lupus anticoagulant and anticardiolipin antibodies
Assays for antithrombin and protein c and s
PCR for factor V Leiden mutation and prothrombin gene mutation
Treat thrombophilia
Acute - heparin then warfarin to target INR 2-3
Lifelong warfarin in recurrence - target INR 3-4
High dose heparin if antithrombin deficiency
Danger in protein c and s deficient treatment
Warfarin can cause skin necrosis
Prophylaxis for thrombophilia in pregnancy
Aspirin and heparin
Risk factors for arterial thrombosis
Smoking
Hypertension
Hyperlipidaemia
Diabetes
Risk factors for venous thrombosis
Surgery Trauma Immobility Pregnancy, OCP, HRT Age Obesity Varicose veins Conditions - heart failure, malignancy, IBD, nephrotic syndrome
What conditions can be made worse by steroids
TB, chicken pox
Hypertension, diabetes
Osteoporosis
Main drug interactions with prednisolone
Antiepileptics and rifampicin lower concentration
Guidance when starting steroids
Carry steroid card with dose and reason
Don’t stop suddenly - takes time for endogenous production to start again, can cause collapse, if >3w or >7.5mg/d
Warn about side effects if long term
Go to doctor if ill - may need to increase dose if ill or stressed
OTC drugs - no NSAIDs as increase DU risk
Prevent osteoporosis if long term - exercise, bisphosphonates, calcium and vit d supplements, smoking cessation
When should steroid withdrawal be gradual
Repeated courses >3w Hx of adrenal suppression >40mg/d Doses at night
Organs with SEs of steroids
GI MSK Endocrine CNS Eyes Immune
GI SEs of steroids
Candidiasis
Oesophageal ulceration
Peptic ulceration
Pancreatitis
Msk SEs of steroids
Osteoporosis
Fractures
Growth suppression
Myopathy
Endocrine SEs of steroids
Adrenal suppression
Cushing’s
CNS SEs of steroids
Depression
Psychosis
Aggravation of epilepsy
Eye SEs of steroids
Cataracts
Glaucoma
Papilloedema
immune SEs of steroids
Increased susceptibility and severity of infections
Fever and raised WCC
DDI of azathioprine and mercaptopurine
Allopurinol, a xantine oxidase inhibitor. Azathioprine and mercaptopurine are metabolised by XO so can reach toxic levels if with allopurinol
What does ciclosporin do, and main SEs
Calcineurin inhibior, with tacrolimus
For reducing rejection in organ and marrow transplant
SE - dose related nephrotoxicity - monitor UEs and creatinine every 2w for 3m, reduce dose if creatinine rises by >30%
Also = gum hyperplasia, hypertension, paraesthesia, confusion, seizures
Lymphoma and skin cancer
How does methotrexate work
Antimetabolite, inhibits dihydrofolate reductive which is needed for synthesis of purines and pyrimidines
How does cyclophosphamide work and SEs
Alkylating agent
Marrow suppression, nausea, infertility, teratogenic
Haemorrhagic cystitis as irritative urinary metabolite, slight increased risk of bladder cancer or leukaemia
2ww criteria lung
> 40yo
Haemoptysis
Smoker
2ww bowel criteria
Abdo pain and unexplained weight loss >40y
Unexplained rectal bleeding >50yo
Iron deficiency anaemia or change in bowel habit >60yo
WHO performance status
0 - asymptomatic 1 - symptoms, fully ambulatory 2 - symptomatic, in bed <50% 3 - symptomatic, in bed >50% but not bedridden 4 - bedridden
Staging and grading in general how
Imaging - staging CT
Biopsy - grading
Lung cancer rf
Smoking x10
Asbestos x5
Where are NSCLC and which is worst
Squamous - central, airways
Adeno - peripheral
Large cell - worst
Lung cancer inv
CXR
Staging CT NTAP
PET CT
Biopsy - percutaneous or bronchoscopy (+endobronchial US and alveolar lavage)
curative lung cancer treatment
Surgery
Radical RT or chemo if unfit for surg
PAlliative lung cancer treatment
Stents
Brachytherapy
Palliative chemo
Curative lung cancer treatment
Surgery
Radical RT or chemo if unfit for surg
Palliative lung cancer treatment
Stents
Brachytherapy
Palliative chemo
RF for colorectal cancer - 4
FAP - APC gene
Lynch syndrome
Smoking
UC (pancolitis for 15y+ = 15-20%)
Inv colorectal cancer
CEA
Staging CT TAP for liver mets
Colonoscopy and biopsy
