Development of a high-power blue diode laser for precision vaporization of prostate tissue for the surgical management of benign prostatic hyperplasia

Abstract

This paper explores the advancement and application of high-power blue diode lasers in treating benign prostatic hyperplasia (BPH). Addressing the challenges posed by existing techniques, the study focuses on optimizing tissue removal methods. Energy platform for BPH should balance a range of factors, such as operative time, patient conditions, urinary functions, complications, durability, accessibility, and cost, all while prioritizing patient care. Blueray Medical's innovation of high-power blue diode laser systems for BPH surgery is explored, with emphasis on achieving a balance among these considerations. By illustrating the biomedical effects of lasers and their interaction with soft tissues, particularly emphasizing the role of photon absorption by biomolecules and proteins in tissue behavior, this study outlines the advantages of the high-power blue diode laser system. The initial laboratory experiments and clinical results consistently align with our theoretical predictions, especially in terms of tissue vaporization efficiency, tissue coagulation, and bleeding control. In conclusion, blue diode lasers hold potential to enhance surgical outcomes for BPH. Their unique properties offer benefits like improved tissue removal rate and reduced thermal damages. Integrating blue laser technology into BPH protocols could lead to shorter hospital stays, cost savings, and expanded patient eligibility, although rigorous clinical studies are needed to fully understand their benefits and limitations.

Graphical abstract

Keywords

blue diode laser / benign prostatic hyperplasia / laser vaporization / preserving sexual functions / soft tissue ablation

1 INTRODUCTION

The prevalence of benign prostatic hyperplasia (BPH) has been on a steady rise alongside the aging global population, leading to substantial healthcare burdens and economic challenges. While medical therapy is an initial option for mild to moderate BPH management, patients with severe symptoms or complications often require surgical intervention. Transurethral resection of the prostate (TURP) has long stood as the gold standard surgical treatment for BPH due to its established efficacy. However, TURP is linked with potential complications, including bleeding, longer hospital stays, longer recovery times, and sexual dysfunction.

In recent decades, alternative techniques have emerged to address limitations of TURP. These techniques generally fall into two categories: procedures involving the removal of prostate tissues and non-tissue removal procedures. The former category includes TURP, holmium laser enucleation of the prostate (HoLEP), green laser enucleation of the prostate (GreenLEP), green laser photoselective vaporization of the prostate (PVP), thulium laser enucleation of the prostate (ThuLEP), and robotic waterjet treatment (Aquablation). The latter category includes water vapor thermal therapy (Rezum) for prostate shrinkage and prostatic urethral lift therapy (PUL, UroLift) for symptom relief. Each approach has distinct advantages and limitations.

Laser-based therapies, in general, have demonstrated favorable clinical outcomes. Laser procedures for BPH offer minimally invasive alternatives to open surgery and TURP, resulting in reduced blood loss, shorter hospital stays, and faster recovery times[1], suitable for patients having anticoagulation therapy[2]. They afford precise control during tissue ablation, enabling selective targeting of the prostatic gland while minimizing damage to adjacent structures[3]. Compared to conventional surgical techniques, laser-based procedures exhibit lower rates of perioperative bleeding, leading to decreased blood transfusion requirements[4]. Laser treatments even enable some patients to undergo outpatient-based surgeries, thereby alleviating the strain on hospital resources and potentially reducing healthcare costs[5]. Similar to traditional surgical methods like TURP, the laser-based procedures, such as HoLEP, ThuLEP, or PVP, still have been associated with some incidence of sexual dysfunction[6,7], which is significantly higher than Rezum and Urolift procedures[8,9].

Despite the advantages of laser techniques, they come with their own set of limitations. Enucleation surgeries like HoLEP and ThuLEP demand specialized expertise with a steep learning curve, making them less appealing, especially among urologists in underdeveloped regions. PVP procedures have faced criticism for their slow tissue vaporization rate, leading to longer operation times and inadequate tissue removal[10]. Some patients have reported the need for reoperation a few years after PVP, raising concerns about its durability[11]. Additional concerns raised regarding PVP procedures include the high expense associated with single-use surgical laser fibers, often surpassing 600 US dollars, and their restricted lifespan of merely 650 kJ. These issues are frequently voiced by urologists.

