Lasers in Urology

Synonyms and related keywords: lasers in urology, laser, laser lithotripsy, laser ablation of prostate, laser prostatectomy, laser surgery, tissue welding, photodynamic therapy, autofluorescence, neodymium:yttrium-aluminum-garnet, Nd:YAG, holmium:yttrium-aluminum-garnet, Ho:YAG, holmium:YAG


INTRODUCTION
Section 2 of 11
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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. Advances in lasers and fiberoptics in recent years 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 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. It was not until 1960, however, that this theory was 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 then is 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 therefore will 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 usually is 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 will be 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 1 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 are 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 either 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 are 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 in a continuous fashion. A true pulse refers to a mode where the power output is built up in between pulses, resulting in a higher peak power than a continuous mode. A superpulse is similar to the above; 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 also is 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 is 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) only penetrates 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, a rapid rise in temperature ensues, 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, one can achieve an increased tensile strength and decreased peripheral destruction.
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INDICATIONS
Section 3 of 11
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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 will be discussed 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 currently is used in a Q-switched mode for removal of 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 also can be used for laparoscopic use.
Neodymium:yttrium-aluminum-garnet laser
Studies in 1961 show neodymium produced stimulated emissions. The ion (Nd3+) then was 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 also 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 also may be used at the end of an optical fiber, which decreases backscatter and allows for precise cutting using a direct touch technique.
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 also can 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 currently are 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:YAG laser
Holmium:YAG (Ho:YAG) is a somewhat recent edition. 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 thermo-mechanical 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. It also may be used for incisions at higher repetition rates.
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, 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 is currently being studied for urologic application. Recent studies suggest 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. 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 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 Er:YAG laser used with a sapphire fiber was also found to be more efficient at calcium oxalate stone lithotripsy than the Ho:YAG.

RELEVANT ANATOMY AND CONTRAINDICATIONS
Section 4 of 11
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Relevant Anatomy: 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 than any other medical subspecialty.
Contraindications: 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.
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WORKUP
Section 5 of 11
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Lab Studies:
Lab studies are specific to treatment.
Imaging Studies:
Imaging studies are specific to treatment.

TREATMENT
Section 6 of 11
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Surgical therapy:
Current laser applications
Urolithiasis
Endoscopic intracorporeal laser lithotripsy commonly is used as a treatment for urinary calculi. Combined with extracorporeal shock wave 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 first was 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 shock wave that disrupts the stone along fracture lines. The small, flexible quartz probes 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 endoscope 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 the newest member to 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 watts, 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.
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 have evolved that are all grouped under the term laser prostatectomy. Individual techniques may vary greatly, but the 2 main tissue effects are 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 increases prostate volume transiently (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. The KTP procedure is a safe and effective treatment option in seriously ill patients or those receiving oral anticoagulants. Drawbacks to the KTP procedure as compared with traditional transurethral prostate resection 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 the 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, one can perform a VLAP 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 reserved for smaller adenomas (<40 cc). For either of the above techniques, the postoperative course may be complicated by irritative voiding symptoms (incidence is approximately 30-40%, with symptoms for more than 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 where optical fibers are introduced transurethrally or perineally directly into the prostate. This can cause large-volume necrosis with atrophy, while preserving the urethral mucosa. The size of gland that can be treated using this method is unlimited, 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 transurethral prostate resection, in recent studies, both procedures were equally effective for relieving obstruction and lower urinary tract symptoms, but HoLEP can lead to a shorter catheterization time and hospital stay.
The criterion standard treatment of BPH for some time has been the transurethral resection of the prostate (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 therapy. The aforementioned laser prostatectomies, in general, have added safety and less perioperative pain when compared to TURP. Less bleeding occurs and the operative time usually is less; therefore, most types may be performed on anticoagulated patients
In terms of efficacy, most studies comparing VLAP to TURP show no significant difference between change in American Urological Association (AUA) symptom scores and urine 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 peak flow rates, a 67% improvement in symptom scores, and an overall 87% improved quality of life. 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 can be 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 usually is not needed. A lower incidence of stricture formation results when compared with electrocautery because fibrotic reaction is minimal. This technique has a decreased need for anesthesia, 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. No pathology specimen is available; thus, determining depth of invasion is impossible unless multiple prior biopsy samples are 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 where 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 suited ideally for this form of therapy because of their monochromaticity and small, maneuverable delivery systems. An example of this type of therapy uses 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 urothelial stricture disease
Urethral strictures classically 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, have a high rate of recurrence. Internal urethrotomy has a success rate of only 20-40%, and repeat procedures, unfortunately, offer little improvement. Nd:YAG, KTP, and Ho:YAG lasers all have been used experimentally to vaporize fibrous strictures. They can have rates of recurrence similar to 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 resulted in a 93% success rate that was durable for a mean of over 2 years.
