Transcript Bladder Cancer - North West Urology Registrar Group

Dickie Robinson
Victoria Hopkinson
M W Lau
Outline / Objectives
Dickie
Victoria
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• Haematospermia
• Cytology and
alternatives to cytology
• Haematuria and key
papers
Epidemiology
Diagnosis
Pathology
Staging
Case 1
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79 female – retired teacher
WHO performance status 2
Presented via A&E with haematuria
Irrigation for 2-3 days, no intervention
required
• Flexible cystoscopy as an outpatient 1 week
later
Case 1 cont..
Solitary tmuour in the
trigone.
Nurse endoscopic, new in the job, asks
should I arrange any scans?
Upper tract imaging in bladder cancer
• In this case also a judgment call as 79 years old and WHO 2.
Palou – J Urol 2005 174(3):859-861
• Retrospective study of 1,529 primary NMIBC
patients - examination of the upper urinary
tract with excretory urography.
• 28 patients (1.8%) had synchronous UUTT,
17.9% were multiple and 46% were invasive.
• 7.5% of trigone tumours were associated with
UUTT, but this only corresponded to 41% of
the UUTTs first diagnosed (ie. if only scan
trigonal tumours will miss 59% of UUTT)
Factor
RR
95% CI
p Value
Grade
1.7
(0.2-14.8)
ns
CIS
1.16
(0.3-3.7)
ns
T stage
2.29
(0.7-7.4)
ns
Trigone tumor
5.8
(2.18-15.9)
0.0005
Bladder tumor size
0.5
(0.1-1.7)
ns
Multiplicity
0.48
(0.1-1.3)
ns
EAU guidelines 2013 on NMIBC –simply references the above paper.
Case 1 cont….
Wednesday morning, patient in surgical
admission lounge having been listed for a
TURBT.
1. Explain the consent process for TURBT
2. Key steps of a TURBT
Consent for TURBT
Should commence in clinic / prior to day of surgery and be backed up with written information / website etc..
Common (greater than 1 in 10)
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Mild burning or bleeding on passing urine for short period after operation
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Temporary insertion of a catheter for bladder irrigation
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Need for additional treatments to bladder in attempt to prevent recurrence of tumours including drugs instilled
into the bladder
Occasional (between 1 in 10 and 1 in 50)
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Infection of bladder requiring antibiotics
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No guarantee of cancer cure by this operation alone
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Recurrence of bladder tumour and/or incomplete removal
Rare (less than 1 in 50)
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Delayed bleeding requiring removal of clots or further surgery
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Damage to drainage tubes from kidney (ureters) requiring additional therapy
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Injury to the urethra causing delayed scar formation
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Perforation of the bladder requiring a temporary urinary catheter or open surgical repair
Hospital-acquired infection
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Colonisation with MRSA (0.9% - 1 in 110)
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Clostridium difficile bowel infection (0.01% - 1 in 10,000)
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MRSA bloodstream infection (0.02% - 1 in 5000)
BAUS – Bladder Tumour Resection – Procedure Specific Information for Patients
http://www.baus.org.uk/Resources/BAUS/Documents/PDF%20Documents/Patient%20information/TURBT.pdf
Steps in TURBT (modified from EAU guidelines on NMIBC 2013)
The goal of the TURBT is to make the correct diagnosis and in Ta-T1 tumours to
remove all visible lesions. It is crucial in the diagnosis and treatment of BC.
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Theatre team briefing, WHO checks, VTE prophylaxis, warming & antibiotics.
EUA
Visualisation of the of the urethra, entire bladder and U.O.’s. Bladder capacity.
Small tumours (< 1 cm) can be resected en bloc.
Larger tumours should be resected separately in fractions, including the exophytic
part of the tumour, the underlying bladder wall with the detrusor muscle, and the
edges of the resection area.
Abnormal areas of urothelium (?CIS) - cold-cup biopsies or biopsies with a
resection loop.
Random (mapping) biopsies, should be performed in patients with positive urinary
cytology and absence of visible bladder tumour. (Recommended biopsies: trigone,
bladder dome, and from the right, left, anterior and posterior bladder walls).
Biopsy prostatic urerthra in cases of suspected CIS or bladder neck tumours.
In patients with palpable mass before TURB, EUA should be repeated after
resection.
Requirement for catheter +/- irrigation dependent upon findings.
Document findings (EUA, capacity, size, multiplicity and location of tumours,
residual tumour at end of procedure).
