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E0491763 • 2.000 • 02/10 • PPU
PDD –
Photodynamic
Diagnosis
Experience the Innovative Therapy
against Benign Prostate Enlargement
An innovative way of
cancer detection
Introduction
This brochure aims at outlining the benefits of
treatment with PDD for bladder cancer. For pa­tients with bladder cancer, their diagnosis is a
frightening realisation. However, these days there
are promising options for the detection and
complete removal of bladder tumours.
Photodynamic diagnosis – often abbreviated
PDD – is an appropriate and up-to-date method
for diagnosing and treating bladder cancer. With
the help of PDD, your doctor can endoscopically
scan the inside of your bladder more thoroughly
in order to accurately detect and treat any malignant anomalies. PDD is the key to optimal
cancer management.
Bladder cancer
The Disease
The bladder is a hollow muscular organ that stores
urine until it is excreted by urination and it is lined with
a membrane made up of transitional cells. Bladder
cancer is a malignant tumour that arises from
abnormal and uncontrolled growth of these cells. It
is the 5th most common type of cancer in the world.1
Most bladder cancers are diagnosed after the age
of 60, with men being affected more often than
women.2
Urinary System
Kidney
Ureter
Bladder
Urethra
Prostate
gland
Fig. 1: The urinary system of women (left) and men (right):
Along with the kidneys, ureters and urethra, the bladder is one of the most
important organs of the urinary system. Among other functions, this system
produces and discharges urine to rid the body of waste products.
Bladder cancer
bladder cancer staging
Fat
Causes
Currently, the causes for bladder cancer are mostly
speculative. So far, however, several risk factors have
been identified that are linked to the disease. Smoking
is probably one of the greatest risk factors for bladder
cancer – due to the cancer-promoting substances
found in tobacco.1, 3
Muscle
Connective tissue
Bladder lining
Superficial
bladder
cancer
Invasive
bladder
cancer
Symptoms1
One of the first warning signs of bladder cancer is blood
in the urine. Other symptoms can include recurrent
urinary tract infections or urination problems such as
painful urination, increased frequency or feeling the
need to urinate but not being able to. However, these
symptoms are not at all specific to bladder cancer and
may also often be caused by other conditions. If these
symptoms occur, patients should have them evaluated
by a doctor. Early clarification is the best way to ensure
successful treatment. As with most cancers, the earlier
bladder cancer is detected, the better is its prognosis.
Staging1
There are various ways to characterise bladder cancer:4
tumour classification helps to inform the doctor about
the tumour’s progression and helps him in deciding
on the most effective way to manage the disease.
Bladder cancer usually begins to grow in the cells
of the upper lining of the bladder wall. Growth remains
superficial in the early stages of the disease (= super-
Fig. 2: Diagram of the bladder showing the different stages of bladder cancer.
ficial bladder cancer). In this stage, the cancer is
confined to the upper layer of the bladder and
usually appears as small papillary tumours shaped
like mushrooms which grow out of the bladder lining
(see Fig. 2).
Among superficial bladder cancers, a form called
carcinoma-in-situ (CIS) is more aggressive and virtually
invisible to the naked eye since it is flat, and does
not stand out against the normal bladder wall. This
makes its detection and therefore its therapy much
more difficult.
Nevertheless, if cancer is detected in the early superficial stages, which happens about 8 times out of 104,
there are good chances that the tumour can be treated
successfully and the prognosis for the patient is good.
If one of the superficial tumours in the bladder remains
untreated, it can gradually infiltrate the muscular wall
of the bladder and potentially spread to the body.
Treatment
This stage is called invasive bladder cancer and
requires a different surgical approach and follow-up
treatment. The treatment of invasive bladder cancer
will be explained by your doctor.
Treating Superficial Bladder Cancer
Depending on the patients’ general health status and
personal preferences, treatment for bladder cancer
is mainly influenced by how deeply the cancer has
invaded the bladder wall. In general, the treatments
available for bladder cancer include surgery, immuno­
therapy, radiation therapy and chemotherapy, all of
which can be further explained to you by your doctor.
Superficial bladder cancer is usually treated or removed
by a minimally invasive surgical procedure that combines
transurethral cystoscopy and bipolar transurethral resection in saline of the bladder tumour (TURis-B). By
entering the bladder through the urethra (transurethral
access), the entire surgical treatment can be performed
without long incisions. Primarily, the diagnosis is
done via cystoscopy. However, once cancer has been
diagnosed and classified, cystoscopy is combined
with TURis-B for the removal of the tumours: In a single
surgical procedure the complete bladder wall is scanned for tumours which are resected upon detection.
Since bladder cancer often occurs in a multifocal way,
i.e. there is more than one tumour in the bladder, complete detection and removal are important. Otherwise,
the remaining tumour cells can spread and cause a
recurrence of the disease. If necessary, the doctor
Treatment
might give additional chemotherapy or immuno­ther­
apy following surgery to complement the procedure
and kill any remaining cancer cells.
