Search Results (865)

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

Background: Systemic inflammatory factors may be altered by periodontitis and/or COVID-19, potentially increasing the risk of adverse pregnancy outcomes, a relationship that remains unclear. Objective: This study aimed to identify associations between periodontitis and COVID-19 during pregnancy, evaluating the influence of dental care on obstetric variables through set theory and probability. Methods: A quantitative, cross-sectional, and correlational study was conducted in two phases. The first phase analyzed 156 medical records from 5 institutions, including gynecological and periodontal data; the second phase examined 104 records from a single institution selected for data completeness (2020–2021). Descriptive statistics, bivariate analysis, chi-square tests, and odds ratios were applied. Set operations (union, intersection) and relative probabilities were calculated using R and Excel. Sets represented dental care, dental disease, COVID-19 diagnosis, gestational age, neonatal weight, and complications. Results: In Phase 1, 37% of pregnant women were COVID-19-positive, 44% vaccinated, 51.9% underwent cesarean section, and 5.12% had periodontitis. In Phase 2, 76 pregnant women did not receive dental care, while 28 did; among them, 6 were COVID-19-positive. Mean neonatal weight ranged from 2336 g (dental care) to 2271 g (no dental care). COVID-19-positive pregnant women showed fewer complications and a higher proportion of normal-weight neonates. Gingivitis was the most frequent periodontal condition (75%). No statistically significant differences were observed between the analyzed sets. Conclusions: no direct relationship was found between periodontitis and neonatal weight in COVID-19-positive cases. Dental care did not influence maternal–fetal outcomes. The methodology provides an innovative framework for clinical analysis through mathematical abstraction. Full article

Studies have widely indicated that the composition of maternal nutrition and diets might affect offspring health later in life. Studies on paternal contribution to the offspring’s disease are relatively scarce but are an important subject to the field. Recent research has suggested that paternal factors influenced by nutrition have been implicated in the transgenerational heritage of health and diseases through epigenetic mechanisms. This review aims to explore the current state of knowledge on nutrition-based paternal impacts on gynecological disease through epigenetics, focusing on the transmission of cancer and metabolic diseases from father to female offspring. We will explore the various mechanisms by which epigenetic landmarks, such as DNA methylation, histone modifications, and non-coding RNAs, are passed on through sperm and reprogrammed in the embryo, influencing offspring development and health. We will discuss the impacts of preconception paternal nutrition on two common cancer such as breast cancer and ovarian cancer in female offspring. Additionally, paternal overweight or obesity has been associated with increased risk of obesity in the offspring and compromised metabolic health, which may link to reproductive conditions such as infertility. Understanding the molecular mechanisms underlying non-genetic inheritance is crucial for elucidating the nutrition-mediated developmental origins of health and disease. This review highlights the mechanistic correlation between preconception paternal nutrition and female offspring gynecological health. Furthermore, it emphasizes the need for additional research to establish evidence-based paternal nutrition consultation and guidelines aimed at optimizing reproductive health and pregnancy outcomes in couples planning to conceive. Full article

Background: Ovarian cancer has the poorest prognosis of all gynecological malignancies, largely due to its chemoresistance, which poses significant treatment challenges. In this context, drug repurposing emerges as an innovative strategy that employs non-cancer treatments to interact with various signaling pathways, enhancing chemotherapy efficacy while minimizing toxicity. This study investigated the cytotoxic effects of galanthamine, currently used as an Alzheimer’s disease, as a potential treatment for high-grade serous carcinoma, both individually and in combination with paclitaxel. Methods: The Presto Blue assay, viability marker assessments, immunocytochemical analysis of apoptosis, and a cumulative assay were employed to evaluate the functionality of P-glycoprotein. Results: The results indicated that galanthamine did not demonstrate cytotoxic or synergistic effects in either high-grade serous carcinoma cell line tested, suggesting that it is not a viable strategy for overcoming paclitaxel resistance in this context. The immunocytochemistry analysis indicated that galanthamine does not affect the expression of proteins related to cell viability and proliferation and is not associated with chemoresistance. Additionally, functional assays showed that galanthamine treatment did not affect its drug efflux function at the cellular level. Conclusions: Overall, the results indicate that galanthamine is unsuitable for reversing paclitaxel resistance despite some literature suggesting its potential interaction with P-glycoprotein. Full article

