Search Results (74)

Background/Objectives: Fallopian tube endometriosis is frequently underreported due to its nonspecific presentation, limitations in imaging detection, and the fact that histologic diagnosis often requires the submission of the entire fallopian tube for microscopic analysis, which is not routinely performed. This study investigates the prevalence of fallopian tube endometriosis on histologic evaluation in patients undergoing laparoscopic salpingectomy for benign gynecologic conditions, and evaluates its association with intraoperative findings such as endometriomas, hydrosalpinx, and peri-tubal adhesions. Methods: A prospective cohort study was conducted from September 2021 to December 2024 at NYU Grossman Long Island School of Medicine, including 80 women ages 18–65 years undergoing unilateral or bilateral salpingectomy. Fallopian tubes were entirely submitted for histologic examination and were evaluated in cross-sections for presence of endometriosis. The association between the presence of fallopian tube endometriosis, the stage of endometriosis, the presence of endometriomas, hydrosalpinx, and tubal adhesions was analyzed, with significance defined as p < 0.05. Results: 47 women were found to have biopsy-proven pelvic endometriosis (58.75%). The prevalence of fallopian tube endometriosis was 42.50% (34/80) in the total study population and 72.34% (34/47) among patients with pelvic endometriosis. The most commonly involved layer was the serosa (75.5%), followed by the muscularis (46.9%) and mucosa (18.4%). Fallopian tube endometriosis was significantly associated with endometriomas (p < 0.0001), hydrosalpinx (p < 0.0001), and tubal adhesions (p < 0.0001). It was also strongly correlated with disease severity, with 92.9% of patients with stage 4 endometriosis exhibiting tubal involvement. Conclusions: Fallopian tube endometriosis is more prevalent than previously recognized and shows a strong association with advanced-stage endometriosis, endometriomas, hydrosalpinx, and tubal adhesions. Full article

Fisetin is a naturally occurring flavonoid, a type of polyphenol found in fruits and vegetables such as strawberries, apples, persimmons, and onions. It has gained increasing attention for its antioxidant properties (enhancement of SOD1 and CAT activity and reduction of ROS), anti-inflammatory effects (suppression of NF-κB signaling), and senotherapeutic activity (senolytic and senomorphic effects). Although numerous studies have examined fisetin in the context of aging and chronic diseases, its role in women’s reproductive health has not been systematically explored. Mechanistically, fisetin regulates several pathophysiological processes, including ovarian aging, fibrosis, angiogenesis, and hormonal regulation, suggesting its potential relevance to female reproductive health and disease. Indeed, emerging evidence indicates that fisetin may support ovarian function and hormonal balance, modulate fibrosis and metabolism in benign gynecologic conditions, and suppress cell growth in gynecologic cancers. Early-phase clinical studies in non-gynecologic conditions suggest an acceptable safety profile, although evidence in reproductive health remains absent. This review summarizes current experimental and clinical evidence, identifies critical gaps in mechanistic understanding, and discusses future directions for advancing fisetin as a promising non-hormonal therapeutic option in reproductive health and diseases. Full article

Introduction: Natural Orifice Transluminal Endoscopic Surgery (NOTES) via the vagina (vNOTES) has recently appeared on the gynecology horizon as a fresh minimally invasive approach. Although vNOTES for benign adnexal conditions is being increasingly employed, very limited experiences exist for its application in ovarian tumors. In this review, the current state of vNOTES applicability for borderline ovarian tumors (BOTs) and estimated early-stage epithelial ovarian cancer (EOC) is assessed. Methods: A narrative literature review was performed to examine operative viability, perioperative safety and functional outcomes, and oncologic details as documented for patients with ovarian tumors undergoing vNOTES. Results: In the current literature, vNOTES has been utilized for adnexectomy, hysterectomy, infracolic omentectomy, peritoneal biopsies, and sampling of selective pelvic lymph nodes in carefully selected patients. The perioperative parameters—bleeding, perioperative pain, and length-of-stay indicators—have been satisfactory with minimal complications. For BOT, vNOTES can meet the requirements for all surgical goals except lymphadenectomy for metastasis evaluation for systemic management. In this context, lymphadenectomy is not necessary for BOT and therefore is no contraindication for vNOTES. However, for invasive EOC, this is a significant drawback as there is no lymphadenectomy for the evaluation and management for this complex subgroup. The oncology follow-up is prematurely limited and is heterogeneous and underpowered. Conclusions: Based on current available data, vNOTES is possible in a selected group of patients with borderline ovarian tumors and in patients with adnexal lesions that are believed to be in early-stage disease based upon imaging studies. For the treatment of invasive epithelial ovarian cancer, vNOTES should not be considered an independent staging procedure at any FIGO stage, but it might find a supplemental place in the setting of a hybrid procedure in a highly selected group of patients in an experienced center. Full article

