Cervical regeneration after diathermy excision of cervical intraepithelial neoplasia as assessed by transvaginal sonography

doi:10.1016/S0301-2115(01)00574-7

European Journal of Obstetrics & Gynecology and Reproductive Biology

Volume 102, Issue 1, 10 April 2002, Pages 88-91

https://doi.org/10.1016/S0301-2115(01)00574-7 Get rights and content

Abstract

Objective: To evaluate regeneration in cervical craters following large loop excision of the transformation zone (LLETZ) and to investigate possible differential healing patterns depending on the cone’s size. Study design: A prospective study of 100 nulliparous women who underwent LLETZ. They underwent transvaginal scanning estimation of the cervical craters (diameter, depth) immediately post-operatively and at 3, 6 and 12 months. The crater dimensions of the women with the 25 largest cones were compared to those of the women with the 25 smallest cones in each of the above points of time. Results: The mean crater size of all women at 12 months was significantly smaller from the crater size immediately post-operatively. Although, there was a statistically significant difference in mean crater dimensions between the two quartile groups immediately post-operatively, no difference was found at 6 and 12 months. Conclusion: There is a healing process of the cervical crater, which is almost completed by the sixth post-treatment month. The defect remaining in the cervix is similar whether a large or small excision was performed.

Introduction

The incidence of cervical intraepithelial neoplasia (CIN) has increased in younger women over the past 20 years. Cold knife conization now has a rather limited use for the treatment of CIN because of the need for hospitalisation and general anaesthetic, as well as its effect on subsequent pregnancies due to cervical incompetence and cervical stenosis which may result in premature delivery and difficulties in labour [1], [2], [3].

Excisional outpatient methods, particularly diathermy loop conization are being increasingly used worldwide. One of the advantages of these methods is that they eradicate the preinvasive lesion with minimal cervical trauma, thus maintaining the potential for childbearing. Some recent controlled retrospective studies examining the possible complications in subsequent pregnancies following diathermy loop excision showed no adverse effect in subsequent pregnancies [4], [5]. These studies have not examined the volume of the removed specimen nor the interval between the operation and conception or delivery. In one retrospective study, the size of the cervical specimen was measured by a ruler immediately following the loop conization and larger diameter specimen were not associated with increased complications in subsequent pregnancies [6]. Other controlled studies however, report an increased incidence of preterm delivery in women who had undergone carbon dioxide laser conization [7], [8]. There is apparently some controversy over the subject of pregnancy complications, which has led many gynaecologists to very conservative loop excisions, and consequently to the high rates of incomplete excision reported [9], [10].

Since cervical shortening has been reported to be a significant risk factor for preterm delivery [11], [12], [13] the purpose of this prospective study was to investigate patterns of cervical regeneration in women who had undergone diathermy loop cervical conization, depending on the size of the excised tissue.

Section snippets

Materials and methods

The study population comprised 100 consecutive nulliparous women scheduled for large loop excision of the transformation zone (LLETZ) for CIN and who completed the entire follow up protocol. They gave written informed consent to undergo serial transvaginal ultrasound assessment of their cervix, before and immediately after the conization, as well as 3, 6 and 12 months post-operatively. None had had previous surgery to the cervix, while nine who defaulted from follow up, four who became pregnant

Results

The mean age of the women of the two groups did not differ significantly (group A: 28.2±3.2 S.D. years, group B: 27.6±4.1 years), (P=0.61 non-significant, t-test). There was no significant difference in lesion grade between the two groups (P=0.148 (ns), Fisher’s exact test). In group A the pathology report showed CIN 1 in 12 cases and CIN 2–3 in 13 cases, while in group B CIN 1 was found in 18 cases and CIN 2–3 in seven. In only one of the women of group A there was a histologic report of

Comment

Cervical shortening is associated with preterm labour [11], [12], [13]. Previous studies have however shown no adverse effects of LLETZ in general use on future fertility or pregnancy outcomes [4], [5], [6]. This study does not present data on pregnancy outcome after loop; it offers however a possible explanation for the results of the above mentioned studies, since it was concerned with the extent of regeneration of the cervix in nulliparous women undergoing routine LLETZ. It has shown that

Acknowledgements

The authors wish to thank Dr. A Kofinas for the critical evaluation and comments on this study.

