[Analysis of adverse late-term pregnancy outcomes after cervical cold knife conization].

Objective: To investigate the effects of cervical cold knife conization (CKC) on preterm delivery, other pregnancy complications and neonatal outcomes, and explore the relationship between preterm delivery risk and the depth and volume of conization. Methods: The clinical data and pregnancy outcomes of 272 women who underwent CKC in Peking Union Medical College Hospital from January 2002 to March 2018 (conization group) and 1 647 pregnant women who gave birth in Peking Union Medical College Hospital during January to December 2019 (control group) were collected. The preterm delivery, premature rupture of membranes, other pregnancy complications and neonatal outcomes of the two groups were compared, and the relationship between the depth and volume of conization and the risk of preterm delivery in postoperative singleton pregnancy was analyzed. Results: (1) There were no significant differences between the two groups in delivery age, parity, proportion of singleton pregnancy, proportion of assisted reproductive technology (all P>0.05). (2) The rate of preterm delivery in the conization group was significantly higher than that in the control group [14.8% (39/264) vs 5.7% (91/1 589); χ2=28.397, P<0.001]. There were still significant differences in preterm delivery rates between the two groups at <34 weeks and 34-37 weeks (all P<0.01). There was no significant difference in the incidence of premature rupture of membrane between the two groups [23.5% (62/264) vs 23.4% (372/1 589); χ2=0.001, P=0.979], but the incidence of preterm premature rupture of membrane in the conization group was significantly higher than that in the control group [11.4% (30/264) vs 2.2% (35/1 589); χ2=56.132, P<0.001]. (3) The rate of cesarean section in the conization group was higher than that in the control group [59.6% (162/272) vs 38.8% (639/1 647); χ2=41.377, P<0.001]. The birth weight of preterm infants in the conization group was significantly higher than that in the control group [(2 409±680) vs (2 150±684) g; t=2.184, P=0.030]. However, there were no statistically significant differences in the incidence of gestational diabetes mellitus, hypertensive disorders in pregnancy, the birth weight of full-term infants, incidence of small for gestational age infant and neonatal intensive care unit admission rate between the two groups (all P>0.05). (4) The preterm delivery rates of coning depth >15 mm, cone size ≥2 cm3 and cone size <2 cm3 were higher than that in the control group (all P<0.05). When the coning depth ≤15 mm, the preterm delivery rate in the conization group was higher than that in the control group, but there was no significant difference (P=0.620). The rate of preterm delivery of pregnant women with coning depth >15 mm was significantly higher than those with coning depth ≤15 mm (RR=3.084, 95%CI: 1.474-6.453; P=0.001). There was no significant difference in the preterm delivery rate between pregnant women with cone size >2 cm3 and those with cone size ≥2 cm3 (RR=1.700, 95%CI: 0.935-3.092; P=0.077). Conclusion: The risk of preterm delivery and preterm premature rupture of membranes in subsequent pregnancies are increased after cervical CKC, and the risk of preterm delivery is positively correlated with the depth of cervical coning.

Persistent HPV infection after conization of cervical intraepithelial neoplasia-- a systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate several factors of persistent human papillomavirus (HPV) infection following conization in patients with cervical intraepithelial neoplasia (CIN). METHODS: PubMed, EMBASE and the Cochrane Library were searched from January 1, 1998 to September 10, 2021. Random-effects models for meta-analyses were used and pooled relative risks with 95% confidence intervals were reported. Literature screening, data extraction, and assessment of the risk of bias in the included studies were conducted independently by two researchers. Data analysis was performed with Stata software, version 12.0. RESULTS: A total of 28 studies were included in this study. Meta-analysis revealed that surgical margin and residual disease were positively correlated with persistent HPV infection after conization. Compared with patients infected with other types of HPV, CIN patients with HPV 16 had a higher persistent infection rate (OR = 1.967, 95% CI (1.232-3.140), P < 0.05). CONCLUSIONS: CIN patients who are postmenopausal, have positive surgical margins and residual lesions, and are positive for HPV 16 are prone to persistent HPV infection after conization.

