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The role of long non-coding RNAs in fibroid pathogenesis remains largely unexplored. In a previous study, we found elevated XIST (X-inactive specific transcript) levels in fibroids, which sponged miR-29c and miR-200c, leading to the overexpression of their target genes. This study aimed to assess the therapeutic potential of XIST downregulation in fibroid treatment. Ovariectomized SCID (severe combined immunodeficiency) mice were implanted with fibroid tumors transduced with XIST siRNA or a control via lentivirus. After 1 month, animals were sacrificed and the xenografts were removed for further analysis. XIST knockdown reduced tumor weight by 15% and increased miR-29c and miR-200c expression by 3.9-fold and 2.2-fold, respectively. The mRNA expression of miR-29c targets (COL3A1, TGF-β3, CDK2, SPARC) and miR-200c targets (CDK2, FN1, TDO2), as well as PRL, E2F1, and EZH2, was significantly decreased. Protein abundance of collagen, COL3A1, FN1, CDK2, SPARC, and EZH2 was also reduced. IHC analysis of xenograft sections using the markers of Ki67 for cell proliferation and cleaved caspase 3 for apoptosis showed decreased cell proliferation and no changes in apoptosis in the XIST knockdown xenografts. This analysis also revealed decreased collagen and E2F1 staining nuclei in the XIST knockdown xenografts. These results indicate that downregulation of XIST in fibroids has beneficial therapeutic effects, by reducing tumor growth and the expression of genes involved in cell proliferation, inflammation, and extracellular matrix regulation., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Rationale: Prostate leiomyoma is a rare condition globally, often challenging to diagnose preoperatively, with most cases being definitively identified through postoperative pathology. This benign tumor generally has a good prognosis and is primarily treated with transurethral resection of the prostate in clinical settings. However, there are no established guidelines or therapeutic protocols for managing this disease., Patient Concerns: The patient was admitted to our hospital's Department of Urology with complaints of hematuria, urinary frequency, and urgency for 1 month. Pelvic computed tomography revealed an irregular, mass-like high-density shadow posterior to the bladder, indistinctly separated from the prostate. The patient had been diagnosed with renal insufficiency during a physical examination 4 years prior but had not received standardized treatment. Six years ago, the patient underwent electrocision of the prostate at our hospital, and postoperative pathology indicated prostate leiomyoma., Diagnoses: Postoperative pathology confirmed a diagnosis of prostate leiomyoma., Interventions: The patient presented with an enlarged prostate and preoperative hematuria. Holmium laser enucleation of the prostate (HoLEP) was performed. The Foley catheter was removed on the second postoperative day, and the patient was discharged 3 days after surgery., Outcomes: Following discharge, the patient was instructed to undergo reexaminations every 6 months. Current follow-up indicates the patient is in good health, with no recurrence of the mass observed., Lessons: Prostate leiomyoma is an extremely rare condition, and the current primary approach for managing prostate smooth muscle tumors involves active patient monitoring, regular evaluations, and timely surgical intervention if clinical symptoms emerge. In this study, we present a new case report of prostatic smooth muscle tumor and review the existing literature to explore treatment options for prostate leiomyoma within this field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Research Question: What influence does an intramural myoma have on the endometrium, and how is this mediated?, Design: Endometrium was collected from 13 patients with non-cavity-distorting intramural myomas (diameter ≤4 cm; International Federation of Gynecology and Obstetrics type 4) and 13 patients without myomas undergoing hysterectomy for benign cervical diseases with a similar clinical baseline. Endometrial organoids were established in vitro and induced to reach the secretory phase by oestrogen and progesterone. Transcriptome sequencing was conducted on endometrial organoids in both untreated and secretory stages from three individuals with myomas and three control participants. Immunofluorescence and real-time quantitative PCR (RT-qPCR) were performed on endometrial organoids from another 10 myoma patients and 10 control patients for validation., Results: The data revealed abnormally increased hormone receptor (PGR) levels in the untreated endometrial organoids with myomas, resulting in potentially abnormal glandular and vascular development. The aberrant responses to oestrogen and progestogen prompted further investigation into the secretory phase. The secretory endometrial organoids with myomas exhibited greater changes in acetyl-α-tubulin, ODF2 and TPPP, demonstrating likely decreased cilia, and COL6A1, used as a marker for increased extracellular matrix (ECM) modelling. Both untreated and secretory endometrial organoids with myoma showed an up-regulation of genes and pathways related to ECM mechanotransduction. The expression pattern of receptivity-related genes was disturbed in endometrial organoids with myoma., Conclusions: This study is the first to reveal that intramural myomas create an abnormal hormonal and mechanical environment in the untreated and secretory endometrial organoids. The intramural myomas negatively impacted gene expression relating to endometrial glands, blood vessels, cilia and ECM, indicating that intramural myomas impair endometrial decidualization and receptivity., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To determine prognosis and factors associated with survival of women with uterine sarcoma found incidentally after myomectomy., Methods: We performed a retrospective study for patients who had previously undergone myomectomy for presumed benign uterine fibroid disease and were found to have uterine confined sarcoma after myomectomy surgery., Results: In total, 50 patients were identified. There were 23 (46.0 %) patients undergoing myomectomy were performed by minimal invasive surgery: laparoscopic (Lap, n = 22, 44.0 %) or transvaginal (TV, n = 1, 2.0 %) approach; while, 24 (48.0 %) and 3 (6.0 %) patients had myomectomy through abdominal (Abd) or hysteroscopic (Hys) approach. All patients received the re-exploration and staging surgery in our center. The median time from myomectomy to the staging surgery was 43 days (range 15-90 days). 17 patients had remnant sarcomas on the remaining uterus and 6 patients had disseminated disease after re-exploration. In the entire cohort, 5-year RFS and 5-year OS was 79.4 % and 88.0 %, respectively. Patients who received initial Lap/TV myomectomy had a tendency towards a worse 5-year RFS compared with Abd/Hys approach (63.0 % vs 88.9 %, P = 0.080). No difference in 5-year OS was found between the two groups (90.3 % vs 91.8 %, P = 0.768). For stage I disease (n = 44), patients who received Lap/TV myomectomy had a worse 5-year RFS compared with Abd/Hys approach (58.3 % vs 95.7 %, P = 0.009). No difference in 5-year OS was found (P = 0.121)., Conclusion: Patients with incidental uterine sarcoma who received primary Lap/TV myomectomy may have a worse RFS. Re-exploration can detect remnant or disseminated sarcomas., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Using dose-painted intensity-modulated radiation therapy, specific dose volume constraints or implantation of tissue expanders prior to radiotherapy are validated options for reducing radiation dose on the bowel and therefore minimizing acute gastrointestinal toxicity during chemoradiation for anorectal malignancies. We describe the rare case of a female patient with a locally advanced anal carcinoma where a large myomatous uterus served as a natural spacer to protect the bowel during radiation therapy., Case Presentation: Initially the patient presented with anal pain, proctoscopy followed by an excisional biopsy confirmed the diagnosis of a squamous cell carcinoma of the anus. Imaging examination showed a locally advanced tumor and in addition a large uterus with typical leiomyomas up to 11.5 cm in diameter. The patient underwent chemoradiation; because of the large leiomyomas there was almost no dose burden for the small intestine and therefore practically no gastrointestinal toxicity., Conclusion: As we know, this report describes the situation that a large myomatous uterus served as a natural spacer during radiation therapy in a way that is unique to date., (© 2024. The Author(s).)

