Prognostic impact of cytoreductive surgery conducted with primary intent, versus cytoreductive surgery after neoadjuvant chemotherapy, in the management of patients with advanced epithelial ovarian cancers: a multicentre, propensity score-matched study from the FRANCOGYN group.

OBJECTIVE: To compare survival and morbidity rates between primary cytoreductive surgery (pCRS) and interval cytoreductive surgery (iCRS) for epithelial ovarian cancer (EOC), using a propensity score. DESIGN: We conducted a propensity score-matched cohort study, using data from the FRANCOGYN cohort. SETTING: Retrospective, multicentre study of data from patients followed in 15 French department specialized in the treatment of ovarian cancer. SAMPLE: Patients included were those with International Federation of Gynaecology and Obstetrics (FIGO) stage III or IV EOC, with peritoneal carcinomatosis, having undergone CRS. METHODS: The propensity score was designed using pre-therapeutic variables associated with both treatment allocation and overall survival (OS). MAIN OUTCOME MEASURES: The primary outcome was OS. Secondary outcomes included recurrence-free survival (RFS), quality of CRS and other variables related to surgical morbidity. RESULTS: A total of 513 patients were included. Among these, 334 could be matched, forming 167 pairs. No difference in OS was found (hazard ratio, HR = 0.8, p = 0.32). There was also no difference in RFS (median = 26 months in both groups) nor in the rate of CRS leaving no macroscopic residual disease (pCRS 85%, iCRS 81.4%, p = 0.76). The rates of gastrointestinal tract resections, stoma, postoperative complications and hospital stay were significantly higher in the pCRS group. CONCLUSIONS: Analysis of groups of patients made comparable by propensity score matching showed no difference in survival, but lower postoperative morbidity in patients treated with iCRS.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) consensus statement on the management of vaginal intraepithelial neoplasia.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vaginal intraepithelial neoplasia (VaIN). The management of VaIN varies according to the grade of the lesion: VaIN 1 (low grade vaginal squamous intraepithelial lesions (SIL)) can be subjected to follow-up, while VaIN 2-3 (high-grade vaginal SIL) should be treated. Treatment needs individualization according to the patient's characteristics, disease extension and previous therapeutic procedures. Surgical excision is the mainstay of treatment and should be performed if invasion cannot be excluded. Total vaginectomy is used only in highly selected cases of extensive and persistent disease. Carbon dioxide (CO2) laser may be used as both an ablation method and an excisional one. Reported cure rates after laser excision and laser ablation are similar. Topical agents are useful for persistent, multifocal lesions or for patients who cannot undergo surgical treatment. Imiquimod was associated with the lowest recurrence rate, highest human papillomavirus (HPV) clearance, and can be considered the best topical approach. Trichloroacetic acid and 5-fluorouracil are historical options and should be discouraged. For VaIN after hysterectomy for cervical intraepithelial neoplasia (CIN) 3, laser vaporization and topical agents are not the best options, since they cannot reach epithelium buried in the vaginal scar. In these cases surgical options are preferable. Brachytherapy has a high overall success rate but due to late side effects should be reserved for poor surgical candidates, having multifocal disease, and with failed prior treatments. VaIN tends to recur and ensuring patient adherence to close follow-up visits is of the utmost importance. The first evaluation should be performed at 6 months with cytology and an HPV test during 2 years and annually thereafter. The implementation of vaccination against HPV infection is expected to contribute to the prevention of VaIN and thus cancer of the vagina. The effects of treatment can have an impact on quality of life and result in psychological and psychosexual issues which should be addressed. Patients with VaIN need clear and up-to-date information on a range of treatment options including risks and benefits, as well as the need for follow-up and the risk of recurrence.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) Consensus Statement on the Management of Vaginal Intraepithelial Neoplasia.

