Journal

Journal of Gynecology Obstetrics and Human Reproduction

Papers (119)

Patterns of first recurrence and outcomes in surgically treated women with vulvar cancer: results from FRANCOGYN study group

Cancer of the vulva recurrences vary considerably over time and are influenced by several pathological, surgical and adjuvant therapeutic prognostic factors. However, limited information is available about patterns of disease recurrence and prognosis. We analysed patterns of vulvar cancer recurrence based on a large French multicentre database. Data of women with histologically proven squamous cell carcinoma (SCC) and other vulvar cancer treated between 1976 and 2016 were retrospectively abstracted from five institutions with prospectively maintained vulvar cancer databases in France. The endpoints were pattern of recurrence, recurrence free survival (RFS) and overall survival (OS). Time to the first recurrence in a specific site was evaluated by using cumulative incidence analysis (Gray's test) and competing risks regression analysis to estimate sub-distribution hazard ratios and 95% CIs. In the whole population, recurrences were observed in 188 of the 617 women (30%) with local-regional, distant and multifocal recurrences in 18% (109/617), 3% (17/617), 10% (62/617), respectively. The median time to recurrence with Interquartile Range (IQR) was 13 months IQR [8-30]. The overall respective 3-years OS and RFS were 78.5% (IC95%: 74.5-82.5) and 75.5% (IC95%: 71.1-80.0). According to FIGO stage, lymph node status and positive lympho-vascular invasion (LVSI), pattern and time of loco-regional and distant recurrence were significantly different. There wasn't interaction between FIGO stage and LVSI in OS neither RFS (p=0.08 and 0.9 respectively). We report specific time and site patterns of first recurrence according to FIGO stage, lymph node status and lymphovascular invasion status. Positive LVSI is an important and independent prognostic factor. Defining patterns of recurrence may provide useful information for developing follow-up recommendations and designing therapeutic approaches.

Robot-assisted myomectomy versus open surgery: Cost-effectiveness analysis

Fibroids are the most common benign uterine tumors. There are different possibilities for surgical approaches, and evaluating the cost of these operations is fundamental in modern surgery. The aim of our study is to evaluate the cost-effectiveness of robotic-assisted myomectomy (RAM) compared to open myomectomy (OM) in France. This is an original, retrospective cost analysis and cost-effectiveness comparison between RAM and OM. Women aged >18 years who had undergone myomectomy for large (>8 cm) or multiple (3-5) fibroids via RAM or OM were included from three French hospitals. Confounding factors were controlled using inverse probability of treatment weighting. Costs and major operative complications were assessed one month post-surgery for both groups. The cost per major operative complication (defined as intraoperative and/or postoperative transfusions and/or intraoperative blood loss ≥500 mL) averted was calculated. The incremental cost-effectiveness ratio was determined by dividing the difference in costs by the difference in complications. Uncertainty was explored through probabilistic and deterministic sensitivity analyses. Other complications were also compared between the two groups. 33 womens were operate by RAM and 66 by OM. A statistically non-significant reduction in intraoperative and/or postoperative transfusions and/or intraoperative blood loss ≥ 500 mL will be in favor of RAM 36.19 % RAM vs. 38.48 % OM; p = 0.85), with a difference of 2.29 % [95 % CI:27.06 % to 16.58 %]. RAM was more expensive than OM, with an additional cost of €3,555 (P < 0.01). The incremental cost-effectiveness ratio at one month was €155,241 per patient without complications. The intervention was 120 min shorter for OM (157) than RAM (277) (p < 0,01). Readmissions were lower on RAM (0 %) vs. OM (1,21 %) (p < 0,01) and the mean on length of stay was lower on RAM (2,90 days) vs. OM (4,34 days) (p < 0,01). RAM reduced the length of hospitalization without increasing the risk of intraoperative complications compared to OM, making it a viable alternative. However, the economic evaluation within our hospitals did not favor RAM. Prospective studies with optimized RAM procedures are needed to confirm these results.

Ovarian carcinoma in patients aged ≥80 years: A retrospective multicenter study of management and survival in the FRANCOGYN population

The aims of this study were to describe survival outcomes in patients with ovarian cancer aged ≥80 years and to explore predictors of poor prognosis. We collected clinical, demographic, histologic, surgical and follow-up data for patients with ovarian cancer aged ≥80 years from a multicenter French cohort (FRANCOGYN) who underwent surgery from 1999 to 2019. Primary endpoints were overall survival (OS) and disease-free survival (DFS). We performed a descriptive analysis of demographic and clinical data and a survival time analysis and comparison using the Kaplan Meier method and log-rank test. Of 1671 patients treated for ovarian cancer during the study period, 83 were aged ≥80 years (median age at diagnosis, 83 years; range, 80-99). Median OS was 39.6 months (range, 23.64-60.24). Factors significantly associated with OS in the univariate analysis were adjusted Charlson comorbidity index (ACCI) (HR 2.32; 95 % CI, 1.00-5.42 for ACCI >4), FIGO stage (HR 4.07 for FIGO stage >IIA; 95 % CI, 1.43-11.54), debulking surgery (HR 0.40; 95 % CI, 0.20-0.78), residual disease after surgery (HR 3.00; 95 % CI, 1.31-6.87), and postoperative complications (HR 2.24; 95 % CI, 1.04-4.81). Significant independent predictors of worse OS in the multivariate analysis were ACCI >4 (HR 4.96; 95 % CI, 1.57-15.75), perioperative complications (HR 5.01; 95 % CI, 1.32-18.95), and residual tumor after surgical debulking (HR 3.78; 95 % CI, 1.23-11.61). Age by itself should not refrain surgeons and oncologist from proposing surgical debulking and chemotherapy, as recommended by international guidelines for patients with ovarian cancer aged ≥80 years.

The impact of adjunctive metformin to progesterone for the treatment of non-atypical endometrial hyperplasia in a randomized fashion, a placebo-controlled, double blind clinical trial

Endometrial hyperplasia (EH) is a premalignant neoplasm. Most recently, metformin has been suggested as an adjuvant medication for treating of EH with better outcome. Recent evidence has suggested that metformin has anticancer activity by inhibiting cell proliferation and tumor growth. The aim of this study was to evaluate the effect of metformin plus megestrol acetate versus megestrol acetate alone on patient with EH without atypia. This double blind placebo-controlled clinical trial was conducted among 60 women with EH without atypia. Participants were allocated to two equal groups. Treatment group (M + M) received 40 mg megestrol acetate for 14 days of one month and 1000 mg metformin daily for three months. In placebo group (M + P) each patient received the same dose of megestrol acetate plus two tablets of placebo. Endometrial biopsy was performed in all patients three weeks after the last day of medication RESULTS: Data were evaluated based on 29 and 27 women in the M + M group and M + P group, respectively. After 3 months of therapy 27 (93.1 %) women in M + M group had not EH and responded to treatment, which was statistically higher than the rate of response (19 women, 70.4 %) in M + P group. This study showed that megestrol plus metformin was significantly better than megestrol alone for the treatment of endometrial hyperplasia without atypia.

A survey of French gynecologists’ knowledge and attitudes toward conservative treatment for fertility preservation in young patients with endometrial cancer

To describe knowledge and attitudes toward fertility preservation (FP) in patients with endometrial atypical hyperplasia or adenocarcinoma (EC/AH) among French gynecologists MATERIALS AND METHODS: A national survey among French gynaecologists: one questionnaire with one common part and two specific parts for gynecological surgeon (GS) or for specialists in reproductive medicine (SRM) was sent from April 2017 to April 2018. Knowledge and attitudes toward FP in EC/AH were evaluated with a "knowledge score" and an "attitudes score" using a four- or five-point Likert scale. One hundred forty physicians completed the survey (87 GS, 53 SRM). The knowledge score was low (59.3% medium/low), but it was significantly higher for GS compared to SRM. The better-known treatments were oral progestins and hysteroscopic resection. Among the participants treating EC/AH, 52.6% found it "difficult" to manage patients and 61.8% regretted the lack of official recommendations. Most physicians seemed to be uncomfortable/unsupportive with FP in EC/AH (57.2% "attitude score' below 11/20). There was a positive correlation between knowledge and attitude scores. GS "usually/always" give advice to patients about FP before EC/AH treatment. After maximum 3-6 months, 56.6% of SRM chose In Vitro Fecundation (IVF) to reduce time-to-pregnancy, with GnRH antagonist protocols (28%) or mild-stimulation (15.1%) to avoid hyperoestrogenism. Despite reassuring results in the literature, French gynecologists are uncomfortable with FP using EC/AH conservative management, which may be because of a lack of confidence in their knowledge. Specific guidelines are needed to help physicians manage these young patients and their fertility.

Proteomic analysis in endometrial cancer and endometrial hyperplasia tissues by 2D-DIGE technique

To compare the protein expression of complex atypical endometrial hyperplasia, endometrial carcinoma and healthy endometrial tissues, and by this way, to identify proteins that can be used for diagnosis, prognosis and therapeutic targets. Histopathological examination of the D&C material had reported "benign endometrial changes", "complex atypical endometrial hyperplasia" and "endometrioid adenocarcinoma" and 30 patients ,who underwent surgery with these diagnosis, were studied. Protein profiles of the study groups were detected using 2D-DIGE technique and compared to the control group. Protein spots which showing different expression, were defined by MALDI TOF/TOF-MS method. In the present study, significant elevations were observed in the levels of K2C8, UAP56, ENOA, ACTB, GRP78, GSTP1, PSME1, CALR, PPIA, PDIA3 and IDHc proteins when comparisons were made among the cancer cases and the healthy and complex atypical hyperplasia cases. We determined that the induction of CALR activity may be a factor that progresses apoptosis, thus, may be a hope for postoperative new chemotherapy treatment methods. Moreover, when the expressions of the CAH1 and PPIB proteins are compared to complex atypical hyperplasia and endometrial adenocarcinoma stages, we determined that the CAH1 and PPIB levels increased in more advanced stages. Among these indicators, the proteins that had the closest relation to advanced stage cancer were determined as K2C8, UAP56 and GRP78. We think that it would be useful to determine the diagnosis, prediction of prognosis and identifying therapeutic targets of the highlighted proteins of our study that are K2C8, UAP56, GRP78 and CALR in endometrial cancer.

Association between ovarian sex cord-stromal tumors and non-hormone-sensitive cancers: A nationwide nested cohort study

Ovarian sex cord-stromal cell tumors (SCSTs) are a rare group of ovarian neoplasms that include both benign and malignant diseases. Previous studies found an increased risk of breast, endometrial and ovarian cancers among women with SCSTs. However, the risk of new primary non-sex hormone-sensitive cancers remains underreported. In this study we investigated the incidence of SCSTs and the associated risks of non-sex hormone-sensitive cancers using a nested nationwide cohort in Denmark. Cases were identified in the Danish National Pathology Registry and matched on birth year to a control cohort of ten women without SCSTs per case using the Danish National Patient Registry. Cancer incidence was determined using the Danish Cancer Registry. Cox proportional hazards regression assessed associations, adjusting for Charlson Comorbidity Index and socioeconomic variables. A total of 1387 women with SCSTs were included, with thecomas (66 %) and adult granulosa cell tumors (26 %) being the most common subtypes. There was an overall increased rate of new primary malignancy (excluding breast, endometrial and ovarian cancers) among women with SCST (HR = 1.36, 95 % CI: 1.16-1.6). Increased rates of malignant melanoma (HR = 1.52, 95 % CI: 1.14-2.03) and lung cancer (HR = 1.2, 95 % CI: 1.01-1.42) were observed in women with thecomas, whereas other SCST subtypes showed no significant associations with risk of new primary cancers. Overall women with SCSTs have a slightly increased rates of non-hormone-sensitive malignancies, whereas women with thecomas showed marginally elevated rates of lung cancer and melanoma.

Effect of mifepristone on uterine fibroids: A systematic review and meta-analysis

Uterine fibroids are common benign tumors that cause symptoms like bleeding and pain, with mifepristone showing potential for treatment. This study examines the impact of mifepristone dosage on fibroid size and clinical outcomes to inform future research and treatment. A comprehensive search of databases including PubMed, Scopus, and Cochrane Library was conducted up to September 2024. Only randomized controlled trials (RCTs) studies were included, with data analyzed using a random-effects model. Subgroup analyses were performed based on dosage and treatment duration. Sixteen RCTs were included in the analysis. The random-effects model showed that mifepristone, compared to placebo, resulted in a non-significant reduction in leiomyoma volume (SMD = -1.11, 95 % CI:2.63 to 0.40, P = 0.15). A daily dose of 25 mg mifepristone significantly reduced leiomyoma volume compared to 10 mg (SMD = -0.54, 95 % CI:1.06 to -0.02, P = 0.04). Extended use of 10 mg/day versus 5 mg/day also showed a non-significant reduction in leiomyoma volume (SMD = -0.05, 95 % CI:0.23 to 0.12, P = 0.56). Mifepristone did not demonstrate a significant advantage over placebo in reducing uterine fibroid volume. While higher doses (25 mg daily) showed a statistically significant reduction compared to lower doses (10 mg daily), the overall clinical significance remains unclear. Further research is needed to clarify the optimal use of mifepristone in treating uterine fibroids.

High-risk patient profiles for ovarian cancer: A new approach using cluster analysis of tumor markers

Ovarian cancer remains a leading cause of cancer-related deaths in women. Early detection improves prognosis, but current diagnostic tools still need improvement. We aimed to identify high-risk patient profiles for ovarian cancer using cluster analysis of age and tumor marker data. A secondary dataset analysis was conducted using unsupervised learning techniques. Data were from a University Hospital, originally collected between July 2011 and July 2018 in Taiwan. In total, 349 women diagnosed with ovarian masses, including both benign and malignant tumors, were included in this analysis. The median age was 45 years, and 49 % were diagnosed with ovarian cancer in pathology. We used a hierarchical clustering algorithm to find groups of patients with similar features. Two clusters were identified (N = 204 and 145), with a high-risk cluster (66.2 % malignancy) characterized by significantly older age, higher CA125, HE4, CEA, and AFP levels, and a lower CA19-9 level than the low-risk cluster (24.8 % malignancy). The assessment of clustering stability and internal validity yielded a figure of merit score of 0.970 and a silhouette coefficient of 0.524. A classification model using age, CA125, HE4, and CA19-9 demonstrated high accuracy (89.4 %), sensitivity (94.5 %), specificity (83.7 %), and a large area under the curve (89.1 %) for the risk stratification. Integrating tumor markers with patient demographics improved the differentiation between benign and malignant ovarian masses. This approach can help clinicians prioritize high-risk patients for further diagnostic evaluation and reduce unnecessary invasive procedures for low-risk patients.

Comparison of 3D and 2D laparoscopy: Initial experience of perioperative outcomes and clinical assessment

This study was designed to compare three-dimensional (3D) laparoscopy and conventional two-dimensional (2D) laparoscopy in surgical performance and clinical assessment during laparoscopic radical hysterectomy with pelvic lymphadenectomy (LRHND) for treating early-stage cervical cancer. In this study, we included 67 consecutive patients underwent LRHND for treating early-stage cervical cancer by the experienced laparoscopic surgeons between August 2018 and December 2020. amongst these patients, 32 patients underwent 3D laparoscopy (2D group) and 35 patients underwent 2D laparoscopy (2D group). Demographic data, clinical and surgical parameters were obtained from each patient. An end-of-operation questionnaire was administered regarding subjective perception of 3D laparoscopy system. Patient characteristics, including age, BMI, FIGO stage, and histology, were comparable between the two groups. Compared with 2D imaging system, 3D system significantly shortened the operation time, especially bilateral lymph node dissection time. Blood loss was lower in 3D group compared with 2D group. There were no significant differences regarding pelvic nodes retrieved, incidence of complications, hospital stay, the recovery time of bowel, abdominal drainage fluid, hospitalization costs and visual symptoms. In addition, 3D system significantly improved depth perception and precision, and reduced surgical strain and eye strain for surgeon. No statistical difference was observed in visual symptoms and adverse events between the two groups. The surgeon was more willing to accept 3D laparoscopy. The 3D laparoscopy is safe, feasible and comfortable, with obvious advantage in depth perception, precision and surgical strain. It triggered no increase in the complications and adverse events.

