Carbon Dioxide Laser Surgery in Gynecology

The key mechanisms of action of the laser were first discovered by Albert Einstein in the early 1900s. Initial results from the use of a carbon dioxide laser for the management of cervical dysplasia were initially less successful than anticipated because of the inability to determine appropriate depth of penetration for prevention of recurrent disease. Not until 1978 did Anderson and Hartley emphasize the actual mechanics for the depth of cervical involvement.[1] Laser technique was further refined and shown to be both practical and efficacious by Jordan in 1985[2] and by Dorsey in 1979,[3]  when the Greater Baltimore Medical Center published the first clinical experience with cervical conizations by carbon dioxide laser. See the image below.

Lasers have provided the laparoscopic surgeon with an efficient method of achieving rapid excision, coagulation, or vaporization of pelvic abnormalities. Most familiar is therapy for pelvic endometriosis or adhesions. When laser is used in combination with other laparoscopic instruments, the variety of procedures performed with the laparoscope may be enhanced.

The carbon dioxide laser has been considered an effective modality for multiple tasks related to the treatment of intraepithelial neoplasia of the lower genital tract, most commonly for large lesions and for multifocal manifestations of human papilloma virus (HPV). The use of this technology is limited in some areas because of healthcare provider training and experience and because of a lack of availability of equipment. Many hospitals require that specific credentials be obtained before using this modality, including documentation of didactic instruction and clinical supervision of initial procedures. 

Since the earliest use of the CO2 laser for managing squamous abnormalities of the lower genital tract and intra-abdominal treatment of endometriosis and adhesions, it has been employed for other medical therapies including : treatment of  condylomata  in women who are pregnant,[4] treatment of Bartholin gland cysts and abscesses,[5] ablation of pigmented follicular cysts of the vulva,[6] treatment of chronic anal fissures,[7] excision of an  imperforate hymen,[8] excision of a vaginal septum,[8] excision of hypertrophied labia minora[9] or vaginal polyps,[8] management of Nabothian cysts[8] and even to assist the treatment and care of girls who have had Type III female genital mutilation.[10]

The C02 laser has also been utilized as an option for management of anal dysplasia[11] or treatment of refractory ano-genital lichen sclerosis.[12, 13]

Intra-abdominal use of the CO2 laser is now being compared to other instruments such as the Ultrasonic scalpel and employed via robotic management of endometriosis. It is of value in not only resection of endometriotic implants and treatment of endometriomas, but of value in deep endometriotic implants and in combination with bowel resections for endometriosis.[14, 15] Case reports also address the use of the CO2 laser in the laparoscopic resection of myomas and adenomyomas.[16, 17] Other traditional uses of the CO2 laser laparoscopically included ovarian “drilling” or even wedge resection for adjuvant therapy of women with polycystic ovaries to assist ovulation.[18]

The most recent focus of attention on gynecologic use of the carbon dioxide laser has been as a treatment option for vulvovaginal rejuvenation and vaginal atrophy. Most studies fail to cite the absence of FDA approval of this device for this purpose and report observational case studies or case series with success defined as patient reports of satisfaction. Little mention is made of postoperative adhesions or pain or need for retreatments (duration of therapy). Although the FDA did clear a fractional CO2 laser for indications of “incision, ablation, vaporization and coagulation of body soft tissues in medical specialties including genitourinary surgery”, the indication for treatment of genital atrophy was not listed. The American College of Obstetricians and Gynecologists (ACOG) published a position statement about fractional laser treatment of vulvovaginal atrophy in 2016 and reaffirmed this position statement July 2018.[19] ACOG has also published a Committee Opinion on vaginal “rejuvenation” and cosmetic vaginal procedures.[20]

Observational studies utilizing the CO2 laser for vaginal atrophy generally lacked comparison to other treatment modalities and have no long term follow-up.[21]   A single study from Menopause 2018 was a randomized, double-blind, placebo-controlled clinical trial comparing the CO2 laser with topical estriol alone, and with use of laser and topical estriol together. It enrolled 45 women and assessed symptoms, vaginal appearance and vaginal maturation at 8 and 20 weeks and noted increased pain in the laser alone group at 8 weeks but at 20 weeks female sexual function scores were comparable for all groups (estriol alone, estriol and CO2 laser and CO2 laser alone).[22] Another study assessed epidermal thickness in an effort to more quantify results of CO2 laser use in women with vaginal atrophy.

Intraepithelial neoplasia is a descriptive histologic term for squamous abnormalities of the vulva (VIN) and perianal area, vagina (VAIN) and cervix (CIN) (see the images below). 

In 2012, the College of American Pathology (CAP) and the American Society for Colposcopy and Cervical Pathology (ASCCP) developed and published the Lower Anogenital Squamous Terminology (LAST) project. This presented the current terminology used to describe Human Papilloma virus associated squamous lesions of the anogenital tract.[23] In the LAST system, histologic cervical findings are described using the same terminology as cytologic findings.

LSIL: low grade squamous intraepithelial lesions - now replaces the designation of CIN I, or mild dysplasia. This category also includes abnormalities previously designated as CIN 2 (moderated dysplasia) which are negative for p16 immunostaining.

HSIL:high grade squamous intraepithelial lesions-represent abnormalities previously designated CIN 3 (severe dysplasia) and also includes prior CIN 2 lesions which are p16 positive, as well as encompassing those cellular abnormalities designated carcinoma in situ.[23]

The ASCCP published in 2012 updated consensus guidelines for the management of abnormal cervical screening tests, but continues to use the terminology CIN (cervical intraepithelial neoplasia), as delegates to the LAST project determined that the classification of LSIL and HSIL does not yet have enough evidence to allow clear risk-based management guidelines.[24]

Pelvic pain related to adhesions or endometrial implants also represents a significant disease burden in the United States. Adhesions may be filmy or dense and may involve any pelvic structures. Endometrial implants may be clear or cystic, red or brown/black. Customarily, the older lesions are more darkly colored and accompanied by an increased depth of involvement with contracture of surrounding peritoneum or tissue surfaces. As the severity of endometriosis increases, the presence and severity of adhesions may also increase and become denser. Visual evaluation of endometriosis may not completely correlate with depth of invasion of implants or with the patient's clinical symptoms.

