Diagnosis and Therapy of Benign…

Diagnosis and Therapy of Benign…

The natural history of nabothian cysts may be rupture (more commonly) with a subsequent small yellow scar, stabilization, or growth. The majority of nabothian cysts, therefore, require no treatment, and the diagnosis is typically clinically obvious. Large nabothian cysts may benefit from being opened with a loop electroexcision procedure (LEEP) or direct cauterization. The key is assuring that the area fully drains, which may be accomplished by ensuring that the squamous covering is adequately resected or that the base is cauterized to decrease mucus production.

CONDYLOMATA ACCUMINATA

Cervical condyloma can take various forms (Figs. 4A and 4B), but generally they appear as one or multiple clearly delineated, elevated, white plaques on the cervical portio and often extend onto the vaginal apex as well. Small lesions may only be apparent through colposcopic views and acetic acid application after a cytology result of atypical cells of uncertain significance (ASCUS). The larger lesions are commonly friable and can have symptoms of postcoital bleeding that would increase concern for malignancy. If a patient has vulvar condylomata, a careful inspection of the vaginal and cervical epithelium for subclinical or clinically apparent condylomata is warranted. Clearly, full evaluation of these lesions requires cervical screening (HPV/cytology) and biopsy of a typical lesion with or without colposcopy at the initial evaluation. While condylomata are most commonly associated with HPV types 6, 11, 42, 43, and 44 and the potential for malignancy is low, their presence suggests that other HPV strains could be present with higher potential for development of preinvasive or malignant disease.

Management on the cervix differs from vulvar areas where direct application of agents such as TCA (trichloroacetic acid) or imiquimod can be accomplished with little direct absorption. Given the nature of the vaginal and cervical skin, management of these lesions tends to rely heavily on direct removal through the use of biopsy forceps, cautery, LEEP, or laser according to the size and location of the lesion as well as the availability of these modalities. All serve to eliminate the bulk of disease and are assumed to decrease the viral load by virtue of the same.

Management is problematic in women who are pregnant, who are immunosuppressed, or who have chronic recurrence of condylomata. During pregnancy, observation alone is preferred. Removal with LEEP-based therapies might be considered only if there is concern about significant hemorrhage associated with cervical and/or vaginal dilatation at the time of delivery but carries uncertain risks. A significant proportion of these condylomata regress after pregnancy, so therapy is preferentially targeted to the postpartum assessment if they are not thought to be significant enough to interfere with delivery. Use of topical solutions is generally prohibited in pregnancy even for external lesions.

Chronic immunosuppression is commonly associated with chronic low-level cytologic abnormalities of the cervix and the presence of subclinical or clinical condylomata. Rather than recurrent surgical removal, if the patient is able to continue close observation with cytology, and/or HPV subtyping as appropriate and colposcopy on a regular basis, this may well be preferable to multiple surgical interventions. Then, either a change in colposcopic appearance, gross appearance, or cytology/ HPV subtype showing HPV 16 and/or 18 should trigger a biopsy to ensure that any advance in the intraepithelial neoplasia associated with condylomata is identified and appropriately treated. If it remains stable in appearance and screening, then close follow-up may suffice. Options for removal include biopsy and/or removal, cryotherapy, laser ablation, and LEEP.

SQUAMOUS PAPILLOMA

Papillomas that are not HPV-related can occur in the cervix and usually originate from the exocervix near the squamocolumnar junction (transformation zone). These are thought to be related to local irritation or scarring and are usually less than 1 cm. Their natural history is not well described, as the usual intervention for these papillomas is excision to ensure that they do not represent malignancy (Figs. 5 and 6).

LEIOMYOMAS

Leiomyoma is the most common tumor of the uterine body, but it is rare to find it isolated to the cervix. In the cervix, leiomyomas can occur wherever there is smooth muscle, so they can be subserosal, intramural, or submucous in analogy to those in the body of the uterus. Endocervical leiomyomas become symptomatic particularly if an endocervical polypoid leiomyoma prolapses, often with significant cramping and bleeding, or if there is endocervical obstruction with hematometra. Exocervical and endocervical leiomyomas can become large enough to obstruct urethral drainage as well as to prolapse into the vagina and cause bleeding. The decision to remove these masses is generally straightforward, both to adequately diagnose the condition and to alleviate the symptoms. The surgical management of these lesions is best undertaken in the operating room with adequate planning for the potential of abdominal as well as vaginal approaches. Removal generally involves a surgical procedure carefully tailored to the individual patient because of the impingement on bladder, bowel, ureter, and even urethra. Use of endoscopic equipment or a LEEP with a loop that fits can assist in removal. Planning for adequate control of the cervical branch of the uterine artery is always an important element. Removal of pedunculated fibroids in the office setting is generally discouraged, because the upper limits of the lesion can rarely be visualized or easily accessed, and vascular relationships of leiomyoma of the cervix are rarely straightforward.

