Medicina

An Assessment of the Effectiveness of Preoperative İmaging Modalities (MRI, CT, and 18F-FDG PET/CT) in Determining the Extent of Disease Spread in Epithelial Ovarian–Tubal–Peritoneal Cancer (EOC)

Background and Objectives: Epithelial ovarian–tubal–peritoneal cancer (EOC) is the most common type of ovarian cancer. Optimal cytoreductive surgery is the most important prognostic factor in its management. When complete cytoreduction is anticipated to be challenging, neoadjuvant systemic chemotherapy (NACT) becomes an alternative. Imaging modalities are utilized in the decision-making process for primary treatment. The purpose of this study is to evaluate the diagnostic performance and accuracy of preoperative MRI, CT, and 18F-FDG PET/CT in detecting the extent of EOC. Materials and Methods: Between 2017 and 2018, 24 patients with primary (with or without neoadjuvant chemotherapy) or recurrent EOC diagnosed at the Department of Gynecologic Oncology, Istanbul University, Istanbul Faculty of Medicine, were enrolled in this study. These 24 women underwent preoperative imaging modalities within 7 days prior to surgery. The results were compared with histopathological findings, considered the gold standard. Results: We evaluated 24 anatomic regions most commonly involved in EOC. The sensitivity of MRI, CT, and PET/CT in detecting ≥ 0.5 cm implants was 95%, 84%, and 86%, respectively. However, when including implants < 0.5 cm, sensitivity decreased significantly to 40%, 38%, and 42%, respectively. The calculated area under the curve (AUC) for tumors, including those < 0.5 cm, was evaluated as weak for all three modalities (MRI: 0.689, CT: 0.678, PET/CT: 0.691), with PET/CT detecting the largest area. For detecting tumors ≥ 0.5 cm, the AUCs were 0.974, 0.921, and 0.923 for MRI, CT, and PET/CT, respectively. The largest AUC was calculated with MRI, and the AUCs for all three methods were evaluated as excellent. Accuracy was comparable among all three imaging modalities, and no statistically significant differences were found (p < 0.05). Conclusions: While imaging modalities are valuable tools for evaluating abdominal spread in epithelial ovarian cancer (EOC), they have demonstrated limited success in detecting miliary disease. The risk of false negatives for miliary tumors on PET/CT may be mitigated by combining it with other imaging modalities such as MRI or CT. Further investigations are necessary to identify more accurate imaging techniques for this challenging clinical scenario.

The Impact of Positive Peritoneal Cytology on the Survival Rates of Early-Stage-Disease Endometrial Cancer Patients: Systematic Review and Meta-Analysis

Background and Objectives: The impact of positive peritoneal cytology has been a matter of controversy in early-stage endometrial cancer for several years. The latest staging systems do not take into consideration its presence; however, emerging evidence about its potential harmful effect on patient survival outcomes suggests otherwise. In the present systematic review and meta-analysis, we sought to accumulate current evidence. Materials and Methods: Medline, Scopus, the Cochrane Central Register of Controlled Trials CENTRAL, Google Scholar and Clinicaltrials.gov databases were searched for relevant articles. Effect sizes were calculated in Rstudio using the meta function. A sensitivity analysis was carried out to evaluate the possibility of small-study effects and p-hacking. Trial sequential analysis was used to evaluate the adequacy of the sample size. The methodological quality of the included studies was assessed using the Newcastle–Ottawa scale. Results: Fifteen articles were finally included in the present systematic review that involved 19,255 women with early-stage endometrial cancer. The Newcastle–Ottawa scale indicated that the majority of included studies had a moderate risk of bias in their selection of participants, a moderate risk of bias in terms of the comparability of groups (positive peritoneal cytology vs. negative peritoneal cytology) and a low risk of bias concerning the assessment of the outcome. The results of the meta-analysis indicated that women with early-stage endometrial cancer and positive peritoneal cytology had significantly lower 5-year recurrence-free survival (RFS) (hazards ratio (HR) 0.26, 95% CI 0.09, 0.71). As a result of the decreased recurrence-free survival, patients with positive peritoneal cytology also exhibited reduced 5-year overall survival outcomes (HR 0.50, 95% CI 0.27, 0.92). The overall survival of the included patients was considerably higher among those that did not have positive peritoneal cytology (HR 12.76, 95% CI 2.78, 58.51). Conclusions: Positive peritoneal cytology seems to be a negative prognostic indicator of survival outcomes of patients with endometrial cancer. Considering the absence of data related to the molecular profile of patients, further research is needed to evaluate if this factor should be reinstituted in future staging systems.

Using a Modified Polysaccharide as a Hemostatic Agent Results in Less Reduction of the Ovarian Reserve after Laparoscopic Surgery of Ovarian Tumors—Prospective Study

Background and Objectives: The study investigated whether the method of achieving hemostasis affects the ovarian reserve in patients undergoing laparoscopic surgery due to ovarian tumors or cysts. Materials and Methods: Patients with unilateral tumors or ovarian cysts, who qualified for laparoscopic tumor enucleation, were randomly selected to receive modified polysaccharides or bipolar coagulation. Ovarian reserve was analyzed by anti-Mullerian hormone (AMH) level. Results: The study included 38 patients: 19 patients in the modified polysaccharide group and 19 in the bipolar coagulation group. Patients after bipolar coagulation treatment had statistically significantly lower AMH 6 months after surgery compared to the group treated with modified starch. The levels of AMH in the study and control groups were 3.96 +/− 2.12 vs. 2.51 +/− 1.39 ng/mL, respectively; p = 0.018. A statistically significant decrease in AMH was also demonstrated in the bipolar coagulation group as compared to the preoperative assessment (p = 0.049). There was no statistically significant decrease in AMH in the group of patients treated with the modified starch. Conclusions: Using a modified polysaccharide during laparoscopic cystectomy is effective and has a positive effect on the ovarian reserve compared to the use of bipolar coagulation. Both the AMH level 6 months after surgery and the percentage decrease in AMH were more favorable in the group of patients treated with modified starch.

Surgical Approach and Outcomes in Early-Stage Endometrial Cancer: A Molecularly Stratified Comparison of Open, Laparoscopic, and Robotic Surgery

Background and Objectives: Previous surgical approach comparisons in endometrial cancer may be confounded by inadequate control for tumour biology—the primary driver of outcomes. This study provides the first surgical approach comparison incorporating molecular classification to control for case selection bias. Materials and Methods: Retrospective analysis of 512 consecutive patients with stage I–II endometrial cancer (FIGO 2009) treated with open (n = 83), laparoscopic (n = 278), or robotic (n = 151) surgery between 2018 and 2024. Molecular classification was available for 219 patients (42.8%) using TCGA criteria and incorporated into analyses to control for case selection bias, with molecular subtype incorporated to control for biological bias rather than as a primary endpoint. Primary outcomes included perioperative metrics and oncological safety. The primary objective was to determine whether apparent surgical outcome differences reflect genuine technique effects or case selection bias based on tumour biology. Results: Molecular subtype distribution varied significantly by surgical approach, with high-risk subtypes concentrated in open surgery, explaining apparent outcome differences. After controlling for molecular subtype and other confounders, minimally invasive approaches demonstrated superior perioperative outcomes: reduced blood loss (laparoscopic 129.8 mL, robotic 157.9 mL vs. open 261.4 mL, p < 0.001), shorter hospital stays (2.4 and 2.2 vs. 5.3 days, p < 0.001), and lower complications (5.7% and 6.6% vs. 21.6%, p < 0.001). In our cohort, recurrence-free survival showed significant differences favouring minimally invasive approaches, with 2-year RFS rates of 92.8%, 96.4%, and 100.0% (p = 0.008) and 3-year RFS rates of 90.4%, 95.0%, and 100.0% (p = 0.003) for open, laparoscopic, and robotic surgery, respectively, although robotic surgery had a shorter follow-up (median 33 vs. 42 months). Within-approach exploratory analyses revealed that p53-abnormal tumours were associated with significantly longer operative times and greater blood loss across all surgical approaches (p < 0.05), although complication rates did not differ significantly by molecular subtype within any approach (open p = 0.124, laparoscopic p = 0.656, robotic p = 0.287). Apparent surgical approach differences largely reflected appropriate case selection based on tumour biology rather than technique superiority. Conclusions: When controlling for tumour biology, minimally invasive approaches offer superior perioperative outcomes with equivalent oncological safety. Higher complication rates in open surgery primarily reflect the inherent morbidity of this approach and appropriate surgeon selection for high-risk cases. Within-approach analyses suggest possible molecular influences on operative parameters that warrant prospective validation. Molecular stratification is essential for fair surgical approach comparison in the contemporary era.

Surgical Ovarian Suppression and Breast Cancer—What Do We Know About It?

Breast cancer (BC) is the most common malignancy in women worldwide, with incidence projected to rise, particularly among younger patients. In premenopausal women with hormone receptor-positive disease, ovarian suppression is an established component of systemic therapy, most often achieved pharmacologically with gonadotropin-releasing hormone agonists (GnRHas). Bilateral salpingo-oophorectomy (BSO) represents a surgical alternative that ensures definitive suppression, eliminates compliance issues, and is more cost-effective in the long term. Despite these advantages, BSO induces irreversible menopause, associated with vasomotor symptoms, cardiovascular morbidity, bone loss, cognitive decline, and reduced quality of life. Evidence suggests that BSO is most appropriate in selected cases, including women unable to tolerate or adhere to medical suppression, those with inadequate estradiol suppression, patients approaching natural menopause, individuals with metastatic hormone receptor-positive disease, and carriers of BRCA1 mutations, especially with triple-negative tumors. Conversely, data on its benefit in BRCA2 carriers remain limited. Overall, BSO provides oncologic outcomes comparable to medical suppression but at the cost of permanent systemic effects. The decision between surgical and medical ovarian suppression should be individualized, balancing oncologic efficacy, comorbidities, genetic background, and patient preference. Further studies are needed to define the optimal duration of medical suppression and clarify the role of BSO in hereditary breast cancer.