For prostatic tissue removal techniques, operative time is one of the important concerns for urologists. Nguyen and Zorn compared procedure time and prostate size for Aquablation, GreenLEP, HoLEP, and ThuLEP for prostates larger than 40 g, concluded Aquablation is the fastest with 0.16 min/g, then 0.32 min/g, 0.28 min/g, and 0.32 min/g for GreenLEP, HoLEP, and ThuLEP, respectively. The slowest is PVP, only 0.63 min/g[12]. Non-tissue removal techniques are general having shorter operative time. Operative time would be less than 10 min for Rezum for averaged prostate volume of 65 mL[13], and less than 20 min for Urolift if the number of implants are less than 4[14].

There are a multitude of challenges associated with both tissue removal and non-tissue removal techniques, encompassing factors such as operative time, preoperative patient conditions, urinary function, postoperative complications (including sexual dysfunction), long-term durability, availability, accessibility, and economic cost. Balancing all of these diverse factors for each individual patient remains the top concern for urologists.

To overcome the various limitations associated with currently available tissue removal or non-tissue removal techniques, in recent years, Blueray Medical (located in Xi'an) has developed high-power blue diode laser systems for the surgical management of BPH, striving to address these multifaceted challenges. In this paper, we first comprehensively outline the biomedical effects of lasers on soft tissues. This is rooted in the biophysical properties of tissue light absorption and the advancements in laser technology. Subsequently, we detail the development of a surgical high-power diode blue laser system with a center wavelength of approximately 450 nm and an output power of up to 200 W, which we successfully materialized surgeons' needs in some degree to a product's specifications.

Furthermore, this paper outlines some published blue diode laser related preclinical studies that compare the diode blue laser with some market available urological lasers, summarizing unique properties of the blue laser. Notably, as of the time of writing this paper, more than 3000 procedures employing our high-power blue diode lasers for BPH have been performed in China. Here, we brief some of this pioneered clinical work, and try to provide an overall picture of blue laser vaporization of the prostate.

As more hospitals adopt high power blue laser as their main tool for the treatment of BPH, we believe more carefully designed multicenter randomized controlled trials (RCTs) are needed, including an RCT study to investigate postoperative sexual functions. This initiative seeks to further explore the advantages and limitations of employing high-power diode blue lasers for BPH management.

2 BIOMEDICAL EFFECTS OF LASERS

The integration of light into the medical field gained various applications following the invention of the laser. The first laser (lamp-pumped ruby laser) was invented in the United States in 1960 and was used in biomedical applications in 1961. Consequently, both the laser technology and biomedical communities embarked on systematic research into the biomedical effects of lasers, from basic research in biophysics, bio-optics, bio-quantum, biochemistry, bio-spectroscopy, and fluorescence to the thermal effects of light on biological tissues, biological effects, biochemical effects, laser medical diagnosis, and DNA analysis. These combined efforts yielded pioneering outcomes.

The phenomenon of light absorption by biological tissue means that biological tissue obtains the energy of light at the molecular level. To understand the process of light absorption, the concept of photon energy is important. Photon energy can be interpreted as photon wavelength. The shorter the wavelength of light, the higher the energy of the photon. Photon energy values (expressed in electron volts, eV) for select commonly used urological lasers are tabulated in Table 1, among which 450 nm blue diode laser has the highest photon energy.

Almost all biomedical materials exhibit selective light absorption or photoselectivity. The penetration depth of a laser mainly depends on the absorption of its wavelength by the specific biomaterial. For laser tissue ablation, water and hemoglobin are two most commonly studied light absorption chromophores because of their simplicity and rich in living tissues. Water molecular is another important chromophore. Examples of commercially available urological water-absorbing infrared lasers are 1470 nm diode laser, thulium laser, and holmium laser.

