Search Results (425)

Uterine leiomyoma (uterine fibroids, UF) are benign myometrium tumors that affect up to 70% of the female population and may lead to severe clinical symptoms. Despite the high prevalence, pathogenesis of UF is not understood and involves cytokines, steroid hormones, and growth factors. Additionally, an increased deposition and remodelling of the extracellular matrix is characteristic for UF. Vitamin D seems to play a new role in UF. Interestingly, hypovitaminosis D correlates with a higher prevalence of myomas and the severity of the myomas. Administration of vitamin D in women with insufficiency (serum level <30 ng/mL) restored the vitamin D status and reduced the mild symptoms of myomas. In addition, inflammatory processes may play a role. In the past years, it has become clear that cessation of inflammation is an active process driven by a class of lipid mediator molecules called specialized pro-resolving mediators (SPM). Inadequate resolution of inflammation is related to several chronic inflammatory diseases and several studies have proven the crucial role of SPMs in improving these diseases. In this review, we will give an overview on processes involved in UF growth and will give an overview on the modern view regarding the concept of inflammation and the role of SPMs in resolution of inflammation, especially in chronic inflammatory diseases. Full article

Lifileucel, a tumor-infiltrating lymphocyte (TIL) cell therapy approved for advanced melanoma, demonstrates promise for treating other solid tumors, including endometrial cancer (EC). The current study evaluates the feasibility of manufacturing TILs from EC tumors using Iovance’s proprietary 22-day Gen2 manufacturing process. Key parameters, including TIL yield, viability, immune phenotype, T-cell receptor clonality, and cytotoxic activity, were assessed. Of the 11 EC tumor samples processed at research scale, 10 (91%) successfully generated >1 × 10⁹ viable TIL cells, with a median yield of 1.1 × 10¹⁰ cells and a median viability of 82.8%. Of the four EC tumor samples processed at full scale, all achieved the pre-specified TVC and viability targets. Putative tumor-reactive T-cell clones were maintained throughout the manufacturing process. Functional reactivity was evidenced by the upregulation of 4-1BB in CD8+ T cells, OX40 in CD4+ T cells, and increased production of IFN-γ and TNF-α upon autologous tumor stimulation. Furthermore, antitumor activity was confirmed using an in vitro autologous tumor organoid killing assay. These findings demonstrate the feasibility of ex vivo TIL expansion from EC tumors. This study provides a rationale for the initiation of the phase II clinical trial IOV-END-201 (NCT06481592) to evaluate lifileucel in patients with advanced EC. Full article

Background: We have previously shown the remarkable impact of a single infusion of supercharged NK cells (sNK) in preventing and eliminating oral, pancreatic, and uterine cancers implanted in humanized BLT (hu-BLT) mice. Objective: In this report, we extended the studies to melanoma tumors to observe whether there were differences in response to sNK cells. Methods: We investigated the safety and tissue biodistribution profile of sNK cells in hu-BLT mice. This included the effect of sNK cell therapy on the peripheral blood-derived PBMCs, bone marrow, and spleen of hu-BLT mice. Results: Our investigation showed promising outcomes, as sNK cell infusions effectively inhibited melanoma tumor growth in hu-BLT mice. These potent cells not only traversed through the peripheral blood, spleen, and bone marrow but also infiltrated the tumor site, triggering in vivo differentiation of melanoma tumors. Moreover, the infusion of sNK cells increased the percentages of NK cells in the peripheral blood of hu-BLT mice, restoring cytotoxicity and IFN-γ secretion within the peripheral blood, spleen, and bone marrow of melanoma-bearing mice. Conclusions: This therapeutic approach not only reversed tumor progression but also revitalized the functionality of endogenous NK cells, potentially reversing the immunosuppressive effects induced by tumor cells in cancer patients. Full article

