Academic Editors: Stefano Cianci and Michael H. Dahan
Background: Prompt detection and treatment of high-grade cervical intraepithelial neoplasia (CIN), namely, CIN3, are important for preventing malignant transformation. In most cases, such treatment is performed through conization, but minimally invasive procedures must also be considered. Therefore, we present a surgical method using a combination of monopolar electrosurgical conization (MESC) and oxidized regenerated cellulose-based haemostat (ORCH) (Surgicel®) and discuss its merits and risk factors. Methods: The medical records of 274 patients treated at our hospital from January 1, 2015, to December 31, 2021, were retrospectively reviewed. To detect risk factors for postoperative problems, we considered 2 indicators: postoperative recurrence and haemostatic suture for severe postoperative bleeding. We also focused on the following 10 representative factors for predicting significant risk for postoperative problems: (1) advanced age, (2) high BMI, (3) nulliparity, (4) smoking history, (5) long operation time, (6) intraoperative suture, (7) positive margin, (8) invasive squamous cell carcinoma (SCC), (9) no dysplasia, and (10) cervical glandular neoplasia (CGN). Results: Among the 274 patients, 19 instances of postoperative recurrence and 8 instances of haemostatic suture were detected. In a multivariate analysis of the 10 factors, we detected no significant impact except for “no dysplasia” on both indicators. This result indicated that our method had no specific risk and could provide a certain extent of usability. Conclusions: The combination of MESC and ORCH for the treatment of CIN3 could be performed effectively and safely with minimal intraoperative haemostatic suturing of the cut surface.
Because untreated high-grade cervical intraepithelial neoplasia (CIN), namely, CIN3, has a cumulative incidence of transitioning to invasive cervical cancer of over 30% at the age of 30 years [1], prompt detection is important. In Japan, over 13,000 cases of CIN3 are reported to the Japan Society of Obstetrics and Gynaecology annually [2]. These cases are mostly detected by cytology screening and cervical biopsy. On the other hand, because cancer risk at 30 years can be decreased to less than 1% with adequate treatment [1], surgical treatment methods for CIN3, including cold knife conization (CKC), monopolar electrosurgical conization (MESC), laser conization and loop electrosurgical excision procedure (LEEP), have been improved. Additionally, because the incidence of CIN3 among reproductive-aged women (aged approximately 35 to 45 years) has increased in Japan [3, 4], we have focused on not just the treatment effects—that is, the prevention of recurrence and positive resection margins—but also on the use of minimally invasive procedures. Among these representative operation methods, at our hospital, a simple MESC method is adopted. In this method, electrocoagulation and suturing of the cone bed are performed if needed to achieve homeostasis. Since the use of these procedures must be minimized to reduce the risk of cervical stenosis, we use oxidized regenerated cellulose haemostat (ORCH) (Surgicel®) to control bleeding from the cone bed. This tool can allow a relatively easy haemostatic procedure; however, it may also increase the risk of postoperative rebleeding. Therefore, in this study, we will introduce the merit of ORCH and simultaneously analyse all cases in our hospital. We elucidated factors that predicted the possibility of postoperative problems, in addition to the recurrence rate, which is generally regarded as important.