Found in as many as 80% of women, uterine leiomyomas are a frequent cause of abnormal uterine bleeding, pelvic pain, and infertility. Despite their significant clinical impact, the mechanisms responsible for driving leiomyoma growth remain poorly understood. After obtaining IRB permission, expression of ecto-5'-nucleotidase (NT5E, CD73) was assessed in matched specimens of myometrium and leiomyoma by real-time qPCR, Western blot, and immunohistochemistry (IHC). Adenosine concentrations were measured by enzyme-linked assay. Primary cultures were used to assess the impact of adenosine and/or adenosine receptor agonists on proliferation, apoptosis, and patterns of intracellular signaling in vitro. When compared to matched specimens of healthy myometrium, uterine leiomyomas were characterized by reduced CD73 expression. Largely limited to thin-walled vascular structures and the pseudocapsule of leiomyomas despite diffuse myometrial distribution. Restricted intra-tumoral CD73 expression was accompanied by decreased levels of intra-tumoral adenosine. In vitro, incubation of primary leiomyoma cultures with adenosine or its hydrolysis-resistant analog 2-chloro-adenosine (2-CL-AD) inhibited proliferation, induced apoptosis, and reduced proportion of myocytes in S- and G2-M phases of the cell cycle. Decreased proliferation was accompanied by reduced expression of phospho-Akt, phospho-Cdk2-Tyr15, and phospho-Histone H3. Enforced expression of the A2B adenosine receptor (ADORA2B) and ADORA2B-selective agonists similarly suppressed proliferation and inhibited Akt phosphorylation. Collectively, these observations broadly implicate CD73 and reduced extracellular concentrations of adenosine as key regulators of leiomyoma growth and potentially identify novel strategies for clinically managing these common tumors., (© 2024 Federation of American Societies for Experimental Biology.)

Objective: Fibroids are hormonally dependent uterine tumors. The literature on adiposity and fibroid prevalence is inconsistent. Previous work usually combined all those with a body mass index (BMI) ≥30 kg/m2 into a single category and relied on clinically diagnosed fibroids, which misclassifies the many women with undiagnosed fibroids. We used a prospective cohort design with periodic ultrasound screening to investigate associations between repeated measures of BMI and fibroid incidence and growth assessed at each follow-up ultrasound., Methods: The Study of Environment, Lifestyle & Fibroids followed 1693 Black/African American women, ages 23 to 35 years from Detroit, Michigan, with ultrasound every 20 months for 5 years. Measured height and repeated weight measures were used to calculate BMI. Fibroid incidence was modeled using Cox models among those who were fibroid free at the enrollment ultrasound. Fibroid growth was estimated for individual fibroids matched across visits as the difference in log-volume between visits and was modeled using linear mixed models. All models used time-varying BMI and adjusted for time-varying covariates., Results: Compared with BMI <25 kg/m2, those with BMI 30 to <35 kg/m2 had increased fibroid incidence (adjusted hazard ratio, 1.37; 95% CI, 0.96-1.94), those with BMI ≥40 kg/m2 had reduced incidence (adjusted hazard ratio, 0.61; 95% CI, 0.41-0.90). Fibroid growth had mostly small magnitude associations with BMI., Conclusion: BMI has a nonlinear association with fibroid incidence, which could be driven by effects of BMI on inflammation and reproductive hormones. More detailed measures of visceral and subcutaneous adiposity and their effects on hormones, DNA damage, and cell death are needed., (Published by Oxford University Press on behalf of the Endocrine Society 2024.)

Visceral obesity (VO), characterized by excess fat around internal organs, is a recognized risk factor for gynecological tumors, including benign uterine leiomyoma (ULM) and malignant uterine leiomyosarcoma (ULS). Despite this association, the shared molecular mechanisms remain underexplored. This study utilizes an integrated bioinformatics approach to elucidate common molecular pathways and identify potential therapeutic targets linking VO, ULM, and ULS. We analyzed gene expression datasets from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) in each condition. We found 101, 145, and 18 DEGs in VO, ULM, and ULS, respectively, with 37 genes overlapping across all three conditions. Functional enrichment analysis revealed that these overlapping DEGs were significantly enriched in pathways related to cell proliferation, immune response, and transcriptional regulation, suggesting shared biological processes. Protein-protein interaction network analysis identified 14 hub genes, of which TOP2A, APOE, and TYMS showed significant differential expression across all three conditions. Drug-gene interaction analysis identified 26 FDA-approved drugs targeting these hub genes, highlighting potential therapeutic opportunities. In conclusion, this study uncovers shared molecular pathways and actionable drug targets across VO, ULM, and ULS. These findings deepen our understanding of disease etiology and offer promising avenues for drug repurposing. Experimental validation is needed to translate these insights into clinical applications and innovative treatments., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Most persistent symptoms of pseudo-Meigs' syndrome (PMS) are alleviated by surgical tumor removal. The present case report suggests that PMS may present with ascites and hypercoagulation and that emergency anticoagulation can improve the patient's condition. We herein describe a postpartum woman with an acute presentation including abdominal pain, ascites, postpartum hemorrhage, and degeneration of a large uterine fibroid. Initial evaluation revealed unexpected massive ascites, pleural effusion, a highly elevated D-dimer level, and a moderately elevated CA125 level. Following anticoagulation therapy, the ascites, abdominal pain, and pleural effusion resolved. There was no recurrence of these symptoms during follow-up, although the large degenerating uterine fibroid and mildly elevated serum CA125 level persisted. Postoperatively, pathological analysis confirmed leiomyoma, the patient's CA125 level returned to normal, and the ascites resolved, meeting the diagnostic criteria for PMS. Further studies are needed to determine whether a hypercoagulable state is common in pregnant patients with PMS and to develop strategies to improve outcomes., Competing Interests: Declaration of conflicting interestsThe authors declare that there is no conflict of interest.

Objective: To explore the utility of the total fibroids-to-uterine volume (FTUV) ratio as a simple, preoperative tool to assist in counseling patients seeking pregnancy who are undergoing myomectomy for intramural (IM) fibroids., Study Design: This is an historical cohort study on reproductive-aged patients seeking pregnancy who underwent laparotomic myomectomy for intramural fibroids from January 2017 to December 2021. Only G3 to G5 fibroids, according to the 2011 International Federation of Gynecology and Obstetrics (FIGO) classification, were included. Pre-operative transvaginal ultrasound (TVUS) was performed to measure the volume of intramural myomas (diameter 1 *diameter 2 *diameter 3 *0.52) and to calculate their total volume. The total fibroids-to-uterine volume (FTUV) ratio was calculated as the proportion of the uterine volume occupied by the sum of IM fibroids volumes., Results: A total of 166 women with pre-surgical TVUS evaluation of IM fibroids were included, with a mean age of 36.22 ± 5.15 years. The FTUV ratio was identified as a positive predictor of clinical pregnancy after surgery (adjOR, 1.04; 95 % CI, 1.02-1.06; p = 0.0001), whereas age showed a negative association (adjOR, 0.90; 95 % CI, 0.83-0.98; p = 0.012). Endometrial cavity distortion prior to surgery was also positively associated with pregnancy post-surgery (adjOR, 3.50; 95 % CI, 1.51-8.08; p = 0.003). Consistent results were found for live births, with the FTUV ratio being a significant positive predictor of live birth after surgery (adjOR, 1.03; 95 % CI, 1.01-1.05; p = 0.001) and age showing a negative association (adjOR, 0.88; 95 % CI, 0.80-0.96; p = 0.004). Parity prior to surgery also positively impacted live birth post-surgery (adjOR, 2.65; 95 % CI, 1.30-5.40; p = 0.007). An FTUV ratio threshold of 53.39 % accurately predicted clinical pregnancy in 68.46 % of cases (sensitivity of 71.70 % and specificity of 66.67 %). For live births, a higher FTUV ratio threshold of 59.21 % predicted outcomes accurately in 69.13 % of cases (sensitivity of 65.85 % and specificity of 70.37 %)., Conclusion: The use of the FTUV ratio in pre-operative ultrasound evaluation of IM fibroids may improve counseling for patients desiring to conceive after myomectomy. By providing a personalized assessment of the amount of myometrial volume occupied by fibroids, the FTUV ratio can help predict fertility outcomes after surgery, enabling better-informed decisions and treatment planning., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: Conflicts of interest None disclosed.

