What are the common genetic abnormalities in bladder cancer?
Superficial tumours = Chr9 deletions
Invasive tumours = p53 mutations + 14q/17q deletions
What are the risk factors for bladder cancer?
- Smoking
- Naphthylamines/benzidine in dye, rubber, leather industries
- Cyclophosphamide treatment (chemo for other Ca)
- Pelvic irradiation (cervical Ca)
- Chronic UTIs
- Schistosomiasis
Who usually gets bladder cancer?
Twice as common in men
50-70yos
How does bladder cancer present?
- Painless, macroscopic haematuria
- Increased urinary frequency
- Urgency
- Nocturia
- Recurrent UTIs
- Rarely pain due to clot retention
- Ureteral obstruction or extension to pelvis
Often no signs O/E
How is bladder cancer investigated initially?
Cystoscopy
Allows visualisation of tumour, biopsy or removal
How can bladder cancer be investigated?
Cystoscopy
USS, IVU - to assess upper and lower UTs as tumours can be multifocal
CT/MRI - staging
Urine cytology
What are the risk factors for breast cancer?
- Female
- Increasing age
- Prolonged exposure to oestrogen - nullparity, early menarche, late menopause, obesity
- FH
What is the lifetime risk of breast cancer for women in the UK?
1:9
Commonest cancer in women
How does breast cancer usually present?
- Painless breast lump or change in breast shape
- Nipple discharge or axillary lump
- Symptoms of malignancy: WL, bone pain, paraneoplastic syndromes
What are the signs of breast cancer O/E?
- Hard, irregular breast lump
- Peau d’orange, skin tethering, fixed to chest wall
- Skin ulceration, nipple inversion
- Axillary nodes - may be spread
- Paget’s disease of nipple: eczematous, ulcerated, discharging nipple (ductal carcinoma in situ infiltrating nipple)
How is breast cancer investigated?
TRIPLE ASSESSMENT
- Clinical examination
- Mammography >35, US<35
- Core biopsy (histo) / FNA (cyto/drainage)
When does breast cancer screening start?
Mammogram
50-71
Every 3 years
How is breast cancer staged?
CXR
Liver US
Isotope bone scan
CT (brain or thorax)
What are CNS tumours?
Primary tumours arising from any of the brain tissue types
What causes CNS tumours in children and in adults?
Children - embryonic errors in development
Adults - unknown
When are the peaks in incidence of CNS tumours?
Children
Elderly
How do CNS tumours present?
- Headache + vomiting - due to raised ICP
- Epilepsy
- Focal neuro deficits - dysphagia, hemiparesis, ataxia, visual field defects, cognitive impairment
- Personality change
What are the signs of CNS tumours O/E?
- Papilloedema/false localising signs - due to raised ICP
- Focal neuro deficits - dysphagia, hemiparesis, ataxia, visual field defects, cognitive impairment
How are CNS tumours investigated?
CT head - initial
MRI brain - higher sensitivity
What is cholangiocarcinoma?
Primary adenocarcinoma of the biliary tree
What causes cholangiocarcinoma?
Unknown
What is cholangiocarcinoma associated with?
UC
PSC
Parasitic infections of biliary tract
Who is cholangiocarcinoma more common in?
Men
Where is cholangiocarcinoma more common?
Developing world due to parasitic infections
How does cholangiocarcinoma present?
- Obstructive jaundice - yellow skin + sclera/pale stools/dark urine/pruritis
- Abdominal fullness or pain
- Symptoms of malignancy - WL, malaise
What are the signs of cholangiocarcinoma O/E?
- Jaundice
- Palpable gallbladder
- Epigastric or RUQ mass
- Hepatomegaly
What is Courvoisier’s law?
In the presence of jaundice, an enlarged GB is unlikely to be due to gallstones - carcinoma of pancreas or lower biliary tree is more likely
What bloods would you do for suspected cholangiocarcinoma?
FBC U+E LFT - raised bilirubin, alkphos, GGT Clotting Tumour markers - CA19-9 raised
What is the tumour marker for cholangiocarcinoma?
Ca19-9
How is cholangiocarcinoma investigated?
Bloods
Endoscopy - ERCP
US - biliary duct dilatation
CT/MRI/MRCP/Bone scan - stage tumour and visualise regional spread
Arteriogram
What is colorectal carcinoma?
Malignant adenocarcinoma of the large bowel
What causes colorectal carcinoma?