Comparison of the safety between cervical conization and hysterectomy for patients with cervical adenocarcinoma in situ.

OBJECTIVE: To compare the safety between cervical conization (CC) alone and hysterectomy for patients with adenocarcinoma in situ (AIS) of the cervix. METHODS: Patients diagnosed with AIS after CC during 2007-2021 were identified by computerized databases at Women's Hospital of Zhejiang University School of Medicine. A total of 453 AIS patients were divided into 2 groups according to uterus preservation: hysterectomy group (n=300) and CC(s) alone group (n=153). The prevalence of residual disease and disease recurrence was compared between patients treated by CC(s) alone and hysterectomy. The prevalence of residual disease in specimens from women who had a hysterectomy and repeat CC were compared between positive and negative margins of CC. The factors influencing residual disease and disease recurrence were assessed. RESULTS: Among 310 specimens from women who had a hysterectomy or repeat CC, the prevalence of residual disease was 50.6% (45/89) for a positive margin and 2.3% (5/221) for a negative margin (p=0.000). Four patients had recurrence of vaginal intraepithelial neoplasia in those treated by hysterectomy and one had recurrence of cervical squamous intraepithelial neoplasia in those treated by CC(s) alone. The prevalence of recurrence was 0.7% (1/153) for CC(s) alone and 1.3% (4/300) for hysterectomy (p=0.431). Hysterectomy did not influence residual disease or disease recurrence. CONCLUSION: CC is an efficacious and safe option for patients with AIS of the cervix provided the margin is negative.

The effect of cold-knife conization on pregnancy outcomes in patients with cervical lesions.

OBJECTIVE: To analyze the pregnancy outcomes of patients with cervical lesions treated by cold-knife conization (CKC). METHODS: Clinical data of healthy pregnant women and pregnant women who underwent CKC in Dalian Women and Children's Medical Group from March 2010 to December 2019 were retrospectively analyzed. These patients were divided into a CKC group and a control group according to inclusion and exclusion criteria. Statistical methods were used to compare pregnancy and delivery outcomes between the two groups. RESULTS: There were 400 patients in CKC group and control group, with 200 patients in each. There was no significant difference in the mode of delivery, abortion, ectopic pregnancy, in-hospital perinatal management, and cervical cerclage between the CKC group and the control group (P>0.05). The rates of preterm delivery, premature rupture of membranes, cesarean section, and neonatal admission in the CKC group were higher than those in the control group (P<0.05). In the CKC group, the incidence of premature rupture of membranes within six months postoperatively was higher than that after six months (P<0.05). The incidences of preterm delivery and premature rupture of membranes were not completely consistent in different conization ranges (P<0.05). CONCLUSION: CKC increases the incidence of preterm delivery, premature rupture of membranes, and neonatal adverse outcomes. Conization height can predict the occurrence of preterm delivery. Delaying pregnancy after surgery can reduce the incidence of adverse outcomes during the perinatal period.

Risk factors predicting residual lesion in subsequent hysterectomy following cold knife conization (CKC) for high-grade squamous intraepithelial lesion (HSIL).

OBJECTIVE: To determine risk factors predicting residual lesion in a subsequent hysterectomy follow a cold knife conization (CKC) for high-grade squamous intraepithelial lesion (HSIL). METHOD: Between January 2010 and December 2021, a total of 740 patients who underwent a hysterectomy within 3 months after CKC for HSIL were included in this study. We analyzed their demographic features and pathological parameters. A logistic regression model was used to analyze the relationship between parameters and residual lesion in subsequent hysterectomy specimens. RESULTS: 104 (14.1%) had residual lesion in the hysterectomy specimen, 3 patients with microinvasive carcinoma. The rate of residual lesion in patients with positive endocervical margin was 31.3%, with positive ectocervical margin was 15.3%, with positive combine margin was 38.6%. In multivariate analysis, positive margin (OR 4.015; 95% CI 2.526-6.381; P < 0.001), glandular involvement (OR 3.484; 95% CI 1.457-8.330; P = 0.005), HPV16/18 infection (OR 2.804; 95% CI 1.705-4.611; P < 0.001) and multiple HR-HPV infection (OR 1.813; 95% CI 1.130-2.909; P < 0.014) were independent risk factors for residual lesion. The AUC calculated by logistic regression model was 0.78. CONCLUSION: Positive margin, positive glandular involvement, HPV16/18 and multiple HR-HPV infection were independent high risk factors of residual lesion in a subsequent hysterectomy following CKC for HSIL.

