Search Results (108)

Background and Objectives: Uterine cancer is the most common gynaecologic malignancy in developed countries, yet the psychosocial sequelae of treatment are incompletely described. This prospective, single-centre study quantified six-month changes in the quality of life (QoL) and perceived stress in women with newly diagnosed uterine cancer and explored clinical moderators of change. Methods: Participants completed four validated self-report questionnaires: the 36-item Short-Form Health Survey (SF-36), the 26-item World Health Organization Quality-of-Life-BREF (WHOQOL-BREF), the 30-item EORTC QLQ-C30 and the 10-item Perceived Stress Scale (PSS-10) before therapy and again six months after surgery ± adjuvant chemoradiation. Subgroup analyses were performed for stage (FIGO I–II vs. III–IV). Results: Mean SF-36 Physical Functioning improved from 58.7 ± 12.1 to 63.1 ± 12.6 (Δ = +4.4 ± 7.3; p = 0.000, d = 0.36). PSS declined from 24.1 ± 5.6 to 20.8 ± 5.4 (Δ = −3.3 ± 5.0; p < 0.001, d = 0.66). The WHOQOL-BREF Physical and Psychological domains rose by 4.4 ± 6.9 and 3.5 ± 7.3 points, respectively (both p < 0.01). EORTC QLQ-C30 Global Health increased 5.1 ± 7.6 points (p < 0.001) with parallel reductions in fatigue (−5.4 ± 9.0) and pain (−4.8 ± 8.6). Advanced-stage patients showed larger reductions in stress (ΔPSS −3.5 ± 2.5 vs. −2.3 ± 2.3; p = 0.036) but similar QoL gains. ΔPSS correlated inversely with ΔWHOQOL Psychological (r = −0.53) and ΔSF-36 Mental Health (r = −0.49) and positively with ΔEORTC Global Health (r = −0.42) (all p < 0.001). Conclusions: Over six months, multimodal uterine cancer treatment was associated with clinically meaningful QoL improvements and moderate stress reduction. Greater stress relief paralleled superior gains in psychological and global health indices, highlighting the importance of integrative survivorship care. Full article

Endometrial carcinoma (EC) is the most common gynaecological malignancy in developed nations, exhibiting significant molecular heterogeneity that impacts prognosis and treatment response, particularly in advanced or recurrent settings. Traditional classification is increasingly supplemented by molecular subtyping (POLE-ultramutated, MSI-high/dMMR, NSMP, p53-mutated/CNH), which provides crucial prognostic information and predicts benefit from immunotherapy. This review summarizes the landscape of predictive biomarkers for immune checkpoint inhibitor (ICI) therapy in EC, emphasizing a new therapeutic scenario for advanced and recurrent EC. Mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H), leading to high tumor mutational burden (TMB) and increased neoantigen production, is the most established predictor, resulting in FDA approvals for pembrolizumab and dostarlimab in this subgroup. POLE mutations also confer hypermutation and high immunogenicity, predicting a favorable ICI response. Other biomarkers, including PD-L1 expression and TMB, show variable correlation with response and require further standardization. The tumor immune microenvironment, including tumor-infiltrating lymphocytes (TILs), also influences treatment outcomes. Clinical trials have demonstrated significant survival benefits for ICIs combined with chemotherapy (e.g., dostarlimab/pembrolizumab + carboplatin/paclitaxel) in first-line settings, especially for dMMR/MSI-H EC, and for ICI combinations with targeted agents (e.g., lenvatinib + pembrolizumab) in previously treated patients. Integrating molecular classification and validated biomarkers is essential for optimizing patient selection and developing personalized immunotherapy strategies for EC. Full article

Background: Cervical dysplasia is a pre-malignant condition of the uterine cervix and is highly prevalent in Sub-Saharan Africa; especially affecting HIV-infected Black women. The anti-dysplastic effect of vitamin D hormones in cervical dysplasia is poorly understood. Therefore, we conducted a cross-sectional case–control observational study to assess the relationship between serum 25-hydroxycholecalciferol (25(OH)D) and cervical dysplasia, amongst Black women with and without HIV infection. Methods: The study participants attended a gynaecologic oncology clinic at an academic hospital in Pretoria, South Africa (n = 109). Patient clinical data were obtained during consultation. Cervical dysplasia was identified by cytology (PAP smear) which classified the case group as high-grade squamous epithelial lesions (HSILs), and the control group as <HSIL. Serum biochemistry measured 25(OH)D and its covariate biochemical variables. The data were statistically modelled to adjust for clinical and biochemical covariates, identify a significant relationship (p ≤ 0.05) between 25(OH)D and cervical dysplasia, and analyse subgroup interaction between HIV status and cervical dysplasia. Results: The data showed high levels of vitamin D insufficiency and deficiency in Black women with and without HIV infection. After covariate adjustment, 25(OH)D demonstrated an inverse relationship with HSIL in HIV-uninfected Black women. Furthermore, an interaction effect between women with and without HIV infection was observed. Conclusions: The role of 25(OH)D in the primary prevention of cervical dysplasia in Black women without HIV infection is promising, and dosing strategies require investigation. Also, future studies exploring the immunomodulatory role of 25(OH)D in cervical dysplasia in HIV-infected women is warranted. Full article

