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.

Interstitial pregnancy management: A multicentric analysis of 98 patients from the FRANCOGENT group comparing surgery and medical treatment.

OBJECTIVE: To evaluate the outcomes associated with each therapeutic option for patients diagnosed with interstitial pregnancy (IP). METHODS: We conducted a multicentric retrospective cohort study within the departments of Gynecology and Obstetrics involved in the Francogent research group. Women treated for an interstitial pregnancy between January 2008 to December 2019 were included. Three therapeutic options were evaluated: surgical treatment (ST); in situ methotrexate combined with systemic methotrexate (IS-MTX); and systemic methotrexate (IM-MTX). Success of first-line treatment was defined by hCG negativation (<5I U/L). Secondary outcomes included the need for secondary surgical procedure, secondary medical treatment, emergency surgery, postoperative complications, duration of hospitalization, and delay before hCG negativation. RESULTS: A total of 98 patients were managed for IP: 42 (42.9%) patients had IM-MTX; 34 (34.7%) had IS-MTX; and 22 (22.4%) had ST. First-line treatment was successful in all patients of the ST group (22/22, 100%), in 31% of patients within the IM-MTX group (13/42) and 70.6% (24/34) in the IS-MTX group. The sole parameter associated with the risk of treatment failure was the mode of methotrexate administration. The size of the gestational sac or the presence of fetal heartbeat was not associated with decreased medical treatment (IS or IM-MTX) efficiency. CONCLUSION: Either ST or IS-MTX are good options for IP treatment associated with high success rates. A single-dose regimen of IM-MTX is less efficient than IS-MTX or ST. Symptomatic patients with severity criteria should always undergo emergency surgery. IP remains a high-risk condition that should be managed, whenever possible, in referral centers to potentialize the chances of favorable outcomes.

Parametrial endometriosis: A predictive and prognostic factor for voiding dysfunction and complications.

OBJECTIVE: Parametrial involvement (PI) in endometriosis is poorly defined resulting in an underestimation of its impact during surgical excision. The aim of our study was to assess the surgical complications associated with parametrectomy during surgery for endometriosis. Our secondary objective was to compare the surgical complications rates of a parametrectomy to the excision of other deep pelvic endometriotic locations. STUDY DESIGN: Patients who underwent surgery for deep pelvic endometriosis from 2013 to 2018 in a French referral center were retrospectively included. Surgical complications were assessed according to whether a parametrectomy had been performed. The extent of surgery (colpectomy, torus, utero-sacral (USL) and/or rectal resection) was also assessed. Voiding dysfunction was defined as the need for self-catheterization ≥1 month and intra and postoperative complications were graded using the Clavien-Dindo classification (CDC). RESULTS: We included 753 patients: 285 (37.8 %) with PI. Patients with PI had higher ASRM scores and more extensive surgery than those without. These patients also had higher rates of voiding dysfunctions (17.5 % versus 8.98 %, p < 0.01), and postoperative complications (44.6 % versus 24.6 %, p < 0.01), including major complications (CDC 3-4) (14.7 % vs 8.5 %, p = 0.01). The extent of the surgical resection of endometriosis was strongly associated with surgical complications after multivariable analysis, and the addition of a parametrectomy during surgery greatly increased rates of adverse postoperative events. Voiding dysfunction was frequent in women with combined resection of the torus, utero-sacral ligaments, parametrium and vagina (adjusted OR = 37.28, 95 %CI = 6.84-203.11, p < 0.01, reference: resection of the USL). CONCLUSION: Parametrectomy significantly impacts postoperative complications in patients undergoing surgery for endometriosis.

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.

A Bioinformatics Approach to MicroRNA-Sequencing Analysis Based on Human Saliva Samples of Patients with Endometriosis.

Endometriosis, defined by the presence of endometrium-like tissue outside the uterus, affects 2-10% of the female population, i.e., around 190 million women, worldwide. The aim of the prospective ENDO-miRNA study was to develop a bioinformatics approach for microRNA-sequencing analysis of 200 saliva samples for miRNAome expression and to test its diagnostic accuracy for endometriosis. Among the 200 patients, 76.5% (n = 153) had confirmed endometriosis and 23.5% (n = 47) had no endometriosis (controls). Small RNA-seq of 200 saliva samples yielded ~4642 M raw sequencing reads (from ~13.7 M to ~39.3 M reads/sample). The number of expressed miRNAs ranged from 1250 (outlier) to 2561 per sample. Some 2561 miRNAs were found to be differentially expressed in the saliva samples of patients with endometriosis compared with the control patients. Among these, 1.17% (n = 30) were up- or downregulated. Among these, the F1-score, sensitivity, specificity, and AUC ranged from 11-86.8%, 5.8-97.4%, 10.6-100%, and 39.3-69.2%, respectively. Here, we report a bioinformatic approach to saliva miRNA sequencing and analysis. We underline the advantages of using saliva over blood in terms of ease of collection, reproducibility, stability, safety, non-invasiveness. This report describes the whole saliva transcriptome to make miRNA quantification a validated, standardized, and reliable technique for routine use. The methodology could be applied to build a saliva signature of endometriosis.

