Comparison of Fragmentation and Dusting Laser Modes for Laser Ureteroscopy Lithotripsy of Ureteral Stones at a Single Center

rate, stone burden, stone number, stone laterality, stone location, ureteral condition, prevalence of pyuria, OP time, lithotripsy effectiveness, stone free rate, presence of push back, secondary intervention (extracorporeal shock wave (ESWL) or URSL), and complications, including ureteral injury and postoperative ureteral stricture rate, were recorded. The type of ureteral stent inserted was also recorded, including retrograde ureteral catheter (RUC; whistle tip ureteral catheter, Cook Medical, Bloomington, United States of America), double J (DJ; Universa soft, Cook Medical, Bloomington, United States of America) or stone basket (Zero Tip 2.4F, Boston Scientic, Marlborough, United States of


Background
Ureteral stones and the symptoms related to ureteral obstruction, usually adversely affect the patients' quality of life. [1] There are several therapeutic options for ureteral stones, including observation and medical expulsive therapy, shock-wave lithotripsy, ureteroscopic lithotripsy, open surgery, laparoscopic stone removal and percutaneous antegrade ureteroscopy. [2,3] The decision of which method is most suitable for each patient depends on the stone's anatomical location and characteristics, and the safety pro le of each technique. [4] Since the development of the semirigid ureteroscope with a smaller caliber, ureteroscopic lithotripsy (URSL) has become an e cacious modality for the treatment of stones in all locations in the ureter. [2] Various different energy sources can be used for lithotripsy during a ureteroscopy, including pneumatic, ultrasound, electrohydraulic and laser. [3,5] Nowadays, holmium laser lithotripsy is one of the most widely used approaches by urologists because it leads to fewer complications and has a lower incidence of upward stone migration. [6,7] The holmium laser breaks down the stone via the power which is generated from a large crystal that is coupled to bers.
[8] The power can be adjusted by the parameters of energy, frequency and pulse width.
[8] The high energy, low frequency setting is de ned as the fragmentation mode, while the low energy, high frequency setting is de ned as the dusting mode. [8,9] The main advantage of dusting is that it produces smaller fragments and results in a shorter operation (OP) time; however, it requires a more advanced laser system which usually requires more expensive equipment.
[8] Some studies thought that using the dusting laser mode could reduce the risk of ureteral injury, however, there is little evidence that one approach is better than the other. [9] Previous studies have compared the e cacy and safety of different energy and frequency settings, but there have been few studies comparing the use of fragmentation and dusting laser systems in a single center. [10,11] The fragmentation laser mode and the dusting laser mode were simultaneously used in our medical center, MacKay Memorial Hospital. In this study, we compared the e cacy and outcomes of these two laser modalities for the treatment of ureteral stones.

Methods
Patients aged ≥20 years who underwent URSL for ureteral stones using a laser system in MacKay Memorial Hospital between September 2018 and June 2020, were retrospectively reviewed. Patients with radiolucent stones, those who were lost to follow-up, and those who had incomplete image records (a lack of either preoperative images or images within 1 postoperative month) were excluded. Patients who underwent concurrent retrograde intrarenal surgery (RIRS) or combination therapy with other treatment modalities were also excluded ( Figure 1). This study was approved by the Institutional Review Board of Mackay Memorial Hospital as a retrospective observational cohort study.
The patients' age, gender, anesthesia method, admission rate, stone burden, stone number, stone laterality, stone location, ureteral condition, prevalence of pyuria, OP time, lithotripsy effectiveness, stone free rate, presence of push back, secondary intervention (extracorporeal shock wave (ESWL) or URSL), and complications, including ureteral injury and postoperative ureteral stricture rate, were recorded. The Depending on the patients' condition and the attending physicians' clinical decision, the patients were either postoperatively admitted to the urology department or they recovered from their URSL at an outpatient clinic. The anesthesia method was determined by the anesthesiologist following their preoperative evaluation. Stone location and number of stones were determined from a preoperative plain radiography of the kidney, ureter, and bladder (KUB). Stone burden was de ned as the area of the stone calculated by our imaging system after the stone was delineated ( Figure 2). Lithotripsy effectiveness was de ned as the stone burden divided by the OP time (mm 2 /minutes). Pyuria was de ned as >10 white blood cell counts in the preoperative urine analysis under a high power eld. The stone's upward push back, ureter condition and postoperative injury were documented according to the surgeons' intraoperative ndings. Follow-up plain radiography KUB or computerized tomography (CT) were performed within 1 month of the URSL. The de nition of stone free is not standardized and differs greatly in previous literature. [9] In the current study, stone-free was de ned as no residual stones >3 mm in the ureter of the affected side within 1 postoperative month. [12] We searched the medical records for any complications and secondary interventions, including a repeat URSL, ESWL or RIRS for stones that remained in the ureter or were pushed back to the renal calyx during the initial operation.
A semirigid 6/7.5-F ureteroscope (Wolf, Knittlingen, Germany) was used for all procedures. All URSL operations were performed by the same experienced urology team for both modes. The initial settings for the fragmentation laser system (Auriga XL 50W, Boston Scienti c, Marlborough, United States of America) with a 365 µm ber were: energy 0.8 Joules and frequency 8 Hertz. The initial settings for the dusting laser system (VersaPulse 60W, Lumenis, Yokneam, Israel) with a 365 µm ber were: energy 0.4 Joules and frequency 40 Hertz. Mild adjustments could be made depending on the surgeon. The patient was placed in a reverse Trendelenburg position and the intraluminal water pressure was decreased by lowering the water bottle. After the lithotripsy was nished, the larger stone fragments were removed using a retrieval basket and the smaller ones were left for spontaneous passage. At the end of the procedure, a ureteral stent was considered, depending on the fragmentation status of the residual stones, the ureteral condition, bleeding, and the index of suspicion for postoperative ureteral stricture. Perioperative intravenous broad spectrum antibiotics were given to all patients and oral antibiotics were given to outpatients postoperatively.
A t-test, a Chi-squared test and Fisher's exact test were used for statistical analysis, and the statistical signi cance was set at p<0.05. SPSS for Windows (version 21.0; IBM SPSS Statistics, IBM Corporation, Chicago, IL, USA) was used to perform the logistic regression analysis of risk factors for stone free rate. The t-test, Chi-squared test and Fisher's exact test were used to explore the differences between the fragmentation and dusting groups. All tests were two-sided, and p values <0.05 were considered to be statistically signi cant.