Altered Apoptosis in Endometriosis Compared with Ovarian Carcinoma

Background and Objectives: Endometriosis has been shown to be associated with an increased cancer risk, and apoptosis may be important in the pathophysiology of endometriosis. To date, it remains unclear whether the tissue cell surface apoptosis marker (annexin V) is an important parameter in terms of cancer and endometriosis. This retrospective study aimed to compare endometriosis cases and ovarian cancer cases in terms of apoptosis and cell proliferation markers’ levels. Materials and Methods: In total, 65 (30 ovarian endometrioma, 35 ovarian carcinoma) paraffin blocks were taken for flow cytometric analysis. The flow cytometry analysis markers and annexin V staining levels were compared. Results: The G2/M stage cell ratio, S-phase fraction, proliferative index, aneuploidy cell ratio, and annexin V apoptotic index ratio were found to be statistically significantly lower in the endometrioma group compared to the carcinoma group. However, the G0/G1 phase cell ratio was found to be higher in the endometrioma group. According to the correlation analysis results, annexin V expression level showed a positive correlation with the G2/M cell ratio and S-phase fraction, while it showed a negative correlation with the G0/G1 level. In addition, as the apoptotic index increased, the cell aneuploidy rate also increased, which was statistically significant. When the apoptotic index was used to distinguish between endometrioma and ovarian cancer (cutoff value 16.05%), the sensitivity was found to be 94.3%, and the specificity was found to be 80%, which was statistically significant for cases below the cutoff value to be accepted as endometrioma. Conclusions: Apoptosis was reduced in endometriosis cases. The cell DNA activity was altered in endometriosis cases, as in cancer cases. Flow cytometric analysis can be used in the diagnosis of endometriosis even in paraffin-embedded tissues. The flow cytometric annexin V analysis provided results in an average of 30 min, making it a promising and highly sensitive differential diagnostic marker to distinguish between endometriosis and ovarian cancer.

Inflammatory Indices and CA 125: A New Approach to Distinguish Ovarian Carcinoma and Borderline Tumors in Suspicious Ovarian Neoplasms from a Retrospective Observational Multicentric Study

Background and Objectives: This study aimed to evaluate the diagnostic potential of systemic inflammatory indices such as Systemic Inflammation Response Index (SIRI) and Systemic Inflammatory Response (SIR). These were assessed in combination with CA 125 to distinguish ovarian carcinoma (OC) from borderline ovarian tumors (BOT) in patients with suspicious adnexal masses. Materials and Methods: A retrospective multicenter observational study including patients undergoing surgery for suspected ovarian neoplasms was conducted. Inclusion criteria required preoperative blood sampling for inflammatory markers and CA 125. SIR-125 and SIRI-125 were developed by combining SIR and SIRI with CA 125 levels. Diagnostic performance was assessed using ROC curve analysis and linear regression models. Results: A total of 63 patients (42 BOT, 21 OC) were analyzed. OC patients exhibited significantly higher SIR-125 and SIRI-125 values (p < 0.001). ROC analysis demonstrated good diagnostic accuracy, with AUCs of 0.83 (SIR-125) and 0.82 (SIRI-125). SIR-125 showed higher specificity (0.83), while SIRI-125 had superior sensitivity (0.86). Conclusions: SIR-125 and SIRI-125 enhance diagnostic differentiation between OC and BOT, providing a simple, cost-effective preoperative tool. Future prospective studies are needed to validate these findings in broader patient populations.

Fertility Preservation Strategies in Female Cancer Patients: Current Approaches and Future Directions

Fertility-sparing treatments (FSTs) have gained importance for young female cancer patients, especially those with early-stage cervical, ovarian, and endometrial cancers. However, concerns about the long-term safety of these procedures, particularly in more advanced cancers, persist. A literature review was conducted using databases such as PubMed, Scopus, and Web of Science. The search terms included “fertility preservation” and “gynaecological cancer”. Articles published between 2014 and 2024 were considered, with 39 articles cited in the paper. The inclusion criteria were female patients undergoing FST. Studies were excluded if prior treatments impacted fertility or if oncological outcomes were inadequately reported. Radical trachelectomy, laparoscopic fertility-sparing surgeries, and cryopreservation techniques, such as ovarian tissue vitrification and oocyte cryopreservation, offer viable options for preserving fertility in early-stage gynecological cancer patients. Radical trachelectomy and cryopreservation showed positive reproductive outcomes, with pregnancy rates of 30–50% in early-stage cases. GnRH analogs during chemotherapy also demonstrated benefits in maintaining fertility. Despite these advances, recurrence in more advanced stages (FIGO IA2 and beyond) remains a concern. Minimally invasive surgeries like robotic-assisted procedures demonstrated comparable fertility outcomes to traditional methods but with fewer complications. FST is a promising option for women with early-stage cancer, offering favorable reproductive and survival outcomes. However, further research is needed to confirm long-term oncological safety in advanced stages. Multidisciplinary approaches and individualized treatment planning are essential for optimizing outcomes.

Endometrial Carcinoma and Associated Secondary Neoplasia: The Role of Clinical Features, Pathology, and Comorbidities in a University-Affiliated Clinical Center from Western Romania

Background and Objectives: Multiple primary malignancies involving endometrial carcinoma (EC) present complex diagnostic and management challenges. This study aimed to identify clinical, pathological, and demographic patterns among patients with EC and a second primary tumor and assess the role of comorbidities in tumor behavior. Materials and Methods: We retrospectively analyzed 35 women diagnosed with EC and a second malignancy between 2017 and 2024. We evaluated clinical variables, tumor characteristics, and comorbidities. Statistical analysis included chi-square tests, Mann–Whitney U tests, Kruskal–Wallis tests, Spearman correlations, and logistic regression. Multiple testing correction was applied using the Benjamini–Hochberg method. Results: Endometrioid EC was the most prevalent subtype (80%), most frequently associated with breast (28.5%) and colorectal cancers (11.4%). Obesity (45.7%), hypertension (62.9%), and diabetes (22.9%) were common. While univariate analysis suggested associations between comorbidities and tumor features (e.g., obesity and tumor type, ρ = 0.30, p = 0.08), no correlation remained significant after adjustment. Logistic regression identified age (OR = 0.88, CI: 0.79–0.98, p = 0.022) and obesity (OR = 0.11, CI: 0.01–0.83, p = 0.033) as independent predictors of non-endometrioid histology. Conclusions: These findings suggest that age and obesity may influence histological differentiation in EC with multiple primaries. This study suggest that age and obesity may play a role in the histological differentiation of EC in patients with multiple primary tumors. The small cohort size (n = 35) limits the statistical power and generalizability of the results; therefore, they should be regarded as exploratory and hypothesis-generating, warranting validation in larger prospective studies.

An Update on Cutaneous Metastases of Internal Malignancies

Skin metastases represent a rare finding in dermatological practice, but their presence signifies an advanced disease and usually portends a poor prognosis. They commonly arise as multiple painless nodules in patients with a cancer history. Differential diagnoses are challenging, and zosteriform metastases should not be mistaken for herpes zoster. Dermoscopy typically reveals a white, structureless pattern. A skin biopsy with routine hematoxylin–eosin staining is essential for an accurate diagnosis, while immunohistochemistry is particularly useful in cases of anaplastic tumors. Breast cancer is the most common cause of skin metastasis in women, and lung cancer is the most common in men. The life expectancy after diagnosis is generally low. Cutaneous metastasectomy, electrochemotherapy, and radiotherapy are generally regarded as beneficial for palliative purposes. Intralesional cryosurgery was found to be beneficial in a few case series. Systemic immunotherapy can induce the regression of cutaneous metastases in selected patients.

Selective Advantage of NACT in Advanced Ovarian Cancer: A Retrospective Single-Centre Analysis

Background and Objectives: Advanced-stage epithelial ovarian cancer (EOC) is associated with poor prognosis, with complete macroscopic cytoreduction representing the strongest modifiable predictor of survival. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is an alternative to primary debulking surgery (PDS) in patients with high tumor burden. However, its impact on surgical complexity remains debated. This study aimed to compare operative characteristics and survival outcomes between NACT + IDS and PDS using standardized scoring metrics in a real-world oncologic setting. Materials and Methods: We retrospectively analyzed 47 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IV high-grade serous EOC treated between January 2018 and August 2022 at a single tertiary center. Twenty-five patients received platinum–taxane-based NACT followed by IDS, and twenty-two underwent upfront PDS with adjuvant chemotherapy. Surgical effort was quantified using the Surgical Complexity Score (SCS), and intra-abdominal tumor burden was assessed via the Peritoneal Cancer Index (PCI). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier analysis. Hazard ratios (HRs) with 95% confidence intervals were derived from Cox proportional hazards models. Results: Complete cytoreduction (R0) was achieved in 76% of the NACT + IDS group and 68% of the PDS group. Mean surgical complexity and operative time were significantly lower following NACT (SCS 5.0 vs. 6.2, p = 0.04; 140 vs. 197 min, p = 0.001), without significant differences in blood loss, complication rates, or length of hospital stay. Median PFS was 25 months in the NACT + IDS group versus 21 months in the PDS group, and the difference was not statistically significant. Among patients with R0 resection, survival outcomes were comparable between treatment arms. Conclusions: NACT + IDS was associated with shorter and less complex surgeries in selected patients, but survival outcomes appeared similar when R0 was achieved. Data suggest that selective use of NACT in patients with extensive disease burden or limited general health status may be suitable, while confirming that complete cytoreduction remains the most critical prognostic factor, although these survival comparisons are exploratory given the retrospective design and limited sample size.