ABSTRACT: The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vaginal intraepithelial neoplasia (VaIN). The management of VaIN varies according to the grade of the lesion: VaIN 1 (low grade vaginal squamous intraepithelial lesions (SIL)) can be subjected to follow-up, while VaIN 2-3 (high-grade vaginal SIL) should be treated. Treatment needs individualization according to the patient's characteristics, disease extension and previous therapeutic procedures. Surgical excision is the mainstay of treatment and should be performed if invasion cannot be excluded. Total vaginectomy is used only in highly selected cases of extensive and persistent disease. Carbon dioxide (CO2) laser may be used as both an ablation method and an excisional one. Reported cure rates after laser excision and laser ablation are similar. Topical agents are useful for persistent, multifocal lesions or for patients who cannot undergo surgical treatment. Imiquimod was associated with the lowest recurrence rate, highest human papillomavirus (HPV) clearance, and can be considered the best topical approach. Trichloroacetic acid and 5-fluorouracil are historical options and should be discouraged. For VaIN after hysterectomy for cervical intraepithelial neoplasia (CIN) 3, laser vaporization and topical agents are not the best options, since they cannot reach epithelium buried in the vaginal scar. In these cases surgical options are preferable. Brachytherapy has a high overall success rate but due to late side effects should be reserved for poor surgical candidates, having multifocal disease, and with failed prior treatments. VaIN tends to recur and ensuring patient adherence to close follow-up visits is of the utmost importance. The first evaluation should be performed at 6 months with cytology and an HPV test during 2 years and annually thereafter. The implementation of vaccination against HPV infection is expected to contribute to the prevention of VaIN and thus cancer of the vagina. The effects of treatment can have an impact on quality of life and result in psychological and psychosexual issues which should be addressed. Patients with VaIN need clear and up-to-date information on a range of treatment options including risks and benefits, as well as the need for follow-up and the risk of recurrence.

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.

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.

Impact of vulvar reconstruction on the accuracy of a nomogram for predicting local recurrence after surgery for vulvar cancer.

BACKGROUND DATA: Vulvar carcinoma is a rare disease accounting for 3%-5% of all gynaecological cancers. Although surgery is the standard treatment at an early stage, the outcomes are highly correlated with clear resection margins. Therefore, surgical defects can be important and require reconstruction. The aim of this study was to evaluate vulvar reconstructions using a previously validated nomogram predicting the risk of local recurrence at 2 years. METHODS: Patients who underwent surgery for vulvar cancer between 1998 and 2017 were extracted from eight FRANCOGYN centres. We estimated the probability of local recurrence at 2 years using a previously validated nomogram and compared it with actual relapse in patients with or without vulvar reconstruction. Patients were clustered into tiertiles according to their nomogram score: low-, intermediate-, and high-risk for local relapse probability. RESULTS: We reviewed 254 patients, of whom 49 underwent immediate vulvar reconstruction. The predicted and actual probability of two-year local relapse were 20.1% and 15.7%, respectively, with a concordance index of 0.75. In the low- and intermediate-risk groups, the difference between predicted and observed recurrence was less than 10% in patients with or without vulvar reconstruction. For the high-risk group, the difference reached 25% and observed recurrence probability was lower in patients who underwent vulvar plasty compared with those who did not (20.0% vs. 36.2%, respectively). Local recurrence-free survival rates following vulvar reconstruction were comparable at two years (82.1% vs. 84.8%, respectively, p = 0.26). CONCLUSION: Vulvar reconstruction after surgical resection for vulvar cancer is safe. Vulvar reconstruction should be considered in aggressive cases to decrease local recurrence.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD) and the European Federation for Colposcopy (EFC) consensus statements on pre-invasive vulvar lesions.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vulvar squamous intraepithelial neoplasia, vulvar Paget disease in situ, and melanoma in situ. For differentiated vulvar intraepithelial neoplasia (dVIN), an excisional procedure must always be adopted. For vulvar high-grade squamous intraepithelial lesion (VHSIL), both excisional procedures and ablative ones can be used. The latter can be considered for anatomy and function preservation and must be preceded by several representative biopsies to exclude malignancy. Medical treatment (imiquimod or cidofovir) can be considered for VHSIL. Recent studies favor an approach of using imiquimod in vulvar Paget's disease. Surgery must take into consideration that the extension of the disease is usually wider than what is evident in the skin. A 2 cm margin is usually considered necessary. A wide local excision with 1 cm free surgical margins is recommended for melanoma in situ. Following treatment of pre-invasive vulvar lesions, women should be seen on a regular basis for careful clinical assessment, including biopsy of any suspicious area. Follow-up should be modulated according to the risk of recurrence (type of lesion, patient age and immunological conditions, other associated lower genital tract lesions).