Uterine fibroids (leiomyomas) are benign tumors whose growth is influenced by estrogen and progesterone. This study aimed to compare the profiles of differentially expressed long non-coding RNAs (lncRNAs) in fibroids from postmenopausal and premenopausal women to identify hormone-responsive lncRNAs. RNA sequencing was performed on six pairs of fibroid (Fib) and adjacent myometrium (Myo) tissues from postmenopausal women. Out of 7876 normalized lncRNAs, 3684 were differentially expressed (≥1.5-fold), with 1702 upregulated and 1982 downregulated in Fib. Comparative analysis with a previously published premenopausal dataset identified 741 lncRNAs that were altered based on their menopausal status, including 62 lncRNAs that were uniquely dysregulated in postmenopausal samples. Overall, 9 lncRNAs were selected for validation by PCR in an expanded cohort of 31 postmenopausal and 84 premenopausal paired samples. Several lncRNAs, including LINC02433, LINC01449, SNHG12, H19, and HOTTIP, were upregulated in premenopausal Fib but not in postmenopausal ones, while ZEB2-AS1 displayed the opposite pattern. CASC15 and MIAT were elevated in Fib from both groups, although the increase was less pronounced in the postmenopausal group. LINC01117 was significantly downregulated in postmenopausal Fib, with no change observed in premenopausal samples. Additionally, analysis based on MED12 mutation status revealed that lncRNAs such as LINC01449, CASC15, and MIAT showed limited or reduced differential expression (mutation-positive vs. mutation-negative) in postmenopausal patients compared to the premenopausal group. These findings indicate that lncRNA expression in fibroids is modulated by menopausal status, likely reflecting hormonal influence. Hormone-responsive lncRNAs may play key roles in fibroid pathogenesis and represent potential targets for therapeutic intervention. Full article

Background: Uterine fibroids are the most common tumors in gynecology, detected in up to 80% of patients at various points in their lives. Uterine sarcomas account for 3% to 7% of all uterine cancers. The diagnosis of uterine fibroids is possible through ultrasonography (US), but this method has many limitations. More accurate examinations include magnetic resonance imaging (MRI) and positron emission tomography (PET) scans. Methods: This study evaluates MRI and PET in differentiating uterine fibroids from sarcomas. MRI uses T2-weighted and diffusion-weighted imaging (DWI), while PET assesses metabolism and estrogen receptor activity using [18F] fluorodeoxyglucose (FDG) and 16α-[18F]-fluoro-17β-estradiol (FES). Results: MRI allows for the identification of uterine fibroids when they exhibit good delineation and low intensity in T2-weighted images and DWI. Uterine sarcoma is characterized by moderate to high signal intensity on T2-weighted imaging, irregular borders, high signal intensity at high DWI values, and a decreased apparent diffusion coefficient. PET imaging with FDG and FES is a useful tool in differentiating uterine fibroids from sarcomas. Uterine sarcomas exhibit greater FDG uptake than smooth muscle fibroids, although cases of similar uptake do occur. On the other hand, FES provides information about estrogen receptors (ERs). Conclusions: Future research should focus on conducting standardized imaging studies, which would facilitate the inclusion of larger patient cohorts. This, in turn, would enable the development of specific diagnostic guidelines, ultimately leading to more accurate diagnoses and reducing the difficulty of differentiating these tumors through imaging. Full article

Gynecologic perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms characterized by the co-expression of melanocytic markers (HMB-45 and Melan-A) and smooth muscle markers (SMA, desmin, and caldesmon). The uterus is the most common organ affected, with approximately 110 cases reported worldwide, while occurrences in the cervix, vagina, ovary, and other gynecologic locations are exceptionally rare. These tumors typically present with nonspecific symptoms such as abnormal uterine bleeding and pelvic pain, often mimicking other uterine neoplasms. Histopathologically, PEComas exhibit epithelioid and spindle cell morphology with variable nuclear atypia, mitotic activity, and characteristic immunohistochemical profiles. Although most PEComas behave benignly, a subset demonstrates malignant potential, associated with larger tumor sizes, an increased mitotic index, necrosis, and vascular invasion; however, standardized diagnostic criteria remain scarce. Molecular alterations frequently involve the mTOR signaling pathway through tuberous sclerosis complex (TSC) 1 and TSC2 gene mutations, offering potential targets for therapy. Surgical resection with clear margins remains the cornerstone of treatment. For advanced or metastatic cases, mTOR inhibitors have shown promising efficacy, whereas the role of radiotherapy remains uncertain. This review aims to synthesize current knowledge regarding the epidemiology, clinical presentation, histologic features, malignant potential, and treatment of uterine PEComas, emphasizing the importance of accurate histopathological classification and molecular profiling to guide individualized therapeutic strategies. Full article