The Surgical Procedure: Cystoscopy/TURis-B
This surgical procedure
can be performed under
spinal or general anaesthesia, so that the
patient does not feel
any pain. For cystoscopy, the doctor carefully and gently passes
a thin optical instrument Fig. 3: Images often relayed to a monitor.
(cystoscope) through the
urethra into the bladder. The fibre-optic light source
and a very small camera incorporated in the cystoscope provide the doctor with a detailed view of the
inner lining of the bladder. As a result, the doctor can
inspect the entire bladder for tumours. If any suspicious
structures are found, a small biopsy can be removed
painlessly to verify the cause for the anomaly. Any
tumour that is diagnosed will be removed by excision
with a small electric loop that extends from the tip of
the cystoscope.
Upon ignition, the loop forms a plasma pocket,
which is very smoothly applied to excise the abnormal
cells precisely. Bipolar resection offers various advantages over the older method of monopolar resection:
No current flows through the patient.
This protects them from unexpected burns, but also
Treatment
from nerve stimuli, that can cause the patient to move
intraoperatively. Furthermore, the irrigation fluid used is
physiological, as compared to the glycine used for monopolar resection. This means that the risk for a TUR
syndrome, due to non-physiological fluid entering the
blood system and causing an imbalance, is greatly reduced. Overall, the bipolar operation is said to be safer
and may allow patients to leave the hospitals quicker.
At present, there are two different cystoscopic procedures available: conventional white-light cystoscopy
and the new, more modern photodynamic diagnosis
(PDD) also known as blue-light cystoscopy or fluorescence cystoscopy.
Under conventional white light, tumours – and especially the flat carcinoma-in-situ (CIS) – can be virtually
invisible and are thus easily missed and/or not removed
completely, as tumour outlines in white light might not
be clearly visible. This fact is responsible for a large
number of tumour recurrences. The use of PDD allows
to limite this problem by enhancing visibility and causing
the tumours to glow a fluorescently bright pink under
the blue light, while the healthy surrounding tissue
appears blue (see Fig. 3).
Treatment
PDD offers doctors the advantage of easy detection
of suspicious regions and provides the best preconditions for adequate cancer management.
The PDD Procedure
One to one-and-a-half hours before the PDD procedure,
the doctor or nurse will instil a solution containing a
drug with fluorescent properties into the bladder. The
drug is preferentially accumulated in rapidly prolifer­
ating cells like the tumour cells.
During the PDD procedure, the bladder is examined in
blue light. The accumulated drug in the tumour cells is
spectrally excited by this blue light and emits a pink
fluorescence. The tumour cells are highlighted pink
and stand out against the normal bladder tissue,
which keeps its blue appearance. Tumours and the
virtually invisible CIS are much easier to identify
white light
PDD
This way, PDD detects bladder cancer that
white light could miss. In studies PDD ...
Ñdetected 30 % more patients with bladder cancer 5
Ñdetected 67 % more CIS lesions6
resulted
in more appropriate treatment in 1 in 5
Ñ
patients with verified bladder tumours7
Fig. 4: Cystoscopic pictures of bladder cancer illustrating the difference
between white light (left) and PDD (right) cystoscopy.
Treatment
by the doctor. Special yellow-light filters in modern
cystoscopes (e.g. from Olympus) enhance the contrast
and emphasise the red fluorescence of the tumours to
allow for clear detection of tumour borders and small
lesions that spread around the primary lesion (= satellite
lesions). Thus tumours can be removed without leaving
any cells behind.
Benefits of PDD
Whilst the procedures for the two kinds of cystoscopy
themselves are almost identical, their results differ
tremendously. Studies have shown that PDD significantly improves the detection of bladder cancer, particularly in the identification of flat CIS.8 With PDD,
tumours can be detected early, easily and more
clearly. Most importantly, this means that the chance
of eliminating all of the tumourous lesions completely
increases significantly. In the final analysis, PDD
improves the prognosis and helps to decrease the
number of recurrences in bladder cancer.9
PDD offers one of the highest standards of diagnosis
and treatment and provides better circumstances for
eliminating all tumourous lesions.
In the Days after the Procedure
Most patients can leave hospital on the day of or after
their PDD procedure. During the following days, some
patients may feel pain or a burning sensation when
urinating or might have an increased urge to urinate. In
Treatment
addition, blood may cause a discolouration of the urine.
These symptoms are no causes for concern. If the discomfort lasts for a longer period though, the patient
should consult a doctor!
However, it is important to understand that the treatment is not completed after the surgical procedure.
Since bladder cancer has a very high recurrence
rate, an intensive follow-up management is necessary.
After treatment, the doctor may be likely to recommend a series of follow-up cystoscopies. This is
done in order to make sure that the cancer does not
return. The frequency of the cystoscopies performed
depends on each patient’s individual history and
should follow the doctor’s guidelines.
