Large loop excision of the transformation zone (LLETZ) compared to carbon dioxide laser in the treatment of CIN: a superior mode of treatment

Summary. A series of 199 patients with histologically confirmed cervical intraepithelial neoplasia (CIN) grade II or III were allocated by hospital number to receive out-patient treatment by carbon dioxide laser vaporization or large loop excision of the transformation zone (LLETZ). All patients received local anaesthesia. The women in the LLETZ group experienced less post operative haemorrhage, less discomfort, operative time was greatly reduced, and histological material was available for confirmation of the diagnosis. There was no significant difference in recurrence of CIN after treatment between the two groups. At 6 month follow-up, recurrence rates of 8.2% (CIN II) and 7.5% (CIN III) were observed in the laser-group and 5% (CIN II) and 5.3% (CIN III) in the LLETZ group. Further advantages of LLETZ are reduced capital expenditure and no hazard to the eyesight of the surgeon, but laser treatment is preferable in patients with widespread vaginal involvement.     

Large loop excision of the transformation zone (LLETZ) compared to carbon dioxide laser in the treatment of CIN: a superior mode of treatment

A series of 199 patients with histologically confirmed cervical intraepithelial neoplasia (CIN) grade II or III were allocated by hospital number to receive out-patient treatment by carbon dioxide laser vaporization or large loop excision of the transformation zone (LLETZ). All patients received local anaesthesia. The women in the LLETZ group experienced less post operative haemorrhage, less discomfort, operative time was greatly reduced, and histological material was available for confirmation of the diagnosis. There was no significant difference in recurrence of CIN after treatment between the two groups. At 6 month follow-up, recurrence rates of 8.2% (CIN II) and 7.5% (CIN III) were observed in the laser-group and 5% (CIN II) and 5.3% (CIN III) in the LLETZ group. Further advantages of LLETZ are reduced capital expenditure and no hazard to the eyesight of the surgeon, but laser treatment is preferable in patients with widespread vaginal involvement.     

Detection of residual disease by cytology in patients with cervical intraepithelial neoplasia III post-large loop excision of the transformation zone

OBJECTIVE: To evaluate the diagnostic accuracy of cytology in detecting residual disease in patients with cervical intraepithelial neoplasia (CIN) III post-large loop excision of the transformation zone (LLETZ). METHODS: This prospective study was performed between February 1994 and August 1999 at the Department of Obstetrics and Gynecology, Ramathibodi Hospital, and involved 90 patients who underwent LLETZ and had histologic confirmation of CIN III. Simple hysterectomy was performed in all patients 2-3 months after LLETZ. Two Papanicolaou smears were taken using Ayre spatula on each patient 6 weeks after LLETZ and 1 day before hysterectomy. Histologic findings of hysterectomy specimens were used as the 'gold standard'. RESULTS: Forty-six cases (51.1%) were found to have residual diseases: seven cases with CIN I, 11 cases with CIN II, 27 cases with CIN III and one case with invasive squamous cell carcinoma. Using the most severe diagnosis of two Papanicolaou smears performed on each patient as the cytologic diagnosis, the sensitivity, specificity, positive predictive value and negative predictive value were 28.3, 93.2, 81.3 and 55.4%, respectively. The accuracy rate was 60.0%. Residual diseases were found in 62.5 and 39.0% of cases with the presence and absence of CIN at the margin of the LLETZ specimen, respectively. CONCLUSION: Cytology using the Ayre spatula has low accuracy in detecting residual disease in the cervix post-LLETZ.     

