Value of Non-Coding RNA Expression in Biofluids to Identify Patients at Low Risk of Pathologies Associated with Pregnancy.

Pregnancy-related complications (PRC) impact maternal and fetal morbidity and mortality and place a huge burden on healthcare systems. Thus, effective diagnostic screening strategies are crucial. Currently, national and international guidelines define patients at low risk of PRC exclusively based on their history, thus excluding the possibility of identifying patients with de novo risk (patients without a history of disease), which represents most women. In this setting, previous studies have underlined the potential contribution of non-coding RNAs (ncRNAs) to detect patients at risk of PRC. However, placenta biopsies or cord blood samples are required, which are not simple procedures. Our review explores the potential of ncRNAs in biofluids (fluids that are excreted, secreted, or developed because of a physiological or pathological process) as biomarkers for identifying patients with low-risk pregnancies. Beyond the regulatory roles of ncRNAs in placental development and vascular remodeling, we investigated their specific expressions in biofluids to determine favorable pregnancy outcomes as well as the most frequent pathologies of pregnant women. We report distinct ncRNA panels associated with PRC based on omics technologies and subsequently define patients at low risk. We present a comprehensive analysis of ncRNA expression in biofluids, including those using next-generation sequencing, shedding light on their predictive value in clinical practice. In conclusion, this paper underscores the emerging significance of ncRNAs in biofluids as promising biomarkers for risk stratification in PRC. The investigation of ncRNA expression patterns and their potential clinical applications is of diagnostic, prognostic, and theragnostic value and paves the way for innovative approaches to improve prenatal care and maternal and fetal outcomes.

French college of gynecologists and obstetricians (CNGOF) recommendations for clinical practice: Place of breast self-examination in screening strategies.

Breast cancer is the most common female cancer in the world. Numerous studies have shown that the risk of metastatic disease increases with tumor volume. In this context, it is useful to assess whether the regular practice of formal breast self-examination (BSE) as opposed to breast awareness has an impact on the number of cancers diagnosed, their stage, the treatments used and mortality. DESIGN: The Commission of Senology (CS) of the Collège National de Gynécologie et Obstétrique Français (CNGOF) respected and followed the Grading of Recommendations Assessment, Development and Evaluation method to assess the quality of the evidence on which the recommendations were based. METHODS: The CS studied 16 questions individualizing four groups of women (general population, women aged over 75, high-risk women, and women previously treated for breast cancer). For each situation, it was determined whether the practice of BSE versus abstention from this examination led to detection of more breast cancers and/or recurrences and/or reduced treatment and/or increased survival. RESULTS: BSE should not be recommended for women in the general population, who otherwise benefit from clinical breast examination by practitioners from the age of 25, and from organized screening from 50 to 74 (strong recommendation). In the absence of data on the benefits of BSE in patients aged over 75, for those at high risk and those previously treated for breast cancer, the CS was unable to issue recommendations. Thus, if women in these categories wish to undergo BSE, information on the benefits and risks observed in the general population must be given, notably that BSE is associated with a higher number of referrals, biopsies, and a reduced quality of life.

Discoid excision for colorectal endometriosis associated infertility: A balance between fertility outcomes and complication rates.

OBJECTIVE: The objective of our study was to study the impact of discoid excision for deep endometriosis (DE) with colorectal involvement on fertility outcomes. METHODS: 49 patients with a desire for pregnancy treated with discoid excision for colorectal endometriosis in our endometriosis expert center between January 2015 and August 2020 were selected from our prospectively maintained database. Indications for surgery were either infertility and / or pelvic pain. Postoperative complications were graded according to the Clavien-Dindo classification. Fertility outcomes, both spontaneous and post-ART pregnancies, were analyzed. RESULTS: Among the 49 patients who underwent discoid excision exclusively (no other digestive resection) with a desire to conceive, 25 had a pregnancy after surgery and 24 did not. Double discoid excision was performed in 6.1 % of the cases (3/49). A colpectomy was performed in 12.2 % of the patients (6/49), and a protective stoma in 12.2 % (6/49). Fenestration of endometriomas was performed in 28.6 % of the patients (14/49), and parametrectomy in 40.8 % (20/49). The postoperative complication rate was 24.5 % (12/49) including 10.2 % (5/49) grade I, 12.2 % (6/49) grade II, and 2 % (1/49) grade III. Prior to surgery, 28 (57.1 %) patients had infertility including 13 (52 %) that successfully conceived following surgery and 15 (62.5 %) that remain infertile. Spontaneous pregnancy was achieved in 60 % (15/25) of infertile patients' prior surgery. The live-birth rate in patients conceiving spontaneously was 75 % (12/16). CONCLUSION: Our results support that discoid excision is safe and associated with good fertility outcomes. Whether first-line surgery using discoid excision is superior to first-line ART remains to be determined.