The precision of the carbon dioxide laser delivered laparoscopically lends itself to intra-abdominal and intrapelvic adhesiolysis or ablation of endometrial implants.

Frequency

According to the US Centers for Disease Control and Prevention, HPV is so common that almost everyone will be infected at some time in their lives.[25]

In 2005, the US Centers for Disease Control and Prevention estimated that 20 million Americans are DNA positive for anogenital types of human papillomavirus at any time.[26] Almost one half of sexually active adolescents or young adults aged 15-24 years may be infected by the human papillomavirus. In the United States, 6.2 million individuals are estimated to become newly infected with human papillomavirus annually.

The most likely etiology of lower genital tract squamous abnormalities is infection with HPV, a double-stranded DNA virus of the Papovaviridae family. The HPV has more than 100 subtypes and is the major causative factor of malignant and premalignant squamous abnormalities of the anogenital tract. Serotypes associated with squamous lesions may be designated as having a high or low risk for progression to malignancy. Ultimate cure of the viral infection can only be achieved by the immune system of the human host.

Papillomaviruses are ubiquitous in higher vertebrates. Approximately 40 types of HPV infect the genital tract. Intercellular cytokine-mediated control plays an important role in suppression of malignant transformation. A genetic change in pathways controlling intracellular or intercellular signaling may allow progression to a malignant phenotype.[27]

Treatment modalities, such as the carbon dioxide laser, destroy or excise infected cells, thus reducing the amount of infected tissue and, presumably, the host viral load. The subsequent healing process of the host stimulates viral combat at the surgical site. Patients with abnormal cytology findings or visible lesions must first be evaluated with visual inspection using a colposcope to help determine the location, extent, and severity of the clinical abnormalities. Colposcopically directed biopsies are indicated when dysplasia is present or malignancy is considered, in the clinical opinion of the healthcare provider. Findings from one or more biopsy samples from the involved areas help document the location and histologic severity of the disease.

The carbon dioxide laser has been used for ablating high-grade lesions or excising abnormal areas, including the transformation zone of the cervix. Ablation may frequently be used for treating VIN and is also considered to be a treatment modality for VAIN requiring therapy.

In the pelvis, endometriosis has been hypothesized to be a result of endometrial cells producing disease in areas outside of the uterus, most likely by retrograde menstrual flow via patent fallopian tubes, but also potentially via vascular or lymphatic channels. Altered immune function within the peritoneal cavity, plus other potential factors, then permit development of endometrial implants, most frequently on the ovaries or in the cul-de-sac. Other sites in the abdomen or pelvis or remote sites may become involved.

Within the pelvis, the CO2 laser can be used to ablate affected sites or excise the peritoneum, thus improving anatomic relationships by lysing adhesions and excising endometrial implants.

When used in the pelvis for therapy of adhesions of other etiologies (eg, postoperative or postinfectious), the CO2 laser allows precise incision of the adhesions, restoring local anatomy with a primary goal of reduced, repeat adhesion formation and decreased risk of damage to adjacent structures.

The carbon dioxide laser is customarily chosen over other ablative or excisional techniques when great precision is needed, particularly in situations involving large surface areas or when precise control over the depth of penetration is desired. Examples of procedures for which the carbon dioxide laser is indicated include (1) ablation or excision of dysplasia in situations in which minimization of tissue destruction or removal is desired; (2) cervical treatment combined with treatment of dysplasia or condylomata of the vulva, vaginal, perineal, or perirectal areas; (3) multifocal disease of the cervix, vagina, or vulva/perianal areas; (4) ablation or excision of endometrial implants or affected peritoneum; and (5) lysis of intra-abdominal or intrapelvic adhesions.

The carbon dioxide laser is used in conjunction with a laparoscope or colposcope. This allows precise application, which is one advantage of this treatment modality. Another advantage of the laser is hemostasis and minimal thermal necrosis (< 100 µm) when properly set. In addition, the procedure time is brief, and the laser may be used in an office or outpatient setting with the patient under local anesthesia when treating the vulva, vagina, or cervix. The office setting may also be more economical than procedures performed in a surgical suite. Surgical advantages of the intra-abdominal CO2 laser include (1) rapid incision and vaporization, (2) safety and predictability, and (3) lack of contact with the organ.

Patients with abnormal cervical cytology findings must first be evaluated using a colposcope to help determine the location, extent, and severity of the clinical abnormalities. Colposcopically directed biopsies are indicated when the health care provider has determined dysplasia is present. Findings from 1 or more biopsy samples from the involved areas and findings from an endocervical curettage help document the location and histologic severity of the disease present.

The carbon dioxide laser has been used for ablating CIN or excising abnormal areas, including the cervical transformation zone.

Patients with visible lesions of the vagina, grossly compatible with HPV-related disorders, may be inspected with the colposcope and biopsy performed if the provider suspects dysplasia or to exclude malignancy.

Visible lesions of the vulva or perineum and perianal areas may indicate a need for biopsy to evaluate dysplasia, exclude malignancy, or further elucidate dermatologic disorders. The colposcope with or without acetic acid to the vulva may be invaluable in determining the presence or extent of disease while providing focused light in the area of interest.

The CO2 laser may be used whenever a diagnostic laparoscopic procedure can combine a diagnosis of disease and the extent of disease with immediate therapy. It may also be used to augment pain management associated with endometriotic implants via partial excision of the peritoneum or through laser destruction of the medial aspect of the uterosacral ligaments, interrupting nerve endings associated with central pelvic pain.