The Impact of COVID-19 Pandemic on Screening Programs for Cervical Cancer Prevention Across Europe.

OBJECTIVE: The aim of the study was to estimate the impact of COVID-19 pandemic on the practice of cervical cancer screening in European countries. MATERIALS AND METHODS: A 3 rounds e-survey was conducted among the 31 European Federation for Colposcopy member countries during 2020. Each representative was asked to answer to each questionnaire for their own country. Questionnaires were not anonymous. The first questionnaire was sent in April 2020 and second and third in June and December 2020, respectively. RESULTS: Twenty five of the 31 European countries solicited responded. A total of 19 countries (70.4%) reported that screening for cervical cancer was suspended at least once during the 3 rounds of questionnaires. In addition, 11 countries reported stopping colposcopy and treatments for cervical precancerous lesions at least once during the 3 rounds of questionnaires. These situations evolved with time, with the highest rate of countries recommending suspension of screening, colposcopy, and treatments during the second round of the survey. At round 3, no country recommended screening, colposcopy, and treatment, and 12 countries (57.5%) reported normal screening was fully implemented. CONCLUSIONS: Our results suggest massive disruption in cervical cancer screening programs across Europe resulting from COVID-19 pandemic. Increase in the incidence of cervical cancer is to be expected.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD) and the European Federation for Colposcopy (EFC) Consensus Statements on Pre-invasive Vulvar Lesions.

ABSTRACT: The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vulvar squamous intraepithelial neoplasia, vulvar Paget disease in situ, and melanoma in situ. For differentiated vulvar intraepithelial neoplasia (dVIN), an excisional procedure must always be adopted. For vulvar high-grade squamous intraepithelial lesion (VHSIL), both excisional procedures and ablative ones can be used. The latter can be considered for anatomy and function preservation and must be preceded by several representative biopsies to exclude malignancy. Medical treatment (imiquimod or cidofovir) can be considered for VHSIL. Recent studies favor an approach of using imiquimod in vulvar Paget's disease. Surgery must take into consideration that the extension of the disease is usually wider than what is evident in the skin. A 2 cm margin is usually considered necessary. A wide local excision with 1 cm free surgical margins is recommended for melanoma in situ. Following treatment of pre-invasive vulvar lesions, women should be seen on a regular basis for careful clinical assessment, including biopsy of any suspicious area. Follow-up should be modulated according to the risk of recurrence (type of lesion, patient age and immunological conditions, other associated lower genital tract lesions).

Lymphovascular space invasion as a prognostic factor of epithelial ovarian cancer: a multicenter study by the FRANCOGYN group.

BACKGROUND: The presence of lymphovascular space invasion (LVSI) is not yet included in international recommendations neither as a prognostic factor nor as a parameter for the decision to use adjuvant chemotherapy in FIGO stage I/IIa ovarian cancer (OC). OBJECTIVE: This study set out to evaluate the impact of LVSI on Overall Survival (OS) and Recurrence-Free Survival (RFS) in patients managed for epithelial OC. DESIGN: Retrospective multicenter study by the research group FRANCOGYN between January 2001 and December 2018. All patients managed for epithelial OC surgery and for whom histological slides for the review of LVSI were available, were included. The characteristics of patients with LVSI (LVSI group) were compared to those without LVSI (No-LVSI group). A Cox analysis for OS and RFS analysis was performed in all the populations. SETTING: French multicenter tertiary care centers RESULTS: Over the study period, 852 patients were included in the 13 institutions. Among them, 289 patients had LVSI (33.9%). There was a significant difference in the distribution of LVSI between early and advanced stages (p < 0.001). LVSI was an independent predictive factor for poorer Overall and Recurrence-Free Survival. LVSI affected OS (p < 0.001) and RFS (p < 0.001), LVSI affected OS and RFS for early stages (p = 0.001; p = 0.001, respectively) and also for advanced stages (p = 0.01; p = 0.009, respectively). CONCLUSION: The presence of LVSI in epithelial ovarian epithelial tumors has an impact on OS and RFS and should be included in the routine pathology examination to adapt therapeutic management, especially for women in the early stages of the disease.

