Ureteroscopic Cryoablation for Patients with Upper Tract Urothelial Carcinoma of a Solitary Kidney: A Porcine Model and Our Pilot Clinical Experience

Abstract

Purpose To investigate the safety and efficacy of ureteroscopic cryoablation by a liquid-nitrogen system in a porcine model and for patients with upper tract urothelial carcinoma (UTUC) of a solitary kidney. Methods In the animal experiment, the right-sided ureter was frozen in nine pigs. Eight were randomly assigned to two different groups according to the freezing duration of 60 or 90 s. The other one was designed to receive a 10-min freeze. The treated ureters were harvested at 30 min, 2 days, 4 weeks, and 3 months after cryoablation for histological evaluation. After the animal study, we conducted a pilot clinical trial that enrolled six patients who were diagnosed with UTUC of a solitary kidney and received therapeutic management with ureteroscopic cryoablation at our center. Perioperative adverse events and oncological outcomes were evaluated. Results In the porcine model, the liquid-nitrogen system was capable of forming a therapeutic ice ball which infiltrated the full-thickness ureter and induced apoptosis and necrosis from mucosa to lamina muscularis through histological examination. In the clinical trial, cryoablation was successfully performed under ureteroscopy in all the patients, without intraoperative ureteral perforation, avulsion, or active hemorrhage. No recurrence in situ was observed during a median follow-up period of 12.5 months. Hydronephrosis and ureteral stricture was observed in one patient and was managed with ureteroscopic balloon dilation. Conclusions Ureteroscopic cryoablation induced by liquid nitrogen is a promising technique for conservative management of UTUC with benefits of improving local tumor control and preservation of a solitary kidney.

Cryoablation inhibits the recurrence and progression of bladder cancer by enhancing tumour‐specific immunity

“… 33 In our previous studies, we confirmed the safety of EBCA in the bladder in beagle and porcine models. 15 , 34 The EBCA‐TUR study was the first multicentre randomised clinical trial to evaluate endoscopic cryoablation in patients with bladder cancer. In addition, we conducted a pioneer study of ureteroscopic cryoablation in patients with upper tract urothelial carcinoma of a solitary kidney as the first worldwide attempt to use cryotherapy as a kidney‐sparing strategy.…”

“…The feasibility and safety of EBCA have been confirmed in animal models and clinical trials. 15 , 16 Herein, we retrospectively analysed the prognosis of patients with bladder cancer who underwent cryoablation and compared it with that of patients who underwent transurethral resection of bladder tumour (TURBT). We present the first intensive investigation comparing the changes in peripheral blood lymphocyte subsets before and after cryoablation to reveal systemic immunomodulatory activities in patients with bladder cancer.…”

The role of endoscopic management and adjuvant topical therapy for upper tract urothelial cancer

“…This process involves application of a liquid nitrogen probe on the residual tumor site, leading to formation of an ice ball and induction of necrosis/apoptosis from mucosa to lamina muscularis. This procedure shows early promise as an additional management technique to reduce r e c u r r e n c e f o l l o w i n g p r i m a r y l a s e r -b a s e d t u m o r destruction (67).…”

Endoscopic balloon cryoablation plus transurethral resection for bladder cancer: A phase 2, multicenter, randomized, controlled trial

“…Percutaneous cryoablation has been widely used to treat malignancies in solid organs, such as the liver, kidney, and prostate. In terms of intraluminal tumors, endoscopic cryoablation has been introduced in recent years 7 . Only a few clinical trials have reported application of endoscopic cryoablation for precancerous gastrointestinal lesions and neoplasms, most of which were single‐arm or retrospective studies 8–11 .…”

“…In terms of intraluminal tumors, endoscopic cryoablation has been introduced in recent years. 7 Only a few clinical trials have reported application of endoscopic cryoablation for precancerous gastrointestinal lesions and neoplasms, most of which were single-arm or retrospective studies. [8][9][10][11] The inspiration for endoscopic balloon cryoablation (EBCA) was derived from the FIRE AND ICE study, which compared cryoballoon with radiofrequency ablation in paroxysmal atrial fibrillation.…”