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Recent evidence suggests that the fimbriated end of the fallopian tube harbors the precursor cells for many high-grade ovarian cancers, opening the door for development of better screening methods that directly assess the fallopian tube in women at risk for malignancy. Previously we have shown that the karyometric signature is abnormal in the fallopian tube epithelium in women at hereditary risk of ovarian cancer. In this study, we sought to determine whether the karyometric signature in serous tubal intraepithelial carcinoma (STIC) is significantly different from normal, and whether an abnormal karyometric signature can be detected in histologically normal tubal epithelial cells adjacent to STIC lesions. The karyometric signature was measured in epithelial cells from the proximal and fimbriated portion of the fallopian tube in fallopian tube specimens removed from women at: 1) average risk for ovarian cancer undergoing surgery for benign gynecologic indications (n = 37), 2) hereditary risk of ovarian cancer (germline BRCA alterations) undergoing risk-reducing surgery (n = 44), and 3) diagnosed with fimbrial STICs (n = 17). The karyometric signature in tubes with fimbrial STICs differed from that of tubes with benign histology. The degree of karyometric alteration increased with increasing proximity to fimbrial STICs, ranging from moderate in the proximal portion of the tube, to greatest in both normal appearing fimbrial cells near STICs as well as in fimbrial STIC lesions. These data demonstrate an abnormal karyometric signature in STICs that may extend beyond the STIC, potentially providing an opportunity for early detection of fallopian tube neoplasia. • Karyometric assessment reveals a signature that is abnormal in serous tubal intraepithelial carcinoma (STIC). • The abnormal karyometric signature extends to histologically normal fallopian tube epithelial cells beyond the STIC. • An abnormal karyometric signature in the fallopian tube has potential as a target for ovarian cancer screening. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate if time to start chemotherapy (TTC) after primary debulking surgery (PDS) impacted relative survival (RS) in advanced epithelial ovarian/fallopian tube/primary peritoneal cancer (EOC). Nationwide population-based study of women with EOC FIGO stages IIIC-IV, registered 2008–2018 in the Swedish Quality Register for Gynecologic Cancer, treated with PDS and chemotherapy. TTC was categorized into; ≤21 days, 22-28 days, 29-35 days, 36-42 days and > 42 days. Relative survival (RS) was estimated using the Pohar-Perme estimate of net survival. Multivariable analyses of excess mortality rate ratios (EMRRs) were estimated by Poisson regression models. In total, 1694 women were included. The median age was 65.0 years. Older age and no residual disease were more common in TTC >42 days than 0–21 days. The RS at 5-years was 37.9% and did not differ between TTC groups. In the R0 (no residual disease) cohort (n = 806), 2-year RS was higher in TTC ≤21 days (91.6%) and 22-28 days (91.4%) than TTC >42 days (79.1%). TTC >42 days (EMRR 2.33, p = 0.026), FIGO stage IV (EMRR 1.83, p = 0.007) and non-serous histology (EMRR 4.20, p < 0.001) were associated with 2-year worse excess mortality compared to TTC 0–21 days, in the R0 cohort. TTC was associated with 2-year survival in the R0 cohort in FIGO stage IV but not in stage IIIC. TTC was not associated with RS in patients with residual disease. For the entire cohort, stage IV, non-serous morphology and residual disease, but not TTC, influenced 5-year relative survival. However, longer TTC was associated with a poorer 2-year survival for those without residual disease after PDS. • Time to chemotherapy after PDS for advanced EOC does not influence 5-year survival. • Time to chemotherapy is associated with 2-year survival in patients with no residual disease (R0) after PDS. • Time to chemotherapy >42 days is associated with excess mortality in patients with FIGO stage IV and R0 after PDS. • Time to chemotherapy is not associated with survival in patients with advanced EOC and residual disease after PDS. [ABSTRACT FROM AUTHOR]

In the last two decades or so, a spectrum of benign, premalignant and malignant cervical glandular lesions exhibiting gastric differentiation has been described, with gastric‐type adenocarcinoma representing the most common human papillomavirus (HPV)‐independent cervical adenocarcinoma. More recently, limited literature has reported a variety of gastric‐type glandular lesions at other sites within the female genital tract and, as in the cervix (the most common site for these lesions), a spectrum of benign, premalignant and malignant lesions has been proposed. We provide an update and review of the emerging spectrum of gastric‐type glandular lesions at female genital tract sites other than the cervix. In the endometrium, putative gastric‐type glandular lesions include mucinous metaplasia of gastric‐type, atypical mucinous proliferation of gastric‐type and gastric‐type adenocarcinoma. Similarly in the vagina, gastric‐type adenosis, atypical adenosis and adenocarcinoma have been described. There have also been occasional reports of gastric‐type lesions involving the ovary and fallopian tube. We provide guidance on how to recognise gastric‐type lesions morphologically and immunophenotypically and stress that sometimes these lesions occur at more than one site within the female genital tract (synchronous/multifocal gastric‐type lesions of the female genital tract), sometimes in association with Peutz–Jeghers syndrome. [ABSTRACT FROM AUTHOR]

This article discusses the detection of primary peritoneal low-grade serous carcinoma in cervical smears. The study reports three cases of asymptomatic women who had abnormal glandular cells in routine Pap smears. Further investigations revealed raised serum CA125 levels and mild ascitic fluid collection in the pelvis. The patients underwent exploratory laparotomy, which confirmed the presence of low-grade serous carcinoma. The article emphasizes the diagnostic value of cellblock immunocytochemistry in confirming the diagnosis. The document also discusses the presence of low-grade serous papillary cell clusters with psammoma bodies in the tubal lumen, which are characteristic of primary peritoneal serous tumors. The document highlights the importance of considering various factors to distinguish primary peritoneal serous carcinomas from other types of serous tumors. The shedding of peritoneal tumor cells into the uterine cavity is proposed as a possible explanation for abnormal Pap tests. [Extracted from the article]

Objective: Underdiagnosis of female genital tuberculosis (FGTB) often leads to infertility. In this study, we aimed to determine the site and histopathologic patterns of FGTB and its correlation with clinical presentation and acid-fast bacilli (AFB) status. Methods: A retrospective cross-sectional study was conducted on 122 patients with a histopathological diagnosis of FGTB at the Department of Pathology, College of Health Sciences (CHS), Tikur Anbessa Specialized Hospital (TASH), Addis Ababa University (AAU), from January 1, 2013, to August 30, 2022. Results: Female genital tuberculosis was found in 0.94% of the gynecology specimens examined. The most common presentations were menstrual disturbance, abdominopelvic pain, and infertility. Among patients with FGTB, 4.6% exhibited misleading clinical and radiologic findings, leading to suspicion of malignancy and subsequent aggressive surgical management. The endometrium was the most frequently affected organ, followed by the fallopian tube, ovary, cervix, and vulva. In the majority of tuberculous endometritis cases (53.3%), histopathology revealed early-stage granulomas. Acid-fast bacilli were found in a significant proportion (42.6%) of FGTB tissues with TB histopathology. The ovary had the highest rate of AFB detection, followed by the fallopian tube, endometrium, and cervix. Conclusion: Female genital tuberculosis should be considered in reproductive-age women presenting with menstrual irregularities, abdominopelvic pain, infertility, or an abdominopelvic mass. The endometrium is commonly affected, displaying early granulomas with low AFB positivity. [ABSTRACT FROM AUTHOR]

Platinum-resistant high-grade serous carcinoma (HGSC) is an incurable disease, so biomarkers that could help with timely treatment adjustments and personalized approach are extensively being sought. Tumor-derived extracellular vesicles (EVs) that can be isolated from ascites and blood of HGSC patients are such promising biomarkers. Epithelial cell adhesion molecule (EpCAM) expression is upregulated in most epithelium-derived tumors; however, studies on prognostic value of EpCAM overexpression in ovarian carcinoma have shown contradictory results. The aim of our study was to evaluate the potential of total and EpCAM-positive EVs as prognostic and predictive biomarkers for advanced HGSC. Flow cytometry was used to determine the concentration of total and EpCAM-positive EVs in paired pretreatment ascites and plasma samples of 37 patients with advanced HGSC who underwent different first-line therapy. We found that higher EpCAM-positive EVs concentration in ascites is associated with shorter progression-free survival (PFS) regardless of treatment strategy. We also found a strong correlation of EpCAM-positive EVs concentration between ascites and plasma. Our findings indicate that EpCAM-positive EVs in ascites of patients with advanced HGSC have the potential to serve as prognostic biomarkers for predicting early recurrence and thereby likelihood of more aggressive tumor biology and development of chemoresistance. [ABSTRACT FROM AUTHOR]

The G-protein-coupled estrogen receptor (GPER; G-protein-coupled estrogen receptor 30, also known as GPR30) is a novel estrogen receptor and has emerged as a promising target for ovarian cancer. GPER, a seven-transmembrane receptor, suppresses cellular viability and migration in studied ovarian cancer cells. However, its impact on the fallopian tube, which is the potential origin of high-grade serous (HGSC) ovarian cancer, has not been addressed. This study was conducted to evaluate the relationship of GPER, ovarian cancer subtypes, i.e., high-grade serous cell lines (OV90 and OVCAR420), as well as the cell type that is the potential origin of HGSC ovarian cancer (i.e., the fallopian tube cell line FT190). The selective ligand assessed here is the agonist G-1, which was utilized in an in vitro study to characterize its effects on cellular viability and migration. As a result, this study has addressed the effect of a specific GPER agonist on cell viability, providing a better understanding of the effects of this compound on our diverse group of studied cell lines. Strikingly, attenuated cell proliferation and migration behaviors were observed in the presence of G-1. Thus, our in vitro study reveals the impact of the origin of HGSC ovarian cancers and highlights the GPER agonist G-1 as a potential therapy for ovarian cancer. [ABSTRACT FROM AUTHOR]

