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How to treat: Visible haematuria

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How to Treat
PULL-OUT SECTION
Complete How to Treat quizzes online
www.australiandoctor.com.au/cpd to earn CPD or PDP points.
Visible
haematuria
Background
VISIBLE haematuria is the presence
of blood in the urine that is appar-
ent to the naked eye, as opposed to
non-visible haematuria that is only
picked up on dipstick or micro-
scopic examination.
There are three reasons why clas-
sifying haematuria as visible or
non-visible is preferable to the pre-
vious classification of macroscopic,
microscopic, or dipstick-positive
haematuria. First, with this new
classification it is easier for both lay
persons and health professionals to
understand and discuss haematuria
using a common language.
Second, the previous classifica-
tion may suggest that microscopic
www.australiandoctor.com.au
haematuria is more reliable than
dipstick-positive haematuria and
thereby incorrectly affect the inter-
pretation of these tests and the clini-
cal decision based on them. In fact,
the sensitivity of urine microscopy
can be inferior to dipstick testing for
detecting non-visible haematuria;
this is particularly so when there are
significant delays between obtain-
ing the specimen and its assessment,
which is often the situation with
community-submitted samples.
Third, it is not useful in a clinical
and research setting to classify non-
visible haematuria as microscopic or
dipstick-positive. Classifying non-
visible haematuria as symptomatic or
asymptomatic (based on the presence
or absence of other lower urinary tract
symptoms, loin pain or abdominal
pain) is much more helpful because it
has a direct effect on management.
It is important to consider the
important differences between the
management of visible and non-
visible haematuria. First, whereas
non-visible haematuria may be
confirmed to be persistent prior to
investigating a potential underly-
ing cause, even a one-off episode
of visible haematuria should be
investigated. Second, whereas non-
visible haematuria may be initially
referred to a urologist or nephrolo-
gist depending on various factors,
www.australiandoctor.com.au
INSIDE
Clinical
assessment
Investigation
Management
Bladder cancer
Case studies
the authorS
Professor Dickon Hayne
urologist, Fremantle Hospital,
Fremantle, WA.
Dr Steve McCombie
urology research registrar,
Fremantle Hospital,
Fremantle, WA.
the referral of a patient with visible
haematuria should always be to a
urologist in the first instance. This
is because about 20% of patients
referred with visible haematuria are
found to have an underlying uro-
logical malignancy, with bladder
cancer accounting for about 85% of
these.1
This article focuses on the man- Copyright © 2014
agement of patients with visible hae- Australian Doctor
maturia. Some of the points covered All rights reserved. No part of this
publication may be reproduced,
are also relevant to patients with distributed, or transmitted in any
non-visible haematuria, however, form or by any means without
the management of these patients the prior written permission of
has been well summarised in a pre- the publisher.
For permission requests, email:
vious How to Treat article.2
howtotreat@cirrusmedia.com.au
cont’d next page
6 June 2014 | Australian Doctor | 21
 How To Treat – Visible haematuria
Clinical assessment
Causes
IT is not possible to cover an
exhaustive list of causes of vis-
ible haematuria in this article. The
focus of assessment and investiga-
tions is placed on the serious and
common underlying urological
causes including bladder cancer
and urinary tract stones (see box,
right).
Loin pain-haematuria syndrome
is a rare and poorly understood
condition in which investigations
do not demonstrate adequate
pathology to explain the two
symptoms of loin pain and hae-
maturia. The syndrome appears to
occur more often in young females
and those with a history of glo-
merular disease or renal stones.
After excluding urological
causes, the possibility of an under-
lying renal cause should be con-
sidered. Additionally, if there is
any uncertainty that the blood is
coming from the urinary tract,
the possibility of an underlying
gynaecological or colorectal cause
should be explored. Given that
investigation of anticoagulated
patients reveals similar rates of
urological malignancy compared
with controls, haematuria should
Investigations
WHILE most patients with visible
haematuria require referral to a
urologist for further assessment,
concurrent investigations should
be requested to identify pathol-
ogy that can be treated (eg, UTI)
or require early management (eg,
renal impairment).
The results of these investigations
should be forwarded to the urologist
to prevent delay in further assess-
ment. For example, a normal renal
function allows contrast imaging to
be undertaken expeditiously, and a
recent normal MSU prevents unnec-
essary delay of cystoscopy. The
decision for further investigation if
cystoscopy and imaging are normal
is also influenced by the results of
these investigations. For example,
further invasive investigations may
not be requested if there is evidence
of an underlying cause explaining
the presenting haematuria, such as
renal disease (renal impairment, dys-
morphic red cells, proteinuria) or
UTI.
Increasingly, patients with hae-
maturia are being assessed at ‘one-
stop’ haematuria clinics in which
necessary investigations, including
cystoscopy, are performed on first
contact with a urologist if there
are no contraindications.
Common investigations are
outlined below, and a suggested
algorithm for investigating visible
haematuria is detailed in figure 1.
MSU
Urine dipstick on an MSU may
be used to identify a possible UTI
(with the presence of nitrites and
leukocytes) or evidence of underly-
ing renal disease (with the presence
of protein) in visible haematuria.
