Evaluating the safety of high-intensity focused ultrasound treatment for rectal endometriosis: results from a French prospective multicentre study including 60 patients.

STUDY QUESTION: Is increasing the intensity of high-intensity focused ultrasound (HIFU) by 30% in the treatment of rectal endometriosis a safe procedure? SUMMARY ANSWER: This study demonstrates the safety of a 30% increase in the intensity of HIFU in the treatment of rectal endometriosis, with no Clavien-Dindo Grade III complications overall, and namely no rectovaginal fistulae. WHAT IS KNOWN ALREADY: A feasibility study including 20 patients with rectal endometriosis demonstrated, with no severe complications, a significant improvement in digestive disorders, dysmenorrhoea, dyspareunia, and health status, although the volume of the endometriosis nodule did not appear to be reduced. STUDY DESIGN, SIZE, DURATION: A prospective multicentre cohort study was conducted between 2020 and 2022 with 60 patients with symptomatic rectal endometriosis. Following the failure of medical treatment, HIFU treatment was offered as an alternative to surgery. PARTICIPANTS/MATERIALS, SETTING, METHODS: As the main objective of this study was to examine safety, all adverse events observed during the 6 months of follow-up were analysed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) and Clavien-Dindo classifications. Secondary objectives included evaluating the evolution of symptoms using validated questionnaires: gynaecological and digestive pain symptoms with a visual analogue scale, health status with the Medical Outcomes Study 36-item Short Form (SF-36) questionnaire, average post-operative daily pain level, and analgesic medication required in the 10 days following treatment. MRI was also performed at Day 1 to detect early complications. Finally, we performed a blinded MRI review of the evolution of the nodule at 6 months post-treatment. MAIN RESULTS AND THE ROLE OF CHANCE: The procedure was performed under spinal anaesthesia for 30% of the patients. The median duration of treatment was 32 min. Fifty-five patients left the hospital on Day 1. MRI scans performed on Day 1 did not highlight any early-onset post-operative complication. Using the Clavien-Dindo classification, we listed 56.7% Grade I events, 3.4% Grade II events, and no events Grade III or higher. At 1, 3, and 6 months, all gynaecologic, digestive and general symptoms, as well as health status, had significantly improved. The evolution of the nodule was also significant (P < 0.001) with a 28% decrease in volume. LIMITATIONS, REASONS FOR CAUTION: The main objective was safety and not effectiveness. The study was not randomized and there was no control group. WIDER IMPLICATIONS OF THE FINDINGS: HIFU treatment for rectal endometriosis results in an improvement of symptoms with low morbidity; as such, for selected patients, it could be a valuable alternative to surgical approaches following the failure of medical treatment. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the company EDAP TMS. Professors Dubernard and Rousset are consultants for EDAP TMS. Dubernard received travel support from EDAP-TMS. Dr F. Chavrier received industrial grants from EDAP-TMS. He has developed a device for generating focused ultrasonic waves with reduced treatment time. This device has been patented by EDAP-TMS. Dr Lafon received industrial grants from EDAP-TMS; he declares that EDAP-TMS provided funding directly to INSERM to support a young researcher chair in therapeutic ultrasound, which is unrelated to the current study. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT04494568.

Surgical Management of Urinary Tract Endometriosis: A 1-year Longitudinal Multicenter Pilot Study at 31 French Hospitals (by the FRIENDS Group).

STUDY OBJECTIVE: To describe the surgical management and risks of postoperative complications of patients with urinary tract endometriosis in France in 2017. DESIGN: Multicenter retrospective cohort pilot study. SETTING: Departments of gynecology at 31 expert endometriosis centers. PATIENTS: All women managed surgically for urinary tract endometriosis from January 1, 2017, to December 31, 2017. We distinguished patients with isolated bladder endometriosis or isolated ureteral endometriosis (IUE) from those with endometriosis in both locations (mixed locations [ML]). INTERVENTIONS: Surgeons belonging to the French Colorectal Infiltrating Endometriosis Study (FRIENDS) group enrolled patients who filled a 24-item questionnaire on the day of the inclusion and 3 months later. Data were collected on operative routes, surgical management, and postoperative complications according to the Clavien-Dindo classification in a single anonymized database. MEASUREMENTS AND MAIN RESULTS: A total of 232 patients from 31 centers were included. Isolated bladder endometriosis was found in 82 patients (35.3%), IUE in 126 patients (54.4%), and ML in 24 patients (10.3%). Surgery was performed by laparoscopy, laparotomy, or robot-assisted laparoscopy in 74.1%, 11.2%, and 14.7% of the cases, respectively. Among the 150 ureteral lesions (IUE and ML), 114 were managed with ureterolysis (76%), 28 with ureteral resection (18.7%), 4 with nephrectomy (2.7%), and 23 with cystectomy (15.3%). Concerning bladder endometriosis, a partial cystectomy was performed in 94.3% of the cases. We reported 61 postoperative complications (26.3%): 44 low-grade complications according to the Clavien-Dindo classification (18%), 16 grade III complications (7%), and 1 grade IV complication (peritonitis). CONCLUSION: The surgical management of ureteral and bladder endometriosis is usually feasible and safe through laparoscopic surgery. Ureteral resection, when necessary, is more strongly associated with laparotomy and with more complications than other procedures. Prospective controlled studies are still mandatory to assess the best surgical management for patients.

