Objective: To compare cone specimen size between loop electrosurgical excision procedure (LEEP) and cold knife cone (CKC), and evaluate the association between specimen size and margin status. Methods/materials: A retrospective review was performed of women with adenocarcinoma in situ (AIS) who underwent CKC or LEEP between 1998 and 2013. Specimen size, including length (distance from the external cervical os to the endocervical margin) and volume were compared between LEEP and CKC, and correlated with margin status. Results: Eighty-five patients underwent a total of 136 procedures, including 91 CKCs (67%) and 45 LEEPs (33%), with 27 removed as a single specimen (one-piece LEEP) and 18 as two specimens with an ectocervical specimen and a deeper endocervical tophat specimen (two-piece LEEP). The two-piece LEEP specimen median length was significantly longer (2.1 cm) versus CKC (1.4 cm, p<0.01) and one-piece LEEP (0.6 cm, p<0.01). Median specimen volume was greater for two-piece LEEP (7.4 cm3) versus CKC (3.4 cm3, p<0.01) and one-piece LEEP (1.6 cm3, p<0.01). A higher rate of positive margins was noted when comparing all LEEP (67.6%) with CKC specimens (34.2%), p<0.01. However, when the LEEP specimens were analysed separately, one-piece LEEPs had a higher rate of positive margins (81.0%) versus CKC (34.2%) (p<0.01), but there were no significant differences between two-piece LEEP (50.0%) and CKC (34.2%), p=0.26. Conclusion: Our results suggest that a two-piece LEEP produces a larger specimen size with similar rates of positive margins compared with CKC. Given the decreased cost and morbidity compared with CKC, a two-piece LEEP should be considered in the management of women with AIS.
Cervical adenocarcinoma in situ, AIS, cold knife cone (CKC), loop electrosurgical excision procedure (LEEP)
Mila Pontremoli Salcedo, Anthony Costales, Mark F Munsell, Preetha Ramalingam, Ricardo Dos Reis, Andrea Milbourne, Patrícia El Beitune and Kathleen M Schmeler have nothing to disclose in relation to this article. This research was supported in part by the National Institutes of Health through MD Anderson’s Cancer Center Support Grant CA016672. No funding was received for the publication of this article.
Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published.
This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit.
November 04, 2016 Accepted
February 10, 2017
Kathleen M Schmeler, Department of Gynecologic Oncology and Reproductive Medicine, Unit 1362, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. E: email@example.com
Cervical adenocarcinoma in situ (AIS) is recognised as a premalignant glandular condition and is a precursor to invasive cervical adenocarcinoma.1 It usually affects women of childbearing age in which a more conservative approach is preferred.1–3 The incidence of both AIS and adenocarcinoma of the cervix has been increasing, especially among young women.4,5 Cervical conisation, or cone biopsy, can be performed using a scalpel (cold knife cone [CKC]), laser, or electrosurgery (loop electrosurgical excision procedure [LEEP]). For patients with squamous dysplasia (cervical intraepithelial neoplasia [CIN]) there appears to be no difference in outcomes between techniques.6,7 However, it remains unclear if CKC is preferred over LEEP in patients with AIS. Studies have consistently shown that patients with AIS with a positive margin after an excisional procedure of the cervix are at significantly higher risk for residual disease.2,8,9 In addition, several studies have shown that a higher proportion of patients with AIS have negative margins if they undergo CKC versus LEEP.8,10,11 However, it remains unclear if this is due to a larger specimen being obtained when CKC is performed compared with LEEP.
For women who desire future fertility, conservative management with cervical conisation is considered a feasible option.1 However, the treatment can be challenging in women with AIS where the lesions are often located high in the endocervical canal, and may be multifocal. Repeat conisations are often required until negative margins are obtained.2 In addition, an unnecessarily large specimen is sometimes removed in an attempt to be certain of obtaining negative margins. These large and repeat cervical conisations are known to be associated with adverse obstetrical outcomes, including preterm delivery and low birth weight infants.12–14 It remains unclear if CKC should be performed over LEEP in patients with AIS in order to obtain negative margins. Furthermore, to date, there are limited data comparing specimen size between LEEP and CKC, and the correlation between specimen size and positive margins is largely unknown. The purpose of this study was to compare cone specimen size obtained using LEEP compared with CKC in patients with AIS. In addition, we sought to determine if there was any association between cone size and positive margins.
Materials and methods
We performed a retrospective cohort study at The University of Texas MD Anderson Cancer Center, of all women diagnosed with cervical AIS between 1998 and 2013. Institutional Review Board approval was obtained with a waiver of informed consent. Patients were identified using computerised databases from the Departments of Gynecologic Oncology and Pathology and were included if they had a diagnosis of AIS on cervical biopsy, cone specimen and/or hysterectomy and had undergone a CKC or LEEP. Patients with invasive disease and those without documentation of cone specimen size and/or margin status were excluded. All pathology slides were read by a gynecologic pathologist with expertise in cervical cancer and pre-invasive disease. Medical records were reviewed for demographic data, treatment history, pathologic findings, including the dimensions of the cone specimens and margin status, as well as outcomes. A positive margin was defined as AIS within 1 mm of the surgical margin. The follow-up period was defined as the time between initial AIS diagnosis and the date of last contact.