Ureteropelvic junction obstructions, posterior urethral valves, and even bladder neck contractures recently 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 when compared with other forms of cutaneous lesion resection. Condyloma acuminata, the most common sexually transmitted disease, often occurs on the penile shaft, glans, or even intraurethrally. 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 followed for a mean of 16 months after laser treatment of urogenital warts revealed a recurrence-free rate of 80%. Because human papilloma virus (HPV) viral particles may be carried in the vaporization cloud, using a smoke evacuator and proper oro-nasal mask protection is important.
Penile carcinoma in the early stages (eg, CIS, T1 or T2) also can 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 difficult to assess initially. 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 carbon dioxide and Nd:YAG lasers. 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 carbon dioxide and 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, also is 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 will dictate the same parameters.

COMPLICATIONS
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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 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, also 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.

OUTCOME AND PROGNOSIS
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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 previous sections.
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FUTURE AND CONTROVERSIES
Section 9 of 11
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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, where 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.
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.

PICTURES
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Caption: Picture 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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BIBLIOGRAPHY
Section 11 of 11
Author Information Introduction Indications Relevant Anatomy And Contraindications Workup Treatment Complications Outcome And Prognosis Future And Controversies Pictures Bibliography
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Montorsi F, Naspro R, Salonia A, et al: Holmium laser enucleation versus transurethral resection of the prostate: results from a 2-center, prospective, randomized trial in patients with obstructive benign prostatic hyperplasia. J Urol 2004 Nov; 172(5 Pt 1): 1926-9[Medline].
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Interstitial Laser Coagulation of the Prostate

Benign prostatic hyperplasia (BPH) is the most common disorder that affects men older than 40 years. BPH usually starts to become symptomatic in men aged 50 years and older. Because of the intimate anatomic relationship between the bladder, urethra, and prostate, prostatic growth can alter the physiology and function of these organs and produce a symptom complex known as prostatism. Almost every man expects to have some type of prostate problem during his lifetime. Although no one knows how to prevent BPH other than with castration or eliminating testosterone production, treatment options are available that can effectively and safely ameliorate its symptoms and maintain normal bladder and kidney function.
Symptoms associated with BPH are either irritative (eg, lower urinary tract symptoms [LUTS]) or obstructive (eg, bladder outlet obstruction [BOO]). Distinguishing the differences in pathophysiology of LUTS and BOO allows the most appropriate therapy to be used.
When symptoms become troublesome, patients seek medical attention from their primary care physician or urologist. Previously, the only therapies were open surgical procedures (eg, suprapubic prostatectomy, retropubic prostatectomy, perineal prostatectomy, transurethral resection of the prostate [TURP]). Now, various therapeutic alternatives are available, including pharmaceuticals, herbal products, or interventional procedures.
Pharmaceutical therapy consists of alpha-adrenergic blockers, 5-alpha-reductase (5aR) inhibitors, various herbal products such as saw palmetto and Pygeum africanum, and a plethora of new procedures, including microwave thermotherapy, prostate vaporization techniques, free-beam laser prostatectomies, thermotherapy with heated water, photodynamic therapy, injection therapy with alcohol, high-intensity focused ultrasound, and interstitial laser coagulation (ILC).
This article focuses primarily on one of the laser therapies, ILC of the prostate, although the other forms of intervention are discussed.
In the 1980s, several investigators began studying the application of interstitial laser energy to treat various neoplasms. The neodymium:yttrium-aluminum-garnet (Nd:YAG) laser energy was transmitted through flexible end-firing fibers inserted directly into the tumor. This produced a focal area of tissue necrosis surrounding the fiber tip. Small tumors could be effectively eradicated.
In 1991, Hofstetter suggested the use of this technique to treat BPH. Studies in animal and human prostates demonstrated the feasibility of this approach and led to clinical trials for men with symptomatic BPH. The original end-firing Nd:YAG laser fibers emitted a high-energy beam from its tip but produced only a small spherical volume of tissue destruction.