Objective: The Primary Objective of this study was to analyse reproductive outcomes in patients with STUMP (Smooth Muscle Tumour of Uncertain Potential) or ALM (Atypical Leiomyoma) who underwent fertility-preserving surgeries. Secondary Objectives were to analyse long-term prognosis for these patients and to study the basic demographic and pathological characteristics of patients with STUMP or ALM., Study Design: This retrospective study was conducted at Amrita Institute of Medical Sciences. Cases of STUMP and ALM were retrieved from the hospital medical database between June 2014 and December 2022. Demographic parameters, clinical presentations, pathological features and clinical outcomes were analysed. Categorical variables were expressed in numbers and percentages. Normal distribution data were presented as mean while non-normal distribution was expressed as median and range., Results: Thirty-eight patients were included in the study with a diagnosis of STUMP or ALM in postoperative histology. Seven patients (18.4%) were nulliparous. Myomectomy was performed in 9 (23.6%), while hysterectomy was done in 29 patients (76.3%). Fertility-preserving surgeries were performed on six patients (15.7%). Of these six patients, 4(66.6%) conceived spontaneously and had successful pregnancies. Recurrences were found in 3 patients (7.8%) out of which one had undergone fertility-sparing surgery. All the patients with recurrences had previous history of myomectomies. Morcellation was reportedly done in 2 of these three patients., Conclusion: Good reproductive outcomes have been demonstrated in patients diagnosed with STUMP or ALM and desiring fertility. However, these patients should be kept under follow-up care as they are prone for recurrences. Patients who have undergone morcellation mayhave an increased chance of recurrence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aims to objectively assess the effect of three surgical approaches for posterior uterine fibroid resection: transumbilical laparoendoscopic single-site surgery (LESS), vaginal natural orifice transluminal endoscopic surgery (vNOTES) in prone position (vNOTES-P), and vNOTES in the lithotomy position (vNOTES-L). A retrospective analysis was conducted on data pertaining to all patients who underwent vNOTES and LESS for single posterior fibroids at our institution from January 2023 to July 2023. Patients were categorized into three groups based on the surgical approach: vNOTES-P group (n = 30), vNOTES-L group (n = 17), and LESS group (n = 32). Comparative analysis was performed on the demographic characteristics and perioperative outcomes among the three groups of patients. All 79 patients underwent surgery without the need for conversion to laparotomy. There were no statistically significant differences among the LESS group, vNOTES-P group, and vNOTES-L group in terms of operative time, intraoperative blood loss, and perioperative complication rates. In the vNOTES-L group, two patients required conversion to LESS during surgery. Patients had faster return of bowel function (less time to flatus) in the vNOTES group compared to the LESS group (P < 0.05). However, three cases of postoperative infection occurred in the vNOTES group, while none were reported in the LESS group. Compared to LESS, vNOTES demonstrates significant advantages in alleviating postoperative pain, shortening time to passage of flatus, speeding recovery and enhancing cosmetic outcomes. Particularly, vNOTES-P for posterior uterine fibroid resection, as an emerging surgical approach, offers certain advantages in facilitating surgical maneuverability and reducing operative time, rendering it more suitable for posterior uterine fibroid resection., (© 2024. The Author(s).)

Benign cardiac neoplasms are relatively uncommon. Cardiac leiomyomas are usually diagnosed as a benign metastasizing leiomyoma or as a part of intravenous leiomyomatosis spectrum. Primary cardiac leiomyomas are extremely rare and should be diagnosed after ruling out the involvement of systemic leiomyomas. Only nine cases were found in the literature that described De novo occurrence of primary intra-cardiac leiomyoma. In this study, we present a case of 60-year-old female patient with a large pedunculated mass located in the left ventricle. Histopathology examination and immunohistochemistry aid confirmed the diagnosis of benign leiomyoma. No evidence of extra cardiac lesions was detected in the patient. The patient remained healthy with no signs of recurrence four years after the surgical resection. Benign cardiac tumors are not often seen, but when they do occur, they can present a serious risk to life. This is particularly significant because these tumors can detach and cause embolization, leading to the development of strokes. Moreover, these individuals do not show any clinical symptoms, making their detection quite challenging. When there is a suspicion, it is advised to utilize echocardiography and other imaging techniques to verify the presence of a tumor. In this report, we present a rare case and provide differential diagnoses, along with a review of the literature., (© 2024. The Author(s).)

Background: Uterine Fibroids (UFs) are common benign tumors in the female reproductive tract, but their progression to intravascular leiomyomatosis (IVL) is rare. Presently, there are few reports on single-stage resection of UFs and IVL., Case Presentation: A 47-year-old woman, G2P2, had been diagnosed multiple UFs four years ago and now developed heart failure. Imaging examinations revealed that UFs had invaded the right iliac vein and extended into the right atrium through the inferior vena cava. Through multidisciplinary collaboration and a single-stage resection, the patient has survived for over 24 months post-surgery, and her heart function has significantly improved compared to preoperative levels, with no recurrence of UFs observed., Conclusions: Single-stage resection of IVL and UF is feasible and advantageous for this case, and selecting the appropriate surgical approach is crucial., (© 2024. The Author(s).)

Introduction: This study analyzed and discussed the characteristics of peripheral blood lymphocytes (PBLs) in patients with endometrial carcinoma (EC) to explore the PBLs' clinical application value., Methods: This single-center case‒control study analyzed the clinical data of patients with EC and uterine fibroids who underwent surgery at the First Affiliated Hospital of Chongqing Medical University between October 2018 and October 2023 retrospectively. The Center for Clinical Molecular Medical Detection of our hospital performed PBLs detection using flow cytometry, and recorded the detection results in the electronic medical records system. Between-group and subgroup comparisons of PBLs in patients with EC were analyzed using t-test or Mann-Whitney U test. The effect of surgery on PBLs in patients with EC was assessed using a paired t-test or the Wilcoxon signed rank test., Results: The immune function of patients with EC was significantly lower than that of healthy people (P < 0.05) and those with benign uterine diseases (P < 0.05) and was related to body mass index (BMI), hypertension, diabetes, and blood lipids (P < 0.05). In patients with EC, the PBLs counts decreased significantly after surgery (P < 0.05) and more kinds of lymphocytes were affected in the laparoscopic surgery group than in the open surgery group., Conclusions: With the decrease of PBLs counts, the immune status of patients with EC is impaired. Metabolic syndrome (Mets), including obesity, hypertension, diabetes, and high blood lipids, also affects the immune function of patients with EC. And for EC patients, the effect of laparoscopic surgery is greater than that of open surgery. PBLs has the potential to be one of indicator during the diagnosis and treatment of EC., Trial Registration: This study was retrospectively registered by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (approval number K2023-578)., (© 2024. The Author(s).)