MicroRNome analysis generates a blood-based signature for endometriosis.

Endometriosis, characterized by endometrial-like tissue outside the uterus, is thought to affect 2-10% of women of reproductive age: representing about 190 million women worldwide. Numerous studies have evaluated the diagnostic value of blood biomarkers but with disappointing results. Thus, the gold standard for diagnosing endometriosis remains laparoscopy. We performed a prospective trial, the ENDO-miRNA study, using both Artificial Intelligence (AI) and Machine Learning (ML), to analyze the current human miRNome to differentiate between patients with and without endometriosis, and to develop a blood-based microRNA (miRNA) diagnostic signature for endometriosis. Here, we present the first blood-based diagnostic signature obtained from a combination of two robust and disruptive technologies merging the intrinsic quality of miRNAs to condense the endometriosis phenotype (and its heterogeneity) with the modeling power of AI. The most accurate signature provides a sensitivity, specificity, and Area Under the Curve (AUC) of 96.8%, 100%, and 98.4%, respectively, and is sufficiently robust and reproducible to replace the gold standard of diagnostic surgery. Such a diagnostic approach for this debilitating disorder could impact recommendations from national and international learned societies.

Clues for Improving the Pathophysiology Knowledge for Endometriosis Using Serum Micro-RNA Expression.

The pathophysiology of endometriosis remains poorly understood. The aim of the present study was to investigate functions and pathways associated with the various miRNAs differentially expressed in patients with endometriosis. Plasma samples of the 200 patients from the prospective "ENDO-miRNA" study were analyzed and all known human miRNAs were sequenced. For each miRNA, sensitivity, specificity, and ROC AUC values were calculated for the diagnosis of endometriosis. miRNAs with an AUC ≥ 0.6 were selected for further analysis. A comprehensive review of recent articles from the PubMed, Clinical Trials.gov, Cochrane Library, and Web of Science databases was performed to identify functions and pathways associated with the selected miRNAs. In total, 2633 miRNAs were found in the patients with endometriosis. Among the 57 miRNAs with an AUC ≥ 0.6: 20 had never been reported before; one (miR-124-3p) had previously been observed in endometriosis; and the remaining 36 had been reported in benign and malignant disorders. miR-124-3p is involved in ectopic endometrial cell proliferation and invasion and plays a role in the following pathways: mTOR, STAT3, PI3K/Akt, NF-κB, ERK, PLGF-ROS, FGF2-FGFR, MAPK, GSK3B/ß-catenin. Most of the remaining 36 miRNAs are involved in carcinogenesis through cell proliferation, apoptosis, and invasion. The three main pathways involved are Wnt/ß-catenin, PI3K/Akt, and NF-KB. Our results provide evidence of the relation between the miRNA profiles of patients with endometriosis and various signaling pathways implicated in its pathophysiology.

Prognosis of triple-negative breast cancer associated with pregnancy: A propensity score-matched analysis from the French CALG (Cancer Associé à la Grossesse) network.

INTRODUCTION: Triple-negative (TN) breast cancer represents one third of pregnancy-associated breast cancers (PABC). The aims of the current study were to describe oncological and obstetrical outcomes of patients with TN-PABC and to compare their prognosis with TN-non-PABC patients using a propensity score. MATERIALS AND METHODS: Between January 2005 and December 2020, data of patients with histologically proven TN-PABC were collected and compared with data of TN-non-PABC patients under the age of 46 years diagnosed during the same period using a propensity score (PS). RESULTS: After PS matching (tumor size and lymph node involvement),there were 59 patients in each group. The median follow-up was 14 months (IQR 4.8-40.1) for the TN-PABC group and 60 months (IQR 30.7-101.4) for the TN-non-PABC group. Eight recurrences occurred in the TN-PABC group and 10 in the TN-non-PABC group (adjusted OR (AOR) = 0.60 (0.21-1.60), HR (Cox adjusted model- AHR) = 1.25 (0.53-2.94)). Two patients died in the TN-PABC group, and six in the TN-non-PABC group with an AOR = 0.23 (0.03-1.01) and an AHR = 0.58 (0.12-2.69). All the patients diagnosed during the second (n = 17) and third trimesters (n = 28) continued their pregnancies, with a median term at delivery of 38 WG (IQR 36-39). All patients gave birth to healthy newborns. CONCLUSION: Although the TN subtype is associated with poor prognosis in pregnant patients due to advanced stage at diagnosis and high lymph node involvement, our PS-matched case-control study showed that pregnancy per se does not worsen the prognosis in terms of recurrence-free and overall survival.