Vulvar biopsy: Punch biopsy or cervical forceps biopsy?

OBJECTIVES: The primary objective of our study is to investigate the rate of non-contributory biopsies between punch biopsy(PB) and cervical forceps biopsy(CFB) for a vulvar lesion seen in consultation. The secondary objective of our study is to evaluate the rate of underestimation of a more severe lesion for patients who have undergone vulvar excision. MATERIAL AND METHOD: This is a retrospective, descriptive, and comparative study conducted at three centers. The study population consisted of patients who underwent vulvar biopsy between 2017 and 2022 in a gynecological surgery consultation at two French hospitals, as well as a city office. The biopsy techniques used were punch or cervical forceps biopsy. Quantitative variables were analyzed using the Mann-Whitney test, while Pearson's or Fisher's Xi2 tests were used for qualitative variables. The significance level was set at 5%. RESULTS: We conducted a retrospective study of 179 vulvar biopsies, of which 100 were punch biopsies and 79 were cervical forceps biopsies, from a total of 107 patients. There was no significant difference in the rate of non-contributory biopsies between the PB and CB groups (p = 1). When analyzing the secondary endpoint of our study, which included 68 patients who underwent vulvectomy after vulvar biopsy, we found that 66 patients (97%) had a good correlation between the pathology of the vulvar biopsy and that of the vulvectomy specimen. CONCLUSION: Vulvar biopsy techniques using punch or cervical forceps appear to have similar diagnostic performance and are associated with comparable and low rates of underestimation of invasive lesions.

[Place of breast self-examination in screening strategies. French College of Gynecologists and Obstetricians (CNGOF) recommendations for clinical practice]. / Recommandations pour la pratique clinique du CNGOF. Place de l'auto-examen des seins dans les stratégies de dépistage.

OBJECTIVES: Breast cancer is the most common female cancer in the world. In France, over 60,000 new cases are currently diagnosed, and 12,000 deaths are attributed to it annually. Numerous studies have shown that the risk of metastatic disease increases with tumor volume. In this context, it is useful to assess whether the regular practice of breast self-examination (BSE) has an impact on the number of cancers diagnosed, their stage, the treatments used and mortality. DESIGN: the CNGOF's Commission de Sénologie (CS), composed by 17 experts and 3 invited members, drew up these recommendations. No funding was provided for the development of these recommendations. The CS respected and followed the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method to assess the quality of the evidence on which the recommendations were based. METHODS: The CS studied 16 questions concerning BSE, individualizing four groups of women (general population, women aged over 75, high-risk women, and women previously treated for breast cancer). For each situation, it was determined whether the practice of BSE compared with abstention from this examination led to the detection of more breast cancers and/or recurrences and/or reduced treatment and/or increased survival. RESULTS: BSE should not be recommended for women in the general population, who otherwise benefit from a clinical breast examination (by the attending physician or gynecologist) from the age of 25, and from organized screening from 50 to 74 (strong recommendation). However, in the absence of data on the role of BSE in patients aged over 75, those at high risk of breast cancer and those previously treated for breast cancer, the CS was unable to issue recommendations. Thus, if women in these latter categories wish to undergo BSE, they must be given rigorous training in the technique, and information on the benefits and risks observed in the general population. Finally, the CS invites all women who detect a change or abnormality in their breasts to consult a healthcare professional without delay. CONCLUSION: BSE is not recommended for women in the general population. No recommendation can be established for women aged over 75, those at high risk of breast cancer and those previously treated for breast cancer.