- Environmental and genetic factors
- Epithelial dysplasia > adenoma > carcinoma
- Accumulation of genetic changes in oncogenes (APC, K-ras) and TSGs (p53, DCC)
What are the risk factors for colorectal carcinoma?
Western diet: High intake of red meat Alcohol Fat Sugar Reduced veg and fibre intake
Presence of colorectal polyps Previous CRC FH IBD, esp longstanding UC FAP
What is the 2nd most common cause of cancer death in the West?
Colorectal carcinoma
What is the average age of diagnosis of CRC?
60-65
Who is rectal carcinoma more common in?
Men
Who is colon carcinoma more common in?
Women
How do L-sided colon and rectal cancer present?
Change in bowel habit
Rectal bleeding
Blood/mucus mixed in with stools
Tenesmus
How does R-sided colon cancer present?
Later presentation Symptoms of anaemia Weight loss Non-specific malaise (Rare) lower abdominal pain
What do up to 20% of CRC tumours present with?
Emergency
Pain and distension due to LBO, haemorrhage or peritonitis due to perforation
What are the signs of CRC O/E?
R-sided: anaemia may be only sign Abdo mass w metastatic disease Hepatomegaly Shifting dullness of ascites Low lying rectal tumours may be palpable
How is CRC investigated?
- BLOODS - FBC (anaemia)/LFT/tumour markers (CEA)
- STOOL - occult or frank blood in stool - screening test
- Endoscopy - sigmoidoscopy/colonoscopy
- Barium contrast studies - apple core stricture
- Contrast CT scan - staging
What does CRC look like on barium enema?
Apple core stricture
How is CRC screened for?
Faecal occult blood
What is the tumour marker for CRC?
CEA
What causes gastric cancer?
Unknown
What is gastric cancer associated with?
Diet high in smoked and processed foods Nitrosamines Smoking Alcohol H pylori infection Atrophic gastritis Blood group A Pernicious anaemia Partial gastrectomy Gastric polyps
Where has the highest incidence of gastric cancer?
Asia esp Japan
Who is gastric cancer more common in?
Men 2x
Over 50
How does gastric cancer present?
Asymptomatic at first Satiety + epigastric discomfort WL, anorexia, n+v Haematemesis, melaena, anaemia Dysphagia (tumours of cardia) Ascites, jaundice (liver mets)
What are the signs of gastric cancer O/E?
Epigastric mass Abdo tenderness Ascites Signs of anaemia Virchow's node - L supraclavicular fossa Sister Mary Joseph's node - umbilicus
How is gastric cancer investigated?
- Bloods - FBC (anaemia), LFT
- CT/MRI - staging
- Bone scan - staging
- Upper GI endoscopy
- Endoscopic USS
What is hepatocellular carcinoma?
Primary malignancy of the liver parenchyma
What are the risk factors for HCC?
Chronic liver damage - ALD, hep C, AI disease
Metabolic disease - haemochromatosis
Aflatoxins - from cereals contaminated w fungi or biological weapons
Where is HCC incidence increased?
Where hep B and C are endemic
South Med
Far East
How does HCC present?
Malaise, WL, loss of appetite
High alcohol intake
Hep B or C, aflatoxins
Fullness in abdo and jaundice
What are the signs of HCC O/E?
Cachexia Lymphadenopathy Hepatomegaly - nodular, tender Jaundice Ascites Liver bruit
How is HCC investigated?
- Bloods - FBC, ESR, LFT, clotting, alpha fetoprotein, hepatitis serology
- Imaging - US, CT, MRI (last 2 for staging)
- Angiography
What type of lung cancer is most common?
Non-small cell (80%)
What causes lung cancer?
Smoking
Asbestos exposure
Both cause genetic alterations –> neoplastic transformation
Also occupational exposures - polycyclic hydrocarbons, nickel, chromium, cadmium, radon, atmospheric pollution
What is the most common fatal malignancy in the West?
Lung cancer
Who is lung cancer more common in?
3x men
How does lung cancer present?
Asymptomatic
If primary: cough, haemptysis, chest pain, recurrent pneumonia
Pancoast tumour: shoulder/arm pain/Horner’s
Left recurrent laryngeal nerve invasion: hoarseness, bovine cough
Oesophagus invasion: dysphagia
Heart invasion: palpitations, arrhythmia
Weight loss, fatigue, bone pain, fractures, fits
What are the signs of lung cancer O/E?
May be no signs Fixed monophonic wheeze Lobar collapse/pleural effusion Virchow's node Hepatomegaly
How is lung cancer diagnosed?