Figure 1 illustrates the optical absorption profiles of oxyhemoglobin (HbO₂) and deoxyhemoglobin (Hb) across from deep blue to orange color (400−600 nm) light spectrum[15]. The absorption peaks at approximately 414 nm for HbO₂ and around 434 nm for Hb, with molar extinction coefficient (cm⁻¹M⁻¹) of 524 × 10³ and 552 × 10³, respectively. For blue diode laser with center wavelength about 450 nm (440−460 nm), the hemoglobin extinction coefficients can be from 44 × 10³ cm⁻¹M⁻¹ up to 413 × 10³ cm⁻¹M⁻¹, higher than 532nm green laser (LBO laser), which is about 44 × 10³ cm⁻¹M⁻¹. Optical energy absorption by hemoglobin leads to an elevation in blood temperature.

The energy of photons from yellow, green, blue, and violet lasers, typically exceeding 2 eV, is sufficient for absorption by diverse organic molecules and proteins beyond hemoglobin. The higher the photon energy, the higher opportunities the photons to be absorbed by soft tissues. As a rule of thumb, shorter wavelength lasers in general result high tissue volume absorption coefficients, thence result higher soft tissue ablation rate.

According to the principle of energy conservation in physics, absorbed laser energy within biological tissues is transformed into various energy forms, including thermal, mechanical, electrical, chemical, or light energy. Often, laser energy is simply converted to heat. In the context of short-wavelength blue laser surgery, for instance, the energy from a 450 nm blue laser is converted into mechanical energy (photovaporization), thermal energy (photocoagulation), light energy (blue photons inducing broadband fluorescence photons), and other forms.

3 DEVELOPING BLUE DIODE LASER FOR SOFT TISSUE VAPORIZATION

Over the past three decades, laser prostate surgery has emerged as an alternative for treating BPH. A high-power laser beam is delivered to target prostate tissue via an optical fiber inserted through a cystoscope. The efficacy of prostate tissue removal in depends on multiple factors, including laser wavelength, power, mode (continuous or pulsed), illumination time, and other considerations.

Traditional visible laser ablation systems used in laser prostate surgery involve the utilization of high-average-power (80−180 W) frequency-doubled Nd:YAG lasers operating at a wavelength of 532 nm. Because the frequency doubling process employs potassium titanyl phosphate (KTP) or lithium borate (LBO) nonlinear optical crystals, these green lasers are sometimes referred to as KTP or LBO lasers. Green Nd:YAG laser can ablate soft tissues, however, this kind of laser is inherently a complicate system, consist of high power lamp or diode laser pumping, Q-switches, sophisticated temperature controlled frequency up conversion device, and other complicate subsystems. This complexity leads to high manufacturing costs and low reliability. Besides these disadvantages, the 532 nm laser wavelength is still considered too long to effectively vaporize soft tissues, especially in the context of large prostate tissue removal. Due to longer operation times than traditional TURP, performing green laser PVP procedures becomes a tedious job for the most urologists when dealing with prostates larger than 80 mL.

To expedite surgery duration, laser manufacturers have worked hard to increase laser power. Although higher laser power augments tissue cutting speed for lasers such as holmium and thulium lasers, LBO lasers, 980 nm or 1470 nm diode lasers, there are always some limits. First, high-power solid-state lasers (holmium, thulium, and LBO lasers) inherently possess significantly higher intracavity laser power than actual output laser power. This high intracavity power occasionally results in optical damage to laser optics, diminishing operational reliability and, in some instances, laser surgeries have to be stopped due to these optical damages. Second, due to the low electrical-to-optical energy conversion efficiency of these solid-state lasers—usually below 4% for LBO lasers and below 2% for holmium lasers—over 96% of input electrical power is converted into heat, which must be properly dissipated, through a very noisy liquid cooling system. These conventional lasers' noise levels create discomfort for both surgical teams and nurses. Third, from a patient perspective, if all input energy can be completely converted into mechanical energy for tissue removal only, there should no unwanted thermal damage to the patient. Thence, it is believed an ideal laser tool should have a suitable laser wavelength for high conversion efficiency from laser energy to tissue removal energy and less thermal damage, reasonable high laser power for short operation time, robust system reliability, and low laser system-related noise.