Cotyledonoid dissecting leiomyoma (CDL) is a rare benign uterine leiomyoma that macroscopically shows multinodular placenta-like growth. Its border with the myometrial layer is unclear, making it clinically difficult to differentiate from uterine sarcoma. CDL is often misdiagnosed. We report a case of CDL in which a subserosal myoma was suspected preoperatively and an abdominal myomectomy was performed. However, due to intraoperative findings and intraoperative rapid histopathological diagnosis, the procedure was changed to total hysterectomy. Peritoneal dissemination had also occurred and was resected simultaneously. It has been reported that CDL is generally a disease with good prognosis and that fertility preservation may be considered depending on the case. On the other hand, some cases of large tumours have caused peritoneal dissemination. We did a literature review of CDL and compared a group with peritoneal dissemination who underwent disseminated resection simultaneously and a group without peritoneal dissemination. We found that the tumour diameter was significantly greater in the peritoneal dissemination group., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Emerging evidence suggests a tentative association between cathepsins and uterine leiomyoma (UL). Previous investigations have predominantly focused on the role of cathepsins in the metastasis and colonization of gynecological malignancies. Still, observational studies may lead to confounding and biases. We employed a bidirectional Mendelian randomization (MR) analysis to elucidate the causative links between various cathepsins and UL. Instrumental variables (IVs) of cathepsins and UL within the European cohort were from extant genome-wide association study datasets. Sensitivity assessments was executed, and the heterogeneity of the findings was meticulously dissected to affirm the solidity of the outcomes. Our findings reveal the association between cathepsin B (CTSB) and an elevated risk of developing UL (all cancers excluded) [Inverse Variance Weighted (IVW) method]: OR = 1.06, 95%CI [1.02, 1.11], P = 0.008895711. Although the association does not persist after multiple testing or Steiger filtering, this finding adds to our understanding of the causal relationship between CTSB of various cathepsins and UL (all cancers excluded) and may herald new therapeutic avenues for individuals affected by this condition., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Bisphenol A (BPA) and its analogues (BPAF, BPS) are ubiquitous environmental contaminants used as plastic additives in various daily life products, with many concerns on their role as environmental estrogens. Uterine leiomyomas (fibroids) are highly prevalent gynecologic tumors with progressive fibrosis. Fibroids are hormone-responsive and may be the target of environmental estrogens. However, the effects of BPA, BPAF, and BPS exposure on uterine fibrosis are largely unknown. Here, we evaluated fibrosis and the crucial role of TGF-beta signaling in human fibroid tumors, the profibrotic effects of BPA, BPAF or BPS in a human 3D uterine leiomyoma (ht-UtLM) in vitro model, and the long-term outcomes of BPAF exposure in rat uterus. In 3D ht-UtLM spheroids, BPA, BPAF, and BPS all promoted cell proliferation and fibrosis by increasing the production of extracellular matrices. Further mechanistic analysis showed the profibrotic effects were induced by TGF-beta signaling activation mainly through SMAD2/3 pathway and crosstalk with multiple non-SMAD pathways. Furthermore, the profibrotic effects of BPAF were supported by observation of uterine fibrosis in vivo in rats following long-term BPAF exposure. Overall, the 3D ht-UtLM spheroid can be an important model for investigating environment-induced fibrosis in uterine fibroids. BPA and its analogues can induce fibrosis via TGF-beta signaling., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Darlene Dixon, DVM, PhD reports financial support was provided by National Institute of Environmental Health Sciences. Darlene Dixon reports a relationship with National Institute of Environmental Health Sciences that includes: employment. Darlene Dixon, DVM, PhD has patent N/A pending to N/A. The corresponding author and co-authors have no conflict of interest relationships to disclose. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Leiomyomas and schwannomas are both types of rare benign soft tissue tumours. Leiomyomas are more commonly found in the lower limbs than in the upper extremities, while schwannomas are rare peripheral nerve sheath tumours that can occur in different anatomical regions. However, they rarely occur in the saphenous nerve. This case study presents a 41-year-old female patient with a solitary mass lesion located deep in the soft tissue of the anteromedial lower extremity. The physical examination revealed a palpable, elastic-hard, mobile and non-tender mass. Magnetic resonance imaging (MRI) showed an oval-shaped subcutaneous mass on contrast-enhanced T1-weighted sections. The initial MRI images suggested a schwannoma, but the tumour was later confirmed to be a leiomyoma after total enucleation. An immunohistochemical study was performed for differential diagnosis. Solitary mass lesions in the lower extremities can be mistaken for various types of tumours and misdiagnosed and require histopathological examination and good radiological imaging for differential diagnosis. Complete surgical excision is usually a safe and effective treatment for leiomyomas., Competing Interests: The authors have no conflict of interest.

Uterine fibroids (UFs), the most common tumors in women of reproductive age, are characterized by sex steroid-dependent growth and excessive deposition of extracellular matrix (ECM) surrounding UF smooth muscle cells. Women with symptomatic UFs experience heavy menstrual bleeding and consequent iron-deficiency anemia. They also have a risk of recurrent pregnancy loss, preterm birth, and cesarean delivery, indicating that UFs can negatively affect reproductive outcomes. Various types of immune cells, including innate and adaptive cells, are observed in UFs; however, the impact of these cells on the pathophysiology of UFs remains unclear. Inflammation may play important roles in the growth of UFs, and expression levels of proinflammatory and inflammatory cytokines, such as interleukin (IL)-1, IL-6, IL-10, TNF-α, and TGF-β, are upregulated in UFs. These cytokines play important roles in the interaction between growth factors and ECM that is regulated by the sex steroids estrogen and progesterone. Furthermore, proinflammatory mediators are upregulated in females with UFs, with higher expression levels in the endometrium with submucosal and intramural UFs than in the endometrium without UFs, indicating that these proinflammatory cytokines may impair endometrial receptivity, leading to implantation failure in in vitro fertilization programs. Hormonal treatments using gonadotropin releasing hormone analogs and the selective progesterone receptor modulator ulipristal acetate significantly shrink UFs and improve UF-related symptoms. These compounds can regulate local inflammation in UFs and adjacent myometrium. Controlling and improving local inflammation caused by UFs may represent a novel therapeutic strategy for UFs and potentially improve reproductive outcomes in women with symptomatic UFs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Hiroshi Ishikawa reports financial support was provided by Japan Society for the Promotion of Science. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Water intoxication is rarely seen in forensic practice and is typically associated with excessive water consumption, amphetamine intake, and child abuse. Iatrogenic water intoxication is rare but usually related to medical disputes. Here, we report a 44-year-old female was admitted to the hospital due to a 3-month history of excessive menstrual bleeding. B-ultrasound revealed multiple substantial intrauterine masses, leading to a diagnosis of multiple uterine fibroids. After admission, she underwent submucous myomectomy, endometrial resection, and transcervical resection of endometrial polyps. During the procedure, the patient suffered dizziness and chest tightness, her blood pressure decreased to 89/52 mmHg, and moist rales were heard in her both lungs; she died despite medical efforts. A forensic autopsy was performed and revealed severe pulmonary edema. Considering the patient's clinical history, acute water intoxication was considered to be the cause of death. This highlights the need for forensic pathologists to be vigilant of postoperative water intoxication, a rare complication in obstetrics, to ensure accurate assessments., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To evaluate the impact of high-intensity focused ultrasound (HIFU) ablation on the histopathological features of locally recurrent fibroids tissue., Methods: Patients who underwent transabdominal hysterectomy or myomectomy for uterine fibroids from January 1, 2021 to July 1, 2023 at a teaching hospital in China were enrolled in this prospective study. The patients who underwent surgery for local recurrence of uterine fibroids after HIFU ablation were categorized as the HIFU group, and patients who had not undergone HIFU ablation for uterine fibroids were the control group. Hematoxylin-eosin (HE) staining, Masson staining, and immunohistochemical staining were performed to analyze the counts of smooth muscle cells (SMCs), collagen content, microvascular count, and the expression levels of estrogen receptor (ER) and progesterone receptor (PR) in the fibroid tissue specimens., Results: The mean SMC counts in the HIFU and control groups were 337.68/field and 328.52/field respectively. The mean collagen content in the HIFU group and control group were 46.06% and 41.69% respectively. The mean microvessel counts in the HIFU group and control group were 13.66/field and 14.08/field respectively. The mean ER scores in the HIFU and control groups were 6.9 and 7.47 respectively, and the mean PR scores were 7.3 and 7.56 respectively. Overall, there were no significant differences in the SMC counts, collagen content, microvascular counts, and the ER and PR expression levels between the HIFU group and control group (p > 0.05)., Conclusions: HIFU ablation has no effect on the pathological characteristics of local recurrent fibroid tissue, and is an ideal non-invasive treatment option., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2024 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objective: This prospective observational study aims to demonstrate the clinical efficacy of dienogest in treating endometriomas with a maximum diameter of ≥4 cm., Methods: Patients ( n  = 81) with endometriomas (diameter of ≥4 cm) were enrolled and administered orally with dienogest (2 mg daily) and followed up for a year [Ethical approval code: 2020 Research 343]. Further, the efficacy was determined by recording the largest diameter and volume of the endometriomas, uterine volume, endometrial thickness, and the largest diameter of uterine fibroids in the patients during 0, 6, and 12 months. The pain symptoms were assessed using the Numerical Rating Scale (NRS), and the side effects of medication were monitored. With the consent, some patients underwent routine blood tests, and serum hormone, as well as Anti-Müllerian Hormone (AMH) levels were measured., Results: The dienogest treatment resulted in a significant reduction of the maximum diameter of these cysts from 50.5 mm to 41 mm in 6 months and 34 mm in 12 months. In addition, the volume of the cysts significantly decreased from 37.8 ml from baseline to 18.5 ml in 6 months and 11.8 ml in 12 months. Among 26 subjects with ultrasonic signs of endometrial polyps, 92.3% of cases displayed no polyps after 12 months. No significant changes were observed in the size of uterine fibroids and AMH levels. The NRS score showed a decrease from an average of 6.6-1.2 in 12 months., Conclusion: Dienogest could effectively reduce the diameter and volume of endometriomas with a maximum diameter of ≥4 cm, improving anemia, as well as pain symptoms and preserving ovarian function.

