Evaluation of ureteral injuries caused by ureteral access sheath insertion during ureteroscopic lithotripsy

To evaluate ureteral injuries caused by insertion of a 13‐Fr ureteral access sheath and identify factors (other than pre‐stenting) that are predictive of ureteral injury.


INTRODUCTION
Ureteroscopic lithotripsy (URSL) using a ureteral access sheath is becoming increasingly popular worldwide because of advantages that include reduced intrarenal pressure, multiple entry and reentry, scope protection, and avoidance of bulking. [1][2][3] However, the risk of ureteral injury after ureteral access sheath use should be considered; Loftus et al. 4 reported that ureteral access sheath-related ureteral injury may lead to ureteral stricture formation. Although the standard ureteral access sheath has an external diameter of 14 Fr, Zelenko et al. 5 reported that the mean diameter of the non-prestented ureter was 3 mm, according to imaging analysis. Concerning high-grade ureteral injury when using a 14-Fr ureteral access sheath, Traxer et al. 6 reported a rate of 13.3% whereas Loftus et al. 4 reported a rate of 23.9%. Thus, there is a risk of ureteral injury when using a 14-Fr ureteral access sheath; we presumed that the risk of injury for non-prestented patients would be lower when using a <14-Fr ureteral access sheath. Because Traxer et al. 6 reported that pre-stenting improved the risk of ureteral access sheath-related ureteral injury, we routinely use a 13-Fr ureteral access sheath for nonprestented patients and a 14-Fr ureteral access sheath for pre-stented patients in our institution. To our knowledge, there have been no reports concerning the incidence of ureteral injury caused by a 13-Fr ureteral access sheath. Here, we evaluated ureteral injuries caused by insertion of a 13-Fr ureteral access sheath and explored factors (other than pre-stenting) that were predictive of ureteral injury.