A urine dipstick that tests nega-
tive for blood should not prejudice
against referral to a urologist if
there is a good history of an epi-
22 | Australian Doctor | 6 June 2014
iated with urolithiases), or previ-
Common or significant urological causes of visible haematuria Risk factors for
ous pelvic radiotherapy (which is
Malignant urothelial cancer
associated with ureteric stricture
Bladder cancer — usually transitional cell carcinoma History of smoking disease and radiation cystitis). A
Age over 50 review of the medications should
Renal cell carcinoma
Male sex be undertaken, paying particu-
Upper urinary tract transitional cell carcinoma (eg, ureteric transitional cell lar attention to anticoagulants or
carcinoma) Occupational history of drugs that may discolour urine
Other urological malignancies (prostate cancer, penile cancer) manufacturing textiles, paints, and therefore mimic haematuria
rubber, leather tanning, dyes, (such as rifampicin or levodopa).
Benign paints or plastics
Finally, risk factors for urothe-
UTI Previous radiotherapy or
lial cancer such as a history of
Benign prostatic hyperplasia cyclophosphamide smoking and past occupational
Urinary tract stones Long-term catheterisation exposure to predisposing carcino-
Recent instrumentation (eg, catheter insertion,
gens should be identified (see box,
stent insertion, transurethral resection of the prostate, prostate biopsies) infection may be the cause) or left).
painless?
Trauma • I s the bleeding ongoing or has it Examination
Stricture disease resolved? Physical examination should be
Radiation cystitis • I s it severe, involving the passage focused on the urological tract to
of clots? detect any renal angle tenderness,
Benign renal masses (eg, angiomyolipoma)
Enquiry should be made about a renal mass or a palpable blad-
Vascular pathologies (eg, renal infarct, arteriovenous malformation, ruptured associated symptoms, particularly der. The external genitalia should
pseudoaneurysm) the presence of new or longstand- be examined to exclude underly-
Loin pain-haematuria syndrome ing lower urinary tract symptoms ing penile or vulval malignancy,
— these may indicate current UTI and a digital rectal examination
only be attributed to anticoagu- ible haematuria. This should begin or longstanding bladder outflow should be performed in men to
lants or other coagulopathies fol- with the bleeding, for which there obstruction, among other things. examine the prostate. A vaginal
lowing adequate investigation.3 are four important questions to ask: Exploring the past medical and speculum examination may
• I s the bleeding definitely in the history may reveal relevant past be appropriate in women, partic-
History urine, and not coming from the urological or non-urological prob- ularly if there is doubt that the
A detailed history is important in vagina or rectum? lems. There may be a history of bleeding is coming from the uri-
the assessment of a patient with vis- • I s it painful (indicating stones or Crohn’s disease (which is assoc- nary tract.
Urine culture on an MSU will clude flexible cystoscopy. Although
Visible haematuria Figure 1: Algorithm for help identify any comorbid UTIs, biopsies can be taken during flex-
investigating visible haematuria. and sensitivities will help guide ible cystoscopy, this is not common
antibiotic therapy. Evidence of an practice as bladder cancers are often
underlying UTI or renal disease visually obvious and will require
Urgent referral to a
urologist should not deter referral to a urol- transurethral resection.
ogist because these disease pro-
cesses can occur concurrently with Supportive investigations
Dipstick, urine MC&S, urea & electrolytes significant urological pathologies. Narrow-band imaging and fluores-
+/- upper tract imaging cence-guided cystoscopy are new
+/- FBC/Coags/PSA Blood tests technologies that may increase the
Creatinine and eGFR should be sensitivity of detecting urothelial
requested to assess renal function. tumours.
Flexible cystoscopy + imaging Cause found An abnormal renal function may
(CT urography if not contraindicated or Treat cause
prompt more rapid specialist assess- Rigid cystoscopy
already performed)
ment and guide imaging decisions. An alternative to flexible cystoscopy
No cause FBC should be requested to assess is rigid cystoscopy. This requires
anaemia or thrombocytopenia. general or spinal anaesthesia, but
Assess risk of underlying urothelial Coagulation studies can help has the added advantage of being
cancer (eg, smoking, age, occupational exclude suspected coagulopathy (eg, able to treat identified pathologies at
exposure, adequate imaging) Cause found
liver disease, warfarin treatment), the time of the investigation. Rigid
and PSA is appropriate in men with cystoscopy is generally reserved
Low risk High risk an abnormal prostate on digital rectal for those with bleeding that is not
examination, although this should be responding to conservative measures.
Discharge back No cause Urine cytology x3 deferred if UTI is suspected because a
to GP +/- retrograde pyelography UTI can falsely raise the PSA. Complications
+/- ureteroscopy
In the days following cystoscopy
Cystoscopy a large proportion of patients will
Most patients with visible haematu- develop new lower urinary tract
Evidence of renal parenchymal disease? ria should have a cystoscopy. This symptoms that quickly resolve.
(hypertension, dysmorphic red cells, red Yes Refer to is usually performed with a flexible Although a UTI must be excluded
cell casts, elevated creatinine or eGFR, nephrologist
proteinuria) cystoscope, following the adminis- with a urinary dipstick or formal
tration of local anaesthetic gel into microscopy and culture, routinely
the urethra. It is a safe and well-toler- prescribing antibiotics for patients
No
ated procedure that is similar to pass- with these symptoms is not required.
ing a urinary catheter.