Early fibers were fragile and had a tendency to break during insertion. Recognizing the potential usefulness of this procedure, new fibers were specially designed for treating the prostate. These sturdy fibers were larger in diameter and had pointed tips to facilitate placement into prostatic tissue.
Currently, the fibers have distal-diffusing tips that radiate 360° laser-light energy along the terminal 3 mm of the fiber. During the 90-second or 3-minute laser application time (depending on which model unit is used), ellipsoid volumes of tissue coagulation are created, which surround the axis of the fiber. The affected tissue area has a diameter of 1.5-2 cm and a length of 2 cm, which corresponds to the length of the energy-diffusing fiber tip.
The laser systems, manufactured by Johnson and Johnson (Indigo), in Cincinnati, and Dornier (Fiber Tome), in Germany, are compact, readily transportable, low-power, diode laser devices that use a 15- to 20-watt variable power source. This process produces a wavelength of 800-850 nm. The current indigo system uses an 830-nm fiber, and laser energy transmits through a sterile fiber enclosed within a 2-cm long, high-temperature resistant, light-diffusing tip that fits through a cystoscope. Low-power settings minimize tissue charring, which impedes light and heat conduction and decreases the amount of tissue coagulation.
The transurethral endoscopically guided technique is preferred; however, both transperineal and transrectal approaches are used. Although the use of transrectal ultrasonography to guide the placement of the fibers was utilized initially, this rarely is necessary. These laser systems (ie, transperineal, transrectal) represent an effective and safe method for relieving BPH-associated symptoms.
History of the Procedure: Although BPH is one of the most common processes affecting the aging male patient, much remains to be learned about its etiology and pathophysiology. Until 10 years ago, the prevailing opinion was that the symptoms associated with BPH were due entirely to an increase in urethral resistance caused by an enlarged prostate constricting the urethra; but, since that time, obstruction has been noted to produce neurologic alterations in the bladder and prostate, which account for many of the symptoms.
The following terms describe BPH, but no uniform acceptance of any terminology exists. Regardless of which term is used, the patient seeks the attention of a urologist when symptoms of difficult urination begin.
Prostatic enlargement
Histologic hyperplasia
LUTS
BOO
Urodynamic obstruction and other appellations
ILC is one of many minimally invasive procedures that have been introduced to alleviate the problems associated with BPH. At this time, stating that one form of therapy is distinctly advantageous over the others is not possible because few comparative studies have been performed. ILC is applicable for prostates smaller than 60 mL in volume, and this procedure, like the others, can be performed in the office with local anesthesia.
Problem: The prostate undergoes significant growth during specific periods (ie, fetal development, puberty, late middle age). At the end of puberty, the prostate size is 15-25 g, and it remains in this range until BPH develops.
Growth of BPH usually begins in men aged 30-35 years. In men aged 30-50 years, the estimated doubling time for prostate weight is 4.5 years. In men aged 50-70 years, the doubling time is 10 years. Researchers postulate that the average age-related growth rate is approximately 6 g per decade.
BPH is the most common tumor that develops in men. Symptoms are thought to develop from the interaction among the following 3 components:
The static component results from enlargement of the inner portion, or transition zone, of the prostate. This zone is adjacent to the urethra and develops into an adenoma that compresses the peripheral zone. The transition zone is the tissue that is removed when a prostatectomy is performed, via transurethral resection, open prostatectomy, or any of the other types of procedures.
The second, dynamic component involves the smooth muscle in the prostate, the prostatic capsule, the bladder outlet, and the proximal portion of the urethra.
The third component is the bladder muscle (detrusor), which responds to changes related to prostate growth and tension in the smooth muscles within the prostate and proximal urethra. The bladder exhibits a decrease in contractility that leads to atony and urinary retention, an increase in uninhibited contractions that produces frequency and urgency, or a combination of both.
Enlargement of the prostatic adenoma produces changes in the detrusor that are responsible for many of the symptoms that men experience. The smooth muscles that encircle the urethra and course through the prostate are responsible for maintaining muscle tone in the urethra. The dynamic changes in these smooth muscles result in symptoms of frequency, urgency that may be accompanied by urge incontinence, nocturia, and postvoid dribbling. These LUTS tend to occur in men younger than 65 years. Often, these men have prostates that are not very enlarged and have relatively good flow rates and empty their bladders fairly well.