Inguino-femoral radiotherapy in vulvar squamous cell carcinoma: clues to revised indications in patients with only one intracapsular lymph node metastasis.

Background and objectives: The aim was to review the clinical impact of groin metastatic nodal disease in women with vulvar squamous cell carcinoma (VSCC) and to evaluate the impact of adjuvant radiotherapy on women with single intracapsular lymph node metastasis (SILNM).Methods: Cohort study of women with vulvar squamous cell carcinoma (VSCC) managed between January 2005 and December 2015 in five institutions in France with prospectively maintained databases (French multicentre tertiary care centres). We evaluated Impact of SILNM on outcome.Results: A total of 176 women (34.6%) had at least one positive lymph node (LN). There were no significant differences for the 5-year overall survival rates between women with one extracapsular LN metastasis and women with one intracapsular LN metastasis, or with two node metastases (p = .62, p = .63 respectively). In women with a SILNM: (1) lymphovascular invasion (LVSI) was an independent negative predictive factor recurrence-free survival (RFS) (HR = 0.10 (95%CI, 0.01-0.90), p = .04) and (2) Adjuvant inguino-femoral radiotherapy was a positive independent factor associated with RFS (HR = 5.87 (95%CI 1.21-28.5), p = .02).Conclusion: A potential positive effect of adjuvant radiotherapy in node positive VSCC, irrespective of the number of affected LN, should be considered especially in the case of LVSI.

Risk Factors of Post-Large Loop Excision of the Transformation Zone Recurrent High-Grade Cervical Intraepithelial Lesion: A Prospective Cohort Study.

OBJECTIVE: The aim of the study was to identify the risk factors of post-large loop excision of the transformation zone (LLETZ) recurrent disease and the impact of colposcopic guidance at the time of LLETZ on that risk. MATERIALS AND METHODS: From December 2013 to July 2014, 204 patients who had undergone LLETZ for the treatment of high-grade intraepithelial lesion with fully visible cervical squamocolumnar junction were included. The use of colposcopy during each procedure was systematically documented. The dimensions and volume of LLETZ specimens were measured at the time of the procedure before formaldehyde fixation. All participants were invited for a follow-up. The primary endpoint was the diagnosis of post-LLETZ recurrent disease defined as the histologic diagnosis of a high-grade cervical intraepithelial lesion. RESULTS: The median duration of post-LLETZ follow-up was 25.8 months. Recurrent disease was diagnosed in 8 (3.6%) patients. Older than 38 years (adjusted hazard ratio [aHR] = 11.9, 95% CI = 1.6-86.0), history of excisional therapy (aHR = 21.6, 95% CI = 3.5-135.3), and the absence of colposcopy for the guidance of LLETZ (aHR = 6.4, 95% CI = 1.1-37.7) were found to significantly increase the risk of post-LLETZ recurrent disease. The dimensions and volume of the specimen were not found to have any impact. Only positive endocervical margins were identified to significantly increase the risk of post-LLETZ recurrent disease (aHR = 14.4, 95% CI = 2.0-101.1). CONCLUSIONS: Risk factors of post-LLETZ recurrent disease are older than 38 years, history of excisional therapy, positive endocervical margins, and lack of colposcopic guidance at the time of LLETZ.

Therapeutic value of surgical paraaortic staging in locally advanced cervical cancer: a multicenter cohort analysis from the FRANCOGYN study group.