Surgical Outcomes after Colorectal Surgery for Endometriosis: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess the impact of type of surgery for colorectal endometriosis-rectal shaving or discoid resection or segmental colorectal resection-on complications and surgical outcomes. DATA SOURCES: We performed a systematic review of all English- and French-language full-text articles addressing the surgical management of colorectal endometriosis, and compared the postoperative complications according to surgical technique by meta-analysis. The PubMed, Clinical Trials.gov, Cochrane Library, and Web of Science databases were searched for relevant studies published before March 27, 2020. The search strategy used the following Medical Subject Headings terms: ("bowel endometriosis" or "colorectal endometriosis") AND ("surgery for endometriosis" or "conservative management" or "radical management" or "colorectal resection" or "shaving" or "full thickness resection" or "disc excision") AND ("treatment", "outcomes", "long term results" and "complications"). METHODS OF STUDY SELECTION: Two authors conducted the literature search and independently screened abstracts for inclusion, with resolution of any difference by 3 other authors. Studies were included if data on surgical management (shaving, disc excision, and/or segmental resection) were provided and if postoperative outcomes were detailed with at least the number of complications. The risk of bias was assessed according to the Cochrane recommendations. TABULATION, INTEGRATION, AND RESULTS: Of the 168 full-text articles assessed for eligibility, 60 were included in the qualitative synthesis. Seventeen of these were included in the meta-analysis on rectovaginal fistula, 10 on anastomotic leakage, 5 on anastomotic stenosis, and 9 on voiding dysfunction <30 days. The mean complication rate according to shaving, disc excision, and segmental resection were 2.2%, 9.7%, and 9.9%, respectively. Rectal shaving was less associated with rectovaginal fistula than disc excision (odds ratio [OR] = 0.19; 95% confidence interval [CI], 0.10-0.36; p <.001; I2 = 33%) and segmental colorectal resection (OR = 0.26; 95% CI, 0.15-0.44; p <.001; I2 = 0%). No difference was found in the occurrence of rectovaginal fistula between disc excision and segmental colorectal resection (OR = 1.07; 95% CI, 0.70-1.63; p = .76; I2 = 0%). Rectal shaving was less associated with leakage than disc excision (OR = 0.22; 95% CI, 0.06-0.73; p = .01; I2 = 86%). No difference was found in the occurrence of leakage between rectal shaving and segmental colorectal resection (OR = 0.32; 95% CI, 0.10-1.01; p = .05; I2 = 71%) or between disc excision and segmental colorectal resection (OR = 0.32; 95% CI, 0.30-1.58; p = .38; I2 = 0%). Disc excision was less associated with anastomotic stenosis than segmental resection (OR = 0.15; 95% CI, 0.05-0.48; p = .001; I2 = 59%). Disc excision was associated with more voiding dysfunction <30 days than rectal shaving (OR = 12.9; 95% CI, 1.40-119.34; p = .02; I2 = 0%). No difference was found in the occurrence of voiding dysfunction <30 days between segmental resection and rectal shaving (OR = 3.05; 95% CI, 0.55-16.87; p = .20; I2 = 0%) or between segmental colorectal and discoid resections (OR = 0.99; 95% CI, 0.54-1.85; p = .99; I2 = 71%). CONCLUSION: Colorectal surgery for endometriosis exposes patients to a risk of severe complications such as rectovaginal fistula, anastomotic leakage, anastomotic stenosis, and voiding dysfunction. Rectal shaving seems to be less associated with postoperative complications than disc excision and segmental colorectal resection. However, this technique is not suitable for all patients with large bowel infiltration. Compared with segmental colorectal resection, disc excision has several advantages, including shorter operating time, shorter hospital stay, and lower risk of postoperative bowel stenosis.

Therapeutic management of uterine fibroid tumors.

Fibroids, which are benign smooth-muscle tumors of clonal origin, are the most common gynecologic tumors occurring in about 20 to 25 % of women over 30 years of age. The most frequent symptoms are pelvic pain and heavy menstrual bleeding resulting in anemia. The role of fibroids in infertility remains debated but probably mostly related to submucosal location due to implantation impairment. Although most women are asymptomatic (80%), fibroids can have a considerable impact on quality of life. Considering this impact and the cost associated with their management, treatment of fibroids is a public health concern. Treatment options for symptomatic fibroids include medical, surgical and alternatives techniques. Medical management is mainly based on the use of progestogens, antifibrinolytics agents, non-steroidal anti-inflammatory drugs, Gonadotropin-releasing hormone analogs selective progesterone receptor modulators. Surgical management includes myomectomy (hysteroscopic, laparoscopic, minilaparoscopic or laparotomic) and hysterectomy. The choice of surgery depends on several factors: the number, topography and size of myomas, the age of the patient and her desire for fertility, treatment history and her desire to keep the uterus. Alternatives techniques to surgery are mainly based on the uterine artery embolization. The aim of this article is to provide evidence based recommendations for the management of uterine fibroids.