The static or obstructive symptoms, which usually occur in older men, include a weak stream, hesitancy, inability to complete urination suddenly without postvoid dribbling, sensation of incomplete bladder emptying, straining to urinate, and urinary retention (in some men). These symptoms are associated with an enlarged prostate.
Category 1: Although a weak stream often is associated with BOO, other disorders (eg, urethral stricture) can produce the same symptom. Researchers define hesitancy as an increase in time from the attempt to initiate micturition and the actual start of the urinary flow. In men without a prostate condition, the start of urinary flow usually takes only a few seconds, but, in men with obstruction, it may take several minutes.
Category 2: This category defines irritative symptoms, including frequency and urgency, which may be coupled with some incontinence and nocturia. Urination frequency depends on many factors (eg, fluid intake, diet, medications, physical activity). Voiding at intervals of less than 2 hours with voided volumes less than 250 mL arbitrarily can be defined as frequency. Urgency describes the sudden, strong desire to urinate and may be associated with incontinence.
This symptom constellation causes most patients to seek medical attention. Most men have some, or many, of these symptoms in various degrees by the age of 70 years. The severity of symptoms and their correlation with urodynamic findings provide the basis for therapeutic intervention.
Frequency: Histologic evidence in unselected autopsy specimens demonstrates that BPH occurs in more than 40% of men aged 50-60 years and in 90% of men aged 80-90 years. The majority of men older than 50 years have some symptoms attributable to BPH. Nearly 2 million office visits per year are from men seeking the evaluation and treatment of BPH. Surgeons perform more than 300,000 procedures per year on the prostate, and an estimated 900,000 men take some type of medication or herbal supplement for a prostate condition.
Approximately 25% of men aged 55 years note a decrease in the force of urine flow, and 50% of men describe this symptom by age 75 years. According to the International Prostate Symptom Score (IPSS) index, the odds of a man aged 40-50 years developing moderate-to-severe symptoms (IPSS >8) increases with age, from 1.9 for men aged 50-59 years to 3.4 for men aged 70-79 years. The chances of men developing moderate-to-severe symptoms with a prostate larger than 50 g is 3.5 times greater than for men with smaller prostates; however, epidemiologic and clinical studies demonstrate that the relationship between prostate size and symptoms is not necessarily linear.
The proportion of men with clinical prostatism at any age is approximately the same as those with pathologic evidence of BPH, even though the correlation is poor between symptoms and prostate size. The dynamic or smooth muscle component associated with the symptoms of BPH explains this discordance; thus, some men with relatively small prostates may have severe symptoms, and some men with very large prostates may have few symptoms.
Patients' symptoms affect their quality of life. Interference with at least 1 daily activity occurs in 50% of patients, and 25% of patients report interference with activity most, or all, of the time.
Epidemiologic studies fail to demonstrate racial differences in prevalence of BPH histopathology, prostate size, or clinical diagnosis.
An inheritable form of BPH may be present in 50% of men younger than 60 years who are treated for this disease. Only 9% of men older than 60 years who are treated for BPH are predicted to have a familial risk. A large prostate size and a mean volume of 82.7 mL in men with hereditary BPH, compared to 55.5 mL in men with sporadic BPH, characterize BPH.
Etiology: BPH is characterized by an increase in the number of epithelial and stromal cells in the periurethral area, or transition zone, of the prostate. Embryonic reawakening describes the presence of new epithelial gland formation. Increases in cell numbers may occur from epithelial and stromal proliferation or apoptosis impairment.
Etiology of the hyperplastic process relates to androgens, nonandrogen testicular factors, estrogen, stromal-epithelial interactions, growth factors, neurotransmitters, and other factors awaiting definition.
The two causative factors necessary for the development of BPH are aging and the presence of functional testes. The prostate is able to grow throughout adult life, and the process may be clinically evident in men as young as age 30-40 years.
The prostate consists of a network of glandular elements embedded in a fibrostromal network with a rich vascular supply. Androgens, estrogens, other growth factors, and various cytokines mediate the close interaction between these glandular and stromal cells. The growth process within the stroma perpetuates itself and exerts control on the gland growth rate and apoptotic cycle. The urine and semen also contain growth factors that may permeate the urethra and influence epithelial cell growth. Interactions between growth factors and steroid hormones may alter the balance of cell proliferation versus apoptosis.