Monitor symptoms, re-refer to urologist if persistent or Imaging
recurrent symptoms
Relative contraindications All patients with visible haema-
There are two relative contraindica- turia should have imaging of the
tions to flexible cystoscopy: ongoing upper urinary tract, even if a likely
All patients with sode of visible haematuria because
bleeding secondary to malignancy
heavy haematuria and a UTI. Ongo-
ing heavy haematuria results in poor
lower-tract cause has been identi-
fied. Previously, imaging for hae-
visible haematuria is typically intermittent. views with cystoscopy. Any instru- maturia has focused on urinary
should have imaging Microscopy of an MSU sample mentation in the presence of a UTI tract ultrasonography and IV
may identify dysmorphic red cells risks precipitating urosepsis. A UTI urography. While these remain
of the upper urinary or red cell casts, which are both may also make it difficult to distin- useful modalities, they have been
tract. indicative of parenchymal renal guish if the abnormalities seen on a largely replaced by CT urography,
disease. Prompt examination of cystoscopy are the result of the infec- which is CT with delayed uro-
specimens is essential for accuracy tion or a different pathology. graphic phase imaging.
of the microscopy. Anticoagulant use does not pre- cont’d page 24
www.australiandoctor.com.au
 How To Treat – Visible haematuria
from page 22
CT urography
CT urography gives highly detailed
images of the abdomen and pelvis
in three different phases related to
the administration of IV contrast:
a non-contrast phase, a nephro-
graphic phase and a delayed
phase. It is much more sensitive in
detecting pathology than urinary
tract ultrasonography or IV urog-
raphy. The non-contrast phase is
useful for detecting urolithiasis,
and the nephrogenic phase enables
full assessment of renal parenchy-
mal lesions (figure 2). The delayed
phase is useful for detecting
both upper tract and intravesical
pathologies, but does not negate
the need for cystoscopy (figure 3).
Additionally, CT urography
prior to a transurethral resection
of bladder tumour provides useful
preoperative staging information.
It is also useful for detecting non-
urological pathologies.
The main disadvantage of CT
urography is that it involves a sig-
nificant radiation dose. It is there-
fore not unreasonable to defer
the decision to proceed with CT
urography in young patients until
results of other investigations are
obtained.
Alternatives to CT urography
Non-contrast CT of the kidney,
ureters and bladder (CT KUB), MRI,
urinary tract ultrasonography and
IV urography remain useful alterna-
tives in patients in whom CT urog-
raphy is contraindicated because of
the risk of radiation, complications
of kidney injury and allergy. These
include people who are pregnant,
contrast-allergic, and those with kid-
ney impairment on serology (eGFR
< 60mL/minute/1.73m2).
CT KUB, with lower radiation
risks than CT urography, is an ade-
quate initial investigation in young
and a sensitivity of up to 90%
Figure 2: Coronal
CT urogram for high-grade urothelial tumours
(nephrographic and carcinoma in situ, however its
phase) sensitivity for low-grade tumours is
demonstrating poor.4 Additionally, interpretation
a large left renal can be difficult in the presence of
mass suggestive stones or infection. It is not required
of a renal cell prior to referral to a urologist, and
carcinoma, with may only be of use in certain sce-
metastases to
narios. These include: suboptimal
the right kidney,
left adrenal and initial investigations, normal inves-
lungs (arrows). tigations but significant risk factors
for urothelial malignancy (see box,
Risk factors for urothelial cancer),
and patients with significant irrita-
tive symptoms that may be sugges-
tive of urothelial carcinoma in situ.
Nonetheless, it is a non-invasive test
Figure 3: Coronal which, if positive, is highly indicative
CT urogram of urothelial malignancy.
(delayed phase) Analysing multiple, separately col-
demonstrating lected specimens increases the sensi-
a right ureteric tivity of urine cytology. It is common
filling defect
practice when collecting urine for
suggestive of an
urothelial tumour cytology to collect three specimens
(circled), and on sequential days. Although
left renal cysts assessment of freshly voided urine
(arrows). is ideal, it is acceptable for speci-
mens to be stored in a fridge and
submitted together.
Patients should be instructed to
retract the foreskin or separate the
labia, and clean the area around
the urethral meatus including the
meatus itself. The urine should be
patients with renal colic. However, collected as a complete void from
there should be a low threshold for initiation to complete emptying of
proceeding to CT urography if the the bladder rather than a MSU. It
results are negative or equivocal. should not be a ‘first void urine’,
that is, the first void of the day in
Urine cytology the morning because the longer
Urine cytology has an overall urine is stored in the bladder, the
specificity approaching 100% greater the amount of cell lysis
that occurs, making tests for red
cells less sensitive.
Urine for cytology can also be col-
lected from a urinary catheter, which
can be inserted temporarily for this
purpose, or immediately after the
bag is changed where the patient
already has an indwelling catheter.
It can also be collected during rigid
cystoscopy or ureteroscopy.
Other investigations
Other investigations may be
undertaken where the above inves-
tigations have failed to identify an
underlying cause.
Retrograde pyelography and
ureteroscopy may help make the
diagnosis in those with positive
urine cytology, or in whom there
is a high clinical suspicion of
underlying malignancy. Although
possible urinary and serological
markers of urothelial cancer have
been reported, use of these has not
been adopted presently.
Urinary protein–creatinine ratio,
24-hour urinary collection for pro-
tein, and blood pressure measure-
ments remain useful investigations
for identifying a nephrological
cause for the haematuria.
