Pope, Alvan John; (1993) Laser treatment of bladder cancer. Doctoral thesis (M.D), UCL (University College London).

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Abstract

Lasers techniques are able to produce precise and sometimes unique tissue effects. These promise an improvement over the conventional techniques for treating both superficial and early muscle invasive bladder cancer. Photodynamic Therapy (PDT) is an experimental treatment that shows great promise for treating superficial bladder cancer, especially resistant carcinoma in situ (Cis). Some clinical studies though have reported serious side effects, mainly in producing an irreversible functional impairment in many bladders due to fibrosis. This thesis presents a study of the effect of changes in dosimetry variables on the normal rat bladder using a new photosensitiser, aluminium chlorosulphonated phthalocyanine. The uptake of this drug into the different layers of the bladder wall has also been investigated using sensitive fluorescence microscopy techniques. The maximum concentration gradient of photosensitiser between the superficial and the deep layers of the bladder wall was reached after 24 h following administration and was increased by the photobleaching observed at low sensitiser concentrations. Morphological and functional changes (bladder capacity and compliance) were also studied and it was found that if PDT damage was restricted to the superficial layers of the bladder, the resulting functional disturbance was less severe and recovered more fully than when the muscle layers were also involved. At low concentrations of photo-sensitiser a selective, superficial necrosis was achieved across a wide range of light doses. If these experimental results can be achieved in clinical practice then PDT should provide an effective and bladder preserving treatment for Cis without the complications that have been seen previously. The possible role of the flashlamp pulsed-dye laser for PDT was studied using cultured human bladder carcinoma cells (MGH-U1) sensitised with dihaematoporphyrin ether. It was found that this clinical laser was of a comparable efficacy to the more complex systems currently used for PDT. The morphology of the coagulation produced by the neodymium:YAG laser on the pig bladder has been compared with conventional electrocautery. A marked qualitative difference was seen between these two modalities in that the laser produced a more even coagulation with little disruption of the tissue architecture. A major attraction for urologists is that, in conjunction with flexible cystoscopy, superficial bladder tumours may be laser coagulated on an outpatient basis using only topical urethral anaesthesia. A study of 33 patients with recurrent tumours treated in this way shows the convenience and economy of this technique though no reduction in the incidence of recurrences was seen after laser therapy.

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