The Use of Large Loop Excision of the Transformation Zone (LLETZ) in an Outpatient Setting

EDITORIAL COMMENT: We accepted this paper for publication because it presents a detailed analysis of the results from one centre of treatment of women with cervical intraepithelial neoplasia by large loop excision of the transformation zone. Importantly it provides a very careful review of the reported literature on the subject: the conclusions warrant special scrutiny.
Summary: An audit of the results of 129 patients treated in the first 12 months of operation of an outpatient large loop excision of the transformation zone (LLETZ) clinic was performed. It confirmed the efficacy of the procedure in treatment of cervical intraepithelial neoplasia (CIN) with a cure rate of 93.8%. Major deficiencies identified were the lack of compliance with recommended follow-up, a major discrepancy between predicted diagnosis on colposcopically directed punch biopsy and LLETZ specimen histology, and a large proportion of LLETZ specimens which had negative histology and may be regarded as overtreatment. Suggested strategies to address these include observation of low-grade lesions and treatment with LLETZ at the first clinic appointment.     

Large loop excision of the transformation zone (LLETZ) as an alternative to both local ablative and cone biopsy treatment: a series of 1000 patients

One thousand patients, referred to the Oxford Colposcopy Clinic, were treated with either large loop excision of the transformation zone (LLETZ, 891 cases) or LLETZ cone (109 cases). Forty-five LLETZ cones were performed empirically, 64 under microcolposcopic guidance. Over 98% of patients were managed as outpatients under local anaesthesia, and 87% of new patients treated with LLETZ had treatment at their first visit. Ninety percent of patients had at least cervical intraepithelial neoplasia grade one (CIN I) and 73% had CIN II or worse. Seventeen cases of invasive or possibly invasive disease were detected, 6 of them unsuspected. The overall rate of complete excision of CIN or worse was 72%. Follow-up was cytologic with or without colposcopy depending on lesion severity. Ninety-one percent of 967 treated patients were free of dyskaryosis at a mean follow-up of 23 months, with complete excision of CIN or worse at LLETZ a significant predictive factor. No cases of invasive carcinoma have developed following treatment. Major morbidity was uncommon, with 3.8% severe hemorrhage. Stenosis was noted in 3.8% cases, mostly after LLETZ cone. One patient (0.1%) has reduced fertility possibly attributable to LLETZ. Questionnaire assessment revealed a very high degree of acceptability of the treatment to patients. LLETZ and LLETZ cone have proved highly acceptable and effective outpatient diagnostic and treatment alternatives to both local ablation and cone biopsy in the Oxford Colposcopy Clinic.     

子宫颈LLETZ手术治疗CINⅢ的临床疗效分析

目的评价子宫颈移行区大环切除（LLETZ）手术治疗子宫颈上皮内瘤变（CIN）的临床疗效。方法回顾性分析我院2003年5月～2008年2月间阴道镜下多点活检诊断CINⅢ患者558例LLETZ手术治疗后的随访结果和临床疗效。结果CINⅢ组患者的平均年龄（34．72±7．27）岁，年龄≤35岁患者所占比例为61．8％。LLETZ手术后切缘CINⅡ／Ⅲ病灶残留率为4．8％，其中CINⅢ残留率为2．0％。LLETZ手术术前术后诊断符合率是72．2％，其中CINⅢ患者术后诊断Ⅰal期子宫颈癌58例，占10．4％。随访12～48个月，目前未见复发。结论LLETZ手术可用于诊断和治疗CINⅢ，但应严密随访，尤其是术后有残留患者。     

Colposcopy and microcolpohysteroscopy qualification for large loop excision of the transformation zone (LLETZ) in the management of cervical intraepithelial neoplasia.

