Conization of Cervix
|INTRODUCTION||Section 2 of 11|
Conization is defined as excision of a cone-shaped or cylindrical wedge from the cervix uteri that includes the transformation zone and all or a portion of the endocervical canal. It is utilized for the definitive diagnosis of squamous or glandular intraepithelial lesions, for excluding microinvasive carcinomas, and for conservative treatment of cervical intraepithelial neoplasia (CIN). Techniques for diagnostic and therapeutic conization are virtually identical. The extent of excision must be adjusted according to individual needs .
Conization can be performed with scalpel (cold-knife conization), laser, or electrosurgical loop. This latter is called loop electrosurgical excision procedure (LEEP) or large loop excision of the transformation zone (LLETZ). Combined conization usually refers to a procedure started with laser and completed with cold-knife technique. Laser conization can be excisional or destructive (by vaporization).
Each of these approaches has distinct benefits and disadvantages. Cold-knife conization provides the cleanest specimen margins for further histologic study, but it typically is associated with more bleeding than laser or LEEP, and it requires general anesthesia in most cases. Laser procedures are lengthier and may, especially if low-power density is employed, "burn" the margins, thus interfering with histologic diagnosis. This procedure’s main advantage is that laser-energy produced "dots" can accurately outline the exocervical margins. However, overall, the benefit of using laser for conization may not justify its high cost.
LEEP procedures have several advantages, including rapidity, preservation of the margins for histologic evaluation, and virtual bloodlessness. Moreover, it is possible to perform them in office or other outpatient settings
History of the Procedure: The precise origin of cold-knife conization is uncertain. Procedures similar to conization were used in the early 19th century in an attempt to excise gross cervical tumors per vaginam. During the second half of the 20th century, conization evolved as an important tool for diagnosing the cause of positive cervical cytology in women without visible lesion, and, later, as treatment of CIN. Its diagnostic application was reduced following widespread use of colposcopically directed cervical biopsies combined with endocervical curettage. Yet conization remains an important diagnostic tool in selected situations. Therapeutic conization for CIN became an accepted modality in management of CIN following publication of rigorous studies by Scandinavian and Austrian researchers (Kolsted, Bjerre, Burhard, Reich).
Problem: Conization of the cervix is an important tool in the diagnosis and treatment of CIN, and consequently, in the reduction of deaths caused by cervical carcinoma.
Frequency: US: Frequency of conization depends on the number of suspected or detected cases of CIN procedures and can only be estimated. There may be 10-20 million cases of human papillomavirus (HPV) infection that can cause CIN or cervical carcinoma. Although a large proportion of these (an estimated 80%) regress spontaneously, detected cases require colposcopy and, at times, conization for definitive diagnosis or treatment. In the US, 13,230 new cases of cervical carcinoma and 6,417 deaths from this disease were reported in 1998.
International: Worldwide, cervical carcinoma is the third most common cause of cancer-induced death. In 1998, 470,606 new cases and 233,372 deaths were reported. Cervical cancer remains a major cause of mortality in regions without effective universal screening programs, particularly in developing countries, such as Latin America and Central and Eastern Europe.
|INDICATIONS||Section 3 of 11|
Diagnostic conization is indicated in the following situations:
Therapeutic conization is currently the preferred modality to treat CIN grades 2 and 3. All described approaches (cold-knife, laser, and LEEP conizations) are equally effective, as found by Mitchell and colleagues.
Historically, carcinoma-in-situ (CIN grade 3), the first identified intraepithelial neoplasia, was treated with hysterectomy. During the last quarter of the 20th century, several large published series had proved the effectiveness of the more conservative conization. Kolstad and Klem (1976) reported 1,122 patients with carcinoma-in-situ treated with conization with a recurrence rate of 2.3% and unexpected discovery of small invasive carcinomas in 0.9%. Bjerre et al reported treatment failure in 7% of their patients who received therapeutic conization.
Controversies exist as to the necessity of removing the entire endocervical canal, including the internal os, in all cases. This approach, recommended by at least 2 studies, may increase the risk of cervical incompetence in women who desire posttreatment pregnancy. It is the authors' belief that it is possible to determine the probability of high endocervical involvement fairly accurately by performing endocervical curettage or by obtaining cytology with an endocervical brush. If these tests are negative for CIN or glandular atypia, and if the patient wishes to preserve her childbearing potential, we preserve the cranial extremity of the endocervical canal.
