Search Results (217)

Background and Objectives: We compared mini-laparoscopic and laparoscopic hysterectomy in terms of surgery duration, postoperative pain, conversion rate, blood loss, postoperative complications (Clavien-Dindo classification), and the length of hospital stay. Materials and Methods: Patients were recruited between 1 January 2017 and 1 January 2024, at the Department of Gynecology, “Villa Sofia-Cervello” Hospital. Indications for hysterectomy included uterine myoma, endometriosis, endometrial hyperplasia, adenomyosis, high-grade cervical dysplasia, early-stage endometrial cancer, and microinvasive cervical cancer. Patients were divided according to treatment into conventional laparoscopic hysterectomy (LH) with all 5 mm ports or the needlescopic approach (minilaparoscopic hysterectomy [MLH]), using 3 mm instruments. Postoperative pain was assessed using the visual analog scale (VAS) at multiple time points (2, 6, 12, and 24 h post-surgery). Results: A total of 308 patients were enrolled, with 153 women in the LH group and 155 in the MLH group. The surgery duration was on average 105.5 min in LH and 98.8 min in MLH (p < 0.0001). The intraoperative blood loss averaged 195.1 mL in LH and 100.3 mL in MLH (p < 0.001). The average length of hospital stay was 4.0 days for women undergoing LH compared to 3.2 days for women undergoing MLH (p < 0.001). Conclusions: This retrospective study demonstrated that MLH is an effective and functional technique for treating various gynecological conditions, with advantages in terms of aesthetic outcomes and reduced perioperative pain and recovery times. The positive results, supported by key parameters such as surgical duration, blood loss, and complications, could serve as a foundation for future studies on larger populations and for improving clinical practices in gynecology. Full article

Background/Objectives: Definitive radiotherapy (RT) is a frequently employed salvage option in early-stage, endometrial cancer (EC) loco-regional recurrence patients. Local control (LC) and survival rates are highly variable in the literature. The aim of this review is to assess the impact of modern salvage radiotherapy (SRT) in this group of patients. Methods: A systematic review of the literature was performed, focusing on studies that included EC local recurrence patients receiving SRT after 2000 to reflect advances in radiotherapy techniques. Our report followed the principles as outlined in the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Nine studies were included in our analysis with a total sample size of 648 patients. Conclusions: SRT offers excellent LC rates in this group of patients with minimal ≥ grade 3 toxicity. Salvage rates are limited by the presence of well-known risk factors for loco-regional relapses, with distant control being the primary mode of failure, resulting in lower survival rates. The decision to omit adjuvant RT should be weighed against the anticipated salvage outcomes in case of relapse. 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

Cancer of the uterine cervix (cervical cancer) is a leading cancer among women worldwide, although its incidence has been reducing in many developing nations. In the majority of cervical cancer cases, the presence of high-risk human papillomavirus (HPV) is usually detected. However, a growing body of evidence currently considers that exclusive HPV infection may not be sufficient for cancer development. Apart from certain common risk factors for cervical cancer, like poor nutritional status and smoking, many studies documented an association with other viral infections, such as human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV-2). Similarly, vaginal bacterial populations perhaps play a key role in cervical cancer. It may be worth mentioning that different bacterial species can immensely influence (either protecting or adversely) the biochemical characteristics of the cervicovaginal environment—for example, Lactobacillus crispatus, Gardnerella vaginalis, and Chlamydia trachomatis. As a result, chronic infections with unfavorable microorganisms (other than HPV) may affect the pathological processes of malignancy. On the other hand, the cervix is an estrogen-sensitive organ like the corpus uteri (i.e., the body of the uterus). Estrogen and different estrogen receptors are implicated in the development and promotion of various cancers, including endometrial cancer. A number of reports also suggest a close association between estrogen and HPV in the development of cervical cancer. Furthermore, estrogen is linked with the characteristics of the vaginal microenvironment including bacteria. Therefore, several of the abovementioned factors (some are preventable) could play an important role in the progression of cervical neoplastic lesions. Full article