BACKGROUND: The prognostic impact of surgical paraaortic staging remains unclear in patients with locally advanced cervical cancer (LACC). The objective of our study was to evaluate the survival impact of surgical staging in patients with LACC and no evidence of paraaortic lymph node (PALN) metastasis on pre-operative imaging work-up. METHODS: Data of 1447 patients with cervical cancer treated between 1996 and 2016 were extracted from maintained databases of 10 French University hospitals. Patients with locally advanced disease (IB2 or more) treated by concurrent chemoradiation therapy (CRT) and no evidence of paraaortic metastasis on pre-operative imaging work-up were selected for further analysis. The Kaplan-Meier method was used to estimate the survival distribution. A Cox proportional hazards model was used to account for the influence of multiple variables. RESULTS: Six hundred and forty-seven patients were included, 377 (58.3%) with surgical staging and 270 (41.7%) without, with a mean follow up of 38.1 months (QI 13.0-56.0). Pathologic analysis revealed positive lymph nodes in 47 patients (12.5%). In multivariate model analysis, surgical staging remained an independent prognostic factor for DFS (OR 0.64, CI 95% 0.46-0.89, p = 0.008) and OS (OR 0.43, CI 95% 0.27-0.68, p < 0.001). The other significant parameter in multivariate analysis for both DFS and OS was treatment by intracavitary brachytherapy (OR respectively of 0.7 (0.5-1.0) and 0.6 (0.4-0.9), p < 0.05). CONCLUSION: Nodal surgical staging had an independent positive impact on survival in patients with LACC treated with CRT with no evidence of metastatic PALN on imaging.

Identification of a low risk population for parametrial invasion in patients with early-stage cervical cancer.

BACKGROUND: Recent studies have challenged radical procedures for less extensive surgery in selected patients with early-stage cervical cancer at low risk of parametrial invasion. Our objective was to identify a subgroup of patients at low risk of parametrial invasion among women having undergone surgical treatment. METHODS: Data of 1447 patients with cervical cancer treated between 1996 and 2016 were extracted from maintained databases of 10 French University hospitals. Patients with early-stage (IA2-IIA) disease treated by radical surgery including hysterectomy and trachelectomy, were selected for further analysis. The Kaplan-Meier method was used to estimate the survival distribution. A Cox proportional hazards model including all the parameters statistically significant in univariate analysis, was used to account for the influence of multiple variables. RESULTS: Out of the 263 patients included for analysis, on final pathology analysis 28 (10.6%) had parametrial invasion and 235 (89.4%) did not. Factors significantly associated with parametrial invasion on multivariate analysis were: age > 65 years, tumor > 30 mm in diameter measured by MRI, lymphovascular space invasion (LVSI) on pathologic analysis. Among the 235 patients with negative pelvic lymph nodes, parametrial disease was seen in only 7.6% compared with 30.8% of those with positive pelvic nodes (p < 0.001). In a subgroup of patients presenting tumors < 30 mm, negative pelvic status and no LVSI, the risk of parametrial invasion fell to 0.6% (1/173 patients). CONCLUSION: Our analysis suggests that there is a subgroup of patients at very low risk of parametrial invasion, potentially eligible for less radical procedures.

A Proposal for a Classification for Recurrent Endometrial Cancer: Analysis of a French Multicenter Database From the FRANCOGYN Study Group.

