Keywords

  • Several non-invasive neoplastic and infectious conditions of the external female genitalia are amenable to treatment with a variety of ablative lasers.

  • Ablative laser treatment of the vulva, vagina and cervix provides a relatively fast treatment modality and results in healing with little scar formation and excellent cosmetic and functional results, as well as fairly uncomplicated postoperative recovery.

  • Intra-abdominal uses of different lasers are valuable alternatives to other thermal or mechanical cutting instruments.

  • Severe side effects and complications of laser use can be minimized by careful patient selection, using the most appropriate instruments, proper surgical technique, and meticulous postoperative care.

  • Good candidates for laser ablative procedures are generally considered to be individuals who have been refractory to medical and/or chemical treatment, and those presenting with extensive disease, as well as patients in whom a single surgical procedure is indicated for medical, psychological, or social reasons.

  • With ongoing advancements in laser technology and techniques, improved clinical outcomes with minimal postoperative recovery will be realized.

Introduction

  • Gynecologists first used laser in 1973 and have used CO2, KTP-532, Argon, and Nd:YAG to treat lower genital tract, intrauterine, and intra-abdominal disease.

The use of CO2 laser in the treatment of uterine cervical intraepithelial lesions is well established, and indications, as well as techniques, have changed very little for over 40 years. The Cochrane Systematic Review from 2013 suggests no obviously superior technique [1]. CO2 laser ablation of the vagina is also established as a safe treatment modality for VAIN (Vaginal Intraepithelial Neoplasia ) and has been used extensively in the treatment of VIN (Vulvar Intraepithelial Neoplasia ) and lower genital tract condylomata acuminata. CO2 laser permits treatment of lesions with excellent cosmetic and functional results. The treatment of heavy menstrual bleeding by destruction of the endometrial lining using various techniques, including Nd:YAG laser ablation, has been the subject of a 2013 Cochran Database Review [2]. Modified laser techniques are among the compared treatment modalities. The conclusion by reviewers is that outcomes and complication profiles of newer techniques compare favorably with the gold standard of endometrial resection. Myoma coagulation or myolysis with Nd:YAG laser through the laparoscope or hysteroscope is a conservative treatment option for women who wish to preserve their child bearing potential. CO2 laser is the dominant laser type used with laparoscopy for ablation of endometriotic implants. The KTP-532 nm laser also has been used for essentially all of the previously mentioned applications of carbon dioxide. It is less widely available, but does offer certain distinct advantages of significantly less post-operative pain and much better hemostasis. These will be discussed further [3]

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History and Procedures

  • In 1973 laser was first used in gynecology by Kaplan for vaporization of infected cervical tissue

  • The use of the laser through a laparoscope was first described by Bruhat in 1979

  • Goldrath first described intrauterine procedures using the Nd:YAG in 1981

  • The media used in gynecologic surgeries are CO2 and argon gases, as well as KTP, Nd:YAG crystals, and diode lasers

Albert Einstein postulated his idea of stimulated emission of radiation in 1917 [4], but it took 40 more years for this idea to be converted into a practical device. In 1958 Arthur L. Schawlow and Charles H. Townes published their initial article covering the basic principles of the laser in the American Physical Society’s Physical Review [5, 6]. This was followed by their first proposal of gas lasers excited by electrical discharge. In 1960 Ali Javan, William Bennett, and Donald Herriott constructed a helium neon laser, the first laser to generate a continuous beam of light [4]. In 1961 the first continuous operation of an optically pumped solid-state laser Nd:CaW04 by L.F. Johnson, G.D. Boyd, K. Nassau, and R.R. Soder was reported [4]. C.K.N. Patel developed the first CO2 laser in 1964 [7]. The same year the Nd:YAG laser was introduced by J.F. Geusic and R.G. Smith [4]. The first experimental medical application was reported in 1965 [8].

In 1973 laser was first used in gynecology by Kaplan for vaporization of infected cervical tissue [9]. The following year Bellina reported the first definitive procedures done on the vulva, vagina and cervix using CO2 [10]. Over the next decade, hundreds of articles were published discussing the techniques of the use of carbon dioxide laser and the treatment of intraepithelial neoplasia and condyloma of the lower genital tract. In 1989 Yandell presented information regarding excisional cone biopsy of the cervix using the argon, KTP-532, and the Nd:YAG lasers, touting marked improvement in hemostasis and application of the energy using the shorter wavelength fiber optic instrumentation [3].

Intra-abdominal and intrauterine applications were also explored. Bruhat first described use of carbon dioxide laser through the laparoscope in 1979 [11]. Three years later, Keye reported on the use of argon laser for the treatment of endometriosis [12]. This was followed very shortly by introduction of the KTP-532 and the Nd:YAG lasers laparoscopically. In 1981 Goldrath first described the use of Nd:YAG laser in the endometrial cavity for the destruction of the endometrium and later, for resection of the uterine septa, submucous myomata, and excision of polyps [13]. In 1984, Rettenmaier first published data on the treatment of gynecologic tumors of the vagina and vulva using photoradiation with hematoporphyrin dyes [14].

Epidemiology of Human Papillomaviruses

Human papilloma virus (HPV) infections, and genital HPV in particular, are serious public health concerns, not just due to their immediate impact on quality of life , but also due to the tremendous economic burden to the affected patient and the public [15]. In the USA, close to $8 billion are spent annually for the treatment of HPV-related conditions [16].

Classifications and Virus Types

Human papilloma viruses only have affinity to the human body. Almost 200 different types have been identified to date. They are subcategorized according to tissue tropism: cutaneous versus mucosal, and oncogenic potential. Depending on the host’s immune competence, these infections may be transient or persistent [17].

Emphasis in this chapter will be placed on anogenital tract infections . There are about 10–15 low-risk types, with types 6 and 11 being most prominent, which are responsible for genital wart growth. There are 15–20 high risk or oncogenic types, which are responsible for precancerous and cancerous transformation of genital epithelial tissue. The most prevalent high risk types are 16, 18, 31, 33, 35, 39, 45, 51, and 52 [18,19,20,21].

Risk Factors

Genital HPV infections are predominately sexually transmitted. Vertical transmission from delivering mother to newborn is confirmed for respiratory papillomatosis [20]. The risk for virus acquisition is directly correlated with the number of sexual partners [17, 22,23,24,25]. Smoking is an additional risk factor , as may be the use of contraceptive pills in women [26]. Condom use appears to provide incomplete protection due to the involvement of uncovered genital contact sites.