Abstract: Benign metastasizing leiomyoma (BML) is a rare disease associated with pelvic leiomyoma. We report 18 F-FDG and 68 Ga-FAPI PET/CT findings in a 51-year-old woman with multiple BMLs. The mass in the abdominopelvic cavity and other metastatic lesions showed highly increased 68 Ga-FAPI uptake, whereas uptake of 18 F-FDG in those lesions was low. Our report demonstrates that 68 Ga-FAPI PET/CT showed a different result in detecting BML to 18 F-FDG PET/CT, and 68 Ga-FAPI PET/CT may be a promising method for whole-body evaluate metastases., Competing Interests: Conflicts of interest and sources of funding: This work was supported by the National Natural Science Foundation of China (No. 82372005 and 81871391) and the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University (No. ZNJC202209). None declared to all authors., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Metastasis of clear cell renal cell carcinoma (clear cell RCC) to the gynecologic tract is infrequent, and involvement of the uterus is extremely rare. A review of the literature identified a total of 12 reported examples with metastasis to the uterine serosa (1), endometrium (5), cervix (5) and only one with metastasis to the myometrium. This report represents the first case of tumor-to-tumor metastasis involving a clear cell RCC with metastasis to a uterine leiomyoma. The patient was a 50-year-old woman status post-radical nephrectomy for newly diagnosed unilateral clear cell RCC (stage pT3a) with negative margins, who subsequently underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy for the incidental finding of multiple uterine masses measuring up to 14.5 cm suggestive of fibroid on pelvic ultrasound. The pathologic exam of the specimen was consistent with metastatic clear cell RCC (1.2 cm) to uterine leiomyoma, confirmed with keratin, vimentin, CD10, CA9, and PAX8 immunohistochemistry. The patient's postoperative course was uneventful, and no new lesions were identified at follow-up during the past 6 months., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The majority of esophageal subepithelial lesions originating from the muscularis propria (SEL-MPs) are benign in nature, although a subset may exhibit malignant characteristics. Conventional endoscopic resection techniques are time-consuming and lack efficacy for small SEL-MPs., Aim: To evaluate the efficacy and safety of ligation-assisted endoscopic submucosal resection (ESMR-L) following unroofing technique for small esophageal SEL-MPs., Methods: From January 2021 to September 2023, 17 patients diagnosed with esophageal SEL-MPs underwent ESMR-L following unroofing technique at the endoscopy center of Shenzhen People's Hospital. Details of clinicopathological characteristics and clinical outcomes were collected and analyzed., Results: The mean age of the patients was 50.12 ± 12.65 years. The mean size of the tumors was 7.47 ± 2.83 mm and all cases achieved en bloc resection successfully. The average operation time was 12.2 minutes without any complications. Histopathology identified 2 Lesions (11.8%) as gastrointestinal stromal tumors at very low risk, 12 Lesions (70.6%) as leiomyoma and 3 Lesions (17.6%) as smooth muscle proliferation. No recurrence was found during the mean follow-up duration of 14.18 ± 9.62 months., Conclusion: ESMR-L following roofing technique is an effective and safe technique for management of esophageal SEL-MPs smaller than 20 mm, but it cannot ensure en bloc resection and may require further treatment., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Over 70% of leiomyoma (LM) harbor MED12 mutations, primarily in exon 2 at c.130-131 (GG). Myometrial cells are the cell origin of leiomyoma, but the MED12 mutation status in non-neoplastic myometrial cells is unknown. In this study, we investigated the mutation burden of MED12 in myometrium. As traditional Sanger or even NGS sequencing may not be able to detect MED12 mutations that are lower than 0.1% in the testing sample, we used duplex deep sequencing analysis (DDS) to overcome this limitation. Tumor-free myometria (confirmed by pathology evaluation) were dissected, and genomic DNA from MED12 exon 2 (test) and TP53 exon 5 (control) were captured by customer-designed probe sets, followed by DDS. Notably, DDS demonstrated that myometrial cells harbored a high frequency of mutations in MED12 exon 2 and predominantly in code c.130-131. In contrast, the baseline mutations in other coding sequences of MED12 exon 2 as well as in the TP53 mutation hotspot, c.477-488 were comparably low in myometrial cells. This is the first report demonstrating a non-random accumulation of MED12 mutations at c.130-131 sites in non-neoplastic myometrial cells which provide molecular evidence of early somatic mutation events in myometrial cells. This early mutation may contribute to the cell origin for uterine LM development in women of reproductive age.

Spheroid culture is a 3D model that provides an improved replication of the in vivo microenvironment compared to traditional two-dimensional (2D) cultures. Invasion is a cellular outcome of utmost interest in cancer biology. In this protocol, we have devised an alternative strategy for evaluating cancer cell invasion in vitro, employing heterospheroids comprised of oral squamous cell carcinoma (OSCC), cancer-associated fibroblasts (CAF), and monocytes. These heterospheroids aim to mimic the tumor microenvironment (TME), including two relevant non-neoplastic cell types alongside the cancer cells. Each cell type was labeled with vital fluorescent markers emitting in distinct wavelengths before spheroid formation. Once formed, heterospheroids were seeded onto a layer of human leiomyoma-derived extracellular matrix in the upper compartment of a microporous membrane. Invasion was assessed in the z-axis using confocal microscopy. Digital images were obtained in the corresponding fluorescent channels at 10 µm intervals, covering a depth of 90 µm in the z-axis. Analysis was performed using freeware image software by calculating the integrated fluorescence intensity in each image and fluorescence channel. This approach enables a more dynamic analysis of cell invasion patterns in a multilayered context, as well as the examination of spatial co-localization of different cell types during invasion.