Recurrent Dysplasia After a Loop Electrosurgical Excision Procedure: Local Versus General Anesthesia.

OBJECTIVE: This study aimed to compare the rates of positive specimen margins and postconization recurrent dysplasia between loop electrosurgical excision procedures (LEEPs) performed under general anesthesia (GA) and LEEP under local anesthesia (LA). METHODS: This retrospective cohort study included all consecutive women who underwent LEEP between 2011 and 2019. Collected data included demographics, LEEP indication, cone dimensions, and margin involvement as well as recurrence rate. Women who had undergone previous conization, cold-knife conization, or those who were lost to follow-up during the first 2 years after the procedure were excluded. RESULTS: Overall, 71 women who underwent LEEP under GA and 75 women under LA were included. Demographic characteristics were similar between the groups, as were the rates of preceding abnormal cytology and high-grade dysplasia before conization. Although cone depth and volume were higher for LEEP specimens done under GA compared with LA, the rate of positive specimen margins was comparable both for the endocervical margin (16/71 [22.5%] vs 16/75 [21.3%], respectively; p = .861) and the ectocervical margin (14/71 [19.7%] vs 11/75 [14.7%], respectively; p = .418). During the first 2 years after conization, the rates of high-grade dysplasia (cervical intraepithelial neoplasia ≥ 2) in repeat biopsy and the need for repeat conization were also not significantly different between the GA and LA groups (4.2% vs 1.3%, p = .356; 7.0% vs 9.3%, p = .614, respectively). CONCLUSIONS: Anesthesia mode does not seem to affect the rate of positive LEEP margins and the need for repeat conization. Our study findings suggest that LA should be preferred instead of GA in LEEP.

Identification of women with high grade histopathology results after conisation by artificial neural networks.

BACKGROUND: The aim of the study was to evaluate if artificial neural networks can predict high-grade histopathology results after conisation from risk factors and their combinations in patients undergoing conisation because of pathological changes on uterine cervix. PATIENTS AND METHODS: We analysed 1475 patients who had conisation surgery at the University Clinic for Gynaecology and Obstetrics of University Clinical Centre Maribor from 1993-2005. The database in different datasets was arranged to deal with unbalance data and enhance classification performance. Weka open-source software was used for analysis with artificial neural networks. Last Papanicolaou smear (PAP) and risk factors for development of cervical dysplasia and carcinoma were used as input and high-grade dysplasia Yes/No as output result. 10-fold cross validation was used for defining training and holdout set for analysis. RESULTS: Bas eline classification and multiple runs of artificial neural network on various risk factors settings were performed. We achieved 84.19% correct classifications, area under the curve 0.87, kappa 0.64, F-measure 0.884 and Matthews correlation coefficient (MCC) 0.640 in model, where baseline prediction was 69.79%. CONCLUSIONS: With artificial neural networks we were able to identify more patients who developed high-grade squamous intraepithelial lesion on final histopathology result of conisation as with baseline prediction. But, characteristics of 1475 patients who had conisation in years 1993-2005 at the University Clinical Centre Maribor did not allow reliable prediction with artificial neural networks for every-day clinical practice.

Comparative effectiveness and risk of preterm birth of local treatments for cervical intraepithelial neoplasia and stage IA1 cervical cancer: a systematic review and network meta-analysis.