OBJECTIVE: Large loop excision of the transformation zone is more and more often used as a treatment for cervical intraepithelial neoplasia. There is still debate as to whether this method should be performed in cases when the lesion extends into the cervical canal. Some colposcopists consider loop excision equal to cone biopsy, while others confine its application to satisfactory colposcopy findings. The purpose of the study was to compare the effectiveness and morbidity of LLETZ performed due to CIN in patients with and without extension of the lesion into the cervical canal. DESIGN: Prospective study of 143 women treated by LLETZ due to cervical intraepithelial neoplasia. METHODS: A series of 143 patients cytologically and colposcopically suspected of cervical intraepithelial neoplasia received outpatient treatment by large loop excision of the transformation zone (LLETZ). Microcolpohysteroscopy examinations of the cervix were performed on all patients. Depending on the involvement of the endocervix the material was divided into two groups. Group A comprised 83 women with a colposcopically visible upper margin of the lesion. Group B consisted of 60 patients with the lesion ranging in the endocervix, but not exceeding 10 mm from the external os. Chi square analyses of indication, morbidity and recurrence of the lesions in the two groups were done. Results were considered significant at p less than 0.05. RESULTS: Minimal thermal damage of excised tissue did not interfere with histological examination in either group. In 139 cases (97.20%) histology examination confirmed the presence of CIN. There were no significant differences between the two treatment groups with respect to mean age, mean parity and indications for LLETZ. The women in the group with an entirely visible lesion experienced less perioperative blood loss. There was no significant difference in secondary haemorrhage, infection, stenosis, incomplete excision of the lesion, visibility of neosquamocolumnar junction and residual disease between the two groups. CONCLUSIONS: On the basis of the results obtained it can be stated that LLETZ performed with colposcopic guidance complemented by microcolpohysteroscopy constitutes a valuable method in the treatment of CIN and it may in selected cases replace cone biopsy.     

Miniconization procedure with C-LETZ conization electrode for treatment of cervical intraepithelial neoplasia: a Swedish study

BACKGROUND: Since 1989 large loop excision of the transformation zone (LLETZ) has become the treatment of choice for cervical intraepithelial neoplasia in many colposcopy clinics. This method has limitations however, in that the resection margins of the cone produced by LLETZ cannot give conclusive histological reassurance, because of thermal injury in 5 30% of the specimens. Furthermore, LLETZ are often taken in several sections, which makes the histopathological examination unnecessarily difficult. As a new and single treatment without these limitations, conization with the contoured loop excision of the transformation zone (C-LETZ) electrode was investigated in the present study. Material and methods. One hundred and seventy-four patients with CIN were treated with the C-LETZ electrode during 12 months at the Gynaecological Department, Karolinska University Hospital, Huddinge. The inclusion criteria were a histological diagnosis of CIN II-III, or persistent CIN I. RESULTS: Eighty-six per cent of the patients had a complete excision according to histological findings, and 12% had an incomplete excision. The frequency of incomplete excisions increased with the severity of the CIN but were found in all groups of patients: 1 (3%) in CIN I, 5 (12%) in CIN II, and 12 (17%) in CIN III. The resection margins and histological diagnoses were certain in 98% of the cases. A cure rate of 90% was observed. Conclusions. Miniconization with the C-LETZ electrode makes it possible to individualize the size of the minicones and produce the minicones as one-piece specimens for histopathological assessment. Our findings confirm that this method is a reproducible, safe, and economical way to treat CIN with a low rate of morbidity in a hospital outpatient setting.     

Clinical applicability of immunotherapy of cervical intraepithelial neoplasia

Immunotherapy for cervical intraepithelial neoplasia (CIN) has not yet reached clinical applicability, but seems sensible and shows promising preliminary results. One of the most promising forms of immunotherapy for CIN may currently be imiquimod, because of its established role in other human papillomavirus (HPV)-induced genital conditions, its promising treatment efficacy in high-grade CIN, and its off-label availability. Although imiquimod cannot yet replace the current gold standard treatment for CIN [i.e., large loop excision of the transformation zone (LLETZ)] in all patients, it may be considered in subgroups of patients; for example, young women who may wish to become pregnant in the future, or patients with recurrent CIN lesions in whom a second LLETZ is to be avoided. Immunotherapy of CIN could be extended to post-treatment vaccination, in order to prevent new HPV infections and disease recurrence.     