Bartholin gland carcinoma (BGC) is a rare malignancy, comprising 3–7% of vulvar cancers and <1% of gynecologic tumors. Due to its low incidence, high-level evidence is lacking, and management is largely extrapolated from vulvar cancer guidelines. This comprehensive narrative review synthesizes current evidence on BGC, emphasizing histotype-specific features, diagnostic criteria, molecular profiling, and treatment strategies. The three most common subtypes are squamous cell carcinoma, adenoid cystic carcinoma (AdCC), and adenocarcinoma. HPV-associated tumors tend to occur in younger women and carry favorable prognoses. Accurate diagnosis requires exclusion of metastases and integration of clinical, imaging, and immunohistochemical data, including p16/HPV for squamous tumors, MYB/MYBL1 fusions for AdCC, and CK20/CDX2/SATB2 for intestinal-type adenocarcinoma. Approximately 50% of cases are diagnosed at an advanced stage due to misclassification as benign cysts or abscesses. Nodal metastasis occurs in >40% of cases, with histotype influencing prognosis. Adenocarcinoma and node-positive disease independently predict worse survival. Treatment hinges on complete surgical excision with 2–3 mm margins, bilateral groin evaluation, and histology-tailored adjuvant therapy. Emerging data support the use of immune checkpoint inhibitors in squamous BGC and targeted agents (e.g., mTOR/CDK4/6 inhibitors) in adenocarcinoma. We propose a practical molecular testing algorithm and highlight the urgent need for prospective, multinational collaboration to establish BGC-specific guidelines. Full article

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, often diagnosed at an advanced stage due to its asymptomatic progression. The high recurrence rate and development of platinum-based chemotherapy resistance contribute to its poor prognosis. Despite advancements in molecular profiling, predictive biomarkers for chemotherapy response and recurrence risk remain limited. In this study, we developed OvarianTag™, a biomarker panel integrating apoptosis and necroptosis pathways, to predict chemotherapy benefit and disease progression in EOC patients. This observational study was conducted in two phases. In the first phase, 45 patients were recruited, and RNA was extracted from fresh ovarian tissues (normal, benign, and malignant). qRT-PCR was performed to assess the relative expression of genes involved in apoptosis and necroptosis-regulated cell death pathways. Machine learning algorithms were applied to identify the relevant prognostic markers, leading to the development of OvarianTag™. In the second phase, 55 additional EOC patients were included, and their formalin-fixed, paraffin-embedded (FFPE) tumor samples were analyzed using qRT-PCR. The classifier algorithm incorporated hierarchical clustering to stratify patients based on gene expression profiles. Significant differences in TNFRSF10C/TRAIL-R3, TNFRSF10B/TRAIL-R2, and CASP8 expression levels were observed between patient groups. CASP8 downregulation was strongly correlated with platinum resistance and a poor prognosis. Decision tree models achieved 83.3% accuracy in predicting platinum response and 79.2% accuracy in recurrence risk stratification. The OvarianTag™ classifier demonstrated high sensitivity and specificity in identifying high-risk patients, supporting its potential as a prognostic tool. The OvarianTag™ panel provides a novel approach for risk stratification in EOC, integrating apoptosis and necroptosis pathways to refine chemotherapy response prediction and recurrence risk assessment. This molecular assay has the potential to guide personalized treatment strategies, enhancing clinical decision-making and improving patient outcomes. Further validation in independent cohorts is warranted to establish its clinical utility. Full article