Current Endocrine Therapy in Hormone-Receptor-Positive Breast Cancer: From Tumor Biology to the Rationale for Therapeutic Tunning

Background and Objectives: The objective of this review is to evaluate the current evidence regarding hormone treatments for both premenopausal and postmenopausal women with early-stage hormone receptor (HR) positive breast cancer. Materials and Methods: An in-depth exploration of the existing literature was conducted, with landmark clinical trials such as TEXT, SOFT, ATLAS, and aTTom serving as primary references. Results: Through an extensive review of the literature, our findings indicate that for premenopausal women with HR-positive, HER2-negative BC with a low risk of recurrence, standard 5-year monotherapy with tamoxifen represents the optimal therapeutic management, given its favorable clinical outcomes and lower associated toxicity. In contrast, for premenopausal women with an intermediate to high risk of recurrence with the same tumor characteristics, the most effective approach stated in the literature is a combination of ovarian suppression therapy (chemical/surgical) and an aromatase inhibitor/selective estrogen receptor modulator (tamoxifen), with a possible extension of the standard therapeutic period. In postmenopausal patients with HR-positive, HER2-negative breast cancer with a low recurrence risk, the first line of treatment is usually a standard 5-year period of treatment with aromatase inhibitors (AIs)(letrozole, anastrozole, or exemestane). On the other hand, in postmenopausal women with an intermediate to high risk, combination therapy might be needed, as well as an extension of the standard therapeutic time. Conclusions: Treatment consensus depends on pre- vs. postmenopausal status and recurrence risk.

Predictive Value of the CA-125 Elimination Rate Constant K (KELIM) in Predicting Progression-Free Survival and Overall Survival in Epithelial Ovarian Cancer

Background: It is crucial to predict the response to chemotherapy and identify prognostic markers for recurrence and survival in patients with epithelial ovarian cancer (EOC), in order to effectively manage patient care. The CA-125 elimination rate constant K (KELIM) has recently been developed as a means of assessing the chemotherapy response and has been tested mainly in patients enrolled in randomized controlled trials. The objective of this study was to investigate whether the KELIM score is a prognostic marker for progression-free survival (PFS) and overall survival (OS) in EOC, utilizing its role in predicting the chemotherapy response in real-life settings. Method: Demographic, surgical, and survival data of patients with EOC operated on in Antalya Training and Research Hospital between January 2015 and December 2021 were obtained from the electronic gynecological oncology clinic database system and analyzed retrospectively. Results: A total of 102 patients with EOC were included; 30 patients (29.4%) had a KELIM score ≥ 1 and 72 (70.6%) patients had a KELIM score < 1. In the group with a KELIM score < 1, recurrence and refractory disease occurred in 49 patients, while it was 11 patients in the group with a KELIM score ≥ 1 (p = 0.004). PFS was 12 months and 32 months in the groups with KELIM scores of <1 and ≥1, respectively (p = 0.012). There was no difference between groups regarding OS (p = 0.139). In the whole group, KELIM score (<1 vs. ≥1) and type of surgery (IDS vs. PDS) were found to be independent prognostic factors for PFS (RR = 0.44; 95%CI: 0.22–0.88; p = 0.021 and RR = 2.97; 95%CI: 1.76–5.01; p < 0.001, respectively). Conclusion: We found that a favorable KELIM score was associated with better PFS in all groups of patients undergoing surgery for EOC in a real-life setting. With the increasing number of studies, the KELIM score will play an important role in providing better guidance to clinicians at the initial presentation of patients and in subsequent treatment planning.

The Effect of MicroRNA 21 and MicroRNA 200b Expression on Carcinogenesis in Endometriosis-Associated Ovarian Cancers and Relationship with Clinicopathological Parameters

(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.

Diagnostic Performance of Gynecologic Imaging Reporting and Data System (GI-RADS) in Preoperative Evaluation of Adnexal Masses

Background and Objectives: Ovarian cancer is a highly lethal gynecological malignancy and the fifth leading cause of cancer-related deaths. Diagnosis mainly involves gynecological examination and transvaginal ultrasonography. To evaluate the diagnostic performance of the Gynecology Imaging Reporting and Data System (GI-RADS) with regard to its ability to evaluate adnexal masses preoperatively, considering a definitive histopathological diagnosis. Materials and Methods: This study was approved by the ethics committee, and informed consent was obtained from all the patients. This research was conducted at Beni-suef University Hospital between June 2021 and January 2023 on 100 women who experienced pelvic pain due to an adnexal mass. Results: Our study results revealed that the combination of IV-V GI-RADS had high specificity (92.2%), sensitivity (87%), and a negative predictive value (95.9%), but moderate other diagnostic characteristics for predicting adnexal mass malignancy. Conclusions: The GI-RADS classification system is a reliable method for reporting ovarian masses, with high diagnostic accuracy for predicting malignancy. It aids in patient triage and clinical decision making. To optimize care, it is essential to inform referring clinicians about the objectives of the GI-RADS before its implementation in a treatment plan.

Prediction of Clavien Dindo Classification ≥ Grade III Complications After Epithelial Ovarian Cancer Surgery Using Machine Learning Methods

Background and Objectives: Ovarian cancer surgery requires multiple radical resections with a high risk of complications. The aim of this single-centre, retrospective study was to determine the best method for predicting Clavien–Dindo grade ≥ III complications using machine learning techniques. Material and Methods: The study included 179 patients who underwent surgery at the gynaecological oncology department of Antalya Training and Research Hospital between January 2015 and December 2020. The data were randomly split into training set n = 134 (75%) and test set n = 45 (25%). We used 49 predictors to develop the best algorithm. Mean absolute error, root mean squared error, correlation coefficients, Mathew’s correlation coefficient, and F1 score were used to determine the best performing algorithm. Cohens’ kappa value was evaluated to analyse the consistency of the model with real data. The relationship between these predicted values and the actual values were then summarised using a confusion matrix. True positive (TP) rate, False positive (FP) rate, precision, recall, and Area under the curve (AUC) values were evaluated to demonstrate clinical usability and classification skills. Results: 139 patients (77.65%) had no morbidity or grade I-II CDC morbidity, while 40 patients (22.35%) had grade III or higher CDC morbidity. BayesNet was found to be the most effective prediction model. No dominant parameter was observed in the Bayesian net importance matrix plot. The true positive (TP) rate was 76%, false positive (FP) rate was 15.6%, recall rate (sensitivity) was 76.9%, and overall accuracy was 82.2% A receiver operating characteristic (ROC) analysis was performed to estimate CDC grade ≥ III. AUC was 0.863 with a statistical significance of p < 0.001, indicating a high degree of accuracy. Conclusions: The Bayesian network model achieved the highest accuracy compared to all other models in predicting CDC Grade ≥ III complications following epithelial ovarian cancer surgery.

The Role of Initial Neutropenia and Neutrophil Dynamics in Personalizing Chemotherapy for Platinum-Resistant Ovarian Cancer

Background and Objectives: Platinum-resistant ovarian cancer (PROC) is associated with limited treatment options and poor outcomes, with median progression-free survival (PFS) and overall survival (OS) remaining suboptimal. Neutropenia, a common chemotherapy-related toxicity, has shown potential as a predictive biomarker for treatment efficacy in several malignancies, including ovarian cancer. However, its role as a prognostic marker, particularly baseline neutropenia, remains underexplored. This study aimed to evaluate the prognostic and predictive value of initial neutropenia and neutrophil dynamics in PROC patients undergoing chemotherapy. Materials and Methods: A retrospective cohort study was conducted on 250 PROC patients treated between 2018 and 2022 at the OncoHelp Medical Center, Timișoara, Romania. Patients were stratified into two groups based on baseline absolute neutrophil count (ANC), as those with initial neutropenia (ANC < 2000/mm3) and without initial neutropenia (ANC ≥ 2000/mm3). Clinical outcomes, including tumor response, PFS, and OS, were assessed using RECIST 1.1 criteria. Hematological toxicities and neutrophil dynamics across three chemotherapy cycles were analyzed. Results: Patients with baseline neutropenia demonstrated significantly higher tumor response rates (47.05% vs. 27.27%; p = 0.002), longer median PFS (8.2 vs. 6.3 months; p = 0.008), and extended median OS (14.5 vs. 11.2 months; p = 0.002). Hematological toxicities, including Grade ≥3 neutropenia and febrile neutropenia, were more frequent in the neutropenic group (p < 0.001). Baseline ANC thresholds effectively predicted clinical outcomes, with an AUC of 0.79 for OS. Conclusions: Baseline neutropenia is a significant prognostic marker in PROC, correlating with improved tumor response and survival outcomes despite increased hematological toxicities. These findings support incorporating baseline ANC into treatment personalization strategies for PROC.

Prognostic and Predictive Value of Systemic Inflammatory Markers in Epithelial Ovarian Cancer

Background and Objectives: Epithelial ovarian cancer (EOC) remains a significant global health challenge. While traditional prognostic factors are well established, emerging biomarkers continue to gain attention. Materials and Methods: This retrospective study evaluated the impact of systemic inflammatory markers on progression-free survival (PFS) and overall survival (OS) in 154 EOC patients. Pre-treatment neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and systemic inflammatory index (SII) were calculated and categorized into low and high groups. Univariate and multivariate analyses were conducted to identify independent prognostic factors, while logistic regression analysis was used to determine predictors of platinum resistance. Results: In the univariate analysis, elevated NLR and PLR were associated with poorer PFS and OS. However, these markers did not maintain statistical significance in the multivariate analysis. Although SII demonstrated a trend toward worse outcomes, it did not reach statistical significance. Histopathological type, PLR, and surgical approach were identified as independent predictors of platinum resistance. Conclusions: Our findings indicate that systemic inflammatory markers may hold prognostic value in EOC; however, further validation through larger prospective studies is necessary.