BPH involves growth stimulatory factors with dihydrotestosterone (DHT) and other hormones modulating their effects, which are as follows:
Epidermal growth factor
Epidermal growth factor receptor
Insulin growth factors 1, 3, 4
Insulinlike growth factor (IGF) receptors and binding proteins
Beta fibroblast growth factor
Keratinocyte growth factor (KGF): It is produced in stromal cells, but its receptors are located on the glandular epithelial cells. Its hormonally regulated production plays a key role in stromal-epithelial interaction
The transforming growth factor beta inhibits epithelial cell proliferation, regulates extracellular matrix synthesis and degradation, and can induce apoptosis.
The role of the testis in BPH involves the production of androgen, estrogen, and nonandrogenic substances. These 2 hormones play a pivotal role in prostatic growth because the prostate is androgen-dependent and estrogen is mitogenic. The nuclear membrane-bound enzyme, 5aR, mediates the biochemical action of testosterone and is responsible for the conversion of testosterone to DHT (ie, the active agent within the cell). Patients with BPH maintain intraprostatic levels of DHT, but these levels are not elevated. DHT levels are the same in hyperplastic and healthy glands.
In adult prostates, androgen receptors are present on glandular and stromal cells, but 5aR is present only in stromal cells. Two 5aR enzymes are encoded by separate genes. Type 1 is the predominate enzyme in extraprostatic tissues, and type 2 is found largely in the prostate.
BPH also seems to have an inheritable genetic component. The hazard-function ratio between men treated surgically for BPH compared to first-degree male relatives of the controls was 4.2, indicating a very strong relationship. A segregation analysis shows that results are consistent with an autosomal dominant inheritance pattern.
Pathophysiology: Benign prostatic hypertrophy
The traditional BPH symptom complex is initiated by enlargement of the prostate, which leads to BOO and its associated symptomatology. However, prostate size, per se, does not determine the severity or the symptom complex associated with this condition. Some men with prostates larger than 75 mL have minimal difficulty voiding, have good flow rates, and empty their bladders. Some men have minimal prostatic enlargement with severe symptoms and need some type of intervention.
Lepor et al report on the results of over 400 men enrolled in the terazosin database. Their research could demonstrate no correlation between prostate size and either peak urinary flow rates or symptom scores. They conclude that treating patients just because of an enlarged prostate may not always relieve obstruction or improve symptoms.
The following mechanisms explain why BPH may produce BOO:
Enlarged middle lobe of the prostate, which acts as a ball valve
Static obstruction, resulting from an enlarged prostate encircling the urethra
Dynamic obstruction related to the contractile properties of the prostatic smooth muscle
Restrictive prostatic capsule
Smooth detrusor muscle tension
Controlled, randomized studies that focus on reducing prostate size and relaxing prostate smooth muscle consistently demonstrate improvement in flow rates and symptoms.
Prostatism
The prostatism theory postulates that increases in urethral resistance, which usually are associated with prostatic hyperplasia in the periurethral glands of the transition zone, result in compensatory changes in detrusor function. The resulting elevated detrusor pressures that are required to maintain urinary flow when outflow resistance is increasing occur at the expense of normal bladder function.
Changes in detrusor function (caused by obstruction), combined with incremental increases in smooth muscle tension and a resistant prostatic capsule and compounded by age-related changes in the detrusor and the nervous system, produce the characteristic symptoms of frequency, urgency, nocturia, and weak urine flow associated with prostatism.
Clinical: Symptoms that characterize BPH and distinguish the need for some type of intervention of the prostate are as follows:
Prostatism can be separated into an obstructive or irritative (dynamic) component: The typical obstructive symptom is a weak flow, which is not pathognomonic of obstruction because other entities (eg, urethral stricture) can produce the same symptom.
Hesitancy in beginning urination: This is described as a prolonged time between patient attempt to initiate voiding and time that voiding actually begins. Normally, this interval takes only a few seconds, but it can take several minutes in men with severe obstruction whose bladder cannot generate enough pressure to overcome urethral resistance.
Patient inability to abruptly terminate urination results in postvoid dribbling, which is caused by detrusor fatigue or urine trapped in the bulbar urethra. This particular symptom often develops in healthy men.