ENDOMETRIOSIS

Cervical endometriosis (Fig. 7) can mimic multiple lesions, including gestational trophoblastic disease (GTD), because of its highly vascular nature. The etiology of endometriosis in the cervix is unclear, but prior trauma to the cervix and a history of endometriosis are potential clues. History and physical examination to evaluate the likely nature of the lesion, including a laboratory assessment of human chorionic gonadotropin are all prudent before consideration for biopsy or treatment. Biopsy of areas of trophoblastic disease are generally avoided, because the invasive neovascularization that accompanies these lesions may lead to significant hemorrhage, unlike endometriotic implants that are less likely to have postbiopsy hemorrhage. Symptoms from a cervical lesion are generally related to bleeding or discharge, and pelvic pain is more likely referred from endometriotic implants elsewhere in the pelvis. These areas should respond to general therapy for endometriosis (the use of Lupron, for example), and failure to respond should lead to biopsy to confirm the diagnosis.

REMOVAL OF CERVICAL LESIONS

Techniques include thermal ablation (cryotherapy), laser ablation, and excision with biopsy forceps, LEEP, laser, or scalpel. The choice among these options is clinically determined by whether endocervical involvement is present and whether there is an uncertainty regarding the pathology or extent of disease that requires accurate assessment of specific margins of resection. In variable to low resource settings, only one of these may be available. Because laser treatment and surgical excision are outlined elsewhere, the following discussion is devoted to thermal ablation and loop excision.

THERMAL ABLATION: CRYOTHERAPY

Cryotherapy is the primary thermal method in use at the present time. Evidence-based review of cryotherapy by the World Health Organization 2 concluded that, while the comparative data were limited, the risk for spontaneous abortions, infections including HIV, and infertility appear to be similar to the general population or acceptable. Cryotherapy may be used for treatment of condylomata or for ablation of low grade CIN. Again, satisfactory pretreatment evaluation and individualization of therapy based on age, disease, and gravidity is important. In particular, if lesions are greater than 75% of the cervical surface, there is high grade dysplasia, or there is disease into the endocervical canal, an excisional approach is recommended (for example LEEP).

Cryosurgery is an office procedure that usually can be performed without anesthesia or analgesia. Occasionally patients will experience discomfort, but it is seldom of a severity to require discontinuation of the treatment. Self-limiting vasomotor reactions characterized by light-headedness and flushing are common. After cryosurgery, patients will usually have 10–14 days of watery discharge requiring four or five sanitary napkins daily. Coitus and intravaginal tampons are not recommended during that time.

Patients should be treated within 1 week of cessation of menstrual periods.

Most cryosurgical instruments use either nitrous oxide (freezing point of −89°C) or carbon dioxide (freezing point of −65°C). If both are available, CO2 is preferred. Proper freezing requires attention to the pressure within the tanks because a decrease in partial pressure changes the freezing rate of the probe. By changing the rate of freezing, the extent of cryonecrosis can be modified. The pressure within the tanks must be at least 40 kg/cm 2 before and at the completion of the freeze. If there is a pressure decrease during cryosurgery, the procedure should be discontinued and repeated with adequate pressure levels.

Probe tips of various configurations are available and should be tailored to individual cervical anatomy. The various flat and cone tips and the 8-mm rod tip are appropriate for most cryotherapy procedures. Areas to be treated should be outlined by a visible lesion or by a colposcopic map, and direct connection of the probe tip to the area to be treated must be possible with the tip chosen.

A thin layer of water-soluble lubricant applied to the tip of the probe allows for better heat transfer between the probe and the cervix, and fills any potential air gaps in the irregular surface of the cervix to provide a more uniform freeze. Freezing of a large ectocervical lesion should begin at the periphery and use overlapping fields of necessary. The ice ball should extend at 4–6 mm beyond the edge of the abnormal epithelium. The depth of cryonecrosis will be approximately 4–5 mm and theoretically should destroy any intraepithelial neoplastic process extending into endocervical glands on the portio. The extent of the ice ball beyond the confines of the lesion is more critical than the length of the freeze. This will usually occur within 2 minutes, so most clinicians use a freeze technique with 3 minutes on, 5 minute thaw, and 3 minute repeat. This was also supported with the WHO guidelines. 3

Cryonecrosis and surveillance

Cellular death occurs at a temperature of approximately −20°C. This temperature is within 2°C of the eutectic point of a sodium chloride solution. Cryosurgery produces severe biochemical and biophysical changes resulting in coagulation of the affected tissues. Rupture of the cell wall occurs with the formation of intracellular and extracellular ice crystals. Avascular necrosis is produced by circulatory compromise because of capillary obstruction and stasis. 4

Regeneration of the epithelium involves the production of initially immature squamous epithelium, which over time will mature into a stratified squamous layer that replaces the neoplastic process. The entire reparative process requires approximately 3–4 months. Subsequent follow-up should be decided on the basis of individual risk parameters.

