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Author: Michael Grasso, MD, Chairman, Department of Urology, Saint Vincent's Medical Center; Professor and Vice Chairman, Department of Urology, New York Medical College

Michael Grasso is a member of the following medical societies: American Medical Association, American Urological Association, California Medical Association, and Endourological Society

Coauthor(s): David A Green, MD, Staff Physician, Department of Urology, New York Medical College

Editors: Raymond Rackley, MD, Professor of Surgery, Cleveland Clinic Lerner College of Medicine at CWRU; Co-Section Head, Section of Voiding Dysfunction and Female Urology, Glickman Urological Institute, Cleveland Clinic Foundation; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Mark Jeffrey Noble, MD, Consulting Staff, Urologic Institute, Cleveland Clinic Foundation; J Stuart Wolf, Jr, MD, FACS, David A Bloom Professor of Urology, Director, Division of Minimally Invasive Urology, Department of Urology, University of Michigan Medical Center; Bradley Fields Schwartz, DO, FACS, Associate Professor of Urology, Director, Center for Laparoscopy and Endourology, Department of Surgery, Southern Illinois University School of Medicine

Author and Editor Disclosure

Synonyms and related keywords: lasers in urology, urologic lasers, urological lasers, laser, laser lithotripsy, laser ablation of prostate, laser prostatectomy, laser surgery, tissue welding, photodynamic therapy, autofluorescence, neodymium:yttrium-aluminum-garnet laser, Nd:YAG laser, holmium:yttrium-aluminum-garnet laser, Ho:YAG laser, holmium:YAG laser, ruby laser, CO2 laser, carbon dioxide laser, frequency-doubled double-pulse Nd:YAG laser, FREDDY laser, potassium-titanyl phosphate crystal laser, KTP laser, potassium-titanyl phosphate laser, dye lasers, coumarin laser, alexandrite laser, semiconductor diode laser, tissue coagulation, thermal treatment, nitrogen laser, erbium:yttrium-aluminum-garnet laser, Er:YAG laser, thulium:yttrium-aluminum-garnet laser, thulium:YAG laser, endoscopic intracorporeal laser lithotripsy, laser coagulation, laser vaporization, Greenlight laser, visual laser ablation of the prostate, VLAP, Ho:YAG prostate enucleation, HoLEP



Shortly after their development, lasers were referred to as a solution eagerly looking for a problem. Indeed, lasers progressed rapidly as an omnipresent part of modern technology and procedural medicine. Recent advances in lasers and fiberoptics make them ideally suited to travel through routes in the human body where no hand or scalpel has gone before. With its widespread use of small-diameter endoscopic instruments, urology has been drastically and positively influenced by this technology, perhaps more so than any other medical subspecialty.

History of the Procedure

Laser is an acronym that stands for light amplification by the stimulated emission of radiation. Albert Einstein proposed the concept of stimulated emission of radiation in 1917. Not until 1960, however, was this theory put to use by T.H. Maimen to produce the first visible light laser. He used a synthetic ruby crystal with silver-coated ends surrounded by a flash tube to produce light energy. In 1966, Parsons, using a similar ruby laser in a pulsed mode, was the first urologist to experiment with laser light in canine bladders. Mulvany attempted to fragment urinary calculi 2 years later, again using the ruby laser. Subsequently, researchers tested many new substrates or lasing materials, leading to diversity in their clinical application.

Laser physics

Einstein used 2 principles of physics as the basis for his discovery: (1) Light travels in packets of energy known as photons, and (2) most atoms or molecules exist naturally in a ground or low-energy state (E0). However, a small percentage of atoms naturally exists at any given time at a higher, discrete energy level (E1, E2, En). By adding electricity, heat, or light energy to atoms in their ground state, their energy level can be raised. The energy is then released spontaneously in the form of photons or electromagnetic (EM) waves to return to the ground state.

Einstein also discovered that, when a photon of light energy of the same wavelength strikes an excited atom (En), that photon and the photon of light that is released are discharged simultaneously and will therefore be identical in frequency and phase. This is the concept of stimulated emission used in the creation of a laser.

Atoms in their ground state undergo absorption of photons of light energy. For stimulated emission to occur, more atoms must exist in the excited state than in the ground state, a situation known as a population inversion. Energy must be supplied to this population. In a laser, the energy source is usually electric or flashlamp driven. The populations of atoms or molecules that become excited are the lasing medium.

Anatomy of a laser

The lasing medium exists between 2 mirrors for light amplification to occur; one is fully reflective and the other only partially reflective. Once the lasing medium at the core is excited by a pumping mechanism that supplies energy, a population inversion occurs. Some photons are emitted spontaneously from the excited atoms or molecules that cause light to travel in all directions within the laser cavity.

The light that is directed perfectly parallel to the laser cavity is reflected back and forth between the 2 mirrors at their ends. These photons become amplified by collisions with excited atoms in the lasing medium that then release photons in exactly the same direction, phase, and wavelength. The partially reflective mirror at one end has an aperture through which the amplified light exits as a laser beam.

The 3 characteristics mentioned above differentiate laser light from natural light. These include coherence (the photons are all in phase), collimation (they travel parallel with no divergence), and monochromaticity (they all have the same wavelength and, therefore, the same color if within the visible light spectrum).

Different lasing mediums (which can be solid, liquid, or gas) emit photons in different wavelengths of the EM spectrum. This is at least partly responsible for the unique characteristics of a particular laser. Other characteristics that affect laser performance include the power output and the mode of emission (eg, continuous wave, pulsed, or Q-switched).