Contraindications to using the carbon dioxide laser for the treatment of lower genital tract disease include (1) an inability to visualize the area to be treated because of anatomic considerations (eg, prolapsing lateral vaginal sidewall), (2) preoperative histology findings indicative of malignancy, and (3) inadequate physician training or experience. Laser ablation is contraindicated if the entire lesion is not visible, although excisional procedures may be performed.

Contraindications to laparoscopic use of the CO2 laser include (1) inability to visualize the site to be treated without risk of damage to adjacent structures, (2) anatomic findings not consistent with the diagnosis of endometriosis or adhesions (eg, neoplasm), (3) inadequate physician training or experience.

The Papanicolaou test has been the initial screening test for cervical cytologic abnormalities. It is a cost-effective cancer screening tool. Population screening has clearly led to a decline in the incidence of cervical carcinoma. However, by definition, it is a screening tool with a specificity of 95% and a sensitivity of 51%.[28]

• The specimen is obtained with an appropriate collection device (brush combined with spatula, or broom with or without spatula). The specimens should be representative of the entire transformation zone.

• The samples obtained may be smeared on a glass slide and sprayed with cell fixative or placed in a liquid-based medium for later cell preparation. The liquid-based evaluation technique may allow the sample to be used for more than cytologic testing. Additional studies that can be performed on the sample may include HPV typing or testing for gonorrhea, chlamydia, or herpes. Future improvements on liquid-based cytology may even allow testing for some other medical diseases.

• Infection with human papilloma virus has been clearly linked to intraepithelial lesions of the cervix and anus, and to a large proportion of vulvar and vaginal intraepithelial abnormalities. Most HPV infections are transient and no longer detected within 1-2 years. Women with persistent HPV infection, however, are at risk of developing premalignant lesions. Persistent disease, especially with HPV 16 increases the long-term risk of intraepithelial lesions or malignancy.[26, 29]

• Development of molecular tests for HPV assist with identifying women whose HPV infections may warrant closer surveillance for dysplasia. Identification of HPV genotypes can also assist with targeted care for prevention of malignancy. The use of cytologic evaluation and HPV co-testing have improved the sensitivity of detection of intraepithelial lesions while providing greater reproducibility.

Vaginal cytologic abnormalities may be detected with Papanicolaou testing or by visual inspection. The colposcope may be used for screening women with intraepithelial neoplasia abnormalities on the genitalia or cervix when visual inspection identifies a lesion or cytology reveals squamous abnormalities.

Vulvar lesions are usually identified by visual inspection following a history of condylomata or intraepithelial neoplasia elsewhere in the genitalia or upon patient complaints of irritation, itching, or a change in skin appearance (raised lesion, red lesion). The colposcope with use of adjunctive acetic acid may identify additional areas of VIN. Cytologic testing by traditional cytologic smear or liquid-based cytology is not indicated and is insufficient for diagnosis on the vulva. A possible exception is cytologic screening of the squamous tissue of the anus and the squamocolumnar junction of the anus and rectum. Colposcopy improves the inspection of the anus and rectum if symptoms are present or a lesion is seen.

All abnormal areas identified require biopsy if malignant or premalignant findings are suspected. Exclusion of malignancy is required prior to medical or surgical therapy.

Additional preoperative laboratory evaluations may be performed to ensure patient safety during anticipated anesthesia, especially in patients with a complex medical history (eg, cardiovascular disease, hypertension, diabetes).

Today there is better understanding of the role of persistent high risk HPV in the development of premalignant and malignant lesions of the anogenital tissues. In the cervix, persistent high risk HPV infections are associated with CIN 3 (severe dysplasia, HSIL) and cancer. Epidemiologic research has shown that HPV 16 and 18 are the most carcinogenic types in the female genital tissues, with HPV 16 associated with 55-60% of cervical cancers and HPV 18 associated with an additional 10-15% of cervical malignancy. These HPV types are also the most oncogenic subtypes identified in malignant and premalignant squamous lesions of the vagina, vulva and anus in women.[30, 31, 32]

Cytology is imperfect in its delineation of lesions with present or future malignant potential and thus the use of molecular tests has been employed. These currently have increased sensitivity, but lower specificity for detection of high risk lesions. Testing for high risk HPV subtypes combined with cytologic screening, co-testing, has the potential for increased disease detection while also allowing increased screening intervals for appropriate women.[33, 34, 35]

Three categories of HPV testing are available: HPV DNA testing, (testing for high or low risk subtypes or genotyping HPV 16, 18) HPV RNA testing (detecting expression of E6 and /or E7 RNA), or detection of cellular markers- particularly cellular p16 protein which is increased when HPV E7 protein disrupts cell cycling and may improve detection of high-grade CIN while excluding immature squamous metaplasia. 

No laboratory tests for adhesions or endometriosis are currently available. Ca-125 levels may be elevated in some women with severe endometriosis, but findings are not specific enough for use as a diagnostic test. Many other disease processes elevate Ca-125 levels, rendering this test unsuitable for screening.

 

Preparation for CO2 laser therapy of dysplasia of the cervix, vulva, or vagina includes the following:

• Reviewing results from cytology; colposcopic examination of the cervical transformation zone, vulva, or vagina; and indicated biopsies to ensure that malignancy is not present.

• Visualizing the full extent of a lesion and ascertaining it is within the planned area of ablation or excision.

• Choosing an alternate procedure if these criteria are not met. Lesions of the cervix considered for excision by laser conization alternatively may be considered for a LEEP or a cold-knife conization procedure.

The following steps should be taken prior to using the CO2 laser in the pelvis.

• Preoperative clinical plans should fully assess the cause of symptoms. All pelvic structures, including the bowel, bladder, internal genital structures, and musculoskeletal system must be considered as possible sources of pain or disease and a decision should be made when to proceed to operative evaluation.

• Intraoperative evaluation of pelvic pain should include careful laparoscopic inspection of the entire pelvis.

• The risks and benefits of both diagnostic laparoscopy and intrapelvic CO2 laser ablation and/or excision must be reviewed by the physician with the patient prior to the procedure. The discussion of the extent of the operative procedure planned should be included.