Incidence and Prevalence

Estimates of the infection rate within populations are challenging because of the unpredictability of the natural history , the lack of requirements to report the disease, and the large variations between different populations and age groups. The overall risk of infection is ultimately related to sexual behavior and risk factors. HPV is considered the leading sexually transmitted infection in the USA. According to data from the Centers for Disease Control (CDC) and the National Health and Nutrition Examination Survey (NHANES), at least 50% of sexually active men and women will acquire HPV infection at some point in their lives [27]. Not surprisingly, adolescents and young adults show the highest incidence numbers [24, 28]. HPV infections in men are less extensively studied, but infection rates appear similar to those found in women and are estimated to be as high as 73% [26, 29]. Male circumcision appears to decrease the risk of infection for the male and probably the risk of transmission of the virus [30].

Studies on the distribution of different virus types within 11 countries from Africa, Europe, and South America demonstrated geographic variation, with the HPV 16 type being more prominent in Europe [31].

Tissue Tropism and Clinical Infections

Several HPV types have a propensity to infect keratinizing epithelium and cause cutaneous warts, such as common warts and plantar warts (types 1, 2, 4), Butcher’s warts (types 2 and 7), and flat warts (type 3 and 10) [32, 33]. Bowen’s disease is a form of squamous cell carcinoma in situ from which numerous virus types have been isolated: 16, 18, 31, 32, 34 and others [21, 32, 34, 35]. Several of the above mentioned virus types also infect non-keratinizing epithelial surfaces, especially within the anogenital region, but also within the mouth and pharynx. Condylomata acuminata are the best known genital warts and affect at least 1% of the sexually active population, with the peak prevalence in the young adult age group [22, 23, 25, 35]. Subclinical infections are very common and constitute a major challenge for the treating physician. Colposcopy and acetic acid are required tools for detection of these latent stages.

There is now ample evidence that links persistence of high risk HPV types to the development of cervical cancer and other surface cancers of anal, vulvar, penile, and oropharyngeal origin [21, 36,37,38,39]. In the past, cervical cancer was the most frequent malignancy among women in developing countries, but it now ranks second after breast cancer [21].

Outlook

The introduction of the quadrivalent papilloma virus vaccine for adolescent and young adult females in 2006, as well as the newly introduced nonavalent vaccine [40], will positively impact the epidemiology of immunized women in the decades ahead, but generations of already infected women will need attention for many years to come. Since 2011 HPV vaccines are also approved for male adolescents aimed at more efficient immunization of the entire population [41].

Laser Use on Vulva, Vagina and Cervix

Indications

  • Intraepithelial Neoplastic Disease

  • Condyloma acuminata refractory to medical and chemical treatment

  • Cervical Stenosis

  • Extensive Disease including extension into anus and urethra/bladder of condyloma acuminatum

Contraindications

  • Patients in whom invasive cancer has not been ruled out

Since the instruments first became available to gynecologists, laser has been used in the treatment of pre-malignant (dysplastic) lesions of the lower genital tract . These include cervical intraepithelial neoplasia (CIN) , vaginal intraepithelial neoplasia (VAIN) , and vulvar intraepithelial neoplasia (VIN) .

The vast majority of these intraepithelial neoplasias are of the uterine cervix. The incidence and prevalence has started to decrease after the HPV vaccine introduction, especially in younger population (≤18 years) [42]. At birth, the squamo-columnar junction between the vagina and the endocervical columnar epithelium lies at the outer aspects of the ectocervix. At menarche, the vaginal pH drops substantially from 7.2 to 4.5. This, coupled with a marked effect on the vaginal flora, causes the onset of metaplastic change over the columnar epithelium that is exposed to the vaginal environment. During the course of metaplastic change, this exposed endocervical tissue is covered by a pseudo-stratified squamous epithelium with small infoldings in the surfaces down to the level of the original columnar tissue. These infoldings are frequently, and incorrectly, described as glands or crypts, for lack of a better term. The entire process takes approximately 8–10 years, and during this time the tissues of this transformation zone are extremely susceptible to the virus. Once the HPV is incorporated into the cells, they may undergo neoplastic transformation or simply remain infected, depending on the specific viral subtype. The body may recognize the virus as foreign and mount an immune response, but in many cases, it does not, allowing persistent infection or neoplastic change, which can then advance in severity. The lesion spreads over the cervical surface and as it does so, it also moves down into these “glands” of the newly formed transformation zone.

When the patient presents, usually following an abnormal pap smear, the work up includes colposcopy with biopsy of the most suspicious areas, to determine the severity of the disease. Because the lesion is intraepithelial, destruction of the epidermis is adequate for treatment of the neoplastic lesion; however, it is known that large areas of the normal appearing transformation zone are infected by the virus despite no visible lesions being present on colposcopic exam. The other concern regarding treatment is that because of the infolding of the epithelium, the dysplastic lesion may extend several millimeters below the surface, and into the endocervical canal. With this in mind, the generally accepted treatment is destruction of the entire transformation zone to a depth of 5–7 mm.

Treatment methods used in the past were diathermy , and later cryotherapy . Neither of these modalities allow the physician to discern the depth of destruction at the time of the procedure. The use of laser, however, allows very accurate vaporization or ablation of the transformation zone down to the desired depth, with extension of that vaporization further up into the endocervical canal to visibly and measurably treat the entire extent of the tissue involved.

Evaluation and treatment of vaginal and vulvar intraepithelial neoplasia is similar, and in some ways simpler, because the epithelium involved is completely exposed, unlike that of the uterine cervix. Care must be taken, especially in the vagina, to not destroy more than the affected epithelium, which generally is less than 1 mm in thickness. Problems also arise in treating the portion of vulva in which there is hair because of the spread of the disease down into the follicles. Another concern with VIN is that it tends to be multifocal, requiring very careful colposcopic exams and frequently several biopsies in order to identify the extent of lesions.