Continuous wave lasers emit a steady-state, uninterrupted beam. Pulsed lasers have further subdivisions, yet they all allow for more precise control and less lateral heat conduction to tissues than a continuous output laser. A gated pulse laser has a timed interrupted output with a peak power no higher than if the beam were emitted continuously. A true pulse refers to a mode in which the power output is built up between pulses, resulting in a higher peak power than a continuous mode. A superpulse is similar to true pulse; however, the frequency of pulses per second is so fast (about 300-1000/s) that the beam appears to be continuous. Finally, a Q-switched mode refers to a pulsing technique that produces very high peak power outputs (on the order of tens of millions of watts) for very short durations (a few nanoseconds). This allows for minimal lateral heat conduction and a more precise, directed effect.

The physical properties of a laser can be described using 4 key concepts—energy, power, fluence, and irradiance. Energy describes the amount of work accomplished and is measured in joules. Power refers to the rate of energy expenditure and is measured in joules per second, or watts (1 J/s = 1 W). The total energy applied to a given tissue is a function of the power multiplied by the duration of time the tissue is exposed. The fluence, otherwise known as power density, describes the amount of energy delivered per unit area (J/cm2) and is far more important in determining a laser's effect on tissues than total energy delivered.

Irradiance is a term used to describe the intensity of a laser beam, and it is measured in watts per square centimeter. Irradiance is also inversely proportional to the square of the spot size radius. Lenses or optical fibers can manipulate the fluence or power density of a laser. Lenses focus or defocus a beam to change spot size even when the laser is kept at a constant distance from tissue.

Optical fibers used in laser beam delivery often allow for 10-15° of beam divergence upon exit from its tip. This results in defocusing of the beam with increasing distance from the tip of the fiber. Within a 1-inch working distance, laser intensity can change from making incisions (closest, most concentrated spot size) to vaporizing tissue surfaces (slightly defocused) to coagulating proteins (greatest distance). Halving the spot size of a laser beam, while keeping the amount of energy delivered constant, increases the energy density by a factor of 4 (energy density is inversely proportional to the square of the spot size radius; equation = E/[pi][r2]).

Pathophysiology

The biophysics of laser-tissue interactions

Local tissue properties, combined with the wavelength of laser light used, further affect the quality of the laser-tissue interaction. Examples of tissue properties include the density, degree of opacity (eg, quantity of pigments), water content, and blood supply of the tissue. The more dense or opaque a tissue is, the greater the degree of absorption of light energy and the greater the degree of transformation to heat.

Molecules, proteins, and pigments may absorb light only in a specific range of wavelengths. Hemoglobin, for example, absorbs light energy that has a wavelength as high as 600 nm and is translucent to light beyond this range. (The argon laser produces light of 458-515 nm and, therefore, is heavily absorbed by hemoglobin.) Water also absorbs in a specific wavelength range, beginning with a small amount of absorption from 300-2000 nm, at which point the degree of absorption increases rapidly and continues for several thousand nanometers. The CO2 laser produces light in the far infrared spectrum, at 10,600 nm. This is heavily absorbed by water contained in tissue and, therefore, does not penetrate deeply.

Local blood circulation affects the degree of laser energy absorption via 2 mechanisms. First, as mentioned above, the absorptive properties of individual blood components (eg, hemoglobin, water) differ and interact with light in specific wavelength ranges. Second, the circulating blood acts as a heat sink or radiator by transporting absorbed thermal energy away from the site of delivery. This effectively blunts laser power by opposing its local thermal effects.

The wavelength of laser light can be proportional to the depth of penetration into specific tissues. The longer the wavelength, the deeper the expected penetration. Tissue composition and molecular absorption are among several other factors that play into the laser end effect. The neodymium:yttrium-aluminum-garnet (Nd:YAG) laser, for example, produces light in the near infrared region (1060 nm) and penetrates to a depth of approximately 5-10 mm in most tissues (at its wavelength, Nd:YAG is not absorbed by hemoglobin or water in any significant quantity). The CO2 laser with a wavelength of 10,600 nm (longer wavelength, thus should penetrate more deeply) penetrates only to a depth of less than 0.1 mm because its wavelength is very highly absorbed by tissue water. Ultimately, laser energy and tissue characteristics interact in a complex manner that determines the degree of absorption, penetration, reflection, and scattering of laser energy.

Surgeons currently using lasers seek 4 different effects—thermal, mechanical, photochemical, and tissue-welding effects (which is actually mediated through thermal energy). The most common utilization is the thermal effect, whereby light energy is absorbed and transformed into heat. This results in the denaturation of proteins at 42-65°C, the shrinkage of arteries and veins at 70°C, and cellular dehydration at 100°C. Once water has completely evaporated from tissue, the temperature rapidly rises, carbonization then occurs at 250°C, and, finally, vaporization occurs at 300°C.

The mechanical effect results, for example, when a very high power density is directed at a urinary calculus and a column of electrons is freed rapidly at the stone surface. This creates a plasma bubble that swiftly expands and acts like a sonic boom to disrupt the stone along stress lines.

The photochemical effect refers to the selective activation of a specific drug or molecule, which may be administered systemically but is taken up in selected tissues. By activation of the molecule or drug by a specific wavelength of light, the molecule is transformed into a toxic compound(s), often involving oxygen-free radicals that can cause cellular death through destruction of DNA crosslinks. This is a novel approach to destroying superficial skin or mucosal malignant and premalignant lesions. Lasers are ideally suited because of their power and specific wavelength.