Anesthesia for CO2 laser treatment of the cervix or external genitalia may be provided by local injection of lidocaine with or without epinephrine.[36, 37]  Prior to injecting local anesthetic, a topical preparation such as an anesthetic spray or gel may be applied to lessen pain from the injection. Use of local anesthetic with a vasoconstrictor solution (1% lidocaine with 1:100,000 epinephrine, 5-10 ml injected circumferentially around the cervical surface may be associated with less pain from the procedure and the vasoconstriction could lessen blood loss.

The surgical procedure may be accompanied by oral or injectable sedation, if desired by the physician or patient. When performed in a surgical suite with anesthesia personnel, additional intravenous, regional, or general anesthetic agents may be used.

Diagnostic laparoscopy with a 2-mm laparoscope may be an office procedure requiring only local anesthesia at incision sites. Moderate sedation protocols using oral or intravenous medications may supplement planned procedures. In office diagnostic laparoscopy may allow pain mapping to assist in formulating a management plan for pelvic pain. Documentation of disease presence and location may facilitate ongoing and future therapy

Treatment of endometriosis or adhesions in the pelvis using the CO2 laser requires general anesthesia.

Positioning

For laser procedures of the cervix, the patient is placed in the dorsal lithotomy position, and a speculum of adequate size is used to fully visualize the cervix. A speculum with a dull surface that is specifically designed to prevent reflection of the laser beam should be used. A speculum of appropriate length and width should be chosen to prevent relaxation of the lateral vaginal walls that could limit cervical exposure and risk inadvertent laser damage.

Safety

For CO2 laser of the external genitalia or cervix, the patient is draped in damp towels to absorb any misdirected laser beams, and the patient's eyes are protected with wet gauze or protective glasses. All personnel, except the physician operating the microscope, should also wear eye protection.

The cervix, vagina, or vulva is bathed in a 3% solution of acetic acid, and abnormalities are noted with the microscope before the laser is fired.

A smoke evacuator system is used to remove the vapor plume. This is accomplished most efficiently with (1) a suction catheter attached to the speculum with a conduit toward the cervix to maximize plume removal, or (2) a suction tip placed as far into the vagina as possible without interfering with the laser beam. Custom specula with smoke evacuation attachments are commercially available.

A small number of reports have noted that viral DNA sequences have been isolated from laser plume. Little information is known about the effects of this plume on operating room personnel. Contamination of objects in the operating room has also been noted. Animal studies have failed to demonstrate worrisome amounts of viral DNA or transmission of virus to animals. Assessment of laser plume for HPV transmission to humans is reassuring, though the number of studies is small.[38] Therefore, customary procedures for use of plume evacuation, including surgical masks, are currently the best practice. No present barrier technique will prevent all possible inspiration of debris or viral parts. The absence of documented infections in personnel is reassuring. Continued study of this situation is in progress.[39, 40, 41]

For intraoperative laser therapy, direct visualization of lesions consistent with endometriosis may be noted. Documentation of the findings are included in the operative dictation and with operative photography. Installation of sterile saline into the pelvis may assist visualization of some endometriotic lesions, particularly those with a cystic appearance.

Careful inspection of existing adhesions or endometriosis must not only include complete visualization of the lesions but careful visual evaluation of adjacent structures to minimize risk of injury with laser therapy. Irrigation fluid provides an excellent backstop to the laser beam and reduces injury to organs behind the site being treated. More recently CO2 laser therapies have been used in combined surgical procedures allowing ablations of disease at various depths and locations combined with resection of endometriosis involving the colon.[22, 42] The laser treatments can be delivered by robotic methods allowing precise delivery of therapy.  Intrapelvic use of the CO2 laser has also been used in laparoscopic myomectomy.[38]

Setting the laser

The desired power-density range for adequate ablation or excision of cervical lesions with minimal thermal damage to adjacent areas is 750-2000 W/cm2 (generally, 20-30 W at a continuous setting), with an effective beam diameter of 1.5-2 mm to maximize ablation and hemostasis while minimizing lateral thermal damage. Super-pulse settings may also be used, and they are preferred by some to also reduce thermal damage.[43] The same laser settings may be used to coagulate an area being ablated or excised, but the overall power density delivered for coagulation may be reduced by enlarging the dot size or by reducing the watt setting on the laser, thus decreasing the watts used per cm2. For treatment of the vagina or vulva/perianal area, 10 W is preferred to minimize scarring and lateral thermal damage.

For CO2 laser procedures of the cervix, the entire transformation zone is identified and marked with an intermittent beam application, taking care to be at least 3-4 mm beyond the affected area of the cervix. If an adequate margin cannot be obtained, another type of treatment may be indicated. The entire circumference of the anticipated ablation area is outlined as if outlining a circle with dots. These dots are then connected, and the entire area is ablated with a consistent continuous movement of the laser beam. The area is measured periodically with a graduated probe used through the colposcope, and the ablation continues to a depth of 7-10 mm. Ablation to an additional depth of 2 mm may be performed at the endocervical margin to evert the endocervix and facilitate future evaluation of the transformation zone.

Any bleeding points encountered are treated with coagulation by increasing the dot size or decreasing the power setting. Additional ablation at the endocervix allows destruction of disease in gland crypts.

A lesion that is difficult to see may be observed in its entirety through the colposcope, through manipulation of the speculum, or with use of skin hooks to manipulate the cervix itself. A probe also may allow a change in angle to more completely visualize the endocervical opening. In addition, use of a vaginal sidewall retractor helps prevent redundant vaginal sidewalls from obscuring vision and helps avoid inadvertent thermal damage. All equipment used must be coated or treated to prevent reflection of stray laser beams.

