Assessment of Holmium:YAG,Pulsed-Thulium:YAG and Thulium Fiber Lasers for Urinary Stone Ablation. In Vitro Study

Abstract

Objective:

To evaluate the ablation speed (AS), laser efficiency and direct thermal lesions during urinary stone lithotripsy with the current available laser technologies: Holmium:YAG (Ho:YAG), pulsed-Thulium:YAG (p-Tm:YAG) and thulium fiber laser (TFL) in vitro using different laser settings.

Materials and Methods:

Ho:YAG, p-Tm:YAG, and TFL laser system were used in an in vitro ureteral model with a volume of 125 mm³ Begostone. The following parameters were tested across all laser devices: 0.6J/10 Hz (6 W), 0.6 J/20 Hz (12 W), 1.5 J/10 Hz (15 W), and 1.5 J/20 Hz (30 W), employing short pulse width for all lasers and long pulse width for Ho:YAG and p-Tm:YAG. Ten participants conducted the experimental setup during 3-minutes laser on time, combining the laser technology, settings, and pulse widths, with a total of 20 different combinations. The efficiency, AS and ureteral damage resulting from each intervention were analyzed.

Results:

p-Tm:YAG and TFL demonstrated significantly higher efficiency compared with Ho:YAG (0.049 ± 0.02 Δgr/KJ and 0.042 ± 0.01 Δgr/KJ vs 0.029 ± 0.01 Δgr/KJ; p < 0.05). In all laser sources, as the power increases, the AS also increases (p < 0.05). Furthermore, only at high-energy settings (1.5 J) higher frequency led to increase AS (p < 0.05). Both, p-Tm:YAG and TFL exhibited higher AS compared to Ho:YAG (0.64 ± 0.33 Δgr/s and 0.62 ± 0.31 Δgr/s vs 0.44 ± 0.22 Δgr/s; p < 0.05). Regarding ureteral injuries, as the power increases, there is a higher chance of ureteral damage (p = 0.031). No differences were observed between laser technologies (p = 0.828).

Conclusions:

Both, p-Tm:YAG and TFL exhibited superior performances during laser lithotripsy compared with Ho:YAG, as they demonstrated higher efficiency and ablation speed. Thermal damage did not appear to be associated with specific laser equipment, but higher grades of lesions are described by increasing power.

Introduction

Laser lithotripsy is a widely used urological technique for treating urinary stones, especially during flexible ureteroscopy.¹ Since Maiman introduced the first ruby laser for commercial use in 1966, multiple lasers have been developed, differing in their lasing characteristics and operational settings.² The holmium:yttrium-aluminum-garnet (Ho:YAG) laser, which emerged in the 1990s, initially became the gold standard. However, in the recent years, promising alternatives such as the thulium fiber laser (TFL) and pulsed thulium:yttrium-aluminum-garnet (p-Tm:YAG) laser have challenged the dominance of Ho:YAG.^3,4

A wide range of settings are available to optimize lithotripsy delivering different pulse energies and frequencies, resulting in variable overall power. Additionally, modifying pulse width, including short pulse (SP) and long pulse (LP) width, can lead to a more accurate technique adjusting for stone fragmentation or dusting, respectively.⁵ However, for TFL, although pulse width can be adjusted, key opinion leaders have rejected the use of LP width due to an inefficient low-peak power resulting in stone dehydration and carbonization effects.^5,6

Following this range of laser technologies and settings, no consensus has been reached on the optimal laser configuration or the best laser technology.^5
–7 Recent metanalysis comparing clinical outcomes between Ho:YAG and TFL concluded that when TFL is employed in retrograde laser lithotripsy, higher stone free rate are achieved.^3,8 While there is a lack of clinical studies comparing with p-Tm:YAG, in vitro studies show promising results.^4,9

As there is lack of evidence comparing all three laser technologies, this study aims to address this knowledge gap by meticulously assessing the laser effects on efficiency, ablation speed (AS), and safety during laser lithotripsy.

Materials and Methods

Laser systems

Ho:YAG (H100 Empower Olympus, Japan), p-Tm:YAG (Thulio 100W, Dornier MedTech, Germany) and TFL (Soltive 60W Olympus, Japan) were used. The settings chosen were: 0,6 J at 10 Hz (6 W), 0,6 J at 20 Hz (12 W), 1,5 J at 10 Hz (15 W) and 1,5 J at 20 Hz (30 W) for all three lasers. SP width and LP width were used for Ho:YAG and p-Th:YAG. For TFL, only SP width was used (Table 1). An optical fiber of 272 µm was used for Ho:YAG and p-Tm:YAG and 200 µm for TFL.