(1) Background and Objectives: Endometriosis is defined as the presence of endometrial glands and stroma outside the uterine cavity. It affects 5–15% of women of reproductive age. Ovarian cancer develops in approximately 1% of patients with endometriosis. Prediction of those with endometriosis who will develop ovarian cancer is among the current research topics. (2) Materials and Methods: With this study, we aimed to reveal the role of miRNA 200b and miRNA 21 in endometriosis-associated ovarian carcinoma (EAOC). Thirteen patients diagnosed as having EAOC between 2015 and 2023 were included, with their endometriosis and eutopic endometrium tissues (Group 3: 13 patients, 39 tissue samples). Two separate groups were then detected to compare with these cases: Group 2 composed of tuba-ovarian endometriosis with its eutopic endometrium (10 patients, 20 tissue samples) and Group 1 composed of eutopic endometrium only (10 patients, 10 tissue samples). The foci marked on H&E sections were determined from the area on the relevant paraffin blocks and small tissue samples were taken in tubes to be studied with real-time PCR. (3) Results: No significant difference was detected for miRNA 21 and miRNA 200b expression levels among eutopic endometrium, endometriosis, and cancer foci in Group 3. However, miRNA 21 and miRNA 200b expression levels in the eutopic endometrial tissue of cases with ovarian cancer were significantly higher than in the eutopic endometrial tissues of cases with (Group 2) and without endometriosis (Group 1). (4) Conclusions: This study suggests that increased miRNA 200b and miRNA 21 expression levels detected in eutopic endometrial tissue of patients with endometriosis may contribute to identifying cases that may develop EAOC. Full article

Endometriosis, a complex inflammatory disease, affects a significant proportion of women of reproductive age, approximately 10–15%. The disease involves the growth of endometrial glands and stroma outside the uterine cavity, leading to tissue remodeling and fibrosis. Hormonal imbalances, accompanied by local and general inflammation and pain, are key features of endometriosis. Endometriotic lesions are associated with the overproduction of cytokines, metalloproteinases, prostaglandins, reactive oxygen radicals, and extracellular vesicles. Genetic predisposition and cytokine gene polymorphisms have been documented. Macrophages, dendritic cells, mast cells, Th1 in the early phase, Th2 in the late phase, and T regulatory cells play a crucial role in endometriosis. Reduced NK cell function and impaired immune vigilance contribute to endometrial growth. The strong inflammatory condition of the endometrium poses a barrier to the proper implantation of the zygote, contributing to the infertility of these patients. Cytokines from various cell types vary with the severity of the disease. The role of microbiota in endometriosis is still under study. Endometriosis is associated with autoimmunity and ovarian cancer. Hormonal treatments and surgery are commonly used; however, recent interest focuses on anti-inflammatory and immunomodulatory therapies, including cytokine and anti-cytokine antibodies. Modulating the immune response has proven critical; however, more research is needed to optimize treatment for these patients. 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

Calpains, calcium-dependent cytosolic cysteine proteases, perform controlled proteolysis of their substrates for various cellular and physiological activities. In different cancers, missense mutations accumulate in the genes coding for the calpain cleavage sites in various calpain substrates termed as the calpain cleavage-related mutations (CCRMs). However, the impact of such CCRMs on the calpain–substrate interaction is yet to be explored. This study focuses on the interaction of wild-type and mutant β-integrins with calpain-1 and 2 in uterine corpus endometrial carcinoma (UCEC). A total of 48 calpain substrates with 176 CCRMs were retrieved from different datasets and shortlisted on the basis of their involvement in cancer pathways. Finally, three calpain substrates, ITGB1, ITGB3, and ITGB7, were selected to assess the structural changes due to CCRMs. These CCRMs were observed towards the C-terminal of the cytoplasmic domain within the calpain cleavage site. The wild-type and mutant proteins were docked with calpain-1 and 2, followed by molecular simulation. The interaction between mutant substrates and calpains showcased variations compared to their respective wild-type counterparts. This may be attributed to mutations in the calpain cleavage sites, highlighting the importance of the cytoplasmic domain of β-integrins in the interactions with calpains and subsequent cellular signaling. Highlights: 1. Calpain cleavage-related mutations (CCRMs) can alter cellular signaling. 2. CCRMs impact the structure of C-domains of human integrin-β subunits. 3. Altered structure influences the cleavability of human integrin-β subunits by human calpains. 4. Altered cleavability impacts the cell signaling mediated through calpain–integrin-β axis. 5. Presence of CCRMS may influence the progression of uterine corpus endometrial carcinoma (UCEC). Full article