This study was reviewed and approved by the Human Ethical Committee of the
University of Teikyo Hospital (trial registration number: 20-054-2). The
deidentified medical records of 274 female patients who underwent MESC from
January 1, 2015, to December 31, 2021, were reviewed retrospectively. To prevent
postoperative bleeding, in all patients, we performed the following 3 procedures:
(1) electrocoagulation of the cone bed by a monopolar electrosurgical device,
appropriately adding suturing; (2) SURGICEL Absorbable Haemostat®
(Johnson & Johnson K.K., Tokyo, Japan), a cotton-like ORCH, was attached to the
cut surface just before the end of surgery; and (3) an intravenous administration
of 1000 mg of tranexamic acid was given after surgery. Among these procedures, we
mainly focused on Surgicel®, which is a cotton-like collagen. We
decomposed one agent (2.5 cm
To identify risk factors predictive of postoperative problems, including
recurrence and abnormal bleeding, we assessed the influence of the following ten
factors: (1) patient characteristics, including advanced age (
Basic patient characteristics are shown in Table 1. The average patient age,
BMI, parity, operation time and intraoperative bleeding were 39.6
Patient characteristics | Avg. |
Total number | n = 274 |
Age (years) | 39.6 |
BMI (kg/m |
21.3 |
Parity | 1.0 |
Nulliparity | n = 129 |
Smoking history | n = 50 |
Operation time (minutes) | 20.1 |
Operative bleeding (mL) | 4.9 |
Intraoperative suture | n = 62 |
Positive margin | n = 22 |
Postoperative recurrence | n = 19 |
Emergency room visit | n = 29 |
Haemostatic suture | n = 8 |
Emergency hospitalization | n = 6 |
Representative patient characteristics obtained from medical records are
summarized in this table. For each item, we calculated averages and standard
deviations, minimal and maximal values, and count data from medical records. Abbreviations: Avg., Average; BMI, Body mass index; Min., Minimum; Max., Maximum; SD, Standard deviation. |
Preoperative pathology | Postoperative pathology | ||||
Cytology | Histology | Definitive diagnosis | |||
HSIL | n = 196 | CIN 1 | n = 1 | CIN 1 | n = 3 |
LSIL | n = 8 | CIN 2 | n = 22 | CIN 2 | n = 14 |
ASC-H | n = 23 | CIN 3 | n = 232 | CIN 3 | n = 198 |
SCC | n = 7 | Carcinoma s/o | n = 19 | CIN3/AIS | n = 5 |
ASC-US | n = 17 | AIS | n = 7 | ||
AGC | n = 2 | Invasive SCC | n = 13 | ||
AGC/HSIL | n = 11 | No dysplasia | n = 22 | ||
AGC/ASC-H | n = 6 | Dysplasia NOS | n = 12 | ||
AIS | n = 1 | ||||
Adenocarcinoma | n = 3 | ||||
For all patients, we performed cytological and histological examinations before
surgery and histological examinations after surgery. The pathological findings
detected before and after conization are summarized in this table. Cases that
included two categories, for example, AGC/HSIL, were defined as cases in which
two different types of cells or tissues were detected simultaneously on
pathological examination. Abbreviations: AGC, Atypical glandular cells; AIS, Adenocarcinoma in situ; ASC-H, Atypical squamous cells; ASC-US, Atypical squamous cells of undetermined significance; CIN, Cervical intraepithelial neoplasia; HSIL, High-grade squamous intraepithelial lesion; LSIL, Low-grade squamous intraepithelial lesion; NOS, Not otherwise specified; SCC, Squamous cell carcinoma; s/o, Suspected of. |
Case number | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 |
Age (years old) | 34 | 36 | 49 | 46 | 35 | 46 | 34 | 34 |
Parity | 2 | 2 | 2 | 0 | 0 | 2 | 2 | 1 |
BMI (kg/m |
18.8 | 17.9 | 18.5 | 23.4 | 20.5 | 19.3 | 18.2 | 17.3 |
Smoking history | No | No | No | No | No | Yes | No | No |
Operation time (minutes) | 28 | 16 | 15 | 23 | 13 | 21 | 18 | 16 |
Bleeding (mL) | 0 | 0 | 20 | 0 | 0 | 25 | 0 | 0 |
Intraoperative suture | Yes | No | Yes | No | No | No | Yes | Yes |
Cytology (*1) | HSIL | HSIL | HSIL | HSIL | HSIL | HSIL | HSIL | HSIL |