Fertility and prognosis of borderline ovarian tumor after conservative management: Results of the multicentric OPTIBOT study by the GINECO & TMRG group.

OBJECTIVES: Description of fertility and prognosis of patients with borderline ovarian tumor (BOT) treated by fertility-sparing surgery through a longitudinal study from the French national cancer network. METHODS: All consecutive patients diagnosed with BOT from the French National Network dedicated to Ovarian Malignant Rare Tumors from 2010 and 2017 were selected. In 2018, an update was made by sending a questionnaire regarding recurrence and fertility to patients aged under 43 years at diagnosis and treated conservatively. We compared the characteristics of the patients with/without recurrence and with/without live birth. RESULTS: Fifty-two patients aged 18 to 42 years presented a desire of pregnancy. Thirty patients (58%) presented a FIGO IA tumor, and 20 patients were treated by bilateral cystectomies (38%). We observed at least one live birth for 33 patients (63%) and local recurrences in 20 patients (38%). Both recurrence and live birth in 17 patients (33%) were reported, with recurrence occurring before pregnancy, after a second fertility-sparing treatment, in half of the cases. No factors associated with recurrence or live birth in this study were identified. Moreover, in this population, both recurrence and live birth were independent of age, with a linear risk along time. Disease-free survival was worse for patients treated with bilateral cystectomy (n = 20, 38%), with no difference in terms of fertility. CONCLUSION: Two third of the patients experienced life birth after conservation surgery. We did not highlight an age/time from surgery for which the risk of recurrence outweighs the chance of pregnancy and to radicalize surgery. Moreover, almost a quarter of the live birth occurred after recurrence, with no more further event to date in these patients. The results encourage to consider a second fertility-sparing surgery after local borderline recurrence in the case of pregnancy desire. All these decisions must be discussed in specialized multidisciplinary boards.

Inhibition of PI3K-AKT-mTOR pathway sensitizes endometrial cancer cell lines to PARP inhibitors.

BACKGROUND: Phosphatase and Tensin homolog (PTEN) is a tumor suppressor gene. Loss of its function is the most frequent genetic alteration in endometrioid endometrial cancers (70-80%) and high grade tumors (90%). We assessed the sensitivity of endometrial cancer cell lines to PARP inhibitors (olaparib and BMN-673) and a PI3K inhibitor (BKM-120), alone or in combination, in the context of their PTEN mutation status. We also highlighted a direct pathway linking PTEN to DNA repair. METHODS: Using endometrial cancer cellular models with known PTEN status, we evaluated their homologous recombination (HR) functionality by RAD51 foci formation assay. The 50% Inhibitory concentration (IC50) of PI3K and PARP inhibitors in these cells was assessed, and western blotting was performed to determine the expression of proteins involved in the PI3K/mTOR pathway. Moreover, we explored the interaction between RAD51 and PI3K/mTOR by immunofluorescence. Next, the combination effect of PI3K and PARP inhibitors on cell proliferation was evaluated by a clonogenic assay. RESULTS: Cells with mutated PTEN showed over-activation of the PI3K/mTOR pathway. These cells were more sensitive to PARP inhibition compared to PTEN wild-type cells. In addition, PI3K inhibitor treatment reduced RAD51 foci formation in PTEN mutated cells, and sensitized these cells to PARP inhibitor. CONCLUSION: Targeting both PARP and PI3K might lead to improved personalized therapeutic approaches in endometrial cancer patients with PTEN mutations. Understanding the complex interaction of PTEN mutations with DNA repair in endometrial cancer will help to better select patients that are likely to respond to some of the new and costly targeted therapies.