Background/Objectives: Lipid metabolism plays a crucial role in uterine corpus endometrial carcinoma (UCEC); however, its specific mechanisms remain to be fully elucidated. This study aimed to construct a lipid-metabolism-related prognostic model and explore its association with the tumor immune microenvironment. Methods: A total of 552 UCEC and 35 normal tissue samples from The Cancer Genome Atlas (TCGA) database were analyzed to identify differentially expressed lipid-metabolism-related genes (DE-LMRGs). A prognostic risk model was established using univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression, and its clinical utility was assessed through nomogram construction. Functional enrichment analysis was performed to explore the biological pathways involved. Tumor immune infiltration patterns were evaluated using single-sample Gene Set Enrichment Analysis (ssGSEA), Estimation of Stromal and Immune Cells in Malignant Tumors using Expression Data (ESTIMATE), and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms. Results: Multivariate analysis indicated that the prognostic model had robust predictive value, with AUCs of 0.701, 0.746, and 0.790 for 1-, 3-, and 5-year overall survival predictions. High-risk patients exhibited a suppressed immune microenvironment characterized by reduced immune cell infiltration, lower tumor mutation burden (TMB), and elevated TIDE scores, suggesting potential resistance to immunotherapy. Furthermore, LIPG was identified as a key hub gene through the intersection of nine machine learning algorithms, demonstrating strong associations with both cancer progression and immune infiltration. Functional validation using Cell Counting Kit-8 (CCK-8), wound healing, and transwell migration assays following small interfering RNA (siRNA) transfection demonstrated that LIPG promotes UCEC cell proliferation and migration in vitro. Conclusions: These findings highlight the critical role of lipid metabolism in UCEC progression and immune modulation, with LIPG emerging as a potential prognostic biomarker. The identified lipid-metabolism-related gene signature may provide new insights into tumor microenvironment interactions. Full article

Uterine serous carcinomas are an aggressive minority of endometrial cancers. They are characterized by mutations in TP53 and extensive copy number alterations and are primarily classified in the copy number-high/p53abn molecular prognostic group, highlighting a unique molecular profile that is crucial for understanding their behavior and treatment responses. Clinical studies have shown that molecular categorization via biomarkers can facilitate proper treatment selection, and this is now widely used. In this context, the scope of this systematic review is to identify molecular characteristics with prognostic significance for these neoplasms to further inform on their treatment needs. We performed a comprehensive literature search of all articles written in English using the PubMed/Medline and Cochrane databases through February 2025. Our review led to the inclusion of 95 studies, from which we identified a total of 66 distinct molecular characteristics along with new cancer signatures that may impact prognosis. These findings have the potential to inform clinical practice by aiding in the development of tailored treatment strategies for patients with uterine serous carcinoma, ultimately improving outcomes in this challenging malignancy. Full article

Thrombomodulin (THBD), hsa-miR-18a-5p, and hsa-miR-18b-5p have been frequently mentioned in numerous cancer-related research studies; however, their specific functions in uterine corpus endometrial carcinoma (UCEC) are not well understood. This study aimed to investigate the roles of THBD, hsa-miR-18a-5p, and hsa-miR-18b-5p within a UCEC cohort. We utilized various web-based tools, including GEPIA2, UALCAN, Human Protein Atlas (HPA), TNM Plot, STRING, TargetScan, and ENCORI for our analysis. The expression level of the THBD gene was found to be significantly downregulated (p < 0.05) in UCEC tissue compared to adjacent normal tissue. In contrast, hsa-miR-18a-5p and hsa-miR-18b-5p were both upregulated in UCEC tissue (p < 0.05). Additionally, THBD exhibited a significant hypermethylation level in UCEC tissue (p < 0.05). The elevated expression of hsa-miR-18a-5p was linked to a shorter overall survival (OS) (p = 0.025), while THBD and hsa-miR-18b-5p showed no association with OS (p = 0.87 and p = 0.56, respectively). Notably, THBD expression was significantly negatively correlated with hsa-miR-18a-5p (p = 0.00407), whereas no significant correlation was found between THBD and hsa-miR-18b-5p (p = 0.25). Thus, it can be concluded that increased levels of miR-18a-5p in the UCEC cohort may serve as a negative prognostic marker and a potential therapeutic target. However, further studies are necessary to validate the implications of decreased THBD and increased miR-18b-5p expression levels on the clinical outcomes of these patients. Full article