Evaluating gynecological mass lesions and reviewing their morphological characteristics based on their imaging appearance on magnetic resonance imaging (MRI), and correlating the MRI findings with histopathological findings, was the central theme of our study. This observational cross-sectional study was conducted on 60 female patients with clinically suspected gynecological mass lesions upon physical examination and/or ultrasonography, referred for MRI at a tertiary care hospital over a 1-year period between June 2022 and July 2023. A broad spectrum of differential diagnoses of gynecological masses was observed. In our study, the ratio of benign versus malignant disease was 1.6:1, with 37 benign and 23 malignant masses identified. The most common benign masses were uterine fibroids (n = 14; 23.3%), followed by endometriosis (n = 8; 13.3%), and ovarian dermoid cysts (n = 4; 6.6%). Among the malignant lesions, cervical cancer was the most common (n = 11; 18.3%), followed by endometrial carcinoma (n = 7; 11.6%), ovarian carcinoma (n = 3; 5%), and vaginal carcinoma (n = 2; 3%). Benign lesions mostly appeared hypo- to isointense on T1-weighted imaging and iso- to hyperintense on T2-weighted imaging, while malignant lesions appeared isointense on T1-weighted and hyperintense on T2-weighted imaging. Hemorrhage and fat were well appreciated on MRI and aided in diagnosis. T2 shading was present in 7 out of 8 endometriotic cysts, demonstrating a specificity of 100% and a sensitivity of 83%. For determining parametrial invasion in cervical carcinoma, MRI showed an accuracy of 91%, specificity of 100%, and positive predictive value, negative predictive value, and sensitivity of 100%, 75%, and 88%, respectively. In cases of endometrial carcinoma, MRI demonstrated a sensitivity and specificity of 87% and 91%, respectively, with a positive predictive value of 87% and a negative predictive value of 91% for identifying myometrial invasion greater than 50%. Compared to other modalities, MRI provided substantial information regarding uterine and adnexal masses and surrounding structures, facilitating accurate staging of lesions., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Lipoleiomyomas are rare variants of uterine leiomyomas rarely studied in the literature. We retrospectively studied 20 cases of uterine lipoleiomyomas showing that these lesions represent 0.7 % of all uterine leiomyomas diagnosed histologically. The patients did not experience any recurrence, and the tumors showed no morphological criteria of malignancy. They did not show significant p16, p53 or MiB1 expression. They showed diffuse and strong expression or estrogen and progesterone receptors by the smooth muscle component but without accompanying expression by the adipocytic component in one third of the cases. Androgen receptors were rarely expressed. They expressed in their majority HMGA2 in both components, while RB1 was usually not found. Fumarate hydratase (FH) is expressed by lipoleiomyomas, while they are negative for HMB45. In conclusion, uterine lipoleiomyomas are rare, benign tumors, characterized by HMGA2 expression, while they show no elements suspicious of malignancy, PEComas or FH deficiency. The role of RB1 in these tumors should be further explored., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Pulmonary benign metastasizing leiomyoma is an uncommon condition, predominantly affecting women of childbearing age with a history of uterine smooth muscle tumors and uterine leiomyoma surgery for uterine leiomyoma. The progression of PBML is often unpredictable and depends on the extent of lung involvement. Generally, most patients remain asymptomatic, but a minority may experience coughing, wheezing, or shortness of breath, which are frequently misdiagnosed as pneumonia. consequently, this presents significant challenges in both treatment and nursing care before diagnosis. This paper reports the case of a 35-year-old woman primarily diagnosed with acute hypoxic respiratory failure who was transferred from the emergency room to the intensive care unit. The initial computed tomography scan of the patient's lungs indicated diffuse interstitial pneumonia, but the sequencing of the alveolar lavage fluid pathogen macro did not detect any bacteria, fungi, or viruses. Moreover, the patient remained in a persistent hypoxic state before the definitive diagnosis. Therefore, our focus was on maintaining the airway patency of the patient, using prone ventilation, inhaling nitric oxide, monitoring electrical impedance tomography, and preventing ventilator-associated pneumonia to improve oxygenation, while awaiting immunohistochemical staining of the patient's biopsied lung tissue. This would help us clarify the diagnosis and treat it based on etiology. After meticulous treatment and nursing care, the patient was weaned off the ventilator after 26 days and transferred to the respiratory ward after 40 days. This case study may serve as a reference for clinical practice and assist patients suffering from PBML., (© 2024. The Author(s).)