BACKGROUND: The trade-off between comparative effectiveness and reproductive morbidity of different treatment methods for cervical intraepithelial neoplasia (CIN) remains unclear. We aimed to determine the risks of treatment failure and preterm birth associated with various treatment techniques. METHODS: In this systematic review and network meta-analysis, we searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials database for randomised and non-randomised studies reporting on oncological or reproductive outcomes after CIN treatments from database inception until March 9, 2022, without language restrictions. We included studies of women with CIN, glandular intraepithelial neoplasia, or stage IA1 cervical cancer treated with excision (cold knife conisation [CKC], laser conisation, and large loop excision of the transformation zone [LLETZ]) or ablation (radical diathermy, laser ablation, cold coagulation, and cryotherapy). We excluded women treated with hysterectomy. The primary outcomes were any treatment failure (defined as any abnormal histology or cytology) and preterm birth (<37 weeks of gestation). The network for preterm birth also included women with untreated CIN (untreated colposcopy group). The main reference group was LLETZ for treatment failure and the untreated colposcopy group for preterm birth. For randomised controlled trials, we extracted group-level summary data, and for observational studies, we extracted relative treatment effect estimates adjusted for potential confounders, when available, and we did random-effects network meta-analyses to obtain odds ratios (ORs) with 95% CIs. We assessed within-study and across-study risk of bias using Cochrane tools. This systematic review is registered with PROSPERO, CRD42018115495 and CRD42018115508. FINDINGS: 7880 potential citations were identified for the outcome of treatment failure and 4107 for the outcome of preterm birth. After screening and removal of duplicates, the network for treatment failure included 19 240 participants across 71 studies (25 randomised) and the network for preterm birth included 68 817 participants across 29 studies (two randomised). Compared with LLETZ, risk of treatment failure was reduced for other excisional methods (laser conisation: OR 0·59 [95% CI 0·44-0·79] and CKC: 0·63 [0·50-0·81]) and increased for laser ablation (1·69 [1·27-2·24]) and cryotherapy (1·84 [1·33-2·56]). No differences were found for the comparison of cold coagulation versus LLETZ (1·09 [0·68-1·74]) but direct data were based on two small studies only. Compared with the untreated colposcopy group, risk of preterm birth was increased for all excisional techniques (CKC: 2·27 [1·70-3·02]; laser conisation: 1·77 [1·29-2·43]; and LLETZ: 1·37 [1·16-1·62]), whereas no differences were found for ablative methods (laser ablation: 1·05 [0·78-1·41]; cryotherapy: 1·01 [0·35-2·92]; and cold coagulation: 0·67 [0·02-29·15]). The evidence was based mostly on observational studies with their inherent risks of bias, and the credibility of many comparisons was low. INTERPRETATION: More radical excisional techniques reduce the risk of treatment failure but increase the risk of subsequent preterm birth. Although there is uncertainty, ablative treatments probably do not increase risk of preterm birth, but are associated with higher failure rates than excisional techniques. Although we found LLETZ to have balanced effectiveness and reproductive morbidity, treatment choice should rely on a woman's age, size and location of lesion, and future family planning. FUNDING: National Institute for Health and Care Research: Research for Patient Benefit.

Risk of recurrent disease following conization of cervical intraepithelial neoplasia grade 3 according to post-conization HPV status and surgical margins.

OBJECTIVE: To examine the absolute risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) following conization according to post-conization HPV status and surgical margins. METHODS: A total of 11,006 women with CIN3 on the cone were followed for up to 14 years using nationwide registries. We estimated absolute risks of recurrent CIN2+ and sensitivity and specificity of HPV testing and margin status in predicting CIN2+ 4 years after conization. RESULTS: Altogether, 2537 women were HPV positive and 8469 were HPV negative. During follow-up, 306 and 140 women were diagnosed with CIN2+ among HPV positive and negative women, respectively. HPV positive women had higher absolute risk of CIN2+ compared to HPV negative women. Specifically, the 8-year absolute risk of CIN2+ was 12.5% (95% CI: 11.2-13.9) for HPV positive women and 1.8% (95%CI: 1.5-2.1) for HPV negative women. Among HPV negative women, the 8-year absolute risk was 2.7% (95%CI: 2.1-3.5) and 1.3% (95%CI: 1.0-1.7) for women with positive and negative margins, respectively. The same pattern was seen among HPV positive women. Combined testing with HPV and margins had a higher sensitivity but lower specificity than HPV testing alone. CONCLUSION: Our results add knowledge on long-term risk assessment of women treated with conization as taking both HPV and margin status into account added further stratification of the risk of recurrent disease compared to HPV status alone. Additionally, combined testing with HPV and margin status had higher sensitivity than HPV testing alone, which is important in high-risk populations, however, the specificity was lower.