Should we perform cervix removal during hysterectomy for benign uterine disease? Clinical practice guidelines from the French College of Gynecologists and Obstetricians (CNGOF)

To provide guidelines from the French College of Obstetricians and Gynecologists (CNGOF), based on the best evidence available, concerning subtotal or total hysterectomy, for benign disease. The CNGOF has decided to adopt the AGREE II and GRADE systems for grading scientific evidence. Each recommendation for practice was allocated a grade, which depends on the quality of evidence (QE) (clinical practice guidelines). Conservation of the uterine cervix is associated with an increased risk of cervical cancer (0.05 to 0.27%) and an increased risk of reoperation for cervical bleeding (QE: high). Uterine cervix removal is associated with a moderate (about 11 min) increase in operative time when hysterectomy is performed by the open abdominal route (laparotomy), but is not associated with longer operative time when the hysterectomy is performed by laparoscopy (QE: moderate). Removal of the uterine cervix is not associated with increased prevalence of short-term follow-up complications (blood transfusion, ureteral or bladder injury) (QE: low) or of long-term follow-up complications (pelvic organ prolapse, sexual disorders, urinary incontinence (QE: moderate). Removal of the uterine cervix is recommended for hysterectomy in women presenting with benign uterine disease (Recommendation: STRONG [GRADE 1-]; the level of evidence was considered to be sufficient and the risk-benefit balance was considered to be favorable).

Identifying risk factors for postoperative complications following staging surgery for endometrial cancer

Endometrial cancer is the most prevalent gynecologic malignancy, with increasing incidence primarily due to aging, obesity, and diabetes. Surgical staging, a gold standard treatment involving total hysterectomy with bilateral salpingo-oophorectomy and sentinel lymph node biopsy, presents various postoperative complications influencing patient outcomes and healthcare costs. This study aims to identify risk factors associated with short term postoperative complications following staging surgery for endometrial cancer. A retrospective cohort study conducted at a single university-affiliated medical center from January 2016 to December 2022. Data were extracted from electronic medical records, including patient demographics and comorbidities, surgical data including intraoperative complications, tumor histology and surgical outcomes. A composite adverse post operative outcome was defined, including need for post-operative blood transfusion, antibiotic treatment, Intensive care unit (ICU) admission, prolonged hospitalization, and 30-day readmission rates. Among 495 patients, 34.3 % experienced at least one postoperative complication. Significant factors associated with complications included age over 65, ASA score >2, pathologic grade 3 tumours, and non-minimally invasive surgical approaches. Prolonged operative time (>75th percentile) and intraoperative complications also correlated with increased risk. Conversely, higher preoperative haemoglobin levels were protective against complications. The findings emphasize the importance of recognizing risk factors such as advanced age, elevated ASA scores, and specific tumor characteristics to enhance preoperative assessments and surgical planning. By tailoring surgical approaches and optimizing patient preparation, healthcare providers may improve postoperative outcomes and reduce complications for patients undergoing staging surgery for endometrial cancer.

Impact of morbid obesity on surgical and oncological outcomes in patients with endometrial cancer undergoing robotic assisted laparoscopic hysterectomy and pelvic lymph node staging

Minimally invasive surgery is the preferred surgical approach in endometrial cancer. Robotic assisted laparoscopy could provide benefits in the obese population. To compare surgical and oncological outcomes between patients with a BMI < 35 kg/m This retrospective monocentric study was conducted at Saint-Louis University Hospital in Paris. The two groups were compared using a univariate analysis. 52 patients were included, 39 patients in Group 1 and 13 patients in Group 2. Operative room occupancy time and operative time were significantly longer in Group 2 than in Group 1 (255.1 min ± 57.0 vs 210.5 min ± 38.3, p = 0.02 and 166.8 min ± 39.7 vs 139.6 min ± 35.3, p = 0.04 respectively). No significant difference was found in length of hospital stay between the 2 groups even if it appears that patients in Group 2 had slightly longer hospitalization than patients in Group 1 (2 days vs 1 day). Only one complication (laparotomy conversion for digestive injury) was observed in Group 2. No significant difference was found in recurrence between the 2 groups. Severe morbid obesity does not affect surgical morbidity or oncological outcomes in women with endometrial cancer who underwent robotic-assisted laparoscopic hysterectomy, bilateral adnexectomy, and pelvic lymph node staging. Optimizing operating room occupancy management must be improved in this patient population.

Impact of cervical excisional dimensions on endocervical margins status in adenocarcinoma in situ of the uterine cervix: A multicenter study from the FRANCOGYN group

Excisional procedures have a central role in the management of adenocarcinoma in situ of the cervix (AIS). We aimed to evaluate the relationship between the excisional specimen dimensions and the endocervical margin status. We conducted a multicentric retrospective study in seven French centers. All cases with proven AIS on a colposcopic biopsy and undergoing an excisional procedure afterwards were included in the analysis. We evaluated the impact of excision length, along with the lateral and anteroposterior diameters on the endocervical margin status. An additional subgroup analysis of the impact of maternal age on endocervical margin status was also conducted. Of the 101 cases of AIS diagnosed on initial biopsy, 95 underwent a primary excisional procedure, among which 80% (n = 76/95) had uninvolved endocervical margins and 20% (n = 19/95) had positive endocervical margins. The excisional specimen length was not significantly related to the endocervical margin status. Conversely, both lateral and antero-posterior diameters were significantly correlated with the negative endocervical margins status: OR = 1,19, 95% CI [1.03, 1.40], p = 0.025, for the lateral diameter and OR = 1.34, 95% CI [1.14, 1.64], p = 0.001 for the antero-posterior diameter. The median lateral diameter was 20 mm, IQR (18, 24) in case of endocervical negative margins vs. 18 mm IQR (15, 24) in case of positive endocervical margins (p = 0.039), and the median anteroposterior diameter was 17 mm IQR (15, 20) in case of negative endocervical margins vs 14 mm IQR (11, 15) in case of positive endocervical margins (p = 0.004), respectively.  Additionally, in patients over 45 years old, endocervical margin were more likely to be positive despite similar excisional dimensions (7/17 (41%) of positive endocercival margins before 45 years old vs 12/78 (15%) after, p = 0.039) CONCLUSIONS: Endocervical margin statues were significantly related to the transverse diameters (lateral and anteroposterior diameters), but not to the excision specimen length. Reducing the excised length may lead to fewer post-procedure complications but would still allow to obtain a large proportion of negative endocervical margins.

RETRACTED: Comparison of the four malignancy risk indices in the discrimination of malignant ovarian masses: A cross-sectional study

To evaluate the accuracy of the four malignancy risk indices to distinguish benign from malignant ovarian masses MATERIALS AND METHODS: This was an observational cross-sectional study conducted on 155 patients between January 2016 and January 2019. Women with ovarian masses planned for surgical management were recruited from the outpatient Gynecology clinic of the hospital. The risk of malignancy index (RMI 1-4) was calculated for all women with ovarian masses. Biopsies obtained from the ovarian masses after the surgical intervention was sent to the pathology lab for histopathological examination. The histopathologic diagnosis of the ovarian masses was considered the gold standard for diagnosis. The participants' mean age in the group of patients with benign masses was 33.50 ± 14.53 years versus 45.09 ± 13.67 years in the malignant group. The two most prominent features in the malignant group were solid areas in 85.3 % of malignant masses and about 91.2 % of malignant masses showing size <7 cm in their largest diameter. The RMI's most sensitive individual parameter was the CA-125 level, while the lowest sensitivity was for the menopausal status. RMI 2 had the highest sensitivity of 76.47 %, while RMI 1 and 3 had the highest specificity, 92.56 %. RMI 2 had the highest AUC, 0.83. RMI 2 is a simple and reliable tool and had the best performance among all RMIs in benign discrimination from malignant ovarian masses with high sensitivity and accuracy.

Borderline ovarian tumors: French guidelines from the CNGOF. Part 1. Epidemiology, biopathology, imaging and biomarkers

The incidence (rate per 100 000) of borderline ovarian tumors (BOTs) increases progressively with age, starting at 15-19 years and peaking at around 4.5 cases per 100 000 at an age of 55-59 years (LE3) with a median age of 46 years. The five year survival for FIGO stages I, II, III and IV is 99.7 % (95 % CI: 96.2-100 %), 99.6 % (95 % CI: 92.6-100 %), 95.3 % (95 % CI: 91.8-97.4 %) and 77.1 % (95 % CI: 58.0-88.3 %), respectively (LE3). An epidemiological association exists between the individual risk of BOT and family history of BOT and certain other cancers (pancreatic, lung, bone, leukemia) (LE3), a personal history of benign ovarian cyst (LE2), a personal history of tubo-ovarian infection (LE3), the use of a levonorgestrel intrauterine device (LE3), oral contraceptive use (LE3), multiparity (LE3), Hormonal replacement therapy (LE3), high consumption of Coumestrol (LE4), medical treatment for infertility with progesterone (LE3) and non-steroidal anti-inflammatory drug use (LE3). Screening for BOTs is not recommended for patients (Grade C). The overall risk of recurrence of BOTs varies between 2% and 24 %, with an overall survival greater than 94 % at 10 years, and the risk of an invasive recurrence of a BOT ranges from 0.5 % to 3.8 %. The use of scores and nomograms can be useful in assessing the risk of recurrence, and providing patients with information (Grade C). The WHO classification is recommended for classifying BOTs. It is recommended that the presence of a microinvasive focus (<5 mm) and microinvasive carcinoma (<5 mm with an atypical nuclei and a desmoplastic stroma reaction) within a BOT be reported. In cases of serous BOT, it is recommended to specify the classic histological subtype or micropapillary / cribriform type (Grade C). When confronted with a BOT, it is recommended that the invasive or non-invasive nature of peritoneal implants can be investigated based solely on the invasion and destruction of underlying adipose or peritoneal tissue which has a desmoplastic stromal reaction where in contact with the invasive clusters (Grade B). For bilateral mucinous BOTs and / or in cases with peritoneal implants or peritoneal pseudomyxoma, it is recommended to also look for a primitive digestive or pancreato-biliary cancer (Grade C). It is recommended to sample ovarian tumors suspected of being BOTs by focusing samples on vegetations and solid components, with at least 1 sample per cm in tumors with a size less than 10 cm and 2 samples per cm in tumors with a size greater than 10 cm (Grade C). In cases of BOTs and in the absence of macroscopic omental involvement after careful macroscopic examination, it is recommended to perform at least 4-6 systematic sampling blocks and to include all peritoneal implants (Grade C). It is recommended to consult an expert pathologist in gynecology when a BOT suspicion requires intraoperative extemporaneous histology (grade C). Endo-vaginal and suprapubic ultrasonography are recommended for the analysis of an ovarian mass (Grade A). In case of an undetermined ovarian lesion on ultrasonography, it is recommended that a pelvic MRI be performed (Grade A). To analyze an adnexal mass with MRI, it is recommended to use an MRI protocol with T2, T1, T1 Fat Sat, dynamic and diffusion sequences as well as gadolinium injection (Grade B). To characterize an adnexal mass with MRI, it is recommended to include a score system for malignancy (ADNEX MR/O-RADS) (Grade C) in the report and to formulate a histological hypothesis (Grade C). Pelvic MRI is recommended to characterize a tumor suspected of being a BOT (Grade C). Macroscopic MRI features should be analyzed to differentiate BOT subtypes (Grade C). Pelvic ultrasound is the first-line examination for the detection and characterization of adnexal masses during pregnancy (Grade C). Pelvic MRI is recommended from 12 weeks of gestation in case of an indeterminate adnexal mass and should provide a diagnostic score (Grade C). Gadolinium injection must be minimized as fetal impairment has been proven (Grade C). It is recommended that serum levels of HE4 and CA125 be evaluated and that the ROMA score for the diagnosis of an indeterminate ovarian mass on imaging be used (grade A). In case of suspicion of a mucinous BOT on imaging, dosage of serum levels of CA 19-9 can be considered (Grade C). If the determination of tumor markers is normal preoperatively, routine dosage of tumor markers in BOT follow-up is not recommended (Grade C). In case of preoperative elevation in tumor markers, the determination of serum CA 125 levels is recommended in the follow-up of BOT (Grade B). When conservative treatment of a BOT has been adopted, the use of endovaginal and transabdominal ultrasonography is recommended during follow-up (Grade B).

Borderline ovarian tumors: French guidelines from the CNGOF. Part 2. Surgical management, follow-up, hormone replacement therapy, fertility management and preservation

