Prospective Randomized Controlled Trial to Compare Dusting vs Fragmentation Using Thulium Fiber Laser in Retrograde Intrarenal Surgery

Abstract

Objective:

To compare the dusting vs fragmentation modes with thulium fiber laser (TFL) in retrograde intrarenal surgery (RIRS) for upper tract stones using the same fixed low-power settings in both the arms. The primary objective was to compare the stone-free rate (SFR) and secondary objectives were to compare mean operating times, hospital stay duration, complication rates, need for secondary procedures, and laser efficacy.

Materials and Methods:

A prospective randomized trial, with patients having proximal ureteral or renal stones of 10–20 mm and planned for RIRS was done at a single institute. A total of 60 consecutively admitted patients with signed consent were included for randomization with 30 patients in each arm of dusting and fragmentation modes.

Results:

Median age in dusting and fragmentation arms of 41.5 and 45.5 years, median stone size of 10.45 and 12.25 mm, median stone volume of 351.6 and 490.7 mm³, and median stone density of 1263.5 HU in both arms with comparable hospital stay of median of 2 days in both arms. Lasing time was significantly lesser in the fragmentation group (20.5 minutes; interquartile range [IQR] 15.12–31.62) than in the dusting group (34.25 minutes, IQR 26.62–38.62, p < 0.001). Higher ablation speed for fragmentation mode (0.405 mm³/sec, IQR 0.337–0.635) than for dusting mode (0.17 mm³/sec, IQR 0.135–0.325, p < 0.001). SFRs and complication rates were comparable in both the arms.

Conclusion:

TFL in fragmentation mode has shorter lasing times and better laser efficacy than dusting mode with comparable minimal complications, SFRs, and hospital stay duration.

Clinical Trial Registration number: CTRI050827.

Introduction

Retrograde intrarenal surgery (RIRS) or flexible ureteroscopy is the treatment of choice for most patients with renal calculi less than 2 cm and proximal ureteral stones more than 1 cm due to the modifications in instrument design, techniques, laser lithotripsy, and working instruments.¹

Continuous evolution of laser in the field of urology has been happening since the early 1960s.² The present gold standard with respect to stone lithotripsy is the holmium:YAG (Ho:YAG) laser, which is challenged by the latest entrant in the field, the thulium fiber laser (TFL), on the basis of the first clinical trial in Russia in 2018 and the subsequent clinical approval by the Ministry of Health of the Russian Federation, but it became widely available only after the Food and Drug Administration (FDA) approval in 2019 and the European CE mark approval in 2020.^3,4 Thereafter, there has been a drastic increase in the number of in vivo studies that are coming up on the TFL in addition to the numerous in vitro studies done previously with also few recent systematic reviews on the same.^3,4

The super pulse diode pumped TFL with a wavelength of 1940 nm, same as the absorption peak of water, has certain proven advantages against the gold standard Ho:YAG laser. The fragmentation efficiency is two times faster, dusting efficiency is four to five times faster, less operating times, more dust quantity, and of a smaller size. Also, reduced retropulsion, good visibility, smaller, more flexible, and energy-resistant laser fibers, resulting in better safety and no temperature differences.^3,5

The optimal laser energy settings are various, described as 1–1.5 J and 15–30 Hz for fragmentation and 0.1–0.3 J and 50–100 Hz for dusting in the kidney and 0.2–0.5 J with 10–15 W for dusting and fragmentation in the ureter. However, these data are preliminary with optimal laser settings not being established and needing further studies.³ What is known is that high frequency, low pulse energy, and long pulse width are used in dusting, and low frequency, high pulse energy, and short pulse width are used in fragmentation, with the high-frequency mode resulting in increased dust formation, higher lithotripsy efficacy, lesser operating times, low retropulsion rates, and lower visibility.⁶ To the best of our knowledge, there is no study comparing the same fixed low-power settings comparing only fragmentation and dusting modes for upper tract stones, including proximal ureteral stones.