Does histological incomplete excision of cervical intraepithelial neoplasia following large loop excision of transformation zone increase recurrence rates? A six year cytological follow up

Objective To determine the risk of recurrent cervical intraepithelial neoplasia (CIN) in women with complete or incomplete excision of cervical intraepithelial neoplasia treated by large loop excision of transformation zone (LLETZ).
Design A retrospective study
Setting One consultant-led colposcopy clinic at Leicester Royal Infirmary
Population Three hundred and ninety-four women referred consecutively to the colposcopy clinic between 1991 and 1992.
Main outcome measures The histological recurrence rate of CIN, length of cytological follow up following treatment related to degree of completeness of excision at initial treatment.
Results Three hundred and twenty-two women had complete cytological or histological follow up. The mean length of follow up was 73 months with a mean number of six smears. Women with incomplete excision of CIN had a significantly higher risk of recurrent CIN (relative risk 8.23) occurring in a significantly shorter time compared with women with complete excision.
Conclusions This study demonstrates that large loop excision of transformation zone is successful in over 95% of cases. Cytological surveillance is satisfactory for follow up of women who have complete excision of CIN. Women with incomplete excision of CIN at initial LLETZ remain at significant risk of developing further CIN and long term colposcopic and cytological follow up is necessary.     

Is large loop excision of the transformation zone (LLETZ) more accurate than colposcopically directed punch biopsy in the diagnosis of cervical intraepithelial neoplasia?

Summary. In 100 women with suspected cervical intraepithelial neoplasia (CIN) attending the colposcopy clinic the histological diagnoses made from excision biopsies taken by large loop excision of the transformation zone (LLETZ) were compared with those from colposcopically directed punch biopsies taken concurrently. One unsuspected micro-invasive tumour was found and the diagnosis made by LLETZ was significantly worse than that made by punch biopsy in 24 cases (24%: 95% CI15.6 to 32.4%). LLETZ improves the accuracy of diagnosis of CIN.     

Is large loop excision of the transformation zone (LLETZ) more accurate than colposcopically directed punch biopsy in the diagnosis of cervical intraepithelial neoplasia?

In 100 women with suspected cervical intraepithelial neoplasia (CIN) attending the colposcopy clinic the histological diagnoses made from excision biopsies taken by large loop excision of the transformation zone (LLETZ) were compared with those from colposcopically directed punch biopsies taken concurrently. One unsuspected microinvasive tumour was found and the diagnosis made by LLETZ was significantly worse than that made by punch biopsy in 24 cases (24%: 95% CI 15.6 to 32.4%). LLETZ improves the accuracy of diagnosis of CIN.     

Is involvement of the surgical margins of large loop excision of the cervical transformation zone specimens for cervical intraepithelial neoplasia III a risk factor for persistent cervical intraepithelial neoplasia?

We aimed to test the hypothesis that patients with cervical intraepithelial neoplasia (CIN) III treated by large loop excision of the cervical transformation zone (LLETZ) are more likely to suffer recurrence of cervical abnormalities if the CIN reaches the margins of the index specimen. Three hundred and forty-five women treated by LLETZ in 1991, and 1992, and in whom the histological diagnosis was CIN III, were studied. The reports were reviewed and the cases were categorised as completely excised, incompletely excised, or undetermined. Cytological follow-up, or in some cases histological follow-up in the same year and in each of the 5 following years was tabulated. Follow-up data were recorded from the same and also surrounding institutions. The chi-squared test was used to compare the differences in recurrence rates between the three groups at the various points in time. A small advantage was demonstrated for those cases where excision was complete. This was statistically significant in the third following year (P=0.022). The resection margin status of LLETZ specimens for CIN III has only a minor effect on the likelihood of recurrence. Nevertheless, recording the status may be important in case of unexpected invasion. The relative reassurance the information will provide when the lesion has been excised may also be seen as worthwhile.     

A review of the treatment failures following cervical intraepithelial neoplasia grade III treated by large loop excision of the transformation zone.

The records of 208 women were reviewed to quantify the long-term treatment failures of large loop excision of the transformation zone (LLETZ) in the treatment of cervical intraepithelial neoplasia (CIN) grade III. The rate of dyskariotic smears fell from 8% at 6 months to 2.3% at 48 months. The excision was considered incomplete in 84 cases (40.3%) of which 40 had endocervical margins involved. Thirty-five per cent of women with incomplete excision of CIN at the endocervical margin and 9% with complete excision had a dyskariotic smear within 4 years following LLETZ. These findings were statistically significant (P = 0.003 and 0.02 respectively). However, 5% only of women in the former group had cytological treatment failure at 6 months. There was no significant association between age and incidence of treatment failure. Further data are required to determine the risk of recurrence beyond 4 years before recommendations could be made about the duration of annual screening.     