Adenocarcinoma in situ or early-stage cervical cancer is a risk factor for preterm delivery after cervical conization: a multicenter observational study.

OBJECTIVE: Pregnancy after conization is associated with a high risk of preterm delivery. However, because risk factors for preterm delivery after conization remain unknown, we conducted a multicenter observational study to investigate risk factors associated with preterm delivery. METHODS: We selected patients who had previously undergone conization and reviewed medical records from 18 hospitals in cooperation with Keio University School of Medicine between January 2013 and December 2019. Women were classified as nulliparous and primiparous, and a multiple logistic regression analysis was performed to evaluate the relative contributions of the various maternal risk factors for preterm delivery (i.e. delivery before 37 gestational weeks). RESULTS: Among 409 pregnant women after conization, 68 women delivered preterm (17%). The incidence of nulliparity (p = .014) was higher and a history of preterm delivery (p = .0010) was more common in the preterm delivery group than in the term delivery group. Furthermore, the proportion of women diagnosed with adenocarcinoma in situ (AIS) and cervical cancer in the preterm delivery group was higher than that in the term delivery group (p = .0099 and .0004, respectively). In multiple regression models in nulliparous women, cervical cancer or AIS (Odds ratio [OR]: 4.16, 95% CI: 1.26-13.68, p = .019) and a short cervix in the second trimester (OR: 13.41, 95% CI: 3.88-46.42, p < .0001) increased the risk of preterm delivery. Furthermore, a history of preterm delivery (OR: 7.35, 95% CI: 1.55-34.86, p = .012), cervical cancer or AIS (OR: 5.07, 95% CI: 1.24-20.73, p = .024), and a short cervix in the second trimester (OR: 4.29, 95% CI: 1.11-16.62, p = .035) increased the risk of preterm delivery in the multiple regression models in primiparous women. CONCLUSION: Pregnant women who previously underwent conization are at risk for preterm delivery. The histological type of AIS and cervical cancer was evaluated as a risk factor for preterm delivery. KEY MESSAGESPrior preterm delivery, presence of a short cervix, and cervical cancer or AIS were predictors of preterm delivery after conization.The depth of conization in cervical cancer or AIS group was significantly larger than that in the CIN group.

A modified transabdominal cervicoisthmic cerclage with the monofilament thread: Its efficacy and safety for women with extremely short cervix due to cervical conization.

AIM: The study aimed to examine the usefulness of modified transabdominal cervicoisthmic cerclage (TAC) using monofilament thread for the prevention of preterm delivery in women with an extremely short cervix after deep conization. METHODS: We devised a monofilament thread for picking up the seromuscular layer of the site that is slightly cephalad to the internal ostium to prevent injury of the vessels around the uterine cervix. From 2017 to 2020, we performed this modified operation in eight women (nine pregnancies) at 12-16 weeks of gestation with a history of deep cervical conization. RESULTS: A modified TAC was successfully performed in all patients. There was no measurable bleeding, and all patients were discharged without postoperative complications. Their pregnancy courses after the operation were uneventful. Of nine, one patient had premature uterine contractions and underwent cesarean section at 36 weeks (preterm delivery). In the other eight pregnancies, planned cesarean section was performed after 37 weeks of gestation. The median birth weight of the babies was 2996 g (range 2604-3374 g). All patients were discharged on the sixth postoperative day without complications. CONCLUSION: A modified TAC can be safely performed and may prolong pregnancy without adverse events in patients with an extremely short cervix.

The Effect of Cervical Conization on Women's' Sexual Function and Psychological Health, A Prospective Observational Study.