Uterine adenosarcoma with sarcomatous overgrowth (ASSO) is an exceptionally rare and aggressive subtype of uterine sarcomas, characterized by high mitotic activity, deep myometrial invasion, and an elevated risk of recurrence and metastasis. We report the case of a 79-year-old institutionalized woman with a history of hypertension, type 2 diabetes, chronic hepatitis B, and mild Alzheimer’s disease. During routine hepatic ultrasound surveillance, an incidental 26 mm endometrial lesion was detected. Initial diagnostic hysteroscopy revealed a benign endometrial polyp. However, due to the patient’s institutionalization and absence of gynecologic symptoms, no specialized follow-up was conducted. Four years later, she presented with profuse postmenopausal bleeding. Imaging revealed a markedly enlarged uterus with a 12–13 cm heterogeneous endometrial mass containing cystic and hemorrhagic areas, demonstrating diffusion restriction and significant contrast enhancement on MRI, with no radiologically suspicious lymphadenopathy. Hysteroscopy demonstrated a giant polyp with a broad implantation base; histology suggested sarcomatous transformation. Definitive diagnosis after total hysterectomy with bilateral salpingo-oophorectomy confirmed high-grade ASSO with homologous sarcomatoid overgrowth, consistent with endometrial stromal sarcoma. This case illustrates the progressive malignant transformation of an initially benign-appearing lesion in a patient with significant comorbidities and limited follow-up. It underscores the importance of clinical vigilance, regular monitoring, and interdisciplinary coordination in the evaluation of uterine enlargement in asymptomatic postmenopausal women. Full article

Background: Uterine leiomyomas are the most common pelvic tumors in women of reproductive age. There is no clear conclusion in the literature regarding the pathophysiology of these conditions. STAT proteins stimulate the transcription of target genes. STAT-3 leads to an increase in VEGF levels and plays a role in tumorigenesis. IL-26 and other cytokines are vital immune response mediators. Cytokine dysregulation affects the immune response of various organs and tissues, making them prone to various diseases, such as inflammation, infection, and tumors. Methods: In the present study, we aimed to determine whether STAT-3 and IL-26 play a role in the development of uterine leiomyoma. This case–control study included 38 patients who underwent hysterectomy due to uterine leiomyoma and 30 patients who underwent hysterectomy due to non-organic benign gynecological causes other than myoma. Sections from the myometrium of the control group and the leiomyoma tissue of the case group were subjected to immunohistochemical staining for STAT-3 and IL-26. Results: When the uterine tissue sections of the control group incubated with STAT-3 were examined under a light microscope, the smooth muscle and fibroblast cells in the myometrium were STAT-3-negative, while the number of smooth muscle and fibroblast cells showing strong STAT-3-staining in the leiomyoma sections was high. When the uterine tissue sections incubated with IL-26 were examined under a light microscope, the normal smooth muscle and fibroblast cells in the control group were IL-26-negative, while there was an increase in the number of cells showing strong IL-26-staining in the leiomyoma smooth muscle and fibroblast cells. Conclusions: Our findings show that STAT-3 and IL-26 levels are significantly increased in uterine leiomyomas, and this increase may play a role in the growth and progression of uterine fibroids. The current results may enable the development of innovative treatment options, as they demonstrate the role of novel pathways in the formation of uterine fibroids. Full article

Background and Objectives: Hysterectomy is a common non-obstetric procedure. Minimally invasive techniques, such as laparoscopy and robot-assisted surgery, have replaced open surgery for benign gynecologic conditions. Robotic surgery offers reduced blood loss and shorter hospital stays but is limited by high costs. Articulating laparoscopic instruments aim to replicate robotic dexterity cost-effectively. However, comparative data on these two approaches in hysterectomy are limited. Materials and Methods: This multicenter study analyzed the outcomes of hysterectomies for benign gynecological diseases using articulating laparoscopic instruments (prospectively recruited) and robot-assisted surgery (retrospectively reviewed). The surgeries were performed by minimally invasive gynecological surgeons in South Korea, Japan, and Taiwan. The baseline characteristics, operative details, and outcomes, including operative time, blood loss, complications, and hospital stay, were compared. Statistical significance was set at p < 0.05. Results: A total of 151 patients were analyzed, including 67 in the articulating laparoscopy group and 84 in the robot-assisted group. The operating times were comparable (114.9 vs. 119.9 min, p = 0.22). The articulating group primarily underwent dual-port surgery (79.1%), whereas the robot-assisted group required four or more ports in 71.4% of the cases (p < 0.001). Postoperative complications occurred in both groups, without a significant difference (9.0% vs. 3.6%, p = 0.17). No severe complications or significant differences in the 30-day readmission rates were observed. Conclusions: Articulating laparoscopic instruments provide outcomes comparable to robot-assisted surgery in hysterectomy while reducing the number of ports required. Further studies are needed to explore the learning curve and long-term impact on surgical outcomes. Full article