For excisional procedures, the dots initially placed in a circumferential fashion are connected and the initial depth is taken to approximately 5 mm. Periodic measurements are performed using a graduated probe. Once a depth of 5 mm is reached, a skin-hook (with a dull surface) is used to pull the specimen medially from all directions while simultaneously firing the laser beam, thus creating a cone-shaped specimen. Once the endocervix is reached, many physicians make the final cut with a knife or scissors to allow the cephalad margin to be more easily evaluated by the pathologist and exclude thermal damage. Bleeding during the excisional procedure or after the specimen is removed from the site is controlled with the laser, by defocusing the beam (increasing the dot size), decreasing the wattage, or both.

For CO2 laser procedures of the vagina, a Teflon-coated speculum with a built-in smoke evacuator is placed into the vagina and the entire area of interest is visualized, both with the operator's eye and then via the colposcope. Acetic acid application may assist visualization of condylomata, but Lugols solution may be preferable for visualization of dysplastic areas. Although these areas had been preoperatively visualized in the office, careful re-evaluation in the operating room should be made before using the laser. CO2 laser therapy is ideally suited for management of multiple lesions with ablation procedures preferred over excisional procedures due to the thin layer of squamous epithelium of the vagina. Excision without careful control of depth may result in injury to the bladder or bowel. CO2 laser of lesions may alternatively be used with a handheld device, but the colposcope provides more accurate depth control.

Lesions should be completely ablated and a 1-cm margin should be left on all sides of the lesions.

The laser is customarily set at 10 W via a super pulse or continuous setting. Laser depth is controlled by varying the spot size. Avoid pinpoint settings, which result in greater cutting and depth with less coagulation. Continuous movement of the beam also prevents inadvertent excess penetration. Coagulation of small vessels may be assisted with additional beam defocusing or reduced power settings. Excess laser use to control bleeding should be avoided. A suture may be required in some areas.

Altering the angle of speculum placement, turning the blades 90 degrees, using a lateral vaginal sidewall retractor, or even shooting the laser through the side of a bi-valve speculum may allow visualization and therapy of all affected areas. The procedure should be conducted from the vaginal apex outward to the introitus. Relaxing the 2 valves of the speculum allows the vaginal sidewalls to move toward each other and may also enhance visualization.

Individual condylomata are ablated and then the margins are treated. VAIN lesions are treated by the same principle of ablation of the individual lesions followed by creation of a 1-cm margin. Although a measuring tool or probe may be used with colposcopic visualization, the preferred depth of 2-3 mm within the vagina is generally easily noted with the operator's eyes and colposcope.

For CO2 laser of the vulva, perineum, or perianal areas, a power setting of 10 W represents a good starting setting. Estrogen-deficient women (premenarchal or postmenopausal) may require decreased power density via increasing the spot size and decreasing the power settings. Children require no more than 2-5 W for laser therapy of condylomata. Higher power settings may result in excess depth and secondary scarring.

Preoperative application of 5% acetic acid improves lesion visualization. This may be applied using a damp gauze while final operative preparations are made and the patient is positioned. Damp towels should be placed around the areas for laser therapy and around the vaginal introitus for cervical, vaginal or vulvar ablations to minimize damage from stray laser beams.

Genital condylomata are ablated to the level of the skin surface and then to surgical plane 1 (see Table below). If fat is seen, the depth of ablation is too deep and destruction of skin structures or bleeding may result. Char should be removed via wiping with a damp gauze using sterile saline or acetic acid.

A hand-held laser device may be used on the vulva, but a colposcope may be preferable for accurate visualization of the individual lesions. An anoscope may assist visualization of both condylomatous or dysplastic lesions at the anal opening. Lesions of the urethral meatus may be treated by the colposcope; however, lesions within the urethra itself may require urologic consultation and urethroscopy.

On the vulva, perineum, or perianal areas, condylomatous and dysplastic lesions are initially treated with a 1-cm margin. Care should be taken not to exceed 2-3 mm of depth for dysplastic lesions and surgical plane 1 only for condylomatous lesions.

Table. The 4 Surgical Planes in Laser Surgery of the Vulva* (Open Table in a new window)

For intra-abdominal and intrapelvic applications of the CO2 laser, lesions must be visualized and all anatomic landmarks identified. Ablation of lesions, lysis of adhesions, or excision of the peritoneum involving an endometriotic or adhesive lesion must be based on individual anatomic findings and operator experience. Failure to use thorough visualization of anatomic landmarks may result in injury to bowel, bladder, or vascular structures. Additional laser procedures, such as bilateral laser destruction of the medial portions of the uterosacral ligaments to decrease pelvic pain have been studied with variable results. Several lasers have been used for intra-abdominal applications. Operator experience may dictate the laser choice. Lasers with gynecologic applications include CO2 laser, KTP laser, Argon laser, and Nd:YAG laser.

Preoperative medical therapy may also enhance visualization of endometriotic lesions and decrease the size of areas to be treated. Additional laparoscopic procedures considered for surgical intervention with laser therapy are as follows:[44]

• Ablation of endometriosis

• Lysis of adhesions

• Resection of endometriosis

• Ovarian cystectomy

• Salpingo-oophorectomy

• Partial salpingectomy

• Myomectomy

• Laparoscopically assisted vaginal hysterectomy

A subumbilical port is the customary place to locate the laser laparoscope. Smoke evacuation is via a secondary port, usually 5 mm in diameter. Adequate visualization of all areas to be treated may require multiple ports, customarily 5 mm. These should be placed by traditional laparoscopic procedure, under direct visualization and with consideration of local skin anesthesia injected before the entry of each port. Likewise, each site should be visualized when removing the trochar at the completion of the procedure. Installation of saline with or without heparin or other substances to decrease adhesions is controversial but warrants individual consideration. Rigorous hemostasis should be used, as this may reduce postoperative adhesion formation.

Preoperative antibiotic therapy is not recommended for intra-abdominal laser applications. Preoperative bowel prep is recommended to maximize safety and decrease complications in the event of a bowel injury. A sponge stick or uterine manipulator should be placed in the vagina or cervix, respectively, to assist movement of the uterus or vaginal apex to enhance visualization.