FAQs
Is the electrical current used for resecting
tumours dangerous for the patient?
No, it is not dangerous for the patient. The new bipolar
TURis-B technique allows for a very concentrated
current flow. Whilst in older (monopolar) techniques
the current flows from the cystoscope through the
patient’s body to a neutral electrode on the leg, the
current in TURis-B is focussed on a small area since
it is diverted directly by the cystoscope. There is no
current flow through the patient anymore. With the
new method, the tissue and nerves surrounding the
surgical field are not damaged and complications or
burns caused by electrical current are avoided.
Are the benefits of PDD scientifically proven?
Yes, many studies have shown that PDD significantly
improves the detection of bladder cancer and results
in a more adequate resection of the tumours.4, 10, 11
Can PDD also be used for check-ups following
surgery?
Yes, PDD is also recommended for patients undergoing
check-up cystoscopies. The enhanced visibility under
PDD cystoscopy can help to find tumour recurrences.
Is TURis-B associated with bleeding?
The risk of bleeding is small. Due to a smoother cut
with bipolar resection, bleedings are reduced to a
minimum. While cutting the tissue, the electric current
simultaneously coagulates (heat seals) the surface of
the bladder tissue. If patients have any predetermined
condition that indicates a higher risk of bleeding, they
need to inform their doctor in advance.
Glossary
Bladder
A hollow organ in the pelvis that collects urine until it can be
passed out of the body through the urethra.
Cancer
A malignant type of disease characterised by cells that
show uncontrolled growth and have the ability to invade and
destroy other tissues.
Chemotherapy
A type of cancer therapy which uses anticancer drugs to
selectively kill cancer cells.
CIS
(Carcinoma in situ)
A form of superficial bladder cancer. CIS is a flat, barely
detectable tumour that is more aggressive that than other
forms of tumours.
Cystoscopy
A diagnostic procedure used to examine the inner wall of
the bladder. In patients diagnosed with cancer, it can also
be used for therapy.
Endoscopy
Examination of natural body cavities or hollow organs
using natural pathways like the urethra to examine inner
organs.
Immunotherapy
Type of therapy that stimulates the immune system of the
patient to reject and destroy tumour cells.
Invasive bladder cancer
Bladder cancer that has already grown into the muscle layers
of the bladder or beyond to other parts of the body.
Multifocal cancer
Cancer in which there is more than one tumour lesion.
Glossary
Glossary
Olympus
One of the world’s most renowned manufacturers of medical
systems. Olympus has invented a number of groundbreaking
new technologies – including technical equipment and
instruments for cystoscopy.
TURis-B
(Transurethral Resection in saline of the Bladder)
Removal of tissue in the bladder using a resectoscope
(a cystoscope incorporating a cutting device) inserted
through the urethra.
PDD
(Photodynamic Diagnosis; Blue-light or Fluorescence
Cystoscopy)
A modern type of cystoscopy in which a special drug solution
is instilled into the bladder about an hour before the procedure.
The drug selectively accumulates in cancer cells. When
excited by blue light, the cancer glows pink and stands out
against the normal, blue-lit bladder tissue.
Ureter
The long thin tubular passage way of the lower urinary tract
that carries the urine from the kidneys, where it has been produced, to the bladder.
Recurrence
Relapse or reappearance of cancer after a period of remission.
Risk factor
A circumstance that increases the possibility of an occurrence,
like disease.
Superficial bladder cancer
Early-stage bladder cancer where the cancer is limited to
the lining of the bladder and has not grown into deeper layers
of the bladder.
Transurethral
Through the urethra.
Urethra
The thin tubular passage through which urine moves from
the urinary bladder out of the body.
White-light cystoscopy
Standard cystoscopy that uses normal white light to illuminate
areas of the bladder to look for abnormalities.
References
1 Botteman MF et al. Pharmacoeconomics 2003;21(18):1315–30.
Burger M et al. British Journal of Cancer 2007;96:1711–1715.
2 Britannica Concise Encyclopedia: bladder cancer.
3 Alternative Medicine Encyclopedia: Bladder Cancer; Britannica Concise
Encyclopedia: bladder cancer.
4Babjuk M et al., Guidelines on TaT1 (Non-muscle invasive) Bladder
Cancer, European Association of Urology 2009.
5 Jichlinski P et al. J Urol 2003;170:226–9.
Tumour
A mass of tissue arising from abnormal cell growth. If
malig­nant, the tumour will spread to the surrounding tissue
and causes cancer.
6 Schmidbauer J et al. J Urol 2004;171:135–8.
7 Jocham D et al., J Urol 2005;174:862–6.
8 Fradet Y et al. J Urol 2007;178:68–73.
9
Data on file.
10
Kriegmair M et al. J Urol 2002;168:475–8.
11
Denzinger S et al. Urology 2007;69:675–9.