Mitomycin-C for Ta-T1 tumours.
Case 1 cont..
• 2 weeks later, asleep in MDT, rumbled and
asked what the histology represents:
Low grade papillay TCC.
What is the difference
between the WHO
1973 and 2004
classification of
urothelial bladder
cancer?
WHO 1973 vs. 2004
• Current U.K. guidelines recommend pathologists
report using both systems to allow prospective
audit of outcomes. It was hoped that 2004
system would be more reproducible.
• PUNLMP’s are not cancers (Harnden – BJUI 2006
99:723-30)
• Conflicting evidence regarding comparisons of
the prognostic power of each
system.(MacLennan – E Urol 2007 51(4):889-897
and Chen – PLosOne 2012 7(10):e471499)
TNM classification
75-80% NMIBC at presentation
T - Primary tumour
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TX Primary tumour cannot be assessed T0 No evidence of primary tumour
Ta Non-invasive papillary carcinoma Tis Carcinoma in situ: ‘flat tumour’
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T1 Tumour invades subepithelial connective tissue
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T2 Tumour invades muscle
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T3 Tumour invades perivesical tissue:
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T2a Tumour invades superficial muscle (inner half)
T2b Tumour invades deep muscle (outer half)
T3a Microscopically
T3b Macroscopically (extravesical mass)
T4 Tumour invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall
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T4a Tumour invades prostate, uterus or vagina
T4b Tumour invades pelvic wall or abdominal wall
N - Lymph nodes
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NX Regional lymph nodes cannot be assessed
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N0 No regional lymph node metastasis
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N1 Metastasis in a single lymph node in the true pelvis (hypogastric, obturator, external iliac, or presacral)
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N2 Metastasis in multiple lymph nodes in the true pelvis (hypogastric, obturator, external iliac, or presacral)
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N3 Metastasis in common iliac lymph node(s)
M - Distant metastasis
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MX Distant metastasis cannot be assessed
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M0 No distant metastasis
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M1 Distant metastasis
Molecular biological grading
• Placing tumours into categories according to their molecular
phenotype will become the standard in the future, H&E grading is
likely to become obsolete in prognostication.
• Occurring in breast cancer.
• Unlikely to be based upon ‘old fashioned’ ideas regarding
biomarkers such as expression of p53 and cell cycle regulators etc..
• It will almost certainly take the form of multiplexed sequencing.
Robinson 2013
Urothelial carcinoma tumour groupings based upon hierarchical
clustering of gene expression.
Sjödahl G et al. Clin Cancer Res 2012;18:3377-3386
©2012 by American Association for Cancer Research
Molecular pathways of development
M Knowles 2006.
Case 2
• 69 male – retired army sergeant.
• Storage LUTS, pelvic pain and visible haematuria.
• Smoker, IHD, type 2 diabetes, walks with 2 sticks.
What next?
• Had flexi cystoscopy shown solid tumour.
• EUA mobile bladder mass.
• TURBT – residual tumour.
Case 2 H&E sections of tumour.
Pearls of keratin in ‘classical’
description of SCC
IHC staining of SCC bladder
cancer tissue for cytokeratin.
Entire tumour filled with whorls
of keratin.
Histological types of bladder cancer
• Urothelial / TCC – 90%
• SCC – 5%
– Higher incidence in areas endemic for
schistosomiasis.
• Adenocarcinoma – 2%
• Other sub-types – 3%
WHO 2004 – Histological types of tumours of the urinary bladder
44 different sub-types listed!