Results
A total of 421 patients were analyzed, including 271 who received dusting laser URSL and 150 who received fragmentation laser URSL. The mean age was 54.1 ± 12.63 years in the dusting group and 53.9 ± 13.57 years in the fragmentation group. The mean stone burden was 56.8 ± 60.71 mm 2 in the dusting group and 48.9 ± 59.23 mm 2 in the fragmentation group. There were no signi cant differences in gender, age, admission rate, anesthesia methods and stone laterality between the two groups. However, signi cantly more patients in the dusting group had multiple ureteral stones (p=0.023) and pyuria (p<0.001) compared with the fragmentation group. There were no signi cant differences in stone location and ureteral condition between the two groups (Table 1). The treatment results revealed that the fragmentation group had a signi cantly higher stone free rate (p=0.012) and a lower stone push back rate (p=0.011) compared with the dusting group. The dusting group had a slightly higher lithotripsy effectiveness (p=0.76) and postoperative ureteral stricture rate (p=0.055) compared with the fragmentation group, but the differences were not statistically signi cant. There were no statistically signi cant differences in the OP time, ureteral stent insertion rate, stone basket usage rate, secondary intervention rate, ureteral injury rate and complication rate between the two groups (all p>0.05) ( Table 2). Complications included three cases of bleeding or oozing during the OP, one case of postoperative prostatitis, one case of leg dropping from the lithotomy position and nine cases of postoperative ureteral strictures. The three patients with intraoperative bleeding or oozing had a prolonged OP time for a hemostasis procedure. The patient who suffered from prostatitis was diagnosed by CT image, admitted again 5 days after the URSL and received intravenous antibiotics for 10 days. The patient with one leg dropping from the lithotomy position received uoroscopic imaging and there was no fracture or dislocation. Among the nine patients with postoperative ureteral stricture, two of them had laser ureterotomy, four of them had DJ re-insertion for 1 to 1.5 months and three of them did not need further treatment.
Univariate analysis showed that patients who were stone free were signi cantly less likely to have received the dusting laser system (odds ratio [OR]=0.533, p=0.012), and had a signi cantly higher stone basket usage rate (OR=2.82, <0.001), fewer multiple stones (OR=0.375, p<0.001), fewer upper ureteral stones (OR=0.102, p=0.002) and less pyuria (OR=0.34, p<0.001) compared with patients who were not stone free (Table 3). Multivariate logistic analysis revealed that patients who were stone free had a signi cantly higher stone basket usage rate (OR=3.026, p<0.001), fewer multiple stones (OR=0.322, p<0.001), fewer upper ureteral stones (OR=0.098, p=0.002) and less pyuria (OR=0.428, p=0.001) compared with those patients who were not stone free. The dusting laser system had a slightly lower stone free rate, however, the multivariate logistic analysis did not reveal a statistically signi cant difference (Table 3).