Background and Objectives: To summarize the evidence on in vivo uterine pelvic lymphatic drainage. Materials and Methods: A literature search was performed in multiple electronic databases from inception to December 2024. We included all the studies that compared two different uterine injection sites in the mapping of pelvic sentinel lymph nodes by injecting two different tracers into two distinct injection sites. The primary outcomes included the concordance and discordance rates in the mapped pelvic sentinel lymph nodes between the pairs of injection sites. The secondary outcomes were the detection rates per injection site and tracer. Four reviewers independently reviewed the records for inclusion, assessed the risk of bias, and extracted the data. Pooled concordance, discordance, and detection rates with 95% confidence intervals (CIs) were estimated using the random effects model. Heterogeneity was quantified using the I² tests. Results: Out of 2512 records, we included 4 studies (172 patients and 344 hemipelves). Three studies injected the cervix with the technetium-99m and the uterine corpus with methylene blue; one study injected the cervix with indocyanine green and the utero-ovarian ligament with methylene blue. Both tracers/injection sites successfully identified a sentinel lymph node in 132 hemipelves (132/344; 38.4%), identifying the same sentinel lymph node in 116 cases (116/132; 87.9%). The pooled concordance rate per hemipelvis was 91.8% (95% CI 0.665–1.000; I² = 92%; chi² p-value < 0.01). Two different sentinel lymph nodes were identified in the remaining 16 hemipelves, with a pooled hemipelvis discordance rate of 8.2% (95% CI 0.000–0.335; I² = 92%; chi² p-value < 0.01). The cervix and technetium-99m were the injection site and tracer with the highest pooled detection rate. Conclusions: Different uterine injection sites appear to share a common pelvic lymphatic pathway and sentinel lymph node in most cases, consistent with the current practice in endometrial cancer. Future research will confirm whether cervical injections might be proposed for pelvic sentinel lymph node mapping in all gynecological cancers. Full article

The expression of members of the progesterone receptor membrane component (PGRMC) family, particularly PGRMC1, is elevated in diverse types of cancers, particularly those of the female reproductive system. While xenograft tumor studies using human transformed cell lines in immunocompromised mice have suggested that PGRMC1 enhances tumor growth and chemoresistance, the exact role of members of the PGRMC family in cancer development in vivo remains unclear. In this study, we examined the effect of deleting Pgrmc2 on the development of endometrial hyperplasia and cancer using a murine phosphatase and tensin homologue (Pten) conditional loss-of-function model. We previously established that PGRMCs are cell survival factors that are required for normal estrogen-induced uterine epithelial cell proliferation and normal female fertility. The deletion of Pgrmc2 reduced the incidence and severity of endometrial hyperplasia and cancer in mice with conditional Pten-heterozygous uteri and increased lifespan in mice with conditional Pten-knockout uteri. Mechanistically, the deletion of Pgrmc2 decreased uterine glandular epithelial cell proliferation. Pten loss-of-function-induced endometrial hyperplasia and cancer elevated uterine inflammation, but this was not impacted by PGRMC2 deficiency. This study identifies PGRMC2 as a potential therapeutic target to be inhibited in the treatment of endometrial hyperplasia and cancer, particularly where PTEN activity is reduced due to gene mutation or loss. Full article

Endometrial cancer is the fourth most common cancer in women in Europe. Its carcinogenesis is a complex process and requires further research. In our study, we focus on finding new and easy-to-diagnose markers for detecting endometrial cancer. For this purpose, we compared the levels of miR-21-5p, miR-205-5p, and miR-222-3p in endometrial cancer tissues with the levels of these miRs in the serum of patients using the dPCR method. Our study is preliminary and consists of comparing the changes in miRNA expression in serum to the changes in miRNA in tissue of patients with endometrial cancer. The study included 18 patients with EC and 19 patients undergoing surgery for pelvic organ prolapse or uterine fibroids as a control group without neoplastic lesions. Endometrial tissue and serum were collected from all patients. The analyses showed an increased expression of miR-205-5p in endometrial cancer tissue and decreased expression of miR-222-3p in tissue and serum samples. These results suggest that miR-205-5p and miR-222-3p may be potential endometrial cancer biomarkers. Only miR-222-3p confirmed its decreased expression in serum, making it a potential and easily accessible marker in the diagnosis of endometrial cancer. This pilot study requires further investigation in a larger group of patients. Its advantages include the possibility of a comparison between miRNA expression in tissue and serum, as well as conducting the study using dPCR. Full article