Recovery of the Decreased Phagocytic Function of Peripheral Monocytes and Neutrophil Granulocytes following Cytoreductive Surgery in Advanced Stage Epithelial Ovarian Cancer

(1) Monocytes and neutrophil granulocytes are the phagocytic cells of the innate immune system, playing a crucial role in recognizing and eliminating tumor-transformed cells. Our objective was to assess the impact of advanced-stage epithelial ovarian cancer (EOC) and cytoreductive surgery on the phagocytic function of peripheral monocytes and neutrophil granulocytes. We aimed to compare the pre- and postoperative phagocytic function of these immune cells in EOC patients with healthy control women. Additionally, we aimed to examine the influence of surgery on phagocytic function by comparing pre- and postoperative samples from patients with benign gynecological tumors. (2) We examined peripheral blood samples from 20 patients with FIGO IIIC stage high-grade serous EOC and 16 patients with benign gynecological tumors as surgical controls, collected before and seven days after tumor removal surgery, and from 14 healthy women. After separation, the cells were incubated with Zymosan-A particles, and the phagocytic index (PI) was assessed using immunofluorescence microscopy. One-way ANOVA, the Kruskal–Wallis H-test, and the paired samples t-test were used for the statistical analysis of the data. A significance level of p < 0.05 was applied. (3) Peripheral monocytes and neutrophils from EOC patients exhibited significantly lower preoperative PI values compared to healthy controls (p < 0.001; p < 0.001, respectively). Following cytoreductive surgery, the PI values of immune cells in EOC patients significantly increased by the 7th postoperative day (p < 0.001; p < 0.001), reaching levels comparable to those of healthy controls (p = 0.700 and p = 0.991). In contrast, there was no significant disparity in the PI values of cells obtained from pre- and postoperative blood samples of surgical controls when compared to healthy women (monocytes: p = 0.361 and p = 0.303; neutrophils: p = 0.150 and p = 0.235). (4) EOC and/or its microenvironment may produce factors that reduce the phagocytic function of monocytes and neutrophils, and the production of these factors may be reduced or eliminated after tumor removal.

Therapy Response and Survival among Patients with Gynecologic Tumors Treated with Transarterial Chemoperfusion and Transarterial Chemoembolization

Background and Objectives: This study aimed to evaluate the tumor response relating to and survival benefit of transarterial chemoperfusion (TACP) and transarterial chemoembolization (TACE) in the treatment of patients with unresectable gynecologic tumors who are intolerant of or have a suboptimal response to chemotherapy and radiotherapy. Materials and Methods: Between January 2000 and October 2023, 75 patients diagnosed with gynecologic tumors underwent 213 TACP and 154 TACE procedures. Of these, 33 patients were treated with TACP, 20 were treated with TACE, and 22 received a combination of both therapies. A retrospective evaluation of local tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST) was conducted, and survival rates were determined using the Kaplan–Meier estimator. Results: Of the total 75 patients, 50 (67%) maintained a stable course of disease until the completion of therapy, 10 (13%) had a partial response, 2 (3%) had a complete response following thermal ablation, and 13 (17%) experienced progression. Furthermore, a 6% reduction in the sum of the longest diameters and an 8% reduction in tumor volume were observed. The median overall survival was 16.15 months, while the median progression-free survival was 13.19 months. Conclusions: TACP and TACE are potential treatment options for local tumor control in patients with unresectable gynecologic tumors who are intolerant of or show a poor response to chemotherapy and radiotherapy. However, further investigation and adjustment of treatment protocols are required to improve therapy response and survival outcomes.

Lynch Syndrome—Impact of the Type of Deficient Mismatch Repair Gene Mutation on Diagnosis, Clinical Presentation, Surveillance and Therapeutic Approaches

In today’s world, with its continuing advancements in genetics, the identification of Lynch syndrome (LS) increasingly relies on sophisticated genetic testing techniques. Most guidelines recommend a tailored surveillance program, as well as personalized prophylactic and therapeutic approaches, according to the type of dMMR gene mutation. Carriers of path_MLH1 and path_MSH2 genes have a higher risk of developing colorectal cancer (CRC), despite intensive colonoscopic surveillance. Conversely, carriers of path_MSH6 and path_PMS2 genes have a lower risk of developing CRC, which may be due to their lower penetrance and later age of onset. Thus, carriers of path_MLH1 or path_MSH2 would theoretically derive greater benefits from total colectomy, compared to low-risk carriers (path_MSH6 and path_PMS2), in which colonoscopic surveillance might achieve an efficient prophylaxis. Furthermore, regarding the risk of endometrial/ovarian cancer development, there is a global agreement to offer both hysterectomy and bilateral salpingo-oophorectomy to path_MLH1, path_MSH2 and path_MSH6 carriers after the age of 40. In patients with CRC, preoperative knowledge of the diagnosis of LS is of tremendous importance, due to the high risk of metachronous CRC. However, this risk depends on the type of dMMR gene mutation. For carriers of the high-risk variants (MLH1, MSH2 and EPCAM) who have already developed colon cancer, it is strongly recommended a subtotal or total colectomy is performed, while partial colectomy followed by endoscopic surveillance is an appropriate management approach to treat colon cancer in carriers of the low-risk variants (MSH6 and PMS2). On the other hand, extended surgery for index rectal cancer (such as total proctocolectomy) is less effective than extended surgery for index colon cancer from the point of view of metachronous CRC risk reduction, and is associated with a decreased quality of life.

Cystic Angiomyofibroblastoma of the Uterus Mimicking Ovarian Cancer

Angiomyofibroblastoma (AMFB) is an exceedingly rare mesenchymal tumor of the lower genital tract. AMFB primarily affects the pelviperineal region, especially the vulvar in premenopausal women. Typically, AMFB is a benign disease and does not have the potential for metastasis or recurrence, requiring complete surgical excision. Its accurate differentiation from aggressive angiomyxoma is critical due to varying prognoses. A 51-year-old woman, diagnosed with mucinous carcinoma of the breast, presented with a 12 cm abdominopelvic mass identified during breast cancer staging. Imaging suggested an ovarian origin; however, surgical exploration revealed a stalk-attached cystic mass in the anterior body of the uterus. Histopathology confirmed AMFB. Immunohistochemical analysis showed positivity for estrogen and progesterone receptors and smooth muscle actin. The patient continued breast cancer treatment postoperatively without pelvic mass recurrence or complications for a postoperative follow-up period of one year. This case highlights AMFB’s potential uterine body origin, expending known tumor sites and complicating diagnosis due to overlapping features with other mesenchymal tumors. Accurate diagnosis using immunohistochemical markers and pathological features is essential to avoid unnecessary aggressive treatments. The uterine location in this case suggests a possible shared pathogenesis with uterine myomas, warranting further research into their connection. Reporting the first case of AMFB originating in the uterine body enhances understanding of this rare condition and underscores the importance of clinical awareness and precise diagnostic strategies to guide management and improve outcomes.

Association of Pregnancy Complications with Endometrial or Ovarian or Breast Cancer: A Case Control Study

Background and Objectives: The relationship between pregnancy complications and the risk of gynecological and breast cancer remains inconclusive, with limited research available. This study aimed to determine whether pregnancy complications, including preeclampsia, gestational diabetes mellitus (GDM), large for gestational age (LGA), or intrauterine growth restriction (IUGR) are associated with the development of endometrial cancer (EC), ovarian cancer (OC), or breast cancer (BC). Materials and Methods: This was a population-based case–control study linked to the National Health Insurance Research Database from 2008 to 2020, using ICD codes to identify parous gynecological cases (n = 6714). The propensity score matching method was used to match control groups (n = 1,153,346). Multivariable logistic regression models were used to determine the association between EC, OC, BC risk and pregnancy complications. Results: In adjusted multivariable logistic regression models, women with a history of preeclampsia did not have a significantly increased risk of endometrial, ovarian, or breast cancer compared to controls. Although women with GDM complications had a significantly increased risk of breast cancer, the increased risk of EC or OC was not significant. The risk of BC in women with a history of IUGR or LGA was not significant, whereas risk statistics for EC or OC in women with a history of IUGR or LGA could not be shown because of the small sample size. Conclusions: GDM is associated with BC risk. Future studies should aim to determine whether there is a causal relationship. Therefore, cancer screening is warranted in women with GDM.

An Ovarian Sertoli–Leydig Cell Tumor with Elevated Alpha-Fetoprotein in an Adolescent: A Rare Case Report and Literature Review

An ovarian Sertoli–Leydig cell tumor is a rare type of sex cord–stromal tumor of the ovary. Typically, it presents as abdominal pain or androgenic manifestations in women in the second to third decade of life. While cases of ovarian Sertoli–Leydig cell tumor associated with increased levels of alpha-fetoprotein are rare, they are reported to be the most common alpha-fetoprotein-producing ovarian non-germ cell tumor. We report the case of a 16-year-old patient, who presented with complaints of amenorrhea that had lasted for one year. Transabdominal ultrasound revealed the presence of a tumor in the right ovary, measuring 9.3 × 5.8 cm in size. The laboratory investigation showed an increased level of alpha-fetoprotein. The patient underwent laparoscopic right salpingo-oophorectomy. Histopathological examination confirmed the presence of a moderately differentiated (G2) Sertoli–Leydig cell tumor in the right ovary. For reproductive-age patients with disease confined to the ovary, fertility-sparing surgery is recommended. According to the current recommendations, the administration of adjuvant chemotherapy is indicated in cases of the presence of heterologous elements, poorly differentiated tumors, or FIGO stages IB–IV. As there were no high-risk factors and no residual disease in this case, there were no indications for further treatment with adjuvant chemotherapy. A recent follow-up visit showed that the patient is in complete remission. This report presents a detailed description of the findings, differential diagnosis, clinical course, chosen treatment, and prognosis. Also, a comprehensive literature review of ovarian Sertoli–Leydig cell tumors, focusing on their clinical presentation, laboratory findings, macroscopic and histopathological features, genetics, clinical management, prognostic factors and follow-up, is provided.