Metformin Increases E-cadherin in Tumors of Diabetic Patients With Endometrial Cancer and Suppresses Epithelial-Mesenchymal Transition in Endometrial Cancer Cell Lines.

PURPOSE: Epithelial-mesenchymal transition (EMT) is a critical process for cancer metastasis and recurrence. Metformin, an effective oral antidiabetic drug, has been associated with decreased cancer risk and mortality. In this pilot study, we started to evaluate the effect of metformin on EMT in vivo and in vitro in endometrial cancer (EC). METHODS: Endometrial cancer cell lines and freshly isolated EC tumor specimens were used to assess EMT after metformin treatment. Cell lines were subjected to wound healing and AlamarBlue assays to determine cell migration and cell proliferation; messenger RNA levels were measured by real-time reverse transcriptase (RT) quantitative polymerase chain reaction (PCR), and protein levels were measured by Western blots to detect EMT marker expression. RESULTS: Protein expression and messenger RNA of E-cadherin was found to be increased (P = 0.02 and 0.04, respectively) in 30 EC tumor specimens of diabetic patients treated with metformin compared with 20 EC tumor specimens of diabetic patients treated with other antidiabetic agents. In vitro, metformin reduced cell migration at 5 mM for 48 hours, as determined by the wound healing assay in EC cell lines (Ishikawa, 45% reduction; HEC50, 40% reduction), whereas more than 90% of the cells remained viable on the AlamarBlue assay. Metformin reduced EMT in the cell lines and regulated the expression of the EMT-related epithelial markers, E-cadherin and Pan-keratin; the mesenchymal markers, N-cadherin, fibronectin, and vimentin; and the EMT drivers, Twist-1, snail-1, and ZEB-1. CONCLUSIONS: Tumors of patients on metformin have increased E-cadherin expression, and metformin decreases EMT in EC cell lines in vitro, suggesting clinical biological relevance of metformin in women with EC.

Suppression of Homologous Recombination by insulin-like growth factor-1 inhibition sensitizes cancer cells to PARP inhibitors.

BACKGROUND: Impairment of homologous recombination (HR) is found in close to 50 % of ovarian and breast cancer. Tumors with BRCA1 mutations show increased expression of the Insulin-like growth factor type 1 receptor (IGF-1R). We previously have shown that inhibition of IGF-1R results in growth inhibition and apoptosis of ovarian tumor cells. In the current study, we aimed to investigate the correlation between HR and sensitivity to IGF-1R inhibition. Further, we hypothesized that IGF-1R inhibition might sensitize HR proficient cancers to Poly ADP ribose polymerase (PARP) inhibitors. METHODS: Using ovarian and breast cancer cellular models with known BRCA1 status, we evaluated their HR functionality by RAD51 foci formation assay. The 50 % lethal concentration (LC50) of Insulin-like growth factor type 1 receptor kinase inhibitor (IGF-1Rki) in these cells was assessed, and western immunoblotting was performed to determine the expression of proteins involved in the IGF-1R pathway. Moreover, IGF-1R inhibitors were added on HR proficient cell lines to assess mRNA and protein expression of RAD51 by qPCR and western blot. Also, we explored the interaction between RAD51 and Insulin receptor substance 1 (IRS-1) by immunoprecipitation. Next, combination effect of IGF-1R and PARP inhibitors was evaluated by clonogenic assay. RESULTS: Cells with mutated/methylated BRCA1 showed an impaired HR function, and had an overactivation of the IGF-1R pathway. These cells were more sensitive to IGF-1R inhibition compared to HR proficient cells. In addition, the IGF-IR inhibitor reduced RAD51 expression at mRNA and protein levels in HR proficient cells, and sensitized these cells to PARP inhibitor. CONCLUSION: Targeting IGF-1R might lead to improved personalized therapeutic approaches in cancer patients with HR deficiency. Targeting both PARP and IGF-1R might increase the clinical efficacy in HR deficient patients and increase the population of patients who may benefit from PARP inhibitors.

Three-dimensional ultrasound in the management of bladder endometriosis.