Descriptive statistics were used to summarise patient demographic and clinical characteristics. Specimen size, including length (distance from the external cervical os to the endocervical margin) and volume were compared between LEEP and CKC and correlated with margin status. The Wilcoxon test was used to compare medians between procedure types. Fisher’s exact test was used to compare distributions of categorical variables between procedure type, excluding “unknown” categories. Study data were collected and managed using Research Electronic Data Capture (REDCap) tools hosted at MD Anderson.15
1. Dunton C, Management of atypical glandular cells and adenocarcinoma in situ,Obstet Gynecol Clin North Am, 2008;35:623–32.
2. Salani R, Puri I, Bristow RE, Adenocarcioma in situ of the uterine cervix: a metaanalysis of 1278 patients evaluating the predictive value of conization margin status, Am J Obstet Gynecol, 2009;200:182.e1–182e5.
3. Polterauer S, Reinthaller A, Horvat R, et al., Cervical adenocarcinoma in situ: update and management,Curr Obstet Gynecol Rep, 2013;2:86–93.
4. Wang SS, Sherman ME, Hildesheim A, et al., Cervical adenocarcinoma and squamous cell carcinoma incidence trends among white women and black women in the United States for 1976–2000, Cancer, 2004;100:1035–44.
5. Sherman ME, Wang SS, Carreon J, et al., Mortality trends for cervical squamous and adenocarcinoma in the United States. Relation to incidence and survival, Cancer, 2005;103:1258–64.
6. Mathevet P, Chemali E, Roy M, et al., Long-term outcome of a randomized study comparing three techniques of conization: cold knife, laser, and LEEP, Eur J Obstet Gynecol Reprod Biol, 2003;106:214–218.
7. Martin-Hirsch PP, Paraskevaidis E, Bryant A, et al., Surgery for cervical intraepithelial neoplasia. Cochrane Database Syst Rev, 2013;CD001318.
8. Wolf JK, Levenback C, Malpica A, et al., Adenocarcinoma in situ of the cervix: significance of cone biopsy margins, Obstet Gynecol, 1996;88:82–6.
9. Young JL, Jazaeri AA, Lachance JA, et al., Cervical adenocarcinoma in situ: the predictive value of conization margin status, Am J Obstet Gynecol, 2007;197:195 e1–7.
10. Azodi M, Chambers SK, Rutherford TJ, et al., Adenocarcinoma in situ of the cervix: management and outcome, Gynecol Oncol, 1999;73:348–53.
11. Costales A, Milbourne A, Rhodes H, et al., Risk of residual disease and invasive carcinoma in women treated for adenocarcinoma in situ of the cervix, Gynecol Oncol, 2013;129:513–6.
12. Kyrgiou M, Koliopoulos G, Martin-Hirsch P, et al., Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and metaanalysis, Lancet, 2006;367:489–98.
13. Arbyn M, Kyrgiou M, Simoens C, et al., Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: meta-analysis, BMJ, 2008;337:a1284.
14. Albrechtsen S, Rasmussen S, Thoresen S, et al. Pregnancy outcome in women before and after cervical conisation: population based cohort study, BMJ, 2008;337:a1343.
15. Harris PA, Taylor R, Thielke R, et al., Research electronic data capture (REDCap) - A metadata-driven methodology and workflow process for providing translational research informatics support, J Biomed Inform, 2009;42:377–81.
16. Baalbergen A & Helmerhorst TJM, Adenocarcinoma in Situ of the Uterine Cervix - A Systematic Review, Int J Gynecol Cancer, 2014;24:1543–8.
17. Kennedy AW, Biscotti CV, Further study of the management of cervical adenocarcinoma in situ, Gynecol Oncol, 2002;86:361–4.
18. Milinovic D, Kalafatic D, Babic D, et al., Minimally invasive therapy of cervical intraepithelial neoplasia for fertility preservation, Pathol Oncol Res, 2009;15:521–5.
19. Kliemann LM, Silva M, Reinheimer M, et al., Minimal cold knife conization height for high-grade cervical squamous intraepithelial lesion treatment, Eur J Obstet Gynecol Reprod Biol, 2012;165:342–6.
20. Papoutsis D, Rodolakis A, Antonakou A, et al., Cervical cone measurements and residual disease in LLETZ conisation for cervical intraepithelial neoplasia, In Vivo, 2011;25:691–5.
21. Castanon A, Brocklehurst P, Evans H, et al., Risk of preterm birth after treatment for cervical intraepithelial neoplasia among women attending colposcopy in England: retrospectiveprospective cohort study, BMJ, 2012;345:e5174.
22. Berreta R, Gizzo S, Dall’Asta A, et al. Risk of preterm delivery associated with prior treatment of cervical precancerous lesion according to the depth of the cone, Dis Markers, 2013;35:721–6.
23. Munro A, Leung Y, Spilsbury K, et al., Comparison of cold knife cone biopsy and loop electrosurgical excision procedure in the management of cervical adenocarcinoma in situ: What is the gold standard?, Gynecol Oncol, 2015;137:258–63.
Cervical adenocarcinoma in situ, AIS, cold knife cone (CKC), loop electrosurgical excision procedure (LEEP)