In the Early Stages (ES) of Borderline Ovarian Tumor (BOT), if surgery without risk of tumor rupture is possible, then laparoscopy with protected extraction is recommended over laparotomy (Grade C). In case of bilateral serous ES BOT treatment with a strategy to preserve fertility and/or endocrine function, bilateral cystectomy is recommended if possible (Grade B). In case of mucinous BOT treatment with a strategy to preserve fertility and/or endocrine function, unilateral adnexectomy is recommended (grade C). In the case of a mucinous BOT in a patient who has had an initial cystectomy, unilateral adnexectomy is recommended (grade C). In the case of treatment of a serous ES BOT in a patient who has had an initial cystectomy, with a strategy to preserve fertility and/or endocrine function, restaging surgery for adnexectomy is not recommended in the absence of suspicious residual lesions at the time of surgery and/or postoperative imaging (reference ultrasonography or pelvic MRI) (grade C). For serous or mucinous ES BOTs, routine hysterectomy is not recommended (Grade C). In cases of ES BOTs, lymphadenectomy is not recommended (Grade C). For ES BOTs, appendectomy is recommended only if there is a macroscopically pathological aspect to the appendix (Grade C). Restaging surgery is recommended in case of a serous BOT with a micropapillary aspect and an unsatisfactory inspection of the abdominal cavity during initial surgery (Grade C). Restaging surgery is recommended in cases of mucinous BOT if only a cystectomy has been performed or if the appendix has not been evaluated (Grade C). If restaging surgery is decided for an ES BOT, the following procedures should be performed: peritoneal cytology (grade C), omentectomy (there is no data in literature to recommend which type of omentectomy should be performed) (grade B), complete exploration of the abdominal cavity with peritoneal biopsies (grade C), visualization of the appendix +/- appendectomy in case of pathological macroscopic appearance (grade C) and unilateral adnexectomy in case of a mucinous BOT (grade C). In advanced stages of BOT it is not recommended to perform a lymphadenectomy as a routine procedure (Grade C). In cases of an advanced stage BOT, in a patient with a desire to fall pregnant, conservative treatment involving preservation of the uterus and all or part of the ovary may be proposed after a multidisciplinary meeting (Grade C). Second surgery aimed at removing all lesions, if not performed initially, is recommended in cases of advanced stage BOT (Grade C). It is not recommended to perform completion surgery after conservative treatment (preservation of the ovaries and the uterus) and after the achievement of fertility desire for a serous BOT (Grade B). After treatment for a BOT, follow-up beyond 5 years is recommended due to the median time to recurrence (Grade B). It is recommended that a systematic clinical examination be carried out during follow-up of a treated BOT (Grade B). In the particular case of an initial elevation of CA 125 levels, it is recommended to monitor CA 125 during follow up (Grade B). In cases treated conservatively (ovarian and uterine conservation), it is recommended to use endovaginal and transabdominal ultrasonography during the follow up period (Grade B). In the event of a recurrence of a BOT, in a woman of childbearing age, a conservative treatment strategy can again be proposed (Grade C). In the presence of non-invasive BOT implants, conservative treatment may be considered after a first non-invasive recurrence in women who wish to preserve their fertility (Grade C). Pelvic MRI is recommended after 12 weeks of amenorrhea in case of an undetermined adnexal mass and should be concluded with a diagnostic score (Grade C). The injection of gadolinium, in case of pregnancy, should be discussed on a case-by-case basis due to the proven risks for the foetus (Grade C). If feasible, a laparoscopic approach should be preferred during pregnancy (Grade C). A consultation with a specialist reproductive physician should be offered to patients with a BOT and of childbearing age (Grade C). It is recommended that patients be provided with full information on the risk of decreased ovarian reserve following to surgical treatment. It is recommended that the ovarian reserve be evaluated prior to surgical management of a suspected BOT (Grade C). When possible, a conservative surgical strategy is recommended to preserve fertility in women of childbearing age (Grade C). There is no specific data on the management of infertility following to conservative treatment of BOT. In case of durable infertility following to conservative treatment of BOT, a consultation with a specialist reproductive physician is required (Grade C). In the case of optimally treated BOT, there is no evidence in literature to contraindicate the use of Assisted Reproductive Techniques (ART). The use of hormonal contraception after serous or mucinous BOT is not contraindicated (Grade C). After treatment of a mucinous BOT, for women aged under 45 years, given the benefit of hormonal replacement therapy (HRT) on cardiovascular and bone risks, and the lack of hormone-sensitivity of mucinous BOTs, it is recommended to offer HRT (Grade C). After treatment of a mucinous BOT, for women over 45 years of age, there is no argument to contraindicate the use of HRT. HRT can be prescribed in case of a climacteric syndrome, as part of an individual benefit to risk assessment (Grade C).

Risk factors for recurrence of borderline ovarian tumors in France: A multicenter retrospective study by the FRANCOGYN group

Borderline ovarian tumors (BOTs) although rare, have shown an increase in the incidence worldwide. Although the survival rate is high, the recurrence rate is estimated to be between 5% and 34%. The objective of this study was to identify risk factors for recurrence of BOTs. This retrospective multicenter study included 493 patients treated surgically for BOT between January 2001 and December 2018. Thirty-seven patients showed recurrence (group R, 7.5%), while 456 did not (group NR, 92.5%). With an average follow-up of 30.5 months (1-276), the overall recurrence rate was 7.5%. Recurrence rates for the BOT and invasive types were 5.7% (n = 28) and 1.4% (n = 7), respectively. The mean time to recurrence was 44.1 (3-251) months. Univariate analysis showed that age at diagnosis, type of surgical procedure, histological type, and FIGO stage were factors influencing recurrence. Multivariate analysis showed that the risk factors for recurrence of BOT were conservative treatment (OR = 7 [95% CI 3.01-16.23]; p < 0.05) and advanced FIGO stage (OR = 5.86 [95% CI 2.21-15.5]; p < 0.05). To the best of our knowledge, this multicenter study was one of the largest studies on the risk factors for BOT recurrence. Conservative treatment and advanced FIGO stage were identified as risk factors for BOT recurrence. These results reinforce the need for restaging of patients who did not have an optimal initial surgical staging so as not to avoid missing a tumor in the advanced stage. Referral to a surgical oncology center is suggested to optimize overall patient management.

Endometrial biopsy: Indications, techniques and recommendations. An evidence-based guideline for clinical practice

This practice guideline provides updated evidence for the gynecologist who performs endometrial biopsy (EB) in gynecologic clinical practice. An international committee of gynecology experts developed the recommendations according to AGREE Reporting Guideline. An adequate tissue sampling is mandatory when performing an EB. Blind methods should not be first choice in patients with suspected endometrial malignancy. Hysteroscopy is the targeted-biopsy method with highest diagnostic accuracy and cost-effectiveness. Blind suction techniques are not reliable for the diagnosis of endometrial polyps. In low resources settings, and in absence of the capacity to perform office hysteroscopy, blind techniques could be used for EB. Hysteroscopic punch biopsy allows to collect only limited amount of endometrial tissue. grasp biopsy technique should be considered first choice in reproductive aged women, bipolar electrode chip biopsy should be preferred with hypotrophic or atrophic endometrium. EB is required for the final diagnosis of chronic endometritis. There is no consensus regarding which endometrial thickness cut-off should be used for recommending EB in asymptomatic postmenopausal women. EB should be offered to young women with abnormal uterine bleeding and risk factors for endometrial carcinoma. Endometrial pathology should be excluded with EB in nonobese women with unopposed hyperestrogenism. Hysteroscopy with EB is useful in patients with abnormal bleeding even without sonographic evidence of pathology. EB has high sensitivity for detecting intrauterine pathologies. In postmenopausal women with uterine bleeding, EB is recommended. Women with sonographic endometrial thickness > 4 mm using tamoxifen should undergo hysteroscopic EB.

Adnexal masses in patients with colorectal cancer

To evaluate the clinicopathological features and outcomes of patients undergone surgery for benign and metastatic adnexal masses during the surveillance of colorectal cancer (CRC). A single institute retrospective study involving 90 patients diagnosed with CRC that undergone surgery at Hacettepe University Hospital between 2000-2018. Clinicopathological and survival data was obtained from hospital records. Elevated blood levels of CEA (HR, 1.23; 95 % CI: 1.03-1.24; p = 0.01), adnexal masses larger than 5 cm (HR, 3.296; 95 % CI: 1.527-7.076; p = 0.002), bilaterality of adnexal mass (HR, 2.200; 95 % CI: 2.464-11.969; p = 0.001) and high PCI score (HR, 0.150; 95 % CI: 0.044-0.479; p = 0.01) were found to be significantly associated with ovarian metastasis. There was a significant difference in overall survival (OS), with respect to complete and incomplete resection in adnexal surgery of ovarian metastasis (46.6 vs. 29.6 months; p = 0.004). The median survival time was 32.8 months for patients with ≤ 24 months interval time to adnexal metastasis surgery, and 48.5 months for patients with >24 months interval time to adnexal metastasis surgery (p = 0.001). This study showed that numerous clinicopathological variables such as bilaterality and size of adnexal mass, serum blood levels of CEA and PCI score may have a significant impact on the prediction and management of ovarian masses diagnosed during CRC surveillance. Complete resection and interval time to adnexal surgery is significantly associated with OS.

Accuracy of peritoneal carcinomatosis extent diagnosis by initial FDG PET CT in epithelial ovarian cancer: A multicentre study of the FRANCOGYN research group

Peritoneal carcinomatosis extent in ovarian cancer is difficult to evaluate by imaging techniques even though it determines the surgical complexity and survival. The aim of this study was to estimate the accuracy of 2-[18F]-fluoro-2-deoxy-d-glucose (FDG)-PET CT (Positron-emission tomography coupled with Computerised Tomography) performed before any treatment, in the diagnosis of the extent of peritoneal carcinomatosis. We compared these results to per-operative observations/ histology samples obtained during surgery (laparotomy/ laparoscopy). All women managed for an epithelial ovarian cancer between 1st January 2000 and 30th June 2016 were included if they had a FDG PET CT, before initiation of any treatment (neoadjuvant chemotherapy or frontline cytoreductive surgery). The extent of disease on histology samples from cytoreductive surgery/observations during exploratory laparoscopy were compared with the PET CT results. Over the study period, 980 women were managed for epithelial ovarian cancer, among them 90 (9.2 %) had a PET CT before any treatment. The diagnostic reliability of an ovarian lesion was 67.8 %, a colon lesion was 61.25 %, a small intestine lesion was 50.6 %, an epiploic lesion was 41.7 %, a pelvic ganglionic invasion was 62.9 % and a paraortic lymph node invasion was 61.5 %. PET CT was less effective than a standard CT examination. PET CT is not the most effective imaging examination to estimate the extent of peritoneal carcinomatosis during the initial management of an epithelial ovarian cancer.

Effect of tumor size on the accuracy of frozen section in the evaluation of mucinous borderline ovarian tumors

This study aims to evaluate the accuracy of frozen section (FS) in mucinous borderline ovarian tumors (BOTs) and to examine the factors associated with misdiagnosis. In this retrospective study, cases diagnosed as mucinous BOTs by FS or final pathologic (FP) results were studied. The results of FS and FP were compared, and the factors associated with misdiagnosis were analyzed. Seventy-nine cases were examined. The median tumor diameter was 16 (6-50) cm, and 89.9 % of cases had tumors ≥10 cm. The overall agreement ratio between FS and FP was 79.7 %. Over-diagnosis and under-diagnosis rates were 3.8 % and 16.5 %, respectively. The sensitivity and positive predictive values were both 88.7 %. None of the underdiagnosed patients (13 cases) had recurrence during the 100-month median follow-up (9-222). Misdiagnosis was more common in tumors <10 cm (p = 0.025). The under-diagnosis rate for tumors <10 cm was 30.8 %. Tumor size <10 cm was significantly associated with misdiagnosis in univariate and multivariate analyses (Odds ratio {OR} 4.92, 95 % Confidence Interval {CI} (1.08-22.45) p = 0.040; OR 5.17, 95 % CI (1.07-25.05) p = 0.041, respectively). Laterality and preoperative CA 125 levels were not associated with misdiagnosis. Tumor size <10 cm is associated with misdiagnosis in mucinous BOTs. Laterality and CA 125 levels do not affect diagnostic accuracy. The evaluation of FS by gynecologic pathologists can help to increase the accuracy of FS.

Is there a correlation of positive peritoneal washing cytology during interval debulking surgery on the survival outcomes of ovarian cancer patients? A systematic review and meta-analysis of the literature

The aim of the present study was to evaluate the prognostic impact of peritoneal washing cytology (PWC) on progression-free (PFS) and overall survival (OS) of patients undergoing interval debulking surgery (IDS) after neoadjuvant chemotherapy (NACT) for ovarian cancer (OC). We systematically searched Medline (1966-2020), Scopus (2004-2020), EMBASE (1980-2020), Cochrane Central Register of Controlled Trials CENTRAL (1999-2020), Clinicaltrials.gov (2008-2020) and Google Scholar (2004-2020). All the studies that investigated the correlation of peritoneal washing cytology with survival outcomes of patients undergoing interval debulking for ovarian cancer, were finally included in the present meta-analysis. A total of 7 retrospective studies were included, comprising 907 patients, of whom 535 had positive peritoneal washing cytology on interval debulking surgery. The methodological quality of the included studies was assessed as moderate, primarily due to the lack of data referring to the adequacy of the follow-up of patients and secondarily due the lack of comparability of patients. Progression - free survival was significantly better in the negative peritoneal cytology group (HR 2.07, 95% CI 1.73, 2.48 respectively), however, overall survival did not reach a significant difference among the two groups (HR 1.90, 95% CI 0.99, 3,65, p = 0.052). Our data support a negative correlation between positive peritoneal washing cytology at interval debulking surgery and the survival of ovarian cancer patients.

Ovarian metastases from breast cancer: A report of 24 cases

The purpose of this study was to investigate the epidemiological, demographical characteristics and survival outcomes of the patients with ovarian metastases from breast cancer. Medical records of 24 patients with pathologically confirmed metastases in ovaries treated at two tertiary hospitals between 2000 and 2019 were reviewed retrospectively. Patients' as well as tumor characteristics, and treatment data were collected. Ovarian metastases of breast cancer were documented using a system of analogous to the FIGO classification for ovarian cancer. Survival after primary breast cancer diagnosis and after diagnosis of metastases in ovaries were calculated. Outcomes were compared between the three different procedures bilateral salpingo-oophorectomy, total hysterectomy with bilateral salpingo-oophorectomy, and total hysterectomy with bilateral salpingo-oophorectomy with omentectomy. The majority of patients had estrogen receptor positive (87 %) and progesterone receptor positive (91 %), 80 % patients were HER2/neu negative. The majority of patients had primary tumor stage by TNM classification T1 (33 %) and T2 (50 %); node- negative (25 %) and node-positive (75 %); 71 % of patients had no distal metastases in primary breast cancer diagnosis (M0) while 29 % of patients had distant metastases. The median age of primary breast cancer diagnosis was 46.5 ± 10.4 years (range 25-69). The mean time to occurrence of secondary ovarian malignancies after primary breast cancer diagnosis was 62.9 ± 62.8 months (range 0-219). The majority of women underwent adnexectomy (37.5 %) or total hysterectomy with adnexectomy (37.5 %). The mean survival after breast cancer treatment was 72 months, and the mean survival after discovery of ovarian metastases was 25 months. Our results showed that more radical surgical treatment of metastases to ovaries has no increase of survival among patients. However, it should be noted that this may be affected by different stage of primary disease. Thus, larger and more standardized studies need to be done in order to confirm prognostic features and the choice of surgical volume.

Nomograms for primary mucinous ovarian cancer: A SEER population-based study

To develop predictive nomograms of overall survival (OS) and cancer-specific survival (CSS) in patients with primary mucinous ovarian cancer (PMOC). Patients diagnosed with PMOC from 2010 to 2015 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, and randomly divided into a training cohort and a validation cohort. Univariate and multivariate Cox regression analyses were conducted to identify the independent risk factors. Nomograms were constructed and then verified by calibration plots, the concordance index (C-index), and the area under the receiver operating characteristic curve (AUC). A total of 991 patients with PMOC were enrolled and randomly divided into a training cohort (n=695) and a validation cohort (n=296) at a ratio of 7:3. Multivariate Cox regression analyses demonstrated that independent risk factors for OS included age, laterality, and American Joint Committee on Cancer (AJCC) stage. Independent risk factors for CSS included age, laterality, grade, and AJCC stage. Predictive nomograms for OS and CSS were developed with respective independent risk variables. In the training cohort, the C-index of the CSS and OS nomograms were 0.88 [95% confidence interval (CI): 0.84-0.92] and 0.85 (95% CI: 0.81-0.89), respectively. In the validation cohort, the C-index of the predictive CSS and OS nomograms were 0.86 (95% CI: 0.80-0.92) and 0.80 (95% CI: 0.74-0.87), respectively. The AUCs were higher in both cohorts. Furthermore, the calibration curves in both cohorts showed good consistency between the predicted results and the actual results. The nomograms demonstrated good predictability for the survival of patients with PMOC, and could serve as an applicable tool to help clinicians improve treatment plans.

Nodal staging in high and high-intermediate risk endometrial cancer surgery: Which role in the molecular classification era?