Sensation of incomplete bladder emptying is frequent but does not necessarily correlate with ultrasound measurements of residual urine.
Overflow incontinence occurs when the detrusor is unable to contract and urine begins spilling through the urethra. This usually is associated with large residual urine or urinary retention.
Urinary retention
This occurs when a patient suddenly is unable to void. Retention is also defined as a bladder that consistently retains more than 150 mL after voiding, as determined with Foley catheterization or bladder scanning.
In some patients, total urinary retention represents the terminal event of steadily progressive urinary obstruction and detrusor decompensation. Some type of invasive procedure is necessary in most of these men, although the recovery of detrusor function is variable and depends on how long the retention has been present. Urodynamics may provide information that predicts bladder recoverability.
Alcohol, antidepressants, anticholinergics, tranquilizers, and antihistamines with alpha-adrenergic activity also may cause retention. This can be reversed in some men with cessation of these agents.
Irritative symptoms (thought to develop from detrusor instability and not directly related to obstruction)
Frequency
Nocturia
Urgency
Urge incontinence
Frequency
To determine whether patient frequency is physiologic or attributable to detrusor instability, evaluate voiding times and compare them with the volume of passed urine.
Patients taking diuretics, those with large fluid intakes, and patients with a large caffeine intake often void frequently but pass substantial amounts of urine with each voiding. Normal voiding volumes diminish with age, but most individuals can expect to pass 250-300 mL of urine with each void.
Abnormal frequency includes patients with a strong urge to urinate at intervals of less than 2 hours, with volumes that average less than 200 mL.
Urgency
This refers to the sudden and strong need to urinate, and incontinence may accompany this symptom.
This is a nonspecific symptom, which may be associated with prostatism but also occurs in patients with bladder stones, neuropathic bladder disease, bladder cancer, and some types of inflammatory bladder disease.
Nocturia occurs in many patients but must be correlated with fluid intake, sleep patterns, and medications. Nocturia occurring more than once may be abnormal in some but readily explainable in others. Nocturia is probably the single most difficult symptom to treat in men with LUTS.Indications for treatment depend on patient symptoms and their severity, the degree to which the symptoms bother the patient, and whether changes in bladder and renal function can be documented objectively. Some men have relatively few symptoms but are extremely bothered by them and desire therapy. Others may have significant symptoms but are quite content to live with them. Still others may have minimal symptoms but serious impairment of bladder and/or renal function.
Many men with mild-to-moderate symptoms or objective findings generally may respond to alpha-blockers, 5aR inhibitors, and herbal products such as saw palmetto and Pygeum africanum. Combinations of these agents are also used. Other interventional strategies should be used if the symptoms are not ameliorated to the patient's satisfaction, which can be judged based on an improvement in their symptom scores, or upon objective findings such as a decrease in urine flow rates, an increase in the postvoid residual, or deterioration of renal function. Some men develop side effects caused by these various agents and want the problem resolved permanently and expeditiously.
Review the options and create a management strategy if the patient's symptoms correlate with the objective data gathered from an evaluation of the urinary tract and the patient desires or needs therapy.
Absolute indications for intervention
Urinary retention
Upper urinary tract obstruction secondary to benign prostatic hyperplasia (BPH)
Diminished renal function caused by BPH
Gross hematuria due to BPH (although this can be managed with medical therapy with 5aR inhibitors)
Recurrent urinary tract infections
Bladder calculi
Progressive deterioration of bladder function - Demonstrated by an increase in the amount of residual urine or decreased bladder muscle tone and pressure on cystometrogram (CMG) or pressure-flow studies
Overflow urinary incontinence
Some men have silent prostatism in which serious deterioration of the bladder and/or renal function occurs with relatively few urinary symptoms.
Relative indications refer to the patient's symptoms and his desire to improve the clinical situation. Use the IPSS index to evaluate and follow the cases of these patients because the patient himself usually has difficulty recognizing changes in voiding, which often are subtle and somewhat variable daily.
After making the decision to intervene, determine next whether to alter the pharmacologic therapy or initiate some type of invasive procedure.
Interstitial laser coagulation therapy
Interstitial laser coagulation (ILC) therapy is among the choices of invasive therapy.
Most patients are not familiar with this particular method for treating BPH.
Almost any patient who is a candidate for an invasive procedure is eligible for ILC.
An advantage of this technique is that it can be offered to anyone regardless of age, symptoms, configuration of the prostate, or severity of symptoms.