If no cause for the haematuria is
identified, it is important to con-
tinue to monitor the symptoms
and maintain a low threshold for
re-referral to a urologist if visible
haematuria is recurrent or persis-
tent. If bleeding were to recur two
years after the previous assess-
ments, in the absence of an iden-
tified cause repeat assessment and
investigations would be indicated.

Management
Referral
AFTER a detailed history and
examination, a decision is required
as to whether the patient can be
investigated as an outpatient, or
whether they require emergency
admission to hospital. The indica-
tions for emergency admission are:
haemodynamic instability, severe
bleeding with clots or clot reten-
tion, pain requiring opiates, or any
history of trauma to the abdomen,
pelvis or loin. Ongoing haemat­
uria is not an absolute indication
for admission to the hospital.
Reducing bleeding risk
Anticoagulants should generally
be ceased if there is ongoing bleed-
ing unless there are strong indica-
tions for them to continue.
Outpatient management
If the decision is made to manage
the patient in the community, every
patient with visible haematuria still
requires urgent referral to a urolo-
gist for cystoscopy within the foll-
owing (ideally two) weeks. This is
because visible haematuria is the
single most predictive symptom
indicating the presence of malig-
nancy.5 It is important to note and
emphasise that patients with a UTI
and visible haematuria require
referral to a urologist because about
10% of urological malignancies pre-
sent in association with a UTI.6
There may be an occasional
exception to this rule, such as a
young non-smoker who presents
with uncomplicated renal colic,
proven on imaging, whose haema-
turia resolves following spontane-
In patients with ous passage of the stone, although
bladder cancer, a a urology referral may still be use-
delay of just two ful on a non-urgent basis. Patients
managed in the community should
weeks between the still be asked to attend the ED
onset of symptoms should they develop indications for
admission.
and referral to a Nonetheless, the safest strategy
urologist has been is to refer all visible haematuria to
a urologist on an urgent outpatient
shown to decrease basis; a written referral is usually
five-year survival by appropriate. This referral should
not be delayed until results of inves-
5%. tigations are obtained, although
these investigations may occur con-
currently. In patients with bladder
cancer, a delay of just two weeks
between the onset of symptoms
and referral to a urologist has been
shown to decrease five-year sur-
vival by 5%.7
Emergency hospital management
Initial management
If the patient is referred for emer-
gency hospital management, the
immediate investigation and man-
agement is directed towards the
likely aetiology and stabilising the
patient’s bleeding.
If the patient has severe haema-
turia (passing large clots or clot-
related urinary retention) then a
three-way catheter is inserted, a
manual bladder washout is per-
formed, and bladder irrigation is
undertaken.
Blood tests are organised and
any anaemia, thrombocytope-
nia or coagulopathy is corrected
as appropriate. Serological renal
dysfunction is managed with IV
rehydration, stopping nephrotoxic
medications, and ensuring there
is no obstructive cause. The latter
is often best assessed with ultra-
sound or non-contrast CT KUB
in the first instance because of the
risk of IV contrast exacerbating an
acute kidney injury.
An MSU microscopy/culture/
sensitivities should be requested in
all patients regardless of infective
symptoms.
The patient should be given
appropriate antibiotic therapy
if there is any evidence of sepsis.
Repeated bladder washouts may
be required before the haematu-
ria usually resolves. If haematu-
ria resolves following this line of
management, the urinary catheter
can be removed and the patient
discharged home after a successful
trial of void. They can then be fully
investigated for their haematuria
on an urgent outpatient basis.
Massive or persistent bleeding
Occasionally haematuria fails to
resolve with this relatively con-
servative line of management,
necessitating further intervention.
Useful indications for the need
for further intervention include:
haemodynamic instability, fall-
ing haemoglobin, non-settling or
severe haematuria, and evidence of
residual clot in the bladder despite
regular bladder washouts and con-
tinuous bladder irrigation.
The initial intervention is usually
a rigid cystoscopy under general
or spinal anaesthesia. This allows
a thorough bladder washout to
be performed while the patient is
anaesthetised, and bleeding points
can be identified and cauterised.
Other treatments and interven-
tions may be considered depend-
ing on the aetiology and site of
the bleeding (see ‘Treatments and
interventions’ box).
Preventing further haematuria
The prevention of further bleed-
ing is directed towards treating the
underlying cause. This will include
resection of any malignancy, but
may also incorporate other strat-
egies that include medications to
reduce bleeding and antibiotics to
cont’d page 26

24 | Australian Doctor | 6 June 2014 www.australiandoctor.com.au

 How To Treat – Visible haematuria
from page 24
prevent recurrent UTIs. For exam-
ple, 5-alpha reductase inhibitors
may be used to reduce bleeding in
benign prostatic hyperplasia, hyper-
baric oxygen therapy may be used
to help the bladder recover in radia-
tion cystitis, and antibiotics may be
used for recurrent UTIs.
The reintroduction of anticoagu-
lants should be weighed against the
risk of further haematuria, partic-
ularly if the underlying cause for the
haematuria has not been identified
or treated.
Bladder cancer
ABOUT 20% of patients referred
with visible haematuria are found
to have an underlying urological
malignancy, 85% of which are
bladder cancers.1 Thus, even a
one-off episode of visible haema-
turia should be referred to a urolo-
gist urgently for investigation and
cystoscopy (figure 4).