Factors affecting outcome after incomplete excision of cervical intraepithelial neoplasia

PURPOSE: Conservative treatment for cervical intraepithelial neoplasia (CIN) by ablative or excisional techniques is widely used. However, women with incomplete excision have a variable risk of CIN recurrence. The aim of this study was to identify possible risk factors for recurrence of CIN after large loop excision of the transformation zone (LLETZ) with involved margins of excision. METHODS: All cases of women treated with LLETZ for CIN between 1989-2000, in whom histological evaluation of the excised specimen revealed extension of CIN to the excision margins, were retrospectively studied. A woman was considered to have recurrence when she had histologically confirmed CIN following a second LLETZ or hysterectomy during the follow-up period. The characteristics that were examined as possible risk factors were age, parity, smoking habit, grade of initial lesion and extension to the endo- or ectocervical margin. RESULTS: Treatment failure was diagnosed in 18 out of 65 (27.7%) women with involved margins. The only characteristic that reached statistical significance was age. The mean age of women with recurrence was 35.8 years, whereas the mean age of women without recurrence was 32.8 years (p = 0.044). Also, a trend was evident in women with high-grade initial lesions (CIN II-III) (p = 0.168) and involvement of the endocervical margins (p = 0.149). No differences were observed between the two groups regarding parity and smoking habit. CONCLUSIONS: Increased age is a risk factor for recurrence in women with incomplete excision of CIN after LLETZ. Larger studies are required for definite conclusions.     

Postoperative Symptoms Following LLETZ or Radical Cervical Diathermy with Fulgaration: A Randomized Double-Blinded Prospective Study

Fifty-five patients were randomized in a double-blinded manner to large loop excision of the transformation zone (LLETZ) (29 patients) or radical cervical diathermy with fulgaration (RCDF) (26 patients) for treatment of cervical intraepithelial neoplasia (CIN). Patients completed a 2-month diary of symptoms and completed a 10-week postoperative questionnaire. White vaginal discharge lasted 7.3 (4.6) days (SD) for RCDF compared to 3.4 (1.6) days (SD) for LLETZ. There was no significant difference in any other symptoms on analysis This appears to be the first report clearly assessing the length and severity of postoperative symptoms following LLETZ or RCDF. There is no reason on length and severity of postoperative symptoms to choose 1 of these 2 treatment methods over the other.     

Value and feasibility of LLETZ procedures for pregnant women with suspected high-grade squamous intraepithelial lesions and microinvasive cervical cancer

ObjectiveTo evaluate the efficacy, safety, and feasibility of large loop excision of the transformation zone (LLETZ) procedures during pregnancy.MethodsA retrospective study included 27 patients who underwent LLETZ during pregnancy for suspected high-grade squamous intraepithelial lesions (HSIL) where microinvasion could not be excluded. The study investigated intraoperative and postoperative complications, and compared preoperative and postoperative results. Questionnaires were used to obtain information about peripartum and postpartum data.ResultsThree (11.1%) women had invasive or microinvasive cancer, 22 (81.5%) had cervical intraepithelial neoplasia (CIN) 3, and 1 (3.7%) had CIN 2. Twenty-four were positive for high-risk human papillomavirus. All cervical cancers were classified as HSIL or CIN 3 before LLETZ. There were positive resection margins in 15 (55.6%) cases. No intraoperative complications occurred. One (3.7%) patient had a postoperative missed abortion. Major complications such as premature labor or cervical incompetence without influence on delivery occurred after LLETZ in 4 (14.8%) patients.ConclusionLLETZ during pregnancy can be performed if invasive cancer cannot be excluded by colposcopy, cytology, or biopsy. The procedure has a diagnostic intention but can also be a curative therapy in pregnancy, with low intraoperative, postoperative, and peripartum complication rates.     