In addition to conization, CIN also can be treated by hysterectomy or by other destructive methods, such as cryotherapy, laser vaporization conization, or radical electrocoagulation. The choice between hysterectomy and conization usually is based on the grade and extent of the disease, the patient’s age, the desire for childbearing, and the history of recurrence after conservative management. Since destructive methods such as cryotherapy yield no specimen for histologic studies, their use should be limited to those women in whom an accurate preoperative diagnosis has been established by directed biopsies.
|RELEVANT ANATOMY AND CONTRAINDICATIONS||Section 4 of 11|
Relevant Anatomy: The cervix is typically 2.5 cm long. It communicates with the endometrial cavity of the corpus uteri through the internal os and with the vagina through the external os. The vaginal portion (also called exocervix or “portio vaginalis? is covered by stratified squamous epithelium, and the cervical canal is covered by columnar epithelium, which also forms endocervical glands, more correctly called clefts. The 2 epithelia meet at the squamocolumnar junction. In most adult women, the squamocolumnar junction is not an abrupt meeting point, but a zone containing irregular areas of glandular and metaplastic squamous epithelium. The size of this transformation zone varies from 2-15 mm . CIN usually arises in the transformation zone and usually extends to a depth of less than 7 mm. The blood supply of the cervix originates mainly from the cervical branches of the uterine artery and from branches of the vaginal and pudendal arteries.
Contraindications: Conization should be avoided during pregnancy if at all possible, since it commonly causes significant (>500 mL) bleeding. About 30% of pregnant patients who undergo conization develop delayed postoperative hemorrhage, and fetal loss has been reported in as many as 10%. Rare indications for performing this procedure include the suspicion of invasive cancer discovered during the first or second trimesters.
|WORKUP||Section 5 of 11|
Table 1. Epithelial cell anomalies according to The Bethesda System: The terms LSIL and HSIL also are used, at times, as histologic diagnosis. This is unfortunate, since correlations between cytologic and histologic diagnoses are poor.
|The Bethesda System:Epithelial Cell Anomalies||Common abbreviations and comments|
|Atypical squamous cells of undetermined significance||ASCUS|
|Atypical glandular cells of undetermined significance||AGUS|
|Low-grade squamous intraepithelial lesion||LSIL or LGSIL
Encompasses HPV (koilocytosis), mild dysplasia, CIN-1
|High-grade squamous intraepithelial lesion||HSIL or HGSIL
Encompasses moderate and severe dysplasia and carcinoma in situ, CIN2, CIN-3
|Squamous cell carcinoma||¡@|
|Adenocarcinoma, not otherwise specified||¡@|
|Other malignant neoplasia||¡@|
Table 2. Histologic diagnoses utilized in cervical epithelial lesions
|Cervical intraepithelial neoplasia, grade I||CIN-1, Mild dysplasia|
|Cervical intraepithelial neoplasia, grade 2||CIN-2, moderate dysplasia|
|Cervical intraepithelial neoplasia, grade 3||CIN-3, severe dysplasia, carcinoma in situ|
|High-grade cervical intraepithelial neoplasia||CIN-2 or CIN-3|
|Carcinoma in situ||CIN-3|
|Microinvasive squamous cell carcinoma||¡@|
|Squamous cell carcinoma||¡@|
|Adenocarcinoma, not otherwise specified||¡@|
|Other malignant neoplasia||¡@|
|TREATMENT||Section 6 of 11|
Preoperative details: Performance of cold-knife conizations has decreased considerably in frequency following the wide acceptance of LEEP, which yields equivalent results, is more cost effective, and appears to cause less intraoperative and postoperative bleeding. However, the cold-knife approach may be preferable where evaluation of the margins is particularly critical, or in situations in which the use of a diathermic loop is impossible due to the exocervical margin’s proximity to the vaginal fornix.
In some centers, the cold-knife approach is used exclusively if microinvasion or glandular lesion is suspected. Cold-knife conization must be performed in a fully equipped operating room under general, epidural, or spinal anesthesia. Local anesthesia may be adequate in relaxed, highly cooperative patients, but unexpected movements and vaginal tightness may interfere with optimal conclusion.
Cold-knife conization can cause significant bleeding. Consequently, it is advisable, either to perform a preconization cerclage as described below, or to inject the cervix with a vasoconstricting solution such as dilute vasopressin, phenylephrine, or epinephrine. The vasopressin solution is prepared by adding 10 units of Pitressin to 30 mL of sterile water for injection. A maximum of 10 mL of this solution is injected in 1-mL increments into the cervical stoma around the transformation zone. Phenylephrine (Neo Synephrine) is used in a concentration of 1:200,000). Epinephrine typically is used in combination with lidocaine in a 1:100,000 dilution (Xylocaine 1% with epinephrine). The author prefers to perform preconization cerclage in most cases, since, in contrast with vasoconstrictor injections, this technique will not induce tachycardia or sudden blood pressure changes and tends to reduce delayed hemorrhage.