Curative treatment colorectal cancer
Surgical, neoadjuvant RT, adjuvant chemo
Palliative management colorectal cancer
Stent/bypass
Chemo
Screening for colorectal
FOB every 2y 60-74yo
5/10 will have normal colonoscopyl, 4/10 will have polyps on colonoscopy, 1/10 will have cancer
Duke staging and 5y survival
A - confined to mucosa 90% B1 - muscularis propria B2 - through muscularis propria and serosa - 60% C1 - 1-4 nodes - 30% C2 - 4+ regional nodes D - distant mets
Upper GI 2ww criteria
> 55
Dysphagia - progressive
Weight loss
Mass
Upper GI RF
Smoking, alcohol
Barret’s
H pylori - ask about ulcers
Inv upper GI cancer
OGD and biopsy
Staging CT TAP, PET CT/staging laparoscopy
Barium swallow = apple core sign
Pallliative upper GI cancer management
[LASER] Laser Analgesia Stent EtOH injection - for pain Radiotherapy
Complications of upper GI cancer
Upper GI bleed
Obstruction - succussion splash, projectile vomiting
Perforation
What is acute leukaemia
Defective maturation of myeloid/lymphoid cells in bone marrow which spill out as immature blast cells that infiltrate
- liver, spleen, node, BM
What is chronic leukaemia
Proliferation of mature myeloid/lymphoid cells in BM which spill out and cause proliferative effects and infiltrate into all lymphatic systtems
What is Lymphoma
Proliferation of lymphoid cells from within lymphoid tissues that infiltrate into lymphatic tissues and bone marrow (sx)
What are lymphoid proliferation/infiltration symptoms
Invasion into HSM, bone, skin, gums, testes, thymus
Lymph nodes to check
Cervical
Inguinal
Axillary
Myeloid proliferation signs
HSM
Hyperviscosity - headache,visual, vte
Hyperuricaemia - gout
Features of blood cancers
B symptoms - BM infiltration FBC symptoms - BM infiltration Lymph nodes Lymphoid proliferation/infiltration Myeloid proliferation
Bloods for blood cancer
Fbc Blood film Flow cytometry LDH, urate, folate = markers of excess cell turnover Clotting - DIC in APML
Biopsy for blood cancer
Cytology - blast/plasma cells, hypercellular, Reed-sternberg
Morphology - M3 = APML
Immunophenotyping - B/T cells
Cytogenetics - Philadelphia t(9:22), APML t(15:17)
imaging for blood cancers
Lymphoma - Ann Arbor - CT TAP, PET CT
Myeloma - skeletal survey, PET CT
CLL features
Elderly, indolent
Lymphocytosis - symmetrical LN
Smudge cells
Features of CML
Adults
Philadelphia
Myeloproliferative
Non-Hodgkin’s lymphoma features
Asymmetrical non-continuous node enlargement
Low (follicular) or high (diffuse) grades
AML features
Auer rods, blasts
BM and tissue infiltration
Less chemoreponsive
ALL
Children
Blasts
BM and Tissue infiltration including CNS
chemo responsive
Myeloma and MGUS differentiate
CRAB in myeloma
IgG high and rest low in myeloma
Rest normal in MGUS
Diagnose Al-amyloid
Rectal biopsy
Types of myeloma/myeloid prolif
Myeloma
MGUS
Al-amyloid
DIC treatmetn
FFP and cryoprecipitate (has fibrinogen)
+- platelets
DIC
Low Hb, Plt, fibrinogen
High INR, APTT, FDP
Schistocytes
2ww skin cancer
ABCDEF
Types of skin cancer histoloy
Superficial - flat
Nodular - worst as can infiltrate
Acral - on hands
Lentigo maligna
Inv skin cancer
Excision biopsy for breslow thickness for planning margin needed
Manage skin cancer
Widen excision margin
+- adjuvant chemo
BCC features
Rodent ulcer
Pearly colour
Rolled edge
SCC features
Ulcerated nodule
Hard everted edge
Diagnostic inv for myeloma
Serum protein electrophoresis
Bad prognostic signs in myeloma
Hb low
Clonal plasma cells high
Inv for sepsis after oesophagectomy
Contrast swallow - likely anastamotic leak
= mediastinitis
Inv when slow growing lymphadenopathy has had a sudden drop in Hb and increase in reticulocytes with splenomegaly
Direct antiglobulin test - warm AI haemolytic anaemia in CLL
Most common type of inherited bowel cancer
Lynch syndrome
What is lynch syndrome and inheritance signs
HNPCC
Extensive GI polyps
Endometrial, renal, CNS cancers
2 generations, 3+ first degree relatives to each other, 1 tumour <50yo
Lung cancer - when is hypercalceamie more likely?