Intraoperative photography may enhance postoperative patient counseling. Trochar incision sites 10 mm or more require suture closure of the fascia, while those of smaller diameter may be closed with a stitch or skin glue.[24]

Pain management following laser procedures to the external genitalia, vagina, or cervix may consist of nonsteroidal anti-inflammatory agents (NSAIDS) and narcotics. Initial dosing should be given preoperatively with oral medications or intraoperatively with IV medications in the office setting and intravenous medications in the operative suite.

Pain management following intra-abdominal procedures may also be maximized with preoperative pain medications and antiemetics. Local anesthesia applied to incision sites decreases pain from trochar placement. Following laparoscopy, rapid progress to normal activity, regular diet, and normal bowel function should be expected or evaluated if absent. Worsening pain, increasing abdominal extension, nausea, or vomiting require prompt attention to exclude intra-abdominal damage of the bowel.

Pain management of vulva or perianal lesions may also be facilitated by topical lidocaine jelly (2%) or ointment (5%), silver sulfadiazine cream, ice packs, and sitz baths of warm water with or without Epsom salts.

Vaginal postoperative care of postmenopausal women not currently using systemic or topical hormone therapy, may include small amounts of estrogen cream, 0.5-1 g intravaginally at night to increase the rate of re-epithelialization of the vaginal tissue and decrease the risk of vaginal scars.

The frequency of postoperative cytologic testing should be correlated to the disease detected at the time of excisional procedures. Consensus guidelines for the management of abnormal cervical cancer screening and cancer precursors were updated in 2012 and published in 2013 in the Journal of Lower Genital Tract Disease.[24]

 

 

 

Postoperative patient instructions may vary from one provider to another and may also change in accordance with additional patient medical conditions. General postoperative instructions include (1) pelvic rest (ie, no tampons, douching, or intercourse) until the scheduled postoperative follow-up examination; (2) light activity for 3-5 days postoperatively, especially no heavy lifting or excessive strenuous activities; and (3) instructions to call if a foul vaginal discharge, pelvic pain, fever, or excess bleeding develops for 2-4 weeks.

Consensus guidelines developed in 2012 by the American Society for Colposcopy and Cervical Pathology (ASCCP) include the following[24] :

CIN grade 1

Cervical intraepithelial neoplasia (CIN) 1 lesions are heterogeneous; most are associated with the presence of high risk types of human papillomavirus (HPV). Others are heterogeneous with respect to markers of neoplasia. CIN 1 rarely progresses to CIN 2 or 3. The risk of having an undetected higher-grade lesion is greater if the biopsy diagnosis of CIN 1 was preceded by cytology showing high grade squamous intraepithelial lesions (HSIL); atypical squamous cells, cannot exclude HSIL (ASC-H); or atypical glandular cells (AGC).

Co-testing at 1 year is recommended; if both cytology and HPV tests are negative, then testing in 3 years is appropriate—using cytology if the patient is younger than 30 years or co-testing if older than 30 years. At that time, if testing is negative, the patient is returned to routine screening for her age. If any testing result is abnormal, then colposcopy is recommended.

When CIN 1 persists for at least 2 years, either continued follow-up or treatment is acceptable. If treatment is selected, then a colposcopy is performed and if adequate, an ablative or excisional procedure is acceptable. A diagnostic excisional procedure is needed if the colposcopy is inadequate, if the endocervical sampling reveals CIN 2 or higher (or ungraded CIN), or if the patient has been previously treated.

In women whose testing reveals CIN 1, or no lesion, preceded by HSIL or ASC-H, observation with co-testing at 12 and 24 months or management with a diagnostic excisional procedure may be undertaken. Observation may be chosen if the colposcopy finding is satisfactory and the endocervical sampling is negative for dysplasia. If the co-testing at 12 and 24 months is negative, then the patient is returned to routine screening for her age. If any tests are abnormal, then colposcopy should be performed. An excisional procedure should be performed if HSIL cytology is found at the 12- or 24-month visit.

For women age 21-24 years, cytology at 12-month intervals is performed; however, HPV testing is NOT recommended. For any cytology results reported as ASC-H or HSIL, colposcopy is recommended. Then, if CIN 1 is diagnosed, continued cytology and colposcopy at 6-month intervals is recommended. Biopsy is performed if a high-grade lesion or HSIL cytology is diagnosed. If the colposcopy study is inadequate, if CIN 2 or higher is found, or if CIN is identified in the endocervix sample, an excisional procedure is performed. Recommendations are similar for women younger than 21 years who have been screened inadvertently. For pregnant women with CIN 1, no treatment is recommended, but testing is repeated postpartum.

CIN grades 2 and 3

Although more than 40% of untreated CIN 2 lesions regress without interventional therapy, approximately one third will persist and 22% will progress to carcinoma in situ or invasive cervical disease.[45] The procedures for cervical ablation or excisional methods can be used to treat women with biopsy confirmed CIN 2, 3 and a satisfactory colposcopic examination. An excisional procedure with positive pathology at the margins followed by an unsatisfactory colposcopy is generally considered a risk factor for recurrent or persistent CIN.

At the time of a diagnostic procedure, endocervical sampling correlates with endocervical margin status. Positive evidence of disease at the endocervical margin is predictive of residual dysplasia in 10-33% of recent studies.[46] Women are recommended to be counseled about their increased risk for recurrent or persistent CIN when pathology results following treatment reveal positive margins. For those patients in whom further treatment is decided, an excisional procedure may be preferred with hysterectomy also a viable option for women who have completed child bearing.

After treatment for CIN 2 or 3, co-testing at 12 and 24 months is recommended. If both tests are negative, co-testing in 3 years is recommended. If all tests are negative, routine testing is recommended for at least 20 years. This testing should be continued even if it extends testing beyond age 65 years. If any abnormalities are identified, colposcopy with endocervical sampling is required.