STUDY OBJECTIVE: To assess the performance of three-dimensional (3D) ultrasound with color Doppler in the diagnosis of bladder endometriosis compared with magnetic resonance imaging (MRI) and cystoscopy. DESIGN: Canadian Task Force classification II-3. SETTING: Department of gynecology and obstetrics of a university hospital. PATIENTS: Eight women who reported urinary tract symptoms suggestive of bladder endometriosis between May 2012 and November 2013. INTERVENTIONS: For all cases, we assessed the size of the endometriotic nodule, its location on the bladder wall, and the distance between the lesion and the ureteral meatus, with pelvic 3D ultrasound (full bladder), uro-MRI, and cystoscopy. The results were compared with the postoperative histopathologic findings. MEASUREMENTS AND MAIN RESULTS: The pathology results differed from those produced by imaging by a mean ± SD of -3.5 ± 6.4 mm on transvaginal ultrasound (TVUS) and -5.75 ± 11.9 mm) for MRI. There was no significant difference between imaging and pathology findings (p = .20) or between the 2 imaging findings (TVUS and MRI) (p = .73). Results showed a trend toward better accuracy for 3D ultrasound than MRI with smaller SDs (p = .08). Cystoscopy and ultrasound were compared; however, without any tools to assess the distance in cystoscopy, no statistical result was possible. CONCLUSION: Ultrasound seems to be superior to cystoscopy and is at least as effective as MRI in diagnosing and planning the surgery for bladder endometriosis.

High-grade undifferentiated sarcomas of the uterus: diagnosis, outcomes, and new treatment approaches.

High-grade undifferentiated sarcomas (HGUS) are rare malignancies accounting for 6 % of all uterine sarcomas and have a very poor outcome. Histological classification of HGUS is currently debated as a subgroup with uniform nucleoli, and frequently YWHAE-FAM22 transcript has been described, constituting a potential target for new therapies. In localized HGUS, surgery involving total hysterectomy and bilateral oophorectomy is recommended. Adjuvant radiotherapy has recently been suggested in a retrospective study to decrease local recurrence and improve survival versus observation in localized HGUS. In metastatic or recurrent disease, chemotherapy with doxorubicin with or without ifosfamide constitutes the standard of care. Gemcitabine plus docetaxel also seems to be an interesting alternative. Targeted therapies such as pazopanib are now available for soft tissue sarcomas and so could be proposed for uterine sarcoma patients after first- or second-line chemotherapy in the metastatic phase. Further investigations are needed to determine their indications and targets. A European Organisation for Research and Treatment of Cancer (EORTC) randomized trial testing maintenance therapy with cabozantinib after first-line chemotherapy in HGUS is ongoing.

Mastectomies for breast cancer: Comparison between peri-operative morbidity after simple mastectomy or after immediate breast reconstruction in a unicentric serie of 210 patients.

BACKGROUND: In breast cancer surgery, IBR (immediate breast reconstruction) is widely proposed to patients without indications of adjuvant treatments and without risk factors of surgical complications. New INCa's guidelines (2022) allow the expansion of IBR indications. OBJECTIVE: A retrospective, unicentric and safety study: post-operative complication rate after IBR in comparison with simple mastectomy (SM, reference treatment). MATERIEL AND METHOD: This retrospective study has included all major patients who have received mastectomy for breast cancer between 2016 and 2020 before application of new guidelines, in Hôpital de la Croix-Rousse, Lyon (France). They were distributed in two groups according to their surgery : IBR and SM. Usual risk factors of post-operative complications were collected (tabacco, obesity…). The primary endpoint was the occurrence of an early post-operative complication (within 3 months after surgery). Two secondary analysis focused on the impact of preoperative risk factors on complications, and the proportion of patients eligibled for an IBR among SM based on new INCA's guidelines. RESULTS: The study included 185 mastectomies: 153 SM, 32 mastectomies IBR.  IBR's patients presented less risk factors, and few indications of adjuvant treatments. The rate of major complications was identical in the two groups (14 % in SM group, 12 % in IBR group), and there were more minor complications in the SM group than in the IBR group (p 0,01). According to our study, the raw proportion of initially possible IBR was 68 % (36 % of breast reconstruction in this study). CONCLUSION: This analyse approve IBR in selected patients. In this context, INCa's guidelines (2022) can generalize IBR's proposal to patients. However, the analysis of pre-operative risk factors stay essential in medical care.

[Laparoscopic ultrasound-guided radiofrequency ablation of uterine fibroid: A retrospective study]. / Myolyse des fibromes utérins par radiofréquence cœlioscopique sous contrôle échographique : à propos d'une série rétrospective.

