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Oncology :Optical imaging
technologies in bladder cancer and
principles of EMDA
29 March 2015
• Principles of Fluorescent Cystoscopy, Narrow
Band Imaging and Photodynamic Therapy in
Bladder Cancer
• Principles of Electromotive drug
administration therapy, EMDA
Fluorescent cystoscopy
• Small papillary tumours or flat tumours (CIS) could be missed
when examined with white light cystoscopy (WLC)
• Fluorescent cystoscopy or photodynamic diagnosis (PDD) is a
technique combining an intravesical agent with a specific blue
light to improve tumour visualization
• Photosensitizing agents (prodrugs) like 5-aminolevulinic acid (5ALA) and hexyl aminolevulinate (HAL) can be used
• Instilled in bladder about 1 hour prior to cystoscopic examination
• Transported in urothelial cells
• Incorporated into cellular hemobiosynthesis metabolism
Fluorescent cystoscopy
• Significant accumulation of protoporphyrin IX (PpIX) in cancer
cells after instillation of photosensitizers due to abnormal enzyme
• Examined with blue light (wavelength = 375-440nm)
• Tumour appears in red against blue-green background
Fluorescent cystoscopy
• HAL and 5-ALA are generally safe and well-tolerated
• Adverse events related to these agents are <2.4%
• High false positive rates in recent TURBT, BCG instillation
• Might need to delay PDD for 3-4 months after the above events
• Inflammation can also cause false positivity e.g. UTI
Fluorescent cystoscopy
• Detection: sensitivity 76-97% vs WLC 46-80%
• Improves detection of papillary NMIBC and CIS
• Residual tumour: PDD-guided TURBT has more complete
resection, therefore less residual tumour in re-resection
• Recurrence free survival: PDD reduces NMIBC recurrence
• Recurrence free interval: PDD prolongs this parameter vs WLC
• Progression rate: impact of PDD on this is not known
Fluorescent cystoscopy
• PDD should be used in the initial resection
• Also can be used for recurrent cases if it has not be applied in the
initial resection
• NOT recommended for surveillance or office-based procedures
Narrow band imaging
• A relatively new technique to enhance visualization of tumour
• Uses 2 narrow band of lights that are strongly absorbed Hb
• The wavelengths are 415nm and 540nm
• The shorter 415nm light focuses on superficial layer (mucosa)
• The longer 540nm light makes deeper capillary network clearer
Narrow band imaging
Narrow band imaging
• The results show that NBI cystoscopy significantly improves the
detection accuracy in bladder cancer, compared with white light
imaging. However, some limitations still exist.
• Multicentre randomized studies are recommended to determine
whether the visual advantages of NBI can translate into real
therapeutic benefit for individual patients.
Photodynamic therapy
• Photosensitizer (PS) + Light = Photodynamic reaction (PDR)
• PS agent transfer light energy and causes photochemical reaction
• Like chorophyll’s role in photosynthesis in plants
• Examples of PS agents: hematoporphyrin derivatives (Photofrin),
M-tetrahydroxophenyl chlorine (Foscan), ALA
• Each PS agent has unique light wavelength and intensity for
successful activation
• Basis of PDT for clinical use is production of singlet oxygen
• Half life of singlet oxygen = 40nanosec, radius of destruction =
Photodynamic therapy
• PDT mechanisms
– Necrosis of tumour, or induce apoptosis
– Vascular cell lysis, disrupt vascular cell wall
– Tumour and vascular necrosis causes immune response
• PDT for bladder cancer
– AUA 2007: Enthusiasm for its use is tempered by its side
effects including skin photosensitivity similar to that in patients
with porphyria.
– In addition, local symptoms including irritating voiding
symptoms, notable tissue sloughing, bladder contracture, and
reflux have also been reported. Photodynamic therapy is not
readily available in the United States.
Photodynamic therapy
• PDT was proposed as a second-line treatment for patients with
multiple comorbidities, who are not surgical candidates.
• ALA PDT given as a single treatment, or in combination with
mitomycin C, resulted in complete response rates of 40%–52% at
18–24 months without persistent reduction in bladder capacity.
• EAU 2015: did not mention PDT for bladder cancer
Electromotive drug modulation
• Principles
– EMDA uses an electrical current to deliver the drugs into the
wall of the bladder
– It is also known as iontophoresis. Ionophoretic enhancement
of drug treatment occurs within the first 10 – 15 mins
– It aims to get more of the drug into the cells of the bladder
wall, to further reduce the risk of the cancer recurrence of high
grade superficial tumours
Electromotive drug modulation
• Active electrode-receptacle containing the drug solution that
is applied to the site of pathology, and a dispersive (ground)
electrode placed on a convenient area of unblemished skin
• The current source was the battery powered (12 V)
Physionizer 30 (Physion s.r.l., Mirandola, Italy)
• The bladder wall comprises both the drug receptacle and the
target area for the drug.
• The electrode consists of a stainless steel wire, insulated for
most of its length and terminating in uninsulated silvercoated spiral (CE-DAS, Urogenics 9301 AG).
Electromotive drug modulation
• The electrode is inserted into a bladder catheter so that the
end of the spiral is flush against the tip of the catheter
• The dispersive electrode (Physion s.r.1.) comprises two
layers of isolating foam with a wire grid in between
• A thin layer of gel is applied on a selected area of the skin
and two dispersive electrodes are soaked with saline and
then laid on the gel. The arrangement ensures even
distribution of current through the large surface area (2 X 50
cm’) of the skin electrodes and thus reduces the risk of
electrical skin damage
Electromotive drug modulation
• The catheter containing the electrode is inserted into the bladder,
which is drained and then lavaged and drained again to remove
residual urinary electrolytes. The electric current is ramped to 15
mA and maintained at this level for 20 minutes
• After the procedure, the bladder is drained and the patient
Electromotive drug modulation
Published August
• EMDA is superior to intravesical passive diffusion in delivering
drugs through the urothelium to the deeper layers of the bladder
• Electric current significantly increases the transport of
mitomycin- C
Thank you