Usually, minimal blood loss occurs.
Patients require only a short hospital stay, or the procedure can be performed on an outpatient basis.
Patients do not experience any adverse effect on potency.
The procedure can be performed with a regional or local anesthesia.
Urologists can perform this procedure in their offices.
Ensure that the patient is not taking anticoagulants during the preoperative period because of potential bleeding from the multiple prostate perforations.
Some patients need to be able to manage a Foley catheter while at home, usually for 5-7 days.Lab Studies:
Conduct a urinalysis, which includes dipstick testing and a microscopic examination, and a urine culture to evaluate the patient for possible infection and hematuria.
Determine lateral lobe length to establish how many probe insertions are necessary to treat each lobe. A 3-cm area of coagulation necrosis develops in each treated area.
Obtain cytology to evaluate men with severe irritable symptoms (particularly with a history of smoking or microscopic hematuria) for possible bladder cancer (carcinoma-in-situ).
Obtain a urine culture and sensitivity for men with a WBC count more than 5 per high-power field (HPF) on spun urine sediment.
Renal function
Evaluate patient renal function with a serum creatinine.
Risk of complications increases for patients with renal failure.
If the creatinine level is elevated, conduct imaging studies or isotope renography to evaluate for upper urinary tract obstruction.
Measure the serum prostate-specific antigen (PSA) as a baseline and use it to determine whether a prostate biopsy to evaluate the patient for possible prostate cancer is necessary. These 2 disorders coexist in many men, and therapy is significantly altered if cancer is present.
One of the disadvantages of ILC and the other procedures is that no tissue is obtained.
Imaging Studies:
Residual urine determination: Perform an ultrasound of the bladder following voiding to evaluate the amount of residual urine. This helps to assess the muscle tone and function of the patient's bladder, but it also reflects the status of the bladder outlet obstruction (BOO).
Upper urinary tract imaging
Obtaining imaging studies of the upper urinary tract depends on the patient's situation. These studies should be performed in patients with hematuria, flank pain, a history of stone disease, or elevated serum creatinine levels. The physician needs to decide the necessity of these studies.
Conduct an ultrasound, a CT urogram, or an intravenous pyelogram, depending on the clinical situation and renal function.
Determine the relevant anatomy, which is the configuration of the prostate related to interstitial laser coagulation (ILC) therapy, with cystoscopic examination and ultrasonography.
Conduct a transrectal or suprapubic ultrasound of the prostate to help measure the prostate length and determine the presence of a middle lobe. The presence of a middle lobe is not a contraindication to this procedure; in fact, middle lobe hyperplasia is well suited for this technique.
Other Tests:
Uroflowmetry
A uroflow test involves the patient urinating into a device that measures the urine volume passed, peak flow rate, and average flow rate. Then, it provides a graph detailing the flow characteristics.
In most men, decreased uroflow results (<10 mL/s) indicates obstruction. However, without concomitant measurement of detrusor pressure, detrusor failure and obstruction are indistinguishable. A pressure-flow study is indicated to differentiate between these two entities. Greater than 15 mL/s is a normal uroflow, and 10-15 mL/s is equivocal.
Compare this test information with age-matched reference ranges. The style and character of the flow curve is more important than absolute numbers. One can exhibit a normal Qmax (maximum uroflow) and still be obstructed if the peak is transient and isolated. A staccato pattern, long voiding times, or a prolonged flat curve can indicate obstruction.
Use that information to determine whether the patient's condition is deteriorating or to evaluate the patient's response to therapy.
If the voided volume is less than 150 mL, the test likely is inaccurate and unreliable.
Questionnaire
Instruct the patient to complete a symptom assessment questionnaire. This helps to evaluate symptom severity, to assess response to therapy, and to detect symptom progression in men who are not on therapy or are taking some form of oral treatment. Most urologists employ the American Urological Association (AUA) symptom score index.
Each of the 7 questions can yield a score of 0-5. A quality-of-life is also scored on a scale of 0-5. This may provide insight into the patient's opinion of his own symptoms.
Patients with total scores of 0-7 have minimal symptoms and rarely require or need any type of therapy.
Scores of 8-19 indicate moderate symptoms and patient discomfort; however, many patients do not need therapy, and those that do generally benefit from medication and phytotherapy.