When an endocervical curettage (ECC) sample is positive at the time of treatment, or margins are positive at the time of treatment, re-assessment with cytology and endocervical sampling should be performed. A repeat excisional procedure or hysterectomy (when repeat excision is not feasible) is acceptable.

Young women, aged 21- 24 years with CIN 2 or 3 histology may either be treated (as outlined above), or they may undergo observation. Observation for 12 months consists of cytology and adequate colposcopy at 6-month intervals. Repeat biopsy is indicated for worsening lesion appearance, evidence of a high-grade colposcopic finding, or HSIL cytology. Treatment is recommended for inadequate colposcopy, if CIN 2 or 3 persists for 24 months or if CIN 3 is diagnosed. Treatment guidelines are the same as those listed above for older women. During pregnancy, periodic cytology and observational colposcopy are sufficient for CIN 2 or 3—unless invasive disease is suspected. In the absence of findings suggesting invasive disease, postponing reevaluation until 6 weeks' or longer postpartum is acceptable.

Algorithms for the management of genital dysplasias are available from the American Society for Colposcopy and Cervical Cytology.

Adenocarcinoma in situ

The management of adenocarcinoma in situ is often difficult since this disease process frequently extends well into the endocervical canal and may be multifocal or possess "skip lesions." Invasion cannot be excluded without an excisional procedure, but negative margins performed after an excisional procedure do not guarantee the disease has been completely removed. In most patients, however, an excisional procedure is curative. The failure rate following an excisional procedure ranges from 0-9%.[47] Positive endocervical cytology at the time of an excisional procedure may also be indicative of residual disease, as is a positive margin in the excised specimen.

Hysterectomy is preferred as a management strategy in women who have completed childbearing and possessed the diagnosis of AIS at the time of an excisional procedure. Women who wish to maintain fertility may be observed. A negative HPV test at follow-up indicates a lower risk of persistent or recurrent disease. Reevaluation at 6 months with co-testing, colposcopy, and endocervical sampling should be performed. A reexcision is indicated if a positive endocervical sample or a positive margin is noted in the excised tissue excised Long-term follow-up is needed if hysterectomy is not performed.

 

Complications associated with ablative or excisional procedures performed using the carbon dioxide laser include bleeding, infection, cervical scarring or stenosis, altered fertility, anesthetic complications, premature labor, and cervical insufficiency.

Bleeding may occur at the time of the procedure or within 4-10 days postoperatively. Procedural blood loss may be minimized by scheduling the procedure during the follicular phase of the menstrual cycle.

Bleeding in the days following the procedure may stem from arterial recanalization. Inspection of the operative site should be performed at any point if the patient feels the amount of bleeding is worrisome. Topical treatments (eg, Monsel solution, silver nitrate) may be applied to any specific bleeding sites. Visualization of a clot in the surgical bed without evidence of active bleeding warrants observation only. Removing the clot often causes the bleeding to resume. The patient should be advised to call if persistent bleeding more than a heavy period occurs.

The rate of bleeding after laser procedures has been reported to be approximately 5%, which is similar to that following other excisional procedures of the cervix.[48]

Long-term complications following laser procedures of the uterine cervix include possible reduced ability to visualize the transformation zone. This can occur after any surgical procedure of the cervix.

Ablative or excisional laser procedures and recurrent or multiple procedures performed on the cervix are also associated with cervical stenosis and may be associated with a loss of endocervical glands due to lasering in the proximity of the internal os. This may be preventable by attempting to destroy a smaller volume of cervix (if feasible without compromising the treatment). In postmenopausal women, the incidence of stenosis may be reduced with the adjunctive administration of vaginal estrogen cream postoperatively. This may also reduce stenosis or foreshortening of the upper portion of the vagina following laser therapy for condylomata or dysplasia.[49]

Any surgical procedure on the uterine cervix, especially recurrent procedures or the destruction of a large volume of cervical tissue, is associated with a loss of cervical volume and may result in cervical insufficiency and secondary premature labor or pregnancy loss.[50, 51] However, fertility rates are not generally altered by a single procedure. Fertility rates may be reduced following multiple procedures, due to destruction of the endocervical glands and secondary reduction of endocervical mucous or cervical stenosis.

Postoperative repeat cytology following CO2 laser therapy management of cervical dysplasia is dictated by the pathology noted on colposcopy-directed biopsies performed preoperatively or on the operative pathology of the excisional specimen of the transformation zone. Guidelines for follow-up may be obtained from the ASCCP recommendations.

Postoperative care following ablation of condylomata of the vulva, vagina, or cervix consist of evaluation for healing and follow-up based on patient symptoms or other gynecologic indications.

Laparoscopic management following adhesiolysis or endometriosis consists of observation. Continued medical therapy to prevent recurrence of endometriosis may be individualized.

Infection can occur after any ablative or excisional procedure on the cervix, vagina, or vulva. Normal healing following CO2 laser procedures to the cervix or vagina is accompanied by a moderate, malodorous discharge associated with sloughing of dead cells. This discharge may be difficult to distinguish from infectious discharge and the altered chemical environment in the vagina may be associated with symptomatic bacterial vaginosis. Signs of true infection may include pelvic pain, fever, and other symptoms associated with endometritis or salpingitis. An infection may also be manifested by prolonged bleeding or delayed postoperative healing.

Postoperative bleeding from the cervix may be decreased by scheduling the procedure during the week following menses (ie, the follicular phase of the menstrual cycle). Careful visual inspection of the cervix and vagina, judicious testing for sexually transmitted infections, and wet mount examination of the vagina prior to surgery may allow preoperative eradication of potential agents associated with infection (eg, gonorrhea, chlamydia, bacterial vaginosis).