Mitochondrial-associated granulocyte macrophage colony-stimulating factor (Magmas) is a unique protein located in the inner membrane of mitochondria, with an active role in scavenging reactive oxygen species (ROS) in cellular systems. Ovarian cancer (OC), one of the deadliest gynaecological cancers, is characterised by genomic instability, affected by ROS production in the tumour microenvironment. This manuscript discusses the role of Magmas and efficacy of its novel small molecule inhibitor BT#9 in OC progression, metastasis, and chemoresistance. Magmas expression levels were significantly elevated in high-grade human OC compared to benign tumours by immunohistochemistry. The inhibition of Magmas by BT#9 enhanced ROS production and reduced mitochondrial membrane permeability, basal respiration, mitochondrial ATP production, and cellular functions, such as the proliferation and migration of OC cell lines in vitro. Oral administration of BT#9 in vivo significantly reduced tumour growth and spread and enhanced the survival of mice without having any effect on the peritoneal organs. These data suggest that Magmas is functionally important for OC growth and spread by affecting ROS levels and that the inhibition of Magmas activity by BT#9 may provide novel clinical benefits for patients with this malignancy. Full article

Objective: To evaluate the safety, adequacy, and accuracy of tru-cut biopsy of gynaecologic tumours in a population of Czech women. Methods: A four-year retrospective study of ultrasound-guided tru-cut biopsy of gynaecologic tumours was conducted in the Department of Obstetrics and Gynaecology, Charles University, Hradec Kralove, Czech Republic. Results: One hundred and four women with gynaecologic tumours underwent transvaginal tru-cut biopsy within the study period. The most common indication for tru-cut biopsy in more than one-half of the women was a suspicion of malignancy/inability to exclude malignancy (59, 56.7%). Most of the tumours were malignant on histopathological examination (71, 68.3%), with advanced ovarian cancer being the most common type of malignancy (43/71, 60.6%). The overall adequacy and accuracy rates of tru-cut biopsy were 93.3% and 93.3%, respectively. Most of the inadequate samples were obtained from overweight and obese women (5/7, 71.4%), with only one biopsy sample taken in the majority of the inadequate biopsies (5/7, 71.4%). Accuracy was higher for malignant than benign tumours (97.7% vs. 82.4%). For malignant tumours, accuracy was highest for advanced ovarian cancers (33/40, 82.5%). Only one case was complicated by bleeding, giving an overall complication rate of 1%. The complicated biopsy was taken by a gynae-oncology trainee. Conclusions: Tru-cut biopsy is a cost-effective and safe preoperative diagnostic modality for patients with gynaecologic tumours, offering high adequacy and accuracy. It is particularly useful in patients with advanced ovarian cancer, most of whom present late with inoperable tumours that contraindicate primary surgery. Full article

Background: The advent of artificial intelligence (AI) has revolutionised many fields in healthcare. More recently, it has garnered interest in terms of its potential applications in histopathology, where algorithms are increasingly being explored as adjunct technologies that can support pathologists in diagnosis, molecular typing and prognostication. While many research endeavours have focused on solid tumours, gynaecological malignancies have nevertheless been relatively overlooked. The aim of this review was therefore to provide a summary of the status quo in the field of AI in gynaecological pathology by encompassing malignancies throughout the entirety of the female reproductive tract rather than focusing on individual cancers. Methods: This narrative/scoping review explores the potential application of AI in whole slide image analysis in gynaecological histopathology, drawing on both findings from the research setting (where such technologies largely remain confined), and highlights any findings and/or applications identified and developed in other cancers that could be translated to this arena. Results: A particular focus is given to ovarian, endometrial, cervical and vulval/vaginal tumours. This review discusses different algorithms, their performance and potential applications. Conclusions: The effective application of AI tools is only possible through multidisciplinary co-operation and training. Full article

