Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
Center of Comparative Medicine and Pathology, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Urology, New York Presbyterian Hospital, New York, New York; Weill-Cornell Medical College, New York Presbyterian Hospital, New York, New York; New York Presbyterian Hospital, New York, New York; Rockefeller University, New York, New York.
J Urol. 2016 Jul;196(1):236-43. doi: 10.1016/j.juro.2016.01.107. Epub 2016 Feb 6.
Surgical management of upper tract urothelial carcinoma requires kidney and ureter removal, compromising renal function. Nonsurgical alternatives have potentially prohibitive safety concerns. We examined the feasibility and safety of ablation of the ureter and renal pelvis using endoluminal vascular targeted photodynamic therapy in a porcine model. We also report the efficacy of WST11 vascular targeted photodynamic therapy in a murine model.
After receiving approval we performed a total of 28 endoluminal ablations in the ureters and renal pelvis of 18 swine. Intravenous infusion of WST11 (4 mg/kg) followed by 10-minute laser illumination was done via percutaneous access or a retrograde ureteroscopic approach. Animals were followed clinically with laboratory testing, imaging and histology, which were evaluated at several postablation time points. A murine xenograft was created with the 5637 human urothelial cell carcinoma line to determine sensitivity to this therapy.
At 24 hours 50 mW/cm laser fluence produced superficial necrosis of the ureter. Deeper necrosis penetrating the muscularis propria or adventitia was produced by treatment with 200 mW/cm in the ureter and the renal pelvis. At 4 weeks superficial urothelium had regenerated over the treatment site. No symptomatic obstruction, clinically relevant hydronephrosis or abnormality of laboratory testing was noted up to 4 weeks. Of the mice 80% had no evidence of tumor 19 days after WST11 vascular targeted photodynamic therapy.
Urothelial cell carcinoma appears to be sensitive to WST11 vascular targeted photodynamic therapy. The depth of WST11 vascular targeted photodynamic therapy treatment effects can be modulated in a dose dependent manner by titrating light intensity. Moreover, when applied to the porcine upper urinary tract, this treatment modality is feasible via antegrade and retrograde access.
上尿路尿路上皮癌的外科治疗需要切除肾脏和输尿管，从而影响肾功能。非手术替代方案存在潜在的安全问题。我们在猪模型中检查了经腔内血管靶向光动力疗法消融输尿管和肾盂的可行性和安全性。我们还报告了 WST11 血管靶向光动力疗法在小鼠模型中的疗效。
在获得批准后，我们共对 18 头猪的输尿管和肾盂进行了 28 次腔内消融。通过经皮或逆行输尿管镜途径，静脉内输注 WST11（4mg/kg），然后进行 10 分钟的激光照射。通过临床检查、实验室检查、影像学检查和组织学检查对动物进行了随访，在多个消融后时间点进行了评估。使用 5637 人尿路上皮癌细胞系建立了小鼠异种移植模型，以确定对这种治疗的敏感性。
在 24 小时时，50mW/cm 激光强度产生了输尿管的表浅坏死。在输尿管和肾盂中用 200mW/cm 处理时，会产生穿透肌层或外膜的更深的坏死。在 4 周时，治疗部位的表面尿路上皮已经再生。在 4 周内，没有出现症状性梗阻、明显的肾积水或实验室检查异常。在 WST11 血管靶向光动力疗法后 19 天，80%的小鼠没有肿瘤的证据。
尿路上皮癌似乎对 WST11 血管靶向光动力疗法敏感。通过调整光强度，可以以剂量依赖性方式调节 WST11 血管靶向光动力疗法治疗效果的深度。此外，当应用于猪的上尿路时，这种治疗方法通过顺行和逆行途径是可行的。