CXR Sputum cytology Bronchoscopy w brushing or biopsy CT/US guided percutaneous biopsy LN biopsy
How is lung cancer staged?
CT chest
CT/MRI head and abdo
Bone scan, PET
What bloods are done for lung cancer?
FBC UE Ca - hyperCa common Alkphos - increased in bone mets LFT
What is mesothelioma?
Malignancy involving the mesothelial cells that normally line body cavities, including the pleura, peritoneum, pericardium, testis
What causes is the main cause of malignant pleural mesothelioma?
Asbestos
Who is mesothelioma more common in?
Men 3x
When does mesothelioma incidence peak?
35-45 years after asbestos exposure
How does mesothelioma present?
Dyspnoea Non-pleuritic chest pain Chest discomfort FL-WS Can be asymp w pleural effusion
What are the signs of mesothelioma O/E?
Pleural effusion
How is mesothelioma investigated?
Bedside - obs, BP, lung function tests
Bloods - FBC, UE, LFT
Imaging - CXR, CT, bronchoscopy
Tissue biopsy
Cytology - aspirates, washings
What is neutropenic sepsis?
Fever > 38C or features of sepsis in a patient with a neutrophil count < 0.5x10^9/L
Medical emergency - must be treated within 1h of detection
What predisposes to neutropenic sepsis?
Congenital - rare:
Congenital neutropenia
Chediak-Higashi syndrome
Acquired:
Malignancy - haematological, tumour infiltration
Infections - HIV, TB, malaria, typhoid
Drugs - cytotoxics
Aplastic anaemia
Folate and B12 deficiency
Hypersplenism (increased neutrophil turnover)
What causes neutropenic sepsis?
Virus - herpes simplex
Bacteria - E Coli, Klebsiella, Pseudomonas aeruginosa, Staph epidermis, Staph aureus, C diff - MOST COMMON
Fungi - candida, aspergillus
How does neutropenic sepsis present?
Fever or hypothermia SOB Confusion Palpitations Decreased UO
What are the signs of neutropenic sepsis O/E?
Pyrexia or hypothermia RR > 20 SBP < 90 Decreased cognition w acute confusion Tachycardia Oliguria < 1mL/kg/hr
How is neutropenic sepsis investigated?
Bloods - VBG, FBC, CRP, UE, LFT, bone profile, clotting
Cultures - blood, line, sputum, urinanalysis, stool, C diff toxin, viral PCR, wound swabs, serology for HIV, HCV, HBV
CXR
LP - meningitis, encephalitis
Echo - IE
What are the 2 major histological types of oesophageal cancer?
Squamous cell carcinoma
Adenocarcinoma
What are the risk factors for squamous cell oesophageal cancer?
Alcohol Smoking Paterson-Kelly syndrome Tylosis Achalasia Scleroderma Coeliac disaese Vitamin deficiencies Nitrosamines
What are the risk factors for adenocarcinoma of the oesophagus?
GORD
Barrett’s oesophagus
Who is oesophageal cancer more common in?
3x men
How does oesophageal cancer present?
Often asymptomatic Progressive dysphagia, initially worse for solids Regurgitation Cough or choking on food Hoarseness Odynophagia WL Fatigue - IDA
What are the signs of oesophageal cancer O/E?
Usually none
Mets - supraclavicular lymphadenopathy, hepatomegaly, hoarseness (RLN involvement)
How is oesophageal cancer investigated?
- Endoscopy - brushings, biopsy, US for staging
- Imaging - barium swallow, CXR
- Staging - CT chest and abdomen
What causes pancreatic cancer?
Unknown
What percentage of pancreatic cancers are hereditary?
5-10%
MEN, HNPCC, Gardner, VHL syndrome
What are the risk factors for pancreatic cancer?
Increasing age Smoking DM Chronic pancreatitis Low fruit and veg intake
Who is pancreatic cancer most common in?
Old men
How does pancreatic cancer usually present?
Non-specific symptoms Anorexia Malaise Nausea Epigastric pain Later - WL, DM, jaundice
What are the signs of pancreatic cancer O/E?
Weight loss
Epigastric tenderness or mass
Jaundice + palpable gallbladder
Hepatomegaly (mets)
How is pancreatic cancer investigated?
- Bloods: CA19-9 and CEA elevated / high bilirubin / high AlkPhos / deranged clotting (liver mets)
- Imaging - US/CT+biopsy/MRI/MRCP/ERCP
- Staging laparoscopy
What is the biggest risk factor for prostate cancer?
Age
What are the risk factors for prostate cancer?