Bladder cancers begin as superfi-
cial tumours and, if left untreated,
become more invasive over time;
longer delays between the occur-
rence of haematuria and uro-
logical assessment result in both
higher stage and poorer survival.7
Data from the Australian Institute
of Health and Welfare show that
bladder cancer is the only major
cancer in Australia for which sur-
vival has significantly deteriorated
in the past 30 years.8 Delays in the
referral, diagnosis and treatment
of patients with bladder cancer
may be contributing to this trend.
The AIHW data also demon-
strates that five-year survival
for women with bladder cancer
(50%) is significantly worse than
five-year survival for men (60%).3
Although the cause of this dispar-
ity is likely to be multifactorial,
proportionally longer delays in the
referral and specialist assessment
of women compared with men
appears to be a factor.9 This seems
to be partly due to women being
more likely to be diagnosed and
treated for a UTI, without under-
going thorough investigation and
urological referral.
Given the high incidence of blad-
der cancer in patients presenting
with visible haematuria, some key
messages regarding bladder cancer
are provided (see box, right).
Management
Patients found to have a bladder
tumour are initially treated with
a transurethral resection of the
tumour. Following this procedure,
one postoperative dose of intraves-
ical chemotherapy (eg, mitomycin)
is often given to reduce the risk of
recurrence.
Further management is deter-
mined by the grade and stage
of the tumour. These are usu-
ally divided into two categories
to guide clinical management:
non-muscle-invasive disease and
muscle-invasive disease (see box
above, far right).
Non-muscle-invasive bladder
cancer
Following their initial transure-
thral resection of that bladder
tumour, some patients may go
on to have a ‘re-resection’ after
26 | Australian Doctor | 6 June 2014
Treatments and interventions that may be required for severe or complicated haematuria
Rigid cystoscopy, cystodiathermy, and bladder washout
Intravesical agents (eg, alum in radiation cystitis)
Pro-coagulants (eg, tranexamic acid)
Hormonal therapies (eg, LHRH analogues in prostate cancer)
External-beam radiation therapy (eg, prostate cancer)
Hyperbaric oxygen therapy (eg, radiation cystitis)
Embolisation (eg, arteriovenous fistula, or intractable bladder bleeding)
Vascular ligation (eg, of internal iliac arteries for intractable bladder bleeding)
Nephrectomy (eg, renal tumour, or trauma)
Cystectomy (eg, radiation cystitis)
Bladder cancer —
take-home messages
• The only cancer in Australia with
deteriorating survival – diagnostic
delay is likely a contributing factor
• Usually caused by cumulative
exposure to urine-borne
carcinogens — especially
smoking
• Bleeding is often intermittent —
even a ‘one-off’ episode should
be fully investigated
• Often associated with infected
urine — visible haematuria should
never be solely attributed to a UTI
• Women have worse prognosis
than men — again longer delays
in referral appears to be a
contributing factor
• Almost all patients with visible
haematuria require a cystoscopy
a few weeks. The repeat resec-
tion is particularly useful for T1
tumours, as up to 25% of them
will be upstaged to muscle-inva-
sive disease.10
Once the tumour is adequately
staged, an assessment is made of
the risk of the tumour recurring or
progressing. Risk factors include:
high-grade disease, lamina pro-
pria invasion, presence of urothe-
lial carcinoma in situ, and large,
multiple or recurrent tumours.
Higher-risk tumours should
be offered a course of intravesi-
cal therapy, such as mitomycin
or BCG. BCG should be given
as an induction course (usually
six-weekly treatments) followed
by a maintenance course (eg,
monthly for one year). Regard-
less of treatment with further
intravesical therapy, all patients
with non-muscle-invasive bladder
cancer require regular cystoscopic
surveillance for recurrence of
disease. Surveillance for higher-
risk tumours may be more fre-
quent, and involve upper urinary
tract imaging and cytology. Rec-
www.australiandoctor.com.au
Figure 4: Cystoscopic
view of a bladder
tumour, showing
neoangiogenesis and a
papillary appearance.
ommended follow-up regimes
for non-muscle invasive bladder
cancer can be accessed via online
European Association of Urology
guidelines.10
Muscle-invasive bladder cancer
Patients with muscle-invasive
bladder cancer require full stag-
ing. Imaging the chest, abdomen
and pelvis with CT, MRI or PET
should include delayed phase
imaging to assess for a synchro-
nous upper urinary tract tumour.
Patients with localised disease
Classification of
bladder cancer
Grade — high or low.
Stage — non-muscle-invasive or
muscle-invasive.
Non-muscle-invasive disease
include:
Ta (non-invasive, papillary tumour)
T1 (tumour invades lamina propria)
CIS (carcinoma-in-situ; flat, non-
invasive tumour)
Muscle-invasive tumours include:
T2 (invade detrusor muscle),
T3 (invade peri-vesical tissue)
T4 (invade prostate, uterus, vagina,
pelvic or abdominal wall)
They are further classified as being
localised, having nodal metastasis
or having distant metastasis
may be offered a radical cystec-
tomy. This involves removing the
bladder and adjacent organs (eg,
prostate, uterus), and a complete
pelvic lymphadenectomy. A sec-
tion of ileum is used to create
either an ileal conduit where the
urine drains continuously via a
stoma, or an orthotopic bladder
where the urine drains voluntarily
via the urethra.
Palliative cystectomy and radio-
therapy may be given for symptom
control in locally advanced dis-
ease.