Objectives: Ovarian cancer is a common gynaecological malignancy. Photodynamic therapy (PDT) mediated by 5-aminolaevulinic acid (5-ALA-PDT) is widely used in clinical practice. However, hypoxia may impact the efficacy of this treatment. In the present study, we combined the bioreductively active drug tirapazamine (TPZ) with PDT to explore its potential in enhancing ovarian cancer cell death. Methods: A cell counting kit-8 assay was used to determine cytotoxicity under different intervention conditions. The distribution of protoporphyrin IX, a metabolite of 5-ALA, was observed using in vivo fluorescence imaging. The effect of the combined treatment was assessed by measuring changes in tumour size following the corresponding interventions and by haematoxylin and eosin staining of tumour tissues. Immunohistochemical staining was used to detect the expression levels of relevant proteins. Results: TPZ exhibited no cytotoxicity under normoxic conditions but was activated under hypoxic conditions, inducing cytotoxic effects that were enhanced when combined with PDT. Over time, protoporphyrin IX achieved systemic distribution, and high drug concentrations were maintained within the tumour. The combination therapy suppressed tumour growth, and pathological staining showed that necrotic tumour areas were significantly enlarged after treatment. The enhanced therapeutic effect may be attributable to the inhibition of the hypoxia-inducible factor-1α/vascular endothelial growth factor axis and PI3K/Akt/mTOR pathway. Conclusions: 5-ALA-PDT combined with TPZ can overcome both the hypoxic state of ovarian cancer tissues and the increased hypoxia induced by PDT, thereby inhibiting tumour growth. Full article

Introduction: The maximum residual tumour size after surgery is the most important prognostic factor related to survival in advanced ovarian cancer. This parameter can be subjectively determined by the surgeon at the end of the operation and by a radiologist with a postoperative CT scan. CT scans after optimal cytoreduction can reveal residual/progressive disease in a significant percentage of patients, ranging from 21% to 49%. The aim of this study was to validate the PCI scale for the systematic reading of postoperative CT scans in patients with advanced ovarian cancer and to establish it as a new prognostic marker. Material and Methods: Patients with advanced ovarian cancer (FIGO II-IV), diagnosed between 2007 and 2019 in Hospital La Fe Valencia, in whom cytoreductive surgery was performed (achieving R0 or R1), and in whom a postoperative CT scan was performed between the third and eighth week post-surgery and prior to the start of chemotherapy, were included. Two different radiologists who specialised in gynaecological malignancy performed a blind analysis of the CT scans. They then read the images using the Peritoneal Carcinomatosis Index (PCI) scale, which divides the abdominopelvic cavity into 12 quadrants. Using the Qualitative Assessment (QA) scale, they established the presence or lack of tumour disease in each of these regions, with QA 1–2 being definitely/probably normal, QA 3 indeterminate and QA 4–5 probably/definitely metastatic. Results: This study included a cohort of 117 patients. The radiological study found measurable tumour disease in up to 49% of patients after optimal primary cytoreduction (R0 or R1). There was “substantial agreement” between the results of the two radiologists according to the Kappa analysis (0.624). Both radiologists’ (A and B) findings were related to a significant reduction in both disease-free survival (DFS) and overall survival (OS) in patients with residual disease in the CT scan (QA 4–5) versus those without macroscopic disease (QA 1–3) (p < 0.05). Conclusions: The finding of radiological tumour disease on a standardised and systematised postsurgical CT scan prior to the initiation of adjuvant chemotherapy is associated with the prognosis of patients with advanced ovarian cancer. Full article