Impact of Preoperative Gum Chewing on Postoperative Anti-Emetic Use in Robot-Assisted Laparoscopic Surgery for Benign Ovarian Masses: A Prospective, Single-Blinded Randomized Controlled Trial

Background and Objectives: Postoperative nausea and vomiting (PONV) is a common issue for females undergoing gynecological surgeries, including those assisted by robotic systems. Despite available prophylactic measures, the incidence of PONV remains high, negatively impacting recovery and increasing healthcare costs. This study evaluates whether preoperative gum chewing reduces the need for anti-emetic drugs in females undergoing robot-assisted laparoscopic surgery for benign ovarian mass. Materials and Methods: This prospective, single-blinded, randomized controlled trial enrolled 92 adult females scheduled for robot-assisted laparoscopic surgery to treat benign ovarian mass. Following exclusions, the remaining participants were randomly assigned to either a gum-chewing group or a no-gum-chewing group. The gum-chewing group chewed sugar-free gum for 15 min in the holding area before surgery. The primary outcome measured was the need for anti-emetics to control PONV during the first hour in the post-anesthesia care unit (PACU). Secondary outcomes included the number of anti-emetic requests. No preemptive anti-emetics were administered during surgery. Results: Out of the initial 92 patients, 88 were included in the final analysis, with 44 in each group. The incidence of PONV requiring anti-emetics in the PACU was significantly lower in the gum-chewing group (79.5%) compared to the no-gum-chewing group (95.5%). Additionally, the number of anti-emetic requests was higher in the no-gum-chewing group. No postoperative complications such as tooth or jaw pain/injury or gastric content regurgitation were reported. Conclusions: Preoperative gum chewing for 15 min immediately before surgery significantly reduced the incidence of PONV in females undergoing robot-assisted laparoscopic surgery for benign ovarian mass. This simple, non-pharmacological intervention improved patient comfort and reduced the need for anti-emetic medications without any adverse effects. Further studies are needed to confirm these findings and to develop guidelines for incorporating preoperative gum chewing into clinical practice.

Fertility-Sparing Treatments in Endometrial Cancer: A Comprehensive Review on Efficacy, Oncological Outcomes, and Reproductive Potential

Endometrial cancer (EC) affects 3–14% of women under 40 who wish to preserve their fertility. The standard treatment for EC is a hysterectomy with salpingo-oophorectomy. However, for those desiring fertility preservation, oral progestogens such as medroxy-progesterone acetate (MPA) or megestrol acetate (MA) are the most common therapies in Fertility-Sparing Treatment (FST). Other treatments include gonadotropin-releasing hormone agonist (GnRHa), levonorgestrel-releasing intrauterine system (LNG-IUS), and metformin plus progestin. This comprehensive review evaluates the best FST options for women with reproductive potential. PubMed, EMBASE, and Scopus were searched in June 2023 using specific keywords. Studies included in the review focused on patients with EC undergoing FST, with outcomes such as complete response rate (CRR), recurrence rate (RR), pregnancy rate (PR), and live birth rate. Eighteen studies met the inclusion criteria, involving 23,976 patients. In only-oral progestin trials, CRR ranged from 18% to 100%; RR ranged from 0% to 81.8%; Death Rate ranged from 0% to 3.6%. In studies combining oral progestin with LNG-IUS, CRR ranged from 55% to 87.5%; RR ranged from 0% to 41.7%; Death Rate was 0%. Most patients with Stage IA EC received MPA or MA. Fertility-related outcomes were reported in 15 studies. PR ranged from 4 to 44 patients in trials involving only oral progestins. When combining oral progestin with LNG-IUS, PR ranged from 1 to 46 patients. Progestin therapy, including oral MPA and MA, is considered safe and effective, with limited evidence supporting the use of LNG-IUS.

Ovarian Cancer and the Microbiome: Connecting the Dots for Early Diagnosis and Therapeutic Innovations—A Review

Ovarian cancer, which ranks eighth among global female cancers and fifth in fatality, poses a significant health challenge owing to its asymptomatic early stages. Understanding the pathogenesis requires extensive research. Recent studies have emphasized the role of the gut and cervicovaginal microbiota in ovarian cancer. This review explores the current understanding of the relationship between the microbiome and ovarian cancer, considering the potential of biomarkers in the serum and various tissues. Insights into the influence of the microbiome on treatments, including surgery and chemotherapy, open doors to innovative approaches, such as fecal microbiome transplantation. This synthesis of recent findings provides crucial insights into the intricate interplay between the microbiome and ovarian cancer, thereby shaping diagnostic and treatment strategies.

Ruptured Ovarian Cystic Teratoma: A Rare Diagnosis, Easily to Be Confused with Peritoneal Carcinomatosis

Although ovarian cystic teratoma is the most common ovarian tumor, complications are quite rare. However, it is important to be recognized by the radiologist in order to avoid inaccurately diagnosing them as malignant lesions. This case report describes a 61-year-old postmenopausal woman, who presented to the emergency room with abdominal pain following a minor blunt abdominal trauma. In this context, a CT scan was performed, which showed the presence of round, hypodense masses randomly distributed in the peritoneum, with coexisting ascites in moderate amount; ovarian carcinoma with peritoneal carcinomatosis was suspected. The patient was hospitalized and an MRI of the abdomen and pelvis was recommended for a more detailed lesion characterization. Following this examination, the patient was diagnosed with mature cystic ovarian teratoma complicated by rupture. Surgery was performed, and the outcome was favorable. The cases of ruptured cystic teratomas are rare, and to our knowledge, this is the first occurrence described in literature. Special attention must be paid when confronting with such a case in medical practice, since it can easily misdiagnosed as peritoneal carcinomatosis.

Significance of Tumor–Stroma Ratio (TSR) in Predicting Outcomes of Malignant Tumors

Background and Objectives: The present study aimed to elucidate the distribution and the prognostic implications of tumor–stroma ratio (TSR) in various malignant tumors through a meta-analysis. Materials and Methods: This meta-analysis included 51 eligible studies with information for overall survival (OS) or disease-free survival (DFS), according to TSR. In addition, subgroup analysis was performed based on criteria for high TSR. Results: The estimated rate of high TSR was 0.605 (95% confidence interval (CI) 0.565–0.644) in overall malignant tumors. The rates of high TSR ranged from 0.276 to 0.865. The highest rate of high TSR was found in endometrial cancer (0.865, 95% CI 0.827–0.895). The estimated high TSR rates of colorectal, esophageal, and stomach cancers were 0.622, 0.529, and 0.448, respectively. In overall cases, patients with high TSR had better OS and DFS than those with low TSR (hazard ratio (HR) 0.631, 95% CI 0.542–0.734, and HR 0.564, 95% CI 0.0.476–0.669, respectively). Significant correlations with OS were found in the breast, cervical, colorectal, esophagus, head and neck, ovary, stomach, and urinary tract cancers. In addition, there were significant correlations of DFS in breast, cervical, colorectal, esophageal, larynx, lung, and stomach cancers. In endometrial cancers, high TSR was significantly correlated with worse OS and DFS. Conclusions: The rate of high TSR was different in various malignant tumors. TSR can be useful for predicting prognosis through a routine microscopic examination of malignant tumors.

Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCTs): A Scoping Review of 511 Cases, Including 2 New Cases

Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCTs) are rare uterine mesenchymal neoplasms with uncertain biological potential. These tumors, which affect both premenopausal and postmenopausal women, usually have a benign clinical course. Nevertheless, local recurrences and distant metastases have been described. By analyzing 511 cases retrieved from individual reports and cases series, we provide here the most comprehensive overview of UTROSCT cases available in the literature, supplemented by two new cases of UTROSCTs. Case 1 was an asymptomatic 31-year-old woman who underwent a laparoscopic resection of a presumed leiomyoma. Case 2 was a 58-year-old postmenopausal woman with abnormal vaginal bleeding who underwent an outpatient hysteroscopic biopsy of a suspicious endometrial area. In both cases, immunohistochemical positivity for Calretinin and Inhibin was noted, typical for a sex cord differentiation. In both cases, total laparoscopic hysterectomy with bilateral salpingo-oophorectomy was performed. In light of the available literature, no pathognomonic clinical or imaging finding can be attributed to UTROSCT. Patients usually present with abnormal uterine bleeding or pelvic discomfort, but 20% of them are asymptomatic. In most cases, a simple hysterectomy appears to be the appropriate treatment, but for women who wish to become pregnant, uterus-preserving approaches should be discussed after excluding risk factors. Age, tumor size, lymphovascular space invasion, nuclear atypia, and cervical involvement are not reliable prognostic factors in UTROSCT. The current research suggests that aggressive cases (with extrauterine spread or recurrence) can be identified based on a distinct genetic and immunohistochemical phenotype. For instance, UTROSCTs characterized by GREB1::NCOA1-3 fusions and PD-L1 molecule expression appear to be predisposed to more aggressive behaviors and recurrence, with GREB1::NCOA2 being the most common gene fusion in recurrent tumors. Hence, redefining the criteria for UTROSCTs may allow a better selection of women suitable for fertility-sparing treatments or requiring more aggressive treatments in the future.