SCC = PTHrP
Immediate management for abdo pain, constipation and high calcium in lung cancer
IV fluids
What is FAP
APC TSG gene
>100 adenomatous polyps in colon and rectum
Can have duodenal and fundic glandula
100% cancer
biggest RF for melanoma
Intense UV radiation
What skin cancer does immunosuppression make more likely
BCC
SCC
types of prostate cancer
Adenocarcioma peripheral zone:
Localised (inside capsule), local advanced (leaves capsule but not in organs) or mets
Prostate 2ww
Craggy or nodular DRE
PSA increased without other cause (increased with age - different cut offs)
Red flags eg bone pain
Inv prostate cancer
DRE and PSA
TRUS biopsy and Gleason grade
Isotope bone scan for sclerotic lesions
Manage CaP
Localised - active surveillance (curative intent - TRUS, rectal exams until found to be progressive then treat) vs watchful waiting (minimally invasive, palliative intent)
Local advanced - radical prostatectomy or RT, hormonal - LHRH agonist
Mets - hormonal, steroids/radio for bone mets
Features of non-seminoma
young, fast growing, tumour markers
Testicular cancer 2ww
Unexplained testicular lump,, usually painless
Inv testicular cancer
Tumour markers - bHCG, AFP, LDH, oestradiol = teratoma US testes, CT TAP Excision biopsy (core = tracking)
types of testicular cancer
Seminoma
Non-seminoma
Teratoma
Manage testicular cancer
Sperm bank
Inguinal orchidectomy
Adjuvant RT for seminoma
Chemo for relapses in non-seminoma
Rf for bladder/renal cancer
Substances - smoking, cyclophosphamide, dye
SCC. - schistosomiasis
2ww for bladder/renal cancer
Visible haematuria >45, unexplained (eg no UTI)
Non visible haemoaturia >60yo, no exercise etc
Inv bladder/renal cancer
Urine microscopy (?sterile pyuria?)
Flexible cystoscopy
Staging CT TAP
manage bladder/renal cancer
Invasive -
- renal = radical nephrectomy and RT
- bladder = cystectomy and ideal conduit and RT
Superficial bladder - TURBT via rigid cystoscopy and intravesicular chemo (BCG = higher risk)
Testicular lump with raised tumour markers
Teratoma
Complication of testicular lump
Torsion - surgery
When can you do PSA after DRE
2w later
Mood problems and flushes with hormonal therapy for prostate cancer
= testosterone flare a couple of weeks after starting hormonal therapy Cyproterone acetate (anti androgen)
PUO and left varicoele?