Of paramount importance is ensuring that there is no invasive disease prior to using local destructive treatments. Any suspicion of invasion requires further excisional tissue diagnosis. For many years, excisional cone biopsy was performed using the “cold” knife, or “hot” electrocautery. This is a markedly inaccurate procedure which removes the entire ectocervix and the distal and middle portion of the endocervical canal for tissue evaluation. The “cold knife” cone is fraught with potential complications including excessive blood loss; inadequate incision depth, which may make it difficult to discern whether the lesion is invasive or microinvasive if it is incompletely excised; and excessive tissue removal, resulting in incompetent cervix and subsequent second trimester pregnancy loss. Because of their precision and hemostatic characteristics, lasers have been used for excisional cone biopsies by many surgeons for the last 30 years.

The other major indication for the use of laser of the lower genital tract is the treatment of condylomata accuminata . These lesions are generally first treated conservatively using cyto-toxic agents such as podophylin, immune modulators such as imiquimod, or acids such as TCA, for the destruction of specific early disease. Cryocautery may also be used for destruction. However, in most cases, each of these requires multiple treatments which can be fairly painful and irritating. The use of cryocautery may also be complicated by excessive destruction into the dermis, which causes scarring and may result in ulceration and infection. Because large areas of skin are infected with the virus and appear normal at the time of initial treatments, it is very common for secondary lesions to become apparent around previously treated lesions. In some cases the local treatment itself may not be adequate to cause destruction of the primary lesions. Frequently, patients present with extensive disease involving large areas of the lower genital tract and local treatment using medical or chemical means is simply impractical. These patients are generally treated primarily with laser in the operating room for the best results. In a significant number of these cases, the condylomata extend into the anal canal and may also extend into the urethra and bladder neck. The KTP-532 laser may be used inside the bladder and urethra for precise destruction of lesions in a fluid environment.

One known complication of conventional cone biopsy of the cervix is stenosis of the cervical os. In this situation, hypertrophic scarring of the surgical defect essentially closes the endocervical canal to the point that menstrual flow may be obstructed, or secondary infertility becomes an issue. The best treatment for this condition is CO2 vaporization of the scar tissue which has occluded the canal. Following this procedure, the endocervical columnar epithelium typically grows outward as the squamous tissue grows in from the exocervix, creating a more normal patent opening.

Techniques

  • Adequate preoperative patient evaluation and education

  • Timing of the procedure to closely follow the menstrual cycle

  • Antibiotics are rarely indicated if the appropriate depth of destruction is maintained

  • The Carbon Dioxide and KTP-532 lasers are both used for the treatment of lower tract disease

  • Although the CO2 laser is the most commonly used, the KTP-532 offers the important benefit of substantially less post-operative pain, which is the single most significant morbidity encountered

  • Care must be taken not to ablate too deeply, especially in the vagina and over opposing vulvar surfaces

  • Early postoperative evaluation is the key to avoiding major complications

Preoperative Management

There is no consensus among laser experts regarding the most appropriate preoperative regimen for laser use in gynecology. Adequate preoperative patient evaluation and education are paramount because of the relatively long and sometimes painful postoperative course, and the relatively high persistence and recurrence rates of both intraepithelial neoplasia and HPV. It is always best to time the procedure just after the menstrual period to allow the longest time possible for healing before the next menses. In some instances, it is appropriate to postpone menstruation by using hormonal therapy such as injectable depomedroxyprogesterone or oral contraceptive suppression.

It is sometimes advantageous to administer a mechanical bowel prep prior to any extensive procedure. This will decrease exposure of the surgical field to bowel flora. The prep should be administered the day before surgery.

Due to the moist, de-epithelialized state of ablative laser treated skin and the possibility of bacterial contamination and overgrowth over the vulva and vagina, some gynecologic laser surgeons advocate oral or topical antibiotic prophylaxis . This practice remains controversial, due to the lack of results of controlled studies. Antibiotics have not been used for laser procedures on the cervix. The one exception to this is the patient who is found to have bacterial vaginosis at the preoperative evaluation. Because of the high bacterial count of anaerobic organisms in the vagina, this condition should always be treated with metronidazole or clindamycin before surgery.

Description of the Technique

Laser in the Treatment of Cervical Disease

When laser was first introduced as a tool for the gynecologist, it was the CO2 laser which was used for treatment of cervical disease [9]. In the early reports of laser surgery, Baggish and Dorsey helped to define and establish the techniques used in CO2 laser therapy. They described using a 0.5–1 mm spot size and power of 25–50 W, resulting in a power density of 2,500–20,000 W/cm2 to cut, versus a 2–3 mm spot size and 20–25 W for vaporization which has a corresponding power density of approximately 500–800 W/cm2. This was done under colposcopic guidance with the laser coupled via a micromanipulator. In 1982, they reported a series of over 400 cases with CIN treated by laser with an overall cure rate of almost 96% at about 1-year follow-up [43]. The only significant changes since then have been the use of slightly higher power densities. However, moving above the 1500 W/cm2 range frequently results in the beam cutting into vessels without first coagulating them and may cause significant bleeding. The higher power density does result in less thermal damage to the specimen, and offers a superior specimen for pathologic evaluation. There are very few current publications on this subject. Cochrane Systematic Reviews published in 2002 on surgery for CIN and compared seven surgical techniques. They concluded that the Loop Electrosurgical Excision Procedure (LEEP) appeared to provide the more reliable specimen for pathology but the overall morbidity was lower with the laser conization. The limited evidence suggests that there is no obviously superior surgical technique for CIN [44].

The KTP-532 laser has also been used for excisional and ablative procedures of the cervix, although there is little published data. The fiber is passed through a 9 in. hand piece with a 30° curve at the tip. This allows a free hand excision of the surgical specimen using 10–15 W (power density of 3600–5000 W/cm2). The most significant benefit is the marked decrease in bleeding encountered, which is generally the most difficult complication to deal with when using other modalities, including the carbon dioxide laser. This is explained by the high photochemical absorption of the 532 nm wavelength in the hemoglobin molecule. The beam passes through the relatively clear vessel wall, coagulating the blood before cutting it. Because of the forward penetration of this wavelength, the fiber is angled toward the patient and away from the specimen to decrease coagulation artifact and increase hemostasis during the incision of tissue. The KTP-532 has been used for the last two decades and has been found to allow for almost bloodless excisional cone biopsies [1] (Fig. 6.1).