Since the introduction of thermal ablation, there has been scepticism about its efficacy in the conservative therapy of CIN. Two concerns need to be addressed. First, factors must be identified that are associated with primary failure of the technique. Second, the ability of the neoplastic process to recur must be considered along with the potential benefits or deficits of a procedure in expediting the long-term follow-up. Observations from British Columbia suggest that for CIN, excisional procedures have a lower rate of recurrence. 5 However, the use of cryotherapy with VIA, particularly in settings with no access to LEEP, for screen and treat strategies remains an important option for prevention of cancer. 2. 3

LOOP ELECTROEXCISION PROCEDURE

The addition of loop procedures to the outpatient setting has had a significant impact on office treatment of preinvasive disease. For the majority of women, adequate colposcopy and biopsy results must be obtained before LEEP should be performed. Clearly “see and treat” strategies (for example HPV screen and rapid treatment) do not follow this pattern in low resource settings.

Potential obstetric sequelae of treatment

The use of LEEP in young women raises a concern of cervical damage similar to that encountered with surgical excision (conization) of the cervix, and some data suggest that there is a potential for preterm births, premature rupture of membranes, and increase in low birth weight babies. 6. 7. 8 The challenge with interpretation of these data is the absence of comparable comparison groups.

A meta-analysis designed to evaluate effect of LEEP on significant prematurity (<32 weeks) and perinatal mortality revealed no association between LEEP procedures and this degree of prematurity. However, this analysis did not address late preterm delivery (34–37 weeks), which is increasingly associated with long-term developmental sequelae in children. 9 Multiple smaller studies do have conflicting results and suggest a relationship between LEEP and subsequent preterm birth.

To this end, there are accumulating data that implicate the depth of the excision and the length of the remaining cervix as the key factors in determining the potential obstetric risks associated with this procedure. A small prospective study of 142 women addressed this issue by assessing cervical dimensions by imaging pre- and post-LEEP treatment, and correlating the volume of cervical excision with subsequent pregnancy outcomes. In the 12 deliveries that were evaluated, there was a correlation noted between cervical excision volume and pregnancy duration. 10 Number of procedures has also been suggested as a risk factor for subsequent poor pregnancy outcomes, with multiple studies suggesting that risk of preterm delivery is increased in women who have undergone two or more cervical excisions. Additionally, short intervals between cervical excision and pregnancy have been associated with subsequent preterm deliveries in some observational studies. This is significantly more controversial. The suggested mechanism for preterm delivery is the possible incomplete healing of the cervix after the procedure. 11 Clearly, data conclusively evaluating obstetric risks associated with LEEP are conflicting, though overall larger studies suggest it is a safe procedure to perform in young, fertility seeking women. While consideration of these possible sequelae is important, it should not keep women from adequate treatment of cervical intraepithelial neoplasia

LEEP uses high-frequency, low-voltage, electrical energy produced by an electrosurgical unit to excise abnormal tissue. There are a variety of units and electrodes used for LEEP procedures, and the healthcare providers using the instrument must understand the various details of operation of each unit. Some variation of a grounding pad application may be required, and adequate suction ventilation with a microbial filter is required. The choice of electrodes used should be determined by careful colposcopic mapping of the disease before treatment and by the individual contour of the vagina (width) and cervix.

LEEP is best performed when patient is not menstruating for simple visualization. Because the procedure does involve thermal injury and tissue removal, local anesthetic with a vascular constrictor can be injected into the cervical stroma before the procedure. A nonconducting speculum is inserted into the vagina, with the suction ventilation incorporated into the body of the speculum. The cervix may be treated with Lugol&#39;s solution for better definition of the lesion. Diathermy power is usually set at 50–60 watts cutting or at 50 watts cutting and 60 watts coagulation. An initial evaluative phantom pass of the selected loop (often approximately 1 cm (10 mm) in width) identifies that the lesion will be encompassed with one or two passes and that no vaginal wall contact will be made.

Large loop excision of the transformation zone (LLETZ) uses a 15 × 7 mm loop and is intended to remove the entire transformation zone. The use of a slow steady movement will reduce thermal injury at the margin. The diathermy unit is turned on only when active movement through the cervix is ongoing. Specimens are then removed for pathologic consultation. This can be performed with one deep or shallow pass, followed by a second pass with a thinner electrode. Then, the base is cauterized with a ball electrode (Fig. 12).

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