Background: Ovarian cancer encompasses a diverse range of neoplasms originating in the ovaries, fallopian tubes, and peritoneum. Despite being one of the commonest gynaecological malignancies, there are no validated screening strategies for early detection. A diagnosis typically relies on imaging, biomarkers, and multidisciplinary team discussions. The accurate interpretation of CTs and MRIs may be challenging, especially in borderline cases. This study proposes a methodological pipeline to develop and evaluate deep learning (DL) models that can assist in classifying ovarian masses from CT and MRI data, potentially improving diagnostic confidence and patient outcomes. Methods: A multi-institutional retrospective dataset was compiled, supplemented by external data from the Cancer Genome Atlas. Two classification workflows were examined: (1) whole-volume input and (2) lesion-focused region of interest. Multiple DL architectures, including ResNet, DenseNet, transformer-based UNeST, and Attention Multiple-Instance Learning (MIL), were implemented within the PyTorch-based MONAI framework. The class imbalance was mitigated using focal loss, oversampling, and dynamic class weighting. The hyperparameters were optimised with Optuna, and balanced accuracy was the primary metric. Results: For a preliminary dataset, the proposed framework demonstrated feasibility for the multi-class classification of ovarian masses. The initial experiments highlighted the potential of transformers and MIL for identifying the relevant imaging features. Conclusions: A reproducible methodological pipeline for DL-based ovarian mass classification using CT and MRI scans has been established. Future work will leverage a multi-institutional dataset to refine these models, aiming to enhance clinical workflows and improve patient outcomes. Full article

Oxidative stress is a state of imbalance between the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and the antioxidant defence system in the body. Oxidative stress may be associated with a variety of diseases, such as ovarian cancer, diabetes mellitus, and neurodegeneration. The generation of oxidative stress in ovarian cancer, one of the common and refractory malignancies among gynaecological tumours, may be associated with several factors. On the one hand, the increased metabolism of ovarian cancer cells can lead to the increased production of ROS, and on the other hand, the impaired antioxidant defence system of ovarian cancer cells is not able to effectively scavenge the excessive ROS. In addition, chemotherapy and radiotherapy may elevate the oxidative stress in ovarian cancer cells. Oxidative stress can cause oxidative damage, promote the development of ovarian cancer, and even result in drug resistance. Therefore, studying oxidative stress in ovarian cancer is important for the prevention and treatment of ovarian cancer. Antioxidants, important markers of oxidative stress, might serve as one of the strategies for preventing and treating ovarian cancer. In this review, we will discuss the complex relationship between oxidative stress and ovarian cancer, as well as the role and therapeutic potential of antioxidants in ovarian cancer, thus guiding future research and clinical interventions. Full article

Endometrial cancer (EC) is a common gynaecological malignancy associated with metabolic dysfunctions such as obesity, diabetes and insulin resistance, as well as hormonal imbalances, particularly involving oestrogen and progesterone. These factors disrupt normal cellular metabolism, heightening the risk of developing endometrioid EC (EEC), the most prevalent subtype of EC. The insulin-like growth factor-1 (IGF1) pathway, a key regulator of growth, metabolism, and organ function, is implicated in EC progression. Recent research highlights the distinct roles of IGF1 isoforms, including IGF1-Ea, IGF1-Eb, and IGF1-Ec, in promoting tumour growth, metastasis, and hormone signalling interactions, particularly with oestrogen. This review examines the function and clinical significance of IGF-1 isoforms, emphasising their mechanisms in gynaecological physiology and their contributions to EC pathogenesis. Evidence from other cancers further underscores the relevance of IGF1 isoforms in driving tumour behaviours, offering valuable insights into their potential as biomarkers and therapeutic targets. Understanding these mechanisms provides opportunities for novel approaches to the prevention, diagnosis, and treatment of EC, improving patient outcomes and advancing the broader field of hormone-driven cancers. Full article

Background: Lichen Sclerosus (LSc) is a chronic inflammatory skin condition predominantly affecting the anogenital regions, with a well-recognised potential for malignancy. This study examines the incidence, demographic characteristics, and regional distribution of LSc in Sweden over a 20-year period. The analysis is based on data from the Swedish National Patient Register (NPR), with a focus on cases diagnosed in specialist care settings. Methods: A nationwide register-based study was conducted using data from the NPR, identifying cases of LSc diagnosed between 1 January 2001 and 1 January 2021. Data analysis explored incidence by region, sex, age, and diagnostic care setting. A total of 154,424 patients with LSc were included, and the control group consisted of the general Swedish population without known LSc. Results: The mean annual incidence of LSc was 0.81 per 1000 individuals across Sweden, with higher rates in females (1.14 per 1000) compared to males (0.47 per 1000). Incidence varied significantly across regions, with Blekinge, Kalmar, and Gotland exhibiting the highest rates. This study analysed the distribution of LSc diagnoses across medical specialties, finding that 29.8% of cases were managed by dermatology and venereology, while 17.2% were handled by gynaecology and obstetrics. The analysis of marital status revealed that the proportion of married and divorced LSc patients was significantly lower than the national averages for men and women. Conclusions: This study highlights significant regional variations in LSc incidence. Future research should investigate whether environmental factors, genetic predisposition, socioeconomic disparities, or variations in healthcare access contribute to the variations in incidence. Such insights could lead to more targeted public health strategies for managing LSc across different regions. Full article