The aim of the study was to compare dusting vs fragmentation modes with TFL in RIRS. The primary objective was to compare the stone-free rate (SFR), and secondary objectives were to compare the mean operating times, hospital stay duration, complication rates, need for a secondary procedure, and laser efficacy.

Materials and Methods

Study design, setting, and study population

This is a prospective, parallel-group, double-blind, randomized controlled trial done at a single center. All patients older than 18 years with a renal stone of 1–2 cm in the kidney or upper ureter and planned for RIRS procedure were included. Patients not willing, not consenting, not eligible, with anatomic abnormalities, with active urinary tract infection or bleeding, incomplete procedure due to technical error or malfunction, inability to reach the stone, and those with previous endoscopic intervention were not included in the study. Trial protocol adherence was upheld for all the participants in the study and there were no deviations from the original protocol.

Procedure details, randomization, and laser settings

All procedures were done under general anesthesia at a single tertiary center. The procedure was done as per standard in all the patients, using the same instruments, same sheath, and same TFL company laser (Urolase SP, 35W; IPG Photonics), and done by a team of three senior urologists at the same institute, with each urologist having the experience of at least 1000 such procedures. After cystoscopy, the ureter was cannulated with a guidewire over which the ureteral access sheath was passed. Then a flexible disposable digital ureterorenoscope—Indoscope Sleek with 7.5F outer diameter (bioradmedisys™), was introduced and laser lithotripsy was done with TFL, and the mode was as per the pre-decided randomization.

Randomization sequence was by a computer-generated random number allocation sequence, which was generated before patient participation. To ensure that there are equal numbers of patients in each group, stratification was done as per the location of stone (renal and ureteral) and also as per stone density (more or less than 1000 HUs at stone center on CT scan by the reporting radiologist). Randomization to each of the four groups was done in blocks of four. Randomization and allocation concealment were conducted using consecutively numbered and sealed envelopes. This was opened by a designated nurse at the time of laser lithotripsy. The operating times and laser activation times were measured by using a stopwatch and the details were entered at the end of the procedure by the same designated person.

With fixed maximum power of 15 W, the laser settings were 0.1 J, 100 Hz for dusting modes and 1 J, 10 Hz for fragmentation modes. If the operating surgeon felt that the stone disintegration was not proper, then he had the option of increasing the energy setting up to 0.15 J, 100 Hz for dusting and 1.5 J, 10 Hz for fragmentation modes, which was also the maximum permissible limit for the same. The laser fiber that was used was 200 μm. There was no other permissible setting such as popcorning nor was the use of basket allowed. At the end of the procedure, a Double-J ureteral stent was placed. The stent was removed at the standard time of 1 month after the procedure when the patients were subjected to noncontrast computed tomography (NCCT) to confirm stone clearance.

Patients remained blinded throughout the study. The operating surgeon was also blinded as he was not aware about the laser mode settings.

Outcomes

The primary outcome that was measured was SFR as seen on NCCT at 1 month of the procedure. The definition was based on no residual fragments or fragments less than or equal to 2 mm.⁷ Secondary outcomes that were studied were the mean operating times, hospital stay duration, complication rates, need for secondary procedure, and laser efficacy on the basis of energy required for ablation of unit volume of stone and ablation speed on the basis of stone volume ablated per unit of time. The complications were classified as intraoperative and postoperative, with postoperative complications further graded by the Clavien–Dindo classification system.⁸

Statistical analysis and approval

Alpha error probability of 0.05 and power of 0.8 were kept. This sample size was arrived at since this is a pilot study comparing both the modes of TFL in RIRS for the first time to the best of our knowledge. The sample size was as per the criteria for a pilot study of a minimum of 55 patients as laid by Sim and Lewis.⁹ Keeping in mind the possibility of non-evaluable patients, to compensate, a total of 60 patients with 30 in each arm were planned for inclusion.