Finally, the tissue-welding effect is derived by focusing light of a particular wavelength to induce collagen cross-linking. By adding proteinaceous materials (eg, 50% human albumin, also known as tissue solder) directly to the tissue edges to be welded or a chromophore that absorbs at the laser's wavelength, increased tensile strength and decreased peripheral destruction can be achieved.



Laser Types and Clinical Applications

This section focuses on the different types of laser energies that have urologic applications and their basic physical properties. The specific urologic applications of each laser type is discussed below in Current Laser Applications.

Ruby laser

The ruby laser was the first visible laser produced using a synthetic ruby crystal surrounded by a flash tube. The laser produces red light at a wavelength of 694 nm. The crystal's lasing properties degrade with high temperatures; therefore, it is best used at low repetition pulse rates, although a short Q-switched mode is now in favor.

The ruby laser is less efficient than more modern lasing materials. The 695-nm emission, however, is highly absorbed by melanin and is currently used in a Q-switched mode to remove pigmented lesions and tattoos, with little scarring. This laser has little use in urology outside of treating cutaneous lesions and removing hair (eg, from perineal skin prior to urethroplasty).

CO2 laser

The CO2 laser emits in the invisible far infrared portion of the EM spectrum, at 10,600 nm. It usually is coupled with a visible helium-neon beam for guidance. Its beam is highly absorbed by water; therefore, it vaporizes water-dense tissues to a superficial depth of less than 1 mm. Heat conduction results in thermal coagulation down to a depth of about 0.5 mm, with only small vessels less than 0.5 mm coagulated effectively. The beam is delivered using an articulating arm with mirrors and a hand piece, which can focus or defocus the lens. A waveguide tube can also be used for laparoscopic use.

Neodymium:yttrium-aluminum-garnet laser

Studies in 1961 showed neodymium produced stimulated emissions. The ion (Nd3+) was then used to dope many different crystals. The Y3Al5O12 crystal affectionately known as YAG is used commonly today because of its efficiency, optical quality, and high thermal conductivity, which permits high rates of repetition.

The Nd:YAG laser emits a beam at 1064 nm (near infrared) and can be delivered in a continuous, pulsed, or Q-switched mode. The 1064-nm wavelength allows for a relatively deep penetration of as much as 10 mm because this frequency is outside the absorption peaks of both hemoglobin and water. It has good hemostatic (coagulates blood vessels as much as 5 mm in diameter) and cutting properties and is suitable for lithotripsy when Q-switched.

An optical fiber is used for delivery, which may be passed through all types of endoscopes. A sapphire or crystal tip, which decreases backscatter and allows for precise cutting using a direct touch technique, may also be used at the end of an optical fiber.

The frequency-doubled, double-pulse Nd:YAG (FREDDY) laser is a short-pulsed, double-frequency solid-state laser with wavelengths of 532 and 1064 nm. It is a low-power, low-cost laser developed for intracorporeal lithotripsy that has been a subject of recent investigation. Although the FREDDY laser is effective for lithotripsy, it is does not have a soft-tissue application.

Potassium-titanyl phosphate crystal laser

This laser, also known as a potassium-titanyl phosphate (KTP) laser, yields a green visible light beam of 532 nm by passing an Nd:YAG-produced beam (1064 nm) through a KTP crystal that doubles its frequency (thus, halves its wavelength). This light penetrates less than Nd:YAG because of its shorter wavelength and its absorption by hemoglobin. It is used for incisions, resection, and ablation and can be passed through an optical fiber and thus through endoscopic instruments. One disadvantage of KTP laser energy is that tissue carbonization can be observed, rather than a true ablative effect.

Dye lasers

The lasing medium is an organic liquid dye that must be excited optically by another laser or flash lamp. The wavelength emitted depends on the type of dye used, which can be changed or adjusted. The emitted light, therefore, can be tuned to cover a wide spectrum of visible light. In the pulsed mode, this laser is used for lithotripsy and ablation of vascular lesions. The most common dye used is coumarin, which produces a wavelength of 504 nm when excited by a flashlamp. As opposed to a solid-state laser, the dye in the lasing chamber requires replacement, which may be inconvenient and expensive compared with the maintenance of newer laser systems.

Alexandrite laser

This is another tunable laser composed of a chromium-doped mineral known as alexandrite (BeAl204). The wavelength range is from 380-830 nm and is strongest at 700-830 nm. This light is absorbed well by melanin; therefore, it can be used for cutaneous lesions. In a 1-ms pulsed mode delivered with an optical fiber, it is used for lithotripsy of pigmented stones. Combined with indocyanine green dye applied to tissues, this laser can also be used for tissue welding.

Semiconductor diode laser

Laser light is produced using light-emitting diodes (LEDs) between reflecting mirrors in a resonator tube. They are smaller, more efficient, and potentially cheaper than most other lasers now in use. Their wavelength can be tuned by adding various elements (eg, aluminum, indium). An 805-nm laser is produced using AlGaAs, and a 1000-nm beam is produced from the active compound InGaAs.

These lasers are currently used for tissue coagulation and thermal treatment of solid organs, including the prostate. In this setting, the laser energy is delivered into tissue with optical fibers and it increases the local temperature. Benign prostate tissue is affected, and, as the denatured protein is reabsorbed over time, bladder outlet obstruction should decrease.