Renal cell carcinoma - compresses left renal vein (drains into left testicular vein)
Prognostic factors in breast cancer
ER+ = better prognosis HER2+ = worse prognosis
2ww for breast cancer
> 30 with unexplained breast lump
50 with unilateral nipple discharge/retraction
? Family history
Most common breast cancer
DCIS/invasive
Histology inv for breast cancer
Cystic - FNAC
Solid, or blood/abn on FNA - core biopsy
MAnage breast cancer
Surgery - wide loop excision and RT, or mastectomy, and axillary clearance if sentinel node biopsy
Hormonal treatment - tamoxifen (ER+) or trastuzumab (HER+)
Screening for breast cancer
47-73yo
Microcalcificatiotn on mammogram = DCIS
What is anastrazole for
Peripheral aromatisation after menopause makes most of oestrogen, it inhibits this
Ovarian cancer RF
BRCA1
Lynch
Ovulation
Reduced by COCP
Histology of ovarian cancer
Epitheilal - serous (most common)/mucinous cystadenoma
Germ cell/stromal
2ww for ovarian cancer
Vague bloating
Then CA125 high
Then TVUS
Then refer
inv ovarian cancer
Ca125, CEA, CA19-9
If young, do atypicals (for germ cell) - HCG, LDH, AFP, oestradiol
TV US - CT TAP for staging - MRI pelvis
Ascetic tap for malignant cells on cytology
Manage ovarian caner
Staging laparotomy - TAHBSO, omentectomy, peritoneal washings, LN
Adjuvant chemo
Tumour marker survaillance
Complication of surgery for heterogenous ovarian cyst removal
Chemical peritonitis
Small RUQ breast lump manage
Adjuvant RT
Wide local excision
Nipple eczema involving nipple and spreading out - what to do and what suspecting?
2ww for punch biopsy
Suspect Paget’s disease
Risks of tamoxifen - 4
DVT
Post meno bleeding - endometrial cancer
Teratogenic
Hot flushes
Recognising death - 3
Progressive physical decline
Reduced oral intake/medication response
Rising EWS
End of life care points
Discuss with family Palliative care referral Anticipatory meds Comfort obs Stop non essential meds Fast tracking Opate prescribing - background (BD)/breakthrough (24h dose/6), syringe driver, patch
Pain medication in end of lfile
Pain - Morphine 2.5-5mg SC PRN max 60mg
Agitation - midazolam 2.5-5mg SC PRN max 60
NV/confusion - Haloperidol, levopromazine
Secretions - Hyoscine, glycopyrronium
Morphine conversion - SC and patch
SC = PO divided by 2
Patch lasts 3d, 30mg PO morphine = 12mcg/h fentanyl patch
Post-death process - 4
Verifying death
Death certificate - immediate cause, plus what led to it and contributing factors
Cremation form
Coroners referral
Post-death process - 4
Verifying death
Death certificate
Cremation form
Coroners referral
When to refer to coroner
<24h admission
Unnatural cause eg substance, accident
Linked to occupational
When to refer to coroner
<24h admission
Unnatural cause eg substance, accident, violence
Linked to occupational
What is on death certificate
- 1a (immediate cause eg pneumonia), plus 1b (what led to it eg COPD) and 2 (contributing factors eg HF)
Causes of hypercalcaemia in oncology - 2
Lytic bone mets
Myeloma
Osteoclasts activating factor or PTH like hormones from tumour
Red flags for GI
ALARM >55yo: Anorexia Loss of weight Anaemia Recent onset Melaena/haematemesis Swallowing difficulty
Red flag sx for back pain
TUNAFISH Trauma Unexplained weight loss Neuro sx Age >50yo Fever Ivdu Steroids Hx of cancer - prostate, renal, breast, lung, thyroid
Assess melanoma
Asymmetry Border - irregular Colour - non uniform Diameter >6mm Elevation
What is BPH and sx
Benign nodular or diffuse proliferation of musculofibrous and glandular layers of tissue in inner transitional zone of prostate, so early sx:
Nocturnal, frequency, terminal dribble, hesitancy, uti, stones, retention
Manage BPH
DRE, MSU, UE, USS for residual volume and hydronephrosis
Rule out cancer - PSA, TRUS USS +- biopsy
Conservative - alcohol, caffeine, bladder training
Medical
- a-blocker tamsulosin reduces smooth muscle tone. ADR hypotension, drowsy, ejaculatory failure
- 5a reductase inhibitor finasteride (reduces conversion of testosterone to dihydrotestosterone). ADR impotence, reduced libido, excreted in semen (use condom), takes a while to work
Surgery - TURP. ADR:
- clot, bleeding, haematospermia, infection
- TUR syndrome (absorption of wash out fluid = hyponatraemia and fits), cross match 2u first
- erectile dysfunction, incontinence, retrograde ejactulation
No driving or sex for 2w, haematuria for 2w, initial increase in frequency for 6w