Continuous variables between both groups were compared using the Mann–Whitney U test. Categorical variables were compared using the chi-square test. Logistic regression was used to adjust for stratification factors for primary and secondary outcomes used. The data were analyzed statistically using IBM SPSS statistics 27 (IBM Corp., Armonk, NY, USA). p-Value <0.05 was statistically significant. Data reporting was as per guidelines as laid out by Assel et al.¹⁰

The study was done as per the Good Clinical Practice Guidelines and as per the Guidelines in the modified Declaration of Helsinki. Informed and written consent was obtained from all the participants. The protocol approval was obtained from the Institutional Review Board before study commencement (IRB No. 4.1/2022) and the ethical clearance was obtained from the Institutional Ethics Committee (815/2022). The randomised controlled trial was done as per the Consolidated Standards of Reporting Trials (CONSORT) guidelines.¹¹

Results

A total of 86 consecutive patients between September 1, 2022, and February 28, 2023, who planned to undergo RIRS procedure at a single tertiary center was enrolled in the study. Out of these, 16 did not meet the inclusion criteria and 10 refused to participate in the study. Of the remaining, 60 RIRS procedures were done in 60 patients. Figure 1 shows the flow of cases through each stage of the study in a CONSORT diagram. There were no exclusions after randomization and none of the patients were lost to follow-up.

FIG. 1.

CONSORT diagram.

Table 1 shows the demographic details of the patients in each group. There are no differences that were significant in both the arms. Table 2 shows the procedural details of both the groups. The lasing time was significantly lesser in the fragmentation group (20.5 minutes; interquartile range [IQR] 15.12–31.62) than in the dusting group (34.25 minutes, IQR 26.62–38.62, p < 0.001), with less laser used in a secondary setting in fragmentation (6 minutes, IQR 3.95–8.87) than in dusting (11 minutes, IQR 8.87–15, p < 0.001). This is reflected by a higher ablation speed for the fragmentation mode (0.405 mm³/sec, IQR 0.337–0.635) than the dusting mode (0.17 mm³/sec, IQR 0.135–0.325, p < 0.001).

Table 1.

Demographic Details

Variable	Dusting	Fragmentation	p
n (%)	30 (100)	30 (100)
Age (years), median (IQR)	41.5 (32.75–56.25)	45.5 (33.5–54.5)	0.86
Gender, n (%)			0.032
Male	23 (76.7)	15 (50)
Female	7 (23.3)	15 (50)
Presenting complaints, n (%)			0.5
Flank pain	26 (86.7)	27 (90)
Incidental	1 (3.3)	2 (6.7)
Fever	1 (3.3)	0
Nausea, vomiting	1 (3.3)	0
Lithuria	1 (3.3)	0
Hematuria	0	1 (3.3)
Stone side, n (%)			0.6
Left	14 (46.7)	16 (53.2)
Right	16 (53.2)	14 (46.7)
Recurrent stone disease, n (%)			0.228
Yes	5 (16.7)	2 (6.7)
No	25 (83.2)	28 (93.3)
Stone number, n (%)			0.553
1	23 (76.7)	26 (86.7)
2	6 (20)	3 (10)
3	1 (3.3)	1 (3.3)
Stone location, n (%)			0.696
Pelvis	12 (40)	12 (40)
Lower calix	3 (10)	7 (23.3)
Upper ureter	9 (30)	8 (26.7)
Another calix	3 (10)	2 (6.7)
Multiple location	3 (10)	1 (3.3)
Stone size (mm), median (IQR)	10.45 (10.1–14.7)	12.25 (10.27–14.72)	0.202
Stone volume (mm³), median (IQR)	351.6 (303–712.5)	490.7 (371–826)	0.167
Stone density (HU), median (IQR)	1263.5 (976–1466.7)	1263.5 (1106–1418.5)	0.982
Hospital stay duration (days), median (IQR)	2 (1–2)	2 (2–2)	0.311

IQR = interquartile range.

Table 2.