Giant Ovarian Tumor

Giant ovarian tumors are rare, as most cases are diagnosed during routine gynecological check-ups or abdominal ultrasound examinations. They are a challenge for gynecologists and surgeons. Diagnosis in such patients is difficult due to the limitations of the medical apparatus. Perioperative management requires specialized anesthetic medical care and is associated with high mortality. The paper presents the case of a 23-year-old woman with a giant ovarian serous tumor, characterized by an enlargement of the abdominal circumference, periodic abdominal pain, irregular menstruation, and infertility. The patient attributed these nonspecific symptoms to obesity; therefore, she was hesitant to schedule a doctor’s appointment. The patient underwent laparotomy, and the cyst originating from the left ovary was removed along with part of the organ. An intraoperative examination was performed. After confirming the benign nature of the lesion, the operation was completed. In our work, we concentrated on the multidisciplinary care of the patient who required enhanced medical care from the internal medicine, cardiology, anesthesiology, rehabilitation medicine, and gynecology specialists. There were no hemodynamic changes in the heart during hospitalization. There were no significant early or late postoperative complications. In this case, we also paid attention to compression symptoms resulting from a giant ovarian tumor and the high risk of intraoperative complications resulting from its resection.

Gramicidin, a Bactericidal Antibiotic, Is an Antiproliferative Agent for Ovarian Cancer Cells

Background and Objectives: Gramicidin, a bactericidal antibiotic used in dermatology and ophthalmology, has recently garnered attention for its inhibitory actions against cancer cell growth. However, the effects of gramicidin on ovarian cancer cells and the underlying mechanisms are still poorly understood. We aimed to elucidate the anticancer efficacy of gramicidin against ovarian cancer cells. Materials and Methods: The anticancer effect of gramicidin was investigated through an in vitro experiment. We analyzed cell proliferation, DNA fragmentation, cell cycle arrest and apoptosis in ovarian cancer cells using WST-1 assay, terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL), DNA agarose gel electrophoresis, flow cytometry and western blot. Results: Gramicidin treatment induces dose- and time-dependent decreases in OVCAR8, SKOV3, and A2780 ovarian cancer cell proliferation. TUNEL assay and DNA agarose gel electrophoresis showed that gramicidin caused DNA fragmentation in ovarian cancer cells. Flow cytometry demonstrated that gramicidin induced cell cycle arrest. Furthermore, we confirmed via Western blot that gramicidin triggered apoptosis in ovarian cancer cells. Conclusions: Our results strongly suggest that gramicidin exerts its inhibitory effect on cancer cell growth by triggering apoptosis. Conclusively, this study provides new insights into the previously unexplored anticancer properties of gramicidin against ovarian cancer cells.

The Management and Diagnosis of Anti-NMDA Receptor Autoimmune Encephalitis in Pregnant Women: A Case Report and Literature Review

Rationale: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a form of autoimmune synaptic encephalitis, often mediated by neuronal surface antibodies. Clinically, it manifests through a diverse range of neurological and psychiatric symptoms, primarily affecting young women with ovarian teratoma, which is rare in pregnant women. Patient concerns: We report a case of a 35-year-old multiparous pregnant patient at 38 weeks of gestation presented to the emergency room with seizure, psychiatric symptoms like delirious speech with mystical visual and auditory hallucinations, bradylalia, and retrograde amnesia. Diagnosis: The diagnosis of autoimmune encephalitis with anti-NMDA antibodies was concluded by considering the lumbar puncture results, brain imaging, and the patient’s persistent symptoms. Outcomes: This case is noteworthy for its rarity and the symptoms’ breadth. At 38 weeks of gestation, the patient underwent a cesarean section, resulting in excellent maternal recovery observed during the 6-month follow-up and good neonatal adaptation. Lessons: Our goals include raising awareness about this condition and emphasizing the significance of early diagnosis. This encephalitis is treatable and potentially reversible, underscoring the importance of prompt identification.

Comparative Diagnostic Value of 18F-FDG–PET–CT and Intraoperative Examination in Cervical Cancer Staging

Background and Objectives: The primary objective of this study is to assess the effectiveness of 18F-FDG–PET–CT in preoperative staging of cervical cancer, focusing on determining surgical operability and exploring the correlation between its quantitative parameters and clinicopathological characteristics. Materials and Methods: This retrospective study included 62 cervical cancer patients treated at the Department of Gynecology, Clinic for Operative Oncology at the Institute of Oncology Vojvodina between January 2016 and January 2020, where preoperative clinical examinations and 18F-FDG–PET–CT were performed to assess the extent of cancer, followed by intraoperative and pathohistological examinations of surgically removed specimens to provide a comprehensive evaluation. Results: The mean tumor size measured by 18F-FDG–PET–CT was slightly greater than that obtained through clinical examination (26.4 mm vs. 26.0 mm), with a strong linear correlation (r = 0.678, p < 0.001) observed between the two measurement methods. The overall prediction accuracy of 18F-FDG–PET–CT for primary tumors is 88.7% (55/62) [sensitivity 86.8%, specificity 100.0%, PPV 100.0%, NPV 56.2%] and for intraoperative examination is 88.7% (55/62) [sensitivity 98.1%, specificity 33.3%, PPV 89.7%, NPV 75.0%]. The agreement with histopathological examination was good for 18F-FDG–PET–CT and moderate for intraoperative examination for primary tumors. Regarding lymph nodes, the overall prediction accuracy of 18F-FDG–PET–CT is 82.2% (51/62) [sensitivity 53.8%, specificity 89.8%, PPV 58.3%, NPV 88.8%] and for intraoperative examination 66.1% (41/62) [sensitivity 76.9%, specificity 63.3%, PPV 35.7%, NPV 91.2%]. The agreement with histopathological examination was moderate for 18F-FDG–PET–CT and poor for intraoperative examination for lymph node metastasis, highlighting that the overall accuracy of 18F-FDG–PET–CT (82.1%) was significantly higher than that of intraoperative examination (66.1%) (p = 0.002). Conclusions: In conclusion, 18F-FDG–PET–CT provides high accuracy in detecting primary tumors and superior predictive value for lymph node metastases compared to intraoperative examination, highlighting the importance of incorporating this imaging modality into the preoperative evaluation process to enhance diagnostic precision and inform treatment decisions.

MicroRNA Expression in Endometrial Cancer: Current Knowledge and Therapeutic Implications

Background and Objectives: An extracellular vesicle is part of a class of submicron particles derived from cells, mediating cellular crosstalk through microRNA (miRNA). MiRNA is a group of RNA molecules, each of which consists of 15–22 nucleotides and post-transcriptionally modulates gene expression. The complementary mRNAs—onto which the miRNAs hybridize—are involved in processes such as implantation, tumor suppression, proliferation, angiogenesis, and metastasis that define the entire tumor microenvironment. The endometrial biopsy is a standard technique used to recognize cellular atypia, but other non-invasive markers may reduce patient discomfort during the use of invasive methods. The present study aims to examine the distribution and the regulation of the differentially expressed miRNAs (DEMs) and EV-derived substances in women with endometrial cancer. Materials and Methods: We systematically searched the PubMed, EMBASE, Scopus, Cochrane Library, and ScienceDirect databases in April 2023, adopted the string “Endometrial Neoplasms AND Exosomes”, and followed the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We selected all the studies that included patients with endometrial cancer and that described the regulation of miRNA molecules in that context. The differences in molecule expression between patients and controls were evaluated as significant when the proteins had a fold change of ±1.5. Results: Seventeen records fulfilled the inclusion criteria: a total of 371 patients and 273 controls were analyzed. The upregulated molecules that had the widest delta between endometrial cancer patients and controls—relative expression ≥ 1 > 3 log2(ratio)—were miR-20b-5p, miR-204-5p, miR-15a-5p, and miR-320a. In particular, miR-20b-5p and miR-204-5p were extracted from both serum and endometrial specimens, whereas miR-15a-5p was only isolated from plasma, and miR-320a was only extracted from the endometrial specimens. In parallel, the most downregulated miRNA in the endometrial cancer patients compared to the healthy subjects was miR-320a, which was found in the endometrial specimens. Conclusions: Although their epigenetic regulation remains unknown, these upregulated molecules derived from EVs are feasible markers for the early detection of endometrial cancer. The modulation of these miRNA molecules should be assessed during different treatments or if recurrence develops in response to a targeted treatment modality.

Prognostic Impact of Pelvic Lymph Node Count in Surgically Staged Endometrial Cancer

Background and Objectives: The prognostic significance of pelvic lymph node (PLN) count in surgically staged endometrial cancer remains controversial. This study aimed to evaluate the impact of PLN count on overall survival (OS), disease-free survival (DFS), and recurrence patterns in a large cohort of patients with endometrial cancer. Materials and Methods: This retrospective cohort study included 560 patients with endometrial cancer who underwent total hysterectomy, bilateral salpingo-oophorectomy, and pelvic and/or para-aortic lymph node assessment between January 2005 and May 2025 at a tertiary referral center. Patients were stratified according to the number of harvested pelvic lymph nodes (≤20 vs. >20). Clinicopathological characteristics, adjuvant treatments, recurrence patterns, and survival outcomes were analyzed. Survival analyses were performed using Kaplan–Meier estimates and Cox proportional hazards regression models. Results: Of the 560 patients, 262 (46.8%) had ≤20 pelvic lymph nodes harvested and 298 (53.2%) had >20. The median follow-up duration was 64.5 months. Patients with >20 pelvic lymph nodes had larger tumors, higher FIGO stage, and more frequent para-aortic lymphadenectomy. In multivariate analysis, age, non-endometrioid histology, advanced FIGO stage, tumor grade, and lymphatic metastasis were independently associated with both OS and DFS. Pelvic lymph node count was not independently associated with OS or DFS. Overall recurrence rates were similar between groups; however, recurrence patterns differed significantly, with distant recurrences more frequent in the ≤20 PLN group and local recurrences more common in the >20 PLN group. Conclusions: In surgically staged endometrial cancer, a higher pelvic lymph node count (>20 nodes) was not independently associated with survival or recurrence outcomes after adjustment for established prognostic factors, although recurrence patterns differed between groups. Survival was primarily determined by age, histologic subtype, FIGO stage, tumor grade, and lymphatic metastasis. Pelvic lymph node count appears to reflect surgical staging intensity and intraoperative risk assessment rather than serving as an independent determinant of prognosis.