OBJECTIVE: To assess clinical and radiological efficacy and safety of laparoscopic ultrasound-guided radiofrequency ablation of uterine leiomyomas. MATERIAL AND METHODS: Thirty-three patients with symptomatic uterine leiomyomas FIGO type 2 to 7, have undergone a laparoscopic ultrasound-guided radiofrequency ablation at Croix Rousse University Hospital Center (Hospices civils de Lyon) and at Saint-Vincent de Paul Hospital in Lille, between June 2020 and December 2022. The characteristics of each myoma and the symptoms were assessed with pelvic MRI and with Higham score, SSS and HRQL scores preoperatively and at 6 months. RESULTS: A total of 54 fibroids have been treated in 33 patients. We observed a significant decrease of the volume 6 months after the surgery, on average 21mL (55.97 vs. 74.37mL, 95% CI [7.13-34.88], P=0.001). The maximum diameter of each fibroid was also significantly reduced on average 11.78mm (41.89 vs. 52.06, 95% CI [8.83-14.73], P<0.05). We noticed a significant decrease of the NRS for dysmenorrhea on average 2.79 points (2.1 vs. 4.89, 95% CI [1.14-4.42], P<0.05). There was also a trend to improvement of menorrhagia, assess by Higham score. Indeed, 70.8% of the patients had menorrhagia. Menorrhagia was improved of 108,3 points with an average Higham score before surgery of 197.3 versus 87.9 after surgery (95% CI [47.9-168.8], P=0.001). Concerning UFS-QOL score: the symptom severity score (SSS) decreased on average 33 points, testifying of symptom improvement (27.04 vs. 60.89, 95% CI [22.92-43.39], P<0.001) and the HRQL score increased on average 20 points testifying quality of life improvement (65.57 vs. 42.7, 95% CI [15.83-37.85]. P<0.001). No severe adverse event has been reported. CONCLUSION: In this first French study about radiofrequency ablation. We confirm its efficiency for improvement of symptoms and quality of life but other study is mandatory to confirm the safety of this procedure in particular in patients with a wish to conceive.

Retrospective analysis of uterine involvement in low grade serous ovarian carcinoma.

OBJECTIVES: Low grade serous ovarian carcinoma (LGSOC) accounts for 2.5% of all ovarian carcinoma more affects younger women than high grade serous ovarian carcinoma. Hysterectomy is performed routinely for LGSOC treatment, but fertility sparring surgery (FSS) is feasible for some early stages. Currently, there is no study about uterine involvement in LGSOC. We evaluate uterine involvement in LGSOC patients and aim to identify pre-operative predictive factors. METHODS: Retrospective observational study of LGSOC patients treated between January 2000 and May 2022 in the Hospices Civils de Lyon. All cases were viewed, reviewed or approved by an expert pathologist. RESULTS: Among 535 serous ovarian carcinomas, 26 were included. Most patients (73 %) had FIGO III disease. Median OS was 115 months and median PFS was 42 months. Uterine involvement was found in 58 % patients who underwent hysterectomy (14/24), serosal involvement was the most frequent type of involvement (n = 13, 54 %). Myometrial involvement was found in 8 patients (33 %) and was associated with serosal involvement (7/8). Among patients with a macroscopic disease-free uterus during exploratory laparoscopy, 31 % had a microscopic serosal involvement. None patient with presumed early stage (FIGO I) were upstaged due to uterine involvement (serosal or myometrial). In patients with stage FIGO IIII, 72 % of uterine involvement were found. Univariate analysis did not show any predictive factor of myometrial involvement. There was no difference on OS nor PFS between patients with or without myometrial involvement. CONCLUSIONS: In early stages LGSOC, FSS may be considered for selected patients. In advanced stages, hysterectomy should be performed routinely, since no predictive factor for uterine involvement were identified.

Anterior sacrospinous ligament fixation by the vaginal route in ten steps.