Nodal staging contributes to risk group definition and the indication to adjuvant treatment in endometrial cancer (EC) patients. However, the role of nodal assessment evolved and requires redefinition. Primary outcome of the study was to assess the impact of surgical nodal staging in defining high-risk (HR) EC. Secondary outcome was to evaluate the contribution of nodal assessment to the decision for adjuvant treatment in both high-risk and high-intermediate risk (HIR) patients submitted to surgery. Clinical stage I-II EC patients with postoperative diagnosis of HR and HIR disease were included. The contribution of nodal staging in prognostic groups allocation was assessed by reviewing HR patients to identify those without any other feature of such class (non-endometrioid histology, p53abn immunohistochemistry, post-operative T3-T4 disease) and HIR cases to assess how nodal staging affected adjuvant treatment indication. Descriptive statistics were conducted to describe the two populations. Fifty-seven patients were included, 46 with HR and 11 with HIR disease. Chemotherapy and external-beam radiotherapy (EBRT) were proposed in 40 HR patients. Considering histology, immunohistochemical profile and FIGO stage, high risk classification was exclusively relied on nodal involvement in 2/46 cases (4.3 %). Omitting retroperitoneal staging, one of them would have been classified in the intermediate risk group and the other as HIR: without nodal staging, chemotherapy and EBRT would have been omitted in 1/40 (2.5 %) case. Among HIR patients, chemotherapy was proposed in 7/11 cases and EBRT in all cases. Adjuvant chemotherapy was indicated in 5/6 (83.3 %) and omitted in 1/6 (16.7 %) pN0 patient (stage Ib G2, substantial LVSI). In HIRpN0 patients, omitting nodal staging could have changed adjuvant treatment indication in 1/6 (16.7 %) case. In HIRpNx patients, adjuvant chemotherapy was omitted in one patient (stage II, grade 2 and LVSI negative): nodal staging unavailability might have changed indication to chemotherapy in 1/5 (20 %) case, without changing indication to EBRT. Unavailable nodal staging could globally be related to omission of chemotherapy in 2/57 (3.5 %) patients and of EBRT in 1/57 (1.8 %) patient. In this series, nodal staging had limited impact on definition of HR class and on the choice of adjuvant treatment in HR and HIR EC patients.

The significance of post-radiotherapy parametrial involvement and the necessity of parametrial resection in locally-recurrent or persistent cervical cancer developed after radiotherapy

To retrospectively evaluated the prognostic significance of post-radiotherapy parametrial involvement (PMI), the necessity of parametrial resection, and the optimal salvage surgery in locally recurrent or persistent cervical cancer developed after radiotherapy. Patients who developed recurrent or persistent cervical cancer in a previously irradiated field and were subsequently treated with salvage surgery were identified, and the prognostic impact of post-radiotherapy PMI on patient's survival was first investigated. Then, the optimal salvage surgery for patients with post-radiotherapy PMI as well as the predictors for post-radiotherapy PMI were evaluated. A total of 60 patients underwent salvage surgery for recurrent or persistent diseases. Of these, 21 (35.0%) showed post-radiotherapy PMI (PMI-group). Patients in PMI-group showed significantly shorter progression-free survival (PFS) than those in non-PMI-group (p = 0.01). In both PMI-group and non-PMI-group, PFS was affected by the completeness of salvage surgery. In non-PMI-group, less radical surgery achieved similar therapeutic efficacy to more radical surgery (3-year PFS rates: 62.5% versus 54.1%, p = 0.91). In contrast, in PMI-group, not less radical surgery but more radical surgery achieved curative therapeutic efficacy (3-year PFS rate: 0% versus 28.9%). Maximum tumor diameter, deep stromal invasion, and LVSI were found to be predictors of post-radiotherapy PMI. Post-radiotherapy PMI is an indicator of short survival after salvage surgery in patients with locally recurrent or persistent cervical cancer developed after radiotherapy. Both less radical and more radical surgery have curative therapeutic efficacies in patients without post-radiotherapy PMI, if the tumor could be resected with an adequate surgical margin. Thus, hysterectomy type should be tailored to the risk for post-radiotherapy PMI.

Nomograms for predicting risk and prognosis of liver metastases in ovarian cancer patients

Liver metastases (LiM) commonly manifest in ovarian cancer (OC) patients. We intended to establish nomograms for predicting the risk and prognostic factors in OCLiM patients. Data from the SEER database (Nov 2022, Sub 1992-2020) were analyzed, excluding patients with missing data on liver metastases, survival months, race, AJCC T stage, marital status, rural/urban status, and metastases to bone, brain, or lung. Logistic and Cox regression analyses identified risk and prognostic factors for liver metastases. Predictive nomograms were developed from the multivariable regression results. The nomograms were evaluated using Harrell's C-index, ROC curve, calibration curve, DCA, NRI, and IDI. Moreover, the efficacy of the treatment in the new risk stratification subgroups was demonstrated by Kaplan-Meier (KM) curves. Among 17,056 OC patients, 5.67% (n = 967) had liver metastases. Nomograms were constructed based on identified risk and prognostic factors, with dynamic web-based nomograms developed for clinical use. The nomogram demonstrated C-index values of 81.9% (training) and 82.9% (validation) for predicting liver metastases. For OS and CSS, the C-index values were 73.3% and 73.7% (training), and 73.3% and 72.8% (validation), respectively. The ROC curves for OS at 1-, 3-, 5-year showed AUC values of 84.1%, 79.8%, 75.9% (training) and 82.9%, 78.5%, 82.2% (validation), respectively. For CSS, AUC values at 1-, 3-, and 5-year were 84.5%, 80.2%, 76.1% (training) and 82.6%, 78.0, 82.0% (validation), respectively. The calibration and DCA curves confirmed favorable performance. NRI and IDI analyses showed superiority over the Grade and AJCC stage systems. Surgery improved prognosis in the low-risk group, while chemotherapy was more effective in both low- and medium-risk groups. we developed nomograms and risk stratification systems to assist clinicians in the individualized prediction, risk stratification, and prognostic assessment of OCLiM patients.

Trachelectomy: How is it actually done? A review from FRANCOGYN group Titre: Trachélectomie: comment faire en pratique ? Revue de la littérature par le groupe FRANCOGYN

Because of the peak incidence of cervical cancer between the ages of 35 and 44 and the increasing age of first pregnancy, the issue of fertility preservation in cases of early-stage cervical cancer in women in this reproductive age category arises. Early-stage cervical cancer patients have a good prognosis and are surgically treated in cases of mildly aggressive human papillomavirus-related histological type (squamous cell carcinoma, adenocarcinoma), FIGO stage IA to IB1 (i.e., <2 cm), with shallow stromal invasion (<10 mm) and without the presence of lymph-vascular space invasion or lymph node or regional involvement. Under these conditions, conservative treatment by trachelectomy, which has recurrence-free and overall survival rates equivalent to that of hysterectomy, may be considered. After a complete pre-therapeutic assessment, including pelvic lymphadenectomy, to eliminate all contraindications to conservative treatment, a simple or enlarged trachelectomy can be chosen. According to some authors, the route of entry (vaginal, simple or robot-assisted laparoscopy, laparotomy) has no significant effect on survival or fertility, although the literature on the subject is limited. Trachelectomy offers good results in terms of fertility, with an estimated pregnancy rate of between 23% and 55% and a live birth rate of 70%. The significant reduction of the cervix associated with the procedure increases the risk of prematurity. However, this can be prevented by the use of a permanent cerclage. Close follow-up of these patients is essential for a minimum period of 5 years in order to detect any recurrence or postoperative complications.

Laser conization for cervical intraepithelial neoplasia: Effectiveness and obstetric outcomes

To evaluate the effectiveness and obstetric outcomes after laser conization for cervical intraepithelial neoplasia. This retrospective study included 757 patients who underwent laser conization between 2014 and 2020. Patients with a diagnosis of invasive lesions or adenocarcinoma in situ were excluded. Histological data from the conization specimen, pre and postoperative histological and virological data (Human PapillomaVirus (HPV) test) and obstetric outcomes were collected from the medical record. The primary endpoint was the negative surgical margin rates after laser conization. The secondary endpoint were the size of the operative specimen, the postoperative virological test results (3 to 6 months after surgery), factors associated with negative or positive margin and postoperative obstetric outcomes (prematurity). Patient characteristics and outcomes were compared using Student's t-test, χ² test, or Fisher exact test. Values of p ≤ 0.05 were considered significant. This study included 757 patients. Negative surgical margins were obtained in 76.1% of the cases and were associated with more negative HPV tests at 6 months (64.9% vs. 52.5%, p = 0.006) and fewer repeat surgeries (0.2% vs. 2.2%, p = 0.013) than for patients with positive margins. Among the patients under 43 years at the time of conization, 71 achieved a pregnancy with a term >22 weeks, and of these 66 (93%) delivered at term (≥37 weeks). Laser conization appears to be an effective technique for the management of cervical intraepithelial neoplasia both in terms of the quality of the resection margins and the obstetric prognosis.

Histological results of para-aortic lymph node dissection in patients with negative PET-CT for locally advanced cervical cancer in Reunion Island

In locally advanced cervical cancer (LACC), para-aortic staging is required to determine therapeutic strategy and may be performed using PET-CT; if the scan is negative in the para-aortic region, surgical staging is optional. The aim of the study was to evaluate histological results of para-aortic lymph node dissection in patients with locally advanced cervical cancer and negative PET-CT in Reunion Island. This is a bicentric retrospective study including patients from January 2014 to December 2023 at Saint-Denis and Saint-Pierre university hospitals. Patients with LACC and negative PET-CT in para-aortic region prior to lymphadenectomy were included. The primary outcome was to evaluate the rate of false negative results on PET-CT in lumbo-aortic region in patients with cervicale cancer. In all, 66 patients were included for analysis. A total of 7 patients (10.6 %) had positive lymph nodes on histology examination when PET-CT was negative. Three patients had positive pelvic PET-CT whereas the 4 remaining patients had a negative pelvic PET-CT. 10.6 % of patients with negative para-aortic PET-CT had positive histology results. There was no significant difference between the para-aortic histological results depending on the pelvic PET-CT results. The PAROLA study, which is currently being recruited, should provide an answer to the question of the benefit of lumbo-aortic lymph node dissection on recurrence-free survival at 3 years.

Comparison of survival outcomes between laparoscopic and abdominal radical hysterectomy for early-stage cervical cancer: A French multicentric study

A recent randomized controlled trial has reconsidered the use of laparoscopy for treating patients with early-stage cervical cancer with radical hysterectomy (RH). We aimed to evaluate if surgical approach had an impact on surgical and oncological outcomes in these patients in a French setting. Data of 1706 patients with cervical cancer treated between 1996 and 2017 were extracted from maintained databases of 9 French University hospitals. Patients, with FIGO stage IA2 to IIB tumors, treated by radical hysterectomy were selected for further analysis. A propensity score matching was used with a ratio of 2:1 in favor of laparoscopic approach was used. The Kaplan Meier method was used to estimate the survival distribution. 34 patients treated with laparotomy were matched with 61 patients treated by minimally invasive surgery (MIS). There was no difference regarding overall survival (91 % vs 81 %, p > 0.05) or disease-free survival (82 % vs 78 %, p > 0.05). There was no difference regarding surgical outcomes with no excess of postoperative complication in patients with MIS. Hospital stay was significantly longer in patients operated on laparotomy. In our study, there was no evidence of a difference in survival between minimally invasive surgery and laparotomy in patients treated with radical hysterectomy for early-stage cervical cancer.

Spotlight on oncologic outcomes and prognostic factors of pure endometrioid ovarian carcinoma

To determine the prognostic factors related to recurrence and survival, and to evaluate the need for adjuvant chemotherapy in patients with endometrioid type epithelial ovarian cancer (EEOC). This study included 63 EEOC patients who were surgically staged. The FIGO 2014 stage was stage I in 41 (65 %) patients, stage II in 8 (12.5 %) patients, stage III in 14 (22.5 %) patients. 5-year failure-free survival (FFS) was 78 % in the entire cohort. 15 (23.8 %) patients had disease failure. In univariate analysis, advanced stage (II&III), high grade tumor, presence of ascites, bilateral tumor, presence of omental metastasis, positive peritoneal cytology were prognostic factors for poor FFS. Only the stage was determined to be an independent prognostic factor for disease-failure. According to multivariate analysis, stage II&III was related to a statistically significant hazard ratio for a disease failure of 3.49 (95 % confidence interval: 1.029-11.841; p = 0.045). The effectiveness of adjuvant chemotherapy was assessed for 41 patients with stage I. Eleven (26.8 %) patients with stage I did not receive adjuvant chemotherapy. Whereas 5-year FFS was 88 % in patients receiving adjuvant chemotherapy, that was 91 % in patients without adjuvant chemotherapy (p = 0.923). The independent prognostic factor for recurrence in EEOC was stage only. Adjuvant chemotherapy was not related to improvement in FFS in the early stage EEOC that were completely staged.

Late cervical and vaginal clear cell adenocarcinoma in women exposed in utero to diethylstilbestrol: Evaluation and screening

We aimed to evaluate the risk of cervical and vaginal clear cell adenocarcinoma (CCA) in women, aged 50 years or more, exposed in utero to diethylstilbestrol (DES) and contribute to a reevaluation of the recommendations for cervical and vaginal cancer and pre-cancer screening for these women. We carried out a retrospective review for patients received in a cancer institute. Two cohorts were consecutively studied, the first from 1970 to 2003 and the second from 2004 to 2021, and then linked. During the first period, we observed 61 CCA cases, with a mean age at diagnosis of 23 years (7-42), 36 (59%) following DES exposure in utero. During the second period, we found 27 cases, with one case of DES exposure (4%) for a women diagnosed at the age of 40 years. The mean age of the second cohort was 38 years (14-79). For the seven women aged 50 years or more at the time of CCA diagnosis, DES exposure was excluded for five and considered unlikely for the other two. In total, 88 cases of cervical or vaginal CCA were observed over a period of 51 years in a cancer center. The 37 cases associated with DES exposure represented approximatively one third of the CCA related to DES expected in France. DES exposure was improbable for the seven cases of CCA for women aged 50 years or more. These results do not support the hypothesis of late cervical or vaginal CCA in women exposed to DES in utero and indicate the need for larger multicentric studies. For the present, we propose specific screening for women exposed to DES in utero in terms of : 1) methods: association of cytology and hrHPV testing, with cervical and vaginal sampling, 2) timing : annual, or without exceeding a three-year interval, continuing after 65 years of age and after hysterectomy.

Preliminary observational study of the implementation of hyperthermic intraperitoneal chemotherapy in ovarian cancer in the gynecological surgery department at the University Hospital of Strasbourg

According to French guidelines, hyperthermic intraperitoneal chemotherapy (HIPEC) can be performed for Federation of Gynecology and Obstetrics stage III primary epithelial ovarian, tubal, and peritoneal cancers that are initially unresectable after 3 or 4 cycles of intravenous chemotherapy. The main objective of this preliminary study was to analyze the components necessary for the establishment of HIPEC in an expert gynecological oncological surgery center. The secondary objective was to compare HIPEC using conventional laparotomy and laparoscopic approaches. We conducted a single-center retrospective study of patients who received HIPEC. All patients who met the criteria of the French HIPEC guidelines were included from 2019 to 2021. Prior to HIPEC, there were a mean of 3.7 courses of neoadjuvant chemotherapy with carboplatin and paclitaxel. Of the 16 patients who received HIPEC, 9 (56.2%) underwent HIPEC laparoscopically, while 7 (43.8%) underwent laparotomy. There were no differences between the rates of intra- and postoperative complications between the two groups. (p > 0.05). The duration of hospitalization was significantly shorter in patients who were operated laparoscopically than in those treated using laparotomy (55.6% <10 days vs. 0 by laparotomy, p = 0.01). There was also a tendency, although not significant, for a more rapid resumption of adjuvant chemotherapy in the laparoscopy group, with 57.1% resuming chemotherapy in <6 weeks compared to 42.9% in the laparotomy group (p = 0.52). This study demonstrates the feasibility of HIPEC in a center with expertise in gynecological surgery when there is a suitable technical platform and close collaboration between the different teams involved. We also showed the first cases of HIPEC using laparoscopy, which seems to be a promising approach.