Some evidence indicates that conization performed during the first, rather than the second half of the menstrual cycle is less likely to be associated with significant blood loss.
Intraoperative details: Cold-knife conization
Technique: Under adequate anesthesia, the patient is placed in dorsal lithotomy position and prepared and draped in the usual manner. A weighted speculum is inserted in the vagina.
Preconization cerclage (recommended to create bloodless operative field, not as prevention of cervical incompetence): 1-chromic catgut sutures with attached general closure needles (cutting needles also can be used, but they tend to cause more bleeding in our experience) are inserted at 3 and 9 o’clock positions close to the vaginal fornix . The needle attached to the 3 o’clock suture is used to perform the anterior portion of the cerclage by imbricating the suture in the anterior lip and by tying it to the needle-free end of the suture already anchored at 9 o’clock. The needle-ended suture of the 9 o’clock suture is used to complete the cerclage posteriorly. It is useful to insert a black silk suture in the cervix at 12 o’clock to help the pathologist orient the specimen.
Conization: Sound the cervical canal to determine its length and the position of the internal os. Paint the cervix with Lugol solution and apply lateral traction to the angle sutures. Conization is performed with a No. 11 blade, which should be pointed toward the planned apex of the cone. It is preferable to start the incision at 3 or 9 o’clock and to cut posteriorly first to avoid loss of visualization from bleeding. The exocervical incision should include the entire transformation zone, with a 2-3 mm margin. If there is no known deep endocervical extension of the lesion into the endocervical canal, the cone’s apex should end approximately 1 cm caudal to the internal os. Deep extension may necessitate excision of the internal os. Remove the cone specimen in one piece if at all possible.
Following completion of the conization, the endocervical canal is curetted with a Kevorkian endocervical curette to rule out residual lesions. Because of the cerclage, blood loss is usually minimal. To reduce oozing, Monsel solution (ferric subsulfate, a long-acting astringent, Mallinckrodt Chemical Co, St. Louis, Mo) may be used.
Historically, conizations were completed by a Sturmdorf procedure, which covers the raw stump with an anterior and posterior exocervical flap. This procedure is felt to be unnecessary by most surgeons, and there are concerns that hiding the coned area may cover deep-seated residual lesions. Sturmdorf procedures have not been shown to reduce the risk of delayed bleeding.
Some operators insert a small rubber drain in the cervical canal to reduce the risk of cervical stenosis. The value of this procedure is uncertain, and the author has not used it in recent years.
One should observe the operative site for a few minutes following the procedure to detect excessive bleeding. Arterial bleeding, uncommon if the cerclage approach is used, can be controlled by coagulation or by inserting “U?or "figure of 8" sutures. General oozing, if significant, is best treated by painting the stump with Monsel solution and/or by inserting a tight vaginal soft gauze pack (eg, Curlex), preceded by a sulfonamide or sterile lubricating cream. The patient herself may remove the packing 12-24 hours following its insertion. Leaving a 5-cm protrusion of the packing beyond the introitus makes removal easy.
While laser conization is effective for treatment of CIN, it offers few advantages over LEEP or cold-knife approaches. Potential disadvantages include costly equipment and possible coagulative effect on the margins that makes their histologic evaluation difficult. Gynecologists performing any type of laser surgery should attend specific courses on laser physics, safety features, and operative techniques. The author confines its use to patients with definitive diagnosis of CIN grades 2 or 3 in whom a large lesion is close to the vaginal fornix or extends into the vault.
The operation is performed with carbon dioxide laser, using a colposcopic micromanipulator. While local anesthesia is used in some settings, we recommend general anesthesia to reduce the chance of laser injury due to unexpected motion. A preconization cerclage can be performed as described above, or one can inject a vasoconstricting agent. Use of a smoke/vapor evacuator is indispensable.
The procedure is begun by outlining the exocervical margins with 0.5- to 1-mm dots produced by laser energy at a power setting of 20-50 W. A laser incision then is performed to connect the dots and extended to a depth of 3-5 mm . Laser, scalpel, or Mayo scissors may complete the procedure. If laser is used for the conclusion, the stromal edge of the incision must be grasped and lifted with a hook to permit the laser beam’s penetration towards the apex. Bleeders in the raw stump can be coagulated with defocused 2-mm laser dots, or with a diathermic coagulator. We find that switching to cold-knife techniques following the initial annular incision with laser reduces the time required for completion.
