Photodynamic diagnostic cystoscopy
Ashoke Roy, Department of Uro-Oncology, University College London Hospital, 250 Euston Road, London, UK. e-mail: firstname.lastname@example.org
carcinoma in situ
Detection of small or multifocal bladder tumours or carcinoma in situ (CIS) can be difficult with traditional white-light rigid cystoscopy. The use of photodynamics is increasing both in bladder cancer diagnosis and in surveillance. This involves instillation of a synthetic porphyrin via a urethral catheter to improve diagnostic assessment of the bladder urothelium.
Photodynamic diagnosis (PDD) rigid cystoscopy is useful as a primary diagnostic tool for newly diagnosed bladder tumours and in situations where urine cytology is positive but no exophytic lesion is seen on diagnostic white-light cystoscopy, raising the possibility of CIS. Additionally, it is helpful in patients undergoing bladder surveillance, including those who have had intravesical therapy, where suspected recurrence is noted on flexible cystoscopy.
- • Hexaminolevulinate hydrochloride (HEXVIX Photocure ASA Hoffsveien Oslo Norway) is a hexyl ester of 5-aminolevulinic acid and is the only licensed product available for PDD cystoscopy. The HEXVIX solution is made up with 50 mL normal saline according to the manufacturer's instructions. This is instilled into the bladder via the catheter for ≥ 1 h preoperatively. Starvation before general anaesthetic ensures minimal urinary contamination of the product. The drug is rapidly taken up into the cytoplasm of transitional (urothelial) cells where it is harmlessly metabolised to haem. However, TCC cells and CIS accumulate protoporphyrin IX, which under exposure to intense blue light will fluoresce a vivid red compared with benign urothelium which remains blue or purple.
- • There is a specialised fluid light-lead that connects the PDD light source to the 30 ° Hopkins rod blue-light cystoscope (which has in-built yellow optical filters to allow detection of fluorescence). The camera back is capped to prevent excessive back light interference. A standard high definition video screen is used in conjunction with the PDD equipment. The camera head control has two buttons that allow toggling between white- and blue-light modes and adjustment of the light gain. The camera shutter speed should be adjusted to between 1/15 s to 1/30 s. This can give rise to a perception of delay between the image capture through the cystoscope and display on the screen, particularly noticed in blue-light mode.
Our institution uses a Karl Storz (Tutlingen, Germany) Photodynamic D Light C. However, other manufacturers provide similar units.
A standard white-light cystoscopy is performed and the bladder emptied of lubricating gel, urine and HEXVIX (which can alter the fluorescence under blue light). The bladder should be filled with irrigating fluid and with the cystoscope held at the bladder neck, the light source switched to blue. Circumferential fluorescence at the bladder neck indicates a positive control, i.e. the HEXVIX product has been instilled and there is a response in the urothelium to blue light.
A systematic examination of the bladder should be completed under white- and then blue-light conditions. This should be done with the bladder relatively full and the cystoscope held close to and perpendicular to the urothelium. Any abnormal or indeterminate areas identified initially under white light should be reviewed under blue light whilst holding the abnormality in view. This will identify whether the abnormality fluoresces red, thereby confirming suspicion for TCC/CIS (Fig. 1). Fluorescent areas under blue light that appear normal under white light suggest the possibility of occult CIS or tumour, and therefore the need for targeted biopsy and histological assessment.
a) Tumour under white light. b) Tumour confirmed under blue light.
Biopsy or resection should then be performed under white light (after having also examined the area under blue light) as the image capture delay and lower light levels in blue light mode make resection in particular relatively difficult. After resection or ablation of tumour, switching back to blue-light mode ensures that clearance includes any margin of fluorescence that may extend beyond the white-light abnormality (Fig. 2). Sources of bleeding can be difficult to see under blue light.
a) Resection completed under white light. b) Residual disease at the tumour margin fluoresces red under blue light.
TIPS, TRICKS AND POTENTIAL PITFALLS
The image is too dark!
- • Ensure the bulb is <400 h old and the light lead, cystoscope and connections are performing adequately.
- • The light intensity should be kept at 100% and light gain should be increased to maximum.
- • The bladder may be too full or the cystoscope is too far from the urothelium being examined.
- • Excessive bleeding may absorb light and result in reduced picture quality, therefore attention should be paid to haemostasis under white light before reverting back to blue-light cystoscopy.
- • The fluorescence effect tends to wane after 10–15 min.
The bladder is too bright!
- • Urothelium viewed at an obtuse angle will appear to fluoresce brightly due to a tangential effect, ensure that the cystoscope is held close and perpendicular to the mucosa.
- • The same tangential effect can be seen on trabeculations and at the edges of diverticulae.
- • The trigone, being a common site for low-grade inflammatory change often fluoresces without malignant pathology.
- • After intravesical BCG immunotherapy or widespread inflammatory change within the bladder under white light can appear as multifocal areas of lower intensity fluorescence (often pink rather than red).
- • Switch between white and blue light while taking a biopsy to ensure that the sample of interest is taken in the biopsy forceps.
- • Areas that appear abnormal under blue light alone should be sent as separate specimens as this will distinguish true positives from false positives, and inform experience with the technique and the utility of future PDD cystoscopy.
- • Where field biopsies are deemed necessary, these can be directed by fluorescence in addition to a standard bladder map.
- • A combination of training and accumulative experience is needed to differentiate positive fluorescence from non-specific or tangential effects and to achieve optimal advantage of PDD cystoscopy.
Manit Arya is funded by Orchid (male cancer charity based in the UK).