Pelvic organ prolapse (POP) is a common condition affecting women, characterized by the descent of pelvic organs such as the vagina and uterus. While POP may not always cause symptoms, it can significantly impact a woman's quality of life. Diagnosis is typically made through clinical examination, and treatment options range from pelvic-floor physical therapy to surgery. Anterior sacrospinous ligament fixation (ASSLF) has emerged as a viable technique for treating apical prolapse vaginally. This procedure involves attaching the cervix or vaginal vault to the sacrospinous ligament, providing satisfactory results in the short term. Compared to the posterior approach, ASSLF shows similar efficacy, shorter operative time, and potentially fewer complications. Vaginal surgery offers advantages such as lower morbidity and cost, ability to address other pelvic conditions simultaneously, and suitability for managing recurrences. The presented case involves a 72-year-old woman with stage 3 cystocele, stage 3 hysterocele, stage 1 rectocele, and severe voiding dysfunction. After unsuccessful attempts with a pessary, surgical intervention becomes necessary. An instructive video article has been created to standardize the essential steps of ASSLF and facilitate resident education. The video demonstrates ten surgical steps, including installation/exposure, anterior vaginal wall infiltration, median anterior colpotomy, vesico-vaginal dissection, paravesical dissection, sacrospinous ligament suture, cystocele correction, colpotomy and vaginal wall repair, uterine anterior isthmus suture and sacrospinous ligament fixation, and colporrhaphy final closure. In conclusion, POP is a prevalent condition that can be effectively managed through techniques like ASSLF. Vaginal surgery offers several advantages, and proper training and standardization of surgical steps contribute to successful outcomes and resident education.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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.

CREB fusion-associated epithelioid mesenchymal neoplasms of the female adnexa: three cases documenting a novel location of an emerging entity and further highlighting an ambiguous misleading immunophenotype.

EWSR1/FUS-CREB-rearranged mesenchymal neoplasms are an emerging heterogeneous group of soft tissue tumors that encompasses low-grade lesions (angiomatoid fibrous histiocytoma/AFH) and a group of predominantly intra-abdominal aggressive sarcomas with epithelioid morphology and frequent keratin expression. Both entities occasionally harbor EWSR1::ATF1 fusions as alternate to the more frequent EWSR1/FUS::CREB1/CREM fusions. Although EWSR1/FUS-CREB-rearranged epithelioid malignant neoplasms have been described in diverse intra-abdominal sites, none involved the female adnexa. Herein, we describe three cases involving uterine adnexa in young females (41, 39, and 42-year-old); two associated with constitutional inflammatory symptoms. The tumors presented as a serosal surface mass of the ovary without parenchymal involvement (Case 1), as circumscribed nodule within ovarian parenchyma (Case 2), and as a periadnexal mass extending into the lateral uterine wall with lymph node metastasis (Case 3). They were composed of sheets and nests of large epithelioid cells with numerous stromal lymphocytes and plasma cells. The neoplastic cells expressed desmin and EMA, and variably WT1. One tumor expressed in addition AE1/AE3, MUC4, synaptophysin, chromogranin, and ALK. None expressed sex cord-associated markers. RNA sequencing identified EWSR1::ATF1 fusions in two cases and an EWSR1::CREM fusion in one. Exome-based RNA capture sequencing and clustering methods showed high transcriptomic proximity of tumor 1 with soft tissue AFH. This novel subset of female adnexal neoplasms should be included in the differential diagnosis of any epithelioid neoplasm involving female adnexa. Their aberrant immunophenotype can be misleading, underlining a wide spectrum of differential diagnosis.

Effects of a physical activity and endometriosis-based education program delivered by videoconference on endometriosis symptoms: the CRESCENDO program (inCRease physical Exercise and Sport to Combat ENDOmetriosis) protocol study.

BACKGROUND: Endometriosis is a chronic disease characterized by growth of endometrial tissue outside the uterine cavity which could affect 200 million women (The term "woman" is used for convenience. Individuals gendered as man or as nonbinary can also suffer from this disease) worldwide. One of the most common symptoms of endometriosis is pelvic chronic pain associated with fatigue. This pain can cause psychological distress and interpersonal difficulties. As for several chronic diseases, adapted physical activity could help to manage the physical and psychological symptoms. The present study will investigate the effects of a videoconference-based adapted physical activity combined with endometriosis-based education program on quality of life, pain, fatigue, and other psychological symptoms and on physical activity. METHODS: This multicentric randomized-controlled trial will propose to 200 patients with endometriosis to be part of a trial which includes a 6-month program with 45 min to more than 120 min a week of adapted physical activity and/or 12 sessions of endometriosis-based education program. Effects of the program will be compared to a control group in which patients will be placed on a waiting list. All participants will be followed up 3 and 6 months after the intervention. None of the participants will be blind to the allocated trial arm. The primary outcome measure will be quality of life. Secondary outcomes will include endometriosis-related perceived pain, fatigue, physical activity, and also self-image, stereotypes, motivational variables, perceived support, kinesiophobia, basic psychological need related to physical activity, and physical activity barriers. General linear models and multilevel models will be performed. Predictor, moderator, and mediator variables will be investigated. DISCUSSION: This study is one of the first trials to test the effects of a combined adapted physical activity and education program for improving endometriosis symptoms and physical activity. The results will help to improve care for patients with endometriosis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05831735 . Date of registration: April 25, 2023.