BACKGROUND: Diagnosis of cervical dysplasia and subsequent conization of the uterine cervix might affect women's' sexual health. AIM: To assess the effect of cervical conization on women's sexual function and psychological wellbeing. METHODS: Patients undergoing conization of the cervix were assessed before, and 6 months after conization. Assessment of sexual distress and function was done using the female sexual distress scale-revised (FSDS-r) and the female sexual function inventory (FSFI), respectively. Risk for anxiety and depression, was assessed using the Hospital Anxiety and Depression Scale (HADS). MAIN OUTCOME MEASURES: FSDS-r, FSFI and HADS scores before and after conization RESULTS: From October 2018 to March 2021, 55 patients undergoing cervical conization were recruited. No significant differences were found in FSDS-r scores before and after conization. An equal number of patients indicated having sexual distress (29 patients, 53%, before and after conization, P=1.0). No significant changes were noticed on any FSDS domains or the total FSDS score before and after conization, (26.8 vs. 26.0, p=0.461). The percent of patients that indicated an overall sexual dysfunction, increased from 49 percent before conization, to 59 percent after conization, P=0.388. A high percent of patients indicated signs of anxiety on the HADS questionnaire, both before and after conization (49% and 47%, respectively). The median anxiety and depression scores did not change after conization, p=1.0. CLINICAL IMPLICATIONS: A high percent of patients undergoing conization suffer from sexual distress, sexual dysfunction and general anxiety, both before and after conization. The conization procedure itself did not seem to effect questionnaire scores. STRENGTHS AND LIMITATIONS: This was a prospective cohort, with comprehensive assessment of female sexual and psychological wellbeing after conization. Not all subjects reported sexual intercourse prior to questionnaire completion. CONCLUSION: Gynecologists should be aware of the psychological and sexual effect of the diagnosis and treatment of cervical pre-cancerous lesions, patients should be counselled accordingly. Michaan N, Loboda N, Ochshorn I, et al., The Effect of Cervical Conization on Women's' Sexual Function and Psychological Health, A Prospective Observational Study. J Sex Med 2022;19:257-262.

Identifying the associated factors with onset of preterm PROM compared with term PROM - A retrospective cross-sectional study.

OBJECTIVE: To determine the risk factors associated with the preterm premature rupture of membranes (p-PROM). MATERIALS AND METHODS: This retrospective cross-sectional study assessed 110 p-PROM cases from among 6642 deliveries at a Japanese perinatal medical center, from June 2016 to September 2018. The control group comprised 220 term PROM (t-PROM) cases. We excluded cases with artificial PROM or rupture of membranes after labor, those with multiple pregnancies, those with p-PROM at 36 weeks and those with t-PROM at 37 weeks. In order to compare p-PROM with t-PROM, univariate and multivariate analysis were performed using several clinical factors at the time of PROM onset. RESULTS: The p-PROM group included 110 cases with 14-35 weeks PROM, and the t-PROM group included 220 cases with 38-41 weeks PROM. Eleven factors were identified as significant factors on the univariate analysis. A history of cervical conization (OR 37.5, 95% CI: 2.31-607.1), cervical length <25 mm at 28 weeks (OR 9.31, 95% CI: 1.76-49.3), negative Lactobacillus (OR 4.01, 95% CI: 1.18-13.7), and bleeding during the second trimester (OR 3.35, 95% CI: 1.18-9.53) were identified as significant factors by the multivariate analysis. Based on the risk factors identified during the multivariate analysis, we divided the 330 cases in the following three groups: 0 group (n = 244), 1 group (n = 60), and 2-4 group (n = 26). The ratio of p-PROM:t-PROM was calculated and compared for each group. The ratios were 21% (0 group), 57% (1 group), and 100% (2-4 group), indicating statistically significant differences between the groups (p < 0.001). CONCLUSION: We found that the following four factors were associated with p-PROM: history of cervical conization, cervical length <25 mm at 28 weeks, negative Lactobacillus, and bleeding during the second trimester. Our results suggest that we can identify patients who are at increased risk for p-PROM, based on these factors. Further research is necessary to determine the optimal treatment approach for these patients to prevent p-PROM.