Value of non-coding RNAs to assess lymph node status in cervical cancer.

Cervical cancer (CC) is the fourth cancer in women and is the leading cause of cancer death in 42 countries. Lymph node metastasis is a determinant prognostic factor, as underlined in the latest FIGO classification. However, assessment of lymph node status remains difficult, despite the progress of imaging such as PET-CT and MRI. In the specific setting of CC, all data underlined the need for new biomarkers easily available to assess lymph node status. Previous studies have underlined the potential value of ncRNA expression in gynecological cancers. In this review, we aimed to evaluate the contribution of ncRNAs in tissue and biofluid samples to determine lymph node status in CC with potential impact on both surgical and adjuvant therapies. In tissue samples, our analysis found that there are arguments to support the role of ncRNAs in physiopathology, differential diagnosis from normal tissue, preinvasive and invasive tumors. In biofluids, despite small studies especially concerning miRNAs expression, promising data opens up new avenue to establish a non-invasive signature for lymph node status as well as a tool to predict response to neo- and adjuvant therapies, thus improving management algorithm of patients with CC.

Insight on Non-Coding RNAs from Biofluids in Ovarian Tumors.

Ovarian tumors are the most frequent adnexal mass, raising diagnostic and therapeutic issues linked to a large spectrum of tumors, with a continuum from benign to malignant. Thus far, none of the available diagnostic tools have proven efficient in deciding strategy, and no consensus exists on the best strategy between "single test", "dual testing", "sequential testing", "multiple testing options" and "no testing". In addition, there is a need for prognostic tools such as biological markers of recurrence and theragnostic tools to detect women not responding to chemotherapy in order to adapt therapies. Non-coding RNAs are classified as small or long based on their nucleotide count. Non-coding RNAs have multiple biological functions such as a role in tumorigenesis, gene regulation and genome protection. These ncRNAs emerge as new potential tools to differentiate benign from malignant tumors and to evaluate prognostic and theragnostic factors. In the specific setting of ovarian tumors, the goal of the present work is to offer an insight into the contribution of biofluid non-coding RNAs (ncRNA) expression.

The Role of Immunohistochemistry Markers in Endometrial Cancer with Mismatch Repair Deficiency: A Systematic Review.

The objective of this systematic review was to summarize our current knowledge of the role of immunohistochemistry (IHC) markers for identifying mismatch repair-deficient (MMRd) tumors in endometrial cancer (EC). Identification of MMRd tumors, which occur in 13% to 30% of all ECs, has become critical for patients with colorectal and endometrial cancer for therapeutic management, clinical decision making, and prognosis. This review was conducted by two authors applying the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using the following terms: "immunohistochemistry and microsatellite instability endometrial cancer" or "immunohistochemistry and mismatch repair endometrial cancer" or "immunohistochemistry and mismatch repair deficient endometrial cancer". Among 596 retrieved studies, 161 fulfilled the inclusion criteria. Articles were classified and presented according to their interest for the diagnosis, prognosis, and theragnostics for patients with MMRd EC. We identified 10, 18, and 96 articles using IHC expression of two, three, or four proteins of the MMR system (MLH1, MSH2, MHS6, and PMS2), respectively. MLH1 promoter methylation was analyzed in 57 articles. Thirty-four articles classified MMRd tumors with IHC markers according to their prognosis in terms of recurrence-free survival (RFS), overall survival (OS), stage, grade, and lymph node invasion. Theragnostics were studied in eight articles underlying the important concentration of PD-L1 in MMRd EC. Even though the role of IHC has been challenged, it represents the most common, robust, and cheapest method for diagnosing MMRd tumors in EC and is a valuable tool for exploring novel biotherapies and treatment modalities.

Overview of non-coding RNAs in breast cancers.