OBJECTIVE: Endometrial cancer (EC) recurrences are relatively common with no standardized way of describing them. We propose a new classification for them called locoregional, nodal, metastasis, carcinomatosis recurrences (rLMNC). PATIENTS AND METHODS: The data of 1230 women with EC who were initially treated by primary surgery were included in this French multicenter retrospective study. Recurrences were classified based on dissemination pathways: (1) locoregional recurrence (rL); (2) nodal recurrence (rN) for lymphatic pathway; (3) distant organ recurrence (rM) for hematogenous pathway; and (4) carcinomatosis recurrence (rC) for peritoneal pathway. These pathways were further divided into subgroups. We compared recurrence free survival and overall survival (OS) between the 4 groups (rL/rN/rM/rC). RESULTS: The median follow-up was 35.6 months (range, 1.70-167.60). One hundred ninety-eight women (18.2%) experienced a recurrence: 150 (75.8%) experienced a single-pathway recurrence and 48 (24.2%) a multiple-pathway recurrence. The 5-year OS was 34.1% (95% confidence interval [CI], 27.02%-43.1%), and the median time to first recurrence was 18.9 months (range, 0-152 months). The median survival after recurrence was 14.8 months (95% CI, 11.7-18.8). Among women with single pathway of recurrence, a difference in 5-year OS (P < 0.001) and survival after recurrence (P < 0.01) was found between the 4 rLNMC groups. The carcinomatosis group had the worst prognosis compared with other single recurrence pathways. Women with multiple recurrences had poorer 5-year OS (P < 0.001) and survival after recurrence (P < 0.01) than those with single metastasis recurrence, other than women with peritoneal carcinomatosis. CONCLUSIONS: This easy-to-use and intuitive classification may be helpful to define EC recurrence risk groups and develop guidelines for the management of recurrence. Its prognosis value could also be a tool to select homogenous populations for further trials.

Risk Factors of Inadequate Colposcopy After Large Loop Excision of the Transformation Zone: A Prospective Cohort Study.

OBJECTIVE: The aim of the study was to identify the risk factors of post-large loop excision of the transformation zone (LLETZ) inadequate colposcopy. MATERIALS AND METHODS: From December 2013 to July 2014, a total of 157 patients who had a LLETZ performed for the treatment of high-grade intraepithelial lesion with fully visible cervical squamocolumnar junction were included. All procedures were performed using semicircular loops. The use of colposcopy made during each procedure was systematically documented. Dimensions and volume of LLETZ specimens were measured at the time of procedure, before formaldehyde fixation. All participants were invited for a follow-up colposcopy 3 to 6 months after LLETZ. Primary end point was the diagnosis of post-LLETZ inadequate colposcopy, defined by a not fully visible cervical squamocolumnar junction and/or cervical stenosis. RESULTS: Colposcopies were performed in a mean (SD) delay of 136 (88) days and were inadequate in 22 (14%) cases. Factors found to significantly increase the probability of post-LLETZ inadequate colposcopy were a history of previous excisional cervical therapy [adjusted odds ratio (aOR) = 4.29, 95% CI = 1.12-16.37, p = .033] and the thickness of the specimen (aOR = 3.12, 95% CI = 1.02-9.60, p = .047). The use of colposcopy for the guidance of LLETZ was statistically associated with a decrease in the risk of post-LLETZ inadequate colposcopy (aOR = 0.19, 95% CI = 0.04-0.80, p = .024) as the achievement of negative endocervical margins (aOR = 0.26, 95% CI = 0.08-0.86, p = .027). CONCLUSIONS: Although the risk of post-LLETZ inadequate colposcopy is increased in patients with history of excisional therapy and with the thickness of the excised specimen, it could be reduced with the use of colposcopic guidance and the achievement of negative endocervical margins.

Is gestational diabetes an independent risk factor of neonatal severe respiratory distress syndrome after 34 weeks of gestation? A prospective study.

