Which is best method for instillation of topical therapy to the upper urinary tract? An in vivo porcine study to evaluate three delivery methods

ABSTRACT Purpose: To compare the staining intensity of the upper urinary tract (UUT) urothelium among three UUT delivery methods in an in vivo porcine model. Materials and methods: A fluorescent dye solution (indigo carmine) was delivered to the UUT via three different methods: antegrade perfusion, vesico-ureteral reflux via in-dwelling ureteric stent and retrograde perfusion via a 5F open-ended ureteral catheter. Twelve renal units were tested with 4 in each method. After a 2-hour delivery time, the renal-ureter units were harvested en bloc. Time from harvesting to analysis was also standardised to be 2 hours in each arm. Three urothelium samples of the same weight and size were taken from each of the 6 pre-defined points (upper pole, mid pole, lower pole, renal pelvis, mid ureter and distal ureter) and the amount of fluorescence was measured with a spectrometer. Results: The mean fluorescence detected at all 6 predefined points of the UUT urothelium was the highest for the retrograde method. This was statistically significant with p-value less than <0.05 at all 6 points. Conclusions: Retrograde infusion of UUT by an open ended ureteral catheter resulted in highest mean fluorescence detected at all 6 pre-defined points of the UUT urothelium compared to antegrade infusion and vesico-ureteral reflux via indwelling ureteric stents indicating retrograde method ideal for topical therapy throughout the UUT urothelium. More clinical studies are needed to demonstrate if retrograde method could lead to better clinical outcomes compared to the other two methods.

摘要
研究目的：在活体猪模型中比较三种上尿路（upper urinary tract, UUT）递送方式的上尿路尿路上皮染色强度。
材料与方法：采用三种不同方式将荧光染料溶液（靛胭脂，indigo carmine）递送至上尿路：顺行灌注、经留置输尿管支架的膀胱输尿管反流、以及经5F开放式输尿管导管的逆行灌注。共测试12个肾单位，每种方法下设4个样本。递送时长2小时后，整块获取肾-输尿管单位。各组中从获取样本至分析的时长均统一为2小时。从6个预设点位（肾上极、肾中极、肾下极、肾盂、输尿管中段及输尿管远端）各取3份重量与尺寸一致的尿路上皮样本，使用光谱仪测量荧光强度。
结果：在上尿路尿路上皮全部6个预设点位中，逆行灌注方法检测到的平均荧光强度最高，且所有6个点位的p值均小于0.05，差异具有统计学意义。
结论：与顺行灌注及经留置输尿管支架的膀胱输尿管反流方式相比，经开放式输尿管导管逆行灌注上尿路可在上尿路尿路上皮全部6个预设点位检测到最高平均荧光强度，提示逆行灌注方法适用于全上尿路尿路上皮的局部治疗。未来仍需开展更多临床研究，以验证逆行灌注方式是否较另外两种方法可获得更优的临床结局。