Purpose: Neoadjuvant chemotherapy is often administered for high-grade serous ovarian carcinoma (HGSC) prior to cytoreductive surgery. We evaluated treatment response by CT (simplified peritoneal carcinomatosis index [S-PCI]), pathology (chemotherapy response score [CRS]), laboratory markers (serum CA-125), and surgical outcomes, to identify predictors of disease-free survival. Methods: For this retrospective, HIPAA-compliant, IRB-approved study, we identified 396 women with HGSC receiving neoadjuvant chemotherapy between 2010 and 2019. Two hundred and ninety-nine patients were excluded (surgery not performed; imaging/pathology unavailable). Pre- and post-treatment abdominopelvic CTs were assigned CT S-PCI scores 0–24 (higher score indicating more tumor). Specimens were assigned CRS of 1–3 (minimal to complete response). Clinical data were obtained via chart review. Univariate, multivariate, and survival analyses were performed. Results: Ninety-seven women were studied, with mean age of 65 years ± 10. Interreader agreement was good to excellent for CT S-PCI scores (ICC 0.64–0.77). Despite a significant decrease in CT S-PCI scores after treatment (p < 0.001), mean decrease in CT S-PCI did not differ significantly among CRS categories (p = 0.20) or between patients who were optimally versus suboptimally debulked (p = 0.29). In a survival analysis, lower CRS (more viable tumor) was associated with shorter time to progression (p < 0.001). A joint Cox proportional-hazard models showed that only residual pathologic disease (CRS 1/2) (HR 4.19; p < 0.001) and change in CA-125 (HR 1.79; p = 0.01) predicted progression. Conclusion: HGSC response to neoadjuvant therapy by CT S-PCI did not predict pathologic CRS score, optimal debulking, or progression, revealing discordance between imaging, pathologic, biochemical, and surgical assessments of tumor response. [ABSTRACT FROM AUTHOR]

Zinc (Zn) plays essential roles in numerous cellular processes. However, there is limited understanding of Zn homeostasis within the bovine reproductive system. This study investigated the influence of estradiol (E 2) and progesterone (P 4) on Zn transporter expression and intracellular free Zn levels in bovine oviduct epithelial cells (BOEC). For this purpose, cells were harvested from slaughtered cows and cultured in vitro. Intracellular Zn concentrations were measured using FluoZin-3AM staining, while real-time polymerase chain reaction assessed Zn transporter gene expression and quantification. Overall, our results confirmed the gene expression of all the evaluated Zn transporters (ZIP6, ZIP8, ZIP14, ZnT3, ZnT7 and ZnT9), denoted and the active role of E 2 and P 4 in intracellular Zn regulation. Our findings suggest an interaction between Zn, E 2 and P 4. • Estradiol and progesterone modify Zn transporter expression in BOEC. • Estradiol and progesterone modify intracellular free Zn levels in BOEC. • Zn modify Zn transporter expression and intracellular free Zn levels in BOEC. [ABSTRACT FROM AUTHOR]

Background: Ovarian clear cell carcinoma (OCCC) is a rare pathological histotype in ovarian cancer, while the survival rate of advanced OCCC (Stage III-IV) is substantially lower than that of the advanced serous ovarian cancer (OSC), which is the most common histotype. The goal of this study was to identify high-risk OCCC by comparing OSC and OCCC, with investigating potential risk and prognosis markers. Methods: Patients diagnosed with ovarian cancer from 2009 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) Program. Logistic and Cox regression models were used to identify risk and prognostic factors in high-risk OCCC patients. Cancer-specific survival (CSS) and overall survival (OS) were assessed using Kaplan-Meier curves. Furthermore, Cox analysis was employed to build a nomogram model. The performance evaluation results were displayed using the C-index, calibration plots, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). Immunohistochemically approach was used to identify the expression of the novel target (GPC3). Results: In the Cox analysis for advanced OCCC, age (45–65 years), tumor numbers (total number of in situ/malignant tumors for patient), T3-stage, bilateral tumors, and liver metastases could be defined as prognostic variables. Nomogram showed good predictive power and clinical practicality. Compared with OSC, liver metastases had a stronger impact on the prognosis of patients with OCCC. T3-stage, positive distant lymph nodes metastases, and lung metastases were risk factors for developing liver metastases. Chemotherapy was an independent prognostic factor for patient with advanced OCCC, but had no effect on CSS in patients with liver metastases (p = 0.0656), while surgery was significantly related with better CSS in these patients (p < 0.0001) (p = 0.0041). GPC3 expression was detected in all tissue sections, and GPC3 staining was predominantly found in the cytoplasm and membranes. Conclusion: Advanced OCCC and OCCC with liver metastases are two types of high-risk OCCC. The constructed nomogram exhibited a satisfactory survival prediction for patients with advanced OCCC. GPC3 immunohistochemistry is expected to accumulate preclinical evidence to support the inclusion of GPC3 in OCCC targeted therapy. [ABSTRACT FROM AUTHOR]

Primary leiomyosarcoma of the fallopian tube (PLFT) is an extremely rare gynecological malignancy that has only been described in case reports. Fertility‐sparing treatment for PLFT has not been reported previously. A 24‐year‐old nulligravida woman was diagnosed with stage IC1 PLFT in the right fallopian tube after experiencing right lower quadrant pain for 2 weeks. She underwent laparoscopic right salpingectomy to preserve fertility followed by adjuvant chemotherapy with gemcitabine/docetaxel. She subsequently became pregnant spontaneously, delivering a term baby 27 months after treatment. This appears to be the only report of the use of fertility‐preserving treatment for PLFT. The success of the treatment provides valuable information on the preservation of fertility in young women with PLFT. [ABSTRACT FROM AUTHOR]

Small‐cell neuroendocrine carcinomas (SCNECs) of the female genital tract are rare and aggressive tumors that are characterized by a high rate of recurrence and poor prognosis. They can arise from various sites within the female genital tract, including the cervix, endometrium, ovary, fallopian tube, vagina, and vulva. They are composed of cells with neuroendocrine features, such as the ability to produce and secrete hormones and peptides, and a high mitotic rate. Immunohistochemical staining for neuroendocrine markers, such as chromogranin A, synaptophysin, and CD56, can aid in the diagnosis of these tumors. This article provides an overview of the epidemiology, etiology, and risk factors associated with these tumors, as well as their clinical presentation, cellular characteristics, diagnosis, and finally the current treatment options for SCNECs, including surgery, chemotherapy, and radiation therapy, alone or in combination. [ABSTRACT FROM AUTHOR]

Key reproductive events such as fertilization and early embryonic development occur in the lumen of the oviduct. Since investigating these processes in vivo is both technically challenging and ethically sensitive, cell culture models have been established to reproduce the oviductal microenvironment. Compartmentalized culture systems, particularly air–liquid interface cultures (ALI; cells access the culture medium only from the basolateral cell side), result in highly differentiated oviduct epithelial cell cultures. The oxygen (O2) tension within the oviduct is 4–10% across species, and its reduced O2 content is presumed to be important for early reproductive processes. However, cell culture models of the oviduct are typically cultivated without O2 regulation and therefore at about 18% O2. To investigate the impact of O2 levels on oviduct epithelium functions in vitro, we cultured porcine oviduct epithelial cells (POEC) at the ALI using both physiological (5%) and supraphysiological (18%) O2 levels and two different media regimes. Epithelium architecture, barrier function, secretion of oviduct fluid surrogate (OFS), and marker gene expression were comparatively assessed. Under all culture conditions, ALI-POEC formed polarized, ciliated monolayers with appropriate barrier function. Exposure to 18% O2 accelerated epithelial differentiation and significantly increased the apical OFS volume and total protein content. Expression of oviduct genes and the abundance of OVGP1 (oviduct-specific glycoprotein 1) in the OFS were influenced by both O2 tension and medium choice. In conclusion, oviduct epithelial cells can adapt to a supraphysiological O2 environment. This adaptation, however, may alter their capability to replicate in vivo tissue characteristics. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What are the costs and effects of tubal patency testing by hysterosalpingo-foam sonography (HyFoSy) compared to hysterosalpingography (HSG) in infertile women during the fertility work-up? SUMMARY ANSWER During the fertility work-up, clinical management based on the test results of HyFoSy leads to slightly lower, though not statistically significant, live birth rates, at lower costs, compared to management based on HSG results. WHAT IS KNOWN ALREADY Traditionally, tubal patency testing during the fertility work-up is performed by HSG. The FOAM trial, formally a non-inferiority study, showed that management decisions based on the results of HyFoSy resulted in a comparable live birth rate at 12 months compared to HSG (46% versus 47%; difference −1.2%, 95% CI: −3.4% to 1.5%; P  = 0.27). Compared to HSG, HyFoSy is associated with significantly less pain, it lacks ionizing radiation and exposure to iodinated contrast medium. Moreover, HyFoSy can be performed by a gynaecologist during a one-stop fertility work-up. To our knowledge, the costs of both strategies have never been compared. STUDY DESIGN, SIZE, DURATION We performed an economic evaluation alongside the FOAM trial, a randomized multicenter study conducted in the Netherlands. Participating infertile women underwent, both HyFoSy and HSG, in a randomized order. The results of both tests were compared and women with discordant test results were randomly allocated to management based on the results of one of the tests. The follow-up period was twelve months. PARTICIPANTS/MATERIALS, SETTING, METHODS We studied 1160 infertile women (18–41 years) scheduled for tubal patency testing. The primary outcome was ongoing pregnancy leading to live birth. The economic evaluation compared costs and effects of management based on either test within 12 months. We calculated incremental cost-effectiveness ratios (ICERs): the difference in total costs and chance of live birth. Data were analyzed using the intention to treat principle. MAIN RESULTS AND THE ROLE OF CHANCE Between May 2015 and January 2019, 1026 of the 1160 women underwent both tubal tests and had data available: 747 women with concordant results (48% live births), 136 with inconclusive results (40% live births), and 143 with discordant results (41% had a live birth after management based on HyFoSy results versus 49% with live birth after management based on HSG results). When comparing the two strategies—management based on HyfoSy results versus HSG results—the estimated chance of live birth was 46% after HyFoSy versus 47% after HSG (difference −1.2%; 95% CI: −3.4% to 1.5%). For the procedures itself, HyFoSy cost €136 and HSG €280. When costs of additional fertility treatments were incorporated, the mean total costs per couple were €3307 for the HyFoSy strategy and €3427 for the HSG strategy (mean difference €−119; 95% CI: €−125 to €−114). So, while HyFoSy led to lower costs per couple, live birth rates were also slightly lower. The ICER was €10 042, meaning that by using HyFoSy instead of HSG we would save €10 042 per each additional live birth lost. LIMITATIONS, REASONS FOR CAUTION When interpreting the results of this study, it needs to be considered that there was a considerable uncertainty around the ICER, and that the direct fertility enhancing effect of both tubal patency tests was not incorporated as women underwent both tubal patency tests in this study. WIDER IMPLICATION OF THE FINDINGS Compared to clinical management based on HSG results, management guided by HyFoSy leads to slightly lower live birth rates (though not statistically significant) at lower costs, less pain, without ionizing radiation and iodinated contrast exposure. Further research on the comparison of the direct fertility-enhancing effect of both tubal patency tests is needed. STUDY FUNDING/COMPETING INTEREST(S) FOAM trial was an investigator-initiated study, funded by ZonMw, a Dutch organization for Health Research and Development (project number 837001504). IQ Medical Ventures provided the ExEm®-FOAM kits free of charge. The funders had no role in study design, collection, analysis, and interpretation of the data. K.D. reports travel-and speakers fees from Guerbet and her department received research grants from Guerbet outside the submitted work. H.R.V. received consulting—and travel fee from Ferring. A.M.v.P. reports received consulting fee from DEKRA and fee for an expert meeting from Ferring, both outside the submitted work. C.H.d.K. received travel fee from Merck. F.J.M.B. received a grant from Merck and speakers fee from Besins Healthcare. F.J.M.B. is a member of the advisory board of Merck and Ferring. J.v.D. reported speakers fee from Ferring. J.S. reports a research agreement with Takeda and consultancy for Sanofi on MR of motility outside the submitted work. M.v.W. received a travel grant from Oxford Press in the role of deputy editor for Human Reproduction and participates in a DSMB as independent methodologist in obstetrics studies in which she has no other role. B.W.M. received an investigator grant from NHMRC GNT1176437. B.W.M. reports consultancy for ObsEva, Merck, Guerbet, iGenomix, and Merck KGaA and travel support from Merck KGaA. V.M. received research grants from Guerbet, Merck, and Ferring and travel and speakers fees from Guerbet. The other authors do not report conflicts of interest. TRIAL REGISTRATION NUMBER International Clinical Trials Registry Platform No. NTR4746. [ABSTRACT FROM AUTHOR]