Fig. 6.1
figure 1

The flexible quartz fiber of the KTP-532 laser is seen passing through a hand piece which allows a 30° angle at the tip. This allows the surgeon to apply the beam parallel to the skin surface for vulvar and vaginal procedures and is advantageous when performing excisional cone biopsies of the cervix

Full size image

The Nd:YAG laser has also been used for excisional procedures, but because it must be coupled with a sapphire tip to do incisional work, it is somewhat more costly and difficult to manipulate inside the confined space of the vagina. It is, however, extremely hemostatic because of this wavelength’s intrinsic coagulation of protein.

Some authors suggest that combining LEEP with additional laser treatment of the cut margins and wound bed may improve long term success [45, 46]. Microscopically guided laser vaporization or laser excisional cone may be a less aggressive, and certainly more controllable treatment modality than a traditional “cold knife cone (CKC) ” and therefore, may be the choice for young women interested in preservation of fertility [46,47,49].

In addition to the previously mentioned complications of CKC, it may result in the removal of too much or all of the endocervical glands, resulting in cervical factor infertility and/or cervical stenosis, which precludes the passage of menstrual tissue. In the case of cervical stenosis, the CO2 laser is the instrument of choice to vaporize the scar tissue which is occluding the canal. A higher power density is used in the range of 5,000 W/cm2 to decrease thermal damage of the surrounding area and allow the normal tissues to grow back into place.

The use of lasers has significantly decreased the complications which have been historically encountered with the traditional cold knife cone.

Laser in the Treatment of Vaginal Disease

The treatment of vaginal dysplasia and condyloma remain challenging, regardless of treatment modalities. Since the vaginal epithelium is less than a millimeter thick, ablation has to be very superficial. Traditionally, the procedure was done in similar fashion to cervical laser vaporization, under colposcopic supervision with the micromanipulator. A 2 mm spot size is chosen at a 20–30 W power setting [8, 50]. Duane Townsend was among those establishing the technique. Because of the sharp tangential angulation of the impact beam delivered to the vaginal wall from a colposcopic delivery system, many surgeons today prefer to use a hand held device. This is incrementally better, but because of the bulky nature of the CO2 hand piece, it is still difficult to deliver a beam at 90° to the surface. The use of a fiber-optic laser such as the KTP-532 delivered through a hand piece with an angled tip as previously described, can allow the surgeon to deliver the beam with a more even distribution of energy to the surgical site. This is done using 10 W and short exposure times to compensate for the increased penetration of this wave length into the underlying tissue. With either technique, it is very important not to overlap exposure applications in order to protect the underlying dermis.

The bulk of the available literature is from the 1980s to the mid-1990s. Uniformly, recurrence or persistence rates in the 30–50% range are reported after the first laser treatment. Even after the second and third treatment courses, 20% relapse or persist. This disease is considered multi focal in the majority of cases. In the case of VAIN III involving the vaginal cuff angles after hysterectomy, upper vaginectomy is proposed over plain laser ablation. Additional superficial lasing of the surrounding vagina is generally recommended [50,51,52,53,54,55,56,58]. The main advantage of the laser procedure in comparison to conventional surgery or the use of cytotoxic agents, is the preservation of the anatomic integrity of the vagina, even after repeated laser courses [55]. The recommended curative and safe depth to be achieved with the laser treatment is only 1.5 mm, which allows for re-epithelialization without scarring [59].

In the case of larger exophytic condyloma , the lesions are vaporized down to a level consistent with the surrounding vaginal wall before the adjacent normal appearing epithelium is treated. Because of the high recurrence rates, it is assumed that substantial areas of this normal appearing epithelium are in fact infected by HPV. In many cases of extensive disease, the correct plane of the original vaginal wall may be extremely difficult to determine. In this case, it is better to err in the direction of removing less tissue and, in some cases, to only treat part of the affected area. In many instances in which only partial vaporization is completed, the post-operative inspection reveals complete clearance of the condyloma. It is believed that these patients’ immune systems are stimulated to recognize the HPV as a result of the surgery and develop an immune response to the virus resulting in clearing of the untreated lesions.

Laser in the Treatment of Vulvar Disease

CO2 laser treatment for vulvar lesions was introduced about the same time as that of the cervix. The first reports were again by Baggish and Dorsey [60, 61]. They established the technique still in use, which employs a spot size of 2–3 mm and power settings of 15–30 W.

The goal is to confine the damage to the epidermis and upper papillary dermis; however, stacking of laser pulses by treating an area with multiple passes in rapid succession or by using a high overlap setting on a scanning device can lead to excessive thermal injury with subsequent increased risk of scarring. This untoward effect can be avoided by moving the beam in a serpentine fashion or in ever increasing concentric circles while avoiding overlap. The depth of ablation correlates directly with the cumulative amount of time x wattage, or work measured in joules, applied to a specific location. Using a power density of 800–1,000 W/cm2 is generally considered ideal for CO2, and should result in instantaneous boiling of the water in the epithelium, causing a vapor pocket above the dermis with elevation of the superficial layer. A power density, which is too high, results in deep vaporization into the dermis, which should be avoided. However, this effect is time sensitive and as the skill and speed of the surgeon increase, a somewhat higher power density may be employed. If the power density is too low, an ablative plateau is reached with less effective tissue ablation and accumulation of thermal injury. This effect is most likely caused by reduced tissue water content after initial desiccation, resulting in less selective absorption of energy. The avoidance of pulse stacking and incomplete removal of partially desiccated tissue is paramount to prevention of excessive thermal accumulation with any laser system. The objective of ablative laser treatment is to destroy tissue down to the papillary dermis. Limiting the depth of penetration decreases the risk for scarring and permanent pigmentary alteration. When choosing treatment parameters, the surgeon must consider factors such as the anatomic location and proximity to vital organs. To reduce the risk of excessive thermal injury, partially desiccated tissue should be removed manually with wet gauze after each laser pass to expose the underlying dermis.

This technique is very reliable when treating the non-hairy vulvar surfaces. In areas containing hair, the method must be altered in an attempt to treat intraepithelial neoplastic disease, which progresses toward the base of the follicle. In most cases this is best done by making a second pass over this tissue after the superficial epithelium has been removed. This characteristic of VIN is felt to be one of the primary causes of persistent disease in cases which have otherwise been adequately treated by laser, and is perhaps the main reason some gynecologists still advocate excision in these areas. When cosmesis is a priority, the laser is still preferable, and the patient must be informed that she must commit to close follow-up and the possibility that further treatment may be needed. Unfortunately, because of the high recurrence rates in all VIN cases, this is more or less true for all patients.