Histology (*2) | CIN 2 | CIN 2 | CIN 3 | CIN 3 | CIN 3 | CIN 3 | CIN 2 | CIN 3 |
Definitive diagnosis (*3) | CIN 2 | HSIL | CIN 3 | No dysplasia | CIN3 | CIN3 | No dysplasia | CIN 3 |
Surgical margin | Negative | Negative | Positive | Negative | Positive | Negative | Negative | Negative |
POD (*4) | 16 | 8 | 12 | 14 | 14 | 11 | 9 | 9 |
Treatment period (*5) | 3 | 1 | 4 | 1 | 2 | 2 | 3 | 2 |
Hospitalization period | 0 | 0 | 4 | 0 | 0 | 2 | 2 | 2 |
Number of suture location | 1 | 1 | 4 (*6) | 1 | 3 | 3 | NA | 2 |
Hb decrease (g/dL) | 13.7 to 9.6 | NA | 14.3 to 7.3 | 12.9 to 9.9 | NA | 11.4 to 10.4 | NA | 10.2 to 7.3 |
The characteristics of eight patients with haemostatic sutures are shown in this
table. *1: This index shows the result of cytological examination before surgery. *2: This index shows the result of histological examination before surgery. *3: This index shows the result of histological examination after surgery. *4: This index shows the day the patient visited the emergency room for postoperative rebleeding. *5: This index shows the total number of days at the hospital for the treatment of postoperative rebleeding, including the hospitalization period. *6: In this case, we performed haemostatic sutures in the 4–5, 5–6, 8–9, and 6–7 o’clock positions of the cone bed under general anaesthesia in the operating room. Abbreviations: BMI, Body mass index; CIN, Cervical intraepithelial neoplasia; Hb, Haemoglobin; HSIL, High-grade squamous intraepithelial lesion; POD, Postoperative day. |
To confirm the effectiveness of our treatment method, we examined 19 cases of
recurrence diagnosed by follow-up cytological tests, including 8 cases of
atypical squamous cells of undetermined significance (ASC-US), 2 cases of
atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion
(ASC-H), 6 cases of low-grade squamous intraepithelial lesion (LSIL), and 3 cases
of high-grade squamous intraepithelial lesion (HSIL). Among these 19 cases, the
definitive diagnosis after conisation included 14 cases of CIN3, one case of AIS,
and 4 cases of no dysplasia. The average time between conization and recurrence
was 304.2
To detect factors that significantly affected the frequency of postoperative problems, the aforementioned 10 factors were compared using multivariate analysis (Table 4). Significant impacts of no dysplasia on haemostatic suture, smoking history and no dysplasia on postoperative recurrence were detected. Although the following combination of factor and indicator did not show a significant impact, intraoperative suture showed a trend towards a higher possibility of postoperative recurrence (p = 0.08). These results indicate the possibility that our method had no specific risk and could provide a certain extent of usability.
Factors | Haemostatic suture | Postoperative recurrence | ||
OR (95% CI, Number) | p value | OR (95% CI, Number) | p value | |
No dysplasia (n = 22) | 4.1 (0.8–21.6, n = 2/8) | 0.04 | 3.5 (1.1–11.7, n = 4/19) | 0.027 |
CGN (n = 30) | NA (NA, n = 0/8) | 0.4 | 0.4 (0.1–3.4, n = 1/19) | 0.5 |
Positive margin (n = 22) | 1.7 (0.2–14.2, n = 1/8) | 0.42 | 1.4 (0.3–6.4, n = 2/19) | 0.22 |
Intraoperative suture (n = 62) | 2.1 (0.5–9.1, n = 3/8) | 0.28 | 2.1 (0.8–5.6, n = 7/19) | 0.055 |
Invasive SCC (n = 13) | NA (NA, n = 0/8) | 0.65 | NA (NA, n = 0/19) | 0.39 |
Smoking history (n = 50) | 0.6 (0.1–5.3, n = 1/8) | 0.72 | 3.7 (1.4–9.7, n = 8/19) | 0.0048 |
High BMI (n = 31) | NA (NA, n = 0/8) | 0.41 | 0.4 (0.1–3.2, n = 1/19) | 0.31 |
Nulliparity (n = 129) | 0.4 (0.1–1.8, n = 2/8) | 0.19 | 0.4 (0.1–1.1, n = 5/19) | 0.1 |
Advanced age (n = 33) | NA (NA, n = 0/8) | 0.23 | 1.4 (0.4–5.1, n = 3/19) | 0.84 |
Long operation time (n = 19) | NA (NA, n = 0/8) | 0.36 | NA (NA, n = 0/19) | 0.17 |
A multivariate analysis of 274 patients with MESC was performed to examine the
influence of 10 representative factors that were collected from medical records.