Chemotherapy may be used
for both localised and metastatic
bladder cancer. In localised blad-
der cancer it may be given before
(neo-adjuvant) or after (adjuvant)
cystectomy, or it may be given
along with radiotherapy as part
of multi-modal bladder-preserving
therapy in those not suitable for
cystectomy.
Follow-up of patients who have
been treated for a muscle-invasive
bladder cancer aims to detect local
or distant recurrence, as well as con-
ducting surveillance on the patient’s
remaining urothelium (including
their urethra and upper tracts). It
may therefore involve urinary tract
ultrasonography, CT, MRI, ure-
throscopy and cytology. Although
some of this follow-up could be
conducted in primary care the need
for urethral surveillance, interpreta-
tion of upper urinary tract imaging
and significant risk of recurrence
and metastatic disease means it may
be best co-ordinated by a hospital
specialist. Recommended follow-up
regimes for muscle-invasive bladder
cancer can be accessed via online
European Association of Urology
guidelines.11
Case studies
Case study 1:
Diagnostic delay
BELINDA, a 63-year-old woman
with no significant comorbidities,
presented to her GP with painless
haematuria and explained that she
was worried she may have blad-
der cancer. The haematuria had
occurred the day before and had
now resolved. She had no assoc-
iated symptoms and had never had
a UTI. She had never smoked.
Belinda was reassured that the
bleeding was probably related to
a UTI or red pigment in her food.
She was also referred for an ultra-
sound scan, blood tests and urine
microscopy/culture/sensitivities,
all of which were normal.
A week later Belinda had fur-
ther bleeding in her urine and
presented to a different GP. A
CT KUB was organised (Belinda
was contrast-allergic and there-
fore could not have IV contrast)
that demonstrated a lesion on the
anterior bladder wall with signs
of backflow obstruction of the
right-sided collecting system.
A referral to a private urolo-
gist was given to further assess
these findings. Unfortunately, no
appointment was available for
Case study 2:
Intractable bleeding
Harold, a 70-year-old male
smoker, presented to his GP with
urinary blood clot retention. He
had a past history of external-
beam radiation therapy for pros-
tate cancer three years earlier,
had bilateral ureteric stents in
situ for obstructive uropathy, and
had a history of radiation cystitis
requiring previous left internal
iliac artery embolisation.
Harold was admitted to hos-
pital as an emergency where a
three-way catheter was inserted,
a manual bladder washout was
performed, and bladder irriga-
tion was commenced. Over the
following 24 hours he continued
to bleed significantly, requir-
ing multiple units of blood and
manual bladder washouts, and
was therefore taken to the oper-
Case study 3: Upper urinary
tract assessment
Peter, a 72-year-old male smoker
with a background of hyperten-
sion, presented to his GP with pain-
less visible haematuria and was
immediately referred to a urolo-
gist on an urgent basis. His renal
function, FBC, urine microscopy/
culture/sensitivities, and urine
cytology were all normal. Flexible
cystoscopy revealed a small blad-
der tumour near the right ureteric
orifice, and a CT urography was
organised that demonstrated a
mass within the right renal pelvis.
Peter subsequently underwent
transurethral resection of bladder
tumour and concurrent right ret-
rograde pyelography. Right ure-
teric washings were sent for urine
cytology and atypical cells were
noted. He received one postop-
erative dose of intravesical chem-
otherapy (mitomycin), and the
the next three months because
the urologist was going on leave.
Belinda presented to an ED to
request a referral to a ‘one-stop’
haematuria clinic that she had
heard about. However, before she
could attend this clinic appoint-
ment she had an episode of severe
haematuria requiring hospital
admission for a three-way catheter,
histology of his bladder tumour
demonstrated a low-grade, non-
muscle-invasive transitional cell
carcinoma. Following adequate
staging investigations for the
bladder washout and irrigation. A
transurethral resection of bladder
tumour revealed high-grade, mus-
cle-invasive bladder cancer. This
was already 70 days after her first
episode of visible haematuria. She
subsequently underwent a radical
cystectomy and is now disease-free,
although she will require close fol-
low-up to monitor for recurrence.
upper-tract mass, which were
clear, Peter subsequently under-
went a right nephroureterectomy.
Histology revealed a low-grade,
non-invasive transitional cell car-
www.australiandoctor.com.au
Comment
This case illustrates a few key
points. Firstly, a history of vis-
ible haematuria should always be
taken seriously, even if the bleed-
ing has completely resolved and
urine dipstick and/or microscopy
are negative for blood.
Secondly, the referral of
patients with visible haematuria
should not be delayed while wait-
ing for results of initial investiga-
tions. Regardless of the results
of these investigations, patients
with visible haematuria will still
require a cystoscopy because the
risk of an underlying malignancy
is 20%.
Thirdly, even with a prompt
referral, the patient may face pro-
longed delays. The importance
of prompt assessment for a vis-
ible haematuria should be clearly
emphasised to the patient.
Finally, women suffer poorer
outcomes from bladder cancer
than men. This may be because of
the haematuria being inappropri-
ately attributed to a UTI without
thorough investigation, and delay
from attributing the bleeding to a
gynaecological cause rather than
a urological cause.
ating theatre for evacuation of
the blood clot and change of
his ureteric stents. Appearances
of severe radiation cystitis were
noted during cystoscopy, and so
a course of hyperbaric oxygen
therapy was given.
