Failure of endoscopic management of ureteral strictures is due to ureteroscopic lithotripsy as a cause and longer length of stricture


 Background

Ureteroscopic lithotripsy is a common treatment for middle and lower ureteral stones. Although effective and minimally invasive, this technique might cause significant complications, including postoperative ureteral strictures, which occur in 1–4% of patients after ordinary ureteroscopic lithotripsy and in 7.8–24% when lithotripsy is performed for impacted stones. The main purpose of the management of ureteral strictures is to improve hydronephrosis and protect renal function. However, factors that influence the success rate of the endoscopic management of US (e.g., the cause and length of stricture, the duration of hydronephrosis, surgical management technique, and the number of placed ureteral stents) are controversial. The aim of this study was to investigate factors determining the outcomes of endoscopic management for stone-related ureteral stricture.
Methods

This multi-center case series study was performed at one of the highest-volume centers and the affiliated institutions in Japan. Data of patients who underwent endoscopic surgery for ureteral stricture from January 2016 to March 2019 were retrospectively analyzed. Laser incision and/or balloon dilation were performed for management; single or double stents were placed at the end of the surgery. Treatment success was defined as improvement in hydronephrosis status.
Results

Nineteen patients were treated for stone-related ureteral stricture. Hydronephrosis successfully improved in 12 patients (63.2%). All seven patients with failed endoscopic management had ureteroscopic lithotripsy-related stricture, whereas 3/12 (25.0%) and 7/12 (58.3%) patients with ureteroscopic lithotripsy-related stricture and impacted stone-related stricture, respectively, underwent successful endoscopic treatment (P = 0.004). Stricture length > 15 mm was observed in five patients (71.4%) with failed management, two patients (16.6%) with successful management (P = 0.046), 7/10 patients (70.0%) with ureteroscopic lithotripsy-related stricture, and 1/7 patients (14.3%) with impacted stone-related stricture (P = 0.049). Among patients with ureteroscopic lithotripsy-related stricture and impacted stone-related stricture, both laser incision and balloon dilation were performed in 5/10 (50.0%) and 2/7 (28.6%) patients (P = 0.874) while double stents were placed in 5/10 (50.0%) and 5/7 (57.1%) patients (P = 0.874), respectively.
Conclusions

Ureteroscopic lithotripsy as a cause and stricture length > 15 mm could strongly affect the success rate of endoscopic management of ureteral stricture. In such cases, reconstructive management should be considered in the early stages.


Conclusions
Ureteroscopic lithotripsy as a cause and stricture length > 15 mm could strongly affect the success rate of endoscopic management of ureteral stricture. In such cases, reconstructive management should be considered in the early stages.

Background
In recent years, the prevalence of ureteral stones has been consistently increasing in the world due to the effects of the increasing incidence of obesity and changes in dietary habits. 1,2 Ureteroscopic lithotripsy (URSL) has become a common treatment for middle and lower ureteral stones. 3,4 Although it is effective and minimally invasive, it could cause signi cant complications such as intraoperative ureteral injury, bleeding, infection, and postoperative ureteral strictures (US). 5 US is reported to occur in 1-4% of patients after ordinary URSL; however, it occurs in 7.8-24% of patients when URSL is performed for impacted stones. 6,7,8 Moreover, there are non-iatrogenic ureteric strictures such as those associated with impacted stones or chronic in ammatory disorders. 9,10 The main purpose of the management of US is to improve hydronephrosis and protect renal function. 11 Recently, a wide variety of therapeutic options has become available to urologists, such as endoscopic management and open/laparoscopic/robot assisted reconstruction. Laser incision (LI) and balloon dilation (BD) as endoscopic management techniques for benign US has been described in previous reports; Razdan et al. reported that these techniques had a success rate of 74% of 50 patients. 9 Further, May et al. reported that 27.5% of 40 patients were successfully managed with endoscopic techniques. 12 The factors that in uence the success rate of the endoscopic management of US (e.g., the cause and length of stricture, the duration of hydronephrosis, surgical management technique, and the number of placed ureteral stents) are controversial.
To identify the factors associated with the successful endoscopic management of US, we retrospectively investigated 19 patients who underwent endoscopic management for benign US related to ureteral stones and/or their treatments.