Objective(s): Tubal factor infertility (TFI) is common female infertility responsible for a large portion of female factor infertility. This study reveals the effect of the quercetin of Huoxuehuayu Tongluo Decoction with azithromycin on the pregnancy rate and inflammation of TFI female rats. Materials and Methods: Female Sprague Dawley rats were constructed into the TFI model and treated with quercetin, Huoxuehuayu Tongluo Decoction, and combination therapy (quercetin and azithromycin). Pregnancy rate and litter size were measured. Network pharmacology was applied to analyze the interaction between Huoxuehuayu Tongluo Decoction and TFI. The combination of quercetin and IL-6 was analyzed by molecular docking. HE staining and electron microscopy were used to observe the histopathology and ultrastructure of fallopian tube tissues. The TNF-α, IL-1β, IL- 6, IL-8, and MPO levels were detected by ELISA. The activation of JAK/STAT, MAPK, and NF-κB p65 pathways was detected by western blot or immunohistochemistry. Results: Quercetin was the main active component of Huoxuehuayu Tongluo Decoction, and could bind to IL-6 in TFI. Target genes were enriched in the IL-17 signaling pathway, JAK-STAT signaling pathway, inflammatory disease, etc. Under the quercetin and azithromycin combination therapy, both rat pregnancy rates and litter sizes increased significantly. quercetin and azithromycin alleviated the symptoms of hydrosalpinx and inflammatory damage in fallopian tube tissues. The phosphorylation of JAK/STAT and MAPK pathways and NF-κB p65 translocation to the nucleus were significantly inhibited by the quercetin and azithromycin therapy. Conclusion: Quercetin and azithromycin combination therapy inhibited inflammation and phosphorylation of JAK/STAT and MAPK pathways to improve TFI inflammation and pregnancy function. [ABSTRACT FROM AUTHOR]

Introduction: Accessory cavitated uterine malformation (ACUM) is a relatively recent term used to describe a noncommunicating, accessory uterine cavity. ACUM have been published under different terms ranging from juvenile cystic adenomyosis to "uterus‐like mass". The objective of this study was to systematically identify all cases of ACUM and definitions described in the literature, regardless of label, and identify morphological, epidemiological, and clinical characteristics as well as management, while also highlighting knowledge gaps. Material and methods: A systematic literature search of three databases was performed, reviewing all records of cystic myometrial lesions. Cases that fitted common definitions for ACUM were included and clinical and imaging characteristics were documented in detail. This work was registered to PROSPERO and reporting followed PRISMA guidelines for scoping reviews. Results: A total of 53 articles were included, comprising 115 cases that met the minimal criteria for ACUM. The median age at onset of symptoms was 17 years, presenting with dysmenorrhea soon after menarche. A total of 19 women were parous. On ultrasound, ACUM appears as unilocular myometrial cysts, usually with ground‐glass content. Hemorrhagic content is also observed on magnetic resonance imaging (MRI), with high signal intensity on both T2 and T1‐weighted images. Ninety‐five (83%) cases were managed surgically, with a trend towards primary nonsurgical options. Although no adverse outcomes were reported, long‐term follow‐up on subsequent fertility and pregnancy was rare. Conclusions: Despite its increasing recognition as a clinical entity, ACUM often remains underdiagnosed as it shares similarities with other myometrial masses. We propose a unified terminology and definition for ACUM based on the data in this review. ACUM presents as a cavitated lesion, surrounded by a myometrial mantle, in continuity with the anterolateral uterine wall and located beneath the insertion of the round ligament and the interstitial portion of the fallopian tube. In contrast to other uterine abnormalities, a normal uterine cavity is visualized. Future studies are needed, using a clear definition for ACUM, and prospectively investigating management strategies, including long‐term follow‐up of patient‐reported symptoms, fertility, and pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Isolated fallopian tube torsion (IFTT) is defined by rotation of the fallopian tube around itself without involving the ipsilateral ovary. It is a rare cause of acute lower abdominal pain in (adolescent) girls, but is commonly overlooked. Due to its rarity, literature is still scarce. Currently there is no generally accepted management and treatment. Methods: A retrospective analysis of all IFTT cases treated in our institution was performed. In addition, a systematic literature research on pediatric IFTT was carried out on Medline/ PubMed database according to PRISMA principles using predefined search terms and inclusion criteria. Patient characteristics regarding age, clinical symptoms, diagnostic methods, treatment, and follow-up were analyzed. Results: Three of our patients and fifty-nine reports totaling one hundred seventy girls were included in the analysis. Mean age was 13.0 years. Left tube was slightly more often affected (52.9%). Abdominal pain was present in 99.4% of cases accompanied with nausea in 57.1%. In only 16.4%, correct preoperative diagnosis was made. Salpingectomy was the most common treatment in 111 (66.9%) cases, 55 (33.1%) patients were treated with detorsion of the tube (organ-sparing management). Girls with symptoms longer than 1 day had a significant higher rate of salpingectomy (95% CI, P = 0.0323). Conclusion: When IFTT is suspected, emergency laparoscopy should be performed to possibly preserve future reproductive potential. In case of detorsion and reinstated blood supply, organ-preserving management should be performed with simultaneous addressment of concomitant pathology if possible. Sufficient long-term follow-up must be assured to get significant results to introduce guidelines for children and adolescents. [ABSTRACT FROM AUTHOR]

Nuclear speckles are compartments enriched in splicing factors present in the nucleoplasm of eucaryote cells. Speckles have been studied in mammalian culture and tissue cells, as well as in some non-mammalian vertebrate cells and invertebrate oocytes. In mammals, their morphology is linked to the transcriptional and splicing activities of the cell through a recruitment mechanism. In rats, speckle morphology depends on the hormonal cycle. In the present work, we explore whether a similar situation is also present in non-mammalian cells during the reproductive cycle. We studied the speckled pattern in several tissues of a viviparous reptile, the lizard Sceloporus torquatus, during two different stages of reproduction. We used immunofluorescence staining against splicing factors in hepatocytes and oviduct epithelium cells and fluorescence and confocal microscopy, as well as ultrastructural immunolocalization and EDTA contrast in Transmission Electron Microscopy. The distribution of splicing factors in the nucleoplasm of oviductal cells and hepatocytes coincides with the nuclear-speckled pattern described in mammals. Ultrastructurally, those cell types display Interchromatin Granule Clusters and Perichromatin Fibers. In addition, the morphology of speckles varies in oviduct cells at the two stages of the reproductive cycle analyzed, paralleling the phenomenon observed in the rat. The results show that the morphology of speckles in reptile cells depends upon the reproductive stage as it occurs in mammals. [ABSTRACT FROM AUTHOR]