PURPOSE: To evaluate if neonates delivered after 340/7 weeks from mothers diagnosed with gestational diabetes (GD) are exposed to an increased risk of neonatal severe respiratory distress syndrome (SRDS). METHODS: Women with singleton pregnancy in labour after 340/7 weeks of gestation or admitted for planned caesarean section and who had been systematically screened for GD were eligible to participate to this prospective cohort study. Diagnosis of SRDS was defined by the association of clinical signs of early neonatal respiratory distress, with consistent radiologic features and requiring mechanical ventilation with a fraction of inspired oxygen (FiO2) >0.25 for a minimum of 24 h and admission to neonatal intensive care unit. RESULTS: A total of 444 women were included. GD was diagnosed in 60 patients (13.5%). A neonatal SRDS was diagnosed in 32 cases (7.2%). Compared to others, neonatal SRDS was significantly more often observed in neonates from women diagnosed with GD: 12 (20%) vs. 20 (5.2%), respectively (p < 0.001). Women whose neonates presented neonatal SRDS were significantly more likely to be obese (p = 0.002), to have undergone a caesarean section (p < 0.001) and to have received corticosteroids therapy before 340/7 weeks (p = 0.013). In multivariate analysis, GD was identified as an independent risk factor of neonatal SRDS (aOR 3.6; 95% CI 1.5-8.6; p = 0.005). Other risk factors were maternal obesity (aOR 2.8; 95% CI 1.1-7.1; p = 0.029) and assisted vaginal delivery (aOR 5.5; 95% CI 1.9-15.9; p = 0.002). CONCLUSIONS: GD is an independent risk factor of neonatal SRDS after 340/7 weeks.

The Accuracy of Large Loop Excision of the Transformation Zone Specimen Dimensions in Determining Volume: A Multicentric Prospective Observational Study.

OBJECTIVE: The aim of the study was to determine which mathematical formula of specimen dimensions is the most accurate method of determining volume of the excised specimen at loop excision of the transformation zone. MATERIALS AND METHODS: A multicenter prospective observational study was conducted. A total of 258 patients who had a loop excision of the transformation zone performed as treatment of cervical intraepithelial neoplasia 2-3 were included. The dimensions and the volume of the specimen were measured at the time of the procedure, before formaldehyde fixation. The volume was measured by immersing the specimen in a graduated cylinder using Archimedes fluid displacement technique. The measured volume was compared with the calculated volume using different volume formulas, that is, a cone, a cylinder, a parallelepiped, and a hemiellipsoid. The main outcome measure was the relationship between calculated volume (using the dimensions of thickness, length, and circumference) and the measured volume of the specimen. RESULTS: The mean (SD) thickness, length, and circumference of specimens were 8.8 mm (3.8), 12.7 mm (5.9), and 45.7 mm (16.8), respectively. The mean (SD) measured volume was 2.53 (1.49) mL. Using the formula for the volume of a cone, a cylinder, a parallelepiped and a hemiellipsoid, estimated volumes were 1.03 mL (1.22), 3.10 mL (3.65), 6.20 mL (7.31), and 2.07 mL (2.44), respectively. The highest intraclass correlation coefficient between measured and calculated volume was observed when using the formula for the volume of a hemiellipsoid specimen (0.47, 95% CI = 0.36-0.56). CONCLUSIONS: The hemiellipsoid formula is the most accurate determinant of the excised volume. Other formulas do not allow for an accurate estimation of the excised volume.

Treatment failure following excision therapy of CIN: the impact of direct colposcopic vision during procedure.

PURPOSE: To assess whether the use of direct colposcopic vision during excision therapy of cervical intraepithelial neoplasia (CIN) has an impact on the risk of treatment failure. METHODS: Data from 285 patients who had had excision therapy with proven CIN at specimen histological analysis were reviewed. Primary endpoint was the occurrence of post-treatment failure defined by the histological diagnosis of CIN 2-3 during follow-up. Data were analysed according to the use of colposcopy at the time of initial therapy of CIN. RESULTS: The use of direct colposcopic vision (DCV) resulted in a significant reduction in the mean height (p = 0.008) and diameter (p < 0.001) of the excised specimen. Patients' median follow-up was 28.4 (±1.3) months. A total of 43 (15.2 %) patients were diagnosed with treatment failure. Compared to excisions performed without any use of colposcopy, DCV was not found to have any significant impact on the risk of treatment failure (HR: 0.58; 95 % CI 0.16-2.13, p = 0.412), neither when compared to excisions performed immediately after colposcopy (HR: 0.91; 95 % CI 0.47-1.79; p = 0.794). The only factors found to have a significant impact on the risk of treatment failure was the identification of clear margins (HR: 0.36; 95 %CI 0.19-0.69; p = 0.002) and the diameter of the surgical specimen (HR: 0.94; 95 %CI 0.89-0.99; p = 0.040). CONCLUSIONS: Although the use of DCV during excision therapy of CIN was associated with a significant reduction in the dimensions of the excised cervical specimen, it did not result in a significant change in the risk of treatment failure.