Holmium:yttrium-aluminum-garnet laser

Holmium:YAG (Ho:YAG) is a somewhat recent addition. It consists of the rare earth element holmium doped in a YAG crystal that emits a beam of 2150 nm. This laser energy is delivered most commonly in a pulsatile manner, using a thermomechanical mechanism of action. It superheats water, which heavily absorbs light energy at this wavelength. This creates a vaporization bubble at the tip of a low–water density quartz or silica fiber used for delivery. This vapor bubble expands rapidly and destabilizes the molecules it contacts. This is ideal for lithotripsy of all stone types. The absorption depth in tissue is 1-2 mm, as long as it is used in a water-based medium. This specific light energy provides good hemostasis when used in a pulsed mode of 250 ms duration and at low pulse repetition rate. At higher repetition rates, it may also be used for incisions.

Nitrogen laser

The nitrogen laser incorporates inert nitrogen gas (N2) as the lasing medium, and, when excited by optical energy, it emits light with a wavelength of 337 nm.

This laser has been studied as a component of a diagnostic test for transitional cell carcinoma (TCC) and other mucosal malignancies using autofluorescence. For this use, the beam is delivered using a quartz optical fiber and the stimulated fluorescence produces light, which is transmitted back through the same fiber to a detection system.

Summary of laser types and current clinical applications

  • For soft-tissue incisions (eg, urethral strictures, posterior urethral valves, endopyelotomy, bladder neck contractures), use Ho:YAG, Nd:YAG, or KTP.
  • For resection and ablation (eg, benign prostatic hyperplasia [BPH], TCC, condylomata, penile carcinoma, bladder and skin hemangiomata), use Nd:YAG, Ho:YAG, KTP:YAG, semiconductor diode, or CO2.
  • For lithotripsy (renal pelvis, ureter, and bladder stones), use Ho:YAG, FREDDY, pulsed dye, or alexandrite.
  • For tissue welding (eg, vasovasotomy; urethral reconstruction for hypospadias, strictures, diverticula, or fistulas; pyeloplasty, bladder augmentation, and continent urinary diversion), use diode, KTP, Nd:YAG, or CO2.
  • For autofluorescence (eg, for diagnosis of bladder malignancies), use a nitrogen laser.
  • For laser hair removal (eg, perineal skin used for local urethral grafts), use ruby, alexandrite, diode, or Nd:YAG.

Upcoming technology

The erbium:yttrium-aluminum-garnet (Er:YAG) laser has been studied for urologic application. Studies have suggested that the Er:YAG laser may be superior to the Ho:YAG laser for precise ablation of strictures with minimal peripheral thermal damage and for more efficient laser lithotripsy.1 The Er:YAG laser cuts urethral and ureteral tissues more precisely than the Ho:YAG laser and produces less peripheral thermal damage. The Er:YAG laser used with a sapphire fiber was also found to be more efficient at calcium oxalate stone lithotripsy than the Ho:YAG laser.2 The Er:YAG laser may represent an alternative to the cold knife and Ho:YAG laser in applications that require minimal mechanical and thermal insult to tissue. A current drawback of the Er:YAG laser is the extremely high cost of the sapphire optical laser fibers.

The thulium:YAG laser has recently been investigated in an attempt to improve on some of the shortcomings of the Ho:YAG laser.3 This new laser more closely matches the water absorption peak in soft tissue to minimize collateral tissue damage. It has also been studied as a new endoscopic lithotrite, with promising initial results. Clinical experience with this laser is limited and reflects technical issues with the fiber delivery systems.



In recent years, advances in laser and fiberoptic technology have made lasers ideally suited to travel through routes in the human body previously unexplored by hand or scalpel. With the widespread use of small-diameter endoscopic instruments in urology, this field has been drastically and positively influenced by laser technology, perhaps more so than any other medical subspecialty.



The composition, location, and the size of urinary stones may direct the type of laser and fiber used, the method of approach (eg, retrograde or anterograde), pulsation mode, and power output. The location, size, and depth of tumors and other lesions will dictate the same parameters.



Lab Studies

  • Laboratory studies are specific to treatment.

Imaging Studies

  • Imaging studies are specific to treatment.



Surgical therapy

Current Laser Applications

Urolithiasis

Endoscopic intracorporeal laser lithotripsy is commonly used as a treatment for urinary calculi. Combined with extracorporeal shockwave lithotripsy (see Extracorporeal Shockwave Lithotripsy), it made open stone surgery virtually obsolete. Most urinary calculi less than 5 mm should pass spontaneously, albeit with pain that frequently requires analgesia. Completely obstructing stones, infected stones, or larger calculi warrant intervention. Depending on the size, shape (eg, staghorn), and location of calculi, either retrograde ureteroscopy or percutaneous nephrostolithotomy may be used. Lasers are ideally suited for either approach. The flexible quartz fibers that deliver the laser energy are particularly useful when treating stones with flexible fiberoptic endoscopes.

Laser lithotripsy was first used clinically in the late 1980s, using the coumarin-based pulsed dye laser. A wavelength of 504 nm of light energy is delivered through optical quartz fiber, directed endoscopically onto a calculus. The mechanism of action occurs via plasma formation between the fiber tip and the calculus, which develops an acoustic shockwave that disrupts the stone along fracture lines. The small, flexible quartz probes are passed easily through working channels of small-diameter ureteroscopes, fragmenting most stone compositions, except cystine. The hardest stones, however, can fragment into irregular shapes that often require endoscopic extraction. In addition, the energy available for fragmentation is limited by fiber diameter. The 200-micron fiber that allows for the most endoscopic deflection, for example, delivers an insufficient amount of energy (about 80 MJ) to fragment calcium oxalate monohydrate (COM) stones.