Breast cancer in women is the second most common cancer and the fifth leading cause of cancer death worldwide. Although earlier diagnosis and detection of breast cancer has resulted in lower mortality rates, further advances in prevention, detection, and treatment are needed to improve outcomes and survival for women with breast cancer as well as to offer a personalized therapeutic approach. It is now well-established that non-coding RNAs (ncRNAs) represent 98% of the transcriptome but in-depth knowledge about their involvement in the regulation of gene expression is lacking. A growing body of research indicates that ncRNAs are essential for tumorigenesis by regulating the expression of tumour-related genes. In this review, we focus on their implication in breast cancer genesis but also report the latest knowledge of their theragnostic and therapeutic role. We highlight the need for accurate quantification of circulating ncRNAs which is determinant to develop reliable biomarkers. Further studies are mandatory to finally enter the era of personalized medicine for women with breast cancer.

ENDO_STAGE Magnetic Resonance Imaging: Classification to Screen Endometriosis.

Introduction: Transvaginal sonography is the first-line imaging technique to diagnose endometriosis, but magnetic resonance imaging is more accurate in staging the extent of lesions, especially for deep pelvic endometriosis. The revised American Society for Reproductive Medicine and Enzian classifications are commonly used to stage the extent of endometriosis. However, a review underlined their weaknesses in terms of complexity, lack of clinical reproducibility and low correlation with surgical complications and fertility outcomes. Thus, to this day, in clinical practice, there is a lack of consensual, standardized or common nomenclature to stage the extent of endometriosis, posing a worldwide challenge. Objectives: The aims of our study were to: (i) develop a new classification (entitled Endo-Stage MRI) based on patterns of endometriosis as observed with magnetic resonance imaging; (ii) compare results with those of the rASRM classification; (iii) estimate the Endo-Stage MRI accuracy to predict the rate of surgical complications; and (iv) propose an Endo-Stage MRI system of triage (low, intermediate, high) that correlates with the risk of surgical complications. The goal is to improve the effectiveness of care pathways and allow for the planning of a multidisciplinary approach when necessary. Patients and methods: A single-center observational study using available clinical and imaging data. According to anatomical locations and the extent of endometriotic lesions, a standardized classification comprising six stages of severity (0-5) was designed. Results: A total of 751 patients with pelvic endometriosis underwent surgery from January 2013 to December 2018 in a tertiary care university hospital. Their Endo-Stage MRI classification was correlated with: (i) the rate of overall complications (grade I-IV Clavien-Dindo classification, (ii) the rate of major complications (grades III-IV) and (iii) the rate of voiding dysfunction requiring self-catheterization lasting more than one month. According to the Endo-Stage MRI classification, stages 0, 1, 2, 3, 4 and 5 were observed in 26 (3%), 156 (21%), 40 (5%), 22 (3%), 290 (39%) and 217 (29%) patients, respectively. Using the proposed Endo-Stage MRI system as triage, low (stages 0-2), intermediate (stages 3-4) and high-risk (stage 5), complications were observed in 29 (13%), 109 (34.9%) and 103 (47.4%) patients, respectively. In multivariate analysis, the Endo-Stage MRI system of triage was strongly predictive of surgical complications and achieved higher accuracy than the revised American Society for Reproductive Medicine classification (AUC: 0.78 (95% CI, 0.76-0.80) vs. 0.61 (95% CI, 0.58-0.64)). Conclusion: Our study proposes a new imaging classification of endometriosis coined Endo-Stage MRI classification. The results suggest that when applied to a clinical situation, it may improve care pathways by providing crucial information for identifying intermediate and/or high-risk stages of endometriosis with increased rates of surgical complications. To make this classification applicable, a multicentric validation study is necessary to assess the relevancy and clinical value of the current anatomical MRI classification.

Relationships between pelvic nerves and levator ani muscle for posterior sacrocolpopexy: an anatomic study.