Background: Genetic studies implicate the oncogenic transcription factor Forkhead Box M1 (FOXM1) as a potential therapeutic target in high-grade serous ovarian cancer (HGSOC). We evaluated the activity of different FOXM1 inhibitors in HGSOC cell models. Results: We treated HGSOC and fallopian tube epithelial (FTE) cells with a panel of previously reported FOXM1 inhibitors. Based on drug potency, efficacy, and selectivity, determined through cell viability assays, we focused on two compounds, NB-73 and NB-115 (NB compounds), for further investigation. NB compounds potently and selectively inhibited FOXM1 with lesser effects on other FOX family members. NB compounds decreased FOXM1 expression via targeting the FOXM1 protein by promoting its proteasome-mediated degradation, and effectively suppressed FOXM1 gene targets at both the protein and mRNA level. At the cellular level, NB compounds promoted apoptotic cell death. Importantly, while inhibition of apoptosis using a pan-caspase inhibitor rescued HGSOC cells from NB compound-induced cell death, it did not rescue FOXM1 protein degradation, supporting that FOXM1 protein loss from NB compound treatment is specific and not a general consequence of cytotoxicity. Drug washout studies indicated that FOXM1 reduction was retained for at least 72 h post-treatment, suggesting that NB compounds exhibit long-lasting effects in HGSOC cells. NB compounds effectively suppressed both two-dimensional and three-dimensional HGSOC cell colony formation at sub-micromolar concentrations. Finally, NB compounds exhibited synergistic activity with carboplatin in HGSOC cells. Conclusions: NB compounds are potent, selective, and efficacious inhibitors of FOXM1 in HGSOC cells and are worthy of further investigation as HGSOC therapeutics. [ABSTRACT FROM AUTHOR]

• Isolated fallopian tube torsion (IFTT) is a rare gynecological emergency. • Common symptoms include unilateral lower abdominal pain, nausea and vomiting. • In general, imaging has low sensitivity and diagnosis is often delayed or missed. • Laparoscopic detorsion is optimal, however currently salpingectomy is most common. • This is the first systematic review consolidating multiple case reports on IFTT. To combine all literature describing cases of isolated fallopian tube torsion in adult non pregnant patients in a systematic manner, to optimize knowledge and practice both for diagnosis and management. EMBASE and PubMed databases were searched for the terms 'tubal' OR 'fallopian tube' AND 'isolated' AND 'torsion' from the inception of these databases to July 5, 2023. All case reports or case series of adult patients (18 years or older) with isolated fallopian tube torsion were included. Exclusion criteria included: all other study types; cases involving children and adolescents (less than 18 years old); pregnant patients of all trimesters; tubo-ovarian torsion; studies not published in English; duplicates and those not available in text. Following the database search, two authors independently screened the studies and search results were subsequently reported in accordance with PRISMA guidelines. Data was extracted independently by two authors and analysed using Excel. All cases were assessed for bias using a modified version of the tool proposed by Murad et al. 92 unique articles enrolling 131 individual cases were included in this systematic review. Isolated fallopian tube torsion most commonly occurs during reproductive ages between 18 and 45 years. It is uncommon in postmenopausal women. The most common presenting symptoms include unilateral lower abdominal or pelvic pain along the affected side with nausea and vomiting. Risk factors can be intrinsic or extrinsic and can include conditions such as hydrosalpinx, sterilization, pelvic inflammatory disease or cysts. Ultrasound is the optimal imaging modality however Computed Tomography and Magnetic Resonance Imaging can also be used. Imaging in general has low sensitivity, however isolated fallopian tube torsion can be identified with appropriate expertise. The gold standard for isolated fallopian tube torsion management is laparoscopy and detorsion however currently, the most common intervention performed is salpingectomy. Isolated fallopian tube torsion is a rare but important gynaecological emergency with significant fertility implications. This study summarizes the most common presentations, investigation findings and surgical interventions in patients with isolated fallopian tube torsion. This study also emphasizes the importance of clinicians maintaining a high degree of suspicion and low threshold for early laparoscopic intervention to retain fertility. [ABSTRACT FROM AUTHOR]

Introduction: Retroperitoneum can be the origin of a wide variety of pathologic conditions and potential space for disease spread to other compartments of the abdomen and pelvis. Computed tomography (CT) and magnetic resonance imaging (MRI) are often the initial imaging modalities to evaluate the retroperitoneal pathologies, however given the intrinsic limitations, F18-FDG PET/CT provides additional valuable metabolic information which can change the patient management and clinical outcomes. We highlight the features of retroperitoneal pathologies on F18-FDG PET/CT and the commonly encountered imaging artifacts and pitfalls. The aim of this review is to characterize primary and secondary retroperitoneal pathologies based on their metabolic features, and correlate PET findings with anatomic imaging. Conclusion: Retroperitoneal pathologies can be complex, ranging from oncologic to a spectrum of non-oncologic disorders. While crosse-sectional imaging (CT and MRI) are often the initial imaging modalities to localize and characterize pathologies, metabolic information provided by F18-FDG PET/CT can change the management and clinical outcome in many cases. (a) Brown fat activation on F18-FDG PET. Axial fused PET image of the abdomen shows hypermetabolic foci in the bilateral perinephric fat (arrows). (b) Adrenal metastasis in a 78-year-old woman with serous ovarian carcinoma. Axial fused PET/CT of the abdomen shows intense uptake in the new left adrenal lesion (arrow), with FDG uptake intensity markedly higher than the liver. (c)Axial contrast-enhanced CT abdomen shows the lobulated mildly enhancing left adrenal metastasis (circle). [ABSTRACT FROM AUTHOR]

To characterize trends in ovarian, fallopian tube, and primary peritoneal cancer incidence and incidence-based mortality based on histology and site of origin. We obtained age-adjusted incidence and incidence-based mortality for patients with ovarian, fallopian tube, and primary peritoneal cancer from 2000 to 2019 from the US SEER 17 database. Joinpoint 4.9.1.0 was used to characterize log-linear time trends. The incidence and incidence-based mortality of all cancers trended down during the study period. The incidence of epithelial cancers decreased from 2004 to 2019 (AAPC −1.2%, p < 0.001), including that of high-grade (2006–2019: APC −1.2%, p < 0.05) and low-grade (2003–2019: APC −2.4%, p < 0.05) epithelial cancers. There was no change in incidence or incidence-based mortality for ovarian stromal and germ cell cancers. There has been a decrease in the incidence and incidence-based mortality of ovarian, fallopian tube, and primary peritoneal cancer, primarily due to reductions in advanced stage epithelial cancers originating in the ovary, fallopian tube, or peritoneum. • There has been an overall decline in the incidence and incidence-based mortality of ovarian cancer over a 15-year period. • This decline is primarily driven by declines in epithelial cancers arising in the ovaries, fallopian tube, or peritoneum. • There are fewer patients diagnosed with epithelial cancers, particularly advanced stage disease. • Contributing factors include advances in early detection, more risk-reducing surgeries, and stage migration. • Other factors include improved treatment options and changes in oral contraceptive and postmenopausal hormone therapy use. [ABSTRACT FROM AUTHOR]

Background: Vaginal bleeding (VB) before 20 gestational weeks of a viable pregnancy is a manifestation of a threatened miscarriage. VB is associated with increased levels of pro‐inflammatory cytokines such as interferon‐gamma, tumour necrosis factor‐alpha and interleukin‐6. Increased levels of these cytokines and oxidative stress are risk factors for cancer. The risk of cancer following a VB‐affected pregnancy that ended in childbirth is unknown. Objectives: To investigate the associations between VB in pregnancy that resulted in delivery and risk of incident cancer. Methods: We conducted a cohort study (1995–2018) in Denmark using administrative and healthcare registries. We included 37,082 VB‐affected deliveries, 1,363,614 VB‐unaffected deliveries, 324,328 pregnancies ending in terminations, and 137,104 miscarriages. We computed the absolute risk of cancer and hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, morbidities, and socio‐economic factors using Cox proportional hazards regression. Multiple pregnancies to the same woman were accounted for in the analysis. Results: The median (25th–75th percentile) follow‐up in the study was 12.6 (6.9, 18.2) years. The prevalence of VB in the present study was 3%. At the end of the follow‐up, there were 1320 cancer cases among the VB‐affected delivery cohort, 40,420 among the VB‐unaffected delivery cohort, 10,300 among the termination cohort and 4790 among the miscarriage cohort. HRs for any cancer among VB‐affected deliveries were 1.03 (95% CI 0.97, 1.08) compared with VB‐unaffected deliveries, 1.03 (95% CI 0.97, 1.09) compared with terminations and 0.90 (95% CI 0.84, 0.95) compared with miscarriages. There were no increased risks of premenopausal breast cancer, cervical cancer, ovary and fallopian tube cancer or uterine cancer following VB‐affected deliveries vs. comparison cohorts. Conclusions: We found no evidence of an association between vaginal bleeding in pregnancy and an increased risk of cancer. [ABSTRACT FROM AUTHOR]

To report a rare case of spontaneous ectopic pregnancy (EP) after partial salpingectomy treated by laparoscopy. Case Report: A 30-year-old gravida 1 para 0 woman with a history of left adnexectomy, due to left ovarian torsion 13 years ago, was referred to our hospital. She had experienced lower abdominal pain for 1 day and amenorrhea for 1 week. Transvaginal ultrasonography did not reveal an intrauterine pregnancy, but showed a suspected extrauterine gestational sac on the left adnexal area. The patient was diagnosed with ectopic pregnancy, and laparoscopy was performed. During the operation, we found a gestational sac on the left fallopian tube stump. Conclusion: The most significant risk factors for ectopic pregnancy (EP) are previous procedures and conditions that cause tubal injury. Therefore, it is necessary to be alert to the occurrence of the disease even if there is a history of tubal resection and ensure no part of the fallopian tube is left behind during removal. [ABSTRACT FROM AUTHOR]