Large loop excision and cold coagulation for management of cervical intraepithelial neoplasia

Objectives: To evaluate the efficacy of large loop excision of the transformation zone (LLETZ) combined with a single application of the cone probe of a Semm Cold Coagulator as a new treatment for women with cervical intraepithelial neoplasia (CIN). Methods: Retrospective case-record review of 666 women treated with large loop excision and cold coagulation (LLECC) from 1992 to 2000. Results: Of the women who had high-grade CIN at their initial consultation, 4.2% had abnormal cytologic results 6 months after treatment and 0.6% had abnormal cytologic results at 12 months. Of the women who had low-grade CIN at initial presentation, 3.8% had abnormal cytologic results 6 months after treatment and none (0%) at 12 months. Furthermore, there were no reported cases of cervical cancer in this cohort of women during the follow-up period. Short-term bleeding complications (within 24 h of the procedure) occurred in 1% of the women assessed. Conclusions: Large loop excision combined with cold coagulation is a new and effective treatment for CIN. Randomized controlled trials are required to confirm these findings and determine the long-term safety of the technique.     

The Use of Large Loop Excision of the Transformation Zone in Management Problems of Cervical Intraepithelial Neoplasia

Summary: We studied 2 groups of women whose management is controversial: those with cervical intraepithelial neoplasia (CIN) grade 2 or 3 on smear, but only CIN grade 1 or no abnormality on target biopsy (Group 1), and those with persistent CIN grade 1 on smear and up to CIN 1 on biopsy (Group 2). We set out to assess whether large loop excision of the transformation zone (LLETZ) was an acceptable method of treating these 2 groups of women. A review of 100 consecutive patients was undertaken. There were 71 women in Group 1 and 29 women in Group 2. The LLETZ procedures were performed under local analgesia and no immediate problems were encountered. Delayed haemorrhage requiring vaginal packing and admission to hospital occurred in 1 patient. In Group 1, histopathology of the LLETZ biopsies showed CIN 2 or 3 in 29 (40.8%) of the women, CIN 1 in 24 (33.8%) and no CIN in 18 (25.3%), and in Group 2, CIN 2 or 3 was seen in 5 (17.2%) of the women, CIN 1 in 11 (37.9%) and no CIN in 13 (44.8%). At 12 months completed follow-up, 4 patients in Group 1 had recurrent CIN 1 or equivocal CIN 1 and 1 patient from Group 2 had recurrent CIN 1, giving an overall recurrence rate of 5 of the 94 patients who completed follow-up (5%). We concluded that LLETZ was a useful procedure in both groups. In Group 1 the provision of a histological diagnosis on the LLETZ biopsy was a check on the accuracy of the cervical smear report. In Group 2, LLETZ offered the advantage of rapidly returning the smear to normal in most patients, and the diagnosis and treatment of those women who actually had a high-grade lesion.     

全子宫切除术后阴道上皮内瘤样病变治疗探讨

阴道上皮内瘤样病变（VAIN）是指局限于女性阴道上皮的癌前病变。目前研究认为感染人乳头瘤病毒（HPV）是VAIN发生的最主要因素,持续HPV感染是VAIN疾病进展的独立危险因素,VAIN患者常同时合并宫颈上皮内瘤变（CIN）,因液基薄层细胞检测（TCT）普及,筛查率提高,能对宫颈病变起到早期诊断并提高诊断率的作用。对于CIN2+抗病毒治疗及环形电极切除术（LEEP）治疗后病变持续存在或复发者,全子宫切除术成为一种治疗选择。因宫颈因素或者非宫颈因素行全子宫切除术后患者的VAIN受多种因素影响,如缺乏特异性临床症状,病灶特殊性、阴道结构的限制,术后解剖结构改变等可能导致延误诊治,且临床上尚无治疗全子宫切除术后VAIN的指南。综述全子宫切除术后VAIN的治疗进展。