Differential Expression of S100A8 in Tumor and Immune Compartments of Endometrial Carcinoma and Its Clinical Relevance

Background and Objectives: S100A8 regulates inflammatory responses and immune cell activation and is overexpressed in several solid tumors. However, its clinicopathological significance in endometrial carcinoma (EC) remains unclear. This study aimed to evaluate the expression patterns of S100A8 in both tumor and immune cells of EC and examine its association with clinicopathological features. Materials and Methods: Fifty-two formalin-fixed, paraffin-embedded EC specimens were analyzed using tissue microarray-based immunohistochemistry. S100A8 expression was assessed in tumor and immune cells. The tumor proportion score (TPS), tumor staining intensity (TI), and immune proportion score (IPS) were dichotomized into low and high categories (TPS/IPS: ≤30% vs. ≥31%; TI: 0–1+ vs. 2–3+). Correlations with clinicopathological parameters were examined using the chi-square and Fisher’s exact tests. Results: A low TPS, high TI, and high IPS were observed in 51.9%, 63.5%, and 57.7% of patients, respectively. TPS and TI showed no significant correlation with clinicopathological variables, including age, tumor size, invasion depth, histologic grade, T stage, and N stage (all p > 0.05). By contrast, IPS was significantly associated with patients’ age (p = 0.044) and histologic grade (p = 0.012), with older patients and those with higher-grade tumors demonstrating a higher IPS. A positive correlation was observed between TPS and IPS (p = 0.044), whereas TI did not correlate with IPS (p = 0.253). Conclusions: S100A8 expression in immune cells, but not in tumor cells, is associated with age and tumor grade in EC. Therefore, immune-related S100A8 expression may serve as a biomarker of the tumor immune microenvironment, warranting further investigation into its prognostic and therapeutic implications.

Oncological Safety of Intrauterine Manipulator Use in Laparoscopic Hysterectomy for Endometrial Cancer: A Propensity Score-Matched Analysis

Background and Objectives: Minimally invasive surgery is considered the standard of care for early-stage endometrial cancer. However, the oncological safety of intrauterine manipulator (IUM) use during laparoscopic hysterectomy remains controversial. The aim of this study was to evaluate the impact of intrauterine manipulator use during laparoscopic hysterectomy on oncological outcomes in patients with clinically early-stage endometrial cancer. Materials and Methods: In this retrospective cohort study, 612 patients with FIGO 2009 stage I–III endometrial cancer who underwent staging surgery at a tertiary center between January 2010 and May 2025 were included. Clinical and pathological characteristics were compared between laparoscopy (n = 168) and laparotomy (n = 444). To reduce selection bias, propensity score matching (PSM) was performed based on age, histological subtype, and FIGO stage. Kaplan–Meier survival analysis and Cox regression modeling were utilized to evaluate disease-free survival (DFS) and overall survival (OS). Results: After matching, groups were balanced except for higher rates of para-aortic lymphadenectomy and adjuvant therapy in the laparotomy group. IUM use was not associated with increased LVSI or positive peritoneal cytology. Recurrence was more frequent after laparoscopy (10.1% vs. 6.0%, p = 0.028), with inferior 5-year DFS (87.6% vs. 97.4%, HR 5.60, p = 0.0006), while OS was similar (82.0% vs. 87.6%, p = 0.842). In multivariate Cox analysis, independent predictors of worse DFS were non-endometrioid histology (HR 3.57), FIGO stage III (HR 3.06), grade 3 tumors (HR 2.63), and laparoscopic surgery (HR 0.51). For OS, non-endometrioid histology (HR 5.12), stage III disease (HR 2.98), and grade 3 tumors (HR 4.51) were independent adverse factors, whereas surgical approach was not. Conclusions: The use of an intrauterine manipulator in laparoscopic hysterectomy for early-stage endometrial cancer was linked to worse DFS but not OS. These findings suggest caution regarding the routine use of IUMs and highlight the need for prospective randomized trials to clarify their oncological safety.

Combined Hesperidin and Gemcitabine Therapy Modulates Apoptosis and Angiogenesis Pathways in ISHIKAWA Human Endometrial Adenocarcinoma Cells

Background and Objectives: Endometrial adenocarcinoma is among the most prevalent malignancies of the female reproductive system, and therapeutic options remain limited, particularly in advanced stages. In recent years, natural agents, especially flavonoids, have gained considerable interest for their capacity to enhance the effectiveness of chemotherapeutic drugs and modulate tumor-related molecular mechanisms. Hesperidin, a citrus-derived flavonoid, is recognized for its antioxidant and anti-inflammatory effects, while Gemcitabine, a nucleoside analog, is widely used in cancer treatment. Investigating their combined effects on endometrial carcinoma cells could yield novel insights into multimodal therapeutic development. This current study aimed to assess the impact of Hesperidin (Hes) and Gemcitabine (Gem) on ISHIKAWA cells, a human endometrial adenocarcinoma model, with particular attention to pathways associated with hypoxia, angiogenesis, apoptosis, and oxidative stress. Materials and Methods: ISHIKAWA cells were treated with varying concentrations of Hes (50–200 µM) and Gem (10–50 nM), either individually or together, for 24 and 48 h. Cell viability was determined using the MTT assay, while apoptosis was measured by Caspase-3/7 activity and NucBlue nuclear staining. Intracellular reactive oxygen species (ROS) generation was quantified via DCFH-DA fluorescence. Expression levels of HIF-1α, VEGF, Bax, Bcl-2, and Caspase-3 were examined by RT-qPCR. Synergistic interactions were analyzed with the Chou–Talalay combination index. Biological enrichment was further explored using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: Both Hes and Gem significantly decreased ISHIKAWA cell viability in a concentration- and time-dependent manner (p < 0.001). The combined treatment induced stronger apoptotic effects, as reflected by increased Caspase-3/7 activity and nuclear morphological changes. RT-qPCR demonstrated upregulation of Bax and Caspase-3, together with downregulation of Bcl-2, HIF-1α, and VEGF. While Hes reduced intracellular ROS, Gem elevated it; their combination produced a balanced oxidative response. All dose combinations displayed strong synergism (CI < 1). GO and KEGG enrichment confirmed the involvement of apoptosis-, angiogenesis-, and hypoxia-related pathways. Conclusions: Co-treatment with Hes and Gem exhibits synergistic anticancer activity in endometrial cancer cells by promoting apoptosis, suppressing angiogenesis- and hypoxia-related gene expression, and modulating oxidative stress. This combined therapeutic approach highlights its potential as a promising adjuvant option, warranting further evaluation in in vivo and translational studies.

Intraoperative Evaluation of Whole Sentinel Lymph Nodes Using a One-Step Nucleic Acid Amplification Assay in Endometrial Cancer: A Prospective Study

Background and Objectives: The aim of this prospective study was to evaluate the diagnostic accuracy of the one-step nucleic acid amplification (OSNA) assay for the intraoperative assessment of sentinel lymph node (SN) metastases, including micrometastases in patients with stage IA low-grade endometrial cancer. Materials and Methods: A prospective analysis was conducted on 204 patients with low-risk endometrial cancer who underwent hysterectomy, bilateral salpingo-oophorectomy, and sentinel node navigation surgery. SNs were analyzed intraoperatively using the OSNA assay, and positive patients underwent systematic pelvic lymphadenectomy. Results: Among the 204 patients included, SN metastases were identified in 12 patients (6%), including 10 patients with micrometastases and 2 patients with macrometastases. No metastases were detected in non-SNs in any of the 12 patients. Recurrence occurred in two patients (1%), involving the vaginal stump and pelvic cavity dissemination, but no lymph node recurrence was observed. The OSNA assay identified a proportion of micrometastases in low-risk endometrial cancer. While a direct comparison with conventional pathological ultra-staging was not performed in this study, the detection rate of micrometastases appears higher than that reported in historical controls. Conclusions: This is the first prospective study to evaluate the intraoperative use of the OSNA assay for whole SNs in endometrial cancer. The results suggest that the OSNA assay enhances the detection of micrometastases, enabling a more accurate assessment of SN metastases. In low-risk endometrial cancer, systematic pelvic lymphadenectomy may be safely omitted in patients with SN-positive micrometastases. Further prospective studies are necessary to validate these findings and support the adoption of this approach in clinical practice.

