European Journal of Obstetrics & Gynecology and Reproductive Biology 151 (2010) 91–95
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A pilot study comparing efficacy of a cervical intraepithelial neoplasia excisor with loop electrosurgical excision procedure§ Olaleye Sanu a,*, Alak Pal b, Samuel George b a b
Department of Obstetrics and Gynaecology, St Marys Imperial College NHS Trust, London W2, United Kingdom Department of Obstetrics and Gynaecology, Colposcopy Services, Ealing Hospital, NHS Trust, Uxbridge Road, Southall, Middlesex, UB1 3HW, United Kingdom
A R T I C L E I N F O
A B S T R A C T
Article history: Received 17 October 2009 Received in revised form 18 January 2010 Accepted 21 February 2010
Objective: To determine whether the proportion of incomplete resection of cervical intraepithelial neoplasia (CIN 1–3) may be reduced by CIN Excisor compared with loop excision of the transformation zone (LLETZ). Study design: A prospective trial during a 2-year period at a district general hospital in London, United Kingdom, including 420 women scheduled for treatment due to CIN, after colposcopy guided biopsy results. This study was expected to demonstrate a statistically significant difference (p < 0.05) in the proportion of women with clear histopathological resection margins after treatment with CIN Excisor compared with LLETZ. Chi-square or Fisher’s exact test were used to compare histopathological resection margins in the CIN Excisor and LLETZ groups. Results: Overall, there is strong evidence of a difference in the proportion of histopathological specimens with clear resection margins for the CIN Excisor group, compared with the LLETZ group (201/210, 95.7% versus 180/210, 85.7%: p < 0.001). Sub-analysis within the two groups, of the proportion of histopathological specimens with clear resection margins in relation to CIN grades, revealed a statistically significant difference in favour of the CIN Excisor group for CIN 1 (99/103, 96.1% versus 82/ 95, 86.3%: p = 0.01), and CIN 2 (73/77, 94.8% versus 68/80, 85%: p = 0.04). There is a numerical difference in the proportion of clear resection margins in favour of the CIN Excisor for CIN 3 (29/30, 96.7% versus 30/ 35, 85.7%), but this difference was not statistically significant (p = 0.21). Perioperative complications were similar between the two groups. Conclusion: CIN Excisor achieved better results than LLETZ for treatment of CIN 1–3 with respect to clear histopathological resection margins. However, further studies including a larger number of women treated for CIN 3 are needed before firm conclusions are drawn. ß 2010 Elsevier Ireland Ltd. All rights reserved.
Keyword: Pilot trial of CIN Excisor
1. Introduction The loop electrosurgical excision procedure of the transformation zone (LLETZ) is well established for the treatment and diagnosis of cervical intraepithelial neoplasia [1]. When colposcopy evaluation is considered satisfactory, and invasive disease is not suspected, LLETZ can be performed in an outpatient setting under local anaesthesia [2]. Histopathological evaluation of the cervical specimens is adequate in over 90% of cases [3]. Women with involved margins, endocervical gland involvement, multiple quadrant disease, and high grade dysplasia are at increased risk of recurrence [4–7]. Age over 40 years and above has also been
§ Source: Ealing Hospital NHS Trust, Uxbridge Road, Southall, Middlesex UB1 3HW, United Kingdom. * Corresponding author. Fax: +44 2084207466. E-mail address:
[email protected] (O. Sanu).
0301-2115/$ – see front matter ß 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2010.02.042
described as a predictor of recurrence [8]. The United Kingdom National Health Service Cervical Screening Programme (NHSCSP) recommends that the proportion of confirmed histological failures should not exceed 5% within 12 months of treatment [9]. Minimising numbers of histopathological specimens reported with incomplete excision may have a positive influence on the number of women, with residual cervical dysplasia following treatment. We performed a pilot study comparing the efficacy of CIN Excisor with the LLETZ. We hypothesized that there would be a statistically significant difference in the proportion of histopathological specimens removed, with clear resection margins at the ecto- and endocervical margins following excisional biopsy for cervical intraepithelial dysplasia (CIN 1–3) in favour of CIN Excisor. 2. Materials and methods This study is a prospective trial involving women between 20 and 60 years old with confirmed cervical intraepithelial dysplasia
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O. Sanu et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 151 (2010) 91–95
Diagram 1. Showing a CIN Excisor in different lengths, shapes and widths.
Fig. 1. A picture of CIN Excisor.