Evaluation of an e-learning program for the diagnosis of rectosigmoid endometriosis with rectal water contrast transvaginal ultrasonography (rectosonography).

This study aimed to evaluate the value of an e-learning program for the diagnosis of rectosigmoid endometriosis lesions using rectal water contrast transvaginal ultrasonography (rectosonography/RSG). Theoretical RSG training using videos with a commentary was offered online to healthcare professionals involved in ultrasound screening for endometriosis. A test (without correction) with 24 RSG video loops was used to assess the participants' baseline level before the training and their improvement afterwards. If the success rate post-training was below 80 %, the participant could start over with another series of 24 videos. Between February and June 2020, thirty participants took the training course (of which 80 % were obstetrics-gynaecology residents). The e-learning program resulted in a significant performance increase in the diagnosis of rectosigmoid endometriosis lesions, with a higher test success rate after the training compared to before (74.4 % and 63.6 % respectively; +10.8 %; 95 % CI [6,6; 15]; p < 0.001). Significant improvement was also observed regarding the overall skills involved in the ultrasound diagnosis of deep infiltrating endometriosis (+9.2 %; p < 0.001), the accurate diagnosis of the height of bowel lesions (+14.7 %; p < 0.001) and uterosacral ligament lesions (+8%; p < 0.005). In conclusion, our e-learning program led to a significant improvement of the diagnostic performance of digestive endometriosis using transvaginal ultrasound with intrarectal water contrast (rectosonography). Adding feedback to the post-test video loops could further increase the efficacy of the e-learning training.

Learning Curve for the Detection of Deep Infiltrating Endometriosis and Adenomyosis with 3-D Transvaginal Water Contrast Sonography.

Three-dimensional rectosonography (RSG) is a transvaginal sonography technique using rectal water contrast and 3-D acquisitions. The main points of interest of 3-D RSG could be its easy accessibility and its quick learning curve, especially with respect to rectosigmoid lesions. The objective of this prospective observational study was to assess the learning curve of 3-D RSG for the diagnosis of rectosigmoid lesions and for various other locations of deep endometriosis (DE), endometriomas and adenomyosis. From April 2017 to November 2017, 116 patients with suspected pelvic endometriosis were referred to the Croix-Rousse University Hospital, and those who underwent 3-D RSG were included in our study. After a short training period, four residents were asked to perform 3-D RSG by themselves. Each procedure was systematically controlled immediately afterward by a single expert sonographer. The success of the procedure involved the correct identification of various locations of endometriosis (rectosigmoid, uterosacral ligament, retrocervical space, vagina, bladder and ovaries) and adenomyosis, using the expert sonographer's examination as the reference technique. The learning curve was generated using these data and assessed using the Learning Curve Cumulative Summation Test (LC-CUSUM) method. The pooled LC-CUSUM revealed that the required level of achievement was reached after 24 3-D RSGs were performed for the diagnosis of rectosigmoid lesions. All four residents were significantly competent in diagnosing rectosigmoid lesions at the end of their training period, with an α risk <0.05 (T1, p = 0.03; T2, p = 0.0002; T3, p = 0.05; T4, p = 0.02). The LC-CUSUM analysis confirmed that competency was achieved for vaginal DE, torus uterinum DE, US DE, bladder DE, endometriomas and adenomyosis within 17, 27, 38, 19, 17 and 33 scans, respectively. This study provides evidence that the skills required to diagnose endometriosis lesions and adenomyosis with 3-D RSG can be acquired after a brief learning period in an expert center.

Surgical management of diaphragmatic and thoracic endometriosis': A French multicentric descriptive study.