Procedural Details

Operative time (minutes), median (IQR)	45 (40–55)	40 (33.75–52.5)	0.173
Lasing time (minutes), median (IQR)	34.25 (26.62–38.62)	20.5 (15.12–31.62)	<0.001
Lasing duration of primary setting, median (IQR)			0.011
0.1 J, 100 Hz	20 (18–25)	NA
1 J, 10 Hz	NA	15.25 (10–22.75)
Lasing duration of secondary setting, median (IQR)			<0.001
0.15 J, 100 Hz	11 (8.87–15)	NA
1.5 J, 10 Hz	NA	6 (3.95–8.87)
Total energy consumed (kJ), median (IQR)	12.35 (7.05–14.6)	12.3 (10.07–13.87)	0.83
Laser efficacy (J/mm³), median (IQR)	29.03 (17.74–45.9)	21.85 (16.05–32.95)	0.074
Ablation speed (mm³/sec), median (IQR)	0.17 (0.135–0.3250)	0.405 (0.337–0.635)	<0.001

Table 3 shows the postoperative period, complications, and follow-up details of both the groups. SFR was comparable in both arms. Despite intraoperative complications in both arms, no procedure was discontinued. Postoperative complications included fever pain. No ureteral strictures or persistent hydronephrosis was observed on follow-up NCCT scan at 1-month duration. Overall, all parameters were comparable.

Table 3.

Complications, Postoperative Parameters, and Follow-Up Details

Intraoperative complications, n (%)			0.355
Bleeding impairing vision	0	2 (6.7)
Mucosal abrasion	1 (3.3)	1 (3.3)
None	29 (96.7)	27 (90)
Postoperative complications, n (%)			0.513
Fever	2 (6.7)	1 (3.3)
Pain	0	1 (3.3)
None	28 (93.3)	28 (93.3)
Complication grade, n (%)			1
0	28 (93.3)	28 (93.3)
1	2 (6.7)	2 (6.7)
Stone-free rates, n (%)			0.554
Complete clearance	28 (93.3)	29 (96.7)
Incomplete clearance	2 (6.7)	1 (3.3)
Secondary surgery requirement, n (%)			0.313
No	29 (96.7)	30 (100)
Yes	1 (3.3)	0

Discussion

In the present study, we performed endoscopic lithotripsy for upper tract stones keeping a fixed laser power, in the primary setting, of 10 W and in the secondary setting of 15 W, keeping in mind that upper ureter stones were also included in the study, consistent with the literature for upper ureteral stones.¹² Performing lithotripsy in the ureter has some difficulties due to the smaller space available, reduced visibility, retropulsion risk, and ureteral injury risk. Here the inherent advantage of TFL vs Ho:YAG laser comes into play. Also, in vivo, the risk of thermal injury specifically in low-power settings was found to be minimal.

As seen in two studies, the greater energy absorption of TFL vs Ho:YAG laser did not translate into higher temperature rise during the procedure.^13,14 The factors that generally affect the choice of strategy of laser modes include surgeon's preference, stone size, and stone location. We did this study to know if all these variables are standardized and the actual difference in the lasing modes.

Dusting mode settings that we used were 0.1 J, 100 Hz in the primary setting and 0.15 J, 150 Hz for the secondary setting. Enikeev et al.⁶ used the setting of 0.15 J, 200 Hz, 30 W for renal stones and reported good laser efficiency, safety, fine dusting, absence of retropulsion, reduced operating times, and occasionally reduced visibility due to snowstorm effect. Another study by Enikeev et al.¹⁵ for ureteral stones recommended the settings of 0.15 J, 100 Hz. A study by Vaddi et al.⁵ used the variable energy settings of 0.1–0.2 J, 100–150 Hz, 10–30 W, followed by the popcorning mode of 0.1–0.2 J, 200 Hz, 20–40 W.