1–3 (CIN 1–3) following colposcopy guided cervical punch biopsy results between January 2006 and April 2008. These women required treatment in accordance with the National Health Service Cervical Screening Programme [9]. It is the policy of our hospital to follow-up women after treatment at 6 months, and yearly for up to 5 years for the detection of recurrent cervical dysplasia and other complications related to excisional procedures [9]. Inclusion criteria were: (i) persistent CIN 1, (ii) CIN 2, and (iii) no previous treatment for CIN. Exclusion criteria were: (i) cervical glandular intraepithelial neoplasia (CGIN), (iii) microinvasive and invasive disease, and (iii) previous treatment for CIN. Written, informed consent was obtained from all women, and the Local Research Ethics Committee approved the study (Ealing & WLMHT Local Research Ethics (REC) Committee, REC Reference number: 05/Q410/91). CIN Excisor is made of an insulated metal shaft which houses an expansion spring mechanism. The expansion spring mechanism enables the fully flexible excision wires (twin boom) to retract to a tight tension whenever they are extended to a maximum diameter of 50 mm or retracted to a minimum of 20 mm, to suit the size of the lesion to be treated (Fig. 1 and Diagram 1). CIN Excisor engages the cervical canal, with adjustable depth precision, to a maximum of 25 mm, and cutting is performed by a rotational wrist movement. The twin boom has the advantage of minimising the degree of wrist rotation by the surgeon to 180 degrees, as opposed
to 360-degree wrist rotation, which may be more difficult [10]. It is an adjustable single device, which is preset to mirror image the lesion to be excised in width and depth. A centralised cone prevents deviation of the shaft from the centre during rotation. An electrosurgical generator, set in blend mode (cut/coagulation), with outputs varying between 30 and 50 W was employed initially, for both LLETZ and CIN Excisor. Activation of the generator during excision of a cervical lesion with CIN can be achieved by pressing a button on the handheld lead. Surgeons involved in the study, however, observed that the activation of the generator by a foot pedal makes wrist rotation much easier, as pressing on the handheld button while rotating the wrist is more difficult and therefore should be avoided. Power output interruption was experienced with use of CIN Excisor in early stages of the trial. This was due to a spring mechanism being of variable strength, which affected the tension of the twin boom. As a result, a dragging sensation was experienced during the excision process with the interruption of the power output. These difficulties were overcome by raising the power wattage to blend 50/50. The manufacturer of CIN Excisor corrected the problem. Subsequently, performance of the device was consistent when a standard strength spring was used. Numbers one to five hundred (1–500) were written on small plain folded papers and concealed in a box, and each patient was asked to pick one paper from the box. The patients who chose even numbers were allocated to receive treatment with CIN Excisor, and those with odd numbers were allocated to receive treatment with LLETZ, using a 15, 18, or 22 mm tungsten diathermy loop. Allocation of patients was coordinated by the colposcopy nurse. Surgeons were not involved with the allocation of patients. Treatment was performed by three colposcopists in the colposcopy clinic at a district general hospital. The three colposcopists, one of whom designed the CIN Excisor, were familiar with using either CIN Excisor or LLETZ. Potential bias introduced by any individual surgeon, in terms of the proportion of women with clear resection margins following treatment with CIN Excisor or LLETZ, was investigated. A schematic representation of size of lesion treated was usually recorded in patient’s notes. Duration of procedure and any perioperative complications such as bleeding requiring additional measures (e.g. cervical suture) were recorded. A linear scale (1–10) was used to document operative pain. Difficulties with use of LLETZ or CIN Excisor were recorded as no difficulty, mild, moderate or severe difficulty. Women involved in the trial were followed up to determine the
O. Sanu et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 151 (2010) 91–95
proportions of patients who required hospital admission due to primary or delayed significant bleeding, upper and lower genital tract infections, and cervical stenosis. The histopathological specimens obtained by the new device are usually in two halves. It is not uncommon that multiple specimens are obtained when using LLETZ to obtain histopathological specimens. In view of potential bias, histopathologists were not informed of the pilot study. Histopathological specimens were measured and their dimensions were documented. The dimensions of specimens obtained using the new device were compared to those obtained with LLETZ. It is mandatory in our hospital to discuss all cases of excision treatment at a multidisciplinary team meeting involving histopathologists when resection margins are uninterpretable. Proportions of histopathological specimens with uninterpretable resection margins were compared between the two groups. The main outcome measure is defined as the difference in the proportion of women with clear histopathological margins (ectocervical and endocervical) for the CIN Excisor compared with the LLETZ groups. The outcome analysis was based on the total number of patients with confirmed CIN 1–3 after excision treatment. Proportions were compared using the Chi-squared analysis, and Fisher’s exact test when appropriate.
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Table 2 The proportion (%)* of complete resection margins in relation to CIN grades and comparison between the two techniques. CIN grades
CIN Excisor
LLETZ
p
z
99 (96) 73 (95) 29 (97) 201(96)
82 (86) 68(85) 30 (86) 180 (86)
0.01 0.04 0.21