(1) Background: The objectives of this study were to assess survival of patients with a diagnosis of brain metastases secondary to gynaecologic malignancy and the impact of clinicopathological factors on prognosis in this population. (2) Methods: A retrospective cohort of patients with gynaecologic cancers diagnosed with brain metastases treated with radiation at a tertiary care centre from 1 January 2004 until 30 September 2023 was studied. Kaplan–Meier method and log-rank test were used to evaluate survival, and cox regression was used to identify significant predictive factors of survival. (3) Results: In total, 103 patients were included in this study. Median age at diagnosis of brain metastases was 59 (range 30–94). Median survival time following diagnosis of brain metastases was 3.6 months (range 0.4–183.8). Survival was significantly longer for patients treated with surgery combined with radiation compared to radiation alone and with stereotactic radiosurgery (SRS) compared to whole brain radiation therapy (WBRT). Cox regression revealed that primary ovarian malignancy, extracranial disease at diagnosis, and ≥3 brain metastases were associated with poorer prognosis, and complete response to prior treatment was associated with more favourable prognosis. (4) Conclusions: Data from this study will assist in providing evidence-based prognostic information to patients with gynaecologic malignancy diagnosed with brain metastases. Full article

Background/Objectives: Uterine carcinosarcomas (UCSs) are rare and aggressive malignancies with limited epidemiological data. This study aims to evaluate the clinical and pathological features and prognostic factors of UCS in a retrospective cohort of 80 patients, contributing to improved management strategies. Methods: We conducted a retrospective analysis of UCS cases treated from 1995 to 2024 at three institutions. Data on demographics, clinical features, histopathology, treatment, and outcomes were collected. Overall survival (OS) and prognostic factors were assessed using Kaplan–Meier and Cox proportional hazards regression analyses. Results: The median age of patients was 66 years, with a median overall survival of 34.5 months. Disease recurrence occurred in 32.5% of cases, with a median disease-free interval of 17.92 months. Age, tumour stage, and size emerged as significant predictors of survival. Stage I–II patients had a significantly better prognosis than those with Stage III–IV (HR = 0.438, p = 0.008). Tumour size >4 cm was associated with increased mortality (HR = 2.154, p = 0.019). Lymphadenectomy was not independently associated with improved survival. Adjuvant chemotherapy, mainly carboplatin and paclitaxel, was administered to 67.5% of patients, achieving a complete response in 66.67%. Conclusions: Tumour stage and age are significant independent predictors of survival in UCS, underscoring the need for early diagnosis and intervention. Tumour size is also crucial in determining prognosis. The role of lymphadenectomy remains uncertain, emphasizing the importance of individualized treatment approaches. Future research should explore molecular profiling to further refine prognostication and therapeutic strategies for this challenging malignancy. Full article

Ovarian cancer (OC) is a leading cause of death among gynaecological malignancies. The haemostatic system, which controls blood flow and prevents clotting disorders, paradoxically drives OC progression while increasing the risk of venous thromboembolism (VTE). MicroRNAs (miRNAs) have emerged as crucial in understanding VTE pathogenesis. Exploring the connection between cancer and thrombosis through these RNAs could lead to novel biomarkers of cancer-associated thrombosis (CAT) and OC, as well as potential therapeutic targets for tumour management. Thus, this study examined the impact of eight plasma miRNAs targeting the tissue factor (TF) coagulation pathway—miR-18a-5p, -19a-3p, -20a-5p, -23a-3p, -27a-3p, -103a-3p, -126-5p and -616-3p—in 55 OC patients. Briefly, VTE occurrence post-OC diagnosis was linked to shorter disease progression time (log-rank test, p = 0.024) and poorer overall survival (OS) (log-rank test, p < 0.001). High pre-chemotherapy levels of miR-20a-5p (targeting coagulation factor 3 (F3) and tissue factor pathway inhibitor 2 (TFPI2)) and miR-616-3p (targeting TFPI2) predicted VTE after OC diagnosis (χ², p < 0.05). Regarding patients’ prognosis regardless of VTE, miR-20a-5p independently predicted OC progression (adjusted hazard ratio (aHR) = 6.13, p = 0.005), while miR-616-3p significantly impacted patients’ survival (aHR = 3.72, p = 0.020). Further investigation is warranted for their translation into clinical practice. Full article