Despite these interventions
the haematuria continued, so he
underwent embolisation of his
right internal iliac artery, and
was also treated with intravesical
alum. Neither of these measures
controlled the bleeding and so
he eventually underwent cystec-
tomy.
Comment
It is important to identify those
patients who require emergency
admission to hospital rather than
an urgent outpatient referral
because haematuria can be life-
threatening.
cinoma of the renal pelvis.
Comment
This case illustrates three key
points. It demonstrates the impor-
tance of adequate upper tract
imaging. A small ureteric or renal
pelvic mass can be easily missed on
ultrasound, non-contrast CT and
even contrast-enhanced CT if high-
quality delayed phase images are
not reviewed.
It also shows the importance of
fully investigating a patient with
haematuria even if a cause has been
identified. In this case, a bladder
tumour was the initial finding but
the same principle should apply to
a patient who had a UTI.
Urine cytology is unreliable,
particularly at detecting low-grade
urothelial cancer. The sensitivity of
urine cytology can be increased by
collecting separate samples on dif-
ferent days.
References
1. E
 dwards TJ, et al. A prospective
analysis of the diagnostic yield
resulting from the attendance
of 4020 patients at a protocol-
driven haematuria clinic. BJU
International 2006; 97:301-05.
2. M
 athew T. How to Treat —
Microscopic haematuria. Australian
Doctor, 27 April 2007.
3. A
 vidor Y, et al. Clinical
significance of gross hematuria
and its evaluation in patients
receiving anticoagulant and aspirin
treatment. Urology 2000; 55:22-24.
4. T
 ravedi D, Messing EM.
Commentary: the role of cytologic
analysis of voided urine in
the work-up of asymptomatic
microhematuria. BMC Urology
2009; 9:13.
5. K
 endall MJ, et al. QED: quick
and early diagnosis. Lancet 1996;
348:528-29.
6. V
 asdev N, Thorpe AC. Should
the presence of a culture positive
urinary tract infection exclude
patients from rapid evaluation
hematuria protocols? Urologic
Oncology 2013; 31:909-13.
7. W
 allace DM, et al. Delay and
survival in bladder cancer. BJU
International 2002; 89:868-78.
8. A
 ustralian Institute of Health and
Welfare 2012. Cancer Survival and
Prevalence in Australia: Period
Estimates from 1982 to 2010.
Cancer Series no. 69. Cat. no. CAN
65. AIHW, Canberra, 2011.
9. N
 icholson BD, et al. Bladder cancer
in women. BMJ 2014; 348:g2171.
10. Babjuk M, et al. Guidelines on
non-muscle-invasive bladder
cancer. In: EAU Guidelines,
edition presented at the 25th EAU
Annual Congress, Barcelona,
2010.
11. Stenzl A, et al. Guidelines on
muscle-invasive and metastatic
bladder cancer. In: EAU
Guidelines, edition presented at
the 25th EAU Annual Congress,
Barcelona, 2010.
cont’d next page
6 June 2014 | Australian Doctor | 27
 How To Treat – Visible haematuria

Conclusion
ABOUT 20% of patients present-
ing with visible haematuria have
an underlying urological malig-
nancy, often bladder cancer.1
Therefore any patient with a hist-
ory of visible haematuria should
be referred urgently to a urologist
for cystoscopy. Visible haematuria
should never be attributed sim-
ply to anticoagulants, UTI, dyed
foodstuffs, or ‘probable’ vaginal
bleeding, without adequate invest-
igation.
History in these patients
should focus on confirming that
the bleeding is from the urinary
tract, assessing the severity of
the bleeding, identifying associ-
ated symptoms and assessing for
the presence of risk factors for
urothelial cancer. For the latter,
these risk factors include: history
of smoking, age over 50, male
sex, occupational exposure to car-
cinogens, previous radiotherapy
or cyclophosphamide, and long-
term catheterisation. Following
a focused examination, it must
be decided whether the patient
requires emergency admission
to hospital. Indications for this
include: haemodynamic instabil-
ity, severe bleeding with clots or
clot retention, pain requiring opi-
ates, or any history of trauma to
the abdomen, pelvis or loin. If
these patients have severe bleeding
then they may require a three-way
catheter, manual bladder wash-
outs and bladder irrigation. Those
Visible haematuria
should never be
attributed simply
to anticoagulants,
UTI, dyed foodstuffs,
or ‘probable’
vaginal bleeding,
without adequate
investigation.
with intractable bleeding may ulti-
mately require more invasive inter-
ventions including cystoscopic
washout under a general or spinal
anaesthetic, embolisation, or even
surgical removal of the bladder or
kidney.
If the patient does not require
emergency admission, then initial
investigations should be organ-
ised. These should include a
urine dipstick, urine microscopy/
culture/sensitivities, and EUCs.
Other helpful tests may include
an FBC, coagulation profile and
PSA. Abnormal results should be
acted upon promptly, however
referral to a urologist should not
be delayed while awaiting results.
While awaiting further assess-
ment, anticoagulants should be
stopped unless there are compel-
ling reasons against this.
Further urological investiga-
tion in addition to cystoscopy
includes upper tract imaging,
ideally CT urography. If these
investigations are normal then the
need for further investigation will
be determined by the urologist’s
assessment of the patient’s risk
of underlying malignancy. Other
investigations may include urine
cytology, retrograde pyelography
and ureteroscopy.