When treating condyloma, the same techniques are generally applicable, but must be modified for larger exophytic lesions. The smaller condylomata may be simply vaporized or excised, but only to the level of the skin with care being taken not to coagulate the deeper dermis. The surrounding normal appearing epithelium is then treated in the same fashion as described above to a distance of 1–2 cm from the original wart. If this is not done, recurrence rates are very high.

For the larger pedunculated lesions, several techniques may be employed to decrease bleeding, which may occur if the CO2 laser is being used. Although the carbon dioxide laser is generally regarded as a very hemostatic instrument, it does so by thermal coagulation of vessels as the tissue is vaporized at the impact site, unlike the KTP-532 and Nd:YAG wavelengths which actually pass through water and coagulate by direct absorption in hemoglobin and protein respectively. When larger vessels are encountered, the CO2 may cut into the wall before the more rapidly moving blood is coagulated, creating bleeding. Further attempts to seal the vessel are then hampered by the complete absorption of the energy at the surface of the emerging blood, which does not allow heat to penetrate to the vessel below. The blood must be cleaned away while pressure is applied to the vessel in order to tamponade the bleeding to allow further progress. Alternatively, pedicles may be coagulated circumferentially before attempting excision. This is more productive if the blood flow can be stopped by pressure at the base. In some cases, it is better to use a much lower power density in the range of 200–400 W/cm2 to essentially cook the tissue initially. The wattage may be decreased or the spot size increased to accomplish the change. This can however, result in thermal spread into the dermis. In some instances, electrocautery or sutures may be needed.

The KTP-532 laser , although much less widely available, may also be used in the treatment of these diseases, and offers significant advantages once the technique is mastered. Because this wavelength is not absorbed in water, there is deeper penetration (1–2 mm) than seen with the CO2. In order to decrease damage to the dermis, a higher power density (2,000–5,000 W/cm2) is used with a shorter application time, resulting in a more immediate coagulation of the epidermis, and less thermal spread. The outcome is somewhat different, because the effect will be desiccation and coagulation, with little or no vaporization. The treated epidermis is then wiped away using a gauze pad. The incidence of bleeding is much lower because of the extremely high absorption of the 532-nm wavelength in hemoglobin, and the ability to move through vessel walls, which are mainly water, before cutting into them. Should bleeding be encountered, the hand piece is backed away a few centimeters, which will rapidly increase the spot size secondary to the 15° divergence of the beam from the fiber tip, resulting in a much lower power density for coagulation purposes (Fig. 6.2a, b).

Fig. 6.2
figure 2

(a) Patient with extensive condylomata acuminata of the vagina, vulva, and peri-anal skin. (b) Same patient following treatment using the KTP-532 laser. There is marked edema forming in the clitoral hood and labia minora before the entire procedure is completed. Note the absence of pitting into the dermis and the extended treatment area around all previously visible lesions

Full size image

The most significant advantage to this wavelength is a marked decrease in postoperative pain compared to the CO2 laser . Significant and prolonged pain is the most common morbidity of vulvar laser treatment. Because the CO2 has very little forward scatter, the equivalent of a second degree burn is being created, with the intact sensory nerves exposed. Although the exact mechanism is uncertain, it is postulated that the 532 nm wavelength is absorbed in these nerve endings, essentially decreasing their response to stimuli for a short time during the healing process. There does not appear to be any long term effect. The increased depth of penetration may also be beneficial in treating VIN in skin containing hair follicles, although this has not yet been substantiated.

Laser therapy of vulvar intraepithelial neoplasia and condyloma results in excellent cosmetic and functional healing, but carries the risk of recurrent and persistent disease. Repeated treatments may be necessary. In light of the multifocal nature of these disease processes in the majority of patients, laser, with its ease of technique and low morbidity, is the treatment of choice, especially for younger women [7, 50, 62, 63]. For extensive VIN III, excisional laser surgery of the more suspicious areas combined with vaporization of the surrounding “normal” epithelium, provides a histologic specimen and appears to be more effective than pure vaporization [63].

Post-operative Management

The post-operative management of the lower genital tract largely centers around the treatment and prevention of pain and bleeding. Following excisional or vaporization cone biopsy of the cervix, the most common complication is delayed bleeding. This occurs as the scar falls away at 10–14 days. Because of this, the base of the excision site may be coagulated at a very low power density to further seal vessels. This is followed by placing Monsel’s solution (Ferrous Sub-Sulfate) on the treated surface to decrease the risk of bleeding.

Following vaginal and vulvar procedures , the management and follow up is more complicated due to the variety of symptoms and complications encountered. The most common problem is pain following vulvar procedures. The most significant complication is that of opposing denuded surfaces of the vagina and labia scarring together. Some gynecologists have routinely coated the treated surfaces with silver sulfadiazine 1% (Silvadene) as is commonly used in severe burn patients to deter infection and stimulate tissue regeneration. The incidence of infection is extremely low after these procedures without using any type of antimicrobial compound. Because of the expense of Silvadene and assuming the depth of destruction is appropriate, the author prefers to use triamcinolone cream applied immediately after the surgery is completed. The steroid cream blocks a substantial amount of the edema and pain associated with the immediate post-operative period and physically separates the denuded tissues, preventing adhesion formation. Application of either of these medications may continue for 1–3 days if they are deemed helpful.

Because of the high incidence of significant pain following CO2 laser vulvar procedures, these patients should routinely be discharged with substantial amounts of oral pain medication. The expectation is that the most significant discomfort will occur at 7–14 days post-operatively. It is not recommended that lidocaine ointment be used secondary to the relatively short time of pain relief it offers and because there may be significant systemic absorption and toxicity. Sitz baths are encouraged two to three times daily, using a physiologic electrolyte solution, which can be easily made by adding a salt water aquarium preparation mixture, which is available at most pet stores, to bath water. The patient is told to keep the area as dry as possible by using a hair dryer with low heat, and by avoiding underwear to keep the area exposed to air. It is also of note that Preparation H, which is marketed for the symptomatic relief of hemorrhoids, has been found anecdotally to offer significant pain relief in these cases.

These patients should have frequent post-operative exams to insure that significant scarring or adhesions are not forming and to evaluate pain control. In patients being treated for condylomata accuminata, evaluation for new lesions should also be done at each visit. These may be found very early following surgery and should be treated locally as soon as they become apparent.

