Introduction

Since the initial introduction of lasers as tools for intracorporeal stone fragmentation thirty-five years ago, there have been a number of innovations in this technology that have revolutionized the field of endourology.^1,2 The development of the pulsed holmium:yttrium-aluminum-garnet (Ho:YAG), in particular was a major milestone in the evolution of safe and effective intracorporeal lithotripsy.^3,4 As experience with the Ho:YAG laser grew, it ultimately emerged as the gold-standard laser. With energy avidly absorbed in water enhancing its safety profile, an ability to fragment stones of all compositions and the availability of fibres of varying sizes, the Ho:YAG laser was a significant upgrade from electrohydraulic and pneumatic intracorporeal lithotripters.

The widespread availability of the Ho:YAG laser ushered in the era of modern day flexible ureteroscopy and improved patient outcomes.

In this review article, the mechanisms behind laser fragmentation will be discussed. Features of the Ho:YAG laser and the newest device the Thulium Fiber Laser (TFL) will be compared.

Features of the holmium: YAG laser

Although the Ho:YAG was not the first laser with clinical application for lithotripsy, soon after its introduction it became the tool of choice for intracorporeal ureteroscopic and cystoscopic lithotripsy. Initial devices were however, somewhat limited by the ability to manipulate only two parameters, pulse energy and frequency. While for many clinical scenarios this was not a major limitation, as more complex stone situations were encountered, having the ability to use higher settings and alter the pulse duration allowed for an expanded use of the laser especially with flexible ureteroscopy and intra-renal procedures. The incorporation of the “Moses effect” whereby an initial short, low energy pulse “parting the waters” then allowed the subsequent pulse to have a more efficient ablative effect was another important innovation.^8-10

The Ho:YAG laser operates via a flashlamp-pumped (Xenon or Krypton) solid-state configured YAG crystal rod chemically doped with Holmium ions inside an optical cavity. The laser pulsation is the light emitted by the flashlamp interacting with the Holmium ions and produces new photons with an infrared wavelength of 2,120 nm. These photons are reflected inside the optical cavity mirrors (reflective mirrors at each end) and multiplied depending on the desired pulse energy. The pulsed laser energy is tightly focused or collimated to exit the cavity when the laser is activated.^8,11-13

The Ho:YAG generator requires a water-cooling system, due to the heat produced inside the optical cavity. The maximal temperature range of the laser crystal cavity limits the power and frequency of each generator. The solution for high power Ho:YAG lasers is to use multiple optical cavities allowing generators to reach >50 watts.

The clinical advantages of the Ho:YAG laser include the ability to fragment urinary stones of all compositions, application with flexible endoscopes and minimal tissue penetration. The Ho:YAG laser also has multipurpose applications including the capacity to cut, coagulate, ablate, enucleate and vaporize soft tissues.^12-14

Despite the incremental technological advances however, there have remained some inherent limitations with the Ho:YAG laser. These issues include:

As a result of some of these shortcomings, evaluations of other wavelengths continued with the hopes of further improving the safety and efficacy of laser lithotripsy.

Features of the thulium fiber laser

The Thulium Fiber Laser (TFL) was first described by Fried in 2005.¹⁵ Several pre-clinical studies then followed providing some insight into its unique properties.^16-18 The TFL operates via an electronic modulated laser diode-pumped configuration, which allows for high and constant peak power levels. A long (10-30 meters), and very fine (10-20 µm) silica fiber chemically doped with Thulium ions, transmits the laser energy to the externally connected laser fiber.^8,11-13

The TFL can operate in a continuous mode or adopt a super-pulsed mode (50 µs to 12000 µs pulse duration). The TFL is more efficient because the spectrum of emission (laser diode) matches the Thulium ions, producing less heat in comparison to the Ho:YAG (flash-lamp produces a broad light spectrum emission). Due to less wasted energy, less heat is produced and the cooling can be performed by an air system (fan ventilation) inside the generator even at a high-power mode (>50 watts). This allows for a smaller laser box and is quieter to use. The fiber laser technology provides a simpler focusing of the beam and the ability to transmit the high energy via smaller fibers (150 microns).^8,11-13

The infrared wavelength of 1,940 nm (closer to liquid water absorption peak than the Ho:YAG laser), produces a four-fold higher absorption coefficient, allowing for a higher ablation efficiency at equivalent pulse energies.^{11,13,17,19-21}

The low pulse energy and high frequency capabilities of the TFL opened the door to a number of possibilities including better dusting mode, a reduction in stone retropulsion and better ablation efficacy of the stone.^11,17,19 Hardy et al. published preliminary results comparing the dusting mode between Ho:YAG and TLF lithotripsy, and showed the TLF demonstrated a higher stone ablation rate and smaller stone fragments under the same laser settings in an experimental model.¹⁷

During Ho:YAG laser lithotripsy applications, stone retropulsion is a common and annoying occurrence requiring the surgeon to chase the stone. With the TFL, the retropulsion threshold is up to four times higher when compared to Ho:YAG at equal pulse energies. Retropulsion is evident when using the Ho:YAG at 0.2 J, and with the TFL it is observed at higher energies above 1 J. This difference is thought to be due to the more constant, prolonged peak power and longer pulse duration with the TFL.^13,21,22 In contrast, Knudsen et. al documented an equivalent retropulsion of the TFL vs the Ho:YAG 120W with Moses mode.²²

The higher pulse frequency, more variable pulse energy, pulse width and symmetrical pulse profile of the TFL energy could have significant benefits during lithotripsy.^8,11,12,17 Table 1 compares the features of the Ho:YAG and TFL.