Malignancies of the female upper reproductive tract, especially endometrial and ovarian cancers, generate a significant burden for women worldwide. The possible etiopathogenetic role of chronic human papillomavirus (HPV) infection in the carcinogenesis of the female upper genital tract is neither clearly established not completely understood. Therefore, we performed a literature review, using the PubMed and SCOPUS electronic databases, of the prevalence of HPV DNA in endometrial, primary fallopian tube, ovarian, and primary peritoneal cancers, as well as uterine sarcomas. The present investigation covered 35 studies from different countries on various continents. Overall, the prevalence of HPV was approximately 15% in all the above cancers. HPV DNA was isolated from 11%, 0%, 0%, and 14% of endometrial carcinomas, uterine sarcomas, primary fallopian tube cancers, and ovarian malignant neoplasms, respectively. No relevant studies on primary peritoneal cancers were retrieved. The predominant HPV strain from tumors of the upper female reproductive tract, regardless of the tumor site, was HPV-16, followed by HPV-18. The HPV DNA identified was exclusively from subtypes HPV-6, HPV-11, HPV-16, HPV-18, and HPV-33, which are responsible for the development of not only cervical cancer, but also condylomata acuminata. The findings of the present review indicate that HPV vaccination might prove to be a useful strategy in the prevention of HPV-related carcinomas of the upper genital tract in women. Full article

Background: Although vitamin D supplementation is simple, inexpensive, and safe, vitamin D deficiency remains widespread, especially in developing communities. The aim of our study was to assess vitamin D levels among patients with gynecological cancers and compare them with those in patients with benign tumors living in rural and urban areas. Methods: This is a clinical retrospective study covering data analysis from March 2021 to July 2023. A total of 686 patients with uterine or ovarian tumors were analyzed. An electrochemiluminescence immunoassay method was used to assess vitamin D concentrations. Other laboratory blood tests were also performed on the admission day. Results: A significant reduction in vitamin D levels in oncological vs. non-oncological patients (median 23 (17, 33) ng/mL vs. 28 [21, 36] ng/mL, p < 0.001) was observed. The lowest vitamin D concentration was found in patients with ovarian cancer (median 22 (16, 32) ng/mL), followed by those with endometrial cancer and cervical cancer—median 24 (18, 35) ng/mL and 26 (20, 31) ng/mL, respectively). We found no differences in the vitamin D concentration between various histopathological types of ovarian cancers (p = 0.07). No correlation between the vitamin D concentration and age (r = 0.03, p > 0.05) was noted. A negligible negative correlation between vitamin D levels and BMI was observed (r = −0.095, p = 0.03). Additionally, those living in cities had a significantly reduced vitamin D concentration compared to those living in rural areas. No significant differences were demonstrated in vitamin D concentrations between malignant and benign tumors among patients living in rural areas (p = 0.17). Conclusions: Gynecological oncology patients have significantly lower vitamin D levels compared to non-oncological patients. In our patient population, ovarian and endometrial cancers were frequently associated with vitamin D deficiency. While this observation does not establish causation, it highlights the potential value of monitoring vitamin D levels and addressing deficiencies as part of broader cancer prevention and management strategies. Full article

Background/Objectives: Carbohydrate antigen 125 (CA125) is a glycoprotein commonly overexpressed in epithelial ovarian cancer and widely recognized as a tumor marker. However, elevated CA125 levels are also observed in various non-malignant conditions, including diseases affecting mucosal surfaces, pleural or peritoneal effusions, cirrhosis (with or without ascites), endometriosis, uterine fibroids, adenomyosis, pelvic inflammatory disease, and pregnancy. This review aims to explore the role of CA125 in non-malignant serous effusions, highlighting its diagnostic and prognostic potential beyond the realm of oncology. Methods: A comprehensive literature search was conducted across multiple databases and clinical trial registries. Eligible studies included full-text original research articles, reviews, and case reports published in English over the past 10 years. Inclusion criteria were limited to studies involving human subjects and focused on the role of CA125 in non-malignant serous effusions. Results: CA125 is produced by coelomic epithelial cells lining the ovary, pleura, pericardium, and peritoneum. Its serum concentration is not significantly influenced by age, body weight, or renal function, even in the advanced stages of the disease. In peritoneal conditions, CA125 is synthesized by mesothelial cells and serves as a potential marker of peritoneal involvement. The prevailing pathophysiological mechanism suggests that mechanical stretching of mesothelial cells due to ascitic pressure stimulates CA125 release. Similarly, in heart failure, mesothelial cells of the pericardium produce CA125, which correlates with congestion severity, supports risk stratification, and may inform diuretic therapy. Conclusions: While a threshold of 35 U/mL is established for malignancy, no standardized cutoff exists for CA125 in non-malignant conditions. The utility of CA125 measurement in peritoneal, pleural, or pericardial effusions—and cardiovascular diseases such as acute heart failure—for purposes of differential diagnosis, treatment guidance, or prognostication warrants further investigation through prospective clinical trials. Full article