Objective: To evaluate fertility outcomes based on size and number of intramural leiomyomas and outcomes after removal., Data Sources: Online searches: MEDLINE, ClinicalTrials.gov , PubMed, Cochrane Library, and PROSPERO Library from 1994 to 2023., Methods of Study Selection: A total of 5,143 studies were identified, with inclusion of 13 study groups., Tabulation, Integration and Results: Outcomes for size and number of leiomyomas were reported with clinical pregnancy rates and ongoing pregnancy or live-birth rates. In data sets with maximum leiomyoma diameters of less than 6 cm for study inclusion, women with leiomyomas smaller than 3 cm had lower clinical pregnancy rates than women without leiomyomas, with an odds ratio (OR) of 0.53 (95% CI, 0.38-0.76) and, for ongoing pregnancy or live-birth rates, an OR of 0.59 (95% CI, 0.41-0.86). The ORs for clinical pregnancy rates in women with intermediately-sized leiomyomas (those between 3 cm and 6 cm) were lower than in women without leiomyomas, with an OR at 0.43 (95% CI, 0.29-0.63) and, for ongoing pregnancy or live-birth rates, an OR at 0.38 (95% CI, 0.24-0.59). In data sets without exclusion for women with larger-sized leiomyomas, clinical pregnancy rates were lower for those with leiomyomas smaller than 5 cm compared with those without leiomyomas, with an OR of 0.75 (95% CI, 0.58-0.96). Women with leiomyomas larger than 5 cm showed no differences in clinical pregnancy rate compared with women without leiomyomas, with an OR of 0.71 (95% CI, 0.32-1.58). Although women with a single leiomyoma in any location had no differences in outcomes, those with more than one leiomyoma had lower clinical pregnancy rates and ongoing pregnancy or live-birth rates, with an OR of 0.62 (95% CI, 0.44-0.86) and 0.57 (95% CI, 0.36-0.88), respectively. The clinical pregnancy rate for women undergoing myomectomy for intramural leiomyomas was no different than those with intramural leiomyomas in situ, with an OR of 1.10 (95% CI, 0.77-1.59)., Conclusion: Even small intramural leiomyomas are associated with lower fertility; removal does not confer benefit. Women with more than one leiomyoma in any location have reduced fertility., Competing Interests: Financial Disclosure Elizabeth A. Pritts is a scientific advisor for Claria, an instrument company that makes morcellators for use during pelvic surgery. The other authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To study the specific mechanisms through which progesterone and selective progesterone receptor modulators impact the growth, synthesis, and accumulation of the extracellular matrix in uterine leiomyomas., Design: Laboratory study., Setting: Academic Research Institutions., Patients (s): This study involved reproductive-age women diagnosed with infertility associated uterine leiomyomas who underwent myomectomy either after selective progesterone receptor modulator ulipristal acetate (UA) treatment or without any pharmacological pretreatment. Control samples included healthy myometrium tissue (n = 100). Specimens were obtained from the Department of Reproduction and Gynecological Endocrinology and Biobank, Medical University of Bialystok, Poland., Interventions: Daily (5 mg/d) UA treated for 2 months (n = 100) and untreated (n = 150) patients with uterine leiomyomas or normal healthy myometrium (n = 100) tissue samples immediately after surgery were collected for transcriptional analysis and assessments., Main Outcome Measures: Progesterone-induced activation of the signaling pathways related to uterine leiomyomas extracellular matrix synthesis, deposition, and growth, as well as the expression profile of progesterone receptors in uterine leiomyomas, were assessed., Results: The results indicated that progesterone activated the transforming growth factor-β and SMAD3 signaling pathways and promoted proliferation, growth, and extracellular matrix remodeling in uterine leiomyomas by up-regulating SMAD3, transforming growth factor-β (TGF-β) receptor type 1 and II, Ras homolog A, vascular endothelial growth factor, or increasing the fibrosis-related gene collagen, type I, ɑ-1, and procollagen, type I, ɑ-1 production. In contrast, UA had inhibitory effects on these processes. The study also showed that both nuclear and membrane progesterone receptors play distinct roles in uterine leiomyoma pathobiology., Conclusions: We showed that both nuclear and membrane progesterone receptors were relevant in the treatment of uterine leiomyomas, especially when combined with selective progesterone receptor modulators. Novel therapeutic approaches combining selective progesterone receptor modulators with or without direct and indirect extracellular matrix targeting through selected specifically TGF-β and SMAD3 (SMAD3, TGF-β receptor types 1 and II, Ras homolog A, vascular endothelial growth factor, collagen, type I, ɑ-1) signaling pathways could therefore be a treatment option for uterine leiomyomas., Competing Interests: Declaration of Interests G.M. has nothing to disclose. D.P.T. has nothing to disclose. P.B. has nothing to disclose. O.L. has nothing to disclose. M.Sz. has nothing to disclose. M.S. has nothing to disclose. A.P.P. has nothing to disclose. M.K. has nothing to disclose. T.B. has nothing to disclose. M.Z.K. has nothing to disclose. A.P. has nothing to disclose. J.T. has nothing to disclose. X.L. has nothing to disclose. I.H. has nothing to disclose. S.W. has nothing to disclose. N.A.R. has nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To study the differences in immune cell profiles in uterine fibroids (Fibs) and matched myometrium (Myo)., Design: Observational study., Setting: Laboratory study., Patient(s): The study included tissue that was collected from 10 pairs of Fib and matched Myo from women, not on hormonal medications, undergoing hysterectomy and myomectomy., Intervention(s): None., Main Outcome Measure(s): Differences in immune cell and cytokine composition between Fib and matched Myo., Result(s): The mass cytometry analysis indicated that Fibs had a significantly higher number of natural killer (NK) cells, total macrophages, M2 macrophages, and conventional dendritic cells when compared with matched Myo from the same patient. In contrast, Fibs had significantly fewer CD3 and CD4 T cells when compared with Myo. The mass cytometry analysis results did not show any significant difference in the number of resting mast cells. Immunoflurorescent and immunohistochemical imaging confirmed the cytometry by time of flight results, showing a significantly higher number of NK cells, tryptase-positive mast cells indicative of mast cell activation, total macrophages, and M2 cells in Fibs and a significantly lower number of CD3 and CD4 T cells. The cytokine assay revealed significantly increased levels of human interferon α2, interleukin (IL)-1α, and platelet-derived growth factor AA and significantly lower levels of macrophage colony-stimulating factor and IL-1 receptor antagonist in Fib., Conclusion(s): Our results show significant differences in immune cell populations and cytokine levels between Fib and Myo. These differences could account for the increased inflammation in fib and a potential mechanism by which these tumors evade the immune system. These findings provide a foundation for further studies exploring the role of immune cells in Fib development., Competing Interests: Declaration of Interests D.S. has nothing to disclose. T.-D.C. has nothing to disclose. A.A. has nothing to disclose. A.L. has nothing to disclose. O.K. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the efficacy of mechanical resection through TruClear™ hysteroscopy in patients with endometrial polyps and submucosal fibroids., Study Design: Descriptive study. Place and Duration of the Study: Department of Obstetrics and Gynaecology, Shifa International Hospital, Islamabad, Pakistan, from June 2018 to 2022., Methodology: Patients diagnosed with endometrial polyps and submucosal fibroids confirmed by abdominal or transvaginal ultrasonography were included. Patients having a history of congestive cardiac failure, chronic kidney disease, and bleeding diathesis were excluded from the study. Data about the complete removal of pathology (endometrial polyps and submucosal fibroids), mean operating time, and postoperative complications such as bleeding and perforation were extracted. The follow-up was set up to 6 months after the procedure., Results: The average age of the 45 patients was 35.62 ± 7.46 years. Heavy menstrual bleeding was the most prevalent symptom, seen in 73.3% of cases, followed by irregular vaginal bleeding (IVB) in 11.1% of cases. The most frequent disease identified by sonography was a polyp in 21 (47%) instances, followed by submucosal fibroids in 12 (27%) cases, mixed pathology in 10 (22%), and malignancy in 2 (4%) cases. The overall average operative time was 36.46 ± 24.94 minutes. A hundred percent removal of lesions was observed in this study. Persistent symptoms were observed in 13% of patients after the surgery so they were treated with other interventions. The most common intervention was an intrauterine hormonal device. Intraoperative bleeding was observed in only one patient and was managed by intraoperative intrauterine balloon insertion. The recurrence rate was 8.9% (4/45)., Conclusion: TruClear™ hysteroscopy showed a major advantage in the successful and complete removal of the pathology, low operation time, and complications., Key Words: Fibroids, Hysteroscopy, Polyps, Endometrial resection, Menstrual bleeding.

Competing Interests: Declaration of Interests M.S.I. is supported, in part, by R01HD111243.

Leiomyoma is the most prevalent benign tumor of the female reproductive system. Benign metastasizing leiomyoma (BML) is a rare phenomenon that presents at distant sites, typically the lungs, exhibiting histopathological features similar to the primary uterine tumor in the absence of malignancy features in both. Fumarate hydratase-deficient uterine leiomyoma (FH-d UL) is an uncommon subtype among uterine smooth muscle tumors (0.5-2%), showing distinctive histomorphology and FH inactivation. The majority of FH-d ULs are sporadic, caused by somatic FH inactivation, while a minority of cases occur in the context of the hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome caused by germline FH inactivation. Metastasizing FH-d UL has not been well documented and might be under-reported. Here, we present two cases (21- and 34-year-old females) who presented with metastasizing FH-d UL after myomectomy/hysterectomy with histologically proven multiple lung metastases in both, in addition to multi-organ involvement in one case (cervical-thoracic lymph nodes, left kidney, perihepatic region, left zygomatic bone, and soft tissues). Pathological examination confirmed FH-d leiomyomas in the primary/recurrent uterine tumors, multiple lung lesions, and a renal mass. The minimal criteria for diagnosis of leiomyosarcoma were not fulfilled. Genetic testing revealed germline pathogenic FH variants in both cases (c.1256C > T; p.Ser419Leu in Case 1 and c.425A > G; p.Gln142Arg in Case 2). These novel cases highlight a rare but possibly under-recognized presentation of FH-d BML. Our study suggests that FH-d BML cases might be enriched for the HLRCC syndrome., (© 2024. The Author(s).)