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Terminology for cone dimensions after local conservative treatment for cervical intraepithelial neoplasia and early invasive cervical cancer: 2022 consensus recommendations from ESGO, EFC, IFCPC, and ESP
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Several approaches have been proposed for the measurement of cone volume. The volumetric fluid displacement technique is likely to represent the most accurate measurement (the gold standard), whereby the difference in fluid level before and after the immersion of a cone is recorded (Archimedes' principle; appendix p 6).15,17,36–42 When this technique is not feasible, researchers have used various formulas to calculate the volume of a cone from its dimensions.16,32,43–54
Local cervical treatment for squamous intraepithelial lesion (SIL) or cervical intraepithelial neoplasia (CIN) removes or ablates a cone-shaped or dome-shaped part of the cervix that contains abnormal cells. This Series paper introduces the 2022 terminology for cone dimensions after local conservative treatment for SIL, CIN, or early invasive cervical cancer. The terminology was prepared by the Nomenclature Committee of the European Society of Gynaecologic Oncology, the European Federation for Colposcopy, the International Federation of Cervical Pathology and Colposcopy, and the European Society of Pathology. Cone length should be tailored to the type of transformation zone. Treatment of SIL or CIN is associated with an increased risk of preterm birth, which escalates with increasing cone length. There is a lack of agreement regarding terms used to report excised specimen dimensions both intraoperatively and in the pathology laboratory. Consensus is needed to make studies addressing effectiveness and safety of SIL or CIN treatment comparable, and to facilitate their use to improve accuracy of antenatal surveillance and management. This Series paper summarises the current terminology through a review of existing literature, describes new terminology as agreed by a group of experts from international societies in the field of cervical cancer prevention and treatment, and recommends use of the new terminology that will facilitate communication between clinicians and foster more specific treatment guidelines that balance obstetrical harm against therapeutic effectiveness.
Does diffusion weighted imaging have a prognostic value in differentiating gynecological diseases?
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Cervical cancer is the second most common malignant tumor in females worldwide. Each year, approximately 450,000 new cases of cancer are detected, approximately 300,000 of which are fatal.3 According to some studies, the mean apparent diffusion coefficient (ADC) values of cervical cancer are lower than those of normal cervical tissue.4,5
Apparent diffusion coefficient (ADC) values are effective in the diagnosis of different gynecological lesions.
A retrospective evaluation was made of 12 patients with uterine cervix carcinoma and 151 patients with uterine lesions, comprising endometrial cancer, endometrial polyps, carcinosarcoma, submucous myoma, adenomyosis, endometrial hyperplasia, gestational trophoblastic neoplasm (GTN), and leiomyomas. As a control group, 20 healthy volunteers with normal endometrium and normal cervix were also evaluated. In three series, one-shot, spin echo, echo planar, b = 1000 s/mm² value and diffusion-weighted imaging (DWI) were applied to all subjects and ADC values were obtained.
The mean ADC values of Group 1 (Endometrial carcinoma) were lower than those of all the other groups (P < 0.001) and the mean ADC value of group 6 (GTN) was higher than that all other groups (P < 0.001). A statistically significant difference was found between the groups in terms of the lesion-myometrium ADC ratios (P < 0.001).
There are few studies in literature related to ADC measurements in GTN. The ADC values of GTN were found to be significantly higher than the other uterine lesions. These results will aid in the design of future studies and might be used to guide management of patients with GTN.
Diffusion-weighted MRI seems to be a promising imaging technique in differentiating different uterine lesions.
Morbidity after local excision of the transformation zone for cervical intra-epithelial neoplasia and early cervical cancer
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Tissue changes in the healed cervix that affects the tensile strength of the healed cervix, changes in the innate immune system and vaginal microenvironment may also be important [37]. In recent studies, only 28% of women having cervical treatment had a length of less than 25 mm, whilst there is evidence that the cervix regenerates after treatment [37–40]. However, overall the mid-trimester mean cervical length was shorter for women with previous cervical treatment [41].
The awareness that cervical intra-epithelial neoplasia (CIN) treatment increases the risk of preterm birth has led to major changes in clinical practice. Women with CIN have a higher baseline risk of prematurity but local treatment further increases this risk. The risk further increases with increasing cone length and multiplies for repeat excisions; it is unclear whether small cones confer any additional risk to CIN alone. There is no evidence to suggest that fertility is affected by local treatment, although this increases the risk of mid-trimester loss. Caution should prevail when deciding to treat women with CIN of reproductive age. If treatment is offered, this should be conducted effectively to optimise the clearance of disease and minimise the risk of recurrence. Colposcopists should alert women undergoing treatment that this may increase the risk of preterm birth and that they may be offered interventions when pregnant. The cone length should be clearly documented and used as a risk stratifier.
Influence of a loop electrosurgical excision procedure (LEEP) on levels of cytokines in cervical secretions
2015, Journal of Reproductive Immunology
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All subjects returned to the clinic six months later for follow-up and provided a post-healing cervical secretion sample. The follow-up period of six months was chosen because cervical tissue healing is complete within six months post-procedure (Paraskevaidis et al., 2002); additionally, the clinic schedules six-month follow-up appointments for LEEP patients. Eligible women were 18–38 years of age with regular menstrual cycles; were not pregnant and had not been pregnant in the past six months; had no previous cervical surgery, dilatation and curettage procedure, or abortive outcomes; and had no history of CIN, cancer, HIV/AIDS or autoimmune disease.