This population-based assessment suggests that diagnosis of high-grade serous tubo-ovarian carcinoma has been rapidly shifting from high-grade serous ovarian to fallopian tubal carcinoma in recent years in the United States. OBJECTIVE: To assess population-level trends, characteristics, and outcomes of high-grade serous tubo-ovarian carcinoma in the United States. METHODS: This retrospective cohort study queried the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population was 27,811 patients diagnosed with high-grade serous tubo-ovarian carcinoma from 2004 to 2020. The exposure was the primary cancer site (ovary or fallopian tube). Main outcome measures were temporal trends, clinical characteristics, and overall survival associated with primary cancer site assessed in multivariable analysis. RESULTS: The study population comprised 23,967 diagnoses of high-grade serous ovarian carcinoma and 3,844 diagnoses of high-grade serous fallopian tubal carcinoma. The proportion of diagnoses of high-grade serous fallopian tubal carcinoma increased from 365 of 7,305 (5.0%) in 2004–2008 to 1,742 of 6,663 (26.1%) in 2017–2020. This increase was independent in a multivariable analysis (adjusted odds ratio [aOR] vs 2004–2008, 2.28 [95% CI, 1.98–2.62], 3.27 [95% CI, 2.86–3.74], and 6.65 [95% CI, 5.84–7.57] for 2009–2012, 2013–2016, and 2017–2020, respectively). This increase in high-grade serous fallopian tubal carcinoma was seen across age groups (4.3–5.8% to 22.7–28.3%) and across racial and ethnic groups (4.1–6.0% to 21.9–27.5%) (all P for trend <.001). Among the cases of tumors smaller than 1.5 cm, the increase was particularly high (16.9–67.6%, P for trend <.001). Primary-site tumors in the high-grade serous fallopian tubal carcinoma group were more likely to be smaller than 1.5 cm (aOR 8.26, 95% CI, 7.35–9.28) and unilateral (aOR 7.22, 95% CI, 6.54–7.96) compared with those in high-grade serous ovarian carcinoma. At the cohort level, the diagnosis shift to high-grade serous fallopian tubal carcinoma was associated with narrowing differences in survival over time between the two malignancy groups: adjusted hazard ratio 0.84 (95% CI, 0.74–0.96), 0.91 (95% CI, 0.82–1.01), 1.01 (95% CI, 0.92–1.12), and 1.12 (95% CI, 0.98–1.29) for 2004–2008, 2009–2012, 2013–2016, and 2017–2020, respectively. CONCLUSION: This population-based assessment suggests that diagnoses of high-grade serous tubo-ovarian carcinoma in the United States have been rapidly shifting from high-grade serous ovarian to fallopian tubal carcinoma in recent years, particularly in cases of smaller, unilateral tumors. [ABSTRACT FROM AUTHOR]

One of the parameters potentially affecting the in vitro growth of preimplantation embryos is the oxygen concentration in the culture environment. An increased oxygen concentration causes the generation of ROS which in turn can cause damage to the cells and seriously disrupt the embryonic development. Previous studies have assessed oxygen concentrations in the fallopian tubes of several mammals of between 5 and 8%, while the oxygen levels in the uterus were found to be even lower; similar measurements have been confirmed in humans. In addition, studies in mammalian embryos showed that low oxygen concentrations improve embryo development. Multiple studies on the effect of the oxygen concentration on human embryos have been conducted so far with diverse methodologies and objectives. Data from these have been included in three meta-analyses. All meta-analyses indicate the potential benefit in favor of a low oxygen concentration, though data are considered to be of a low methodological quality and further studies are considered necessary. However, based on the existing evidence, it is suggested that a low oxygen concentration should be adopted in the routine of the IVF laboratory, especially in the case of blastocyst culture. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite consensus recommendations, national genetic counseling and testing rates for gynecological cancers remain relatively low. Prior studies have also shown that referrals are fewer for people of minority backgrounds. This initial study aimed to determine what genetic counseling and testing rates are found in a diverse patient setting. High rates of genetic counseling and testing are demonstrated, with no racial disparities. Both endometrial and ovarian cancer data are presented simultaneously in a single study in the first of its kind, helping provide a broader combined perspective. Point-of-care genetic counseling and testing by gynecologic oncologists is a strategy that can be similarly adopted at other institutions to potentially reduce disparities. Further studies can identify other factors responsible for the successful counseling and testing rates and how they can be used to broaden the reach of these services at other centers with similar diverse populations. We investigated genetic counseling and testing rates for patients with gynecologic malignancy at a tertiary care center with a large minority population. Our retrospective cohort included newly diagnosed epithelial ovarian, fallopian tube, peritoneal, or endometrial cancer patients between January 2014 and June 2022. For endometrial cancer, 373 patients were identified. A total of 207 (55%) patients were screened using mismatch repair immunohistochemistry (MMR IHC). A total of 82 (40%) had MMR deficiencies on IHC. Of these, 63 (77%) received genetic counseling. A total of 62 (98%) underwent genetic testing, and ultimately, 7 (11%) were diagnosed with Lynch syndrome (LS). The overall rate of LS was 1.9%. MMR IHC testing increased steadily, reaching 100% in 2022. For ovarian cancer, 144 patients were identified. A total of 104 (72%) patients received genetic counseling, and 99 (95%) underwent genetic testing. Rates were not influenced by race, ethnicity, insurance type, or family history of cancer. They were significantly different by cancer stage (p < 0.01). The proportion of patients who received genetic counseling increased from 47% in 2015 to 100% in 2022 (p < 0.01). Most counseling was performed by a gynecologic oncologist (93%) as opposed to a genetic counselor (6.7%). Overall, 12 (8.3%) patients were BRCA+. High rates of counseling and testing were observed with few disparities. [ABSTRACT FROM AUTHOR]

Simple Summary: The perspective of this paper will focus on high-resolution imaging of collagen alterations in high-grade serous ovarian cancer (HGSOC). We will highlight the use of the collagen-specific/sensitive Second Harmonic Generation (SHG) microscopy in delineating changes across multiple size scales between HGSOC, other ovarian tumors, HGSOC precursors and normal tissues. Specifically, we utilize machine learning techniques to differentiate these tissues with high accuracy and further exploit the underlying SHG physics to determine sub-resolution information on fibril assembly and macro/supramolecular collagen structure. We also describe how SHG can be combined with other modalities including fluorescence and optical coherence tomography (OCT). Lastly, we discuss challenges and opportunities for translation to in vivo applications, focusing on advances in endoscopic technology. We postulate that successful diagnosis/treatment of HGSOC requires an integrated approach of ex vivo microscopic and molecular analyses to establish the foundation for in vivo imaging. High-grade serous ovarian cancer (HGSOC) is the predominant subtype of ovarian cancer (OC), occurring in more than 80% of patients diagnosed with this malignancy. Histological and genetic analysis have confirmed the secretory epithelial of the fallopian tube (FT) as a major site of origin of HGSOC. Although there have been significant strides in our understanding of this disease, early stage detection and diagnosis are still rare. Current clinical imaging modalities lack the ability to detect early stage pathogenesis in the fallopian tubes and the ovaries. However, there are several microscopic imaging techniques used to analyze the structural modifications in the extracellular matrix (ECM) protein collagen in ex vivo FT and ovarian tissues that potentially can be modified to fit the clinical setting. In this perspective, we evaluate and compare the myriad of optical tools available to visualize these alterations and the invaluable insights these data provide on HGSOC initiation. We also discuss the clinical implications of these findings and how these data may help novel tools for early diagnosis of HGSOC. [ABSTRACT FROM AUTHOR]

Background: Uterine rupture in pregnant women can lead to serious adverse outcomes. This study aimed to explore the clinical characteristics, treatment, and prognosis of patients with complete uterine rupture. Methods: Data from 33 cases of surgically confirmed complete uterine rupture at Chenzhou No.1 People's Hospital between January 2015 and December 2022 were analyzed retrospectively. Results: In total, 31,555 pregnant women delivered in our hospital during the study period. Of these, approximately 1‰ (n = 33) had complete uterine rupture. The average gestational age at complete uterine rupture was 31+4 weeks (13+1–40+3 weeks), and the average bleeding volume was 1896.97 ml (200–6000 ml). Twenty-six patients (78.79%) had undergone more than two deliveries. Twenty-five women (75.76%) experienced uterine rupture after a cesarean section, two (6.06%) after fallopian tube surgery, one (3.03%) after laparoscopic cervical cerclage, and one (3.03%) after wedge resection of the uterine horn, and Fifteen women (45.45%) presented with uterine rupture at the original cesarean section incision scar. Thirteen patients (39.39%) were transferred to our hospital after their initial diagnosis. Seven patients (21.21%) had no obvious symptoms, and only four patients (12.12%) had typical persistent lower abdominal pain. There were 13 cases (39.39%, including eight cases ≥ 28 weeks old) of fetal death in utero and two cases (6.06%, both full term) of severe neonatal asphyxia. The rates of postpartum hemorrhage, blood transfusion, hysterectomy were 66.67%, 63.64%, and 21.21%. Maternal death occurred in one case (3.03%). Conclusions: The site of the uterine rupture was random, and was often located at the weakest point of the uterus. There is no effective means for detecting or predicting the weakest point of the uterus. Rapid recognition is key to the treatment of uterine rupture. [ABSTRACT FROM AUTHOR]

