Shackley D C, Briggs C, Gilhooley A, Whitehurst C, O'Flynn K J, Betts C D, Moore J V, Clarke N W
Department of Urology, Hope Hospital, Salford Royal Hospitals Trust, Salford, UK.
BJU Int. 2002 May;89(7):665-70. doi: 10.1046/j.1464-410x.2002.02743.x.
To evaluate the use of local anaesthesia (LA) in 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) for superficial transitional cell carcinoma (TCC) of the bladder, and to provide further toxicity and tolerability data on this new method within the context of a phase 1 trial.
ALA PDT was administered to 19 patients with recurrent superficial TCC (stage Ta/carcinoma in situ, grades 1-3) using escalating doses of ALA (3-6%) and 633 nm laser light (25-50 J/cm2) under various LA (lignocaine) protocols. Pain was assessed using a linear analogue scale from 0 to 10. The endpoints of tolerability and toxicity were assessed for the different LA, light and ALA doses, with lignocaine levels.
ALA PDT is painful and requires some form of anaesthesia. The discomfort was immediate, associated with bladder spasm, and was a function of the ALA concentration rather than the total light dose given. Simple passive diffusion (PD) of 2% lignocaine instilled for 40 min before PDT gave adequate anaesthesia with 3% ALA (n=8; median pain score 1, range 0-2). With 6% ALA the pain was dramatically increased using PD (n=6; median pain score 8, range 5-10) and therefore the more potent LA technique of electromotive drug administration (EMDA) of 2% lignocaine was used, with excellent results (n=3; median pain score 1, range 0-2). All patients had transient bladder irritability that typically lasted 9-12 days, with no subjective/objective change in long-term bladder function. No other toxicity was reported. Serum lignocaine levels were minimal.
Bladder ALA PDT is both safe and feasible under LA. At a dose of 3% ALA, the procedure was well-tolerated using PD of lignocaine. At higher doses (6% ALA) more effective anaesthesia is required and this can be obtained satisfactorily with EMDA of lignocaine. With refinement, ALA PDT may be feasible as an outpatient treatment for superficial bladder TCC.
评估局部麻醉（LA）在5-氨基酮戊酸（ALA）光动力疗法（PDT）治疗膀胱浅表性移行细胞癌（TCC）中的应用，并在1期试验的背景下提供关于这种新方法的进一步毒性和耐受性数据。
对19例复发性浅表性TCC（Ta期/原位癌，1-3级）患者采用递增剂量的ALA（3%-6%）和633nm激光（25-50J/cm²），在不同的LA（利多卡因）方案下进行ALA PDT治疗。使用0至10的线性模拟量表评估疼痛程度。根据不同的LA、光照和ALA剂量以及利多卡因水平评估耐受性和毒性终点。
ALA PDT会引起疼痛，需要某种形式的麻醉。不适是即时的，与膀胱痉挛有关，并且是ALA浓度的函数，而不是所给予的总光剂量的函数。在PDT前40分钟滴注2%利多卡因进行简单的被动扩散（PD），对于3%的ALA可提供充分的麻醉（n=8；中位疼痛评分1，范围0-2）。对于6%的ALA，使用PD时疼痛显著增加（n=6；中位疼痛评分8，范围5-10），因此采用了更有效的2%利多卡因电动药物给药（EMDA）LA技术，效果良好（n=3；中位疼痛评分1，范围0-2）。所有患者均有短暂的膀胱刺激症状，通常持续9-12天，长期膀胱功能无主观/客观变化。未报告其他毒性。血清利多卡因水平极低。
在LA下，膀胱ALA PDT既安全又可行。在3%ALA的剂量下，使用利多卡因的PD该操作耐受性良好。在更高剂量（6%ALA）时，需要更有效的麻醉，而利多卡因的EMDA可以令人满意地实现这一点。随着技术的改进，ALA PDT作为浅表性膀胱TCC的门诊治疗可能是可行的。