Clinical experience with the TFL

The first clinic experience with the TFL was a retrospective series reported by Martov et al. in 2018.²³ Fifty-six patients were included with upper and lower urinary tract stones. Twenty-four patients underwent treatment by retrograde intrarenal surgery (RIRS) and the size of the upper urinary tract stones was 0.6-1.8 cm. The authors reported 100% stone fragmentation with 47.7% requiring additional stone removal techniques. The mean stone disruption time was 19 minutes and at follow-up (4-6 weeks), one patient was found to have a residual symptomatic stone. The first TFL case series in North America was a retrospective study by Carrera et. al, and included 118 treated urinary stones most commonly treated by RIRS (76.3%).²⁴ The mean operative time was 59.4±31.6 minutes and a ureteral access sheath was used in 71.1% of procedures. Dusting technique was the preferred treatment (67.1%) with mean total laser-on-time of 10.8±14.1 minutes, mean frequency of 228±299 Hz and mean pulse energy of 0.2 ± 0.3 J. No signs of ureteral thermal injuries were observed. They concluded the TFL was able to ablate various stone compositions with a safety profile comparable to the Ho:YAG.

Corrales et. al. reported an initial clinical experience in the first 50 patients from Tenon hospital in Paris.²⁵ Forty-one patients were treated for renal stones. The median renal stone volume was 1800 (IQR 682-2760) mm3 with a median stone density of 1200 (IQR 750-1300) HU. The median pulse energy was 0.3 (IQR 0.2-0.6) J with a median pulse frequency of 100 (IQR 50-180) Hz. The median laser-on-time was 23 (IQR 14.2-38.7) minutes. Two complications were noted in the group of renal stones but none related to the TFL. The authors concluded the TFL was a safe and effective modality for lithotripsy during RIRS, and suggested keeping the settings to less than 15-30 Watts. Their experience with dusting was similar to the findings of Enikeev et. al., in that higher dusting efficiency was observed with higher frequencies.²⁶

Ulvik et al. documented the results of the first prospective randomized clinical trial of TFL (60W) versus Ho:YAG (30W) for ureteroscopy lithotripsy.²⁷ After a single procedure, the renal stone-free rate at 3 months was 49% and 86% for Ho:YAG and TFL respectively (p =0 .001). The operative time was shorter for the TFL (49 compared to 57 minutes, p = 0.008) but the mean laser-on-time time was similar 13 (IQR 6-17) minutes for the TFL and 13 (IQR 4-19) for the Ho:YAG (p = 0.9) with a mean total energy of 3.5 (IQR 0.9-5.1) vs 4.2 (IQR 0.6-6) KJ (p = 0.4).

Haas et al. recently reported a single center prospective randomized trial comparing the high-power super-pulsed Ho:YAG with “Moses 2.0” technology versus the TFL.²⁸ One hundred and eight patients were randomized with ureteric and kidney stones measuring 3-20 mm. No difference in ureteroscopy time was noted when subdivided based on stone size, >1,023 HU or <1,023 HU or stone location. A comparable stone-free rate was noted for both lasers at 4-8 weeks using different imaging modalities (X-ray, ultrasound and CT scan). Median Laser-on-time was similar (Ho:YAG 4.8 VS TFL 5.1 minutes, p = 0.3) and less energy (Ho:YAG 3.1 VS 4.3 kJ, p = 0.046) was noted for disruption as well as ablation efficiency in favor of the Ho:YAG laser (p = 0.009). The authors describe that similar starting laser settings and modifications were left at each surgeon’s discretion, which may have influenced results given the optimal TFL settings are still not entirely known.

Various laser settings have been proposed based on stone location and whether dusting or fragmentation is the intention.^29,30 At this time, the general advice has been to keep the total energy to under 50 watts in the bladder, 25 watts in the kidney and less than 10 watts in the ureter.^30-32 Suggested settings for dusting and fragmentation are listed in Table 2.

Safety cosiderations with the TFL

Both the Ho:YAG and TFL generate heat during the process of intracorporeal lithotripsy. Both wavelengths are highly absorbed in water, however which helps to minimize collateral damage to surrounding tissues. The wavelength of the TFL is closer to the liquid water absorption coefficient than that of the Ho:YAG, resulting in a lower optical penetration in tissue in favor to the TFL (0.077 VS 0.314 mm), providing a high safety profile due to four times less tissue depth penetration.^8,12

Despite the theoretical safety margin, concerns have been raised with respect to potential thermal effects of the TFL, although this is a subject of some controversy. With the higher TFL water absorption, it has been theorized that higher temperatures may still be generated and the potential for thermal injury to nearby tissues. Andreeva and colleagues demonstrated in an in-vitro ablation model comparing the Ho:YAG and TFL that there were no temperature differences at equivalent power settings.²¹ An ex vivo study by Molina et. al comparing the two wavelengths noted equivalent temperatures rises during dusting but higher temperatures during TFL fragmentation.³³ None of the recorded temperatures in their experiments reached the threshold for thermal injury, however. With the TFL capable of much higher frequency settings, the operator much ensure precise laser fiber placement on the stone as fiber movement may be more difficult to control and lead to inadvertent contact with surrounding tissues.

Summary

The development and availability of TFL lithotripsy for clinical use is another quiver in the endourologist’s armamentarium for the treatment of complex stones. Clinical experience to date would suggest this wavelength provides improved dusting capabilities. This feature maybe especially advantageous when tackling larger renal stones, obviating the need for more invasive percutaneous procedures. The reduced retropulsion during laser activation may allow for more efficient and quicker stone disruption. The smaller diameter fiber may allow for more consistent access to the lower pole when treating stones in this challenging location.

Although initial clinical experience is encouraging, further work is needed to identify optimal settings based on stone location, composition and therapeutic goals (dusting vs fragmentation). As this work continues we must also remain cognizant of producing optimal lithotripsy effect while minimizing the potential for tissue injury. It is an exciting time in endourology!