Table 1.

Experimental Setup Laser Settings with Holmium:YAG (Ho:YAG), Pulsed Thulium:YAG (p-Tm:YAG) and Thulium Fiber Laser (TFL). Pulse Durations (ms) were Provided by Laser Manufactures according to Laser Settings. Laser Fluence (J/cm2) for Each Experimental Condition is Detailed for Each Optical Fiber Used (272 µm was Used for Ho:YAG and p-Tm:YAG and 200 µm for TFL)

Laser settings	Ho:YAG			p-Th:YAG			TFL
Laser settings	Long-pulse width (ms)	Short-pulse width (ms)	Laser fluence (J/cm2)	Long-pulse width (ms)	Short-pulse width (ms)	Laser fluence (J/cm2)	Short-pulse width (ms)	Laser fluence (J/cm2)
0.6J × 10Hz [6W]	0.12	0.06	810	0.84	0.37	810	1.2	1500
0.6J × 20 Hz [12W]	0.12	0.06	810	0.84	0.37	810	1.2	1500
1.5J × 10Hz [15W]	0.3	0.15	2027	1.08	0.07	2027	3	3750
1.5J × 20Hz [30W]	0.3	0.15	2027	1.08	0.07	2027	3	3750

Artificial kidney stones

Matching Begostone Plus (Bego France^®, Villeurbanne, France) powder combined with distilled water (15:3) was used to create 125mm³ cubic hard stone phantoms according to previously described techniques.^10,11 After preparation, the stones underwent a drying period of 48 hours at ambient temperature. All stones were weighted with a digital balance of 0.001 accuracy (Fig. 1).

FIG. 1.

(A) BegoStones 125mm³, dry before lithotripsy; (B) Live endovision of the ureteral model in the Pusen screen (Zhuhai Pusen^©, China) with a BegoStone in it during the procedure; (C) BegoStone weighing before and after the procedure; (D) Experimental setup showing four 17 cm-length polymer tubes, closed on one side and masked with an opaque tape submerged in saline and irrigation system settle at 40 cm H₂O.

Experimental setup

The experimental set up replicates previously published research consisting of a ureteral model created with a transparent polymer tube of 17 cm length and 5 mm diameter, closed on one side.¹² An opaque tape was used to cover it up to minimize biases due to stone observation (Fig. 1). Different stone and ureteral models were used for each test. Trials were conducted using a digital flexible ureteroscope (Pusen, 7.5Fr, WC 3.6Fr, Zhuhai Pusen^©, China). Irrigation was ensured by a combination of gravity irrigation at 40 cm H₂O above the saline tray and a hand-assisted irrigation system (Irri-Flo II, Olympus^©, Japan) providing on-demand forced irrigation for proper visibility (Fig. 1).

Ten urologists participated in the trial, each participant had completed at least 1 year of endourology training, performing clinical cases independently. Most of the participants were residents, ranging from their 3rd to 5th year of residency. All of them, conducted the experimental set up once, testing the 20 different laser settings during 3 minutes laser on time (LOT): 8 lithotripsy sessions with both, Ho:YAG and p-Tm:YAG, and 4 lithotripsy sessions with TFL.

Stone ablation measurement

After the lithotripsy session, the resulting material included fine dust, small fragments, and occasionally larger pieces. All fragments that could be manually collected from each ureteral model were weighed after a drying period using a digital balance. Ablation was measured as the difference in weight between the pre-treatment stone phantom and the mass of the residual fragments, effectively representing the total mass loss due to the lithotripsy process, excluding the fine dust particles that could not be collected divided by pre-treatment stone phantom weight.

Laser efficiency

Laser parameters were obtained from each laser after every lithotripsy session, including laser settings, total energy (KJ), LOT (s) and lasing time (s). After the procedure, ureteral model and stone fragments were labeled and dried at room temperature (21°C) and were weighted again.