Background: Peritoneal stretching from CO₂ insufflation is a primary mechanism of pain associated with laparoscopy. Cyclooxygenase-2 inhibitors are promising anti-inflammatory and analgesic agents. This study aimed to evaluate the effect of celecoxib on postoperative pain reduction and associated changes in peritoneal gene expression after laparoendoscopic single-site (LESS) surgery for benign gynecologic disease. Methods: In this randomized, double-blind, placebo-controlled pilot study, 70 patients were randomly assigned to receive either celecoxib or placebo (400 mg) 40 min before surgery. Peritoneal tissues were collected before and after CO₂ insufflation. We analyzed changes in expressions of prostaglandin I₂ synthase, prostaglandin E synthase (PTGES), PTGES3, aldo-keto reductase family 1 member C1, and 15-hydroxyprostaglandin dehydrogenase (HPGD). Numeric Rating Scale (NRS) pain scores were also compared between groups. Results: A total of 62 patients completed the study: 30 in the celecoxib group and 32 in the placebo group. The mean CO₂ exposure time was 60.4 min. In a quantitative real-time polymerase chain reaction analysis, HPGD mRNA expression significantly increased after surgery in patients exposed to CO₂ for more than 60 min. Patients treated with celecoxib showed a significantly higher rate of grade 3 expression (83.3% vs. 37.5%; p = 0.01) and a level 2 increase in HPGD expression on in situ hybridization (58.3% vs. 12.5%; p = 0.01), despite no significant difference on immunohistochemistry. Moreover, celecoxib effectively reduced NRS pain scores compared to placebo. Conclusions: In this pilot study, celecoxib appeared to reduce postoperative pain and was associated with increased HPGD mRNA expression in the peritoneal tissue of patients with prolonged CO₂ exposure during LESS surgery. These exploratory findings warrant confirmation in larger trials with functional validation of HPGD expression (ClinicalTrials.gov, NCT03391570). Full article

Background/Objectives: Endometriosis and high-grade serous ovarian cancer (HGS-OC) share common features within the peritoneal immune microenvironment, yet they exhibit divergent clinical outcomes. This study aimed to dissect the immune–metabolic landscape of the peritoneal cavity in patients with endometriosis and ovarian cancer by evaluating macrophage polarization, intracellular signaling pathways, and iron-driven oxidative stress. Methods: A prospective cohort study enrolled 40 patients with endometriosis, 198 with ascitic ovarian cancer (178 HGS-OC), and 200 controls with benign gynecological conditions. Peritoneal and peripheral blood samples were analyzed via flow cytometry for macrophage (M1/M2) polarization markers, mTOR/AKT expression, and glucose uptake. Inflammatory markers (IL-6, CRP), oxidative stress (ROS), and iron metabolism parameters (hepcidin, ferritin, transferrin, serum/free iron) were quantified. Results: HGS-OC displayed a predominance of M1-polarized tumor-associated macrophages (TAMs) (CD14⁺/CD80⁺/Glut1⁺) and a high M1/M2 ratio (2.5 vs. 0.8 and 0.9; p = 0.019), correlating positively with IL-6 (p = 0.015), ROS (p = 0.023), hepcidin (p = 0.038), and ferritin (p = 0.043). Conversely, endometriosis showed a dominant M2 profile (CD14⁺/CD163⁺), elevated intracellular mTOR and AKT expression in both TAMs and epithelial cells (p < 0.01), and significantly higher ascitic ROS and free iron levels (p = 0.047 and p < 0.0001, respectively). In endometriosis, the M1/M2 ratio correlated inversely with free iron (p = 0.041), while ROS levels were directly associated with iron overload (p = 0.0034). Conclusions: Endometriosis exhibits a distinct immune–metabolic phenotype characterized by M2 macrophage predominance and iron-induced oxidative stress, contrasting with the inflammatory, M1-rich profile of HGS-OC. These findings suggest that iron metabolism and macrophage plasticity contribute to disease persistence in endometriosis and may inform future immunomodulatory strategies. Full article