Background: Radioactive colloids are considered the standard of care for sentinel lymph node (SLN) detection. An alternative detection method using superparamagnetic iron oxide (SPIO) nanoparticles is well documented in breast cancer but poorly studied for gynecological tumors, including vulvar cancer (VC). Objective: Our aim was to evaluate the feasibility, accuracy, and safety of SPIO nanoparticles for SLN mapping in patients with VC as a stand-alone technique compared with the combination of two methods: the standard of care using a radioactive isotope (technetium-99; Tc-99) and SPIO as a new tracer. Methods: We conducted a prospective and observational study of SLN mapping in patients with stage IB VC and tumor size ≤ 4 cm. We calculated detection and malignancy rates per patient and per groin in both study groups. During the 36-month follow-up, the groin recurrence rate was estimated for positive and negative SLNs. Kaplan–Meyer curves were used to analyze the probability of survival, depending on disease-free survival. Results: A total of 110 groins assessed by SLN in 60 patients included in this study were analyzed (70 groins from 40 patients in the group with a single tracer and 40 groins from 20 patients in the group of combined tracers). At least one sentinel lymph node was detected in every patient while the bilateral detection rate was 92.3% for the SPIO group and 88.2% for the Tc-99 and SPIO group. The groin detection rate was 94.3% and 90%, respectively. SLN mapping failure was similar in both groups (2.8% and 2.5%, respectively). During a 3-year follow-up, the isolated groin recurrence rate was 2.1% for negative groins and for disease-free survival it was 28.9 months in the combined tracer group versus 32.8 months in the SPIO group. The Kaplan–Meyer curves showed the increased probability of survival for the SPIO group (87.5%); however, it was insignificant. Conclusions: SLN mapping using the SPIO technique in patients with VC is non-inferior to the combined SPIO and Tc-99 method. Full article

Background: Vulvar squamous cell carcinoma (VSCC) is an uncommon yet increasingly relevant malignancy characterized by two distinct etiopathogenetic pathways: HPV-associated and HPV-independent. Data from Eastern Europe remain scarce, where demographic and diagnostic variability may influence disease presentation and outcomes. Purpose: This study aimed to assess the epidemiologic characteristics, HPV status, surgical management, and postoperative morbidity of VSCC in a Romanian single-center cohort, providing real-world evidence from an underrepresented region. Methods: A retrospective analysis was conducted on all 35 consecutive patients with histologically confirmed vulvar squamous cell carcinoma (VSCC) diagnosed and treated between January 2017 and December 2024 at the Department of Obstetrics and Gynecology, County Emergency Clinical Hospital of Craiova, Romania. Demographic, histopathologic, and surgical data were reviewed. HPV genotyping was performed on formalin-fixed paraffin-embedded (FFPE) tissue using PCR-based methods. Results: HPV DNA was detected in 31.4% of cases, predominantly genotypes 16, 18, and 33. HPV-positive patients were significantly younger than HPV-negative ones (median 58 vs. 72.5 years, p < 0.001), supporting the dual-pathway model of carcinogenesis. Early postoperative complications occurred in 65.7% of patients and late morbidity in 71.4%, secondary lymphedema. Surgical radicality was not significantly associated with early complications or length of hospitalization. Conclusions: This study highlights the epidemiologic and surgical patterns of VSCC in an Eastern European population, showing that conservative surgical strategies can maintain oncologic safety while reducing morbidity. These findings emphasize the need for standardized HPV testing, optimized perioperative care, and improved surveillance programs to enhance outcomes and survivorship. Full article

Primary dysmenorrhea (PDM) is a typical gynecologic disease in which uterine contractions and inflammation cause pain. Stachydrine (Sta) possesses multiple pharmacological activities but its effect on PDM has not yet been clarified. In vitro uterine contraction and oxytocin (OT)-induced PDM mouse models were used to evaluate the effect of Sta. Sta (10^−6.5 to 10⁻⁴ mol/L) dose-dependently inhibited spontaneous and OT-induced uterine contractions, with maximum inhibition rates of 47.1% and 40.4%, respectively. This effect was reversed by N-nitro-L-arginine (L-NAME) and indomethacin (Indo), suggesting the involvement of the nitric oxide and prostaglandin pathways. In vivo, Sta (20, 10, 5 mg/kg) significantly reduced writhing episodes, prolonged latency to the first response, and alleviated OT-induced uterine damage and inflammation. Additionally, Sta downregulated cyclooxygenase-2 (COX-2) expression in uterine tissue and decreased serum malondialdehyde (MDA) and prostaglandin F₂α (PGF2α) levels. These findings suggest that Sta alleviates PDM by modulating the COX-2/PGF2α pathway, inhibiting uterine contractions, and reducing inflammation and oxidative stress, making it a promising therapeutic candidate for PDM. Full article