The innovation of gallium nitride (GaN) based semiconductor lasers and LED has reshaped various industries and people's lives globally. For their pioneering work on GaN-based blue LEDs and lasers (diode lasers having similar semiconductor structures as their counterpart LEDs), Japanese scientists Isamu Akasaki, Hiroshi Amano, and Shuji Nakamura were awarded the Nobel Prize in Physics in 2014. By 2016, commercially available blue semiconductor diode lasers achieved an output power of 1.6W with a center wavelength of 450 nm, ranging from 440 nm to 460 nm. This advancement prompted us to consider using such blue diode lasers for soft tissue ablation and coagulation. However, for parenchymal organ tissue removal, like prostate tissue ablation, a few watts of laser power are insufficient; much higher power is required. To attain a reliable 200 W of blue laser power, we engineered and employed multiple single packaged diode lasers, integrating several laser optical technologies such as optical beam shaping, high-brightness blue diode laser fiber coupling, and laser beam-combining, ultimately achieving over 200W from the surgical fiber tip.

We chose the 450 nm center wavelength diode lasers, as opposed to 405nm (violet-blue), 488nm (blue-green), or 520 nm (green) diode lasers. Among all commercially available visible diode lasers, only the 450 nm blue diode laser can attain the highest power, reaching up to 5.5W in year 2020 from a single TO (transistor outline) packaged diode laser, at the lowest cost per watt. An added benefit of selecting the 450nm diode laser is its efficient absorption by soft tissues, resulting in high energy conversion efficiency from laser energy to ablation energy.

Bleeding poses another challenge that demands attention. While laser prostatectomy generally achieves hemostasis, lasers like holmium, green or blue lasers that produce thin coagulation layers often struggle with bleeding control. When encountering intraoperative large diameter bleeding arteries, which are hard to reach hemostasis by simply applying lower laser power settings or manipulate longer distance from fiber tip to illuminate nearby area around bleeding site[16], a different but more efficient hemostatic tool is needed. It is a fact that 980 nm near-infrared laser has exhibited excellent hemostatic capabilities. To compensate for the shortcomings of visible laser hemostasis, which sometimes troubles surgeons dealing with intraoperative bleeding from large arteries during LBO laser PVP, we integrated a fiber-coupled near-infrared diode laser with a center wavelength of 976 nm and an output power of up to 50 W into the high-power blue diode laser system. Surgeons can switch between the blue laser for ablation and the near-infrared laser for coagulation using a dual foot-pedal switch. Figure 2 depicts the building blocks of the high-power blue diode laser system, including an assembly with up to 200 W of blue diode laser power and an assembly with up to 50W of near-infrared diode laser power.

The primary source of noise in high-power laser systems is the high cooling capacity water chiller. There are two key reasons why a high-power blue laser can eliminate the need for a water chiller. First, GaN blue diode lasers can operate at temperatures up to 65°C, significantly higher than gallium arsenide (GaAs) based near-infrared diode lasers, which operate below 30°C. This higher operating temperature enables us to dissipate heat generated by blue diode lasers into the temperature unregulated ambient air through forced air cooling. Second, there is no need for a wavelength converter, which typically has low energy conversion efficiency, as seen with LBO lasers using an 808nm diode laser converted to a 1064 nm near-infrared laser, then further converting to a 532nm green laser by using an LBO nonlinear crystal. All these wavelength converters substantially decrease the efficiency of electrical-to-optical power conversion. Furthermore, the blue diode laser system doesn't require inefficient lamps to pump a holmium crystal, eliminating pulsed lamp related noise. Although the design eliminating the need for a high cooling capacity chiller considerably reduces noise, cooling fans inside can still generate some unwanted noise. To further reduce noise from fans, we chose low-noise fans and employed conduct cooling electrical power supplies which have no fans within the diode blue laser system. Consequently, the operational noise of the diode blue laser system measures around 55 dB, significantly lower than the noise from a holmium laser, which is approximately 67 dB[17], making it more friendly for everyone inside the operating room. The actual product (Figure 3) received regulatory clearance from the National Medical Products Administration (NMPA, China FDA) in April 2022.