Background/Objectives: Adenomyosis is a benign gynecological disorder associated with abnormal uterine bleeding, dysmenorrhea, and subfertility. Its pathogenesis has not yet been elucidated. The most widely accepted theory points to repeated mechanical or hormonal stress at the endometrial–myometrial interface, leading to activation of the tissue injury and repair (TIAR) mechanism. Studies suggest that the immune system may play a role in disease pathogenesis, but inconsistencies persist due to differences in studied samples and evaluated menstrual cycle phases. The goal of our study was to apply a novel technique (multiplex) to investigate different immune cell phenotypes in uteri from adenomyosis patients according to the cycle phase. Methods: This study analyzed immune cell populations in adenomyotic uteri using immunohistochemistry and multiplex immunofluorescence on 30 adenomyotic and 15 healthy hysterectomy samples. Results: Compared to eutopic endometrium, transitional and adenomyotic lesions displayed reduced immune infiltrates, particularly T cells, NK cells, B cells, macrophages, and dendritic cells. Conversely, mast cells were significantly elevated in transitional lesions. Conclusions: The present study suggests mast cell implication in adenomyosis development and pain, through their implication in tissue remodeling, angiogenesis, and neurogenic inflammation. Transitional lesions highlighted the progressive nature of adenomyosis, supporting the TIAR hypothesis. These findings emphasize the importance of mast cells in disease progression and underscore the need for further studies to explore immune-targeted therapies. Full article

Background: Ovarian cancer remains the most lethal gynecological cancer, primarily due to its asymptomatic nature in early stages and consequent late diagnosis. Early detection improves survival, but current biomarkers lack sensitivity and specificity. Cell-free DNA (cfDNA) released from tumor cells captures tumor-associated epigenetic alterations and represents a promising source for minimally invasive biomarkers. Among these, aberrant DNA methylation occurs early in tumorigenesis and may reflect underlying disease biology. This study aimed to investigate genome-wide cfDNA methylation profiles in patients with ovarian cancer, benign ovarian conditions, and healthy controls to identify cancer-associated methylation patterns that may inform future biomarker development. Results: We performed genome-wide cfDNA methylation profiling using cell-free methylated DNA immunoprecipitation sequencing (cfMeDIP-seq) on plasma samples from 40 patients with high-grade serous ovarian carcinoma, 38 patients with benign ovarian conditions, and 38 healthy postmenopausal women. A total of 536 differentially methylated regions (DMRs) were identified between ovarian cancer and controls (n = 76), with 97% showing hypermethylation in ovarian cancer. DMRs were enriched in CpG islands and gene bodies and depleted in repetitive elements, consistent with known cancer-associated methylation patterns. Fifteen genes showed robust hypermethylation across analyses. These genes exhibited methylation across intronic, exonic, and upstream regulatory regions. Separate comparisons of ovarian cancer to each control group (benign and healthy) supported the reproducibility of these findings. Gene Ontology enrichment analysis revealed enrichment in gland development, embryonic morphogenesis, and endocrine regulation, suggesting biological relevance to ovarian tumorigenesis. Conclusions: This study identifies consistent cfDNA hypermethylation patterns in ovarian cancer, affecting genes involved in developmental regulation and hormone-related processes. Our findings underscore the potential of cfMeDIP-seq for detecting tumor-specific methylation signatures in plasma and highlight these 15 hypermethylated genes as biologically relevant targets for future studies on cfDNA methylation in ovarian cancer. Full article