Laser efficiency, stablished by the volumetric ablation performance in relation to the energy resource used, was calculated by dividing the weight difference before and after lithotripsy by the total energy used: $\frac{Artificial Stone Weight before the lithotripsy (gr) - Artificial Stone Weight after the lithotripsy once dried (gr)}{Total energy (KJ)}$

Laser ablation speed (AS)

Was calculated by dividing the weight difference before and after the procedure by the LOT (s): $\frac{Artificial Stone Weight before the lithotripsy (gr) - Artificial Stone Weight after the lithotripsy once dried (gr)}{LOT (s)}$

Assessment of ureteral lesions

Ureteral models were collected and labeled. A post-test examination was performed, classifying ureteral damage in a scale (0–3) according to the findings in the surface of the ureteral model as previously reported.¹² The absence of lesions (0), small/superficial impacts (1), large/profound impacts (2), burn areas (3) (Fig. 2). If there were different types of injuries, the highest grade was prioritized for classification. Plastic tubes were blindly classified regarding the damage score by consensus between two authors (A.S. and E.C.).

FIG. 2.

Ureteral damage classification. Score 0–3 according to impacts and burns’ magnitude in the ureteral model’s surface after lithotripsy.

Statistical analysis

SPSS v26 software (IBM Statistics) was used for statistical analysis. All used laser equipment and settings were included and analyzed. Laser efficiency and AS were assessed using one-way ANOVA and a posthoc analysis were conducted with Bonferroni Tests and T-student test. Ureteral damage was evaluated using one-way ANOVA and chi-square tests. A p-value of 0.05 or less was considered statistically significant.

Results

Laser performance

Statistical analysis revealed no significant differences in the efficiency of each of the lasers between the laser settings (energy and pulse frequency) (p = 0.118). For Ho:YAG technology, no differences were observed between SP and LP width (p = 0.436), neither for p-Tm:YAG (p = 0.739) (Table 2). Across different laser technologies, both p-Tm:YAG and TFL demonstrated superior laser efficiency compared to Ho:YAG (0.049 ± 0.02 Δgr/KJ and 0.042 ± 0.01 Δgr/KJ vs 0.029 ± 0.01 Δgr/KJ; p < 0.05) (Table 2).

Table 2.

Overall Mean Laser Efficiency (Δgr/KJ) according to Laser Generator and Settings during 3-Minute Laser on Time (LOT) Lithotripsy

	Short pulse width			Long pulse width
	Δgr/KJ (mean±SD)			Δgr/KJ (mean±SD)
	Ho:YAG	p-Th:YAG	TFL	Ho:YAG	p-Th:YAG
0.6J/10 Hz	0.026 ± 0.01	0.047 ± 0.01	0.051 ± 0.01	0.027 ± 0.01	0.046 ± 0.02
0.6J/20 Hz	0.031 ± 0.01	0.041 ± 0.01	0.041 ± 0.01	0.027 ± 0.01	0.045 ± 0.01
1.5J/10 Hz	0.036 ± 0.01	0.056 ± 0.02	0.044 ± 0.01	0.040 ± 0.01	0.056 ± 0.02
1.5J/20 Hz	0.022 ± 0.01	0.051 ± 0.02	0.034 ± 0.01	0.028 ± 0.00	0.041 ± 0.02
Total	0.029 ± 0.01	0.049 ± 0.02	0.042 ± 0.01	0.030 ± 0.01	0.047 ± 0.02

Regarding AS, when comparing settings, higher power corresponded to higher AS for both SP and LP widths across all laser sources (p < 0.05) (Table 3). Furthermore, isolated variations in frequency were found to modify AS only when high energy (1.5 J) was delivered for both SP and LP pulse widths. At different pulse width, no differences were found in AS between Ho:YAG-SP and Ho:YAG-LP (p = 0.463) neither between p-Tm:YAG- SP and p-Tm:YAG-LP (p = 0.712). When comparing laser technologies, there were no differences between p-Tm:YAG and TFL and both demonstrated superior AS compared with Ho:YAG (0.64 ± 0.33 Δgr/s and 0.62 ± 0.31 Δgr/s vs 0.44 ± 0.22 Δgr/s; p < 0.05) (Table 3).

Table 3.