Collagen Vitrigel Membrane-Coated Nylon Line Prevents Stenosis After Conization of the Cervix Uteri.

Cervical stenosis is a postoperative complication of conization for uterine cervical malignancy, but a standard method of preventing this complication has yet to be established. Collagen vitrigel is a collagen-based biomaterial that has antifibrotic and epithelization promoting actions. We evaluated the antistenotic effect of an indwelling collagen vitrigel membrane-coated nylon line (CVNL) after cervical conization in rabbits. In one group of rabbits, a CVNL was placed in the cervical canal after conization. In another group, a nylon line without a collagen coating was placed in the cervical canal after conization. The control group underwent cervical conization without placement of a device. The control (conization alone) and nylon (conization plus indwelling nylon line) groups exhibited cervical swelling. Rabbits in the CVNL group (cervical conization plus indwelling CVNL in the xerogel state) had a normal cervical surface. The cervical canal in the control group was enlarged and showed cystic changes attributed to cervical stenosis. The nylon group exhibited a trend toward cervical canal dilatation. In the CVNL group, the cervical canal was normal and did not show cystic dilatation. Fibrosis occurred to a lesser degree in the nylon group than in the control group, and the CVNL group exhibited minimal interstitial fibrosis. The control and nylon groups showed increased numbers of myofibroblasts in the regenerated cervix, but few myofibroblasts were observed in the CVNL group. Abundant collagen type III was observed in regenerated cervical tissue in the control and nylon groups but not in the CVNL group. The number of proliferative mesenchymal cells in the regenerated cervix was lowest in the CVNL group. The expressions of connective tissue growth factor (CTGF, a regulator of fibroblast growth and extracellular matrix secretion), extracellular signal-regulated protein kinases 1 and 2, and c-Jun N-terminal kinase (which are involved in the induction of CTGF by transforming growth factor-ß) were lower in the CVNL group than in the control or nylon groups. This study describes an indwelling CVNL that prevents cervical stenosis and cystic changes after conization. These effects were likely mediated by inhibition of fibrosis, myofibroblast emergence, CTGF expression, and collagen type III deposition in regenerating cervix. Impact statement Collagen vitrigel is a high-density collagen material that promotes epithelization, inhibits fibrosis, and suppresses inflammation in regenerating tissue. We evaluated whether a collagen vitrigel membrane-coated nylon line would prevent cervical stenosis after conization in the rabbit. We found that an indwelling collagen vitrigel membrane-coated nylon line prevented cervical canal stenosis and cystic changes after cervical conization by inhibiting fibrosis, myofibroblast emergence, connective tissue growth factor expression, and collagen type III deposition in the regenerating cervix. Our device has potential as a new method of preventing cervical canal fibrosis and stenosis after conization for cervical cancer.

Preoperative Conization and Risk of Recurrence in Patients Undergoing Laparoscopic Radical Hysterectomy for Early Stage Cervical Cancer: A Multicenter Study.

STUDY OBJECTIVE: To investigate the factors associated with poorer oncologic outcomes in patients undergoing laparoscopic radical hysterectomy (LRH) for early stage cervical cancer. DESIGN: Multicenter retrospective study. SETTING: Three gynecologic oncology referral centers. PATIENTS: Patients with International Federation of Gynecology and Obstetrics 2009 stage IA (positive lymphovascular space invasion)-IB1 cervical cancer between January 2006 and June 2018. INTERVENTIONS: LRH (Piver type II-III hysterectomies). Lymph-node dissection was accomplished according to the tumor characteristics. MEASUREMENTS AND MAIN RESULTS: Surgical and oncologic outcomes were analyzed. Overall, 186 patients met the inclusion criteria, 16 (8.6%) experienced a recurrence, and 9 (4.8%) died of the disease (median follow-up period 37.9 months). Surgery-related complications did not influence disease-free survival. All the recurrences (16/16; 100%) occurred in patients with stage IB1 disease (p = .02), and 15 (93.7%) in cases involving tumors ≥2 cm. No association between positive lymph node and recurrence was detected (p =.82). Patients who had a preoperative diagnosis through conization (93; 50%) had a significantly lower rate of recurrence than those who underwent cervical biopsy (93; 50%): 1/93 (1.1%) vs 15/93 (16.1%); p <.001). The subanalysis of patients with International Federation of Gynecology and Obstetrics stage IB1 cervical cancer showed that patients undergoing preoperative conization (vs cervical biopsy) were less likely to experience a recurrence (odds ratio 0.09; 95% confidence interval 0.01-0.55). CONCLUSION: We confirmed that LRH was associated with a recurrence rate similar to that reported in the Laparoscopic Approach to Cervical Cancer trial. Tumor size ≥2 cm represents the most important risk factor influencing disease-free survival. However, we found that preoperative conization plays a potentially protective role in patients with an IB1 tumor.

