Lasers in Urology Treatment & Management

Specific laser applications are discussed below.

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. ^[11] 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. ^[12] 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. ^[13] 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).

The principle representative procedures in the laser coagulation category include visual laser ablation of the prostate (VLAP) using Nd:YAG and interstitial laser coagulation (ILC). VLAP uses a direct transurethral viewing source (eg, cystoscope and video) along with a laser that is supplemented by a visible (usually helium-neon) aiming beam.

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.

In several studies these coagulative procedures have proven to have unacceptably high adverse events, namely irritative voiding, dysuria, and other storage symptoms, as well as high reoperation rates. Additionally, more efficient and improved laser applications such as Ho:LEP and photo-vaporization (PVP) techniques have shown to be more effective largely replacing VLAP and ILC.

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. Additionally, the KTP laser’s ease of use has made it an attractive option for urologists. 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.

In a 2005 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. ^[14] In this study, prostates with volumes of up to 136 mL were safely treated, although some required prolonged operative times of 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 (Q_max).

A higher-powered 120-W LBO laser (GreenLight HPS) was developed and even more recently the 180-W LBO system (GreenLight XPS) has been marketed to improve upon current vaporization speed. Whether these newer generation KTP lasers are clinically superior to their predecessor remains to be seen.

A study comparing patient outcomes after GreenLight XPS photoselective vaporization of the prostate and GreenLight laser enucleation of the prostate used to surgically manage benign prostatic obstruction found both were safe and provide satisfactory short-term functional outcomes. However, the surgical time was longer in the photoselective prostate vaporization group, which also had a higher rate of unplanned hospital readmission, and lower decreases in prostate specific antigen and prostate size. ^[15]

Laser energy has been used to incise or enucleate prostate adenomas down to the capsule, making this procedure the endoscopic analog of open simple prostatectomy. 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.

Meta-analyses have shown the efficacy of Holmium laser enucleation of the prostate (HoLEP) to be similar to TURP, at times favoring TURP, particularly with larger glands. Gilling et al found that urodynamic proven relief of obstruction favored HoLEP for prostates of more than 50 g. When comparing HoLEP with traditional TURP using pooled data, Tan et al suggested that catheterization time, hospital stay, and blood loss were significantly lower in the HoLEP group. ^[16]

In addition, Jaeger et al found HoLEP for recurrent lower urinary tract symptoms after failed prior BPH surgery to be safe and effective, with similar efficacy and incidence of complications regardless of prior transurethral prostate surgery. ^[17] HoLEP has also been shown to be a safe and effective treatment for BPH regardless of age, with similar overall morbidity, hospital stay, and 1-year functional outcomes among all age groups, ranging from age 50-59 year to up to 80 years. ^[18]

For some time, the criterion standard treatment for BPH has been TURP and 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 medical therapies. Additionally, the preponderance of urology patients taking chronic oral anticoagulants and anti-platelet therapy mandate the need for techniques that can be safely performed in this setting. 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.

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 largely abandoned because of post-operative symptomatology and the availability of other modalities. Vaporization techniques, particularly Greenlight PVP, has achieved widespread popularity, largely because of its ease of use and the ability to perform these procedures on an outpatient basis. HoLEP is also a viable vaporization technique and in fact a RCT showed essentially equivalent efficacy and complication rates when compared with Greenlight PVP. Only operative time favored PVP. ^[19]

HoLEP requires the most technical expertise with a correspondingly steep learning curve but is likely the optimal endoscopic approach to the very large gland.  A variety of HoLEP techniques have been described in the literature including the 3-lobe, modified 2-lobe, enbloc enucleation, as well as bladder neck preserving techniques.  Each technique requires a high level of expertise and a lengthy learning curve. ^{[20, 21]}

Although all of the modalities mentioned are efficacious, 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. ^[22] 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 thattheareaofdestructionisdeepandnotfullyvisualized. Somereportsofbowel 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.

In light of extended clamping times during laparoscopic partial nephrectomy (LPN) that result in uncompensated tissue hypoxia, alternative techniques using lasers have been developed to simplify the excision of renal cell carcinomas (RCC) in a bloodless manner without renal vessel clamping. The thulium laser is a continuous or pulsed solid state laser that emits a wavelength of 2013 nm and penetrates tissue to a depth of 0.5 mm. A single center prospective study of 10 high-risk patients found thulium laser-assisted enucleation for RCC to be a feasible, safe, and effective procedure, with no positive surgical margins and without blood loss exceeding 40 mL. ^[23] Similarly, a pilot study of 15 patients who underwent zero-ischemia LPN using thulium:YAG showed minimal blood loss, negative tumor margins, and preservation of renal function. ^[24] The results of these preliminary studies are promising but have yet to be conclusively determined and need further study.

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. ^[25]

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%. ^[26] 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. ^[27] 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 CO₂ 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, 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.

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. ^[28]

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.