One variety of laser conization is called vaporization conization. It involves vaporization to a depth of 7 mm of the entire transformation zone, including a 2-3 mm margin. To accomplish this procedure, a spot size of 2 mm and a power setting of 25 W commonly are used. A gauge must be used to determine the precise depth of the vaporized area. Dorsey recommends dividing the area to be vaporized in 4 quadrants and completing the procedure by vaporizing an additional 2-3 mm of the endocervical canal.
Since vaporization conization does not provide a specimen for histologic evaluation, it should only be used in cases in which the entire lesion is visible colposcopically and where it does not extend into the endocervical canal. Pretreatment histologic diagnosis based on directed biopsies is mandatory.
Loop electrosurgical excision procedure
LEEP (LLETZ) procedures use diathermy current for excising all or selected areas of the transformation zone. The thin wire loop electrodes are insulated to prevent thermocoagulative artifacts; consequently the excised tissues are preserved for histologic examination. The author prefers to use pure cutting rather than blended current, since cutting current causes fewer thermal artifacts in the excised specimen.
LEEP is a precise and inexpensive technique that causes less bleeding than cold-knife or laser conizations. The author believes that it has proven itself as the best approach to conization in the overwhelming majority of patients. In rare patients with CIN, the size of the transformation zone exceeds the size of the largest loop. In such cases, as well as in patients with vaginal fornix involvement, laser conization may be a better approach. The equipment for LEEP procedure consists of a generator that creates high-frequency (350-1,200 kHz), low-voltage (200-500 V) electric current. The generator is connected to an insulated thin wire loop, which is available in various sizes.
Technique: Most loop electrosurgical procedures can be performed under local anesthesia in an outpatient setting. The patient is placed in lithotomy position and is attached to a grounding pad. An insulated speculum, connected to a smoke evacuator tubing, is used to prevent electric shock, which can occur if an uninsulated metal speculum is touched inadvertently by an active loop. For local anesthesia, we inject 2-5 mL of lidocaine with epinephrine in 3, 6, 9, and 12 o'clock sites 1-2 mm beneath the surface of the cervical epithelium, using a 25-gauge spinal needle. The use of epinephrine (or dilute vasopressin) is crucial to prevent intraoperative bleeding that could obscure the field of vision. If a patient is unable to relax, it may be safer to perform the procedure under general anesthesia, since accidental burns of the vaginal wall can occur in patients who move during the procedure.
The loop size, usually 1.5-2 cm in width and 0.8-1.0 cm in depth, should be appropriate to remove the entire transformation zone with a 3-mm margin in one pass. In the first pass, tissue is ablated to a depth of approximately 1 cm. Using a 1-cm x 1-cm loop, more of the endocervical canal can be excised in a second pass from the crater base. Once the cervix is adequately exposed, LEEP procedures can be performed with extreme rapidity, usually in less than 1 minute. The loop can be directed in a transverse direction (eg, from 9 to 3 o'clock), or anteroposteriorly . Following the loop excision, the surface of the cervix appears raw. Painting it with Monsel solution usually can control oozing. Larger bleeders should be cauterized with a ball cautery.
Loop electrosurgical excision in “see and treat?settings
Conization procedures usually are performed following an HSIL or LSIL cytologic report and confirmation of CIN grade 2 or 3 by colposcopically directed cervical biopsy. While this classic approach is reliable, it necessitates 3 or 4 encounters and thus risks losing patients who do not return for follow-up.
“See and treat?bypasses the colposcopically directed cervical biopsy; the indication for LEEP, performed during the first or second encounter, is based solely on the cytology report. This approach has the advantage of guaranteeing treatment of most high-grade CINs. Its only disadvantage is the possibility of performing a LEEP in those in whom colposcopy would have excluded lesions that necessitate therapy, and who could have opted for follow-up observation. Considering the LEEP’s high degree of safety, the benefit of prompt treatment of CIN most likely outweighs the risk in women in whom the indication is ambiguous. The universal application of “see and treat?is not accepted at this writing. This approach, however, is most valuable when follow-up of women is often unsuccessful, such as in the lowest socioeconomic groups both in the US and in developing countries.
Postoperative details: Following any method of conization, complete healing of the cervix takes up to 6 weeks. Intercourse and/or use of vaginal tampons during the early healing period may cause significant bleeding and infections and should be restricted for at least 2-3 weeks.
Follow-up care: Conization sites usually heal in 6 weeks. Re-examination of patients 2 weeks postoperatively is useful to determine whether restrictions, such as coitus, can be lifted. Final postoperative examination is recommended at 6 weeks. To ascertain the absence of residual or recurrent CIN, Papanicolaou smears should be performed every 3 months during the first postoperative year, and every 6 months thereafter. A single follow-up smear is positive in fewer than 25% of women with residual disease. Multiple studies report that any of the conization techniques cure at least 95% of patients who have CIN. Recurrence or persistence is significantly more common; 16.5% versus 1.9% according to Felix et al, in patients who had a positive margin for CIN in the postoperative specimen.