Relationship between cervical excisional treatment for cervical intraepithelial neoplasia and obstetrical outcome.

INTRODUCTION: The aim of our systematic review was the assessment of effects of excisional treatments for the management of cervical intraepithelial neoplasia (CIN) on preterm delivery (PD), lower birth weight (LBW), preterm premature rupture of membrane (PPROM) and obstetrical outcomes. EVIDENCE ACQUISITION: A structured search was carried out in PubMed-Medline, Embase, and Cochrane Controlled Trials Register databases through November 30, 2019. The search included a combination of the following terms: "loop electrosurgical excision procedure (LEEP)," "large loop excision of transformation zone (LLETZ)," "cold-knife conization (CKC)," "laser cervical conization (CLC)," "preterm delivery" and "neonatal outcome." EVIDENCE SYNTHESIS: Thirty-two of 561 publications considered were included: 28 retrospective series, 2 prospective studies and 2 multicenter trials. Globally in several studies there was a significant increase in PD, measured by the relative risk, in the women underwent a surgical procedure for the CIN. In their majority, the studies were retrospective and therefore a high risk of bias. CONCLUSIONS: This systematic review shows that the surgical treatment of the CIN was associated with an increased risk of PD, LBW and pPROM before 37 pregnancy weeks compared to untreated women, especially in a CKC and LLETZ procedure. Moreover, the increase of the of PD was associated with cone size, cervical length, repeated treatment and a short conization-to-pregnancy interval.

Value of large loop excision of the transformation zone (LLETZ) without histological proof of high-grade cervical intraepithelial lesion: Results of a two-year continuous retrospective study.

OBJECTIVE: Large loop excision of the transformation zone (LLETZ) conization has been associated with adverse obstetrical outcomes. In an approach to reduce the number of performed LLETZ procedures, we conducted this study to evaluate whether "diagnostic" LLETZ should still be performed, by analyzing their yield in terms of detection (and treatment) of real high-grade squamous intraepithelial lesion (HSIL). METHODS: During a two-year study period, all patients who underwent a LLETZ procedure in our institution were retrospectively included. Study participants were divided into two groups according to LLETZ indication: a biopsy-proven HSIL group, and a non-biopsy-proven HSIL group. The results of the final histological examination were recorded, as well as excision margin status and specimen dimensions. RESULTS: During the two-year study period, 396 LLETZs were performed, 283 (71%) of which were indicated by biopsy-proven HSIL. In the non-biopsy-proven group, final histology showed 50 cases of HSIL (44%) and 4 cases of carcinoma (3.6%), versus respectively, in the biopsy-proven group, 221 (78%) HSIL and 28 (9.9%) carcinoma (p<0.001). Regarding margin status and specimen dimensions, no intergroup difference was observed between the two groups. CONCLUSION: So called "diagnostic" LLETZ allowed the detection of severe cervical lesions in almost half of cases, without increasing specimen dimensions in comparison with classical conization indications. Moreover, they also allowed an efficient treatment as showed by similar margins status. Our results therefore strengthen the idea that "diagnostic" LLETZ, when specific indications are respected, should not be overlooked as a major part of our therapeutic arsenal.

Cervical ripening balloon: An off-label but effective use to manage massive hemorrhage during outpatient cervical conization.

A double­balloon catheter may be very helpful in managing a major hemorrhage following outpatient conization.