Vulvar and vaginal melanomas: A retrospective study spanning 19 years from a tertiary center

Mucosal melanomas (MM) of the female genital tract are rare a. We aimed to study the prognostic factors of vulvar and vaginal locations of MM. A multicenter, retrospective cohort study conducted between 01/01/2000 and 01/06/2019. Of the 33 patients included 25 (75.8 %) had vulvar (VuM) and eight (24.2 %) vaginal melanomas (VaM). VaMs were deeper: median Breslow index: 17.5mm [3.5-22] versus 4.3mm [0.35-18] (p=0.013). Average follow-up was 24.0±59.8 months. Twenty-six patients (78.8 %) experienced recurrence. Disease-free survival was 52.9 % at 1year (64.7 % for VuM and 14.3 % for VaM) and 8.4 % at 3 years (11 % for VuM and 0% for VaM) (p=0.002). Median time to the first recurrence was 9.01 months [CI95 %: 2.07-56.71]. VaM recurred earlier than VuM (3.12 months [CI95 %: 2.07-12.49] versus 17.72 [CI95 %: 3.58-56.71], p=0.011). VaM had a higher risk of recurrence (HR=5.64 [CI95 %: 2.01-15.82], p=0.001) in multivariate analysis. Overall survival was 88.5 % at 1year (100 % for VuM and 50 % for VaM), and 59.4 % at 3 years (69.3 % for VuM and 25 % for VaM). Women with VaM died earlier: median specific death occurrence of 8.76 months [CI95 %: 6.54-24.72] versus 39.61 [CI95 %: 21.89-209.21], p=0.013 (HR=5.08 [CI95 %: 1.39-18.60], p=0.014). A lesion size ≥3cm was associated with an increased risk of mortality (HR=8.45 [CI95 %: 1.60-44.52], p=0.012). In multivariate analysis, vaginal location remained an independent and predictive variable of a higher risk of specific death (HR=8.56 [CI95 %: 1.95-37.64], p=0.005). A vaginal location of MM is associated with a poorer prognosis than a vulvar location.

A pre-operative radiological score to predict lymph node metastasis in advanced epithelial ovarian cancer

Lymphadenectomy is part of cytoreductive surgery for patients with advanced epithelial ovarian cancer (AEOC) in case of abnormal lymph nodes before and during surgery. The aim of this study was to develop and validate a pre-operative radiological score to predict pelvic and/or para-aortic lymph node metastasis (LNM) in patients with AEOC undergoing cytoreductive surgery. We conducted a multicentre retrospective study. The construction sample was composed of 53 patients operated within two referral centers. The validation sample was composed of 39 patients operated in a third referral center. The score was built with a logistic regression model with internal validation by bootstrap. Two variables were associated with the prediction of pelvic and/or para-aortic LNM at computerized tomography (CT) and/or positron emission tomography (PET/CT): "para-aortic lymph node involvement" (adjusted diagnostic odds ratio) (aDOR) = 8.77 95CI [1.42-54.09], p = 0.02) and "colon involvement" (aDOR = 7.97 95CI [1.28-49.58], p = 0.03). Bootstrap procedure showed that the model was stable. The 2-points LNM pre-operative radiological score was derived from these 2 radiological variables and a high-risk group was identified for a score ≥ 1: the probability of pelvic and/or para-aortic LNM was 76%, the specificity was 85.7% 95CI [67.3-96.0] and the positive likelihood ratio was 3.6 95CI [1.4-9.7]. In the validation sample, a score ≥ 1 had a specificity of 78.3% and a LR+ of 1.2. LNM pre-operative radiological score could help the surgeon's decision to perform pelvic and para-aortic lymphadenectomy in patients with AEOC undergoing cytoreductive surgery. The research protocol was approved by the Ethics Committee for Research in Obstetrics and Gynecology (CEROG 2016-GYN 1003).

Surgical management of patients with advanced ovarian cancer: Results of a French National Survey

Desire to homogenize advanced stage ovarian cancer management has led to a debate on the need to centralize cares. The aim was to assess current practices to compare them with centralization motivation and to overview possible perspectives of evolution. An anonymous questionnaire of 57 questions has been submitted from August 2021 to October 2021 to members of French gynecological oncological surgical societies. Questions encompassed all aspects of ovarian cancer surgical management, including institutions, technics, indications, and outcomes. Of the 40 responses, 77.5% managed less than 20 cases by themselves, but 67.5% practiced in institution managing more than 30 cases annually. Since the LION trial results' publication, 95% of practitioners have evolved their lymphadenectomy indications. More than 10% of surgery needed digestive resection for 90% of practitioners. Digestive resections rate was significantly higher for practitioners managing more than 20 cases (p<0.01), but it was not for institutions managing more than 30 cases annually (p=0,07). Surgeons performing more than 20 ovarian cancers annually reported less severe complications (p=0.04) compared to low-volume surgeons independently of institution volume. For more than a quarter of the practitioners, less than half of the patients can benefit from the enhanced recovery after surgery program despite benefits of such care. Our survey provides an overview of French practices in ovarian cancer management. This survey seems to confirm that minimum volume thresholds could lead to better outcomes. It also underlines that individual performances are as valuable as center volume.

Interval debulking surgery after neoadjuvant chemotherapy in advanced ovarian cancer - retrospective study comparing surgery after 3 cycles or more of chemotherapy

To evaluate and compare overall survival and progression-free survival in two groups of patients with advanced ovarian cancer, managed by neoadjuvant chemotherapy (3 cycles or more) followed by interval debulking surgery. Secondary objectives regarded surgical morbidity and extent of cytoreduction. We conducted a retrospective study, in a referral center, evaluating the management of patients diagnosed with advanced ovarian cancer (FIGO IIIC-IV) beneficiating of interval surgery after neoadjuvant chemotherapy. We compared two groups, one in which patients underwent 3 cycles of chemotherapy before surgery, and a second group in which patients underwent more than 3 cycles. 140 patients underwent interval surgery after neoadjuvant chemotherapy. Among these patients, 45 patients underwent 3 or less cycles (group 1) and 95 patients more than 3 cycles (group 2). There was no statistical difference for overall and progression free survival. The mean overall survival was 58,4 months for group 1 and 58,3 for group 2 (p.value = 0.56). The mean progression free survival was 30,5 months for group 1 and 23,8 months for group 2 (p.value = 0.17). More posterior pelvectomies were realized in group 1 compared to group 2 with a statistically significant difference (p=0,01). There was no difference regarding complete macroscopic difference during the surgery between the 2 groups (p=0,09). Debulking surgery is an invasive and heavy procedure and is not always possible in first line. Neoadjuvant chemotherapy followed by interval debulking surgery is an accepted alternative. The number of administered cycles is questionable, and does not seem to have a significant impact on overall survival and progression free survival. However, surgical morbidity is significantly reduced by increased cycles of chemotherapy.

Cervical traction suture technique during large loop excision of the transformation zone increases complete lesion excision

A surgical technique was developed in the past by our group to reduce the rate of inadvertent complications. It was then seemed that it also increased the rate of complete lesion excision. The objective of the study was to evaluate the effectiveness of a cervical traction suture technique in increasing the prevalence of complete lesion excisions and reducing the incidence of unintended injuries to adjacent tissues during large loop excision of the transformation zone (LLETZ). A retrospective cohort study, including all consecutive patients who underwent LLETZ between January 2016 and June 2018, at the outpatient Colposcopy clinic of a general hospital in Galilee Medical Center. We divided patients into two groups based on whether their LLETZ utilized the cervical traction suture technique. We compared these two groups using an independent-samples t test, and we compared the study-specific proportions to those reported in the literature using the proportion test. A total of 66 patients were included in the analysis; 33 had undergone LLETZ with a traction suture, and 33 had undergone LLETZ without a traction suture. The prevalence of complete lesion excision was 93.3 % among patients undergoing LLETZ with a traction suture and 72.7 % among those without a traction suture (p = 0.04). The incidence of unintentional injuries to adjacent organs was 12.1 % in women with a traction suture and 18.2 % in women without a traction suture (p = 0.73). Using a cervical traction suture along with LLETZ can increase the rate of complete lesion excision and may reduce the prevalence of unintended injuries.

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

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). 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. 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. 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.

Vulvar Paget's disease: A population-based cancer registry descriptive study

Although vulvar Paget's Disease (VPD) is a rare skin cancer associated with an excellent prognosis, high recurrence rates are associated with impaired quality of life. Our objective was to investigate the epidemiological and clinical features of VPD diagnosed in a French administrative area (Franche Comté). This retrospective study investigated clinical, histologic, therapeutic and follow-up data of patients with VPD diagnosed between 1981 and 2021, including data from the Doubs cancer registry. Among the 21 patients included (19 intra-epithelial and 2 invasive VPD), the median time to diagnosis was 24 months [0-110 months], with a median age of 72 years [38-88 years]. An associated cancer was present in 6 patients (29 %). At 5 years of follow-up, the recurrence rate was 26 %, but then increased to 42 % after a median follow-up of 145 months [31-503 months]. Among the 14 patients first surgically treated, incomplete resection (positive margins) was observed in all patients (100 %), associated with a postoperative recurrence rate of 86 % which was much higher than the rate observed in patients first topically treated (20 %). Postoperative adjuvant therapy (surgical revision, laser, imiquimod) significantly increased the recurrence-free survival (p < 0.001). Postoperative recurrence of VPD is frequent, mainly after 5 years, proving the importance of prolonged follow-up. Recurrence-free survival was significantly higher after postoperative adjuvant treatment.

The effect of the delivery mode on the evolution of cervical intraepithelial lesions during pregnancy. A meta-analysis

The aim of the present study was to evaluate the impact of the mode of delivery on the natural evolution of cervical squamous intraepithelial lesions in pregnant patients. Α systematic search was conducted in Medline (1966-2021), Cochrane Central Register of Controlled Trials CENTRAL (1999-2021), Scopus (2004-2021), Google Scholar (2004-2021) and Clinicaltrials.gov (2008-2021) along with the reference lists of electronically retrieved full-text papers. All the studies that investigated the correlation of the mode of delivery with the natural evolution of cervical squamous intraepithelial lesions of patients during pregnancy, were included in the present meta-analysis. Eight retrospective studies were finally included, comprising 813 patients whose premalignant lesions were evaluated cytologically, of whom 685 delivered via the vaginal route, and 233 patients whose squamous intraepithelial lesions were evaluated histologically, of whom 162 delivered vaginally. The methodological quality of the included studies ranged between moderate and serious. Regression rates were comparable among women that delivered with caesarean section compared to patients that delivered vaginally, both in the cytological (OR 1.32, 95% CI 0.56, 3.12) and in the histological evaluation (OR 1.87, 95% CI 0.50, 6.96) of the lesions. Subgroup analysis revealed consistent results for all subgroups of premalignant lesions. Finally, the results observed for both the persistence and the progression rates of these lesions were proportional. Our meta-analysis suggests that the delivery mode does not alter the natural evolution of squamous intraepithelial lesions in pregnant women and therefore their presence should not determine the mode of delivery.

Regression of cervical high-grade squamous intraepithelial lesions (HSIL/CIN2) managed expectantly

Many women with cervical high-grade squamous intraepithelial lesions (HSIL/CIN2) are managed expectantly, because about half of them will regress spontaneously, thus avoiding systematic loop electrosurgical excision procedure and related adverse effects. However, most of the guidelines have restricted this strategy to the youngest women. The objectives of our study were to determine the rate and the predictors of regression of HSIL/CIN2 managed expectantly. This retrospective study included 128 patients under 40 years of age (median 29, range 21-39), and HSIL/CIN2 diagnosed by biopsy between 2012 and 2019. They were followed-up without treatment in the department of gynecology at Bordeaux University Hospital, France. The regression of HSIL/CIN2 was defined by the regression or the disappearance of initial colposcopic findings, cytological and/or histological results. The lesion spontaneously regressed or disappeared in 76 (59%) patients during a median follow-up of 25 months (range, 7-86). In the multivariable analysis, minor change at colposcopy (odds ratio OR = 2.8 (CI95% 1.2-6.9), P = 0.02), low grade lesions (ASC-US/LSIL) by cytology (OR = 4.1 (CI95% 1.7-10.1), P < 0.001), and infection by HPV other than HPV-16 (OR = 5.4 (CI95% 2.3-13.9), P < 0.001) predicted the spontaneous regression of HSIL/CIN2. Colposcopic findings, cytological results, and HPV genotyping, but not the age, were baseline factors predicting the evolution of HSIL/CIN2 in patients under 40.

Evaluating the role of secondary surgery and PARP inhibition in platinum-sensitive ovarian cancer relapse

To assess the benefit of secondary cytoreductive surgery (SCS) in patients with platinum-sensitive recurrent epithelial ovarian cancer (EOC), and to evaluate how survival outcomes are influenced by second-line PARP inhibitor maintenance therapy. This retrospective study included 52 patients with platinum-sensitive recurrent EOC treated at the National Cancer Institute of Aviano, Italy, between 2015 and 2022. Patients received either SCS followed by chemotherapy (SCS+CT group) or chemotherapy alone (CT-only group). The primary endpoints were progression-free survival (PFS) and post-recurrence survival (PRS). Secondary analyses explored the impact of second-line PARPi maintenance on survival outcomes within each treatment group. Patients in the SCS+CT group experienced significantly longer PFS compared to those in the CT-only group (median 19.2 vs. 10.0 months, p=0.007). Among patients receiving PARPi maintenance, the benefit was even more pronounced: median PFS was 40.3 months in the SCS+CT group versus 21.9 months in the CT-only group (p=0.026). A non-significant trend toward improved PRS was observed in the SCS+CT group (48.3 vs. 36.0 months, p=0.23). PARPi maintenance was associated with longer PRS in both treatment arms (p=0.0056 for SCS+CT; p=0.033 for CT-only). In patients with platinum-sensitive recurrent EOC, SCS combined with chemotherapy significantly improves PFS, particularly when followed by second-line PARPi maintenance. These findings support the role of SCS in carefully selected patients and emphasize the synergistic effect of integrating surgical and molecularly targeted strategies.

Evaluating the applicability of ESGO quality indicators in the surgical management of endometrial cancer: Insights from a Francogyn cohort

Endometrial cancer (EC) is a significant health concern in France, necessitating high-quality surgical care to improve patient outcomes. The European Society of Gynaecological Oncology (ESGO) established quality indicators (QIs) to standardize and improve management. This study evaluates the applicability of ESGO QIs in a real-world setting across 13 centers in France. This retrospective multicenter cohort study included 2789 patients surgically treated for EC from 2001 to 2020. Demographic data, surgical techniques, adherence to ESGO QIs and trends over time were analyzed. Key indicators analyzed included multidisciplinary team discussions, pre-operative imaging adequacy, surgical techniques employed, and molecular classifications. All patients were discussed in multidisciplinary meetings. Adequate preoperative imaging was achieved in 80.63 % of cases. Minimally invasive surgery was performed in 66.12 % of early-stage patients, showing a significant year-on-year increase from 12 % in 2001 to 85 % in 2020. Among obese patients, 60.78 % underwent laparoscopic procedures, with a conversion rate to open surgery of 3.57 %. Molecular classification results highlighted 35 % of patients as low risk and 32 % as high risk. Our findings indicate that adherence to actual ESGO QIs has substantially improved the quality of surgical management for endometrial cancer in France, despite some areas requiring further enhancement. A coordinated political approach is essential to address existing barriers and ensure consistent implementation of these quality standards across all centers, ultimately aiming to elevate patient care and outcomes in the French healthcare system.