Benign
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Urothelial papilloma
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Inverted papilloma
Papillary urothelial neoplasia of low malignant potential
Malignant papillary
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Papillary carcinoma
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low grade
high grade
with squamous
with glandular differentiation
Malignant non-papillary
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Flat carcinoma in situ
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Invasive carcinoma
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Variants of invasive carcinoma
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Nested pattern
Small tubular pattern
Microcystic pattern
Inverted pattern
Squamous differentiation
Glandular differentiation
Micropapillary
Sarcomatoid carcinoma
Clear cell urothelial carcinoma
Plasmocytoid
With syncitiotrophoblasts
With unusual stromal reactions
Pseudosarcomatous stroma
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Stromal osseous or cartilaginous metaplasia
Osteoclast-type giant cells
With prominent lymphoid infiltrate
Squamous cell carcinoma
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Usual type
Variant
Verrucous
Basaloid
With sarcomatoid features
Adenocarcinoma (from bladder mucosa, urachal, with extrophy)
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Usual intestinal type
Mucinous (including colloid)
Signet-ring cell
Clear cell
Hepatoid
Mixture of above patterns
Adenocarcinoma NOS
Tumours of mixed cell types
Undifferentiated carcinomasa
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Small cell carcinoma
Large cell neuroendocrine carcinoma
Lymphoepithelioma-like carcinoma
Giant cell carcinoma
Undifferentiated carcinoma NOS
Metastatic carcinoma
Variants
TCC variants (80% all TCC have mixed
differentiation)
Other non-TCC variants
• Nested
• Small cell
– Can be confused with Vonn Brunn
nests
– M:F = 6:1
– Neo-adjuvant chemo ineffective
– V poor prognosis (30% 3 year
survival)
• Micropapillary
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0.7-2.2%
M:F = 10:1
BCG ineffective
Neo-adjuvant chemo ineffective
Adverse phenotype
– Men >70 yrs
– Consider metastatic
– Chemo-radiothepy treatment of
choice
– V poor prognosis (20% 5 year
survival)
• Sarcoma
– M:F = 2:1
– Previous chemo or XRT other
tumours
– Normal overlying urothelium
– Not related to smoking
– Treatment with cystectomy
SCC
Risk Factors
• Chronic urinary tract
infection
• Schistosomiasis
– Increased urothelial
proliferation
– N-butyl-N-(4hydroxybutyl)nitrosamine is
generated in very high levels
in the urine.
– Chronic infection with S
hematobium converts nitrates
to nitrites and subsequently
to nitrosamines.
Myths
• SCC in Egypt
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only 27% of MIBC
was 80% in 1980
improved eradication
increased smoking
similar pattern elsewhere
• Incidence in SCI is only <1%
– latency 17 yrs
– Previously quoted at 10%
Global distribution schistosomiasis
Scistosomiasis
80-120
days
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5 different types classified into:
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schistosmulum
Intestinal (4)
Urogenital (1)
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Terminally spiked
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Treatment
200-500
eggs/day
20%
Bulinus genus
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Praziquantel two oral doses of 40 mg/kg in 1
day
Increases permeability of the schistoscomes
membranes to calcium ions
Interferes with adenosine uptake and thus
purine synthesis
SE related to immune response . 90%
stomach cramps, diarrhoea, malaise
Epidemiology
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U.K. statistics
– 2ndmost frequently occurring malignancy of the urinary tract, after prostate cancer and 7th
commonest cancer overall.
– 4th commonest cancer in men
– 11th commonest in women
– 10754 new cases diagnosed in 2009
– 4907 deaths in 2009
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The highest rates occur in developed countries with age standardised incidence
rates (ASR) of 19.5 and 4.2 per 100 000 for men and women. (wide variation in the
reporting and registration of bladder cancer, particularly with respect to the variable inclusion of CIS and stage Ta
transitional cell carcinoma (TCC) in registries).
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In the U.K. progressive decline since a peak in the early 1990’s
– U.K ASR falling from 18.4 per 100 000 in 1993 to 11.5 in 2008
– this decline is far more pronounced in men than women.
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Incidence of bladder cancer is predicted to rise in less developed areas of the
world as smoking rates increase in these countries.
– Tobacco use has increased by 16.1, 8.7 and 6.5% in Africa / Middle East, Eastern Europe /
former Soviet Union and Asia / Australia between 1998 and 2008 respectively.
Average Number of New Cases Per Year and Age-Specific Incidence Rates per 100,000 Population, UK
Please include the citation provided in our Frequently Asked Questions when reproducing this chart: http://info.cancerresearchuk.org/cancerstats/faqs/#How
Prepared by Cancer Research UK - original data sources are available from http://www.cancerresearchuk.org/cancer-info/cancerstats/
European Age-Standardised Incidence Rates per 100,000 Population, by Sex, Great Britain
Please include the ciation provided in our Frequently Asked Quesitons when reproducing this chart: http://info.cancerresearchuk.org/cancerstats/faqs/#How
Prepared by Cancer Research UK
Original data sources:
1. Office for National Statistics. Cancer Statistics: Registrations Series MB1. http://www.statistics.gov.uk/statbase/Product.asp?vlnk=8843.