Discussion
Due to advances in technology, there are now a wide variety of power generators that can be used for ureteroscopic lithotripsy. In addition to pneumatic lithotripsy, laser lithotripsy has now become a predominant method for urinary stone treatment worldwide.
[8] Pneumatic lithotripsy is thought to have a lower risk of ureteral perforation compared with laser lithotripsy, but it is associated with a higher rate of stone push back into the renal pelvis. [13] Chen et al. reported that laser lithotripsy is superior to pneumatic lithotripsy for the management of ureteral stones in terms of the stone free rate and the secondary intervention rate for stones of all sizes, at their institute. [12] Yin et al. also found that laser lithotripsy had advantages over pneumatic lithotripsy, with a high stone-free rate and a low migration rate in their meta-analysis.
[6] If properly used, the laser generator provides a highly effective tool for disintegrating stones in the urinary tract with minimal additional safety concerns. [14] Furthermore, there have been large improvements in the laser technique. For example, the Moses and vapor tunnel modulations have been designed, which help urologists to deal with stones in the urinary tract. Bozzini et al. found that the vapor tunnel technique signi cantly reduced retropulsion of the stone, the procedure time and ureteral lesions, and they thought that the vapor tunnel technique would be an excellent setting option for use with vulnerable ureteral walls. [15] Ibrahim et al. also found that Moses technology was associated with a signi cantly lower procedure time and less retropulsion in their doubleblinded prospective randomized trial.
[16] The vapor tunnel technique had a signi cantly higher stone free rate compared with the regular settings, while the Moses technique showed a mild improvement. [15,16] In our study, we found that the dusting mode had a signi cantly lower stone free rate in the univariate analysis compared with the fragmentation mode but there was no signi cant difference in the multivariate analysis. Therefore, we believe that both of these techniques are effective and safe for ureteral lithotripsy. However, because some of these technologies are relatively novel, more comprehensive studies may be needed to con rm the e cacy and safety of these innovations.
Among the different types of laser sources, holmium: yttrium-aluminum-garnet (Ho:YAG) is the most popular source for URSL because of its ability to fragment stones of any composition and its excellent safety pro le.
[16] The laser power of Ho:YAG can be highly absorbed in water and has a low penetration depth, therefore, Ho:YAG does little injury to the surrounding tissue.
[8] The laser is generated and releases its energy from the tip of a ber. The stones are then disintegrated into fragments or dust.
[8] The pulse energy settings for the holmium laser usually range from 0.2 to 2.0 Joules and the frequency setting usually ranges from 4 to 80 Hertz depending on the manufacturer and the model of laser console used.
[9] Different settings may cause diverse effects on the stones. The higher the pulse energy used, the more stone retropulsion occurs. Whereas, changes in frequency had a minimal effect on retropulsion when the energy and ber diameter were kept constant. [17] In our study, the dusting group had a signi cantly lower stone free rate and a higher stone push back rate compared with the fragmentation group. However, in the multivariate analysis, the laser mode used was not signi cantly related to the stone free rate. The authors hypothesize that these ndings could be due to the signi cant diversity of the patients' characteristics, especially pyuria and multiple stones, which may have hindered the URSL procedure and its outcomes.
Although URSL has become a common surgery, its associated risk of urinary tract infection is about 25% in patients without prophylactic antibiotics.
[18] To prevent patients from postoperative urosepsis, surgeons need to accomplish the URSL as quickly as possible, particularly for patients with pyuria. [19] If the patient is simultaneously suffering from a severe infection, the surgeon should break through the obstructive ureteral stone rapidly and place a ureteral stent for emergent drainage of the renal pelvis, instead of crushing the stone into smaller pieces. Under these circumstances the stone free rate can be decreased, and in the current study patients with pyuria had a signi cantly lower stone free rate. On the other hand, compared with solitary stones, multiple stones can also decrease the stone free rate in lithotripsy surgery. [20] In our study, multiple stones were also a signi cant risk factor for a lower stone free rate. Stone location also has a signi cant effect on stone clearance. Degirmenci et al. stated that the stone clearance rate was higher for lower ureteral stones compared with upper ureteral stones. [21] In our study, patients with upper ureteral stones showed a signi cantly lower stone free rate compared with stones in other locations. Furthermore, a review by Brain et al. found that using a stone basket was associated with a more complete initial stone clearance. [9] We also found similar results, as URSL with basket use had a higher stone free rate compared with URSL without basket use.
The current study had several limitations. First, this was a retrospective study, which means there was a patient selection bias, including some signi cant differences in the patient characteristics. Second, we did not set a standard follow-up duration for all of the patients. Our postoperative follow-up time depended on the patient's symptoms and their willingness to engage with clinicians. Asymptomatic patients tended to have a longer follow-up time compared with patients who suffered from immediate symptoms. Third, we did not do a complete analysis of the stone composition, which could have in uenced the effectiveness of lithotripsy. However, in Asia, calcium oxalate is the most frequent component of stones and it accounts for about 90% of all calculi in the urinary tract. [22] Therefore, the bias caused by stone composition may not have a large effect. Fourth, we used two different machines for the two different laser settings. There may be more bias between the two machines than if the two different settings were used on the same machine. Finally, not all of the URSL in the present study were performed by the same urologist. However, all the urologists involved in this study had achieved the same quali cation. In other words, there was only a little operating difference between each surgeon in the urologist team.

Conclusions
Both laser modes were effective and safe for ureteral lithotripsy. The energy and frequency settings did not have a signi cant effect on the stone free rate in these two modalities. Risk factors for a lower stone free rate included multiple stones (OR=0.322), pyuria (OR=0.428) and upper ureteral stone location (OR=0.098). Risk factors for a higher stone free rate were the use of a stone basket (OR=3.026).