Background: Extracellular vesicles (EVs) present in oviductal (OF) and uterine fluid (UF) have been shown to enhance bovine embryo quality during in vitro culture by reducing lipid contents and modulating lipid metabolism-related genes (LMGs), while also influencing cell proliferation, suggesting their involvement on the regulation of different biological pathways. The regulation of signaling pathways related to cell differentiation, proliferation, and metabolism is crucial for early embryo development and can determine the success or failure of the pregnancy. Bioactive molecules within EVs in maternal reproductive fluids, such as microRNAs (miRNAs), may contribute to this regulatory process as they modulate gene expression through post-transcriptional mechanisms. Results: From the 20 differentially expressed miRNAs, 19 up-regulated in UF-EVs (bta-miR-134, bta-miR-151-3p, bta-miR-155, bta-miR-188, bta-miR-181b, bta-miR-181d, bta-miR-224, bta-miR-23b-3p, bta-miR-24-3p, bta-miR-27a-3p, bta-miR-29a, bta-miR-324, bta-miR-326, bta-miR-345-3p, bta-miR-410, bta-miR-652, bta-miR-677, bta-miR-873 and bta-miR-708) and one (bta-miR-148b) in OF-EVs. These miRNAs were predicted to modulate several pathways such as Wnt, Hippo, MAPK, and lipid metabolism and degradation. Differences in miRNAs found in OF-EVs from the early luteal phase and UF-EVs from mid-luteal phase may reflect different environments to meet the changing needs of the embryo. Additionally, miRNAs may be involved, particularly in the uterus, in the regulation of embryo lipid metabolism, immune system, and implantation. This study evaluated miRNA cargo in OF-EVs from the early luteal phase and UF-EVs from the mid-luteal phase, coinciding with embryo transit within oviduct and uterus in vivo, and its possible influence on LMGs and signaling pathways crucial for early embryo development. A total of 333 miRNAs were detected, with 11 exclusive to OF, 59 to UF, and 263 were common between both groups. Conclusions: Our study suggests that miRNAs within OF- and UF-EVs could modulate bovine embryo development and quality, providing insights into the intricate maternal-embryonic communication that might be involved in modulating lipid metabolism, immune response, and implantation during early pregnancy. [ABSTRACT FROM AUTHOR]

Ovarian cancer describes a group of disorders that start in the ovaries or adjacent fallopian tubes and peritoneum. It is becoming increasingly clear that chemotherapy alone is ineffective for ovarian cancer. For dual chemo/photothermal treatment, we effectively developed camptothecin (CPT) and gold nanocomposites (AuNCs)-loaded nanostructured lipid carriers (CPT + AuNCs@NSLCs). Gold nanocomposites (AuNCs) of varying shapes and sizes (gold nanorods [AuNRs] and the gold nanospheres [AuNSs]) were placed in NSLCs to take advantage of their photothermal capability and to theorize the blend of drug delivery systems for chemo/photothermal treatment. Before and after being subjected to near-infrared light (808 nm), NSLCs were tested for their ability to spontaneously release CPT. AuNRs had the maximum heating potential of ΔT = 22 °C in 5 min with the 19.8 µg Au/mg lipids. HeLa ovarian cancer cells were used to assess the cytotoxic impact of various formulations, and under 5 min of NIR exposure, CPT + AuNRs@NSLCs showed the most significant growth inhibition (81%) of the bunch. It has been discovered that the photothermal capability of AuNCs is directly affected by their structure, that the cytotoxic property of CPT and the local hyperthermia delivered by AuNCs may suggestively improve cellular damage, and that the established advanced nanoformulations have excellent promising as a chemo/photothermal agent. As a result, the results of this research show promise for fabricating a lipid-mediated multifunctional biocompatible nanoplatform applicable to combination treatment and amenable to fine-tuning its features. [ABSTRACT FROM AUTHOR]

Background: Infertility is a prevalent medical issue that can arise from challenges in male or female or both partners. Pivotal contributing factors to female infertility include dysfunction, tubal issues, and peritoneal factors. Hysterosalpingography (HSG) holds significant importance in assessing abnormalities associated with the uterus and fallopian tubes. Aims and Objectives: This study aimed to assess the clinical profile and hysterosalpingographic findings of women with infertility who visited the department of radiodiagnosis for HSG. Materials and Methods: This is a cross-sectional study, where consecutive convenience-based sampling was used, with ethical clearance in place. Sixty-three infertile women of reproductive age were recruited for the study and were referred for HSG by the Department of Obstetrics and Gynecology. Results: The majority of the participants had primary infertility (71.88%) and was in the 31-35-year age group with the majority having 3-6 years of infertility and endometriosis. On HSG uterine pathology was found in 9.37% of participants and unilateral and bilateral tubal blocks were seen in 18.75% and 14.06% of cases approximately. Conclusion: HSG is a minimally invasive procedure, secure, and plays a crucial role in diagnosing uterine and tubal factors contributing to infertility. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Incidence of bilateral inguinal hernia encompassing bilateral ovaries in adult female is very thin and concomitant association with Mayer–Rokitansky–Küster–Hauser syndrome is out of ordinary. Along with surgical management of hernia, these females need multidisciplinary slant to manage gynecological, social, and emotional issues. In mature females, bilateral ovarian inguinal hernias are a rarity. In this situation, ultrasonography is the basic adjunct to confirm the diagnosis. Mayer–Rokitansky–Küster–Hauser syndrome is typically linked to ovarian hernias in grown‐up females. The most important ways to avoid problems are early diagnosis and surgical repair. A 25‐year‐old lady presented to our outpatient clinic with a history of swelling in bilateral inguinal region for 1 month. On the ultrasound examination, the right ovary was visualized in the right high inguinal canal, and the left ovary was seen at the level of deep inguinal ring with no visualization of the uterus in its normal anatomical position. The patient underwent bilateral inguinal exploration under spinal anesthesia, and herniated contents were successfully reduced back to anatomical locations. Clinical care for such a clinical condition must be multifaceted, involving intensive counseling, relocating the uterus, fallopian tube, and ovary to preserve fertility, and preventing consequences like incarceration and strangulation. [ABSTRACT FROM AUTHOR]

Purpose: Fragile sites are specific chromosomal regions showing gaps, poor staining, contractions, or even breaks in the chromosomes. These spontaneous and heritable fragile sites are prone to structural variations which can lead to adverse reproductive outcomes. This paper aims to present a specific case study of a female patient, with a mosaic karyotype involving chromosome 16q22 fragile site which is very rare in clinic and her experience of infertility. Case Presentation: A 37-year-old woman is diagnosed with ten-year primary infertility. She worked in a factory, and she was occasionally exposed to paint. She underwent two cycles of follicular monitoring with intrauterine insemination (IUI) using her husband's sperm six years ago but failed. Most of her prepregnancy tests were normal, except a not smooth right fallopian tube. Her G-band karyotype of peripheral blood lymphocytes was mos 46, XX, del(16)(q22)[40]/46, XX, fra(16)(q22)[29]/46, XX, fra(16)tr(16)(q22)[3]/46, XX[28] which inherited from her mother. The SCE assay detected a significantly higher frequency of SCEs in the 16q region of the patient's chromosomes compared to her mother and a healthy control. However, the average SCEs per chromosome were quite close. Moreover, copy number variation (CNV) sequencing showed no deletion nor duplication at 16q22. Conclusion: Infertility cannot be completely attributed to the fragile site on chromosome 16q22. Assisted reproductive technology combined with preimplantation genetic testing may help in achieving a healthy live birth. [ABSTRACT FROM AUTHOR]

Introduction: Pregnancy‐associated gynecological cancer (PAGC) refers to cancers of the ovary, uterus, fallopian tube, cervix, vagina, and vulva diagnosed during pregnancy or within 12 months postpartum. We aimed to describe the incidence of, and perinatal outcomes associated with, invasive pregnancy‐associated gynecological cancer. Material and methods: We conducted a population‐based historical cohort study using linked data from New South Wales, Australia. We included all women who gave birth between 1994 and 2013, with a follow‐up period extending to September 30, 2018. Three groups were analyzed: a gestational PAGC group (women diagnosed during pregnancy), a postpartum PAGC group (women diagnosed within 1 year of giving birth), and a control group (women with control diagnosis during pregnancy or within 1 year of giving birth). We used generalized estimation equations to compare perinatal outcomes between study groups. Results: There were 1 786 137 deliveries during the study period; 70 women were diagnosed with gestational PAGC and 191 with postpartum PAGC. The incidence of PAGC was 14.6/100 000 deliveries and did not change during the study period. Women with gestational PAGC (adjusted odds ratio [aAOR] 6.81, 95% confidence interval [CI] 2.97–15.62) and with postpartum PAGC (aOR 2.65, 95% CI 1.25–5.61) had significantly increased odds of a severe maternal morbidity outcome compared with the control group. Babies born to women with gestational PAGC were more likely to be born preterm (aOR 3.11, 95% CI 1.47–6.59) and were at increased odds of severe neonatal complications (aOR 3.47, 95% CI 1.45–8.31) compared with babies born to women without PAC. Conclusions: The incidence of PAGC has not increased over time perhaps reflecting, in part, the effectiveness of cervical screening and early impacts of human papillomavirus vaccination programs in Australia. The higher rate of preterm birth among the gestational PAGC group is associated with adverse outcomes in babies born to these women. [ABSTRACT FROM AUTHOR]

Introduction: Pelvic inflammatory disease (PID) is defined as an acute and subclinical infection of the upper genital system, including the uterus, fallopian tubes, ovaries, and ligaments. It can lead to various complications, such as salpingitis, endometritis, oophoritis, perihepatitis, peritonitis, and tubo-ovarian abscess (TOA). Case Presentation: In our case, a 22-year-old Afghan woman presented with generalized pain in the abdomen and pelvis, accompanied by vaginal discharge and fever, following 17 days of normal vaginal delivery (NVD) and septic shock. She had no previous history of PID. Abdominal ultrasonography revealed a significant amount of free fluid in the paracolic grooves and pelvis, along with a perforated mass on the right adnexa. As a result, she underwent laparotomy and right adnexectomy. A 10-day course of meropenem and vancomycin was prescribed, and the woman was discharged with oral antibiotics. Conclusions: Tubo-ovarian abscess following NVD is a rare condition that can occur in patients with preterm premature rupture of membranes (PPROM) and episiotomy. Therefore, it is essential to prescribe antibiotics in cases involving episiotomy and rupture of the membranous. [ABSTRACT FROM AUTHOR]