2. Welsh Cancer Intelligence and Surveillance Unit. http://www.wcisu.wales.nhs.uk.
3. Information Services Division Scotland. Cancer Information Programme. www.isdscotland.org/cancer.
European and Global Age-Standardised Incidence Rates per 100,000 Population 2008
Percentage of population smoking or diagnosed with
lung cancer
Risk factors for bladder cancer
Effect
Age
Increased risk with older age
Gender
Male 3 x  incidence
Smoking
2 – 6 x  incidence (risk related to exposure)
Occupation
Risk varies with occupation
Family history
2 x risk with affected 1relative
Genetic
NAT1 and GSMT1 null genotypes associated with increased risk
Chronic UTI
Increased risk
Chemotherapy
Cycophosphamide only (related to duration and intensity of exposure)
Radiation exposure
Latency period 15-30 yrs
Ethnic origin
Black lower risk but worse prognosis
Coffee
Increased risk (smoking confounding)
Acetaminophen
Conflicting evidence
Fresh fruit & veg
Protective effect (stating the obvious!)
Alcohol
No effect
There is no substantially increased risk of bladder
cancer for most occupations that have been studied
Occupation
RR
Agent responsible
miners
1.31
agent unknown
bus drivers
1.29
diesel exhaust
rubber workers
1.29
numerous agents*
mechanics
1.27
mineral oils
leather workers
1.27
tanning agents and dyes
blacksmiths
1.27
metal fumes
machine setters
1.24
mineral oils
hairdressers
1.23
dyes
*historically responsible 2- napthylamine – but banned since 1950’s
Agricultural workers have the lowest risk of all occupations.
Ruelen – Scan J Urol and Neph 2011 42(s218):64-78
NAT2 and GSMT1
• N-acetyltransferase 2 (NAT2) is an enzyme involved in the
metabolism of aromatic amines. The status of an individual
is designated as either a ‘slow or fast acetylator’ and has
been implicated in bladder cancer risk. The slow acetylator
genotype is associated with a 40% increased risk of bladder
cancer.
• Glutathione S-transferase 1 (GSMT1) status, involved in the
metabolism of polycyclic hydrocarbons and detoxification
of reactive oxygen species, is also a significant risk factor
with the null genotype conferring a 50% increased risk of
bladder cancer, although this association is only strong in
non smokers.
Case 3
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53 year male barber.
No previous history.
60 pack yr smoking history.
2 months history of storage LUTS.
2+ blood in urine.
Examination normal.
What would you do next?
TURBT – solitary tumour. No visible residual tumour end of resection.
What does this histology represent?
G3pT1 TCC – scant deep muscle in specimen.
What else is required ?
Re-resection
• Residual tumour following resection of T1 tumours has been observed in
33-53% of patients.
• Tumour is often under-staged by initial resection.
• Probability that T1 under-staged and is ≥T2 is 4-25%.
• A second TUR should be considered when:
– the initial resection is incomplete
– when the pathologist has reported that the specimen contains no muscle
tissue
– high-grade tumour
– T1 tumour
• 2-6 weeks after initial TUR.
EAU guidelines on NMIBC 2013
Imaging in MIBC
Imaging parameters required for staging MIBC
are:
1. the extent of local tumour invasion
2. tumour spread to lymph nodes
3. the upper urinary tract and other distant
organs.
Re- resection 6 weeks later – no residual tumour.
Staging in MIBC
Current gold standard methodology is poor.
Upstaging occurs at the time of cystectomy in around 40% of
all cases and up to 60% in T2 tumours.
• EUA – very poor, although if fixed then significant finding.
• TURBT – under stages 20-80% compared to cystectomy
pathology.
• Imaging
Turker – BJUI 2012 110:804-811
Local staging of bladder cancer
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Both CT and MRI can be used.
Timing in relation to TURBT is important.
Unable distinguish T2 from T3a.
Evidence referenced in EAU guidelines comparing MRI and CT is almost 20
years old!! Technology as moved on a little.
Multi-detector CT scanning
– Overall 50-90% accuracy for local
staging
– sensitivity differentiate ≥T3 from
≤T2 up to 90%
– specificity differentiate ≥T3 from
≤T2 60-70%
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Recent study looking at MRI alone:
– overall 63% accuracy for local
staging.
– sensitivity differentiate ≥T3 from
≤T2 90.5%
– specificity differentiate ≥T3 from
≤T2 60%
Rajesh – Clin Radiology 2011 66(12):1140-5
RCR – Recommendations on Cross-Sectional
Imaging in Cancer Management 2006
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MRI is superior to CT for staging bladder cancer, due to its ability to
demonstrate muscle wall invasion or penetration.