The number of patients with each factor, the ORs and 95% CIs for the occurrence
of surgical complications and the p-values are shown in this table. Abbreviations: BMI, Body mass index; CGN, Cervical glandular neoplasia; CI, Confidence interval; NA, Not available; OR, Odds ratio; SCC, Squamous cell carcinoma. |
Conization of the cervix is a standard conservative treatment for patients with high-grade CIN to prevent progression to invasive cancer and preserve fertility. It is also an efficient diagnostic method for suspicious invasive carcinomas. Recently, various surgical methods, such as electrocautery, cryotherapy, laser ablation, CKC, MESC, and LEEP, have been applied [4]. At our hospital, MESC is used as a basic treatment and diagnostic method for cervical lesions because it is regarded as an acceptable alternative to CKC [5, 6] and does not need specific tools such as those required for LEEP [7, 8]. Additionally, since there is some evidence that haemostatic suturing has an adverse effect on blood loss, cervical stenosis and satisfactory colposcopy [9], we also tried to develop a new technique to treat intraoperative bleeding with minimizing suturing of the cone bed. In this process, by referring to some reports that identified the haemostatic effects of electrocoagulation and haemostatic agents [10, 11], such as a fibrin sealant patch [12] or chitosan tampon [13], we used ORCH (Surgicel®) just before finishing the operation to minimize the use of haemostatic electrocoagulation and suturing. However, when haemostatic sutures are needed, cases might be regarded as difficult. Since, to the best of our knowledge, the application of combined of haemostatic electrocoagulation and ORCH during conization has not yet been published, we aimed to present the merits and risk of this procedure for the first time.
Compared with some previous large studies, the recurrence rate was approximately 6.9%. This result seemed superficially high, and there was the possibility that this technique showed a slightly poor treatment effect, although the possibility of involvement of positive surgical margins was relatively low [5, 6, 14]. However, since only one patient was diagnosed with CIN2, which might represent a very low recurrence rate compared to some past studies [15, 16], our procedure might show a sufficient treatment effect. On the other hand, one weakness of this technique was detected; namely, the frequency of postoperative rebleeding was slightly higher than that reported in some past studies [5, 6]. Therefore, the risks of this technique need to be evaluated in a multivariate analysis of several representative factors, however, one limitation was that we could not set the control group, since we used this technique for all patients and could not collaborate with colleagues at different hospitals. The main role of our hospital was daily clinical activities themselves. We could not clearly indicate the efficacy of ORCH as a haemostatic agent, and room for improving this technique remains. We also had the other limitation that we could not collect information on various factors, and the analysis for the two postoperative complications showed similarity. However, the most meaningful results of this analysis (Table 4) were the trends in the impact of intraoperative suture and no dysplasia on at least one of 2 indicators, including haemostatic suture and postoperative recurrence. These tendencies could be interpreted as indicative of atypical and difficult surgeries that might increase the possibility of postoperative problems, although long operation time, invasive SCC and CGN did not show differences in impact. Unlike some past studies [17, 18], we also found that smoking history had a significant impact on postoperative recurrence. These results that our procedures are sufficiently safe. Since our procedure does not require special equipment, the combination of MESC and ORCH could be regarded as an efficient treatment method for high-grade CIN.
By identifying risk factors for postoperative problems, the combination of MESC and ORCH for the treatment of high-grade CIN could be performed effectively and safely while minimizing intraoperative haemostatic suturing of the cut surface.
WI collected and analysed the data and wrote the manuscript. AT and ON supervised the whole study. AT, AO, MH, AS, RM and HT performed medical care on the subjects. AF and ON determined the methods of the operation and supervised all medical procedures. All authors read and approved the final manuscript.
This retrospective study was approved by the Institutional Review Board of Teikyo University. The study registry number, registry name and registration date are as follows: 20-054-2, clinical outcomes of surgery, chemotherapy and radiotherapy for gynaecological malignant tumours: retrospective analyses, 2021/5/31. Written informed consent was obtained from the patients for the publication of this report.
This research was supported by the Mizonokuchi Hospital of Teikyo University with regard to the provision of medical information. The author(s) disclose the receipt of financial support from the Japan Society for the Promotion of Conventions for the research, authorship, and/or publication of this article.
The author(s) disclose the receipt of financial support from the Japan Society for the Promotion of Conventions (201902081) for the research, authorship, and/or publication of this article.
The authors declare no conflict of interest.
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