Patients
The present study was approved by the Institutional Review Board of Nagoya City University Hospital. All patients provided informed consent for the use of their data.
Patients diagnosed with benign US between January 2016 and April 2020 were analyzed. These patients underwent LI and/or BD management and one or two ureteral stents or nephrostomy catheter were placed at the end of the surgery at Nagoya City University Hospital and two a liated institutions. Patients with a solitary kidney, urinary diversion, poorly controlled diabetes, and those who were pregnant were excluded from this study. We obtained patients' demographics, such as sex, age, and BMI from the medical records. Additionally, the laterality, location, cause, and length of the US as well as the status of hydronephrosis were also captured. The US related to URSL was de ned as follows: US without stone impaction, which was related to damage caused by the laser or access sheath during URSL. US related to an impacted stone was de ned as follows: US with stone impaction which was observed during prior URSL.

Surgical techniques
All patients were placed under general anesthesia, and the operation was performed in the lithotomy position. Before treatment, the status of the stricture was con rmed using retrograde ureteropyelography. A semi-rigid ureteroscope (Olympus, Tokyo, Japan) was inserted and used to observe the stricture site.
Then, we inserted a 0.035-inch guide wire through the stricture site. As the LI procedure, we cut the mucosa and muscular layer of the stricture site using a 200 µm ber (Cyber Ho, Quanta system, Milan, Italy), including 5 mm before and after, until we could visualize the fat tissue outside of the ureter. The energy setting was 60 W and the incision was conducted using the 'Soft Tissues' mode. For the BD, we dilated the ureteral lumen up to 15 Fr using a balloon catheter (URO MAX Ultra™; Boston Scienti c Japan, Tokyo, Japan). One or two double-J ureteral stents

Statistical analysis
Non-normally distributed variables are expressed as medians (25%, 75% interquartile range). Categorical variables are presented as frequencies (percentages). Data were analyzed using EZR for R (R project 3.6.3). 13 To compare the patients with failed or successful management and the factors associated with the cause of US, Fisher's exact test and Mann-Whitney U tests were used. To compare preoperative and postoperative renal function, the Wilcoxon signed-rank test was used. P-values < 0.05 were de ned as statistically signi cant.

Results
A total of 19 patients were identi ed as having undergone endoscopic treatment for US. The characteristics of the patients are summarized in Table 1. The stricture cause was identi ed as URSL in 10 patients (52.6%), impacted stone in 7 patients (36.8%), and chronic in ammatory disorders in 2 patients (10.5%). The median length of the stricture was 10 mm, and the median duration of hydronephrosis before surgery was 4.0 months. Preoperative hydronephrosis was Grade 1 in 3 patients (15.8%), Grade 2 in 5 patients (26.3%), Grade 3 in 5 patients (26.3%) and Grade 4 in 6 patients (31.6%). Prestenting before surgery was performed in 5 patients (26.3%).   3 shows the data classi ed as failure or success of the treatment. URSL-related US occurred in 7 and 3 patients in the failure and success groups, respectively (P = 0.004). Contrarily, all seven patients with impacted stone-related US were successfully treated with endoscopic management. Five patients (71.4%) had a US longer than 15 mm in the failure group, whereas two patients (16.6%) had a US longer than 15 mm in the success group (P = 0.045). In all ve patients who underwent presenting, endoscopic management was successful. The median duration of hydronephrosis before surgery was 5    Renal function is shown in Table 5. The median preoperative and postoperative Creatinine (Cre) levels were 0.90 and 0.86, respectively, and the median estimated glomerular ltration rates (eGFRs) were 60.6 and 60.9, respectively. In the patients with failed endoscopic management, the median preoperative and postoperative Cre were 0.89 and 0.82, while the median eGFRs were 62.1 and 65.2, respectively. In the patients with successful endoscopic management, the median preoperative and postoperative Cre were 0.96 and 0.98, while the median eGFRs were 55.7 and 50.9, respectively. The difference in the data reported in Table 5 are not signi cant.