The alexandrite laser, introduced in 1991, is effective for most stone compositions. Stone-free success rates are upwards of 90%. It is relatively weak against nonpigmented calculi. This laser is similar to the pulsed dye in effect but is solid state. It has been used only at a limited number of sites in the United States.

The Ho:YAG is one of the newest members of the endoscopic lithotrites. Light energy of 2150 nm is delivered in a pulsatile fashion through low–water density quartz fibers. In water, a vaporization bubble surrounds the fiber tip. This bubble actually destabilizes stones, creating fine dust and small fragments. With a pulse duration of 100-300 microseconds and a power range of 3-20 W, the cavitary effects produced allow for segmental resection of all stones, regardless of their composition. Accurate fiber contact against a calculus is the primary safety factor. The beam is fully absorbed within the first few millimeters of tissue; therefore, when applied in water or saline irrigant, minimal risk of surrounding thermal injury exists as compared to Nd:YAG.

Other advantages of Ho:YAG include its minimal fragment migration and retrograde propulsion when low settings are used, its ability to fragment all stones regardless of composition or size, and its ability to deliver higher energy settings even through the smallest of delivery fibers. Hard stones in difficult locations (eg, lower pole caliceal calculi), therefore, can be treated using a thin, 200-micron, quartz fiber that is easily deflected. Finally, the type of eye protection used for the Ho:YAG wavelength does not distort color perception, as do those worn with alexandrite and coumarin dye lasers.

The FREDDY laser combines the characteristics of solid and dye lasers with a thin flexible optical fiber. It has been compared with Ho:YAG lasers across several parameters relating to stone treatment in 2 recent in vitro studies. The first compared stone retropulsion and fragmentation.4 In this artificial stone model, fragmentation was significantly better with the FREDDY laser than with the Ho:YAG laser. However, in a 2006 clinical series, the FREDDY laser provided suspect fragmentation of calcium oxalate monohydrate stones and ineffective fragmentation of cystine stones.5 Additionally, stone retropulsion was significantly greater with the FREDDY laser. 

A 2007 in vitro study compared Ho:YAG laser with FREDDY laser with respect to generation of transient cavitation bubbles and acoustic emissions associated with shockwaves as a function of fiber-to-calculus distance.6 The FREDDY laser requires closer proximity to the stone to generate cavitation bubbles and shockwaves, representing important clinical implications for the operator.

Laser therapy for benign prostatic hyperplasia

BPH is the most prevalent disease entity in elderly men. In the late 1980s, lasers became a novel way to open a wider channel and improve voiding dynamics. Many different techniques under the term laser prostatectomy have evolved. Individual techniques may vary greatly, but the 2 main tissue effects include coagulation and vaporization. Coagulation occurs when somewhat diffusely focused laser energy heats tissue and temperatures reach as high as 100°C. Proteins denature, and necrosis ensues. This results in subsequent sloughing of necrotic tissue, ie, a debulking of the prostate. This process may take as long as several weeks to complete and often initially results in edema, which transiently increases prostate volume (and therefore may require short-term urethral catheterization).

Vaporization occurs when greater laser energy is focused (increased power density) and tissue temperatures reach as high as 300°C. This causes tissue water to vaporize and results in an instantaneous debulking of prostatic tissue. The high-power (80-W) potassium-titanyl phosphate laser (KTP, or Greenlight) is commonly used for its vaporization effects on prostate tissue. This procedure is associated with significantly less bleeding and fluid absorption than standard transurethral prostate resection. Because of this, the KTP laser is safely used in seriously ill patients or those receiving oral anticoagulants. 

In a recent study of KTP laser treatment in candidates for transurethral resection of the prostate (TURP), no patients developed significant postoperative gross hematuria although more than half of the patients were on antiplatelet therapy immediately prior to surgery.7 In this study, prostates with volumes of up to 136 mL were safely treated, although some required operative times up to 99 minutes. After a mean follow-up of 3.5 years, most patients in this study saw at least a 50% improvement in their American Urological Association Symptom Index (AUA-SI) and a 100% improvement in peak urinary flow rate (Qmax). 

Drawbacks to the KTP procedure compared with traditional TURP include the lack of tissue obtained for postoperative pathological analysis and the inability to diagnose and unroof concomitant prostatic abscesses.

Nd:YAG is used most commonly for its coagulative effect. In a procedure termed visual laser ablation of the prostate (VLAP), a direct transurethral viewing source (eg, cystoscope and video) is used along with a laser that is supplemented by a visible (usually helium-neon) aiming beam. Under direct vision, an end or side delivery fiber is aimed at the prostatic urethra to direct thermal energy into different portions of the prostate. Typically, segmental coagulation is achieved by aiming for the 12, 3, 6, and 9 o'clock positions for varying periods of time (often only 30 s to 1 m).

Using higher energy and a smaller spot–size laser beam, VLAP can be performed, with vaporization as the primary physical effect. This causes the immediate formation of a cavity or channel. Because of the smaller spot size, this is more time consuming and, therefore, is usually reserved for smaller adenomas (<40 mL). For either of the above techniques, the postoperative course may be complicated by irritative voiding symptoms (incidence is approximately 30-40%, with symptoms for >14 d) or prostatitis/urinary tract infections (UTIs) (incidence is approximately 1-3%) because of the disrupted urethral epithelium.