Overall Mean Total Ablation Speed (Δgr/s) according to Laser Generator and Settings during 3-Minute Laser on Time (LOT) Lithotripsy

	Short pulse width			Long pulse width
	Δgr/s (mean ± SD)			Δgr/s (mean ± SD)
	Ho:YAG	p-Th:YAG	TFL	Ho:YAG	p-Th:YAG
0.6J/10 Hz	0.16 ± 0.08	0.28 ± 0.1	0.3 ± 0.11	0.16 ± 0.06	0.28 ± 0.14
0.6J/20 Hz	0.37 ± 0.13	0.47 ± 0.12	0.48 ± 0.13	0.33 ± 0.13	0.53 ± 0.07
1.5J/10 Hz	0.55 ± 0.08	0.78 ± 0.36	0.67 ± 0.18	0.6 ± 0.08	0.79 ± 0.21
1.5J/20 Hz	0.67 ± 0.16	1.03 ± 0.31	1.03 ± 0.31	0.84 ± 1.2	1.12 ± 0.42
Total	0.44 ± 0.22	0.64 ± 0.37	0.62 ± 0.31	0.48 ± 0.25	0.68 ± 0.39

Ho:YAG, holmium YAG; p-Th:YAG, pulsed -thulium YAG; TFL, thulium fiber laser; SD, standard deviation.

Ureteral damage

Ureteral injuries were evaluated using a grading system ranging from 0 to 3. Variations in settings significantly influenced the occurrence of ureteral damage (p = 0.031). As illustrated in Figure 3, minimal lesions were detected at low-power settings, whereas more sever lesions were observed at high-power settings. Notably, the application of high-energy combined with high frequency (1.5 J/20 Hz) resulted in a higher incidence of type 3 lesions for both, SP and LP width. However, no statistically significant differences were observed when comparing ureteral damage based on the laser generator used (p = 0.828).

FIG. 3.

Bar chart analysis of the severity of direct thermal lesions generated in each trial by different laser settings in the plastic tubes. The bars are segmented to display the distribution of lesion severity ratings (ranging from 0 to 5). Each segment within the bars represents the proportion of lesions categorized at a specific severity level.

Discussion

The experimental results underscore the key factors to be considered during laser lithotripsy: efficiency, AS, and safety. To our knowledge, this is the first study comparing these three laser technologies during in vitro laser lithotripsy. Importantly, our results reveal that, when using the same laser settings, both p-Tm:YAG and TFL outperform the gold standard in terms of efficiency and AS. Furthermore, there are no differences in safety among the laser sources. However, increasing the power leads to greater direct thermal damage for all laser technologies.

A recent systematic review concludes that p-Tm:YAG appears to be a potential alternative to Ho:YAG and TFL.⁴ In our study, both p-Tm:YAG and TFL showed comparable results, surpassing Ho:YAG in terms of efficiency and AS. These results align with previous findings by Kraft et al., who examined the dusting performance of p-Tm:YAG in vitro compared with TFL and found no significant disparities in the amount of stone ablation.¹³ Moreover, using a 35W Ho:YAG laser source, the same group previously reported that p-Tm:YAG demonstrated superior stone ablation when longer pulse durations were employed.¹⁴ This suggests that regardless of the power output of the Ho:YAG laser, p-Tm:YAG consistently demonstrates favorable outcomes.

These findings are important as TFL has previously been shown to achieve consistently better lithotripsy performance compared with the Ho:YAG laser, including higher ablation efficiency and smaller powder particles.^12,15 Our study supports these results with the two alternative technologies to the gold standard. This difference can be explained by different laser pulse shapes, different water absorption coefficients of the laser, and different peak powers (PP).^2,16 The Ho:YAG laser pulse exhibits a spiky profile characterized by a very high PP value at the pulse’s onset (1800–14500 W). In contrast, the TFL delivers a lower PP at 500 W and a rectangular pulse shape.¹⁶ p-Tm:YAG appears to be midway between Ho:YAG and TFL, as the company declared a PP between 1300–3700 W. Both, the lower PP and the more uniform profile inherent in TFL and p-Tm:YAG, play a major role in retropulsion, which allows for a longer time of contact from the fiber tip to the stone, thus allowing greater fragmentation for both p-Tm:YAG and TFL in comparison to Ho:YAG.^17
–19