Quality of information and decision regrets during fertility-sparing management for atypical hyperplasia and endometrial cancer in a prospective cohort study

To evaluate satisfaction with information, treatment, and decision regret during management to preserve fertility for atypical hyperplasia (AH) or endometrial cancer (EC). A cohort study with standardized management using chlormadinone acetate was established through a national referral centre between January 2013 and November 2019. During this period, a questionnaire was given to 136 patients aged 19 to 43 years who were followed for fertility preservation for AH or EC. The questionnaire included the validated EORTC-QLQ-INFO25, as well as questions from the validated EVAPIL questionnaire, the Treatment Satisfaction with Medicines Questionnaire, and the Decision Regret Scales concerning treatment tolerability and general satisfaction. The main outcomes measured were the quality and satisfaction with the information and treatment received and the decision regret. 75 patients (55.1 %) responded to the questionnaire. Overall, patients were satisfied with the information received (median 75.0, range: 25-100) and thought it was helpful (median 100.0, range: 25-100). However, 54.7 % wished for more information. Most women (52.0 %) indicated that psychological support should be available. Patients who were less satisfied with the information received or wished to receive more information thought about stopping treatment more frequently. Decision regret was not related to treatment outcome (remission, hysterectomy, live birth), and 47 of the 56 patients who did not obtain a live birth did not regret fertility preservation. None of the nine patients who regretted fertility preservation obtained a live birth. Almost all the patients reported side effects. Dedicated information tools that detail conservative treatment for AH and EC as well as its secondary effects should be provided to improve adherence to treatment and follow-up. Furthermore, psychological support should be systematically proposed.

A study evaluating liquid-based endometrial cytology test and transvaginal ultrasonography as a screening tool for endometrial cancer in 570 postmenopausal women

To evaluate the combination of transvaginal ultrasonography (TVS) and endometrial cytology test (ECT) as a potential diagnostic strategy for endometrial cancer and endometrial precancerous lesions in postmenopausal patients. 570 postmenopausal patients admitted in our hospital due to abnormal bleeding or other symptoms and/or with endometrium thickness over 5 mm on ultrasound. The endometrial thickness was evaluated by TVS. Following obtainment with written consent, all patients underwent ECT, hysteroscopy and then dilatation and curettage (D&C). Cytological sampling was conducted by scratching the uterus cavity using SAP-1 and the samples were prepared as liquid-based smear using SurePath technology. The samples were stained using Papanicolaou method. The correlation between cytological diagnosis and TVS results with the D&C histological diagnosis was analyzed. The WHO classification was used for diagnosis. Sensitivity of ECT, TVS, ECT or TVS positive, ECT and TVS positive to diagnose atypical hyperplasia or worse were estimated at 80.7%, 86.8%, 97.4%, 70.2%, specificity at 94.7%, 20.4%, 17.5%, 88.4%, positive predictive value at 58.2%, 21.1%, 22.8%, 60.2%, negative predictive value at 94.4%, 86.1%, 96.4%, 92.2%, and accuracy at 84.6%, 33.7%, 33.5%, 84.7%, respectively. Transvaginal ultrasonography and Endometrial cytology test may be regarded as a effective first-line method in endometrial pathology detection in postmenopausal women.

Aortic sentinel node detection in endometrial cancer: 6 year prospective study

The aim of this study was to describe our final results using dual cervical and fundal indocyanine green injection for the detection of sentinel lymph nodes (SLNs) in endometrial cancer along parametrial and infundibular drainage pathways. We conducted a prospective observational study between 26 June 2014 and 31 December 2020 enrolling 332 patients that underwent laparoscopic surgery for endometrial cancer at our hospital. In all cases, we performed SLN biopsy with dual cervical and fundal indocyanine green injection identifying pelvic and aortic SLNs. All SLNs were processed with an ultrastaging technique. A total of 172 patients also underwent total pelvic and para-aortic lymphadenectomy. The detection rates were as follows: 94.0% overall for SLNs; 91.3% overall for pelvic SLNs; 70.5% for bilateral SLNs; 68.1% for para-aortic SLNs, and 3.0% for isolated paraaortic SLNs. We found lymph node involvement in 56 (16.9%) cases, macrometastasis in 22, micrometastasis in 12 and isolated tumor cells in 22. Fourteen patients had isolated aortic nodal involvement, representing 25% of the positive cases. There was one false negative (SLN biopsy negative but lymphadenectomy positive). Applying the SLN algorithm, the sensitivity of the dual injection technique for SLN detection was 98.3% (95% CI 91-99.7), specificity 100% (95% CI 98.5-100), negative predictive value 99.6% (95% CI 97.8-99.9), and positive predictive value 100% (95% CI 93.8-100). Overall survival at 60 months was 91.35%, with no differences between patients with negative nodes, isolated tumor cells and treated nodal micrometastasis. Dual sentinel node injection is a feasible technique that achieves adequate detection rates. Additionally, this technique allows a high rate of aortic detection, identifying a non-negligible percentage of isolated aortic metastases. Aortic metastases in endometrial cancer account for as many as a quarter of the positive cases and should be considered, especially in high-risk patients.

Application of thrombin gel matrix for the prevention of lymphocele in patients with endometrial cancer: A prospective randomized trial

To evaluate a thrombin gel matrix (TGM), Floseal, for the prevention of lymphocele in patients with endometrial cancer who underwent pelvic lymphadenectomy. A total of 79 consecutive patients with endometrial cancer were randomly allocated to one of two groups: the TGM group and control group. After completion of the lymphadenectomy, 5 mL of Floseal was applied to the bilateral pelvic sidewalls, especially the femoral canal, obturator, and common iliac vessels areas. Computed tomography scans were obtained for lymphocele evaluation 2 months after the surgery. Three patients from the TGM group, and four patients from the control group were lost during follow-up, and data from 36 participants from each group were analyzed. As the primary outcome, lymphocele developed in 12 patients in both groups (33 %). There was no significant difference between the groups in terms of lymphocele and symptomatic lymphocele development. Lymphocele localization was also not different between the two groups, but the diameter of the lymphoceles detected in the TGM group was significantly greater (p = 0.021). The mean drainage days was significantly shorter in the TGM group (p = 0.015). The amount of drainage was also less in the TGM group, but the difference was not statistically significant. Thrombin gel matrix applied to the pelvic sidewalls does not reduce the incidence of symptomatic or asymptomatic lymphoceles after pelvic lymphadenectomy in endometrial cancer. However, it can reduce the amount of drainage and the number of drainage days so it can help to shorten hospitalization.

Clinical significance of risk-reducing salpingo-oophorectomy in patients with BRCA1/2 mutation

Serous tubal intraepithelial carcinoma (STIC) is a precursor lesion which is located in the distal fallopian tube and causes high grade serous ovarian carcinoma (HGSOC). The incidence of STIC for women underwent risk reducing salpingo-oophorectomy for BRCA mutation varies from 0.6 to 7% and its clinical outcomes are still unclear. The aim of this study was to demonstrate the incidence of STIC and HGSOC in BRCA1/2 mutation carriers after risk reducing salpingo-oophorectomy (RRSO) and the clinical outcomes of these patients. We retrospectively reviewed the records of 48 BRCA1 and/or 2 mutation carriers who underwent prophylactic salpingo-oophorectomy with or without hysterectomy at the Department of Obstetrics and Gynecology, Bursa Uludag University between January 2000 and January 2022. BRCA 1 and/or 2 mutation carriers diagnosed by genetic testing, asymptomatic patients with no abnormal findings on pelvic examination. patients with no abnormal findings on pelvic examination and a presence of a personal history of ovarian, fallopian tube or peritoneal cancer. A total of 48 BRCA 1 and/or 2 mutation carriers underwent RRSO. STIC was diagnosed in 1 (2,0%) patient and restaging surgery was not performed. Primary peritoneal carcinoma (PPC) did not develop during the 20 months follow-up period. One (2.0%) patient was diagnosed with occult ovarian cancer. Restaging surgery was performed and chemotherapy treatments were given after surgery. A pelvic recurrence developed 25 months after the occult cancer diagnosis in the follow up period. One (2.0%) patient with normal histopathological findings after RRSO was diagnosed with peritoneal cancer 57 months after the operation. The risk of PPC continues after RRSO. Therefore, close follow-up procedure is very important for early diagnosis and effective treatment of patients with PPC after RRSO.

Predictors for negative large loop excision of the transformation zone (LLETZ) in a primary HPV screened population

To assess rates of histologically negative large loop excisions of the transformation zone (LLETZ) and potential predictive factors within a single UK Colposcopy Unit. Retrospective cohort study. Jessop Wing Colposcopy Unit, Sheffield, U.K. Patients coded upon the Colposcopy database as having undergone a LLETZ procedure. Univariate (Chi squared, t-test) and multivariate logistic regression analysis. Histological negative LLETZ sample. 2,969 patients underwent a LLETZ procedure; 291 (10 %) procedures resulted in a negative LLETZ. Older age group (p < 0.0001), referral with negative cytology high risk human papillomavirus (hrHPV) detected (p < 0.0001), unsatisfactory colposcopy (p < 0.0001), repeat LLETZ (p < 0.0001), and biopsy and treat procedures (p = 0.0005) were found significant predictors of negative LLETZ. Patients with negative LLETZ were significantly less likely to have had a 'select & treat' procedure (p < 0.0001). Due to the increased sensitivity of HPV testing in combination with cytology for the detection of high-grade disease, it is more likely a negative LLETZ will occur following positive biopsy. This may be due to the detection of small volume high-grade disease removed by the punch biopsy alone, spontaneous regression of disease, or resolution due to localised immune responses and healing. As increasing age and unsatisfactory colposcopy are significant risk factors for obtaining a negative LLETZ, the authors recommend further studies are conducted in this more challenging referral population.

Exploring uterine involvement in hysterectomy samples following conization for adenocarcinoma in situ of the uterine cervix: Insights from a multicenter study by the FRANCOGYN group

Adenocarcinoma in situ (AIS) of the cervix can progress to invasive adenocarcinoma. While hysterectomy is standard, conservative management may be considered for women desiring future pregnancies. This study aimed to determine the prevalence of residual disease in hysterectomy specimens following excisional therapy with clear margins for AIS. A retrospective FRANCOGYN cohort study was conducted on patients who underwent a hysterectomy after conization with clear margins for AIS between 2008 and 2021. The primary goal was to assess the prevalence of residual disease in the hysterectomy specimens. Secondary objectives included identifying preoperative predictors of residual disease and comparing recurrence rates between patients with and without residual disease. Of 53 hysterectomies performed after conization with negative margins for AIS, 20.8% (11/53) showed residual disease in the final histology. None of the patients had invasive cancer. In the residual disease group, 18% (2/11) had persistent CIN 3, and 82% (9/11) had persistent AIS. These patients tended to have higher BMI (27.5 kg/m² vs. 23.6 kg/m², p=0.04) and shorter endocervical margins (2mm vs. 5mm, p=0.01). No recurrences were observed during follow-up. Despite clear margins on the initial conization for AIS, 20% of patients had residual disease in their hysterectomy samples, though no invasive cancer was found. A hysterectomy should be considered after completing childbearing, even if initial margins are clear.

Retrospective analysis of the incidence and predictive factors of parametrial involvement in FIGO IB1 cervical cancer

Radical surgery is the standard primary treatment for patients with stage IB1 (FIGO 2009 staging) cervical cancer due to latent parametrial involvement. Recent studies suggested that less radical surgery was applicable for patients with no or low risk of parametrial involvement. In this study, we aimed to determine the incidence and possible predictive factors of parametrial involvement in patients with stage IB1 cervical cancer so as to evaluate whether less radical surgery was suitable for selected patients. Clinical data of patients who underwent type C radical hysterectomy with pelvic lymphadenectomy and diagnosed as stage IB1 cervical cancer at Union Hospital, Wuhan, China from October 2014 to December 2017 were collected and analysed retrospectively. The incidence of parametrial involvement was calculated and the risk factors for parametrial involvement were evaluated by univariate and multivariate logistic regression. Among 282 eligible patients, 33 (11.7%) had parametrial involvement. Postmenopause, lymphovascular space invasion (LVSI), lymph node metastasis (LNM), deep stromal invasion (outer 1/3) and tumor size larger than 2 cm were statistically associated with parametrial involvement. Multivariate analysis showed that LNM (OR = 11.431; 95%CI: 3.455 - 37.821), deep stromal invasion (OR = 6.080; 95%CI: 1.814 - 20.382) and LVSI (OR = 7.147; 95%CI: 1.863-27.411) remained as independent risk factors for parametrial involvement in patients with stage IB1 cervical cancer. The incidence of parametrial involvement in stage IB1 cervical cancer is non-negligible. Only LNM, LVSI and deep stromal invasion were independent predictors, which were not easy to evaluate accurately before surgery. Less radical surgery requires modified pre-treatment evaluation methods and prospective data support.

Prognostic value of BRCA1 promoter methylation for patients with epithelial ovarian cancer

BRCA1 promoter methylation (BRCA1pm) is suspected to alter prognosis of patients with epithelial ovarian cancer (EOC). We aimed to evaluate the prognostic impact of this epigenetic modification. We conducted a retrospective, monocentric study from 11/2006 to 08/2018. Patients with EOC and available status concerning somatic BRCA1/2 mutation and BRCA1pm were included. Three groups were defined: patients without BRCA1/2 mutation or BRCA1pm, patients with BRCA1/2 mutation and patients with BRCA1pm. BRCA1/2 mutations were analyzed in current care settings by next-generation sequencing (NGS). BRCA1pm analysis was assessed and quantified from bisulfite converted DNAs using fluorescent methylation specific polymerase chain reaction (PCR) and fragment analysis. All patients signed a consent form and the study was authorized by a Personal Protection Committee. Descriptive statistics were used to describe groups. Multivariate analysis was performed using the logistic regression model and including the variables that could be known at the time of diagnosis and that were significant at univariate analysis. Survival was compared between the groups. Kaplan-Mayer curves were used to express the differences in survival that were compared using log rank tests. 145 patients were included: 95 (65.5 %) patients without BRCA1/2 mutation or BRCA1pm, 32 (22.1 %) patients with BRCA1/2 mutation, 18 (12.4 %) patients with BRCA1pm. Median survival was decreased in patients with BRCA1pm. Comparison of survival revealed a significant difference in overall survival (p = 0.0078) with a worse prognosis for patients with a BRCA1pm. BRCA1pm in patients with EOC is an independent factor associated with a decreased overall survival. BRCA1 promotor methylation in patients with epithelial ovarian cancer is an independent factor associated with a decreased overall survival.