Background: Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. While early-stage disease has favorable outcomes, advanced or recurrent EC remains associated with poor prognosis. Novel prognostic markers are needed to refine risk stratification. Systemic inflammation-based indices such as Pan-Immune Inflammation Value (PIV), Systemic Inflammation Response Index (SIRI), and Systemic Immune Inflammation Index (SII) have shown prognostic potential in solid tumors. Methods: We retrospectively evaluated 78 patients with endometrioid EC who had undergone hysterectomy with adnexectomy and lymphadenectomy. Demographic, clinicopathological, and laboratory data were extracted from electronic medical records. PIV, SII, and SIRI were calculated from the preoperative complete blood counts. Survival was assessed using Kaplan–Meier analysis, while prognostic factors were determined using univariate and multivariate Cox regression analyses. Results: The median age was 59 years, and 64.1% of the patients presented with early-stage disease. A high PIV (≥802) was significantly associated with a shorter overall survival (64 vs. 111 months, p < 0.001). PIV demonstrated the highest discriminatory accuracy (AUC = 0.776), followed by the SII (0.747) and SIRI (0.718). Univariate analysis identified that age, grade, LVSI, PNI, stage, distant metastasis, and high PIV, SII, SIRI, and NLR were predictors of poor survival. Multivariate analysis confirmed grade, distant metastasis and SIRI ≥ 1.5 as independent prognostic factors. Conclusions: Inflammation-based indices, particularly PIV and SIRI, correlated with survival outcomes in patients with EC. The SIRI retained an independent prognostic value, whereas PIV showed a strong discriminatory capacity. Incorporating these indices into established risk models may improve prognostic precision and support individualized management. Full article

Background: Ovarian cancer (OC) is the second most common gynecologic malignancy in the United States and remains the leading cause of death among cancers of the female reproductive system. Alarmingly, mortality rates have risen disproportionately among women of African ancestry compared to those of European or Asian descent. Identifying microRNA (miRNA) signatures that contribute to these disparities may enhance prognostic accuracy and inform personalized therapeutic strategies. Methods: In this study, we identified prognostic markers of overall survival in serous ovarian cancer (SOC) using data from The Cancer Genome Atlas (TCGA) and the Human Protein Atlas. Integrative bioinformatic analyses revealed three key prognostic genes—TIMP3 (Tissue Inhibitor of Metalloproteinases-3), BRAF (v-raf murine sarcoma viral oncogene homolog B), and ITGB1 (Integrin Beta-1)—as critical molecular determinants associated with survival in patients with SOC. Candidate miRNAs regulating these genes were predicted using TargetScanHuman v8.0, identifying a core regulatory set comprising miR-192, miR-30d, miR-16-5p, miR-143-3p, and miR-20a-5p. To validate their clinical relevance, formalin-fixed, paraffin-embedded (FFPE) and fresh SOC tumor samples were obtained from African American and Caucasian patients who underwent surgery at Loma Linda University (LLU) between 2010 and 2023. Results and Discussion: Among all these, ITGB1 (p = 0.00033), TIMP3 (p = 0.0035), and BRAF (p = 0.026) emerged as statistically significant predictors. Following total RNA extraction, cDNA synthesis, and quantitative reverse transcription PCR (qRT-PCR), the expression levels of these miRNAs and their target genes were quantified. In the LLU cohort, ITGB1 and TIMP3 were significantly upregulated in African American patients compared to Caucasian patients (p < 0.01 and p < 0.02, respectively). Among the miRNAs, miR-192-5p was particularly noteworthy, showing marginally differential expression in LLU samples (p = 0.0712) but strong statistical significance in the TCGA cohort (p = 0.00013), where elevated expression correlated with poorer overall survival (p = 0.021). Pathway enrichment and gene ontology analyses (miRTargetLink2.0, Enrichr) revealed interconnected regulatory networks linking miR-192, miR-16-5p, miR-143-3p, and miR-20a-5p to ITGB1; miR-143-3p/miR-145-5p to BRAF; and miR-16-5p and miR-30c/d to TIMP3. Conclusions: Collectively, these findings identify distinct miRNA–mRNA regulatory signatures—particularly the miR-192-5p–ITGB1/TIMP3 axis—as potential clinically relevant biomarkers that may contribute to racial disparities and disease progression in ovarian cancer. Full article