Interstitial coagulation using a diode laser is another coagulative technique in which optical fibers are introduced transurethrally or perineally directly into the prostate. This can cause large-volume necrosis with atrophy while preserving the urethral mucosa. This method can be used to treat glands of any size, and, because the urothelium is not disrupted, theoretically less irritative symptoms and UTIs occur.

Other laser energies have been used to incise or enucleate prostate adenomas down to the capsule. The Ho:YAG is ideally suited for this task because it creates precise incisions, cuts by vaporizing tissue with adequate hemostasis, and leaves minimal collateral damage. Advantages of this method include the availability of a specimen for histologic examination, less postoperative catheter time, and the ability to excise large adenomas. Drawbacks include greater training time and the need to transport the adenoma (in toto or portioned) into the bladder to morcellate it prior to removal. When comparing Ho:YAG prostate enucleation (HoLEP) with traditional TURP, in recent studies, both procedures were equally effective in relieving obstruction and lower urinary tract symptoms, but HoLEP can lead to a shorter catheterization time and hospital stay.

A 2005 study compared HoLEP with Ho:YAG bladder neck incision (HoBNI) in patients with prostates smaller than 40 g.8 HoBNI was an efficacious procedure in men with prostates smaller than 30 g, but reoperation rates were high in men with prostates between 30 40 g. After up to one year of follow-up, the differences in Qmax, AUA symptom score, and quality-of-life score between the two groups were insignificant. However, all 5 of the patients who required reoperation were in the HoBNI group, 4 of whom had prostates larger than 30 g.   

For some time, the criterion standard treatment for BPH has been TURP. This is the standard by which all of the above techniques are compared. TURP is used less frequently because of associated complications, including bleeding and transurethral resection (TUR) syndrome and the improved efficacy of other medical therapies. In general, the laser prostatectomies mentioned above have added safety and less perioperative pain compared with TURP. Less bleeding occurs and the operative time is usually less; therefore, most types may be performed on patients who are receiving anticoagulants.
 
In terms of efficacy, most studies comparing VLAP to TURP show no significant difference between change in AUA symptom scores and urinary flow rate. Other studies do show, however, the advantage of TURP in the above parameters, especially in the immediate postoperative period. Among the laser modalities, none stands above others in terms of efficacy, efficiency, and a lack of complications, but all modalities in current use have demonstrated an improvement in flow rate, symptom scores, and postvoid residual.

A 1996 study by Kabalin of 227 men using the Nd:YAG coagulative approach revealed a 133% improvement in Qmax, a 67% improvement in symptom scores, and an overall 87% improved quality of life.9 The effects appeared to be durable 3 years after the procedure. Complications included urethral stricture (1.8%), bladder neck contracture (4.4%), prostatitis (2.6%), and reoperation for residual prostate tissue (5.3%).

Laser modalities are safer than TURP in the perioperative period, although some may have a similar long-term complication profile. The coagulative approaches have been associated with prolonged postoperative catheterization secondary to inflammation and edema of necrotic prostate tissue. This has been overcome in some studies by combining the Nd:YAG coagulation with KTP or Ho:YAG vaporization to form a channel that prevents urinary retention in the immediate postoperative period. All of the modalities mentioned are efficacious, but none is efficacious enough to make the old-fashioned TURP obsolete.

Laser treatment of urothelial malignancies

Various laser energies have been used to treat bladder and upper urinary tract urothelial tumors. Most commonly, holmium and Nd:YAG are used in this setting. They are used through quartz fibers, which are directed endoscopically. The Nd:YAG laser energy is used to coagulate and ablate with a thermal effect that extends deeper than other lasers. Holmium is more precise, with less of a coagulative effect.

The advantages of laser therapy for tumor ablation include less bleeding; consequently, catheter drainage is usually unnecessary. A lower incidence of stricture formation results when compared with electrocautery because fibrotic reaction is minimal. This technique decreases the need for anesthesia, causes less postoperative pain, and allows a quicker return to work. The Ho:YAG laser can be used through a flexible cystoscope to ablate recurrent superficial bladder tumors in an office setting. A recent review of patients treated with the flexible cystoscope reported a high degree of satisfaction because this method avoided the need for general anesthesia, and 83% of the patients scored their pain as 2 or less out of a possible 10.10 No pathology specimen is available; thus, determining depth of invasion is impossible unless multiple prior biopsy samples were obtained. Another drawback, especially with the Nd:YAG laser, is that the area of destruction is deep and not fully visualized. Some reports of bowel perforation exist when treating bladder dome lesions even without visible bladder perforation secondary to the effect of Nd:YAG. In this setting, Ho:YAG is a better choice.

Photodynamic therapy is another form of tumor ablation in which a systemically administered compound is absorbed or retained preferentially by cancer cells and converted by laser light to a toxic compound. This compound usually acts through oxygen radicals to destroy malignant cells. Lasers are ideally suited for this form of therapy because of their monochromaticity and small, maneuverable delivery systems. An example of this type of therapy involves Photofrin II, a hematoporphyrin that is retained by malignant cells long after it clears healthy epithelium. By using an argon laser to excite the dye rhodamine B, a red light of 630 nm is produced that can be aimed at the entire bladder several days after administering the Photofrin. This is especially promising for TCC–carcinoma in situ (CIS), which shows complete responses.