• MRI is the imaging modality of choice for staging patients considered
suitable for radical treatment, that is cystectomy or radical radiotherapy.
• In those patients who are not suitable for radical treatment or where
there is clinical suspicion of locally advanced or metastatic disease, CT of
the abdomen and pelvis is suitable of staging purposes.
Again this guidance is very much out of date.
Nodal and distant staging
• Neither CT or MRI is able to detect the presence of malignant cells
in normal or minimally enlarged nodes.
• Sensitivity and specificity of both modalities ranges from 50-90%
with an inverse correlation.
• Short axis diameter 8mm pelvic and 10mm abdominal are
significant (EAU guidelines 2013 – open to debate).
• Advantage of CT – shorter image acquisition, cheaper, allows
evaluation of upper tracts and staging for distant metastases.
EAU guidelines 2013 - In patients with confirmed muscle-invasive bladder
cancer, CT of the chest, abdomen and pelvis is the optimal form of staging,
including excretory-phase CT urography for complete examination of the upper
urinary tracts.
FDP PET CT
(18Flurodeoxyglucose positron emission CT)
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Evolving evidence of it’s role in staging.
Trial of 96 patients.
Underwent standard CT and FDP PET CT.
Upstaging in 19.8% & downstage 2.1%.
Caused a change in management in 13.5%.
Switch from curative to palliative intent in 8.5%.
Detection of second malignancies that changed
management in 4.6%.
Mertens – BJUI 2013 112:729-734
Royal College Radiologist Guideline: Evidence-based indications for the use
of PET-CT in the United Kingdom 2012
Does not even mention bladder cancer – let alone give an opinion on its use.
Case 4
• 57 year old – works for HMRC, currently
investigating spurious expenses claims by Mr.
Dukic
• Previous prostatitis.
• On tamsulosin.
• Otherwise well.
• Deterioration in his LUTS.
• Non-visible haematuria in primary care.
Case 4 cont..
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Small prostate
PSA 0.84
MSU – no growth
Flexible cystoscopy normal
USS – multiple renal cysts
KUB AXR – normal
Cytology – suspicious for malignancy
What next?
• CTU – poor opacification of the right ureter, cannot
exclude ureteric lesion.
Case 4 cont..
• GA cystoscopy – normal, Bx’s taken.
• Bilateral URS – normal.
• Selective ureteric urine sampling –
samples are processed for MC&S
not cytology.
What now?
Secretary arranges repeat cytology prior to returning to clinic while you're on
leave.
Comes back to clinic – cytology highly suspicious.
Biopsies from bladder wall – normal urothelium.
What now?
Reads the daily mail – reading about a chap in Baisingstoke who puts this dye in
peoples bladders when he does cystoscopies.
Rink – E Urol 2013 64:624-638
Case 4 biopsy results
CIS
How does fluorescence cystoscopy / photodynamic
diagnosis (PDD) work) and what are the drawbacks?
• Photoactive porphyrins [5-ALA, HAL (esterised ALA for better
uptake), Hypericil] instilled into bladder prior to cystoscopy.
• Accumulate preferentially in neoplastic tissue.
• Under blue light (375-440nm) they emit red fluorescence.
• Disadvantages
– Cost of equipment and HAL (particularly in the NHS as the concept of
spending money to save money in the long term does not exist!!)
– Time: catheterisation and administration of HAL required prior
to cystoscopy.
– False positive , particularly at re-resection.
PDD
Details
5-ALA 5-aminolevulinic acid
Pre-treat for 3 hrs
HAL (Hexvix®) Hexaminolevulinate
Pre-treat 1 hr
Hexyl Aminolevulinate–Guided Fluorescence Cystoscopy in the Diagnosis and Follow-up of
Patients with Non–Muscle-invasive Bladder Cancer: A Critical Review of the Current
Literature. E Urol 2013 64:624-638
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Included reports used 5-ALA (in 26 studies), HAL (15 studies), or both (three studies)
PDD increased the detection of:
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papillary tumours by 7–29%
CIS by 25–30%
Reduced the rate of residual tumours TURBT by an average of 20% compared to WLC
alone.
Superior recurrence-free survival (RFS) rates. Recurrence-free rates at 12 and 24
months were 10.9–27% and 13–24% higher with PDD than WLC.