INCREASING AGE Afro-Caribbean - younger, more aggressive disease FH - BRCA2, Chr1 gene Diet - high fat, meat, alcohol Occupational exposure to cadmium
Where is prostate cancer most common?
North America
Europe
Low in Far East
What is the 2nd most common cause of male cancer deaths?
Prostate cancer
How does prostate cancer present?
Asymptomatic
LUTS - frequency, hesitancy, poor stream, nocturia, terminal dribble
Mets - bone pain, SC compression, malaise, anorexia, WL
PNP syndromes - hypercalcaemia - polydipsia + polyuria
What does a malignant prostate feel like?
Asymmetrical hard nodular prostate gland
Loss of midline sulcus
How is prostate cancer investigated?
DRE Bloods - FBC, UE, PSA, acid phosphatase, LFT, bone profile CT/MRI TRUS and needle biopsy - Gleason score Isotope bone scan
Which inherited conditions is renal cell carcinoma associated with?
VHL disease
Tuberous sclerosis
Polycystic kidneys
Familial RCC
What are the risk factors for renal cell carcinoma?
Smoking Chronic dialysis VHL disease Tuberous sclerosis Polycystic kidneys Familial RCC
What kind of cancer are the majority of renal cell carcinomas?
Renal clear cell carcinoma - 80%
10% papillary
10% transitional cell - renal pelvis
Who usually presents with renal cell carcinoma?
Men
40-60yo
How does renal cell carcinoma present?
LATE - asymptomatic in 90%
Triad = haematuria + flank pain + abdominal mass (only 10% patients)
Systemic signs - WL, malaise
PNP syndromes - pyrexia of unknown origin, hypercalcaemia, polycythaemia
What are the signs of renal cell carcinoma O/E?
Palpable renal mass
HTN
Anaemia
How is renal cell carcinoma investigated?
Dipstick - haematuria
Urine cytology
Bloods - FBC, UE, Ca, LFT, ESR (raised in 75%)
What are the risk factors for testicular cancer?
Testicular maldescent or ectopic testis - 40x risk
Contralateral testicular tumour
Atrophic testis
What is the most common malignancy in 18-35yo men?
Testicular cancer
How does testicular cancer present?
Swelling/discomfort of testes
Backache - due to para-aortic LN enlargement
Resp symptoms - SOB, haemoptysis from lung mets
What are the signs of testicular cancer O/E?
Painless, hard testicular mass
Lymphadenopathy - supraclavicular, para-aortic
Signs of pleural effusion
Gynaecomastia - tumour HCG production
How is testicular cancer investigated?
BLOODS - FBC, UE, FLT, AFP, beta-HCG, LDH
Urine pregnancy test - +ve if tumour produces beta-HCG
CXR - lung mets/effusion
US
CT abdo/thorax/brain - mets
What are the tumour markers for testicular cancer?
Alpha-fetoprotein
Beta-HCG
LDH
What is tumour lysis syndrome?
A constellation of metabolic disturbances that may follow the initiation of cancer treatment
How does tumour lysis syndrome usually occur in?
Patients with bulky, rapidly proliferating, treatment-responsive tumours
Most often = acute leukaemia with high WBC
What 2 things is tumour lysis syndrome associated with?
- Elevated pre-treatment LDH
2. Renal insufficiency prior to therapy
How does tumour lysis syndrome present?
Within 72h of admin of cytotoxic treatment
Abdo pain/distension
Urinary - dysuria, oliguria, flank pain, haematuria
Hypocalcaemia - anorexia, vomiting, cramps, seizures, spasms, altered mental status, tetany
Hyperkalaemia - weakness, paralysis
Other - lethargy, oedema, CHF, cardiac dysrhythmias, syncope, sudden death
What are the signs of tumour lysis syndrome O/E?
Hyperkalaemia - paraesthesia, weakness, cardiac arrhythmias
Hypocalcaemia - paraesthesia, tetany, Chvostek, Trousseau, anxiety, carpal and pedal spasms, bronchospasm, seizures, cardiac arrest
Calcium phosphate deposition - pruritis, gangrene, iritis, arthritis
Uraemia - fatigue, weakness, malaise, n+v, anorexia, metallic taste, hiccups, restless legs
How is tumour lysis syndrome investigated?
Urine dipstick - ALKALI Urine output - assess hydration Imaging - CXR/CT abdo ECG Bloods - FBC/UE/LDH
What is the first life-threatening abnormality in tumour lysis syndrome? Therefore what must you do?
Hyperkalaemia
U+E bloods