4 PRESSURED WATER FLOW SURGICAL FIBER

The high photon energy emitted by the blue diode laser introduces a potential challenge: the susceptibility of surgical fibers to damage when laser power exceeds 80W during soft tissue ablation. This fiber damage arises from tissue debris attaching to the fiber tip, causing it to rapidly absorb a substantial amount of blue laser energy, leading to catastrophic fiber burnout starting from the fiber tip. To prevent fiber damage, we developed a specialized fiber with a continuous pressured water flow to protect the fiber tip from contacting soft tissues and debris (Figure 4). For optimal results, we recommend diode blue laser tissue ablation using a non-contact approach.

Two types of pressured water flow surgical fiber are available for high-power blue diode laser BPH surgery: front-firing fiber and side-firing fiber. The front-firing fiber is ideal for tissue vaporization and vaporesection, maintaining a clear surgical view as the fiber body is not obstructing it. Concerns over potential damage to bladder walls due to improper manipulation of the front-firing fiber have been addressed. Xu and his colleagues' study[18] determined that at distances exceeding 5 cm from the fiber tip to illuminated tissue (beam diameter >17 mm, Table 2), high-power blue diode laser tissue damage is negligible if the fiber is continuously moving. Laser thermal damage also depends on laser energy density (joules per area) on the tissue surface, inversely proportional to laser spot size. For a fiber with core diameter of 0.76 mm and numeric aperture of 0.22, Table 2 lists laser spot sizes at varying fiber-to-tissue distances in water. The pressured water flow side-firing fiber features a right-angle laser beam reflection, entirely averting accidental bladder wall illumination is another ideal option particularly for the BPH surgery. This type of fiber is user-friendly, especially for surgeons accustomed to side-firing fiber Greenlight PVP. The laser spot shape from the side-firing fiber is also circular, distinct from traditional side-firing fibers such as Boston Scientific's Moxy fiber. The laser spot sizes in Table 2 are also applicable to Blueray Medical's pressured water flow side-firing fibers. Our laboratory testing verified both types of fiber can effectively ablate ex vivo tissue samples for over 2 h at 200 W blue diode laser power without fiber tip degradation.

5 OPTIMIZING LASER TISSUE VAPORIZATION EFFICIENCY

Efficiently optimizing tissue vaporization while mitigating undesirable thermal damage and minimizing fluffy tissue formation presents a challenge for many urologists working with specific lasers like the blue diode laser or green laser. Laser tissue vaporization follows a nonlinear process, where a threshold laser energy density must be attained for laser-induced biophysical phenomena to occur. With increasing laser power density, vaporization efficiency rises, though not necessarily linearly. This intricate process lacks a simple mathematical formula for description. The best description of this process was experimentally demonstrated by Kang and his colleagues[19]. They found the best fiber moving speed was between 4 mm/s and 6 mm/s for optimized vaporization efficiency for green lasers.

Tissue vaporization efficiency depends on laser energy volumetric density within the tissue. For 450 nm blue light, soft tissue absorbs more energy than for 532 nm green laser, resulting in shallower laser penetration and higher vaporization efficiency. Consequently, the laser energy volumetric density for 450 nm blue laser is higher than for 532 nm green laser, yielding thinner coagulation layers, reduced unwanted thermal tissue damage, and fewer fluffy tissues.

Laser energy density at the site of illumination is the total energy per given area, calculated as energy density = (laser power) × (illumination time)/(illumination area). For a moving laser beam, as shown in Figure 5, this area approximately equals to (beam diameter) × (laser beam moving speed) × (duration time). Simplified, (laser energy density) = (laser power)/([laser spot diameter] × [laser beam moving speed]).