Symptom scores greater than 20 imply significant symptoms, but they do not always correlate with significant patient discomfort. Men with this score often benefit by some type of therapy.
Diagnostic Procedures:
Pressure-flow studies
Compared to uroflowmetry, pressure-flow studies provide more specific information about detrusor function and the etiology of the voiding dysfunction.
Perform these studies to help differentiate between patients with a low–peak flow rate caused by obstruction and those with a decompensated or neurogenic bladder.
These studies also may identify high-pressure obstruction in symptomatic men with normal flow rates.
This data may be particularly useful in men who are planning to have surgery or those who have had a previous surgery because it distinguishes between bladder dysfunction and outflow obstruction.
Two independent variables: Although pressure-flow studies provide valuable information for clinical decisions, they do not correlate necessarily with symptom scores.
Cystourethroscopy
This rarely is necessary to diagnose or evaluate patients with benign prostatic hyperplasia (BPH). Many urologists perform this test routinely in the evaluation of men with lower urinary tract symptoms (LUTS).
Conduct cystourethroscopy in patients with gross or microscopic hematuria, urethral stricture disease, history of urethral trauma, history of bladder cancer, or prior lower urinary tract surgery. In addition, this study can be performed if the treating urologist feels it will aid in treatment planning.
Also, conduct this procedure to confirm suspicion of a bladder stone or to help determine the most appropriate invasive procedure.
Histologic Findings: The prostatic tissue treated with ILC undergoes coagulative necrosis. Each treated area has approximately 2-3 mL of tissue destruction. Sloughing of necrotic tissue in the urine may occur if coagulation of the urethra is evident, but this is minimal and most of the tissue is absorbed over 6-8 weeks. No tissue is obtained from this procedure for the pathologist to examine.
If the PSA is elevated or if a suspicion of prostate cancer exists, biopsies should be obtained prior to any therapy. Medical therapy: Medical treatment therapy of benign prostatic hyperplasia (BPH) consists of 3 classes of agents: alpha-adrenergic blockers, 5aR inhibitors, and phytotherapeutics.
Alpha-adrenergic blockers
These represent a class of medicines that affect the rich supply of alpha-adrenergic receptors in the smooth muscles at the base of the bladder, the bladder outlet, and the smooth muscles within the prostate and proximal urethra. Blocking these receptors reduces tension in these smooth muscles, relieving the irritative symptoms manifested by urgency and frequency and improving urinary flow.
Several subtypes of the alpha-adrenergic receptors have been identified. The primary alpha-receptors in the prostatic urethra are alpha-1a and alpha-1d. The prostatic stromal tissue is largely alpha-1a. Alpha-adrenergic blockers can be divided into 3 groups, depending upon the affected receptor and their duration of action—nonselective, selective, and selective long acting.
The alpha-receptors in prostatic stromal tissue are largely the alpha-1a subtype. Inhibition of these receptors in the prostate and prostatic urethra reduces the symptoms associated with bladder outlet obstruction (BOO). Inhibition of the alpha-1d receptors diminishes the irritative symptoms, which frequently accompany this condition.
The 4 most common agents include terazosin, doxazosin, tamsulosin, and alfuzosin. These agents have similar therapeutic effects. They improve voiding dynamics and provide symptom relief. In contrast to the nonspecific inhibitors, these agents are long acting (once-per-day dosing) and have fewer adverse effects. Long-term outcome studies of these drugs indicate that their effectiveness persists indefinitely. Because they do not affect prostate growth, patients who are receiving only alpha-blockers often develop increasing difficulty with urination as their prostate enlarges.
Nonselective blockers were the first agents found to be effective but are rarely administered today because of adverse side effects. Selective alpha-adrenergic blockers include prazosin (Flomax), alfuzosin (UroXatral), and terazosin (Hytrin). These agents have fewer side effects compared with the nonselective alpha blockers.
The most common adverse effects, which occur in less than 20% of patients, include dizziness (19%), postural hypotension (6%), lightheadedness, asthenia (6%), and nasal stuffiness. No sexual dysfunction develops, but all of these agents except alfuzosin may cause retrograde ejaculation. This is an advantage for many men.
Tamsulosin and alfuzosin are the most selective of these agents for the prostate/bladder receptors. Dizziness and lightheadedness are problematic for some patients; those who are taking antihypertensive medications need to be cautious when they first start these medications. The use of these agents in conjunction w