The observed damage in our in vitro study likely resulted from direct laser contact. Our statistical analysis revealed no correlation between the number or severity of lesions and the used laser technology. Nonetheless, higher-grade lesions were more prevalent at higher power settings. Additionally, high-power settings coupled with high-frequency parameters can induce a “snowstorm” effect, impairing visibility and prompting operators to adjust their duty cycle to enhance visibility. Conversely, steady-state lasing ensures continuous beam delivery, facilitating optimal visibility and effective stone fragmentation, typically achieved at lower frequencies. It is essential to emphasize that all lasers are equally safe; concerns primarily arise from the use of high-power settings rather than inherent technological differences. These findings are consistent with prior research.^5,8,12

The concept of AS compresses both efficiency and safety considerations. Enhanced endoscopic visualization, coupled with the reduced retropulsion offered by TFL and p-Tm:YAG, could contribute to minimizing operative time reported in our investigation. Regarding AS, similar findings have been documented, showing that TFL is consistently at least 2 times faster than Ho:YAG laser across all settings, including pulse modifications.^3,8,12 To date, this is the first publication reporting AS in p-Tm:YAG.

While this study is conducted in vitro, our findings align with those observed in clinical studies. Notably, a recent meta-analysis supports our findings by indicating a higher stone-free rate favoring TFL, along with higher efficiency and shorter operative time over Ho:YAG.^3,8 Although no study evaluating the efficiency and safety of p-Tm:YAG in vivo has been released, there are a few clinical series with p-Tm:YAG.^4,20 A series reported by Panthier et al. with 25 patients shows a similar AS in real life, being 0.75 mm³/s with similar laser setting range.²⁰

While our study provides valuable insights into laser performance and safety, it is essential to acknowledge certain limitations. Identical lithotripsy conditions were difficult to obtain, leading to an incomplete simulation of essential aspects of the procedure, such as blood circulation, which plays a major role in preventing and repairing thermal injury.²¹ Moreover, while BEGO stone phantoms are widely used in vitro for their consistency and ease of use, it is important to acknowledge that these phantoms may not absorb optical energy in the same manner as human stones which can significantly influence the interaction with laser energy during lithotripsy. BEGO stone phantoms are designed to mimic the general physical properties of human stones but do not replicate the complex optical absorption and thermal properties. Specifically, certain laser settings and energies that are effective on BEGO phantoms may not yield the same results on human stones due to differences in absorption, fragmentation patterns, and thermal effects. However, despite these limitations, we consider that the use of BEGO phantoms provides a controlled and reproducible environment to evaluate and compare laser settings and techniques. The endpoint was to determine whether different laser generators and/or settings could lead to varying laser performance and distinct grades of injury. Additionally, it was not possible to use identical pulse durations due to technical limitations of the examined laser devices. This reflects real-world practice, where exact pulse durations are dictated by laser manufacturers. In addition, it is known that prolonged lithotripsy sessions and high-power settings can elevate the temperature of the lithotripsy water, which could lead to indirect thermal damage to the ureter.^21

–24 We have not measured temperature during the test, however, with proper irrigation management, as implemented in our experimental setup, we mitigate the risk of temperature increase. Furthermore, our study did not exceed the critical threshold of 30 W associated with temperature elevation.²⁴ In conclusion, while these limitations exist, they do not detract from the overall findings regarding the performance and safety of different laser settings.

Conclusions

Both p-Tm:YAG and TFL demonstrated superior laser performance during lithotripsy compared with Ho:YAG, exhibiting higher efficiency and AS. While ureteral damage did not show significant differences between laser generators, higher power settings were associated with more severe lesions. These findings underscore the importance of choosing appropriate laser technology and energy parameters based on clinical needs and the potential impact on surgical outcomes. Consideration of these factors, along with further research to address limitations and validate findings, is crucial for optimizing stone management strategies and minimizing complications in urological practice.

Footnotes

Authors’ Contributions

A.S.: Project Development. Data collection. Data analysis. Article writing; F.P.: Data analysis.; E.C.: Data collection; A.M.: Data collection. Article editing; L.P.: Article editing; A.A.: Article editing; O.T.: Project development; J.M.L.: Project development, article editing; M.P.L.: Article editing.

Research Involving Human Participants and/or Animals

This research does not involve research in humans or animals

Ethical Approval

Not applicable

Author Disclosure Statement

The authors declare that they have no conflict of interest.

Funding Information

Frederic Panthier is a consultant for Dornier Medtech. Alba Sierra certifies that all the other authors have no specific conflicts of interest relevant to this study, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the article (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending).

Supplementary Material

Supplementary Table S1

Abbreviations Used

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Supplementary Material

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