Benefits of Direct Colposcopic Vision for Optimal LLETZ Procedure: A Prospective Multicenter Study.

OBJECTIVE: The aim of the study was to assess whether direct colposcopic vision (DCV) of the cervix during large loop excision of the transformation zone (LLETZ) is associated with a decrease in the volume and dimensions of specimens or affects margin status at histology. MATERIALS AND METHODS: A prospective multicenter observational study of 216 women who underwent LLETZ for grades 2 and 3 cervical intraepithelial neoplasia was conducted. The volume and dimensions (circumference, length, and thickness) of the surgical specimens were measured before fixation. Data were compared according to the use of colposcopy during LLETZ. The following 3 groups were considered: LLETZ performed without colposcopy (n = 91), LLETZ performed immediately after colposcopy (n = 51), and LLETZ performed under DCV (n = 74). RESULTS: Patient characteristics were comparable with regard to age, parity, history of excision, indication of the procedure, and the size of the cervix. We found a significant decrease in all dimensions of the specimens obtained under DCV (p < .001). Margin status was not affected. After adjusting for confounders, the mean volumes were significantly lower in the DCV group (adjusted mean difference = -0.66 mL; 95% CI = -1.17 to -0.14). The probability that negative margins would be achieved together with the attainment of a volume less than 5 mL and a thickness less than 10 mm was the highest in the DCV group (adjusted OR = 2.80; 95% CI = 1.13 to 6.90). CONCLUSIONS: Direct colposcopic vision is associated with a significant decrease in the volume and in all dimensions of LLETZ specimens with no compromise in the margin status.

Relationship between HPV 16, 18, 31, 33, 45 DNA detection and quantitation and E6/E7 mRNA detection among a series of cervical specimens with various degrees of histological lesions.

Better understanding of the correlation between high-risk HPV DNA testing, viral load quantitation, and E6/E7 mRNA detection is required. The aim of this study was to assess the relationship between these markers and the severity of cervical lesions. One-hundred and fifty one directed cervical specimens were analysed (normal, cervical intraepithelial neoplasia, and cancer). HPV types 16, 18, 31, 33, and 45 DNA detection and quantititation and E6/E7 mRNA detection were performed. DNA was detected in 87 (57.6%) samples and increased from 0% (normal) to 93.9% (cancer). E6/E7 mRNA was detected in 65 (43%) samples and increased with the severity of the lesions from 0% (normal) to 78.8% (26/33) (cancers) (P < 0.001). HPV DNA and E6/E7 mRNA detection were compared in the 141 samples harbouring HPV16, 18, 31, 33, or 45 infection: 45.4% (64/141) of specimens were DNA-/mRNA-, 46% (65/141) were DNA + /mRNA+ and 8.5% (12/141) were DNA + /mRNA-. The proportion of DNA + /mRNA+ specimens increased with the severity of the lesions (P < 0.001). All normal cervix specimens were DNA-/mRNA-. Among grade 2 cervical intraepithelial neoplasia, prevalence of DNA was higher than that of mRNA: 41.6% (5/12) versus 25% (3/12), whereas it was 79.3% (46/58) versus 62% (36/58) among grade 3 cervical intraepithelial neoplasia. Full concordance was observed in cancers as all the 26 DNA+ specimens were mRNA +. Median overall HPV load was higher in DNA + /mRNA+ than in DNA + /mRNA- specimens (1.41 × 10(6) vs. 9.1 × 10(2) copies per million cells, P < 0.001). Both E6/E7 mRNA detection and concordant DNA + /mRNA+ detection increases with the severity of the lesions and with the HPV DNA load.