Employing Matlab (MathWorks), a mathematical calculation tool, we computed laser energy density (J/mm²) across different laser power settings (P = 20−200 W), laser spot size in diameter (D = 1.0−3.5 mm), and fiber swiping speeds (v=1−9 mm/s), as shown in Figure 6. To achieve optimal tissue vaporization or maximize tissue volume without uncontrolled deep cutting or holes forming, and to prevent unwanted damage and fluffy tissues, the red regions in Figure 6 better to be avoided. For blue diode laser BPH surgery at a given power, maintaining an appropriate fiber tip-to-tissue distance and continuous fiber swiping speed is recommended. For example, if the power setting is increased from 150 W to 200 W, either the fiber swiping speed should be higher while maintaining the same fiber distance, or the fiber distance should be increased while keeping the same swiping speed.

Fluffy tissues often result from incomplete tissue ablation during diode blue laser or green laser tissue vaporization. Due to their semitransparent nature, eliminating fluffy tissues can be challenging. To prevent their formation, we suggest optimizing the balance between laser power, fiber distance, and fiber swiping speed to ensure complete ablation of target tissues.

6 PRECLINICAL STUDIES

To comprehend the interactions of the diode blue laser with soft tissues, both animal studies and in vitro tissue experiments are essential for gathering detailed information. These studies can provide insights into vaporization efficiency, coagulation layer thickness, potential damage or disturbance to surrounding tissues, and the wound healing process following animal surgery. A research team led by Dalin He at the First Affiliated Hospital of Xi'an Jiaotong University conducted a series of animal experiments and in vitro tissue studies to evaluate the safety and effectiveness of the high-power 450 nm blue diode lasers. In their investigation, they compared the high-power 450 nm blue diode laser (Blueray Medical Ltd) with a 532 nm green laser (Realton), a 980 nm near-infrared diode laser (INTER-medic), and a 1470 nm near-infrared diode laser (Miracle Laser), all operating at 120W output power in vitro ablation of a human prostate[18]. They found that at a fiber tip swiping speed of 1.5 mm/s, the prostate tissue vaporization efficiency, which was measured cubic millimeters per second, greatly favored the 450 nm blue laser, measuring over 25 mm³/s, compared to approximately 9 mm³/s, 7 mm³/s, and 15mm³/s for the 532 nm green laser, 980 nm diode laser, and 1470 nm diode laser, respectively. They concluded the blue diode laser had the highest tissue vaporization rate among these lasers.

In the same study, they compared the coagulation effects of these lasers on the vaporization of porcine kidney tissues, observing coagulation thicknesses of approximately 0.7 mm, 1 mm, 3 mm, and 2mm for the 450 nm laser, 532 nm laser, 980 nm laser, and 1470 nm laser, respectively. The thickness of the coagulation layer presents a double-edged sword: a thin coagulation layer potentially reduces postoperative recovery time but may make it challenging to control intraoperative bleeding, while a thicker layer has the opposite effect. To address hemostatic challenges, the Blueray Medical high-power blue diode laser integrates a 50W 976 nm diode laser. The occasional use of the 976 nm laser produces a localized area of coagulation, minimizing undesired tissue damage.

Precision in tissue ablation can be gauged by assessing adjacent tissue damage caused by vaporization. While the 450 nm blue diode laser and 532 nm green laser serve mainly as ablation energy sources, the 980 nm diode laser and 1470 nm diode laser do not. In the same study, He's group concluded that the degree of tissue damage induced by the 450 nm and 532 nm lasers increased as the fiber distance to tissue decreased and the illumination duration increased, which is in line with biophysics of laser soft tissue interactions. To enhance the precision of laser ablation while maximizing vaporization efficiency, a balance between laser power settings, distance from the fiber tip to the target tissue, and fiber tip swiping speed should be optimized.

The verdict on the wound healing process adds another dimension to the safety of the tissue ablation energy platform. Xu and Yang from He's research group conducted an experiment to study the wound healing process in elderly beagles through transurethral vaporization of the prostates[20]. One group of beagles underwent the procedure using a blue diode laser with a maximum output of 200 W, while another group used the traditional monopolar resectoscope (Shenda Ltd) TURP method. Cystoscopy examinations were performed at 1, 2, 3, and 5 weeks post-surgery, and histopathology examinations were conducted after sacrificing the beagle dogs. The results showed that the urethras of the prostates in the blue laser group were healed three weeks after the surgery, while in the TURP group, healing took 5 weeks. Hematoxylin and eosin staining confirmed that the coagulation necrosis layer in the TURP group was thicker than in the blue laser group, and it took longer time to eliminate the coagulation necrosis after the surgery. Additionally, the change in macrophage polarity occurred earlier in the blue laser group compared to the TURP group.