Adenomyosis is a benign gynecologic disease that mainly affects women aged 30–50 years old. Background: This pathology is characterized by glands and stroma of the endometrium that enter the myometrium and is confirmed through histopathological examination after hysterectomy. Transvaginal ultrasound is the most accepted imaging approach for the diagnosis and classification of adenomyosis. Existing medical treatments are not curative and are associated with several side effects. Uterine artery embolization is an alternative treatment for controlling the symptoms of adenomyosis with less trauma while preserving the uterus. Methods: The aim of our study was to observe the utility of uterine artery embolization (UAE) compared to hysterectomy in specific cases of adenomyosis. A retrospective cohort study was carried out between February 2024 and April 2025. We included 52 patients in our study: 27 opted for hysterectomy, while the other 25 chose to receive uterine artery embolization between January 2017 and December 2018. Clinical follow-up was assessed using a questionnaire regarding symptomatic changes in menorrhagia, pelvic pain, and quality of life before and after the surgical procedure. Statistical analyses were performed. Results: Patients opted for hysterectomy in cases of severe abnormal uterine bleeding before surgery that severely affected quality of life (p < 0.03 and p < 0.001). After surgery, pelvic pain improved for women who underwent UAE, but patients also reported no pelvic pain after hysterectomy. Furthermore, mild to moderate abnormal uterine bleeding was reported in cases of UAE, and bleeding stopped completely for women who had their uterus removed (p < 0.001). Quality of life improved for both groups and was reported as being good after the interventions. Conclusions: Embolization remains an alternative therapeutic option in adenomyosis but not a substitute for hysterectomy. This was concluded based on a case-by-case evaluation, depending on the desire for pregnancy, with a focus on improved clinical outcomes. Full article

CEA (carcinoembryonic antigen), which belongs to the acidic glycoproteins, is primarily produced during the fetal period. Following this stage, low levels of CEA are considered physiological, while elevated concentrations are associated with a range of both benign and malignant pathologies. The liver plays a key role in CEA metabolism. The most common material used to determine CEA concentrations by various techniques is blood, and measuring CEA in peritoneal fluid holds clinical value. CEA has been found to contribute to carcinogenesis, metastasis, and treatment resistance. Therefore, its serum concentration is widely used in oncology for prognosis, disease monitoring, and recurrence detection, despite its limited sensitivity and specificity, which prevent it from serving as a standalone diagnostic tool. Elevated serum CEA levels are linked to worse outcomes in lung, liver, breast, colorectal, and pancreatic cancers. Imaging and multi-marker panels that include CEA enhance diagnostic accuracy, but its role remains context-dependent and varies by cancer type. CEA levels in peritoneal fluid have been explored as a potential marker for detecting malignancy and predicting recurrence, particularly in gastric, gynecological, and colorectal cancers. Peritoneal fluid CEA has also been proven useful in differentiating the etiology of ascites. While cytology remains the standard for the detection of tumor cells in body fluids, its limited sensitivity provides a strong rationale for incorporating peritoneal fluid CEA measurements as a complementary diagnostic tool, potentially alongside other markers. Additionally, the lack of standardized measurement techniques and cut-off values underlines the methodological challenges that still need to be addressed in future research for both serum and peritoneal CEA levels. Full article

Objective: Oophorectomy is a common procedure for benign uterine conditions, historically recommended for women aged 40–45 and older due to the belief that ovarian preservation had no significant benefits. This review evaluates the literature on the optimal age for oophorectomy in women with benign conditions to assess its risks and benefits and guide clinical decision-making. Methods: A narrative review was conducted using a literature search of articles published between January 2000 and February 2025, focusing on the age-related outcomes of ovarian conservation versus removal. Results: Oophorectomy remains a complex decision in gynecological surgeries, especially among perimenopausal and postmenopausal women. Evidence supports ovarian conservation in average-risk women, highlighting reduced risks of cardiovascular disease, osteoporosis, and all-cause mortality. Conversely, oophorectomy is favored in high-risk populations, such as BRCA mutation carriers, due to significantly lower risks of ovarian and breast cancers. Despite declining rates, unnecessary oophorectomies persist, influenced by age, socioeconomic status, comorbidities, and surgical approaches. The development of a risk stratification tool offers promise for improving individualized decision-making. Conclusions: The decision to perform oophorectomy for benign conditions should be personalized, balancing patient-specific factors to optimize outcomes and long-term health benefits. Full article