Discussion
The development and innovation of endourologic tools has enabled urologists to choose endoscopic management techniques, such as endoureterotomy and endoscopic dilation, for patients with US. 14 These techniques are safer and less invasive than open surgical repair; however, success rates vary widely between reports. 9, 15 We would investigate the factors which in uence the success rate of the management for US.
Intraoperative ureteral damage during URSL is one of the causes of US. 6 US caused by ureteral damage is associated with ischemic changes, which results in lower success rates following treatment for US 7 . On the other hand, it is reported that stones embedded in the ureteral mucosa stimulate in ammation, which might result in US. 16 US caused by stones embedded in the ureteral wall does not always involve ischemic changes; therefore, it is likely to be curable with additional treatment. 11 Netto et al. reported that the success rates of BD for non-ischemic and ischemic US were 89% and 29%, respectively. 17 In the current study, 52.6% of the USs were related to URSL; the success rate of the management for URSLrelated US was signi cantly lower compared to that of the management for impacted stone-related US (P = 0.01). The US length was signi cantly longer in the patients with URSL-related US. The ischemic changes in the ureteral wall caused by laser lithotripsy may be associated with the development of a longer stricture. Together, these data suggest that to treat URSL-related US with endoscopic management is challenging.
US length is thought to be an important predictor of the outcome after endoscopic management for US in several reports. Netto et al. reported a lower success rate for the management of USs longer than 10 mm. 17 Thomas et al. reported a poorer outcome of BD for USs longer than 15 mm. 18 Meretyk et al. reported that the 20 mm in length was the most reliable predictor of success rate of LI. 15 The current study demonstrated that more than 70% of patients failed with endoscopic treatment had a US longer than 15 mm. Consistent with previous reports, our study revealed that a length of 15 mm was likely to be an important factor to affect success rate of endoscopic treatment, even if the combination of LI and BD, as well as double stenting were utilized as novel techniques.
Prior studies report that the duration of the US is associated with the success rate for endoscopic management. Byun et al. reported that the duration of US (shorter or longer than 3 months) was an important factor which affected the success rate. 19 On the other hand, Wolf et al. reported that the duration of the US did not signi cantly affect the success rate of US treatment. 20 In the current study, the median duration of hydronephrosis before surgery was not signi cantly different between the patients with endoscopic treatment failure and success.
The success rate of LI using a holmium YAG laser was reported to be 67-68.4%. 21,22 Moreover, previous reports demonstrated that the success rate of BD for US was 50-76%. 23,24 A Holmium YAG laser with both cutting and coagulating functions provides precise incision to a depth of the fat tissue outside of the ureter with effective hemostatic effect. 25 However, the laser incision or placement of a ureteral stent do not always su ciently expand the lumen; therefore, we believe that the combination of LI and BD enables the equally centered expansion of the lumen on the incision line, which prevents restenosis. The current study showed that 57% patients underwent both LI and BD in the failure group; whereas one third of the patients underwent both procedures in the success group. There were no signi cant differences in the management between the patients with success or failure. However, the median length of US in the patients treated by both LI and BD in the success group of endoscopic management tended to be longer than that in the patients treated by both LI and BD in the failure group, although there was no signi cant difference. Thus, US length might affect the success rate of the combination of LI and BD as well.
Ureteral stents are preoperatively used for avoiding infection and kidney failure before the management of urolithiasis. They dilate the ureteral lumen and straighten the ureter, which makes it easy to insert a ureteroscope or ureteral access sheath. 26 For these reasons, prestenting would also elevate the success rate of endoscopic management for US. In our study, all ve patients with prestenting had successful endoscopic management.
The placement of two ureteral stents was rst reported in cases of malignant obstruction. 27 The authors suggested that two stents have more power to stand up to the comprehensive force of the tumor than one thick stent. The use of two ureteral stents has been applied for the management of benign US. 9,28,29 Some urologists prefer to insert as large of a ureteral stent as possible; however, larger stents cause ischemia of the ureter, which tend to develop restenosis. 29 It is reported that two stents slide each other via peristalsis of the ureter, which maintain the expanded lumen. 30 This motion may prevent ischemia or pressure necrosis of the ureter, which is believed to result in a better success rate. We found no statistical differences in treatment success rates between the patients with single and double stents. However, the median length of the US in patients in the success group who underwent double stent placement tended to be longer than in patients with double stents in the failure group, though there was no signi cant difference. Thus, the length of the US might affect the success rate.
Our study is limited by its relatively small number of patients. Moreover, it is di cult to assess which factor is most important for the success rate because we conducted different treatments for each patient.
Furthermore, given that identifying the beginning of US development was di cult without close monitoring, we may not have been able to provide an accurate estimate of the US duration. Despite these limitations, we believe that our study ndings are useful for improving the management of treatment for stone-related US.

Conclusions
In conclusion, we investigated the outcomes of endoscopic management for stone-related US at our institution. URSL as a cause and longer than 15 mm in length could strongly affect the success rate of the endoscopic management of US. In such cases, reconstructive management for US should be considered in the early stages.