7 CLINICAL OUTCOMES

Between July 2022 and October 2023, over 3000 high-power blue diode laser BPH surgeries were performed nationwide in China. Some of the users of the blue diode laser published their clinical outcomes and experiences[21–23]. Xu's urological group from Xianyang Central Hospital reported on their first 100 cases of blue diode laser BPH surgeries using a pressured water flow front-firing surgical fiber[21]. They statistically analyzed key BPH surgery indicators, including the International Prostate Symptom Score (IPSS), quality of life (QoL) score, maximum urinary flow rate (Q_max), bladder residual urine volume (PVR) before and 3 months after the surgeries (Table 3), as well as intraoperative and postoperative complications (Table 4). Other recorded parameters included operative time, hemoglobin change, postoperative catheterization time, and hospital stay. They concluded that the clinical outcomes of high-power blue diode laser BPH surgery were satisfactory, with fast vaporization speed and near-hemostasis performance.

Zhao's urological group from Tai'an Central Hospital reported their experience with 30 cases of 450 nm high-power blue diode laser BPH surgeries using a pressured water flow side-firing surgical fiber[23]. The average operative time was 12.5 ± 5.4 min for a preoperative prostate volume of 53.2 ± 4 mL. The urinary flow rate before surgery, 1-day and 1-month after surgery were 10.6 ± 3.5 mL/s, 24.2 ± 5.6 mL/s, and 27.2 ± 3.1 mL/s, respectively. The residual urine was 57.3 ± 3.2 mL before surgery, and 5.6 ± 3.1 mL 1-month after the surgery. The average preoperative IPSS and QoL scores were 25.1 ± 1.6 and 5.4 ± 0.7, and 3-months after surgery were 9.5 ± 1.4 and 2.9 ± 0.6, respectively. Their conclusion was that side-firing blue diode laser tissue vaporization was highly efficient, provided near-hemostasis, and resulted in a short postoperative catheterization time.

Preserving sexual functions has gained prominence as an important research topic in the surgical management of BPH in the global urological community. Zhao's group has been at the forefront of applying high-power diode blue lasers while preserving patients' sexual functions. In their report on 20 cases of transurethral BPH surgery using pressured water flow front-firing fibers with a high-power blue diode laser output ranging from 150 W to 200 W, they developed a unique surgical technique that anatomically protects tissue around the verumontanum and sphincter muscle[24]. At a distance of 1 cm proximal to the verumontanum in the 6 o'clock direction, the prostate tissues were vaporized until they aligned with the plane of the bladder neck. They ensured that the vaporization surface in this area was flat and then expanded the vaporization surface to both lateral lobes. The urethral mucosa from 11 to 1 o'clock was left intact. In addition to improving key urological indicators, they observed that all 20 patients reported no retrograde ejaculation, and erectile function remained unchanged. The international index of erectile function (IIEF-5) questionnaire indicated that these patients' IIEF-5 scores remained consistent pre- and postoperations.

8 DISCUSSION

Blue diode laser technology, an innovative extension of conventional laser systems, operates at shorter wavelengths, typically centered around 450 nm (440−460 nm). This unique feature endows blue lasers with superior tissue absorption properties, resulting in reduced penetration depths and enhanced precision during surgical procedures. The blue laser's high-efficient tissue ablation ability for highly vascularized tissues, such as the prostate, allows for selective and controlled tissue ablation, minimizing damage to surrounding structures.

Moreover, the intrinsic absorption characteristics of blue light by hemoglobin and melanin-rich tissues significantly reduce the risk of collateral thermal injury, leading to reduced postoperative complications, such as bleeding and urinary tract irritation. This exceptional level of precision offered by blue laser technology positions it an attractive option for the treatment of BPH, potentially surpassing the outcomes of existing tissue-removal surgical techniques.