Background and Clinical Significance: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis in adults, typically following a chronic course that often leads to end-stage kidney disease. Rapidly progressive glomerulonephritis is a rare and severe variant of IgAN with a poor prognosis. Case Presentation: We present the clinical case of a 68-year-old Caucasian female with a history of systemic lupus erythematosus and untreated chronic hepatitis B, who was admitted to the Transplant-Nephrology Department, University Hospital Martin, with acute kidney injury and nephrotic syndrome accompanied by hematuria. The clinical picture was marked by lower limb oedema and poorly controlled hypertension, both of which responded well to conservative management. Extrarenal causes were excluded through otolaryngologic, stomatologic, and gynecologic assessments, and autoantibody screening was negative. Renal biopsy revealed crescentic glomerulonephritis with endocapillary and mesangial proliferation and IgA deposits. Due to active hepatitis B, initial treatment was limited to corticosteroids. Following a decrease in viral load, pulse therapy with cyclophosphamide was administered, followed by mycophenolic acid; however, renal function did not recover. Conclusions: The rapidly progressive form of IgA nephropathy in the context of active hepatitis B presents a rare and challenging clinical case. Management requires a highly individualised, multidisciplinary approach due to the risk of infectious complications and the need to preserve renal function. Full article

Background: To identify prognostic factors related to survival in patients with early-stage cervical cancer treated with radical surgery in six high-volume gynecologic oncology centers in Turkey. Methods: This retrospective analysis examined a cohort of 612 patients diagnosed with cervical cancer who underwent type II/III radical hysterectomy and pelvic lymphadenectomy, with or without para-aortic lymphadenectomy at six gynecologic oncology centers. A total of 537 patients between 1993 and 2023 were included. According to the 2009 FIGO staging system, 411 patients (76.5%) were stage IB1, 76 (14.2%) were stage IB2, 40 (4.7%) were stage IIA1, and 10 (1.9%) were stage IIA2. Patients underwent either type II or type III radical hysterectomy with pelvic lymphadenectomy, with para-aortic lymphadenectomy performed in 93.1% of cases. Among the 537 patients, 258 (48%) underwent type II radical hysterectomy and 279 (52%) underwent type III. Univariate and multivariate analyses of 5-year overall survival (OS) and 5-year disease-free survival (DFS) were performed. Results: In the entire cohort, 258 (48%) patients underwent radical surgery alone, while 279 (52%) patients underwent radical surgery followed by adjuvant therapy. The 5-year DFS and 5-year OS rates were 85.3% and 98.4%, respectively. In the multivariate logistic analysis, lymph node metastasis was identified as an independent prognostic factor for DFS and OS. Conclusions: Lymph node metastasis was the most important prognostic factor for survival in this large multicenter Turkish cohort. These findings highlight the prognostic value of nodal status, stromal invasion, margin status, and LVSI, while underscoring the importance of tailored adjuvant treatment strategies. Full article

Endometriosis is a common gynecological condition that affects fertility in many women of reproductive age worldwide. This multifaceted disease exhibits a pathogenesis characterized by hormonal and immune system dysregulations, alongside increased angiogenic activity within the peritoneum. The aberrant proliferation of endometrial tissue outside the uterus is associated with vascularization in ectopic endometriotic lesions. Consequently, RNA interference (RNAi)-based angiogenic therapies targeting the VEGFA gene present a promising strategy for the treatment of endometriosis. To ensure the efficacy of RNAi-based therapy, it is critical to develop carriers capable of precisely delivering small interfering RNA (siRNA) to target cells. Additionally, the instability of polyplexes in vivo must be regarded as a pivotal aspect influencing the success of non-viral delivery. In this study, we introduce ternary polyplexes comprising siRNA and a carrier derived from an arginine–histidine-rich peptide, which is further coated with a glutamate–histidine-rich polymer modified using an SDF-1 chemokine-derived ligand for targeting CXCR4-expressing cells. The physicochemical characteristics of the siRNA-polyplexes, along with cellular toxicity and GFP gene silencing efficacy, were assessed in vitro. The anti-angiogenic potential of anti-VEGFA siRNA-polyplexes was evaluated by measuring the size of endometrial lesions, conducting immunohistochemical staining, and analyzing VEGFA gene expression. For in vivo experiment, a rat model of endometriosis induced by subcutaneous auto-transplantation of uterine tissue was utilized. A significant reduction in the growth of endometriotic implants and silencing of VEGFA gene expression was observed when compared to the saline-treated control group. The results of this study strongly suggest that the developed ternary polyplexes have significant potential as an efficient tool for the development of anti-angiogenic RNAi-based therapies for endometriosis. Full article