In patients with no urological
pathology identified that explains
their haematuria, the possibility of
an underlying renal parenchymal
disease must be considered. Evi-
dence for this includes hyperten-
sion, dysmorphic red cells, red cell
casts, elevated creatinine or eGFR,
and proteinuria. If any of these are
present then referral to a nephrol-
ogist is recommended.

Instructions

How to Treat Quiz
Visible haematuria — 6 June 2014
1. Which TWO statements are correct not recommended in visible haematuria
regarding the clinical features of visible
haematuria? 4. W hich TWO statements are correct
a) Visible haematuria is clinically defined as regarding the urinary investigations of
blood in the urine that is detectable without visible haematuria?
microscopy a) Urine culture positive for UTI excludes
b) Visible haematuria secondary to malignancy sinister causes for visible haematuria
is typically intermittent b) P rompt examination of an MSU sample
c) 20% of visible haematuria are associated improves the accuracy of microscopy
with an underlying urologic malignancy c) Urine collected for cytology should have
d) There is a higher incidence of urological been in the bladder for more than eight
malignancies in anti-coagulated patients hours to maximise sensitivity
presenting with visible haematuria d) U rine cytology has poor sensitivity for low-
grade urothelial tumours
2. Which THREE diagnoses are common
and/or significant causes of visible 5. W hich TWO statements are correct
haematuria? regarding the cystoscopic investigations
a) Bladder or renal cell cancer of visible haematuria?
b) Renal artery stenosis a) Most patients with visible haematuria will not
c) Benign prostatic hyperplasia need a cystoscopy
d) Radiation cystitis b) O ngoing heavy haematuria and a UTI are
two relative contraindications to flexible
3. Which TWO statements are correct cystoscopy
regarding the clinical history and c) Anticoagulants need to be stopped for one
examination of a presentation of visible week before flexible cystoscopy
haematuria? d) In the days following cystoscopy a large
a) Current use of antibiotics is an important proportion of patients will develop new lower
history to assess in visible haematuria urinary tract symptoms that quickly resolve
b) Past medical history usually has no bearing
on an acute episode of visible haematuria 6. W hich TWO statements are correct
c) A penile examination should be performed to regarding the imaging investigations of
exclude malignancy visible haematuria?
d) A vaginal examination is not necessary and a) CT KUB is the principal imaging test for
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visible haematuria
b) CT urography is much more sensitive in
detecting pathology than urinary tract
ultrasonography or IV urography
c) CT urography with delayed phase imaging
negates the need for cystoscopy
d) All patients with visible haematuria should
have imaging of the upper urinary tract,
even if a likely lower-tract cause has been
identified
7. Which TWO statements are correct
regarding the outpatient management of
visible haematuria?
a) Patients with severe loin pain and visible
haematuria should be managed as
outpatients for renal colic
b) Tranexamic acid may be given for severe
haematuria not responding to conventional
treatment
c) Ongoing haematuria is not an absolute
indication for referring to the ED
d) Visible haematuria not requiring ED
management should be monitored for six
weeks before referral to a urologist
8. Which THREE treatments may be given in
the hospital for emergency management
of visible haematuria?
a) A three-way catheter with manual bladder
washout and bladder irrigation
b) Rigid cystoscopy that allows bleeding points to
be identified and cauterised
c) Transurethral resection of the prostate to stop
bleeding from benign prostatic hyperplasia
d) Arterial embolisation for intractable bladder
bleeding
9. Which THREE statements are correct
regarding interventions that can be
given for various causes of severe or
complicated visible haematuria?
a) External-beam radiation therapy may be
given for visible haematuria secondary to
prostate cancer
b) Intravesical alum may be given to treat visible
haematuria secondary to urinary tract stones
c) Cystectomy may be performed in
complicated visible haematuria secondary to
radiation cystitis
d) Vascular ligation of the internal iliac arteries
may stop intractable bladder bleeding
10. Which THREE statements are correct
regarding preventive management of
further visible haematuria?
a) Intravesical BCG may be given to prevent
further visible haematuria in severe
complicated cases
b) Preventive antibiotics may be used for
recurrent UTIs leading to visible haematuria
c) 5-alpha reductase inhibitors may be used to
reduce future bleeding in BPH
d) Hyperbaric oxygen therapy helps the
bladder recover in radiation cystitis and
prevents further visible haematuria

CPD QUIZ UPDATE

The RACGP requires that a brief GP evaluation form be completed with every quiz to obtain category 2 CPD or PDP points for the 2014-16 triennium.
You can complete this online along with the quiz at www.australiandoctor.com.au. Because this is a requirement, we are no longer able to accept how to treat Editor: Dr Steve Liang
the quiz by post or fax. However, we have included the quiz questions here for those who like to prepare the answers before completing the quiz online. Email: steve.liang@cirrusmedia.com.au

Next week Domestic violence is a major contributor to morbidity and mortality for women under 45. GPs may suspect domestic violence and are well positioned to initiate action to help victims and
perpetrators escape the cycle of violence. The next How to Treat is an update of a 2009 article on this topic. The author is Associate Professor Kelsey Hegarty, director, Researching Abuse and Violence
primary care program, department of general practice, University of Melbourne, Carlton, Victoria.

28 | Australian Doctor | 6 June 2014 www.australiandoctor.com.au

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