The fragmentation mode settings that we used were 1 J, 10 Hz for the primary setting and 1.5 J, 10 Hz for secondary settings. Enikeev et al.⁶ used the setting of 0.5 J, 30 Hz, 15 W for fragmentation in renal stones. Another study by Enikeev et al.¹⁵ for ureteral stones recommended the same settings stating that this was the optimal balance between power and frequency, with higher energy causing higher retropulsion and theoretical risk of thermal injury, and that higher frequency reduces visibility in which case pulse frequency can be reduced to 12 Hz. The available practical data show that the TFL is safe with low laser penetration and thermal damage depth.¹⁶ The study by Vaddi et al.⁵ recommends the fragmentation settings of 1–2 J, 10–20 Hz, 10–40 W for upper tract stones followed by the popcorning mode.

To study the efficacy of laser in upper tract stones, Ventimiglia et al.¹⁶ introduced the concepts of laser efficacy, which is the total energy required to ablate 1 mm³ of stone, and ablation speed, which is stone volume divided by total laser time, initially for Ho:YAG laser and later extrapolated to TFL. In our study, the median laser efficacy in dusting was 29.03 J/mm³ and in fragmentation was 21.85 J/mm³ and the difference was not significant. A lesser value indicates higher work efficiency for the fragmentation mode. The median ablation speed was 0.17 mm³/sec for dusting and 0.405 mm³/sec for fragmentation, which was significant. Higher ablation speed shows higher work efficiency for the fragmentation mode.

In the study by Vaddi et al.,⁵ with a mean stone volume of 1061.85 mm³, the laser efficacy was 14.35 J/mm³ and ablation speed was 0.86 mm³/sec and they showed that the larger the stone, lesser the energy required per unit volume and faster the rate of ablation reflecting better work efficiency and that the TFL worked efficiently across different stone densities. Enikeev et al.,⁶ using fragmentation settings of 0.5 J, 30 Hz, 15 W and dusting settings of 0.15 J, 200 Hz, 30 W for renal stones, found that laser efficacy and ablation speeds were more in the dusting mode than in the fragmentation mode (2.7 J/mm³ vs 3.8 J/mm³ and 5.5 mm³/sec vs 8 mm³/sec), but as we can see, the dusting mode was with high frequency and power, not comparable.

The intraoperative complications included bleeding and mucosal abrasion in the present study with three in the fragmentation mode and one in the dusting mode, which was not statistically significant, and the procedure could be completed even in the presence of bleeding. The postoperative complications included fever and pain with two in each arm of Clavien–Dindo Grade 1. This is supported by the study by Taratkin et al.¹⁴ and Vaddi et al.,⁵ which showed the safety of TFL due to greater absorption of TFL in water and a low penetration depth. The SFRs in the present study were 93.2% in the dusting and 96.7% in the fragmentation arms, which are similar to the 93.6% SFR in the study by Vaddi et al.,⁵ 92.5% by Enikeev et al.,⁶ and 89% by Taratkin et al.¹⁷

Fragmentation mode also resulted in the creation of dust. This result is reflected in the comparable SFRs even without the use of basketing in fragmentation mode. Low-energy settings were effective even in dusting mode. Higher frequencies resulted in finer dust, reducing visibility, and increasing operating times, which was actually counterproductive. There was more fiber burn-back in fragmentation modes. There was minimal stone retropulsion with upper ureteral stones. Work efficacy was more in fragmentation mode despite having a larger stone volume. These were not the objectives that were focused on in the study but helped in building up practical experience on the same.

The present study has its limitations. These include the single-center setting, which could also be considered its strength since the operating instruments and operating surgeons are uniform. The initial laser settings were the same in both the groups and the increase in power and the timings of such an increase were at the discretion of the operating surgeon. Also, complete blinding of an experienced surgeon is difficult, since they can get a rough idea regarding the laser mode based on the way the stone is being lased, introducing an element of potential bias. Stone composition analysis was not included in either of the groups, which could have affected the efficacy of TFL. The limited sample size, hence, the results cannot be generalized to an entire such population, requiring further studies for external validation.

Conclusions

TFL in fragmentation mode has shorter lasing times and better laser efficacy than dusting mode with comparable minimal complications, SFRs, and hospital stay duration.