Adverse Events

  • Severe scarring and contracture of the vagina is a known complication.

  • Attempts to treat the entire lower genital tract in an attempt to rid the area of HPV is futile and frequently results in major complications.

  • The most important preventative factor is the avoidance of excessive depth of destruction.

Side Effects/Complications

Pain, bleeding, and persistence of HPV are the most common problems encountered following laser therapy of the lower genital tract, as was previously discussed. These issues are present to a greater or lesser degree in the majority of cases. The more serious complication of vaginal and vulvar scarring and contracture are much less common today than in the past, but require constant diligence and attention to detail during surgery to be avoided. During the 1980s there was a period in which it was believed that laser treatment of the skin and mucosa of the entire lower genital tract could eradicate human papilloma virus entirely. As a result of such attempts, and almost certainly coupled with an excessive depth of destruction, there were a number of cases in which the patient’s vagina scarred/contracted down to a fraction of the original size. These patients generally had very severe post-operative pain and had not been examined until several weeks after their surgery. This complication can take on several different presentations. If the upper vagina scars to the contralateral side it can completely occlude the cervix from the vagina thus obstructing menstrual flow. If similar scarring occurs at the introitus, the vaginal opening may be closed to the point of precluding intercourse. In the worst case scenario, the entire length of the vagina may react similar to the skin following third degree burns with extensive fibrosis and contracture. In all of these situations, the treatment as discussed below is lengthy, usually requiring one or more plastic surgeries, and frequently does not result in a good outcome.

Prevention and Treatment of Side Effects/Complications

The most important aspect of prevention of side effects revolves around having an experienced surgeon who is meticulous about maintaining the depth of tissue damage at the level of the basement membrane. As previously alluded to, the use of inherently hemostatic wavelengths, which also tend to seal off exposed nerves such as the KTP-532, is advantageous but not widely available. The treatment of the minor side effects was previously discussed under post-operative management and must be individualized.

The prevention of the vast majority of severe complications noted above can be accomplished through education and mentoring of physicians regarding surgical technique. The concept that multiple procedures and longer term treatments are preferable to these types of complications is paramount. Despite the best efforts, these severe complications will continue to be encountered occasionally secondary to hypertrophic scarring, infection, and idiopathic responses. Treatment may be dramatically affected if the problems associated with excessive depth of tissue destruction and abnormal scarring are identified early in the post-operative course. Estrogen cream and steroids may be employed to increase epithelialization and decrease scarring. There is frequently an indication for manual dilation and the placement of vaginal obturators to counteract contracture formation. Obviously infectious processes, although rare, may be dealt with much better if identified early.

Once the scarring has matured, the effect of vaginal dilators is slow and usually very uncomfortable. Obturators are usually progressively enlarged over prolonged intervals, if possible. They are generally kept in place constantly except for cleansing. If the scarring occludes menstrual flow, or if no progress can be made using dilators, relaxing incisions and at times grafting must be considered. The overall treatment course can be protracted, and in some cases the patient must have extensive counseling to deal with a lifelong problem of dysparunia and orgasmic dysfunction.

Intrauterine and Intra-abdominal Laser Procedure

  • Menorrhagia , leiomyomata, endometriosis, and pain from pelvic adhesions are leading causes of hysterectomy worldwide.

  • Nd:YAG laser has been used for endometrial ablation, resection of uterine septae, and removal/destruction of intrauterine submucosal leiomyomata for over a quarter century.

  • Destruction of larger leiomyomata (3–6 cm) can be accomplished laparoscopically using laser techniques.

Endometrial Ablation

Twenty percent of women worldwide are affected by menorrhagia , a condition defined as excessive uterine bleeding [46]. More than one-third of the 700,000 hysterectomies performed yearly in the US are for symptomatic menorrhagia [64]. As previously stated, Goldrath first reported using the Nd:YAG laser for the destruction of the endometrium in 1981 [13]. Alternative treatment modalities for the permanent control of excessive uterine bleeding include several newer devices that destroy the endometrium through cautery much more rapidly than can be accomplished using a solitary laser beam. Two of these instruments freeze the tissue (CryoGen’s First Option, Gynecare’s Soprano). The following is a sampling of the devices that heat the tissue to achieve destruction:

  • Roller ball ablation using electrocautery

  • Hot water thermal balloon: Thermachoice (Gynecare, Menlo Park, CA)

  • Radiofrequency thermal balloon: Vesta (Valleylab, Boulder, CO)

  • Hydrothermal ablation: Genasys (Boston Scientific, Marlborough, MA)

  • Bipolar three-dimensional device: Novasure (Hologic, Inc, Marlborough, MA)

  • Microwave 9.2 GHz applicator: Microsulis (Hologic, Inc, Marlborough, MA)

  • Bipolar Radio Frequency (RF) + Thermal Conductive Energy (Plasma) + Thermal Fluid Energy: Minerva (Minerva Surgical, Redwood City, CA)

The gold standard is generally considered to be hysteroscopically directed endometrial resection. In concordance with the Cochrane Database Review from 2013, this gold standard is being challenged by the rapid development of these new endometrial destruction devices [2]. Most of these techniques are performed blindly and are much simpler to master than hysteroscopic procedures. The expense of the equipment and competition for market share are probably confounding factors.

Despite the widespread use of the previously mentioned instruments for endometrial ablation, the Nd:YAG is still the laser of choice to resect uterine septae and in many cases, larger pedunculated and submucous leiomyomata.

The wavelength of the Nd:YAG laser is 1,064 nm in the near infrared spectrum. Because of this, a helium-neon aiming beam, has to be incorporated. As with the argon and KTP lasers, the flexible fibers used for delivery are suitable for laparoscopic and hysteroscopic equipment. The Nd:YAG laser wavelength is less absorbed by hemoglobin rich tissue and it has a greater depth of penetration, 3–7 mm with “bare-fiber” non-contact use. Both air-cooled and water-cooled units are available. The development of sapphire and quartz tips has expanded the spectrum of application and increased the safety. Even with these advances, care must be taken not to allow the energy to scatter through the uterine wall and damage extrauterine structures.