Robot-assisted versus conventional laparoscopic hysterectomy in endometrial cancer: An observational study in a French tertiary teaching hospital at the beginning of the learning curve

The role of Robotic Assisted Laparoscopy (RAL) versus conventional laparoscopy (CL) in the surgical treatment of endometrial cancer remains a matter of debate. We aimed to compare RAL and CL in terms of clinical outcomes (hospital stay characteristics and 3-month complications) in patients undergoing hysterectomy for endometrial cancer. We conducted a single-center, retrospective study in a tertiary teaching hospital comparing two groups of women who underwent hysterectomy for endometrial carcinoma by RAL performed by a surgeon during the beginning of learning curve, or CL. Of the 110 patients included, 56 were in the RAL group and 54 in the CL group. The patients in the RAL group were significantly older (71.6±8.7 vs 67.8±9.7, p=0.031) and had a higher BMI (33.1±7.0 vs 29.8±6.1, p=0.030) than those in the CL group. Operating room occupancy time was higher with RAL (4.6 hours±1.3 vs 3.5±1.3, p<0.001). Although less spinal analgesia was used in the RAL group (35% vs 74%, p<0.001), the patients in this group consumed less postoperative paracetamol (9.4g±5.3 vs 13.0±9.9, p=0.032) meaning faster recovery. Conversely, there was a higher rate of unplanned consultations during the 3-month follow-up in the RAL vs CL group (18.5% vs 3.6%, p=0.012). RAL was associated with less postoperative pain even at the beginning of learning curve. Surgeons were more likely to perform RAL than CL for older and/or obese patients, suggesting they intuitively consider RAL of added benefit for these patients.

Recommendations for the surgical management of gynecological cancers during the COVID-19 pandemic - FRANCOGYN group for the CNGOF

In the context of the COVID-19 pandemic, specific recommendations are required for the management of patients with gynecologic cancer. The FRANCOGYN group of the National College of French Gynecologists and Obstetricians (CNGOF) convened to develop recommendations based on the consensus conference model. If a patient with a gynecologic cancer presents with COVID-19, surgical management should be postponed for at least 15 days. For cervical cancer, radiotherapy and concomitant radiochemotherapy could replace surgery as first-line treatment and the value of lymph node staging should be reviewed on a case-by-case basis. For advanced ovarian cancers, neoadjuvant chemotherapy should be preferred over primary cytoreduction surgery. It is legitimate not to perform hyperthermic intraperitoneal chemotherapy during the COVID-19 pandemic. For patients who are scheduled to undergo interval surgery, chemotherapy can be continued and surgery performed after 6 cycles. For patients with early stage endometrial cancer of low and intermediate preoperative ESMO risk, hysterectomy with bilateral adnexectomy combined with a sentinel lymph node procedure is recommended. Surgery can be postponed for 1-2 months in low-risk endometrial cancers (FIGO Ia stage on MRI and grade 1-2 endometrioid cancer on endometrial biopsy). For patients of high ESMO risk, the MSKCC algorithm (combining PET-CT and sentinel lymph node biopsy) should be applied to avoid pelvic and lumbar-aortic lymphadenectomy. During the COVID-19 pandemic, management of a patient with cancer should be adapted to limit the risks associated with the virus without incurring loss of chance.

Rationale for opportunistic salpingectomy during gynecological surgery for a benign condition: A review of the available literature

Recent discoveries have shed light on the benefits of opportunistic salpingectomy in the prevention of ovarian cancer. However, in this time of increasing interest in the parameters of ovarian reserve, there are no national recommendations on the subject. This literature review provides an enlightened look at the rationale for performing an opportunistic salpingectomy. To evaluate the benefits and risks associated with opportunistic salpingectomy during surgery for a benign gynecological condition. We carried out a systematic review of the literature using the Pubmed/Medline search engine and the Cochrane database. A total of 61 articles were selected from over 300 references. The protective impact against cancer, which is widely demonstrated in the literature, is proof of the benefit of this procedure. Furthermore, no increase in intraoperative morbidity has been noted. However, the clinical impact on the ovarian reserve remains uncertain (in particular the occurrence of early pre-menopausal symptoms during the perimenopausal period). Nonetheless, the socioeconomic analysis supports performing opportunistic salpingectomy. Performing opportunistic salpingectomy does not appear to cause an increase in morbidity but the impact on ovarian function is uncertain. The fact that there is a proven benefit of such a procedure against cancer indicates that prior to any surgery a clear discussion should be held with the patient in which they should be fully informed.

Incidence, prognostic factors, and a nomogram of cervical cancer with lung metastasis: A SEER-based study

The purpose of this study was to investigate the incidence, survival and prognostic factors of cervical cancer with lung metastasis at the initial diagnosis and to develop a visual nomogram to predict the prognosis of these patients. We used the Surveillance, Epidemiology and End Results (SEER) database to screen patients diagnosed with cervical cancer from 2010 to 2015. After strict inclusion and exclusion, the chi-square test was used to evaluate the differences in the clinical characteristics of patients with cervical cancer, and then we used Kaplan-Meier method to perform survival analysis among cervical cancer patients with lung metastasis. Next, univariate and multivariate Cox proportional hazard regression models were used to estimate prognostic factors of these patients and we developed a visualized and novel nomogram to judge the prognosis. 476 patients with lung metastasis and 12,016 patients without lung metastasis were included in this study. The incidence of lung metastasis was higher in unmarried white cervical cancer patients between the ages of 40 and 60, and grade III cervical squamous cell carcinoma patients were more likely to have lung metastasis. In addition, grade, surgery, radiotherapy, sequence of surgery and radiotherapy and chemotherapy were significantly related to the outcomes of cervical cancer patients with lung metastasis. Furthermore, our nomogram could predict the 3-year and 5-year overall survival (OS) of these patients. Finally, the AUC of 3-year OS and 5-year OS were confirmed to be 0.969 and 0.939 respectively by ROC curves, with good consistency. Age at diagnosis, race, marital status, and characteristics of the tumor can influence the incidence of lung metastasis in cervical cancer patients. Besides, grade, surgery, radiotherapy, sequence of surgery and radiotherapy and chemotherapy may deeply affect the prognosis of cervical cancer patients with lung metastasis. The nomogram built in this study may help clinicians to formulate individualized treatment strategies and encourage the development of more and more comprehensive and accurate predictive models.

The optimal endometrial thickness threshold for prediction of endometrial cancer in postmenopausal women without bleeding remains uncertain–Systematic review and meta-analysis

The incidental finding of endometrial thickness (ET) >4 mm in the absence of postmenopausal bleeding (PMB) is a common cause of referring women to secondary care. However, there is lack of consensus amongst gynecologists as regards the management. It is estimated that up to 15 % of endometrial cancers occur in women without PMB. The aim this study was to determine the optimal ET threshold, on trans-vaginal ultrasound scan, that discriminates normal endometrium from endometrial hyperplasia and cancer in this cohort. On using a thorough search strategy, a total 16 studies including 4088 women were deemed eligible. However, the data were not amenable to meta-analysis. There were wide variations in the thresholds reported with potential bias given the retrospective nature of the majority of the studies. Despite contacting authors, we could not obtain the primary data to generate a Receiver Operating Characteristic (ROC) Curve. No linear or curvilinear association was found between ET thresholds and the percentage of women diagnosed with endometrial hyperplasia and cancer using either Pearson's correlation, linear or curvilinear regression, or a simple visual scan/scatter diagram. The result of this study reveals the lack of evidence to inform clinical practice in this area, and there is a need for a well-designed multi-center prospective study.

Margin status after loop electrosurgical excision procedure (LEEP) and laser excision in patients with high-grade cervical neoplasia

Early management of high-grade cervical intraepithelial neoplasia is one of the key steps in cervical cancer prevention after vaccination and screening. It relies on lesion removal by surgical excision, and the French National Cancer Institute (INCa) in 2016 recommend using a loop electro excision procedure (LEEP). However, the laser excision method seems to be as effective with similar rates of negative excision margins and postoperative clearance of HPV. The main objective of our study was to compare the laser excision method to LEEP by evaluating the quality of the surgical margins. We also studied factors associated with the status of the margins and the depth of cones. We conducted a retrospective unicentric study between 2009 and 2017. Two hundred and thirty-one patients were included: 154 laser excisions and 77 LEEP. Negative surgical margin was achieved in 69.5 % of laser excisions and 72.7 % of LEEP (p = 0.649). Concerning factors predicting margin status, only a greater cone depth was associated with negative margins (OR: 0.91 (95 %CI: 0.84, 0.89); p = 0.02). The surgical technique was not found to be associated with the status of the margins (OR: 0.85 (95 %CI: 0.46,1.56); p = 0.61). Concerning factors predicting cone depth, only the LEEP was associated with a shorter cone depth (OR: 0.24 (95 %CI: 0.08, 0.69); p 0.008). Significant results are based on univariate analysis. No difference was found between the two technics concerning the rate of negative margins. However, LEEP seems to be associated with shorter cone depth in this study.

Ovarian masses in children and adolescents: Analysis on 146 patients

Ovarian masses in pediatric population are the most common genital neoplasms, and these masses are often benign. The purpose of this study is to evaluate the pediatric ovarian masses operated in our hospital. The records of patients, under the age of 18 who were operated in our hospital due to ovarian mass between 2012 and 2018 were reviewed retrospectively. Clinical findings, operational procedures, histopathologies, tumor markers and radiological images were evaluated. During the study, 146 patients (5 patients were bilateral) were evaluated. The average age of the study patients was 14.01 ± 4.02 years. 107 of the study patients were benign, 37 were malignant and 2 were borderline. The most common symptom in benign masses was tenderness in lower abdominal (75.7 %). 124 of the patients (86.1 %) were in post-menarche period. 34 of the patients had ovarian torsion. Open surgery was conducted on 79.5 % (116/146) of the patients, and laparoscopic surgery was conducted on 20.5 % (30/146). The rate of oophorectomy was 24.6 % (36/146) throughout the operations. The most frequently conducted surgical procedure was cyst excision in benign masses and oophorectomy in malignant masses. In neoplastic masses, the ratio of pelvic mass palpation; and in non-neoplastic masses, lower abdominal tenderness was more apparent. The rate of ovarian torsion was 23.6 % (25/107) in benign masses and 24.3 % (9/37) in malignant masses. Pediatric and adolescent ovarian masses are mostly benign and majority of these occur at post-menarche period. The most common symptom was pelvic tenderness in benign masses, and palpable pelvic masses in malignant masses. For future fertility and low incidence of malignancy in these patients, ovarian preserving surgery should be considered for the first operation.

What is this vaginal bulge? An atypical case of vaginal paraurethral leiomyoma. A case report and literature systematic review

Vaginal paraurethral leiomyomas are uncommon benign tumors of the female genitourinary tract. We report a case of anterior vaginal paraurethral leiomyoma. Furthermore, we performed a systematic review of the literature to provide information that can help the physicians in the diagnosis and management of women with this rare pathology. A case of anterior vaginal paraurethral leiomyoma in 53-year-old, primiparous, caucasian woman with history of pelvic pressure, vaginal bulging and overactive bladder symptoms, was described. Furthermore, a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement was performed between January 1, 2000 to Dec 30, 2019. Only articles that reported cases of vaginal or paraurethral leiomyoma (b) case series and case reports with literature review were included. we screened a total 2281 records; 70 articles published from 2000 to 2019 were included. Vaginal paraurethral leiomyoma is a rare benign tumor of the vagina with a wide spectrum of symptoms and good prognosis. The recurrence and transformation into malignant condition are rare. Histopathological examination is the gold standard for diagnosis, but MRI and US can be help to define the size and localization of the tumor. Management requires surgical vaginal excision in the majority of cases; however, abdominal approach could be considered when it is large and located high in the vagina.

Correlation of poly (adenosine diphosphate[ADP]-ribose) polymerase expression and prognosis in ovarian cancer: A systematic review and meta-analysis

This meta-analysis evaluated the correlation between poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) expression and prognosis in patients with ovarian cancer. Eligible studies were extracted from the electronic databases of PubMed, Web of Science, and EMBASE until 1 August 2019. The included studies investigated the correlation between PARP expression and clinical outcomes in patients with ovarian cancer. Clinical outcomes are overall survival (OS) and progression free survival (PFS). The clinical data of patients, such as clinicopathologic characteristics and survival, were analyzed. The language was limited to English, and studies conducted at the cellular level, animal studies, and non-original research were excluded. The odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were used for this meta-analysis. A total of 9 eligible studies involving 1230 patients were included in our meta-analysis. Based on the analysis, higher PARP expression was correlated with worse overall survival [OS] (HR,1.64; 95% CI, 1.08-2.49; P = 0.020) in the univariate analysis, whereas results from multivariate analysis indicated that PARP overexpression wasn't statistically associated with worse OS (HR, 1.36; 95% CI, 0.98-1.90; P = 0.069). Moreover, the pooled results revealed that patients with PARP overexpression were not associated with worse histologic grade (OR,2.22; 95% CI, 0.98-5.02; P = 0.06). PARP overexpression maybe associated with poor prognosis and survival in patients with ovarian cancer. The patients with PARP over expression were not tended to have a worse histologic grade. Findings require further validation.

Presentation of the ENDO-SFOG CAMPUS app: An easy therapeutic decision support app in endometrial cancer created by the French Society of Young Gynecological Oncologists (SFOG Campus)

This study evaluates a new decision support tool-a computer/mobile application designed to align with the latest ESGO guidelines, French practices, and molecular biology data-to aid in decision-making for endometrial cancer management. An observational, multicenter, retrospective study was conducted. It compared management decisions from multidisciplinary tumor boards (MTBs) with those suggested by the application for patients with histologically confirmed endometrial cancer, irrespective of their FIGO stage. Each center included the last 20 cases discussed in multidisciplinary tumor boards between May to December 2022. Thirteen centers participated: eight university hospitals (61.5 %), four cancer centers (30.8 %), and one private center (7.7 %). A total of 259 patients were included, with a mean age of 69 years (range 30-96 years). Most patients had endometrioid tumors (77.2 %), low-grade (62.6 %), FIGO stage IA (41.3 %), no lymphovascular invasion (77.9 %), and a non-specific molecular profile (50.6 %). The application's recommendations matched the MTB decisions 76.6 % of the time. Discrepancies arose mainly from the non-administration of brachytherapy (22.8 %), rare presentations or pathological discordance (22.8 %), and patients' deteriorated conditions precluding standard treatments (19.3 %). The SFOG campus application demonstrates a high concordance with multidisciplinary tumor board decisions, indicating its potential as an efficient, and valuable tool for managing endometrial cancer.

Complementary surgery for cervical cancer patients inadequately treated with extrafacial hysterectomy

To evaluate surgical outcomes and survival outcomes of cervical cancer patients who underwent complementary surgery after an extrafacial hysterectomy METHODS: Patients with cervical cancer, who underwent extrafacial hysterectomy initially and thereafter underwent complementary surgery were reviewed retrospectively. Complementary surgery consisted of radical parametrectomy, proximal vaginectomy and pelvic lymphadenectomy. Twenty patients were evaluated. Histopathologic subtype was squamous cell carcinoma in twelve patients, adenocarcinoma in six patients and adenosquamous carcinoma in two patients. Route of surgery was laparotomy in 19 patients and laparoscopy in one patient. Two patients were staged as stage 1A2, nine were staged as stage 1B1, four were staged as stage 1B2, one was staged as stage 2A1, one was staged as stage 2B and three were staged as stage 3C1. The median tumor size was 16.5 (Range, 4-40) mm. Grade ≥ 3 complications related to surgery occured in 8 (40%) patients. Four of them were managed intraoperatively and recovered problem free. Remaining four (20%) needed reoperation. Pathology reports revealed involvement of parametrium in one (5%) patient, involvement of the proximal vagina in one (5%) patient, matastasis to pelvic lymph nodes in 3 (15%) patients. Five (25%) patients received adjuvant radiotherapy. Consequently, 5-year and 10-year cumulative survival was calculated as 94%. Complementary surgery and radiotherapy show similar oncologic outcomes in patients with early-stage cervical cancer who had undergone simple hysterectomy initially. Complementary surgery is associated with slightly higher rate of morbidity compared with radiotherapy, however significant proportion of complications can be noticed and repaired intraoperatively.