Over the past decade, there has been heightened interest in determining if there is an increased risk of adverse reproductive outcomes among women who had a loop electrosurgical excision procedure (LEEP) to remove cervical intraepithelial neoplasia (CIN). The objective of this exploratory study was to determine if the treatment of CIN with a LEEP is associated with changes in cervical soluble immune markers. Cervical cytokine concentrations were measured in women treated with LEEP and a control group of women who had colposcopy only and did not undergo LEEP. Cytokines were examined in cervical secretions collected in Merocel^® sponges at study entry and at 6-month follow-up. Cytokines were measured using a Luminex 18-plex cytokine bead assay. The mean cytokine levels were not significantly changed from baseline to follow-up in either group, with the exception of TNF-α, which decreased among women who underwent a LEEP. When the mean levels of cytokines of the treated and untreated groups at baseline or follow-up were compared, cytokine levels tended to be lower in the treated group (particularly IFN-γ, IL-6, IL-8, and MCP-1). Findings from adjusted repeated measures analyses revealed no differences between the two groups with regard to changes in cytokine levels over time. Overall, women undergoing a LEEP showed few changes in the cervical microenvironment relative to untreated women. Future studies with additional cervical environment markers and larger sample sizes are needed to determine if a LEEP is associated with dysregulation of the cervical microenvironment.
Proportion of cervical excision for cervical intraepithelial neoplasia as a predictor of pregnancy outcomes
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Although most obstetricians would think that this is attributable to a lack of mechanical support (“cervical incompetency”), other factors may be important. Changes in the composition and tensile strength of the healed regenerated tissue (composition and organization of collagen fibers) [20,21], in the normal cervical microflora, and in the immunologic milieu (altered cytokines) may lead to an impairment of the host defense mechanisms that prevent ascending infections. More recent evidence indicates that CIN itself increases the risk of adverse outcomes in women when pregnant [4,13,22,23].
To assess how the proportion of the cervical volume/length removed during treatment for cervical intraepithelial neoplasia (CIN) varies and whether this correlates to the pregnancy duration at delivery.
The present prospective observational study included 142 women undergoing CIN treatment at a university hospital during 2009–2013. The pretreatment and post-treatment cervical dimensions and cone size were measured with magnetic resonance imaging, three-dimensional transvaginal ultrasonography, or two-dimensional transvaginal ultrasonography, and the correlation between pregnancy outcomes and the relative proportion of the cervix excised was assessed.
Pretreatment cervical volumes and cone volumes varied substantially (range 11–40 cm³ and 0.6–8 cm³, respectively). The proportion of the volume excised ranged from 2.2% to 39.4%. Sixteen (11%) women conceived following treatment; 12 had a live birth (seven at term, three preterm). The pregnancy duration at delivery was significantly correlated with the proportion of the cervical volume (r = –0.9; P < 0.001) and length (r = –0.7; P = 0.01) excised and the cone volume (r = –0.6; P = 0.04).
The pretreatment cervical dimensions and the proportions of the volume/length excised vary substantially, and the latter correlates with the pregnancy duration. Assessment of the proportion excised might help to stratify women at risk who need intensive surveillance when pregnant.
Predictive value of volume of cervical tissue removed during LLETZ on subsequent preterm delivery: A cohort study
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A cut-off value of >14% of initial cervical volume was established at which point <75% of the tissue was regenerated and >25% deficit remained [18]. Time is an essential prerequisite for regeneration to occur with at least six months appearing to be the optimal time interval [19]. Whether delaying pregnancy influences the subsequent gestational age at delivery is unknown.
To evaluate the impact of volume of tissue removed during large loop excision of transformation zone on subsequent preterm birth rates.
A retrospective cohort study was carried out in a single, large tertiary referral unit in UK. A total of 556 women who delivered between January 2008 and December 2011 following a previous large loop excision of transformation zone procedure or punch biopsy were identified from the maternity and colposcopy databases. Demographic data, gestational age at delivery, birthweight, neonatal outcome and dimensions of excised cervical specimen were collected. Pregnancy outcomes for women who had a previous loop excision were compared to a matched control group who had undergone punch biopsies only.
There was a significant increase in preterm birth rate in the large loop excision group compared to the control group (9.0% vs. 3.6%, respectively, RR 2.5, 95% CI 1.224–5.107). Women who had undergone at least one previous loop excision had more than a threefold increased risk of spontaneous preterm birth compared with their matched controls. However, no relationship between volume or depth of cervical tissue excised and subsequent gestation at delivery could be demonstrated.
Whilst LLETZ is associated with an increased rate of preterm birth, the volume of tissue removed does not appear to influence the subsequent gestational age at delivery. This should reassure clinicians who should continue to perform LLETZ with adequate tissue margins to ensure complete resection of disease.

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Cervical regeneration after diathermy excision of cervical intraepithelial neoplasia as assessed by transvaginal sonography

Abstract

Introduction

Section snippets

Materials and methods

Results

Comment

Acknowledgements

Am. J. Obstet. Gynecol.

Obstet. Gynecol.

Obstet. Gynecol.

Int. J. Gynecol. Obstet.

Am. J. Obstet. Gynecol.

The 1993 British Society for Colposcopy and Cervical Pathology/National Coordinating Network United Kingdom Colposcopy Survey. Comparison with 1988 and the response to introduction of guidelines

Br. J. Obstet. Gynaecol.

Large loop conization for early invasive cervical cancer

Int. J. Gynecol. Cancer

The outcome of pregnancy after cone biopsy of the cervix: a case-control study

Br. J. Obstet. Gynecol.