Laser in the Treatment of Vaginal Atrophy and Relaxation

Vaginal atrophy is a common condition of postmenopausal women. Symptoms include vaginal dryness, itching, discomfort, dysuria and dyspareunia. This disorder is closely related to the dramatic decrease in ovarian estrogens due to natural or iatrogenic menopause, leading to significant changes in the structure of the vaginal mucosa, with consequent impairment of many physiological functions. Local or systemic estrogen (with or without concomitant progesterone) is a mainstay treatment option for vaginal atrophy but may cause adverse effects such as abnormal uterine bleeding or endometrial hyperplasia. Additionally, hormone therapy may be related to an increased risk of breast cancer or cardiovascular disease such as stroke or heart attack [65].

The effectiveness of vaginal or systemic estrogen therapy to alleviate vaginal dryness and improve dyspareunia has been well established [66]. More recently, microablative fractional CO2 laser therapy has been utilized in the treatment of menopausal vaginal atrophy. Fractional CO2 laser has been proven to determine tissue remodeling with neoformation of collagen and elastic fibers on atrophic skin [67].

Salvatore, et al., evaluated sexual function after fractional microablative CO2 laser in women with vulvovaginal atrophy and found that laser treatment is associated with a significant improvement of sexual function and satisfaction with sexual life in postmenopausal women with symptoms of vulvovaginal atrophy [68].

In a recent study by Lee, the Erbium:YAG Laser has been successfully utilized in treating vaginal relaxation syndrome [69]. Vaginal relaxation syndrome is defined as laxity of the vaginal walls. It can result in the loss of friction and sexual satisfaction for both a woman and her partner. The most common cause of vaginal relaxation is extreme distention of the vaginal wall during childbirth. Other causes include congenital connective tissue weakness and aging. Until now, effective results for vaginal relaxation syndrome could only be achieved through aggressive surgical intervention such as anterior and posterior vaginal colporrhaphy. Outcome data from Lee’s study using the Er:YAG laser showed a significant improvement in vaginal wall relaxation, including vaginal wall tightening and firming, as well as for sexual satisfaction by the patient and her partner. In addition there was significant improvement of mild-moderate stress urinary incontinence in postmenopausal women [69].

Laser Treatment of Leiomyomata

Thermal coagulation of uterine leiomyoma was first introduced in the late 1980s in Europe [70, 71]. Initially, this procedure was used as an alternative to major surgery for women interested in further childbearing. The principle of action involves taking advantage of the relatively deep penetration of the Nd:YAG and later diode laser wavelengths (up to 7 mm) whose bare fibers are inserted or drilled into the center of the leiomyoma, causing protein denaturation of the actual myoma, as well as destroying the blood supply [70,71,72,74]. Pre-treatment with GnRH may decrease the size of the leiomyomata before surgery [75, 76]. Besides bare laser fibers, bipolar needles have also been used. It takes about 50–75 punctures to coagulate a 5-cm leiomyoma [77]. Goldfarb used 50–70 W continuous power with the moving laser tip. Chapman, 1997, warned about the use of high power settings with interstitial laser because the vapor that develops during the heating has no avenue of escape and may cause burns and explosions as well as breakage of fibers. The alternative technique uses 4–8 W for photocoagulation of the leiomyoma [78].

In 2000, MRI guided percutaneous laser treatment of uterine leiomyoma was introduced [79, 80]. Shrinkage rates of 30–50% have been reported for laparoscopic and percutaneous approaches [78,79,81].

There are no randomized controlled trials in the published literature, which is comprised only of observational series. It can be concluded from the publications however, that these modalities are safe and well tolerated alternatives for women who desire preservation of their fertility and have fibroids less than 6 cm in diameter in challenging locations.

Nevertheless, technical problems, high costs, and unfulfilled or unrealistic expectations by physicians and patients alike hinder widespread use of this technique [82].

Laparoscopic Laser Surgery for Endometriosis and Adhesiolysis

CO2 laser treatment has been used for the treatment of endometriosis laparoscopically since the mid-1980s [83, 84]. Especially in Europe it has been widely used. High power densities are preferred for vaporization of lesions to avoid any charring. Charring causes high temperatures in vital surrounding tissues and should be avoided under all circumstances. CO2 laser is believed to be superior to electrocautery because of its shallow penetration [71, 83, 85]. In the case of ovarian endometriomas, excision of the capsule rather than vaporization appears to be more beneficial for long-term cure [86].

The majority of publications are case series and few comparative studies have been published. Available evidence suggests that laser treatment of endometriosis may have long-term benefits in slightly more than half of the treated women [87]. The shorter wavelength lasers (KTP, argon, and in some cases Nd:YAG) have distinct advantages over CO2 laser in that they are delivered through 600 micron flexible quartz fibers, eliminating the cumbersome delivery arms and optic couplers necessary with CO2 lasers. When using the visible wavelength of the KTP-532 and argon instruments, the aiming beam is the attenuated surgical beam. Because of this, they may be more accurately delivered and are more clearly visible in the abdomen than the HeNe laser that must be simultaneously superimposed on the CO2 laser beam. These lasers do require some restraint when used directly over vital tissues because of their deeper penetration. This may be 0.3–1 mm depending on the specific tissue parameters such as pigmentation and hemoglobin content. The 4 mm depth of penetration is a much larger concern with the Nd:YAG laser, and because of this issue, it is used only for very specific laparoscopic indications. All fiber optic delivery systems do, however, have the advantage of rapid divergence of the beam from the fiber tips, which allows the power density to drop off very rapidly over a short distance, when compared to the CO2 laser beam. The much longer CO2 wavelength must be focused via lenses outside the body, and is therefore essentially in focus over a large depth of field, requiring the use of backstops to avoid injury of tissues distant from the surgical target [8]. KTP, to a slightly lesser extent, and argon lasers also have the advantage of extremely high absorption in hemoglobin and hemosiderin, which are typically very prevalent in lesions associated with endometriosis . They may also be used through a clear fluid medium allowing use under water and while irrigating to obtain hemostasis.

The Cochrane Database Systematic Reviews published a meta-analysis of randomized comparative studies involving different treatment modalities for endometriosis including laser. The limited evidence suggested that the combined surgical approach of laser ablation , adhesiolysis , and uterine nerve ablation is likely to be beneficial in alleviating pain [88].