INTRODUCTION: Surgical management of Diaphragmatic and thoracic endometriosis (DTE) is still controversial, a thoracic or an abdominal approach can be proposed. METHODS: We conducted a multicentric retrospective study in 8 thoracic, gynecology or digestive surgery units in 5 French university hospitals. The main objective was to review the current management of DTE. RESULTS: 50 patients operated for DTE from 2010 to 2017 were included: 26 with a thoracic approach and 24 with an abdominal approach. Preoperative pelvic endometriosis (PE) concerned 25 patients. In 38 patients, DTE diagnosis was made on clinical symptoms (pneumothorax (n = 19), chronic or catamenial chest pain (n = 18) or hemopneumothorax (n = 1)). Median time from onset of symptoms to diagnosis was 47 months (0-212). PE surgery concurrently occurred in 22 patients. We report diaphragmatic nodules, pleuropulmonary nodules and diaphragmatic perforations in 42, 5 and 22 women respectively. Lesions were right-sided in 45 patients. Nodules were destructed in 12 cases and resected in 38 cases. When a diaphragmatic reconstruction was needed (n = 31), a simple suture was performed in 26 patients, while 5 patients needed a mesh repair. Pleural symphysis was performed for all patients who received a thoracic approach. DTE resection was considered complete in 46 patients. Three patients had severe 30-days complications of DTE surgery. Median follow-up was 20 months (range 1-69). Recurrence occurred in 10 patients. CONCLUSION: The results emphasize the importance of systematically looking for chest pain in patients suffering from PE and underline the lack of a standardized procedure and treatment in DTE.

Clinical characteristics of urinary tract endometriosis: A one-year national series of 232 patients from 31 endometriosis expert centers (by the FRIENDS group).

OBJECTIVE: To review prospectively the clinical characteristics of patients suffering from urinary tract endometriosis (UTE) in France, in 2017. STUDY DESIGN: We conducted a prospective observational multicenter study including women managed surgically for UTE in 31 French endometriosis expert centers (FRIENDS group) from January 1, 2017 to December 31, 2017. We distinguished patient with isolated bladder endometriosis ("IBE") or isolated ureteral endometriosis ("IUE") and patients associating both locations (mixed locations "ML"). Surgeons belonging to FRIENDS group enrolled patients by filling a 24 items questionnaire the day of the surgery and 6 weeks later. Data on the locations of UTE, preoperative assessment, urinary symptoms and associated pelvic locations were collected in a single anonymized database. RESULTS: A total of 232 patients from 31 centers were included. IBE concerned 82 patients (35.3%), IUE 126 patients (54.4%) ML 24 patients (10.3%). 111 patients reported urinary symptoms (47.8%). IUE was more often asymptomatic than the rest of the locations (59.5% versus 43.3%, OR 1,92, p = 0.017). Associated deep infiltrating endometriosis (DIE) lesions were found in 193 patients (83.1%). IUE was significantly associated with other DIE lesions (82.5% versus 66%, OR2.4, p = 0.006), particularly with rectum or sigmoid nodules (57.1% versus 36.8%, OR 2.3, p = 0.002) and retrocervical space nodules (31.7% versus 19.8%, OR 1.9, p = 0.05). CONCLUSION: Our study reports the second largest series of patients operated from a UTE and shows that ureteral location seems more frequent, less symptomatic and more frequently associated to other DIE locations than bladder endometriosis.

The Increasing Prognostic and Predictive Roles of the Tumor Primary Chemosensitivity Assessed by CA-125 Elimination Rate Constant K (KELIM) in Ovarian Cancer: A Narrative Review.

Ovarian cancer is the gynecological cancer with the worst prognosis and the highest mortality rate because 75% of patients are diagnosed with advanced stage III-IV disease. About 50% of patients are now treated with neoadjuvant chemotherapy followed by interval debulking surgery (IDS). In that context, there is a need for accurate predictors of tumor primary chemosensitivity, as it may impact the feasibility of subsequent IDS. Across seven studies with more than 12,000 patients, including six large randomized clinical trials and a national cancer registry, along with a mega-analysis database with 5842 patients, the modeled CA-125 ELIMination rate constant K (KELIM), the calculation of which is based on the longitudinal kinetics during the first three cycles of platinum-based chemotherapy, was shown to be a reproducible indicator of tumor intrinsic chemosensitivity. Indeed, KELIM is strongly associated with the likelihood of complete IDS, subsequent platinum-free interval, progression-free survival, and overall survival, along with the efficacy of maintenance treatment with bevacizumab or veliparib. As a consequence, KELIM might be used to guide more subtly the medical and surgical treatments in a first-line setting. Moreover, it could be used to identify the patients with poorly chemosensitive disease, who will be the best candidates for innovative treatments meant to reverse the chemoresistance, such as cell cycle inhibitors or immunotherapy.