Effect of Preoperative Hydronephrosis on Ureteral Stenosis after Flexible Ureteroscopy: A Propensity Scores Matching Analysis

OBJECTIVES: Ureteral stenosis is a serious complication after flexible ureteroscopy. Other studies have confirmed that stone impaction and intraoperative ureteral injury are important factors causing stricture, and how to predict the occurrence of stricture before surgery may be an important topic. This study retrospectively studied the influence of preoperative hydronephrosis degree on ureteral stenosis after flexible ureteroscopy to explore whether preoperative hydronephrosis degree could predict postoperative ureteral stenosis. METHODS: A retrospective study was conducted on patients who received flexible ureteroscopy in our hospital for upper ureteral calculi from January 2015 to June 2018. The postoperative follow-up was performed for 36 months, and intraoperative and postoperative complications were recorded. According to the degree of hydronephrosis, the patients were divided into mild hydronephrosis group and moderate and severe hydronephrosis group. Preoperative clinical baseline data of the patients were adjusted by propensity matching score, and differences in intraoperative mucosal injury, operative time, incidence of postoperative ureteral stricture, and SFR 1 month after surgery were statistically analyzed. Kaplan- Meier method and Log-rank test were used to compare the differences in the cumulative incidence of ureteral stenosis between the two groups. Cox regression analysis was used to compare the hazard ratio of ureteral stenosis between the two groups. RESULTS: A total of 447 patients with 469 sides surgery were included, including 349 sides in the mild hydronephrosis group and 120 sides in the moderate and severe hydronephrosis group. 30 sides in 29 patients developed ureteral stenosis. The stenosis rate before propensity matching analysis was 6.4%, and 8% after propensity matching analysis. However, the SFR and operation time were not statistically consistent. Kaplan-Meier showed a significant difference in the cumulative incidence of ureteral stenosis between the two groups. CONCLUSIONS: Preoperative patients with moderate to severe hydronephrosis are more likely to have intraoperative mucosal injury, and the incidence of ureteral stricture is higher after flexible ureteroscopy. Preoperative hydronephrosis is an important predictor of ureteral stricture. Preoperative hydronephrosis is an important predictor of ureteral stricture.

studied the influence of preoperative hydronephrosis degree on ureteral stenosis after flexible ureteroscopy to explore whether preoperative hydronephrosis degree could predict postoperative ureteral stenosis.
METHODS: A retrospective study was conducted on patients who received flexible ureteroscopy in our hospital for upper ureteral calculi from January 2015 to June 2018. The postoperative follow-up was performed for 36 months, and intraoperative and postoperative complications were recorded. According to the degree of hydronephrosis, the patients were divided into mild hydronephrosis group and moderate and severe hydronephrosis group. Preoperative clinical baseline data of the patients were adjusted by propensity matching score, and differences in intraoperative mucosal injury, operative time, incidence of postoperative ureteral stricture, and SFR 1 month after surgery were statistically analyzed. Kaplan-Meier method and Log-rank test were used to compare the differences in the cumulative incidence of ureteral stenosis between the two groups. Cox regression analysis was used to compare the hazard ratio of ureteral stenosis between the two groups.
RESULTS: A total of 447 patients with 469 sides surgery were included, including 349 sides in the mild hydronephrosis group and 120 sides in the moderate and severe hydronephrosis group. 30 sides in 29 patients developed ureteral stenosis.
The stenosis rate before propensity matching analysis was 6.4%, and 8% after propensity matching analysis. However, the SFR and operation time were not statistically consistent. Kaplan-Meier showed a significant difference in the cumulative incidence of ureteral stenosis between the two groups.
CONCLUSIONS: Preoperative patients with moderate to severe hydronephrosis are more likely to have intraoperative mucosal injury, and the incidence of ureteral stricture is higher after flexible ureteroscopy. Preoperative hydronephrosis is an important predictor of ureteral stricture. Preoperative hydronephrosis is an important predictor of ureteral stricture.

