Diagnostic and Therapeutic Cold Knife Conization for Cervical Intraepithelial Neoplasia

Discussion

Conization of the cervix has been widely used for the diagnosis and conservative treatment in patients with CIN. Because cold knife conization is performed under general anesthesia, and because of the risk of some complications, the traditional surgical technique has been recently replaced by laser conization and LEEP in many Western countries^[5-7]. Although these methods can provide histologic information including the depth of invasion and the involvement of the surgical margins, several randomized trials have demonstrated that there were no statistically significant differences in cure rates for CIN among these methods^[4,8,9]. Krebs et al.^[3] demonstrated that fragmentation and cautery damage interfered with the orientation of tissue and with histologic evaluation of the margins in 19% of cases. Mathevet et al.^[10] showed that thermal artifact induced by coagulation prohibited evaluation of cone margins from specimens in 38% of patients who underwent conization by laser and in 31% of those with conization by loop. Thus, cold knife conization is still the gold standard for diagnosis and therapy.

The main advantage of cold knife conization is that it produces a good histologic sample which can be used to make an accurate diagnosis. Margin status is an essential component of pathologic examination because of its significant impact on the prediction of residual dysplasia in the remaining uterus^[11,12]. Reich et al.^[13,14] reported that only 0.35% of patients who received cold knife conization and had CINIII with clear margins on histologic examination developed new high grade squamous intraepithelial lesions. However, 22 of the patients who underwent the procedure and who had involved margins were found on follow up with persistent or recurrent CINIII, or they developed invasive carcinoma after a median of 3 years (ranging from 2 to 28 years). Therefore, cold knife conization is an effective method for the treatment of CINIII patients who have clear margins, and in patients with positive margins, careful follow up should be performed in order to detect early CIN or invasive carcinoma. In another study, Costa et al.^[15] reported that the width, depth and margin of the cone had no influence on the cure rate. In our study, 8 patients with CINIII had positive margins (4.3%), and 2 of them had CINIII recurrence within 6 months and 12 months, respectively after conization. Six patients with positive margins showed no abnormality in cytology or in colposcopy during the 67-month follow-up. The cure rate was 98.9%, while the failure rate was only 1.1%. Rates of residual or recurrent disease after incomplete removal of CINIII with different excisional techniques have been reported as 5%-22%^[14,16-18]. Positive margins do not equate to residual disease, and regular follow-up colposcopy and cytological examination should be performed to identify the small number of women with residual CIN after therapy^[14,18]. Residual CIN posttreatment is probably due to the effects of diathermy on the cut surface of the cervix after removal of the cone, while the inflammatory response is associated with wound healing. Dysplastic or malignant epithelium in the inner zone of necrosis and white cell infiltration in the outer zone appear to be eradicated after cold knife conization. Only lesions outside these zones can persist, regress, or progress^[14]. On the other hand, persistent CINIII lesions have a potential to regress during follow up, and some of these high grade lesions evolve to normal or to a lower grade abnormality without therapy^[19,20].

The diagnostic concordance rate of colposcopic multiple punch biopsies and cervical conization is reported as 66%-84%^[21-23]. Our study showed that the rate was 74.2%. The reason for the discrepancy is that the colposcopic multiple punch biopsies technique is limited in the amount of tissue removed from the cervix. Thus conization can provide for a more accurate diagnosis and for a better histologic representation of the disease process; moreover, it has significant therapeutic effect.

The main complication induced by conization is hemorrhage and cervical stenosis. The hemorrhage rate has been reported between 1.1%-10%^[24-26]. The reported rate of cervical stenosis after conization has varied from 2% to 17%^[20,21]. Bleeding occurred in 4.3% of our patients, and cervical stenosis occurred in 1.6%. Post-conization stenosis can be related to the length of the cone removed, being more likely to occur with cone biopsies more than 20 mm long^[27,28].

In this review, we discovered 5 cases with early invasive carcinoma (Ia₁, 2.7%), and 3 of these patients underwent subsequent hysterectomy. Within 3-5 years of follow-up, the other 2 patients who only underwent conization did not have recurrence. Lü et al.^[29] demonstrated that microinvasive cancer was found unexpectedly in up to 11.8% of specimens through conization, and Ueda et al.^[17,30] reported the excellent therapeutic effects of laser conization with vaporization of the base for micro-invasive cancer. This means that conization for patients with early invasive cancer is likely to be a curative method. Nevertheless, recurrence may occur and regular cytologic examination and colposcopy during follow up remain essential.

In conclusion, cold knife conization remains an acceptable option in the management of CIN and microinvasive carcinoma of the cervix, and the excellent diagnostic and therapeutic efficacy of cold knife conization is well known and has been confirmed. If properly performed, the procedure has a low risk for complications, and it provides an accurate histologic representation of the disease process; moreover it is curative in most cases. Of course, excellent clinical outcomes still require careful, long-term careful follow-up.