Objective: Uterine fibroids increase the risk of preterm birth. The current study highlights uterine fibroid necrosis as a possible cause of (extreme) preterm birth., Study Design: Retrospective cohort study in one Dutch academic hospital. Cases were selected from the 526 participants of the MyoFert study (Netherlands Trial Register, NL7990), which included patients who presented between 2004 and 2018 and were between the age of 18 and 45 years at the time of diagnosis of uterine fibroids. Of these participants, 414 women became pregnant. A retrospective chart review of the first pregnancies was performed. The main outcomes were (imminent) preterm birth and signs of fibroid necrosis on ultrasound. In women with signs of fibroid necrosis, the following data were collected systematically: fibroid characteristics, clinical presentation, pregnancy outcome, and postpartum period., Results: In total, 66 women had a preterm birth (16 %, 66/414), of which 25 pregnancies ended between 16 and <24 weeks (38 %, 25/66) and 41 pregnancies ended between 24 and <37 weeks of gestation (62 %, 41/66). Of all women with preterm birth and available ultrasound images, 15 % (7/48) had fibroid necrosis at the time of labour. These seven patients, supplemented with three patients with fibroid necrosis during their first pregnancy and at least one episode of imminent preterm birth, are described in more detail. In these ten patients, the fibroids increased substantially in size during the first and second trimester, leading to severe abdominal pain in all patients and hospital admission in seven patients. Ultrasound examination of the fibroids showed heterogenic changes and focal transonic areas in the fibroid, which are characteristics that indicate fibroid necrosis. In four patients, myomectomy was performed and necrosis was confirmed histologically., Conclusion: Fibroid necrosis during pregnancy is likely associated with (imminent) preterm birth. Clinicians are advised to structurally evaluate the myometrium in pregnancy, specifically in women presenting with abdominal pain in the second trimester., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Aims: Giant esophageal leiomyoma usually requires a thoracotomy or thoracoscopic surgery, which is more invasive than an endoscopic treatment. The purpose of this study is to evaluate the efficacy and safety of piecemeal submucosal tunneling endoscopic resection (P-STER) for giant leiomyoma originating from the muscularis propria (MP) layer of the esophagus., Methods: This is a retrospective study. Patients with giant esophageal leiomyoma (transverse diameter ≥ 3 cm) who underwent P-STER were enrolled from November 2012 to May 2023. Clinical data and results were investigated., Results: A total of 16 patients were enrolled for analysis. The lesion mean transverse diameter and longitudinal diameter were 4.22 ± 1.20 cm and 6.20 ± 1.57 cm, respectively. Our mean operation time was 195.38 ± 84.99 min. The mean number of piecemeal resected was 4.31 ± 2.36. An adverse event noted was an esophageal fistula that occurred in one case (6.25%) and was treated conservatively. The mean length of hospital stay was around 11.81 ± 7.30 days. The mean total hospitalization cost was U.S. dollars (USD) $5976.50 ± 2866.39. No recurrence or metastasis was found during the follow-up period., Conclusions: P-STER can be an effective and safe treatment for giant leiomyoma originating from the MP layer of the esophagus., Competing Interests: Conflict of interest We declared that no conflicts of interest or financial ties to disclose., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Rationale: Primary ovarian leiomyoma is a rare benign tumor. The exact histological origin and pathogenesis of primary ovarian leiomyoma are still unclear, while its preoperative imaging diagnosis is often challenging and prone to misdiagnosis. The study aims to elucidate the diagnosis of primary ovarian leiomyoma and to distinguish it from fibroma., Patient Concerns: A 34-year-old female was admitted to the hospital with complaints of pelvic mass found for one year. One years ago, the patient went to a local hospital for examination due to irregular menstruation., Diagnoses: The ultrasound report of the patient showed ovarian teratoma. The postoperative pathological results showed ovarian leiomyoma and calcification., Interventions: The patient underwent laparoscopic right ovarian leiomyoma resection., Outcomes: The patient was discharged home three days after surgery. At the most recent follow-up (five months after operation) of the patients, ultrasound was performed and no abnormal echoes were suggested in the adnexal region., Lessons: In the diagnosis of primary ovarian leiomyoma, our case emphasizes the importance of microscopic features as an effective approach to distinguish it from ovarian fibroma, leiomyosarcoma, and stromal tumors. Additionally, personalized treatment should be considered based on the patient age and fertility needs., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Leiomyoma is a benign tumour of smooth muscle origin. Leiomyoma arising in major salivary gland is under-reported. We report a case of a woman in her 40s with a submandibular gland tumour which represented a diagnostic challenge during preoperative assessment. The core needle biopsy of submandibular gland tumour revealed a spindle cell tumour suggestive of an undifferentiated tumour. As a malignancy could not be excluded, the submandibular gland tumour was removed en bloc with surrounding lymph nodes in level Ib of the neck. Leiomyoma may be included in the differential diagnosis of spindle cell salivary gland tumours, particularly when there are no signs of infiltration and preoperative investigations are inconclusive., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Abstract: Primary vaginal squamous cell carcinoma (SCC) is extremely rare. Primer vaginal SSC developed by the coeffect of leiomyoma and Human papillomavirus (HPV) is presented. We report a case of primary vaginal SCC in a 62-year-old woman presenting dyspareunia. On macroscopic examination, the surface of the operation material was partly ulcerated. On the cut surface, the material was solid, firm, white, and whorled. Microscopic examination revealed leiomyoma ulcerating the mucosa and SCC at the base of the ulcer. The case, in which vaginal SCC developed in the vagina due to the irritation of the leiomyoma, as well as its relationship with HPV, is important to be the first to our knowledge., (Copyright © 2023 Copyright: © 2023 Journal of Cancer Research and Therapeutics.)

Background and Aims: This pilot study aimed to evaluate safety and tissue sampling from subepithelial lesions (SEL) in the upper gastrointestinal tract with a novel electric motor driven endoscopic ultrasonography (EUS)-guided 17-gauge (G) size core needle biopsy (CNB) instrument., Methods: An investigator-led prospective open label, performance and safety control study, including seven patients (female n  = 4, median 71 y, range 28-75) with a determined SEL (median size 30 mm, range 17-150 mm) in the upper digestive tract (stomach n  = 6, duodenum n  = 1) were eligible and later followed up 14 days after index procedure. All investigations were completed according to protocol with three FNB 22-G passes with four fanning strokes and two EndoDrill ® 17-G passes with three fanning strokes., Results: Quality of samples as 'visible pieces' (>5 mm): FNB ( n  = 5/7) (fragmented/blood imbibed n  = 1, poor tissue quantity n  = 1) compared with 17-G CNB ( n  = 7/7). Histological result which led to final diagnosis (leiomyoma n  = 2, adenocarcinoma n  = 1, schwannoma n  = 1, neuroendocrine tumour n  = 1, desmoid tumour n  = 1 and gastrointestinal stromal tumour (GIST) n  = 1) could be obtained with the 17-G CNB instrument in all seven patients. FNB technique reached correct diagnosis in six patients. No serious adverse event were recorded., Conclusions: By using an electric driven 17-G biopsy device, a true cylinder of core tissue can be obtained in one single puncture from the area of interest reducing the need for a second sampling. The absolute benefit of EUS-guided CNB is that the sample can be handled and histologically prepared in the same manner as standard percutaneous core needle sample, e.g., breast and prostate cancer.

Background: The cutoff value for stereomicroscopic on-site evaluation (SOSE) in endoscopic ultrasound-guided tissue acquisition (EUS-TA) has high diagnostic sensitivity when a Franseen needle is employed for upper gastrointestinal subepithelial lesions (SELs) (stereomicroscopically visible white core [SVWC] ≥ 4 mm)., Aim: We aimed to determine whether high diagnostic sensitivity could be obtained when EUS-TA was performed using a Fork-tip needle., Methods: Twenty-one patients were prospectively registered. Patients underwent EUS-TA using a Fork-tip needle for upper gastrointestinal SELs at Kitasato University Hospital between January and November 2022. Punctures were made twice using the needle, and SOSE was conducted for each specimen. Blood and physical examination were performed to assess adverse events. Pathological diagnosis was made using hematoxylin and eosin-stained sections and immunohistochemical staining. Statistical comparisons were completed using Fisher's exact tests., Results: The diagnostic rate of EUS-TA was 100% (21/21 cases). The final diagnosis was gastrointestinal stromal tumor in 17 (81.0%) and leiomyoma in 4 (19.0%) patients. SOSE was conducted on all 42 punctures, and the tissue sampling rate was 100% (42/42 punctures). Specimens with SVWC ≥ 4 mm were collected in 97.6% punctures (41/42 punctures) and the diagnostic sensitivity for these specimens was 100% (41/41 punctures), which is significantly higher (p < 0.0238) compared to the absence of cutoff value (diagnostic sensitivity of 0%). No EUS-TA-related adverse events occurred., Conclusions: EUS-TA combined with SOSE for upper gastrointestinal SEL using a fork-tip needle had a high diagnostic rate, and the cutoff value of SVWC ≥ 4 mm had high diagnostic sensitivity., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)