Anesthetic complications of office procedures include risks associated with local anesthesia and systemic absorption of the anesthetic agent. These include ringing in ears, dizziness, and rarely seizures and cardiac arrest. Care in these instances consists of systematic measures and if seizures or cardiac arrest occurs, transfer for hospitalization and evaluation. Office procedures should only be performed when staff and equipment are available to deal with any emergency, including items and persons for cardiopulmonary resuscitation and a crash cart. Patients with known pre-existing medical disorders (eg seizure disorder) should be considered for procedures in the surgical setting with anesthesia administered by a physician or nurse anesthetist.

Injuries to members of the operating team or to the patient may result from improper deployment of the laser or an accidental burn due to deflected laser beam. Appropriate draping with damp towels and eyewear by all members of the team, except the surgeon operating the microscope, is important.

Complications of the CO2 laser procedures in the vagina include scarring and obliteration of the vaginal apex with secondary loss of length and configuration. Dyspareunia may result and foreshortening may limit adequate future evaluation.

Laser therapy of the vulva, perineum, or perirectal areas generally results in minimal scarring or loss of architecture, but excess depths of laser therapy increase the chance of alteration of anatomy due to scarring, dyspareunia, pain with defecation, or labial adhesions.

Intra-abdominal laser therapy may result in a failure to eradicate adhesions or endometriosis, new adhesion formation or dyspareunia. Intraoperative injury to bowel or bladder usually manifests itself in the early postoperative period and requires a high index of suspicion, prompt therapy, and possible surgical intervention with further therapy to injured organ.

Complications associated with any laparoscopic procedure are as follows:

• Injury to vessels or intra-abdominal structures

• Cardiorespiratory problems secondary to pneumoperitoneum

• Pneumothorax

• Decreased venous return

• Gas embolism

• Cardiac arrhythmias

• Abdominal wall hematomas

• Incisional infections

• Incisional hernias

Disease eradication and recurrence rates following carbon dioxide laser therapy compare favorably with other excisional or ablative procedures. Outcomes are compared with the assumption that similar preprocedural evaluations (eg, cervical cytology, colposcopy, biopsies) have been performed.[36]

Carbon dioxide laser procedures eradicate CIN in up to 90% of cases.[52] Likewise, eradication of VAIN or VIN is similar in comparison to other excisional or ablative procedures in these locations. However, because of the pathophysiology of HPV, an operative procedure results in a reduced viral load and excision of overtly diseased tissue, but does not completely eradicate the virus from the host. Complete eradication of the virus is a function of the patient's immune system.

A randomized trial of cryotherapy, carbon dioxide laser vaporization, and LEEP for CIN, showed relatively similar rates of disease persistence and recurrence with each of the modalities over follow-up periods of 6-37 months. Recurrences are more likely to occur in women (aged 30 years or older), women with HPV type 16, and women with prior dysplasia. Persistent disease was more common in women with larger lesions, a factor that in other studies has been shown to be better managed by carbon dioxide laser procedures than other modalities.[45] Many recurrences of cervical dysplasia are associated with prior positive ectocervical or endocervical margins.[48]

The 2012 Updated Consensus Guidelines for the Management of Abnormal Cervical Cancer Screening Tests and Cancer Precursors recommends that women with HIV or other immunosuppression be managed in the same fashion as immunocompetent women.[24]

In immunologically intact women, appropriate dysplasias treated with carbon dioxide laser procedures may result in complete eradication of the HPV genome.[53]

In a study by Kjellberg et al, cervical dysplasias ranging from mild to severe were evaluated with colposcopy and biopsy results, and the patients were treated with carbon dioxide laser conization. The presence of HPV in the removed specimen was documented by HPV testing and was positive in 73.2% of patients before excision. At follow-up, only 3 women were positive for HPV, but no women had the same HPV type at 2 follow-up visits over 22-46 months. Only 2 postoperative samples had squamous cell atypia.[53, 54, 55, 56, 57, 58, 59, 60]

Several investigators have found that the results of carbon dioxide laser procedures are similar to those of cold-knife conization procedures or LEEPs for the recurrence of neoplasia. Many recurrences are associated with positive ectocervical or endocervical margins at the prior procedure.[48]

Recurrence or persistence of endometriosis in pelvic organs may also be dependent on individual host factors and immune function. Both endometriosis and adhesions may result in altered pelvic anatomic relationships leading to dyspareunia, reduced fertility rates, and increased risk of ectopic pregnancy. Therapy following CO2 laser treatment must be individualized based on patient presentation, clinical symptoms, and individual anatomic findings.

Extensive review of publications incorporated in the development of the 2012 Consensus Guidelines Conference and conference participants identified several areas important for the clinical care of women but which currently have insufficient evidence for definitive recommendations.[24]  Note the following:

1. More information is needed to determine post treatment outcomes and optimal long-term followup of women treated for CIN 2 and 3 managed with serial co-testing.
2. More evidence is needed before developing management guidelines for women with negative colposcopy evaluation, but with abnormal cytology or with CIN1. 
3. More followup studies of women whose management utilized HPV genotyping, immunostains or cytogenetics are needed to incorporate these new testing modalities into management guidelines.
4. Information about the long-term effects of HPV vaccinations on viral natural history and management of HPV related disease is currently not known.
5. Evidence of the safety of observation and fertility protection of young women with high grade histologic lesions and the rates of regression or progression of HPV disease of the cervix is not yet available.

As evidence in these areas emerges, management recommendations utilizing the CO2 laser may also be modified.[61]

The utilization of the bivalent (human papillomavirus [HPV] types 16,18) or quadrivalent (HPV types 6,11,16,18) vaccines for HPV remain the best preventive strategy.[24] These vaccines provide clear benefit when administered to women and men ages 9-26 years, and they may be of benefit to other populations based on research in progress. Vaccines in development will include more HPV types.

The effects of vaccinations of large populations over the long term remain unknown. It is also unknown if vaccination alters the natural history of HPV disease or whether it should alter management strategies in cases of histologic abnormalities. Therefore, women who have received an HPV vaccine should undergo the current guidelines' recommended cytologic testing and treatment.