METHODS
The study protocol was approved by our institutional review board (approval number: R03-0201). This study adhered to the tenets of the Declaration of Helsinki (as revised in Fortaleza, Brazil, in October 2013).
We performed a retrospective review of prospectively collected data for 201 consecutive patients who underwent URSL from August 2018 to February 2021. We excluded 80 patients who underwent ureteral stent insertion before URSL, 10 patients who did not use a ureteral access sheath (because the stones were located in the distal ureter), and 2 patients in whom a ureteral access sheath could not be inserted. In total, 109 patients were analyzed; all underwent insertion of a 13-Fr ureteral access sheath.
Two endourologists performed URSL using the following procedure. Stones were approached using a guide wire and semi-rigid ureteroscope (6.5/8.5 Fr; Richard Wolf). For proximal ureteral and renal stones, a ureteral access sheath was placed under fluoroscopic guidance (a safety guidewire was not placed outside of the ureteral access sheath), and the stones were fragmented using a holmium YAG laser (5-10 Hz and 0.5-1.0 J; VersaPulse 30W; Lumenis). All fragments larger than 2 mm were extracted using a tipless basket with a flexible ureteroscope (URF-P5 or P7; Olympus or LithoVue; Boston Scientific). The ureteral access sheath was a Flexor 12/14 Fr (Cook Medical) or Navigator HD 11/13 Fr (Boston Scientific). In accordance with our institution's criteria for sheath size selection, we used a 14-Fr ureteral access sheath for patients who underwent insertion of a ureteral stent before URSL and a 13-Fr ureteral access sheath for patients who did not undergo insertion of a ureteral stent before URSL. The length of the ureteral access sheath was determined by sex (male: 46 cm, female: 36 cm). For mid-and distal ureteral stones, we performed the procedure as described above, but we omitted the ureteral access sheath. No patients required dilation of the ureteral orifice or ureter, and the ureteral stent was left in place after the procedure.
We investigated patient demographics and surgical outcomes, including ureteral access sheath-related ureteral injury; patients were divided into two groups (non-highgrade ureteral injury and high-grade ureteral injury) for comparison. The ureter was inspected with a flexible ureteroscope during withdrawal of the 13-Fr ureteral access sheath; the withdrawal procedure was recorded. All procedural videos were evaluated by a single endourologist. The Traxer ureteral injury scale (Table 1) was used to grade ureteral injury caused by a 13-Fr ureteral access sheath. The primary endpoint of the study was high-grade (i.e., grade 2-4) ureteral injury caused by a 13-Fr ureteral access sheath. The secondary endpoint was the incidence of postoperative ureteral stricture; this respective endpoint was determined by computed tomography at 1 month postoperatively and by ultrasonography at 3 months postoperatively. Patients were considered stone-free if their residual stones were <2 mm in diameter; postoperative ureteral stricture was defined as the onset or exacerbation of hydronephrosis after URSL. Preoperative urinary tract infection was defined as the presence of significant symptoms, pyuria, and/or a positive urine culture, and an impacted stone was defined as failure to pass a guidewire on the first attempt during URSL. The chi-squared test was used to compare nominal variables, and Student's t-test was used to compare continuous variables between the two groups. Multivariate analysis was used to investigate factors (other than pre-stenting) that were predictive of ureteral injury. Logistic regression analysis was used to evaluate associations between ureteral injuries and predictive factors. Statistical analyses were performed using BellCurve for Excel 3.20 (Social Survey Research Information Co., Ltd.), and the significance level was set at p < 0.05. Table 2 shows the overall and group-specific patient demographics and surgical outcomes. There were significant differences in the sex ratio and stone diameter between the two groups (p = 0.03 and p = 0.01, respectively). No patients received b-agonists or a-adrenergic antagonists. There were 21 (19.3%) cases of ureteral access sheath-related ureteral injury (grades 2-4). Postoperative ureteral stricture did not occur in any cases. Table 3 shows the ureteral injury severity and locations. There were 11 (52.4%) grade 2 injuries and 10 (47.6%) grade 3 injuries ( Figure S1). The ureteral injury location was the proximal ureter in 20 cases (95.2%), middle ureter in 1 case (4.8%), and distal ureter in 0 cases. Table 4 shows the factors predictive of ureteral access sheath-related ureteral injury. Sex and stone diameter showed statistical significance in the univariate analysis; therefore, they were further analyzed in the multivariate analysis. Multiple logistic regression analysis revealed that male sex and stone diameter were significant predictive factors for ureteral injury (p = 0.037, odds ratio [OR]: 5.19, 95% confidence interval [CI]: 1.11-24.3 and p = 0.02, OR: 0.83, 95% CI: 0.71-0.97, respectively). Ureteral mucosal erosion without smooth muscle injury High grade (2)(3)(4) 2 Ureteral wall injury including mucosa and smooth muscle, with adventitial preservation (periureteral fat absent) 3

RESULTS
Ureteral wall injury including mucosa and smooth muscle, with adventitial perforation (periureteral fat evident) 4 Total ureteral avulsion