Background
With the development of flexible ureteroscope technology in recent years, the treatment of upper ureteral calculi with flexible ureteroscope is gradually increasing. Guideline of EAU [1] suggests that "percutaneous nephrolithotomy is considered for ureteral stone larger than 15mm with stone impaction". However, in practical work, the indications for flexible ureteroscope are gradually broadened.
Some doctors prefer flexible ureteroscope because it is more minimally invasive and have a lower risk of bleeding. Compared with percutaneous nephrolithotomy, flexible ureteroscope causes less postoperative pain and are more acceptable to patients. But more minimally invasive does not mean better, and what we find in surgery is that as the flexible ureteroscope is used more often, the number of postoperative complications increases. The incidence of ureteral stenosis, a rare complication after ureteroscopy, is now increasing, and stenosis often requires reoperation, causing more pain to the patient and increasing the financial burden.
Ureteral stenosis is commonly reported in hard and semi-hard endoscopic surgery, and the reported incidence is (0.30%-23.81%) [2]. Some scholars have studied the risk factors of ureteral stenosis, and believe that stone burden, stone impaction and operation time are important factors causing Ureteral stenosis [3]. "Stone impaction" has been mentioned in the EAU guideline and many literatures[1, 4,5].
It has been shown that renal parenchyma thickness and thickness of the ureteral wall on CT is related to stone impaction [6,7]. In addition, few other studies have been conducted on how to determine "stone impaction". In clinical diagnosis and treatment, we found that regardless of the size of stones, the degree of hydronephrosis is closely related to the occurrence of intraoperative mucosal injury and ureteral stricture. The degree of hydronephrosis may represent the severity of stone incarceration, which is another indicator for preoperative prediction of ureteral stricture. We conducted a retrospective study to confirm this conclusion. We selected patients with mild hydronephrosis as the case group, and patients with moderate and severe hydronephrosis as the control group. The main observed outcome was ureteral stenosis, and the secondary outcomes included operative time, intraoperative mucosal injury and stone clearance rate 1 month after surgery.

Definition of terms in this paper
Onset time: the time from the onset of symptoms or the detection of stones by examination to the date of surgery.
Calculi size and hydronephrosis: refer to the CT measurement of urinary system.
The width of renal pelvis less than 2cm was considered mild hydronephrosis, while that larger than 2cm was considered moderate and severe hydronephrosis.

Postoperative and perioperative management
Preoperative CTU examination excluded ureteral stenosis. Double J tubes were placed preoperatively for 1 to 2 weeks to dilate the ureter. All patients received general anesthesia. The ureteroscope (Wolf 6/7.5 or 8/9.8) was used to remove the stent, and then the ureteral orifice was found. The middle and lower sections of the ureter were explored by ureteroscope, and the guide wire was placed through the working channel. After the endoscope was removed, the sheath of F12 (Cook Company) was placed through the guide wire, and the flexible ureteroscope (Olympus8F) was placed through the sheath to the middle and upper sections of the ureter. Postoperative follow-up All patients were followed up in the outpatient department, KUB was reexamined 1 month after surgery, and B-ultrasound of urinary system was reexamined 3 months, 6 months, 1 year, 2 years and 3 years after extubation. If there was no aggravation of hydronephrosis, no follow-up was performed.

Postoperative complications
Postoperative complications were graded according to the Clavien -Dindo grading system. The system is divided into 5 grades according to the severity of complications, different treatment measures and prognosis [9] .