RFS intervals increased by 6-9 months with PDD, compared to WLC.
PDD did not appear to reduce disease progression.
Although cost effectiveness has been demonstrated for 5-ALA, it has not been studied
for HAL.
EAU guidelines 2013: Photodynamic diagnosis is most useful for detection of CIS, and
therefore it should be restricted to those patients who are suspected of harbouring a
high-grade tumour, e.g. for biopsy guidance in patients with positive cytology or with a
history of high-grade tumour (published prior to review above).
How does narrow band imaging work?
• The basis of this optical technique
is represented by white light
being filtered into two discrete
wavelengths: blue (415 nm) and
green (540 nm).
• Easily switch between white light
and NBI.
• These light bands are strongly
absorbed by hemoglobin and only
penetrate the tissue surface,
therefore, the vascular structures
appear dark brown (capillary
vessels) and green (veins).
• Does not require precatheterisation and instillation.
CIS
Narrow band imaging diagnosis of bladder cancer: systematic review and
meta-analysis
Zheng - BJUI 2012 110:680-687
Eight studies including 1022 patient cystoscopies.
NBI
WLI
Sensitivity overall
0.943
0.848
Specificity overall
0.847
0.870
AUC overall
0.978
0.8944
Sensitivity detecting CIS
0.927
Specificity detecting CIS
0.768
AUC detecting CIS
0.939
NBI is an effective method for the identification of abnormal lesions including
carcinoma in situ and can provide higher diagnostic precision of bladder
cancer than WLI.
Confocal LASER microendoscopy.
• Subsurface imaging of tissue microarchitecture and cellular features.
• Optical sectioning of the tissue micron-scale resolution is achieved using a
488 nm laser as the light source and fluorescein.
• Differentiation between benign and neoplastic tumours and delineation of
tumour boundaries.
Optical Coherence Tomography
• OCTutilises near infrared light to generate
an image at micrometer scale.
• Able to distinguish normal from neoplastic
tissue.
• Able to assess depth of invasion and
tumour margin.
Normal Urothelium
Flat mucosa lined by less than
approx 7 layers of urothelial
cells
Covered by an umbrella cell
layer.
Pathology
Papillary Hyperplasia
Characterized by slight
“tenting”, undulating, or an
elevated configuration of the
urothelium of varying
thickness, lacking nuclear
atypia.
Papillary urothelial neoplasm of low malignant potential PUNLMP or G1
PUNLMP/G1 have an orderly
arrangement of cells within
papillae with minimal
architectural abnormalities
and minimal nuclear atypia.
The urothelium is much
thicker than in papillomas
and/or the nuclei are
significantly enlarged and
somewhat hyperchromatic.
Mitotic figures are infrequent
Recurrence rate: 27-47%,
Grade Progression rate: 11%
Stage Progression rate: 0-4%
Urothelial Papilloma /G1
Discrete papillary growth with
a central fibrovascular core
lined by urothelium of normal
thickness and cytology.
In contrast to papillary
hyperplasia, discrete papillary
fronds are identified.
Relapse rate: 0-8%
Grade progression: 2%
Stage progression: 0%
Low grade papillary urothelial carcinoma G2
Characterized by an overall
orderly
appearance
but
recognizable variation of
architectural and or cytologic
atypia eg. variation of polarity
nuclear size, shape, and
chromatin texture.
Mitotic figures are more
frequent than G1
Recurrence rate: 48-71%,
Grade Progression rate: 7 %
Stage Progression rate: 2-12%
High grade papillary urothelial carcinoma G3
Architecturally, cells appear
irregularly clustered.
Cytologically, the nuclear
chromatin tends to be
clumped and nucleoli may be
prominent.
Mitotic figures, including
atypical forms, are frequently
seen
Focal necrosis, a feature not
seen with lower grade lesions.
Recurrence rate: 55-85%,
Grade Progression rate: n/a
Stage Progression rate: 1540%
G3 invasive
Muscularis
propria
Carcinoma in situ
Flat lesion of the urothelium
characterized by the presence
of cells with large, irregular,
hyperchromatic nuclei that
may be either present in the
entire thickness of the
epithelium or only part of it.
Mitotic activity is frequently
observed.
Note urothelium is becoming
detached from the lamina
propria.
Recurrence 80%
Stage progression 40%
http://www.pathology.jhu.edu/bladde
r
• Pathology resource on bladder and prostate
histopathology
– images
– explanations of the different grades etc..