TWENTY-YEAR EXPERIENCE WITH LARGE LOOP EXCISION OF THE TRANSFORMATION ZONE AT SESTRE MILOSRDNICE UNIVERSITY HOSPITAL CENTRE

SUMMARY

The 20-year experience with large loop excision of the transformation zone (LLETZ) at Gynecologic Oncology Unit, Department of Gynecology and Obstetrics, Sestre milosrdnice University Hospital Centre from Zagreb is presented. This retrospective observational study included 1407 women with cervical dysplasia treated by LLETZ technique during the 1995-2016 period. LLETZ was most commonly performed in the 25-35 age group (51%), followed by the 36-45 age group (22%), and least frequently in the >65 age group (2%). Histopathologic results lower than high-grade squamous intraepithelial lesion were found in 23% and high grade squamous intraepithelial lesion or worse findings in 77% of patients. Positive margin as a sign of possible residual dysplasia was found in 25% of cones, 80% of which included endocervical positive margin. Cervical canal biopsy result was positive in 18% of cases. Accurate colposcopy and its findings can help avoid overtreatment, the rate of which was higher than expected in our retrospective study. Long-term follow up is an imperative for proper assessment of the procedure success. This method is the best choice for complete disease removal without unnecessary overtreatment, but it requires continuous education and training of the whole team.

Introduction

Large loop excision of the transformation zone (LLETZ) is an inexpensive and simple first choice of minimally invasive surgical gynecologic treatment of premalignant and early malignant cervical lesions. Proper understanding the disease along with right indication set for operative procedure and patient informed consent considering its limitations, complications and possible treatment failure are prerequisites for good outcome of the procedure. In comparison to cold knife cone biopsy, it has many advantages (1-4).

The purpose of this study was to review the 20-year experience with LLETZ in the Gynecologic Oncology Unit, Department of Gynecology and Obstetrics, Sestre milosrdnice University Hospital Centre in Zagreb.

Materials and Methods

This retrospective observational study included 1407 women with cervical dysplasia treated with LLETZ technique during the 1995-2016 period. Patients were divided into subgroups according to age, cone biopsy and cone margin results, and histopathologic findings of the excochleated cervical canal. Cervical cytology, followed by colposcopy evaluation and colposcopy-directed biopsy were performed in all patients to confirm cervical dysplasia. All patients signed the informed consent form to participate in the study, which was approved by the institutional Ethics Committee.

Results

Patient distribution according to age showed that LLETZ was most commonly performed in the 25-35 age group (51%), followed by the 36-45 age group (22%), and least frequently in the >65 age group (2%). Histopathologic findings lower than high-grade squamous intraepithelial lesion (HSIL) were recorded in 23% and HSIL or worse findings in 77% of patients. Four (0.29%) patients were diagnosed with invasive squamous cell carcinoma or adenocarcinoma. Positive margin as a sign of possible residual dysplasia was found in 25% of cones, 80% of which included endocervical positive margin. Cervical canal biopsy result was positive in 18% of cases.

Discussion

Large loop excision of the transformation zone is a simple and rapid technique which is highly favored by gynecologists and patients in therapy of premalignant and early malignant cervical lesions because of its numerous advantages (1, 2). LLETZ offers individual approach to each patient with good performance and avoidance of excessive excision thanks to the availability of diverse shapes and size of loops (1-4).

Premalignant and early malignant cervical lesions can be found at any age, but the 25-35 age group is most vulnerable (5). These patients are of childbearing age and the need of minimally invasive surgical gynecologic treatment for these lesions is more pronounced than in older age groups, as demonstrated by the figure of 51% conducted LLETZ procedures in the 25-35 age group recorded in our study. LLETZ is a procedure associated with a lower rate of complications than cold knife conization, such as postoperative bleeding and cervical stenosis, as well as a lower rate of preterm births, perinatal mortality and morbidity (6-8).

In 77% of our patients, histopathologic finding confirmed colposcopy evaluation and colposcopy-directed biopsy, or it was worse. Four (0.29%) patients were diagnosed with invasive squamous cell carcinoma or adenocarcinoma. Incompatibility of LLETZ specimen showing lower grade cervical dysplasia than colposcopy-directed biopsy was recorded in 23% of cases. Although we expected a lower rate of this kind of incompatibility, Herrero y Saenz de Cabezon et al. report on almost the same discordance (2).

It should also be considered that high-grade dysplasia found in biopsy specimen may have been completely removed with colposcopy-directed biopsy, as well as that previously diagnosed dysplasia has not been removed by LLETZ technique. This assumption was considered in the study by Duesing et al. (9).

Positive cone margins were found in 25% of our cases, 80% of which had positive endocervical cone margin. The prevalence of positive margins after LLETZ technique in our study was similar to the average reported in the literature (6, 10, 11). A meta-analysis by Jiang et al. revealed a similar prevalence of positive margins after LLETZ (22%; 343/1595), and so did a meta-analysis by Gheaem-Maghami et al. (23%) (6, 12).

The most compromised margins in our study were endocervical margins (80%), as in other studies in the literature (13). Although the finding of endocervical positive margins is of greater concern, it need not necessarily confirm the presence of residual disease (10, 13, 14).

There are many disagreements about cone margins following LLETZ, so long-term follow up is important, regardless of the outcome of margin status (11). Margin status is of particular importance in women with carcinoma in situ (11, 15). In our study, there were four (0.29%) patients diagnosed with invasive squamous cell carcinoma or adenocarcinoma.

When cervical canal biopsy is performed during surgical procedure, the result correlates with endocervical margin status, so it can be considered as an important item in further workup (16). Cervical canal biopsy result was positive in 18% of our cases.

It should be considered that residual disease is more frequent in women with positive margin status (16, 17). Although LLETZ technique is superior in many ways to other excisional techniques, some reports claim that thermal artifacts and specimen fragmentation can have negative impact on histopathologic interpretation (18, 19). According to the National Health Service Cervical Screening Programme (NHS-CSP) standards from the United Kingdom, at least 80% of the specimens obtained by LLETZ technique should be in single form (20). It should also be considered that LLETZ is a minimally invasive technique, where it is desirable to balance maximal removal of dysplastic tissue with minimal cervical damage (17). Sparic et al. in their study conclude that expert colposcopists have a lower incidence of positive margins after LLETZ, as well as thermal artifacts (21). Constant investment in education and training of medical staff can provide optimal results in the treatment of cervical dysplasia with LLETZ technique (22).

Accurate colposcopy and its findings can help avoid overtreatment, the rate of which was higher than expected in our retrospective study. Long-term follow up is an imperative for proper assessment of the procedure success. LLETZ is a highly effective, affordable and low-cost treatment option for premalignant cervical lesions. However, it requires continuous education and training of the whole team. This method is the best choice for complete removal of the disease without unnecessary overtreatment.