Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Oncology :Optical imaging technologies in bladder cancer and principles of EMDA Arun 29 March 2015 Topics • 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 activity • 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 = 20nm 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 discharged. Electromotive drug modulation Published August 2006 • 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