Statistical analysis
Excel 16 was used for data record and IBM SPSS 25 was used for data statistical analysis. Continuous variables was expressed as mean plus or minus the standard deviation, and clinical features were compared between the two groups using the independent sample t-test (continuous variable) or the independent sample chi-square test (categorical variable). The clinical baseline characteristics of patients were adjusted by 1:1 propensity scores matching analysis. After propensity scores matching analysis, paired sample T test (continuous variable) or McNEMA test (categorical variable) was used to compare the clinical characteristics of the two groups. The Kaplan-Meier method was used to estimate the rate of cumulative events, and log-rank test was used to compare the differences between the two groups. A Cox proportional-hazards model was used to evaluate the hazard ratio for each event in both groups. After surgery, 17 patients were lost to follow-up, including 13 patients with stenosis, 4 patients did not return to the outpatient department, and 9 patients went to other hospitals for diagnosis and treatment. Four patients with nonstenosis were lost to follow-up. The differences of observed outcomes before and after propensity scores matching analysis are shown in Table 2. A total of 29 patients had ureteral stenosis on 30 sides after operation. The stenosis rate before the propensity scores matching analysis is 6.4%, while that after the propensity scores matching analysis is 8%. The SFR and operation time tend to be significantly different in the moderate and severe hydronephrosis group before propensity scores matching analysis but is similar in both groups after propensity scores matching analysis. The while the remaining two patients did not get better after extubation, so they went to other hospitals for further treatment.

Discussion
The main results of our research are as follows. First, the incidence of stenosis in moderate and severe hydronephrosis group is higher than that in mild hydronephrosis group. Second, in the moderate and severe hydronephrosis group, the incidence of intraoperative mucosal injury is higher, the duration of operation is longer, and the postoperative SFR is lower. However, there is no difference in the SFR and operation time between the two groups after the adjustment of baseline characteristics. Third, the Kaplan-Meier curve shows that the cumulative incidence of ureteral stricture was higher in the moderate and severe hydronephrosis group.
There are several retrospective studies on the risk factors of ureteral stricture. There are many speculations about the mechanism of ureteral stenosis after Ureteroscopic surgery, such as stone impaction, soft sheath compression injury, large stone burden, intraoperative ureteral perforation and the surgeon's experience [2,11]. Daniel A Wollin et al. designed an in vitro model to study the water temperature at different perfusion rates during holmium laser lithotripsy.
The authors found that, even with high laser power, adequate irrigation could still maintain a relatively stable temperature. With the decrease of the perfusion velocity, the maximum temperature of the laser can be significantly increased even with the use of lower laser power, which may cause damage to the ureteral tissue [12]. Shiulian Chen et al. included 1555 patients in 8 studies in a metaanalysis, and the results showed that the incidence of ureteral stenosis after holmium laser lithotripsy was higher than pneumatic lithotripsy. The authors believe that further studies should be conducted to evaluate this problem [13].In our actual work, we find that if the calculi can not be pushed during the operation, the possibility of ureteral stricture after the operation is higher. If the ureteral stone loosens or is pushed into the renal pelvis after brief intraoperative holmium laser lithotripsy, there is almost no postoperative ureteral stenosis, which is consistent with Daniel A Wollin's model. The above studies suggest that stone impaction and mucosal injury may be causal, and the key is how to predict the likelihood of these events before surgery. Stone impaction is a vague concept, which is difficult to judge only by preoperative findings. The thickening of ureteral wall on CT may indicate that the ureteral wall is thickened and the stones are surrounded by polyps, which can predict postoperative stenosis [6].In our practice, we found that the degree of hydronephrosis was associated with postoperative stenosis, which might be another indicator for predicting postoperative stenosis after flexible ureteroscope surgery. Therefore, we grouped according to the degree of hydronephrosis and confirmed this conclusion through retrospective study.
The present study has several limitations. First，this is a single-center retrospective study with a limited sample size.

Conclusions
Moderate and severe hydronephrosis increases the incidence of mucosal injury during flexible ureteroscopy and postoperative ureteral stenosis, and the prevalence of ureteral stenosis increases with time. The degree of hydronephrosis may be related to stone impaction. Preoperative CT diagnosis of moderate and severe hydronephrosis is an important factor in predicting postoperative ureteral stenosis, which suggests clinicians to change the surgical method and adopt ureterolithotomy or percutaneous nephrolithotomy. Availability of data and material

List of abbreviations
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.