Abdominal radical trachelectomy during pregnancy: A systematic review of the literature

Lack of large trials or randomized studies characterize any type of treatment for cervical cancer during pregnancy experimental. To accumulate the existing evidence on abdominal radical trachelectomy (ART) during pregnancy. Medline, Scopus and Google Scholar databases were thoroughly searched up to September 2018 for relevant studies in this field using the terms "Radical Trachelectomy", "Pregnancy", "Cervical cancer", "fertility sparring". Observational studies and case reports which addressed cases of pregnant women who underwent ART for cervical cancer during pregnancy were included. A total of ten studies which recruited 19 patients were finally included. At the time of ART, the gestational age of patients ranged from 7th to 22th weeks. Mean operative time of ART was 351.8 min while mean blood loss was 1,040.35 ml and 5 patients (50%) received blood transfusion. Fetal loss rate was 21.1% (n = 4) and from the completed deliveries 7 (46,66%) were preterm. Postoperative maternal related complication rate was 23.1% (n = 3/13). The mean follow-up was 16.89 months (SD 12.69), whereas all cases were free of disease without evidence of recurrence during their follow-up. According to the existing evidence, ART may be a tolerable option for pregnant women with early-stage cervical cancer with acceptable oncological and obstetrical outcomes. Future multicenter randomized trials are of particular importance to elucidate the optimal treatment option.

Less extensive surgery for patients with FIGO stage IA2 cervical cancer: A population-based study

The objectives of this study were to study the feasibility of less extensive surgeries for stage IA2 cervical cancer and to examine the incidence of positive nodes in stage IA2 cervical cancer. Patients with stage IA2 cervical cancer treated surgically between 1998 and 2015 were identified from the Surveillance, Epidemiology, and End Results database. Overall survival (OS) and cervical cancer-specific survival (CCSS) were compared among patients who underwent different types of surgery (simple hysterectomy VS radical hysterectomy, lymphadenectomy VS without lymphadenectomy). The Cox proportional hazards regression model was applied to evaluate multiple prognostic factors. 1343 patients were included in this study. The overall incidence of positive nodes in stage IA2 was 2.53%. For well-differentiated IA2 cervical cancer, the incidence of regional lymph node involvement was as low as 1.42%. Compared with patients who underwent lymphadenectomy, the patients who did not undergo lymphadenectomy had the same OS (HR, 1.336; 95% CI, 0.923 to 1.933; P = 0.149) and CCSS (HR, 1.038; 95% CI, 0.504 to 2.140; P = 0.920). The log-rank test also indicated that simple hysterectomy was not associated with decreased OS (HR, 1.048; 95% CI, 0.750 to 1.466; P = 0.781) and CCSS (HR, 1.259; 95% CI, 0.655 to 2.420; P = 0.490). Multivariable analyses showed that lymphadenectomy and type of hysterectomy were not independent predictors of survival for patients with stage IA2 cervical cancer. The incidence of nodal involvement in well-differentiated stage IA2 cervical cancer was fairly low, lymphadenectomy may be omitted in these patients. The excision range of parametrial tissue was not associated with the oncological survival of women with stage IA2 cervical cancer, simple hysterectomy may be an appropriate alternative for this group of patients.

Developing an online calculator to estimate the overall survival benefit from adjuvant radiotherapy in patients with early-stage type II endometrial carcinoma

The impact of adjuvant radiotherapy (aRT) on overall survival (OS) in early-stage type II endometrial carcinoma (EC) remains uncertain. This study aimed to develop nomograms and a web-based calculator to identify these patients who may benefit from aRT. Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and divided into the developing and validation cohorts. LASSO Cox regression identified prognostic factors, and nomograms were constructed to predict 1-, 3-, and 5-year OS with/without aRT. The expected OS benefit from aRT was reflected in the difference between the two predicted OS nomograms. Validation involved ROC analysis, calibration curves, and decision curve analysis. A web calculator was created for estimating aRT's net OS benefit. Among the 6084 patients, aRT did not improve OS across all patients but showed benefits in specific subgroups, such as those with clear cell carcinoma and carcinosarcoma. Nomograms were constructed for patients with/without aRT to predict 1-, 3-, and 5-year OS, and they can accurately forecast OS. Additionally, the web-based calculator was developed to estimate the net OS benefit of aRT. The nomograms provide accurate OS estimates for early-stage type II EC patients with/without aRT, thereby supporting individualized treatment decisions. The web calculator offers a quantitative tool for optimizing aRT use based on clinicopathological characteristics.

Risk factors for postoperative complications following hysterectomy in endometrial cancer patients: A systematic review

Endometrial cancer is the most prevalent type of cancer of the female reproductive system. Certain risk factors have been linked to a range of severe postoperative complications following hysterectomies in this patient population. Therefore, this systematic review aims to encompass all the significant risk factors identified that lead to postoperative complications in endometrial cancer patients following hysterectomy and possible risk factor mitigation strategies that can be made to limit these postoperative complications. The authors conducted the search across four libraries, including Cochrane, VHL, Web of Science, and PubMed. The authors identified original studies published from inception till November 2, 2024, that were relevant to the research question and fit the eligibility criteria. Preoperative factors include cancer staging, diabetes, frailty, obesity, medications, ASA class, and smoking; while intraoperative considerations include blood loss, operative time, length of hospital stay, lymphadenectomy, and surgical complexity. These risk factors were found to lead to a variety of postoperative complications ranging in grades on the Clavien Dindo classification (CD), including surgical site infections, urinary tract infections, lymphedema, lymphorrhea, lymphocyst, wound disruption, wound dehiscence, respiratory issues, ileus, and prolonged hospital stays. Before undergoing hysterectomies, endometrial cancer patients should be screened for risk factors to decrease the risk of postoperative complications. The employment of tailored mitigation strategies for individual patients through preoperative optimization, intraoperative management, and patient counseling is essential in preventing postoperative complications. By improving patient care and reducing hospital-acquired costs, surgeons will be more equipped to handle complex procedures and prevent unwanted outcomes.

Evaluation of pre-therapeutic imaging work-up in the staging of endometrial cancer: Interest in a systematic second opinion in a cancer center

To evaluate the interest of a systematic second opinion in quality assessment and FIGO staging in the pretherapeutic imaging work-up. A retrospective observational study was conducted on 156 patients who underwent surgery for endometrioid cancer in our institution. 42 % had their initial MRI scans performed in expert centers (University Hospital and Cancer center) and 58 % in non-expert centers. Quality assessment, concordances between initial reports, and second opinions by a junior and a senior ICL radiologist versus histopathological data were analyzed. MRI scans performed in expert centers were more complete and more likely to be rated as higher quality. The overall accuracy of T staging from initial reports vs gold standard was 0.59 (95 % CI, 0.46-0.71) in expert centers and 0.49 (95 % CI, 0.38-0.60) in non-expert centers. The overall accuracy and Kappa of a second opinion for FIGO 2009 staging from expert center and non-expert center examinations were 0.61 (95 % CI, 0.48-0.72) vs 0.50 (95 % CI, 0.39-0.60) and 0.37 vs 0.27 for junior reader and 0.62 (95 % CI, 0.49-0.74) vs 0.48 (95 % CI, 0.37-0.58) and 0.39 vs 0.24 for senior reader, respectively. There was also a significant lower confidence level of the junior radiologist in MRI FIGO staging for non-expert center examinations (p 0.003). Accuracy in the FIGO 2009 staging and quality assessment are higher for MR examinations performed from expert centers than in non-expert centers. A systematic second opinion by radiologists in expert centers should be proposed before pre-treatment multidisciplinary consultation.

Use of uterine manipulator and uterine perforation in minimally invasive endometrial cancer surgery

Safety of the uterine manipulator (UM) within endometrial cancer (EC) surgery is being questioned. Its use might be one of the issues for potential tumor dissemination during the procedure, especially in the case of uterine perforation (UP). No prospective data on this surgical complication, nor on the oncological consequences exist. The aim of this study was to assess the rate of UP while using UM when performing surgery for EC and the impact of UP on the choice of adjuvant treatment. We conducted a prospective single-center cohort study from November 2018 to February 2022, considering all EC cases surgically treated by a minimally invasive approach with the help of a UM. Demographic, preoperative, postoperative and adjuvant treatment corresponding to the included patients were collected and comparatively analyzed according to the absence or presence of a UP. Of the 82 patients included in the study, 9 UPs (11%) occurred during surgery. There was no significant difference in demographics and disease characteristics at diagnosis that may have induced UP. The type of UM used or the approach (laparoscopic vs. robotic) did not influence the occurrence of UP (p = 0.44). No positive peritoneal cytology was found post hysterectomy. There was a statistically significantly higher rate of lymph-vascular space invasion within the perforation group, 67% vs. 25% in the no perforation group, p = 0.02. Two out of nine (22%) adjuvant therapies were changed because of UP. The median follow-up time for patients was 7.6 months (range 0.5-33.1 months). No recurrence was found in the UP group. Our study found a uterine perforation rate of 11%. This information needs to be further integrated to consider the usefulness of MU for EC surgery.

Prediction of endometrial cancer recurrence by using a novel machine learning algorithm: An Israeli gynecologic oncology group study

Endometrial cancer is the most common gynecologic malignancy in developed countries. The overall risk of recurrence is associated with traditional risk factors. Machine learning was used to predict recurrence among women who were diagnosed and treated for endometrial cancer between 2002 and 2012 at elven university-affiliated centers. The median follow-up time was 5 years. The following data were retrieved from the medical records and fed into the algorithm: age, chronic metabolic diseases, family and personal cancer history, hormone replacement therapy use, endometrial thickness, uterine polyp presence, complete blood count results, albumin, Ca-125 level, surgical staging, histology, depth of myometrial invasion, LVSI, grade, pelvic washing cytology, and adjuvant treatment. We used XGBoost algorithm, which fits the training data using decision trees, and can also rate the factors according to their influence on the prediction. 1935 women were identified of whom 325 had recurrent disease. On the randomly picked samples, the specificity was 55% and the sensitivity was 98%. Our model showed an operating characteristic curve with AUC of 0.84. A machine learning algorithm presented promising ability to predict recurrence of endometrial cancer. The algorithm provides an opportunity to identify at-risk patients who may benefit from adjuvant therapy, tighter surveillance, and early intervention.

The evolving role of targeted metformin administration for the prevention and treatment of endometrial cancer: A systematic review and meta-analysis of randomized controlled trials

The aim of the present study was to evaluate the role of metformin in endometrial cancer (EC), focusing on its potential preventive effect in breast cancer and obese patients and its safety and efficacy when added to progesterone monotherapy in EC patients who wish to preserve their fertility. We reviewed the literature and then conducted a meta-analysis of the relevant parameters. A total of 6 studies was included in the meta-analysis. Regarding the pre-surgical treatment with metformin versus placebo, meta-analysis of mean difference in Ki-67 after treatment among two groups, revealed no difference (MD -7.10, 95% CI -23.31 to 9.11, p = 0.39). Meta-analysis of fertility sparing EC management with a combination of megestrol acetate (MA) and metformin (500 mg three times a day) in comparison with monotherapy with 160 mg daily MA revealed no difference in either complete response or partial response rates (166 patients OR 2.94, 95% CI 0.85 to 10.15, p = 0.09 and 166 patients OR 0.76, 95% CI 0.34 to 1.66, p = 0.49, respectively). As far as breast cancer survivors under tamoxifen are concerned, metformin was associated with significantly reduced median endometrial thickness after 52 weeks of evaluation compared to women in placebo group (2.3 mm vs 3.0 mm, p = 0.05). Metformin neither was found to be an anti-proliferative agent against the development of endometrial cancer nor beneficial in addition to the progesterone monotherapy for EC fertility sparing candidates. However, a protective effect of metformin was demonstrated in breast cancer survivors under tamoxifen. Clinical outcomes of the ongoing trials are warranted to evaluate the therapeutic use of metformin in EC.

An analysis of 635 consequetive laparoscopic hysterectomy patients in a tertiary referral hospital

The objective of this retrospective observational study is to analyse the properties of laparoscopic hysterectomy cases that are performed for benign indications and also endometrial cancer indications. Operation time, postoperative complicaton rate, blood transfusion need, and hospitalization time are compared according to benign and malign indications and also body mass index of the patients. Patients who were operated between September 2012 and December 2017 are included in this study. Patients' age, body mass index, medical histories, operation indications, operation time, pathology reports, pre and postoperative hemoglobine values and postoperative complications are obtained from medical records.Body mass index is classified as underweight for <19 ; normal for 19-25 ; overweight for 25-30 and obese for ≥30. Operation and hospitalization times were significantly higher for high BMI and malign gynecologic indication groups than lower BMI and benign gynecologic indication groups (p:0.0001). Complication rates and transfusion needs were similar in between malign and benign gynecologic disease groups (p :0.443; P:0.670 respectively) and also in between high and lower BMI groups (P:0.813 ; P:0.468 respectively). Laparoscopic approach for hysterectomy operations in high BMI patients and endometrial cancer patients seem to be safe in terms of postoperative complication and bleeding that necessitate transfusion.

Conservatively treated endometrial intraepithelial neoplasia/cancer: Risk of intrauterine synechiae

To determine whether progestin type or number of dilation and curettage procedures (D&Cs) were associated with intrauterine synechiae (IS) or pregnancy outcomes in patients conservatively treated for endometrial intraepithelial neoplasia (EIN) or endometrial cancer (EC). We evaluated patients conservatively treated for EIN or EC from 2000 to 2017 at an academic center. IS were identified hysteroscopically. We calculated proportions for categorical variables and tested associations between D&C number, progestin, and pregnancy outcomes using Pearson chi-squared and Fisher's exact tests. A post-hoc power analysis indicated sufficient power to detect livebirth. We analyzed 54 patients, 15 with EIN (28 %) and 39 with EC (72 %), with a mean age of 34 ± 1.2 years. Progestin treatment types included megestrol acetate (MA) (n = 24), MA with levonorgestrel intrauterine device (LngIUD) (n = 10), MA followed by LngIUD (n = 3), and LngIUD alone (n = 6). Mean number of D&Cs was 3.9 ± 0.9. Overall, 53 subjects underwent hysteroscopy; 10 (19 %) had IS. When D&Cs were grouped into 0-2, 3-4 and ≥5, each increase in D&C group had a 2.9 higher odds of IS (OR: 2.91, p = 0.04, CI: 1.05-10.02). LngIUD was associated with a nonsignificant 46 % decrease in the odds of IS (OR: 0.54, p = 0.66, CI: 0.08-2.87). Twenty-two women attempted pregnancy; 14 women achieved a total of 20 pregnancies and 9 women had total of 15 livebirths (41 % livebirth rate). The number of D&Cs and progestin treatment type were not associated with pregnancy outcomes. Among 54 patients conservatively treated for EC/EIN, nearly 20 % developed IS. However, hysteroscopic and/or fertility treatments may improve pregnancy outcomes.

Publisher

Elsevier BV

ISSN

2468-7847