Venous thromboembolism is significantly affected by hormonal and reproductive factors that pose unique challenges in women. Among various risk factors, the role of uterine fibroids, which are the most common benign tumors in women, is not well understood. The relationship between venous thromboembolism and fibroids is mainly attributed to the physical compression caused by large fibroids on pelvic veins, particularly the iliac veins, leading to venous stasis and thrombosis. This review explores the prevalence, pathogenesis, risk factors, possible racial influences, and management strategies of venous thromboembolism associated with fibroids. It highlights the need for better awareness, considering the asymptomatic nature of many fibroids and their potential to lead to serious thromboembolic complications. There is a clear need for screening methods, detailed guidelines, and treatments to prevent such complications and improve women’s health care. Full article

Objectives: CA19-9 elevation in non-gastrointestinal tumor patients may be influenced by various non-tumor factors, which poses challenges for clinical diagnosis. This study aims to assess the consistency between initial elevated CA19-9 levels detected by the ARCHITECT/Alinity i system (Abbott Diagnostics) and subsequent retesting using the Elecsys CA19-9 assay (Roche Diagnostics) in 5372 non-gastrointestinal tumor patients, and to explore potential factors contributing to CA19-9 non-specific elevation. Methods: Bland-Altman and Passing-Bablok analyses were used to assess the agreement between the two assays. Nonparametric Spearman and Pearson’s chi-square tests were used to assess the correlation between CA19-9 and different clinical comorbidities/antigen concentration strata and to compare the categorization by age/disease, respectively. Results: Bland–Altman and Passing–Bablok regression analyses revealed that the CA19-9 test results from Abbott and Roche platforms show significant systematic bias and weak correlation, making the two methods not directly interchangeable. After excluding common confounders, the study focused on heterophilic antibodies (HAs) as target. Blood samples were treated with a commercial blocking agent demonstrated alignment with baseline Elecsys CA19-9 results but differed significantly from initial ARCHITECT/Alinity i measurements. Furthermore, non-specific CA19-9 elevation was also associated with comorbidities such as diabetes mellitus, pulmonary infections, breast nodules, uterine leiomyoma, and its incidence increased with age. Conclusions: The study highlights the need to consider potential interferences and underlying disorders when results conflict with clinical diagnoses. Method-specific validation and comprehensive clinical correlation are crucial for accurate interpretation of CA19-9 levels to prevent misdiagnosis and ensure appropriate patient management. Full article

Endometrial stromal sarcoma (ESS) is a rare malignant tumor of uterine mesenchyme, accounting for 15–20% of uterine sarcomas. It is classified into low-grade (LG-ESS) and high-grade (HG-ESS) subtypes, each defined by distinct histopathological and molecular features. LG-ESS exhibits slow progression, resembling proliferative-phase endometrial stroma, with genetic alterations like JAZF1-SUZ12 fusions. HG-ESS is more aggressive, characterized by high mitotic activity, necrosis, and genetic markers such as BCOR internal tandem duplication, often leading to advanced-stage diagnosis. Surgical resection is the cornerstone for managing early-stage ESS. A total hysterectomy with bilateral salpingo-oophorectomy (BSO) is recommended to prevent recurrence. Fertility-preserving approaches may be considered in LG-ESS but are associated with high recurrence rates. Lymphadenectomy is not routinely performed, given its limited prognostic value. HG-ESS, due to its aggressiveness, often requires additional treatment, including chemotherapy. Adjuvant therapy varies by subtype. LG-ESS responds well to hormonal treatments such as aromatase inhibitors and progestins, while tamoxifen is contraindicated. HG-ESS, lacking hormonal receptor expression, is managed with chemotherapy, often incorporating doxorubicin-based regimens. Radiotherapy may improve local control in select cases but shows limited impact on overall survival. Advanced-stage ESS treatment focuses on complete cytoreduction, supplemented by systemic therapies. Hormonal therapy remains the standard for advanced LG-ESS, whereas HG-ESS relies on chemotherapy. Prognosis depends on the subtype and stage. LG-ESS has favorable outcomes, with five-year survival exceeding 90% in early stages, but recurrent disease remains common. HG-ESS is associated with poorer survival due to its aggressive nature. Advances in molecular profiling offer promising avenues for personalized therapies, integrating genomic insights with targeted treatments to improve outcomes in this rare malignancy. Full article