Intraoperative and postoperative bleeding are the most common complications of cervical conization. Both of these can be eliminated or significantly reduced if the above-described cerclage technique is practiced. Intracervical injection of dilute epinephrine or vasopressin in the cervix, contraindicated in hypertensive and cardiac patients, reduces intraoperative bleeding but not delayed bleeding, which usually occurs 7-14 days postoperatively in about 2% of the patients who undergo cold-knife conization. Delayed bleeding, uncommon after LEEP, may be managed successfully by vaginal packing in most women. Failure to respond to packing necessitates resuturing of the operative area. According to anecdotal reports, an emergency hysterectomy had to be performed in rare patients in whom extreme Intraoperative hemorrhage was triggered by conization. Such a complication is avoidable with the use of proper operative technique.
Cervical stenosis may occur in a few women. Inserting a rubber drain following the procedure has a limited role in the prevention of this often negligible complication. Cervical incompetence can be caused if the apex of the cone involves the internal os. Women who get pregnant after conization should be closely followed for this potential complication, which is manageable by cerclage.
Both laser conization and LEEP generate smoke. Inhalation of smoke may be dangerous for the operator, since it may contain HPV particles. Use of smoke evacuators is therefore indispensable, and wearing a mask during the procedure is recommended.
|OUTCOME AND PROGNOSIS||¡@|
The majority of reports indicate that conization cures CIN in over 90% of cases. However, these excellent results are not universal, and cure rates as low as 60% also have been reported. The reasons for treatment failure are unknown in most cases; positive margins are implicated by some studies. Because of the possibility of residual or recurrent disease, close follow-up observation of all treated women is mandatory.
|FUTURE AND CONTROVERSIES||¡@|
In the 1930s, more American women died of cervical cancer than of breast cancer. Since the universal adoption of effective screening programs that lead to the diagnosis and treatment of high-grade intraepithelial neoplasias, invasive cervical carcinoma has become a relative rarity.
Despite these successes, controversies remain. Our knowledge of the natural history of cervical cancer precursors is still incomplete. We now realize that the presumed continuum from CIN-1 to CIN-3 to invasive cancer is absent in the majority of cases. We have no tests that will tell us which case of CIN-1 will progress and which will regress. We do know that leaving CIN-3 untreated leads to invasive cancer and to death.
Based mainly on economic considerations, some groups recommend reduction of screening frequency and intermittent cytologic follow-up only for women with ASCUS or LSIL. The cost-effectiveness of performing colposcopy on all women with ASCUS or SIL cytology is being questioned. The author considers cytology a risk indicator rather than a diagnostic test and believes that we have an obligation to our patients to reach an accurate diagnosis. Recent data on the usefulness of testing for high-risk HPV-DNA raises hope that its performance may reduce the need for directed biopsies and diagnostic conizations. Despite the existence of major disagreements among observers regarding the interpretation of cytologic and histologic specimens, cytology, in combination with HPV-DNA tests and histology for the diagnosis and grading of CIN, is expected to remain the backbone of screening for years to come. The ultimate decision on evaluating and treating is still in the hands of the clinical gynecologists.
The author believes that we better serve our patients by diagnosing and treating any cytologic change that is associated with a reasonable probability of CIN-3. Colposcopically directed biopsies and LEEP conizations resolve most of these issues with rare complications and at a relatively low cost. We are hopeful, however that better understanding the natural history and pathogenesis of CIN will yield even less traumatic approaches some time in the future.
|Caption: Picture 1. Conization site as related to uterine anatomy|
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|Caption: Picture 2. The exocervical incision should be placed 2-3 mm beyond the limits of the transformation zone and must be adjusted to its size.|
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|Caption: Picture 3. In cases of histologically diagnosed cervical intraepithelial neoplasia (CIN) grades 2 and 3, prebiopsy cytology was reported as high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL), and atypical squamous cells of undetermined significance (ASCUS) in nearly equal proportion (data from 6 independent studies).|
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|Caption: Picture 4. Site of preconization cerclage|
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|Caption: Picture 5. Laser conization is initiated by outlining the exocervical margins with 0.5- to 1-mm dots produced by laser energy at a power setting of 20-50 W. A laser incision is then performed to connect the dots and is extended to a depth of 3-5 mm.|
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|Caption: Picture 6. Loops for loop electrosurgical excision procedure|
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|Caption: Picture 7. Loop electrosurgical excision procedure|