Photodynamic Therapy

In 1984, Rettenmaier first published data on the treatment of gynecologic tumors of the vagina and vulva using photoradiation with hematoporphyrin dyes [14]. Photodynamic therapy (PDT) is a treatment modality employed to destroy a specific type of tissue. It uses a photosensitizing drug such as aminolevulinic acid (ALA) which when given, is absorbed in large quantities in the targeted cell line. These drugs exhibit very high absorption of specific wavelengths of light and once the cell is exposed to these wavelengths, it may be destroyed. The German physician Friedrich Meyer-Betz was the first to perform photodynamic therapy using porphyrins in humans in 1913. The most frequently used photosensitizer is aminolevulinic acid (ALA) which may be given systemically, but is most often applied topically as a 10–20% concentration several hours before the procedure. A light of a defined wavelength, most commonly using a laser, is directed onto these superficial lesions for treatment. The power density of the beam is below that necessary to produce tissue injury under normal conditions. ALA is absorbed into the cells and converted to protoporphyrine IX [88,89,90,92]. The affinity of porphyrins by neoplastic tissue enables treatment to be concentrated at the tumor site [93]. When exposed, the protoporphyrine absorbs the light resulting in the formation of triplet protoporphyrine IX and free oxygen radicals, which lead to cell destruction within the illuminated tissue areas [93,94,96]. Photodynamic therapy is well established for the treatment of Barrett’s esophagus [90,91,92,93,94,95,97] and certain skin conditions such as psoriasis [91, 98]. PDT using topically applied ALA (trademark Levulan, Berlex/DUSA Pharmaceuticals, Inc., MA) was registered by the FDA for the treatment of actinic keratoses of the skin in 2000. There are also several case studies and series that report complete or partial response in patients treated for external anal dysplasia low and high grade [98,99,101]. Similar results have been reported for the treatment of dysplastic and cancerous vulvar [101,102,103,105], vaginal [106, 107] and uterine cervical [108] disease. In the treatment of vulvar intraepithelial neoplasia (VIN) the lesions are typically irradiated with 75–150 J/cm2 of laser light at a wavelength of 635 nm (argon or KTP/YAG ion pumped dye laser) about 2–3 h after sensitizing drug application [12, 102, 109]. The treatment time varies between 10 and 40 min [106, 109]. In Europe, PDT is usually performed on the awake patient, after pretreatment with a systemic non-steroidal or narcotic pain medication or sedative. Despite this being a “cold” laser application, most patients complain about severe burning sensations at the site during the first several minutes of the treatment cycle. Following the procedure only mild burning is reported, and depending on skin complexion, a pronounced erythema is noted [109]. Photodynamic treatment has also been used for non-dysplastic vulvar conditions such as lichen sclerosis [109]. The decreased recurrence rate for VIN and condylomata following PDT is attributed to a specific immune mechanism which is stimulated by this unique procedure. It may, in part, also be secondary to the improved visibility and subsequent destruction of subclinical lesions [107]. Skinfolds, hyperkeratosis and marked pigmentation can block the illumination and lead to failure [107]. It should be noted that research is ongoing to perfect this methodology for the treatment of the intraperitoneal spread of ovarian and other malignancies by delivery of the light laparoscopically.

In summary, photodynamic therapy is a minimally invasive procedure that provides unique properties especially suited for the local treatment of superficial epithelial lesions in different organ systems, including the genital tract. There is evidence that it is well tolerated and at least as effective as other conventional modes of treatment.

Conclusion

The literature of the past decades was reviewed for outcome data and put into perspective by integrating the personal clinical experience of the authors. The result is this conclusion on the current state of the art use of lasers in gynecologic surgery.

Unchanged from the laser’s introduction as a tool in gynecologic surgery, differences in penetration, absorption, and suitable delivery media for the different laser wavelengths dictate their clinical application. The use of CO2 laser in the treatment of cervical intraepithelial lesions is well established, and indications and techniques have not changed considerably over the past 40 years. The KTP laser may also be used for this procedure and may offer some advantages in hemostasis and application, but is not widely available. Randomized controlled trials comparing the CO2 laser to other treatment modalities are scarce. The Cochrane Systematic Review from 2013 suggests that there is no obvious superior technique. The recent literature and personal observation suggest that laser treatment appears to be less complicated by infection and bleeding and is the preferred method for young females who desire future fertility. Persistence and recurrence rates are in the 10% range and independent of clear surgical margins.

CO2 laser ablation for vaginal intraepithelial neoplasia is also an established, as well as safe, treatment modality. Repeated treatment may be necessary, since persistent disease is not infrequent, particularly when treating multifocal disease. In case of VAIN III at the vaginal cuff after hysterectomy, upper vaginectomy appears to be the treatment of choice and is often combined with CO2 laser ablation of surrounding vaginal tissue. CO2 laser surgery permits treatment of vulvar condyloma and vulvar intraepithelial neoplasia with excellent cosmetic and functional results. Again, persistent and recurrent disease in the 20% range is a known problem and close follow-up and retreatment are frequently indicated. VIN III may be better treated with laser excision than pure laser vaporization. Other benign lesions of the vulva can also be treated with laser, but published data are scarce. The KTP laser offers the significant advantage of decreased pain, especially when applied to vulvar procedures.

The treatment of abnormally heavy menstrual bleeding by destruction of the endometrial lining using various techniques has been the subject of a 2013 Cochrane Systematic Database Review. Among the compared treatment modalities are also newer and modified laser techniques. The conclusion of the reviewers is that outcomes and complication profiles of newer techniques compare favorably with the gold standard of endometrial resection via the hysteroscope. The majority of new destruction techniques are performed in a blind fashion.

CO2 laser is also the dominant laser type used with laparoscopy for ablation of endometriotic implants, although the KTP laser offers several advantages because of its preferential absorption in hemoglobin and hemosiderin, and ease of application. Recurrence rates are known to be as high as 50%. With endometriomas, excision of the capsule appears to be more beneficial than simple coagulation or vaporization. Myoma coagulation or myolysis with Nd:YAG laser through the laparoscope or hysteroscope is a relatively recent addition to the armamentarium of the gynecologic surgeon. Even MRI guided percutaneous approaches have been described. In addition, MRI guided high intensity focused ultrasound (HIFU) is an alternative to laser therapy for fibroid myolysis.

Laser is a well-accepted treatment modality among patients and physicians. Disadvantages are the high cost involved and the sophistication of equipment and maintenance. Decreasing expenses, increasing safety and ease of application will further support the use of laser in gynecology.