Uterine fibroids represent a prevalent category of tumors encountered in females of reproductive age, may present as singular or multiple entities and can manifest a variety of symptoms, which can negatively affect women’s daily lives. Pharmacological interventions may prove to be ineffective, occasionally costly, and associated with adverse effects. In instances where symptoms escalate in severity, myomectomy becomes a requisite as uterine-preserving operative therapy. Myomectomy can be performed utilizing laparoscopic, robotic, laparotomic, vaginal or hysteroscopic techniques. Given the abundant vascular supply to the myometrium, with blood being delivered to the uterus via the uterine arteries, myomectomy carries a considerable risk of significant hemorrhage during and subsequent to the surgical procedure, with the related complications. This paper aims to elucidate the conventional methodologies employed to mitigate hemorrhage during myomectomy and in the immediate postoperative phase, evaluating the effect of chemical interventions (such as vasopressin, octreotide, tranexamic acid, and uterotonics) alongside mechanical strategies (including uterine artery clamps, embolization, and tourniquets) to curtail bleeding during the myomectomy process. Furthermore, the potential of employing the intracapsular myomectomy technique without reliance on other traditional approaches was explored. This surgical method is grounded in the principles of the biological and anatomical characteristics of the fibroid, facilitating the enucleation of the myoma from its pseudocapsule. This anatomical entity, which is formed by the myoma throughout its development within the myometrium, enables the fibroid to be detached from the uterine musculature and supplies the requisite neurovascular support for its sustenance. Finally, the narrative review also shows how the intracapsular approach, which uses the fibroid’s biology, reduces bleeding during myomectomy. Full article

Objective: To evaluate the diagnostic and prognostic potential of preoperative serum steroid levels in endometrial cancer (EC) alone and in combination with clinical parameters and biomarkers CA-125 and HE4. Methods: This single-center observational study included 62 patients with EC and 70 controls with benign uterine conditions who underwent surgery between June 2012 and February 2020. Preoperative serum levels of classic androgens, 11-oxyandrogens, glucocorticoids and mineralocorticoids were measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Machine learning was used to assess their diagnostic and prognostic value alone and combined with clinical parameters and tumor biomarkers. Results: Patients with EC had significantly higher serum levels of classic androgens (androstenedione, testosterone), 11-oxyandrogens (11β-hydroxy-androstenedione, 11β-hydroxy-testosterone) and glucocorticoids (17α-hydroxy-progesterone, 11-deoxycortisol) compared to controls. While individual steroids had limited diagnostic value, a multivariate model including classic androgens, CA-125, HE4, BMI and parity achieved an AUC 0.87, 79.1% sensitivity and 74.7% specificity in distinguishing EC from benign uterine condition. This model outperformed our previously published model based on CA-125, HE4 and BMI (AUC: 0.81, p < 0.0001). Prognostically, HE4 was the strongest marker for lymphovascular space invasion (LVSI) (AUC: 0.79) and deep myometrial invasion (MI) (AUC: 0.71). Among steroids, androstenedione was the most predictive of LVSI (AUC: 0.67), while 11β-hydroxy-testosterone was the strongest predictor of deep MI (AUC: 0.64). Conclusions: Patients with EC exhibit distinct steroid hormone profiles. While steroids alone offer modest diagnostic and prognostic value, integrating them into multivariate models improves diagnostic accuracy. Full article

Background: Cervical cancer treatment with advanced radiotherapy techniques benefits from image guidance, particularly when anatomical changes occur during therapy. This case emphasizes the need for adaptive radiotherapy when target volume shifts significantly. Methods: A 70-year-old woman with International Federation of Gynecology and Obstetrics (FIGO) IIIC2 9th edition cervical squamous cell carcinoma presented with a distended uterine cavity due to fluid accumulation. She underwent definitive chemoradiotherapy using Volumetric Modulated Arc Therapy (VMAT) and weekly cisplatin. Results: Daily Cone Beam Computed Tomography (CBCT) imaging revealed progressive uterine shrinkage as intrauterine fluid drained, significantly altering target volume and organ-at-risk (OAR) positioning. These changes necessitated two re-planning CT scans during external beam radiotherapy to maintain accurate dosing and avoid OAR toxicity. The patient completed treatment, including image-guided brachytherapy, without complications. Adaptive planning ensured adequate tumor coverage and minimized normal tissue exposure. Conclusions: This case highlights the critical role of daily CBCT in detecting anatomical changes during radiotherapy. Adaptive re-planning, though rarely required more than once, was essential here to preserve treatment accuracy. CBCT should be considered a standard verification tool in cervical cancer radiotherapy, particularly in cases involving intrauterine fluid. Full article