Lasers for nephron-sparing surgery
 
The use of ablative techniques for the treatment of renal masses has evolved from the oncologic success of nephron-sparing surgery and the need for a minimally invasive technique with a learning curve less steep than that of partial nephrectomy. Cryoablation and radiofrequency ablation (RFA) are at the forefront of this category, but laser interstitial therapy (LITT) has also been investigated. 
 
LITT, which has been used extensively in treatment of hepatic lesions, involves placement of a laser fiber directly into a lesion. Laser light is converted to heat energy in the lesion and tissue necrosis ensues. LITT is performed using MRI to guide Nd:YAG laser placement and to monitor treatment. Temperature-sensitive magnetic resonance sequences are used to monitor thermal changes in tissue during treatment. In a single case series including 9 patients, mean lesion enhancement tended to decrease with treatment, but no complete ablations were reported.

Lasers for urothelial stricture disease

Urethral strictures have been a frustrating entity for the urologist to treat. Many different procedures are available to deal with them, but all of them, except open urethral reconstruction, are associated with a high rate of recurrence. Internal urethrotomy yields a success rate of only 20-40%, and repeat procedures, unfortunately, offer little improvement. Nd:YAG, KTP, and Ho:YAG lasers have all been used experimentally to vaporize fibrous strictures. They can yield recurrence rates similar to those of the cold-knife internal urethrotomy. Recently, some hope of using an Nd:YAG laser with a crystal contact tip at the end of a delivery fiber has occurred. In a study of 42 patients with urethral strictures, the Nd:YAG crystal tip contact method of vaporization yielded a 93% success rate that was durable for a mean of over 2 years.11

Ureteropelvic junction obstructions, posterior urethral valves, and even bladder neck contractures have been treated using laser energy. Ho:YAG is most likely the best form of laser energy for these tasks because of its safety, precision, superior cutting properties, and minimal collateral injury. Ureteroscopic laser endopyelotomy is a minimally invasive, short-stay outpatient procedure associated with a 65.4% symptomatic and 73.1% success rate based on radiographic findings. Long-term success appears to decrease over time and is usually better in secondary obstructions of the ureteropelvic junction.

Lasers for the ablation of skin lesions

Lasers offer minimal scarring and superior cosmetic results compared with other forms of cutaneous lesion resection. Condyloma acuminata, the most common sexually transmitted disease, often occurs on the penile shaft, on the glans, or even in the urethra. A good vaporization response is obtained with the CO2 laser if lesions are superficial or with Nd:YAG and KTP lasers for deeper lesions, frequently treated after administration of a local anesthetic. An endoscopic optical fiber can be used for intraurethral lesions with minimal scar tissue and stricture formation. A study by Schneede et al (1994) of 161 patients whose cases were observed for a mean of 16 months after laser treatment of urogenital warts revealed a recurrence-free rate of 80%.12 Because human papillomavirus (HPV) viral particles may be carried in the vaporization cloud, using a smoke evacuator and proper oronasal mask protection is important.

Penile carcinoma in the early stages (eg, CIS, T1 or T2) can also be treated, with excellent cosmetic results. CO2 can be used for superficial lesions, and Nd:YAG can be used for more invasive lesions. Accurately staging lesions with biopsy prior to treating with laser vaporization is important. Close follow-up also is a key because the depth of laser penetration can be initially difficult to assess. No significant difference in the rate of local recurrence after conservative surgical excision compared with laser ablation appears to exist.

In a prospective study from 1986-2002, a total of 67 men with newly diagnosed penile carcinoma were treated with laser therapy using a combination of CO2 and Nd:YAG lasers.13 Thirteen patients developed local recurrence, and 2 patients died of penile carcinoma after a median follow-up of 42 months. Ten of the 13 patients with recurrence underwent repeat laser treatment. The results of this study show that treating penile carcinoma with the combination of CO2and Nd:YAG lasers can be safely performed with highly satisfactory cosmetic results, as well as acceptable local tumor control.

Cutaneous hemangiomas of the penis or scrotum may be undesirable to excise because of their propensity to bleed and the undesirable cosmetic results. These are best treated with the KTP laser because of its 532-nm wavelength, which is highly absorbed by hemoglobin. Argon, with its 488- and 524-nm wavelengths, is also absorbed by hemoglobin and melanin, but it has very limited tissue penetration. Nd:YAG can be used to coagulate deeper lesions, even large cavernous hemangiomas, with excellent cosmetic results using a thermal effect, despite its low absorption by hemoglobin.

Preoperative details

For urinary stones, the composition, location, and the size may direct the type of laser and fiber used, the method of approach (eg, retrograde or anterograde), pulsation mode, and power output. For tumors and other lesions, the location, size, and depth of the lesion dictate the same parameters.



Complications are associated with the specific laser energy used. Scarring and fibrosis may be prevented by precisely placing the laser energy under direct endoscopic localization. Pulsed modes help to improve control and minimize lateral heat conduction, thus improving precision and minimizing scarring. In addition, when performing a ureteroscopic or percutaneous endoscopic procedure, using sufficient cooling irrigant to prevent thermal damage to collateral tissue is important.

Use care when working with Nd:YAG and an open-ended delivery fiber. This laser energy is not significantly absorbed by water, and a free beam is not weakened much by irrigants. It may penetrate deeply and inadvertently into tissues and cause bowel perforation when working within the dome of the bladder or ureter. With Ho:YAG laser energy, use caution if using endoscopic baskets and guidewires, as they can be damaged or fragmented easily, causing shards to migrate and making them a challenge to recover.