Background: Interstitial ectopic pregnancy is an ectopic gestation developing in the uterine part of the fallopian tube. The condition is rare and presents challenges for clinical as well as radiological diagnosis. This case report presents a rare case of interstitial ectopic pregnancy diagnosed intraoperatively. Case presentation: A 36-year-old Black woman, referred from a peripheral health facility, presented at the emergency department with severe abdominal pains, vaginal spotting, nausea, and vomiting, with a 2-month history of irregular menstrual flow. Clinical and laboratory findings were suggestive of an acute abdomen likely due to a ruptured ectopic pregnancy (ultrasound was not available). An emergency exploratory laparotomy was done, which revealed a right adnexal ruptured interstitial pregnancy of a lifeless female fetus weighing 500 g (estimated mean gestational age of 22–23 weeks). The left fallopian tube looked normal. The site of rupture was repaired, followed by cleaning and closure of the abdomen. The post-operative period was uneventful, and the patient was discharged on postoperative day 7. Conclusion: Interstitial pregnancies are uncommon and rarely attain advanced gestational ages, as in this case, compared with other tubal ectopic pregnancies. However, women presenting with signs of hypovolemic shock and acute abdomen, with a positive pregnancy test, warrant a high index of suspicion. [ABSTRACT FROM AUTHOR]

Introduction: Surgery is the cornerstone of ovarian cancer treatment. However, surgery and perioperative inflammation have been described as potentially pro-metastagenic. In various animal models and other human cancers, intraoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) appears to have a positive impact on patient outcomes. Materials and methods: In this unicentric retrospective study, we provide an exploratory analysis of the safety and potential benefit of intraoperative administration of ketorolac on the outcome of patients undergoing surgery for ovarian cancer. The study population included all patients who were given a diagnosis of ovarian, fallopian tube or peritoneal cancer by the multidisciplinary oncology committee (MOC) of the Cliniques universitaires Saint-Luc between 2015 and 2020. Results: We included 166 patients in our analyses, with a median follow-up of 21.8 months. Both progression-free survival and overall survival were superior in patients who received an intraoperative injection of ketorolac (34.4 months of progression-free survival in the ketorolac group versus 21.5 months in the non-ketorolac group (p = 0.002), and median overall survival was not reached in either group but there was significantly higher survival in the ketorolac group (p = 0.004)). We also performed subgroup analyses to minimise bias due to imbalance between groups on factors that could influence patient survival, and the group of patients receiving ketorolac systematically showed a better outcome. Uni- and multivariate analyses confirmed that administration of ketorolac intraoperatively was associated with better progression-free survival (HR = 0.47 on univariate analysis and 0.43 on multivariate analysis, p = 0.003 and 0.023, respectively). In terms of complications, there were no differences between the two groups, either intraoperatively or postoperatively. Conclusion: Our study has shown a favourable association between the use of ketorolac during surgery and the postoperative progression of ovarian cancer in a group of 166 patients, without any rise in intra- or postoperative complications. These encouraging results point to the need for a prospective study to confirm the benefit of intraoperative administration of ketorolac in ovarian cancer surgery. [ABSTRACT FROM AUTHOR]

Tissue inhibitor of metalloproteinases-3 (TIMP3) is vital in regulating several biological processes. TIMP3 exerts antitumour effects via matrix metalloproteinase (MMP)-dependent and MMP-independent pathways. Due to promoter methylation and miRNA binding, TIMP3 expression has been observed to decrease in various cancers. Consequently, the migration and invasion of cancer cells increases. Conflicting results have reported that expression levels of TIMP3 in primary and advanced cancers are higher than those in healthy tissues. Therefore, the role of TIMP3 in cancer biology and progression needs to be elucidated. This review provides an overview of TIMP3, from its biological function to its effects on various cancers. Moreover, gynaecological cancers are discussed in detail. TIMP3 has been associated with cervical adenocarcinoma as well as cancer development in serous ovarian cancer and breast cancer metastasis. However, the relationship between TIMP3 and endometrial cancers remains unclear. TIMP3 may be a useful biomarker for gynaecological cancers and is a potential target for future cancer therapy. [ABSTRACT FROM AUTHOR]

Context: Declining fertility is an issue in multiple mammalian species. As the site of fertilisation and early embryo development, the oviduct plays a critical role in embryo survival, yet there is a paucity of information on how the oviduct regulates this process. Aims: We hypothesised that differences in steroid hormone signalling and/or immune function would be observed in a model of poor embryo survival, the peripubertal ewe. Methods: We examined expression of steroid hormones in systemic circulation, oviductal expression of oestrogen receptor α and genes important in steroid hormone signalling, and immune function in pregnant and cyclic peripubertal and adult ewes on day 3 after oestrus. Key results: Concentrations of progesterone, but not oestradiol, were decreased in the peripubertal ewe compared to the adult ewe. Oestrogen receptor α protein expression was increased in the peripubertal ewe, but pathway analysis of gene expression revealed downregulation of the oestrogen signalling pathway compared to the adult ewe. Differential expression of several genes involved in immune function between the peripubertal and adult ewe was consistent with an unfavourable oviductal environment in the peripubertal ewe lamb. Oestradiol concentration was positively correlated with the expression of multiple genes involved in the regulation of immune function. Conclusions: Differences in the immune environment of the oviduct, potentially linked to differential modulation by steroid hormones, may partially underly the poor fertilisation and early embryo survival observed in the peripubertal ewe. Implications: A unfavourable oviductal environment may play an important role in limiting reproductive success. Declining fertility is an issue in multiple mammalian species, with around 15% of couples experiencing infertility. Differential expression of genes involved in inflammation, linked with altered steroid signalling in the oviduct, was observed in peripubertal ewes, a model of poor fertility. Ensuring that the oviductal environment does not become hostile to fertilisation and early embryo development may provide a novel approach to improve fertility, particularly in conditions associated with chronic low-grade inflammation. Photograph by Jenny Juengel. [ABSTRACT FROM AUTHOR]

Investigating the human fallopian tube (FT) microbiota has significant implications for understanding the pathogenesis of ovarian cancer (OC). In this large prospective study, we collected swabs intraoperatively from the FT and other surgical sites as controls to profile the microbiota in the FT and to assess its relationship with OC. Eighty-one OC and 106 non-cancer patients were enrolled and 1001 swabs were processed for 16S rRNA gene PCR and sequencing. We identified 84 bacterial species that may represent the FT microbiota and found a clear shift in the microbiota of the OC patients when compared to the non-cancer patients. Of the top 20 species that were most prevalent in the FT of OC patients, 60% were bacteria that predominantly reside in the gastrointestinal tract, while 30% normally reside in the mouth. Serous carcinoma had higher prevalence of almost all 84 FT bacterial species compared to the other OC subtypes. The clear shift in the FT microbiota in OC patients establishes the scientific foundation for future investigation into the role of these bacteria in the pathogenesis of OC. [ABSTRACT FROM AUTHOR]

Background: In Canada, individuals with gynecologic reproductive organs (ovaries, fallopian tubes, uterus) over the age of 70 comprise a large proportion of epithelial ovarian cancer patients. These patients often have co-morbidities, polypharmacy, or decreased functional status that may impact treatment initiation and tolerance. Despite this, there is limited evidence to guide treatment for older patients diagnosed with ovarian epithelial carcinoma. Methods: This is a retrospective study with data from Manitoba, Canada. The data were obtained from the Manitoba Ovarian Cancer Database, the Manitoba Cancer Registry, and electronic health records. All individuals with epithelial ovarian, fallopian tube, or peritoneal cancer diagnosed between 2009 and 2018 were identified. Patients aged > 70 at the time of diagnosis were included in the study cohort. Results: Four hundred and forty individuals were included. The majority had advanced stage disease (56%). Moreover, 59% of patients received no chemotherapy. Of the patients who received chemotherapy, 20% received <2 cycles and 21% required a dose reduction due to toxicity. Univariable and multivariable analysis identified advanced stage (p < 0.001), treatment modality (p < 0.001), and advanced age at diagnosis (p < 0.001) with poorer overall survival. Conclusions: Our study demonstrated a high rate of chemotherapy dose reduction and discontinuation in the elderly epithelial ovarian cancer population. Further research is needed to identify risk factors for treatment discontinuation and intolerance in this population. [ABSTRACT FROM AUTHOR]

Hysterosalpingography (HSG) is a practical and reliable imaging method to evaluate the cervical canal, uterine isthmus, uterine cavity, and fallopian tubes. Using HSG, opaque pathologies outside of contrast media can be detected as well as pathologies of uterus and fallopian tubes. We aim to present and categorize some uncommon and interesting abnormal findings that are located outside of the contrast areas in HSG. This is a pictorial review that depicts various types of HSG images that include opaque pathologies outside of the contrast areas. Images have been extracted from valuable archives collected over 50 yr by professor Shahrzad. A plain pelvic film contains soft tissues of the pelvis, bony structures, artifacts, or foreign bodies. Categorization might easily help the radiologist to interpret the HSG cliché. Opaque pathologies outside of contrast area in HSG can be categorized into 2 groups: "Pelvic Tissue Related" and "Foreign Bodies". Pelvic tissue abnormalities might have a gynecologic or nongynecologic source. Foreign bodies can be located in the pelvis or outside of the body. HSG is a reliable and inexpensive procedure. Familiarity with the pathologies of pelvic tissues and the accurate interpretation of HSG images are important. [ABSTRACT FROM AUTHOR]

Hemangioma in female reproductive organs, particularly in the fallopian tube (FT), is a sporadic disease. In this report, we describe a case of hidden capillary hemangioma in FT in a 39-year-old woman who suffered from uterine leiomyoma. During the preoperative stage, pelvic sonography, computed tomography, and diagnostic laparoscopy revealed a subserous leiomyomatous nodule located along the posterior wall of the uterus. Despite this, intraoperatively, a benign vascular neoplasm was diagnosed. Histologically, it is characterized by multiple thin-walled vascular spaces lined with a single layer of endothelial cells, in which single mitoses were observed. The diagnosis was then confirmed immunohistochemically by CD31 and CD34 expression in the endothelial cells lining the inner surface of the spaces and the low mitotic activity of the tumor cells. It is virtually impossible to diagnose this asymptomatic neoplasm before and during surgery, which can result in an inadequate number of surgeries. Incorrect interpretation of a benign tumor at a young age can lead to unnecessary radical surgery with a resulting loss of fertility, and an unrevealed malignant process can threaten life. [ABSTRACT FROM AUTHOR]