Ovarian cancer (OC) is an aggressive and lethal gynecologic cancer due to its asymptomatic nature resulting in a late diagnosis. OC encompasses distinct histological subtypes, with serous OC representing the most common and aggressive form. However, within the same histological OC subtype, additional heterogeneity has been found in terms of genetic mutations and metabolic profiles probably contributing to treatment response. In cancer, metabolic reprogramming strongly involves mitochondria. Mitochondrial function can be regulated by the cAMP pathway, and its deregulation has been reported in various cancers including OC. Here we analyzed two serous OC cell lines, OC316 and OV56, and eleven human OC tissues. OC316 cell lines showed elevated cAMP level with respect to OV56. The high cAMP levels were associated with activation of thecAMP/PKA/CREB/PGC-1α axis resulting in increased mitochondrial biogenesis, respiratory chain activity, modulation of mitochondrial dynamics and apoptosis resistance. Accordingly, principal component analysis (PCA) of the twenty-three biochemical parameters, in eleven human OC tissues, classified OC into two groups showing different cAMP levels associated with distinct mitochondrial profiles. This analysis highlights a cAMP-dependent stratification revealing two mitochondrial subpopulations within serous OC. These findings indicate that the molecular heterogeneity of OC poses a challenge for understanding disease mechanisms and developing effective targeted therapies. Full article

A laparoscopic approach has been incorporated into the surgical management of a great variety of gynecologic pathologies during the decades following the first description of the method. As knowledge and experience about the use of laparoscopy is accumulating, it is gradually being recognized as an oncologically safe and effective option for the surgical management of various types of gynecological cancer, and the indications for its applications are increasing, as controversial topics are resolved through research. Endometrial cancer is the gynecological malignancy with the most straightforward indications of laparoscopy in its treatment, since a minimally invasive approach is considered the standard of care for both the surgical treatment of early-stage disease and surgical staging through sentinel lymph node biopsy. The role of laparoscopy was significantly decreased in the surgical management of cervical cancer after the publication of the LACC trial which reported worse survival outcomes for patients treated with laparoscopy, and laparotomy has emerged as the preferred approach. However, laparoscopy can be acceptable for carefully selected cases of early-stage cervical cancer and has also been introduced as an effective method for the surgical staging of the disease. The use of laparoscopy in the diagnostic and therapeutic management of ovarian cancer is not fully established but is receiving growing attention, as increasing evidence supports the safety of this approach, especially in the treatment of early-stage disease, where it is considered an acceptable alternative approach to laparotomy. Finally, as laparoscopic advancements are continuously achieved, new indications for laparoscopy have been explored for both vulvar and breast cancer. Future research will identify and highlight new ways to further integrate laparoscopy into the diagnostic and therapeutic management of gynecological malignancies. Full article

Background/Objectives: Accurate diagnosis, prognosis, and prediction of treatment response are essential in managing gynecologic cancers and maintaining patient quality of life. Computational pathology, powered by artificial intelligence (AI), offers a transformative opportunity for objective histopathological assessment. This review provides a comprehensive, user-oriented overview of existing AI tools for the characterization of gynecological cancers, critically evaluating their clinical applicability and identifying key challenges for future development. Methods: A systematic literature search was conducted in PubMed and Web of Science for studies published up to 2025. The search focused on AI tools developed for the diagnosis, prognosis, or treatment prediction of gynecologic cancers based on histopathological images. After applying selection criteria, 36 studies were included for in-depth analysis, covering ovarian, uterine, cervical, and other gynecological cancers. Studies on cytopathology and pure tumor detection were excluded. Results: Our analysis identified AI tools addressing critical clinical tasks, including histopathologic subtyping, grading, staging, molecular subtyping, and prediction of therapy response (e.g., to platinum-based chemotherapy or PARP inhibitors). The performance of these tools varied significantly. While some demonstrated high accuracy and promising results in internal validation, many were limited by a lack of external validation, potential biases from training data, and performance that is not yet sufficient for routine clinical use. Direct comparison between studies was often hindered by the use of non-standardized evaluation metrics and evolving disease classifications over the past decade. Conclusions: AI tools for gynecologic cancers represent a promising field with the potential to significantly support pathological practice. However, their current development is heterogeneous, and many tools lack the robustness and validation required for clinical integration. There is a pressing need to invest in the creation of clinically driven, interpretable, and accurate AI tools that are rigorously validated on large, multicenter cohorts. Future efforts should focus on standardizing evaluation metrics and addressing unmet diagnostic needs, such as the molecular subtyping of rare tumors, to ensure these technologies can reliably benefit patient care. Full article