DISCUSSION
To identify factors (other than pre-stenting) that were predictive of ureteral injury, we evaluated ureteral injuries caused by the insertion of a 13-Fr ureteral access sheath in nonprestented patients; we had three main findings. First, the rate of ureteral injury (grade ≥ 2) by a 13-Fr ureteral access sheath was 19.3%, which was considerable. Second, most ureteral injuries occurred in the proximal ureter. Third, male sex and smaller stone diameter were significant predictive factors for ureter injury, according to multiple logistic regression analysis. To our knowledge, there have been no reports concerning the incidence of ureteral injury caused by a 13-Fr ureteral access sheath. Although 13-Fr ureteral access sheaths are not very large in diameter, we consider that the rate of high-grade ureteral injury was high in this study. The reason for the high incidence of ureteral injury may be the racial differences among the patients. In future studies, we should examine the effects of racial and physical differences on the thinness of the ureter. We must also consider the sheath material used. Sheaths made of hard materials may be easier to insert, but they may also increase the incidence of ureteral injury. In addition, we always evaluate the thinness of the ureter with a rigid ureteroscope before inserting the ureteral access sheath; however, alternative simple and precise methods for measuring ureteral thinness, such as the use of a dilator, may be required. Therefore, the risk of ureteral injury should be carefully considered. Furthermore, there have been no reports concerning the locations of ureteral access sheathrelated ureteral injuries. Because most ureteral injuries occurred in the proximal ureter in our study, we recommend assessment of the ureteral wall with a flexible ureteroscope at the end of URSL. Particular attention should be given to male patients and patients with small stones; it may be better to use a smaller-diameter sheath during URSL in these patients. Ureteral access sheaths have become popular because of their ability to access the upper lumen and evaluate any part of the kidney, repeatedly and rapidly enter the ureter and collecting system, improve drainage, improve visibility, reduce intrarenal pressure during pulse irrigation, protect the scope, and avoid ureteral lesions during stone fragment removal. 7,8 However, there have been some concerns about ureteral access sheath-related ureteral injuries. 6 Additionally, ureteral access sheath-related intraluminal compression of the ureter may compromise ureteral blood flow and cause secondary stricture. 8-10 Therefore, Breda et al. 11 considered the ureteral access sheath to be safe and useful, although its use is associated with some risks and limiting factors.
Traxer et al. 6 prospectively evaluated ureteral injuries by a 14-Fr ureteral access sheath using a new classification Note: Ureteral injury grade 2: ureteral wall injury including mucosa and smooth muscle, with adventitial preservation (periureteral fat absent); grade 3: ureteral wall injury including mucosa and smooth muscle, with adventitial perforation (periureteral fat evident); grade 4: total ureteral avulsion.   system; they found that the rate of high-grade (grade ≥ 2) injury was 13%. Furthermore, they reported that male, older, and non-prestented patients had greater risks of severe ureteral access sheath-related ureteral injuries. In a prospective randomized trial, Loftus et al. 4 found the rate of high-grade (grade ≥ 2) injury caused by a 14-Fr ureteral access sheath was 23.9%. Furthermore, they reported that male sex, high stone burden, longer sheath insertion time, and a more difficult subjective rating of sheath placement were associated with high-grade ureteral injuries. In the present study, the rate of high-grade injury was 19.3%. Because pre-stenting was not performed in our patients, whereas it was in the study by Traxer et al., 6 our data were higher than the data of Traxer et al. Furthermore, our data were lower than the data of Loftus et al. 4 Because pre-stented patients were not included in the study by Loftus et al., we presumed that the difference in ureteral access sheath size led to the difference in results between studies (Loftus et al. used 14-Fr access sheaths, whereas we used 13-Fr access sheaths). Thus, although there are reports of ureteral injury by a ureteral access sheath, there are no similar reports from Japan. At our institution, the ureter is always observed by ureteroscopy after removal of the access sheath, but this may not be performed in all institutions. Japanese data are needed to evaluate the incidence of ureteral injury by a ureteral access sheath and the impact of differences in the size of the ureteral access sheath on the incidence of ureteral injury in the Japanese population. It is also important to observe the ureteral wall after removing the ureteral access sheath. Some investigators have described ureteral access sheathrelated ureteral injuries and the risk factors for such injuries. Traxer and Thomas 6 reported that the absence of pre-stenting was the strongest predictor of severe ureteral injury, whereas Tracy et al. 12 reported that use of a large-caliber (14/16-Fr) ureteral access sheath did not increase the risk of ureteral injury in a patient who was pre-stented. Thus, pre-stenting has been presumed to reduce the risk of ureteral access sheath-related ureteral injury. 