Ectopic pregnancies are a frequently encountered cause of first-trimester metrorrhagia. They occur when an embryo is implanted and grows outside the normal uterine space. Uncommonly, the embryo can be implanted in the intramural portion of the uterine tube, a condition referred to as interstitial localization. This specific type of ectopic pregnancy may have an unpredictable course, potentially leading to severe uterine rupture and catastrophic bleeding if not promptly diagnosed and managed. We present a rare case of a multiparous 36-year-old female patient who underwent pelvic ultrasonography in the emergency department for intense pelvic pain associated with hypotension and moderate anemia. A history of right salpingectomy for a ruptured tubal ectopic pregnancy 10 years previously was noted. High beta-HCG levels were also detected. A pelvic ultrasound allowed us to suspect a ruptured ectopic interstitial pregnancy at 8 weeks of amenorrhea. An association with hemoperitoneum was suspected, and an emergency laparoscopy was performed. The condition was confirmed intraoperatively, and the patient underwent a right corneal wedge resection with suture of the uterine myometrium. The postoperative course was uneventful, and the patient was discharged on the fourth day postoperatively. Interstitial ectopic pregnancy is a rare yet extremely perilous situation. Timely ultrasound-based diagnosis is crucial as it can enable conservative management with Methotrexate. Delayed diagnosis can lead to uterine rupture with consecutive surgery based on a transection of the pregnancy and cornual uterine resection. [ABSTRACT FROM AUTHOR]

Introduction: Intravasation on hysterosalpingogram (HSG) is defined by the flow of injected contrast from the uterine cavity into adjacent myometrial vessels. Evidence suggests intravasation can result in consequences such as pulmonary and cerebral embolisms. However, adverse events are poorly reported across published studies. Reported intravasation ranges from 0.0% to 13%, with higher rates attributed to oil‐soluble contrast medium (OSCM) use. Recent reviews of OSCM's fertility‐enhancing benefits have prompted rapid clinical uptake by fertility specialists worldwide. This instigates increased concern for intravasation and its associated sequelae. We aim to assess the prevalence of intravasation in fluoroscopic HSGs and its reporting in Western Australia (WA). Methods: A two‐year retrospective analysis of all fluoroscopic HSGs in one public teaching hospital within WA was conducted. All HSGs were retrieved from the public radiology information system and a blinded method was utilised to verify the presence and grading of intravasation in captured HSG images. Grading of intravasation was attributed by anatomical spread: 1 to myometrium, 2 to parametrium and 3 to para‐iliac vessels. Results were subsequently compared with reported intravasation to assess for discrepancies. Results: Of 308 successful HSGs, an intravasation rate of 7.1% was identified. Of these cases, 45% were reported and 32% were graded. Majority (73%) of intravasation events were classified as grade 1, with 9.0% and 18% of cases classified as grade 2 and 3, respectively. Conclusion: Under‐reporting of intravasation emphasises a need for increased vigilance of radiologists. Standardised classification can provide interpretational consistency and should be considered to improve safety in future practice. [ABSTRACT FROM AUTHOR]

During the anatomical dissection of the pelvis, a duplication of the uterine artery was identified unilaterally on the left side in a 59-year-old Korean female cadaver. The first uterine artery was found to arise directly from the anterior division of the internal iliac artery and supply the upper uterine body and tube. The second uterine artery shared a common stem with the superior and inferior vesical arteries, supplying the lower uterine body. The external diameter of each uterine artery at its origin on the left side was smaller than that of the right uterine artery. One vaginal artery was identified to arise from the left internal pudendal artery. Embryologically, a duplicated uterine artery could imply the presence of two primordial arteries separately supplying the cranial and caudal parts of the Müllerian duct during the early fetal period. This case of variational anatomy is noteworthy: clinicians could elucidate it and successfully perform uterine artery embolization or hysterectomy with minimal complications. [ABSTRACT FROM AUTHOR]

Platinum-resistant epithelial ovarian cancer (EOC), recurrent endometrial cancer (EC), and triple negative breast cancer (TNBC) are difficult to treat after failing standard therapies. This phase I study evaluated mirvetuximab soravtansine (MIRV) and gemcitabine in patients with recurrent FRα-positive EOC, EC, or TNBC to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) (primary endpoint). FRα-positive patients with platinum-resistant EOC, EC, or TNBC with ≤4 prior chemotherapy regimens (2 for EC) were enrolled. FRα expression requirement varied among eligible tumors and changed during the study. Twenty patients were enrolled; 17 were evaluable for DLT. Half the patients received ≥3 prior chemotherapy lines. Most EOC and EC patients (78%) were medium (50–74%) or high(75–100%) FRα expressors. TNBC patients were low (25–49%) FRα expressors. The MTD/RP2D was MIRV 6 mg/kg AIBW D1 and gemcitabine 800 mg/m2 IV, D1 and D8, every 21 days (Dose Level [DL] 3), where 5/7 patients demonstrated a partial response (PR) as their best response, including 2 confirmed ovarian responses whose time-to-progression and duration of response were 7.9/5.4 and 8.0/5.7 months respectively. Most common treatment-related adverse events at MTD were anemia and neutropenia (3/7 each, 43%), diarrhea, hypophosphatemia, thrombocytopenia, and leukopenia (2/7 each, 29%). DLTs were thrombocytopenia (DL1), oral mucositis (DL4) and diarrhea (DL4). Nine of 20 patients (45%; 95% CI: 21.1–68.9%) achieved PR as their best response, with 3/20 patients or 15% (95%CI, 0–32.1%) confirmed PR. MIRV and gemcitabine demonstrate promising activity in platinum resistant EOC at RP2D, but frequent hematologic toxicities. • Platinum-resistant EOC, recurrent EC, and TNBC are difficult to treat after failing standard therapies. • This phase I study evaluated MIRV/gemcitabine in patients with recurrent FRα-positive platinum-resistant EOC, EC, or TNBC. • The MTD/RP2D was established at MIRV 6 mg/kg AIBW D1 and gemcitabine 800 mg/m2 IV, D1 and D8, every 21 days. • MIRV/gemcitabine showed promising activity in platinum-resistant EOC at RP2D, but frequent hematologic toxicities. • Developing MIRV/Gemcitabine in EOC is unlikely due to alternative MIRV regimens offering improved efficacy and tolerability. [ABSTRACT FROM AUTHOR]

Simple Summary: Female moths display a rhythmic motor pattern, a "calling behaviour", to release sex pheromones and attract of conspecific males for mating. Pheromone release occurs through a squeezing mechanism consisting of turtleneck-like folding and unfolding of the ovipositor cuticle during its rhythmic extensions and retractions. They are under the control of the terminal abdominal ganglion (TAG). The physiology of the production and release of sex pheromones in moths has been an object of great interest. In the present study we investigate the anatomical and physiological basis of calling by using the female spongy moth Lymantria dispar as a model insect. Our results show that the three terminal abdominal segments S7, S8 and S9 (ovipositor) are specialized structures, containing cuticular appendages, hinges, apodemes and several large muscles, innervated by TAG nerves N4 and especially by N5. N6 mainly innervates the oviduct. We also identified a number of specific motor units from nerves N4 and N5 responsible for the ovipositor movements observed during calling. Overall, extensions and retractions of the ovipositor leading to pheromone release are sustained by a coordinated motor program, which involves the activity of a few motor units under the control of TAG nerves N4 and N5. "Calling behaviour" is a stereotyped rhythmic motor pattern displayed by female moths, by which they emit the sex pheromone to attract of conspecific males. Calling occurs through a squeezing mechanism based on the turtleneck-like folding and unfolding of the ovipositor cuticle during its telescopic extensions and retractions. This mechanism is under the control of the terminal abdominal ganglion (TAG). By combining anatomical and electrophysiological approaches, here we studied the morpho-functional organisation of the abdominal muscles and the activity of motoneurons from TAG nerve N4-N6 as correlated to the ovipositor movements during calling in the female spongy moth Lymantria dispar. Our results show that the three abdominal segments S7, S8 and S9 (ovipositor) are highly specialized structures containing cuticular appendages, hinges, apodemes and several large muscles, innervated by N4 and especially by N5. N6 mainly innervates the oviductal tract. We also identified a number of motor units from N4 and N5, the spike activity of which is correlated with the ovipositor movements during calling. In conclusion, the release of sex pheromones in the female spongy moth is obtained by extensions and retractions of the ovipositor operated by a coordinated motor program, which is mainly sustained by the activity of a few motor units under the control of TAG nerves N4 and N5. [ABSTRACT FROM AUTHOR]

Adenomatoid tumor (AT) is a benign growth that originates from mesothelial cells. Typically, it encompasses the uterus, fallopian tubes, and paratesticular area. One-third of all AT is in paratesticular area, and it accounts for 60% of all benign paratesticular tumors. ATs have been seldom reported as a case report in adrenal gland, liver, pleura, and mediastinal cavity. To date, English literature has only documented 46 instances of adrenal AT. We present the occurrence of a new clinically unexpected case of adrenal AT in a 37-year-old male patient. Computed tomography (CT scan) incidentally revealed the presence of a tumor. To the best of our knowledge, this is the first reported instance of primary adrenal gland AT reported in Saudi Arabia and the 47th instance worldwide in the English-based published literature. It is crucial to thoroughly investigate these tumors, utilizing techniques such as histopathological analysis and immunohistochemical staining to correctly diagnose AT. [ABSTRACT FROM AUTHOR]