Footnotes

Authors' Contributions

N.P.: Writing—original draft; methodology; project administration; and formal analysis (supporting). N.G.: Data curation and acquisition (lead). C.V.: Data curation and acquisition (supporting). N.S.: Formal analysis (lead). A.S.: Study conceptualization and design (lead) and supervision. A.G.: Writing—review and editing (supporting) and study conceptualization and design (supporting). R.S.: Writing—review and editing (lead) and validation. M.D.: Writing—review and editing (supporting). The article has been read and approved by all the authors, the requirements for authorship have been met, and each author believes that the article represents honest work.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

Abbreviations Used

References

EAU Guidelines on Urolithiasis—Introduction—Uroweb [Internet]. Uroweb—European Association of Urology. Available from: https://uroweb.org/guidelines/urolithiasis [Last accessed March 7, 2023 ].

Corrales

, Traxer

. Initial clinical experience with the new thulium fiber laser: First 50 cases. World J Urol, 2021; 39(10):3945–3950.

Kronenberg

, Hameed

, Somani

. Outcomes of thulium fibre laser for treatment of urinary tract stones: Results of a systematic review. Curr Opin Urol, 2021; 31(2):80–86.

Traxer

, Corrales

. Managing urolithiasis with thulium fiber laser: Updated real-life results—A systematic review. J Clin Med, 2021; 10(15):3390.

Vaddi

, Ramakrishna

, Ganeshan

, et al. The clinical efficiency and safety of 60W superpulse thulium fiber laser in retrograde intrarenal surgery. Indian J Urol, 2022; 38(3):191–196.

Enikeev

, Taratkin

, Klimov

, et al. Superpulsed thulium fiber laser for stone dusting: In search of a perfect ablation regimen—A prospective single-center study. J Endourol, 2020; 34(11):1175–1179.

Ghani

, Wolf

. What is the stone-free rate following flexible ureteroscopy for kidney stones?. Nat Rev Urol, 2015; 12(5):281–288.

Dindo

, Demartines

, Clavien

. Classification of surgical complications: A new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg, 2004; 240(2):205–213.

Sim

, Lewis

. The size of a pilot study for a clinical trial should be calculated in relation to considerations of precision and efficiency. J Clin Epidemiol, 2012; 65(3):301–308.

10.

Assel

, Sjoberg

, Elders

, et al. Guidelines for reporting of statistics for clinical research in urology. Eur Urol, 2019; 75(3):358–367.

11.

Schulz

, Altman

, Moher

. CONSORT 2010 statement: Updated guidelines for reporting parallel group randomised trials. J Pharmacol Pharmacother, 2010; 1(2):100–107.

12.

Enikeev

, Shariat

, Taratkin

, et al. The changing role of lasers in urologic surgery. Curr Opin Urol, 2020; 30(1):24–29.

13.

Pasqui

, Dubosq

, Tchala

, et al. Impact on active scope deflection and irrigation flow of all endoscopic working tools during flexible ureteroscopy. Eur Urol, 2004; 45(1):58–64.

14.

Taratkin

, Laukhtina

, Singla

, et al. Temperature changes during laser lithotripsy with Ho:YAG laser and novel Tm-fiber laser: A comparative in-vitro study. World J Urol, 2020; 38(12):3261–3266.

15.

Enikeev

, Grigoryan

, Fokin

, et al. Endoscopic lithotripsy with a SuperPulsed thulium-fiber laser for ureteral stones: A single-center experience. Int J Urol, 2021; 28(3):261–265.

16.

Ventimiglia

, Pauchard

, Gorgen

ARH

, et al. How do we assess the efficacy of Ho:YAG low-power laser lithotripsy for the treatment of upper tract urinary stones? Introducing the Joules/mm3 and laser activity concepts. World J Urol, 2021; 39(3):891–896.

17.

Taratkin

, Azilgareeva

, Korolev

, et al. Prospective Single-Center Study of SuperPulsed Thulium Fiber Laser in retrograde intrarenal surgery: Initial clinical data. Urol Int, 2022; 106(4):404–410.