All endoscopic laser modalities should be used under direct vision, through the working channel of an endoscope. With any laser, all intraoperative personnel should wear proper eye protection that blocks the specific laser's wavelength to avoid corneal or retinal damage should an optical delivery fiber crack or break. This especially is true with Nd:YAG, which penetrates deeply and can burn the retina faster than the blink reflex can protect it. Ho:YAG, which does not penetrate as deeply, may cause corneal defects if aimed at the unprotected eye.

Finally, strategic and adequate draping should be used around external areas to be lasered. Wet towels should be draped around cutaneous lesions to be treated. Reflective surfaces (eg, metal instruments) should be kept away from the field if possible and, if not possible, should be draped with a wet towel. Furthermore, use caution if oxygen is in use anywhere near the operative field. Oxygen in proximity to a laser beam can result in a laser fire and cause significant burns.



The outcomes are specific to the various forms of treatment used, which range from lithotripsy to the ablation of tumors or prostate tissue and are mentioned in the above sections.



Tissue welding

Laser energy is applied in a constructive manner to reapproximate tissues. The results are very promising thus far, with good tensile strength, watertight seals, and minimal scar formation. Tissue solders (albumin solutions) and chromophores added to tissue edges before reapproximation speed the welding process, increase tensile strength, and minimize collateral injury.

This technology may be particularly helpful in laparoscopic surgery, in which current methods of reapproximation are clumsy and time consuming. Vasovasotomy for vasectomy reversal using a tissue welding technique has a reported patency rate near 95% and a subsequent pregnancy rate of 35%. This is comparable to current microsurgical techniques, yet the required technical skills are less, operating time is decreased, and, so far, reported complications are fewer. Hypospadias repair is another technically tedious operation that is lending itself, mostly in the laboratory, to tissue-welding repair. Other reported applications of tissue welding in urology include pyeloplasty, augmentation cystoplasty, and continent urinary diversion.

Proposed future laparoscopic applications include ureteroureterostomy, pyeloplasty, ureteroneocystostomy, and bladder and bowel anastomoses.

Local temperature control of tissue to be reapproximated is the main parameter that affects the quality of a tissue weld. This has been difficult to control, and the end-point is too subjective for consistent results. One group overcame this using a dual-chamber optical fiber that delivers laser energy and senses surface temperature simultaneously. The optimal temperature for lasers to denature and weld tissue proteins is 70-80°C.

Because urine lacks the clotting ability of blood, tight anastomoses of urothelial structures are even more important than in vascular surgery. Laser welding can provide the urologist and patient an immediate watertight seal with a tensile strength that exceeds conventional closures. This application is in its clinical infancy; however, the future may bring a ubiquitous, mature technology.

Autofluorescence

The ability to ablate and weld increases the laser's use as a diagnostic tool. In this capacity, light of a specific wavelength is used to differentiate healthy from dysplastic or malignant tissue. This may involve the use of dyes that are metabolized differentially by normal and abnormal tissues. With bladder tumors, the sensitivity of this method is near 100%; however, false-positive results secondary to inflammatory lesions make the specificity only 60-70%. This can lead to too many unnecessary biopsies. Koenig et al (1996) developed a novel approach using the innate fluorescing ability of tissues without the addition of dyes, a process called autofluorescence.14

Light of 337 nm emitted by a nitrogen laser and applied to bladder tissue was absorbed then re-emitted at 385 nm and 455 nm by tissue collagen and nicotinamide adenine dinucleotide (NADH), respectively. Because of the blood supply, thickness, and relative lack of collagen in tumors, they can be distinguished from healthy tissue. By using a pulsed beam for delivery, the same optical fiber may be used to detect the return of fluorescence and then obtain absorption spectra. Healthy tissue fluoresces with greater intensity than malignant tissue and, more importantly, has 2 absorption peaks at 385 and 455 nm. Malignant tissue, on the other hand, usually has only 1 absorption peak at 455 nm.

Inflammatory tissue, which can mimic malignancy in appearance, almost always emits at both the 385- and 455-nm peaks, the same as healthy tissue. This method of detection has yielded a very high sensitivity, specificity, and positive and negative predictive values, (97, 98, 93, and 99% respectively), making it a potentially useful diagnostic tool.

Conclusion

The future of lasers in urology will be based on developing new wavelengths that are more precise and applicable to evolving treatment schemes. Er:YAG is a great example; it is much more precise than holmium, with less than a millimeter of collateral tissue effect. This could make an excellent endoscopic scalpel; however, at this time, no user-friendly delivery system for this laser that allows for endoscopic use exists. Further developments are anticipated eagerly.

New lasing mediums are the subject of intense research and development worldwide. Plastic conjugated polymers are one of the most promising mediums under study. With these mediums, scientists have generated emissions across the entire visible spectrum. They have been proven to amplify light, even through microscopic blocks of polymer. The hope for the future is a widely tunable, highly cost-effective laser using thin films of conjugated polymers and packaged in an ultracompact device.



Media file 1:  This is a central stone defect, which is the product of holmium:yttrium-aluminum-garnet (Ho:YAG) laser lithotripsy. This particular stone was composed of cysteine, which will not fragment with the pulsed dye laser. In addition, Ho:YAG produces sulfur dioxide gas when treating cysteine stones, producing a characteristic odor during treatment.
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Media type:  Photo



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Lasers in Urology excerpt

Article Last Updated: Jan 15, 2008