BACKGROUND: The placement of posterior mesh during pelvic organ prolapse laparoscopic surgery has been incriminated as responsible for postoperative adverse outcomes such as digestive symptoms, chronic pelvic pain, and sexual dysfunction. These complications may be related to neural injuries that occur during the fixation of the posterior mesh on the levator ani muscle. OBJECTIVES: The aim of our study was to describe the course of the autonomic nerves of the pararectal space and their anatomical relationship with the posterior mesh fixation zone on the levator ani muscle. STUDY DESIGN: Twenty hemi-pelvis specimens from 10 fresh female cadavers were dissected. We measured the distance between the posterior mesh fixation zone on the levator ani, and the nearest point of adjacent structures: the hypogastric nerve, inferior hypogastric plexus, uterosacral ligament, uterine artery, and ureter. Measurements were repeated starting from the inferior hypogastric plexus. RESULTS: Nerve fibers of the inferior hypogastric plexus spread out systematically above the superior aspect of the levator ani muscle. Median distance from the posterior mesh fixation zone and the inferior hypogastric plexus was around 2.8 (range 2.1-3.5) cm. CONCLUSIONS: The inferior hypogastric plexus lies above the superior aspect of the levator ani muscle. A short distance between the posterior mesh fixation zone on the levator ani muscle and inferior hypogastric plexus could explain in part postoperative digestive symptoms. These observations support the development of nerve-sparing procedures for posterior mesh placement in the context of pelvic organ prolapse repair and suggest that postoperative complications could be improved by changing the fixation zone.

Robotic Radical Trachelectomy with Primary Vaginal Closure to Spare Fertility in Young Patients with Early-Stage Cervical Cancer.

OBJECTIVE: Our aim was to present the surgical technique of robotic radical trachelectomy (RRT) for early-stage squamous cell cervical cancer in women with a desire to preserve fertility. DESIGN: A surgical case to illustrate the entire surgical technique of RRT and sentinel lymph node dissection. Institutional Review Board approval was not required for this video presentation. SETTING: University hospital. INTERVENTIONS: A 30-year-old patient with one child and no medical history. Pap smear and cervical biopsy were in favor of high-grade squamous intraepithelial lesion, and a conization procedure allowed the diagnosis of a 15 mm squamous cell carcinoma (International Federation of Gynecology and Obstetrics [FIGO] 1B1). An RRT was performed to preserve the fertility of this young patient, after bilateral sentinel lymph node dissection to ensure the absence of nodal metastasis. The trachelectomy specimen was negative at final pathology examination and the disease was confirmed as stage 1B1 (FIGO 2018). There were no surgical complications and no adjuvant treatment was indicated. Fertility-sparing surgery is acceptable for women of childbearing age who want to become pregnant. CONCLUSION: Minimally invasive surgery is safe, effective, and particularly adapted for women who wish to preserve their fertility without compromising oncological outcomes.1-2 This option may be safely proposed in expert centers for tumors smaller than 2 cm, with primary vaginal closure, and without use of a uterine manipulator.3 Complete information about oncological and obstetrical outcomes is mandatory and patients should agree to comply with a close follow-up protocol.

MicroRNA as Epigenetic Modifiers in Endometrial Cancer: A Systematic Review.

The objective of this systematic review is to summarize our current knowledge on the influence of miRNAs in the epigenetic deregulation of tumor-related genes in endometrial cancer (EC). We conducted a literature search on the role of miRNAs in the epigenetic regulation of EC applying the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The following terms were used: microRNA, miRNA, miR, endometrial cancer, endometrium, epigenetic, epimutation, hypermethylation, lynch, deacetylase, DICER, novel biomarker, histone, chromatin. The miRNAs were classified and are presented according to their function (tumor suppressor or onco-miRNA), their targets (when known), their expression levels in EC tissue vs the normal surrounding tissue, and the degree of DNA methylation in miRNA loci and CpG sites. Data were collected from 201 articles, including 190 original articles, published between November 1, 2008 and September 30, 2020 identifying 313 different miRNAs implicated in epigenetic regulation of EC. Overall, we identified a total of 148 miRNAs with decreased expression in EC, 140 miRNAs with increased expression in EC, and 22 miRNAs with discordant expression levels. The literature implicated different epigenetic phenomena including altered miRNA expression levels (miR-182, -230), changes in the methylation of miRNA loci (miR-34b, -129-2, -130a/b, -152, -200b, -625) and increased/decreased methylation of target genes (miR-30d,-191). This work provides an overview of all miRNAs reported to be involved in epigenetic regulation in EC including DNA methylation and RNA-associated silencing. These findings may contribute to novel strategies in diagnosis, risk assessment, and treatments aimed at miRNAs, their target genes or DNA methylation.