From the theoretical analysis of blue diode laser interactions with soft tissues to the practical implementation of the high-power diode blue laser system and pressured water flow surgical fiber, the preclinical experimental findings and clinical outcomes are consistent with our theoretical predictions. Particularly notable are the alignment in results concerning tissue vaporization efficiency, tissue coagulation, and bleeding control. While research on the application of blue lasers for BPH treatment is still in its early stages, preliminary studies and clinical trials have yielded promising outcomes, emphasizing the safety and effectiveness of this innovative approach. By leveraging the advantages of blue laser technology, BPH surgeries could become less invasive, with shorter operative times, reduced catheterization periods, and faster patient recovery. To deeper understand clinical benefits and limitations, however, more rigorous multicenter studies are necessary in the future to address aspects such as prostate removal speed, depth of tissue resection, postoperative incontinence, bleeding, irritative symptoms, preservation of sexual functions, and economic cost analysis in comparison to BPH medication and other surgical management techniques.

High photon energy blue light can generate visible fluorescence with continuous spectrum. High power diode blue laser induced bright white color fluorescence is not easy to be eliminated. Long time concentrating watching a monitor screen in diode blue laser BPH surgery, especially back-to-back surgeries may cause surgeon eye tiredness. To reduce such white color fluorescence is an engineering challenge, more research and engineering development work will be dedicated to overcome this issue.

In recent decades, various laser techniques were initially developed with the aim of replacing TURP. However, several factors contributed to the failure of these attempts. High costs associated with surgical laser systems and fiber optics had a detrimental impact on the urological community and hindered the widespread adoption of laser-based surgeries, particularly in developing countries.

In contrast to solid-state lasers such as holmium, thulium, and green lasers, the cost structure of blue diode laser systems is distinct. High-power blue diode laser system comprises a number of TO-packaged single GaN diode lasers, primarily used in commercial electronics applications like laser TV projectors, laser metal processing, and laser lighting. By repurposing commercial-grade blue diode lasers for medical applications, the manufacturing cost of high-power blue diode laser systems is expected to be significantly lower than that of other BPH lasers.

Traditional surgical laser manufacturers often rely on fiber optic devices as a major source of profit to offset the high manufacturing costs of laser systems themselves. By reducing the cost of making high-power blue diode laser systems, the pricing of blue diode laser surgical fiber optic devices is also expected to be competitive with the pricing of electrodes used in TURP.

Newer non-tissue removal techniques for managing BPH, such as UroLift and Rezum, provide less invasive options compared to laser-based surgeries while preserving sexual function. These methods have gained rapid acceptance, especially in developed countries. However, concerns about their long-term durability for large prostates linger in the urology community. On the other hand, Aquablation has emerged as an alternative with impressive tissue removal rates and demonstrated long-term effectiveness. Blue diode laser BPH surgery is a novel technique, and comprehensive long-term clinical data is still lacking. More clinical studies are needed to evaluate the durability and efficacy of this new approach over extended periods, possibly up to 5 years.

One common feature among UroLift, Rezum, Aquablation, and blue diode laser BPH surgeries is their significantly shorter operative times. Based on the experience of numerous urologists who have performed over 3000 blue diode laser BPH surgeries in China, most have reported shorter operative times compared to TURP. Many have demonstrated the blue diode laser's ability to vaporize prostates of various sizes, ranging from 30 mL to 270 mL, less than half the time required for TURP.

The feasibility of outpatient-based procedures could be actualized, leading to decreased hospital stays and related expenses. Moreover, incorporating blue laser technology into BPH surgical protocols could create opportunities for addressing the needs of a variety of patient groups. This could encompass younger patients seeking to preserve sexual functions, elderly patients, and high-risk patients who are unable to tolerate extended operating times, as well as patients undergoing anticoagulation therapy. Extensive research is required to thoroughly assess the eligibility of this intervention for these diverse patient categories.

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