6,12,13 However, several complications have been reported in relation to ureteral stenting, including incomplete emptying, bladder pain, frequency, hematuria, and migration. Additionally, ureteral stenting reportedly diminished urinationrelated quality of life in 80% of patients who underwent the procedure. 14 Accordingly, the American Urological Association and European Association of Urology guidelines recommend avoiding routine pre-stenting, although some methods to improve stent-related symptoms have been reported. [15][16][17] Thus, there is a need to investigate techniques that can reduce ureteral access sheath-related ureteral injury without pre-stenting. Loftus et al. 4 suggested that surgeons should have a low threshold for switching to a smaller sheath when resistance is encountered or if placement time is prolonged. In our multiple logistic regression analysis, male sex and smaller stone diameter were significant predictive factors for ureteral injury. Although this predictive factor has not been previously described, Traxer et al. suspected that ureteral injury is related to differences in sex hormones or to the higher tonic effect of the psoas muscle in male patients. 6 Loftus et al. 4 also reported an association between ureteral injury and male sex, noting that the tonic effect from the psoas muscle may be higher in men than in women and contribute to ureteral injury. Moreover, the urethra is longer in men than in women, and the longer insertion path in men may result in an angle more prone to ureteral injury. Using a long ureteral access sheath to accommodate for the long male urethra may also cause ureteral injury. Furthermore, with respect to small stones as a predictive factor, the ureter may be too narrow to allow small stones to pass. Thus, a smaller sheath may be preferable for URSL in male patients. However, the ureteral access sheath size should be carefully selected. The ureteral access sheath size was 14 Fr in the studies by Traxer et al. 6 and Loftus et al., 4 whereas it was 13 Fr in our study. Therefore, a smaller sheath (e.g., 12 Fr or 11.5 Fr) may be more appropriate. Notably, Koo et al. 18 investigated the efficacy of preoperative a-adrenergic antagonists to reduce the force of ureteral access sheath insertion. They concluded that preoperative a-adrenergic antagonists and slow sheath placement may reduce the maximum force of ureteral access sheath insertion. The technique for ureteral access sheath insertion and the medication used during the procedure may also be important for reducing ureteral injuries during ureteral access sheath insertion.
This study had some limitations. First, it used a retrospective design. Second, long-term outcome data were not available for patients in this study. No ureteral stricture was recorded; however, the effect of the short observation period should be considered. At our hospital, postoperative ureteral stents are left in place for 2 to 3 weeks regardless of whether ureteral injury is present. Although a ureteral stent is usually placed after ureteral injury has occurred, the duration of stenting is not standardized. Some reports recommend 3-6 weeks, 6 while others suggest that 1 week of placement may be sufficient. 19 In future, it will be necessary to clarify the appropriate duration of stent placement after ureteral injury. Third, this study used a non-randomized design and included only one comparison group. However, all patients were nonprestented patients who were presumed to require the use of a ureteral access sheath, and all patients underwent insertion of a 13-Fr ureteral access sheath. This approach may have reduced the potential for selection bias.
In conclusion, we evaluated ureteral injuries caused by the insertion of a 13-Fr ureteral access sheath. The rate of ureteral injury (grade ≥ 2) by a 13-Fr ureteral access sheath was 19.3%, and most ureteral injuries occurred in the proximal ureter. Furthermore, male sex and smaller stone diameter were significant predictive factors for ureteral injury, according to multiple logistic regression analysis. Although we recommend confirmation of a whole ureter, it is important to at least confirm the proximal ureter when using a 13-Fr ureteral access sheath, particularly in male patients and patients with small stones. visualization; project administration; writing-original draft; writing-review and editing. Kaneki Yasuda: Writingreview and editing. Hidefumi Kinoshita: Writing-review and editing; supervision.

Supporting information
Additional Supporting Information may be found in the online version of this article at the publisher's web-site: Figure S1.

Editorial Comment
Editorial Comment to Evaluation of ureteral injuries caused by ureteral access sheath insertion during ureteroscopic lithotripsy The use of a ureteral access sheath has great advantages. The debate on whether or not to use access sheath is over. Today, it matters which size you choose.
Traxer et al. reported a grading system for ureteral damage caused by the insertion of access sheath. 1 They examined total 359 patients. The patients were not systematically prestented, but 47% of the patients were pre-stented. They used a Flexor® 12/14-Fr 35 cm access sheath. They reported that high-grade damages were occurred in 48 patients (13%). From this study, we can understand that 13% of patients in