Impact of Para-Aortic Lymphadenectomy on Clinically FIGO Stage IIIC1 High-Grade Endometrial Cancer: A Retrospective Cohort Study from Two Tertiary Centers in Korea and Taiwan

Background and Objectives: The therapeutic effect of para-aortic lymphadenectomy in patients with clinically para-aortic node-negative diseases remains controversial. In this study, we investigated whether combined pelvic and para-aortic lymphadenectomy has a survival benefit compared with pelvic lymphadenectomy alone in patients with clinically FIGO stage IIIC1 high-grade endometrial cancer. Materials and Methods: We retrospectively reviewed patients with clinically FIGO stage IIIC1 high-grade endometrial cancer in the period between January 2000 and December 2020 at two tertiary centers. The patients were stratified according to type of lymphadenectomy and subgroup analyses performed. Kaplan–Meier analysis and a Cox proportional-hazards model were used to evaluate survival outcomes. Results: A total of 56 patients were identified. Of these patients, 18 underwent pelvic lymphadenectomy alone and 38 underwent combined pelvic and para-aortic lymphadenectomy. After staging surgery, 34 (60.7%) patients had pathologically confirmed lymph node metastases. Within a median follow-up of 57.5 months, there were no significant differences in recurrence-free survival (RFS) and overall survival (OS) between the two groups. In subgroup analyses, the node- and lymphovascular space invasion (LVSI)-positive patients characterized by grade 3 endometrioid histologic type (p = 0.010) or negative peritoneal washing cytology (p = 0.035) had an RFS benefit from combined pelvic and para-aortic lymphadenectomy. Conclusions: The addition of para-aortic lymphadenectomy to pelvic lymphadenectomy did not improve survival in patients with clinically FIGO IIIC1 endometrial cancer. However, para-aortic lymphadenectomy may have RFS benefit for patients with grade 3 endometrioid histologic type and positive LVSI.

Ovarian Leydig Cell Tumor and Ovarian Hyperthecosis in a Postmenopausal Woman: A Case Report and Literature Review

Ovarian Leydig cell tumor is a rare type of ovarian steroid cell neoplasms, presenting in only 0.1% of all ovarian tumor cases, and is generally androgen-secreting and unilateral. Although they are often malignant non-spreading tumors, which have excellent prognosis, benign ovarian Leydig cell tumors with low-risk malignancy can be also detected. Ovarian hyperthecosis is a rare non-neoplastic disorder, in most cases bilateral. Ovarian tumors and ovarian hyperthecosis are one of the main causes of hyperandrogenism in postmenopausal women, a condition strongly associated with both hormonal and metabolic changes. Here, we report a 65-year-old patient with complaints of excessive body hairiness and alopecia. The laboratory investigation showed increased levels of serum testosterone and dehydroepiandrosterone sulfate (DHEA-S). Imaging, including transvaginal ultrasound and pelvic MRI revealed the presence of two masses in the ovaries. The patient underwent a laparoscopic bilateral salpingo-oophorectomy due to the ovarian tumors unknown etiology, and histopathological examination revealed a unilateral benign left ovarian Leydig cell tumor with bilateral ovarian stromal hyperplasia and ovarian hyperthecosis. Making differential diagnosis between ovarian tumors and ovarian hyperthecosis is difficult. Bilateral salpingo-oophorectomy is the treatment of choice in postmenopausal women with benign Leydig cell ovarian tumor, as well as ovarian hyperthecosis, as it offers both a cure and diagnostic confirmation.

Meta-Analysis of Survival Effects of Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1)

Background and Objectives: Identification and targeting of membrane proteins in tumor cells is one of the key steps in the development of cancer drugs. The receptor tyrosine kinase-like orphan receptor (ROR) type 1 is a type-I transmembrane protein expressed in various cancer tissues, which is in contrast to its limited expression in normal tissues. These characteristics make ROR1 a candidate target for cancer treatment. This study aimed to identify the prognostic value of ROR1 expression in cancers. Materials and Methods: We conducted a comprehensive systematic search of electronic databases (PubMed) from their inception to September 2021. The included studies assessed the effect of ROR1 on overall survival (OS) and progression-free survival (PFS). Hazard ratios (HR) from collected data were pooled in a meta-analysis using Revman version 5.4 with generic inverse-variance and random effects modeling. Results: A total of fourteen studies were included in the final analysis. ROR1 was associated with worse OS (HR 1.95, 95% confidence interval (CI) 1.50–2.54; p < 0.001) with heterogeneity. The association between poor OS and ROR1 expression was high in endometrial cancer, followed by ovarian cancer, and diffuse large B cell lymphoma. In addition, ROR1 was associated with poor PFS (HR 1.84, 95% CI 1.60–2.10; p < 0.001), but heterogeneity was not statistically significant. In subgroup analysis, high ROR1 expression showed a significantly higher rate of advanced stage or lymph node metastasis. Conclusions: This meta-analysis provides evidence that ROR1 expression is associated with adverse outcome in cancer survival. This result highlights ROR1 as a target for developmental therapeutics in cancers.

Urologic Complication after Laparoscopic Hysterectomy in Gynecology Oncology: A Single-Center Analysis and Narrative Review of the Literature

Background and Objectives: Minimally invasive surgery (MIS) has recently increased its application in the treatment of gynecological malignancies. Despite technological and surgical advances, urologic complications (UC) are still the main concern in gynecology surgery. Current literature reports a wide range of urinary tract injuries, and consistent scientific evidence is still lacking or dated. This study aims to report a large single-center experience of urinary complications during laparoscopic hysterectomy for gynecologic oncologic disease. Materials and Methods: All patients who underwent laparoscopic hysterectomy for gynecologic malignancy at the Department of Medicine and Surgery of the University Hospital of Parma from 2017 to 2021 were retrospectively included. Women with endometrial cancer, cervical cancer, ovarian cancer, uterine sarcoma, or borderline ovarian tumors were included. Patients undergoing robotic surgery with incomplete anatomopathological data or patients lost during follow-up were excluded from the analysis. Intraoperative and postoperative UC were analyzed and ranked according to the Clavien-Dindo classification. Results: Two hundred-sixty patients were included in the study: 180 endometrial cancer, 18 cervical cancer, nine ovarian cancer, two uterine sarcomas, and 60 borderline ovarian tumors. Nine (3.5%) UCs were reported (five intraoperative and four postoperative complications). No anamnestic variables showed a statistical correlation with the surgical complication in the univariable analyses. C1 radical hysterectomy, a higher FIGO stage, and postoperative adjuvant treatment (p-value = 0.001, p-value = 0.046, and p-value = 0.046, respectively) were independent risk factors associated with the occurrence of UC. Conclusions: The urological complication rates in patients with oncological disease are relatively rare events in the expert hands of dedicated surgeons. Radical hysterectomy, FIGO stage, and adjuvant treatment are independent factors associated with urinary complications.

Impact of the COVID-19 Pandemic on Diagnosis and Management of Gynecological Cancer: A Single-Center Analysis

Background and Objectives: The COVID-19 pandemic impacted health systems worldwide, particularly cancer care. Because the actual implications of these changes on gynecological oncology healthcare are still unclear, we aim to evaluate the impact of this pandemic on the diagnosis and management of gynecological cancer. Materials and Methods: This is a single-center retrospective observational study, including patients diagnosed with gynecological malignancies between January 2019 and December 2021. Patients were included into three groups based on the timing of cancer diagnosis: pre-pandemic (2019), pandemic with high restrictions (2020) and pandemic recovery (2021). Results: Overall, 234 patients were diagnosed with gynecological cancer during the period of study. A decrease in the number of newly diagnosed cervical cancers and other rare tumors (leiomyosarcoma, invasive hydatidiform mole) was apparent in 2020. Some aggressive histological types of endometrial and ovarian cancer were more commonly diagnosed in the pandemic recovery group (p < 0.05), although no differences were demonstrated concerning tumor staging in all gynecological cancers. The median time between the first multidisciplinary team meeting and the treatment initiation was higher after the COVID-19 pandemic in endometrial cancer (23.0 vs. 34.0 vs. 36.0 days, p < 0.05). Patients with ovarian cancer were more frequently proposed for neoadjuvant therapy in 2020 compared to the other periods (33.3% vs. 55.0% vs. 10.0% p < 0.05). A significant reduction in the laparoscopic approach was observed during 2020 in endometrial cancer (32.1% vs. 14.3% vs. 36.4%, p < 0.05). No significant differences were registered regarding median hospitalization days or intra- and post-operative complications between these periods. Conclusions: The COVID-19 pandemic had a significant impact on the diagnosis and management of most gynecological malignancies, namely, on time to first treatment, chosen oncological therapies and surgical approaches. These results suggest important clinical and healthcare implications that should be addressed in future prospective studies.

Progression Free Survival, Overall Survival, and Relapse Rate in Endometrioid Ovarian Cancer and Synchronous Endometrial-Ovarian Endometrioid Cancer (SEO-EC): Results from a Large Retrospective Analysis

Background and Objectives: We aimed to evaluate Progression Free Survival (PFS), Overall Survival (OS), and relapse rate in women affected by endometrioid ovarian cancer and synchronous endometrial-ovarian endometrioid cancer (SEO-EC). As secondary outcome, we assessed whether systematic pelvic and para-aortic lymphadenectomy could be considered a determinant of relapse rate in this population. Materials and Methods: We performed a retrospective analysis of women with diagnosis of endometrioid ovarian cancer or SEO-EC between January 2010 to September 2020, and calculated PFS, OS and relapse rate. Results: In almost all the patients (97.6%) who underwent systematic pelvic and para-aortic lymphadenectomy, there were no lymph node metastases confirmed by histology. We did not find a significant difference (p = 0.6570) for the rate of relapse in the group of women who underwent systematic pelvic and para-aortic lymphadenectomy (4/42; 9.5%) compared with the group of women who did not undergo the same procedure (1/21; 4.8%). During a median follow-up was 23 months, both PFS and OS were excellent. Conclusions: Women affected by early-stage low-grade endometrioid cancer and SEO-EC without apparent lymph node involvement at pre-operative imaging showed a very low rate of lymph node metastasis and similar relapse rate with or without lymphadenectomy.

Gynecological Insights into Lynch Syndrome—A Comprehensive Review of Cancer Screening and Prevention

Lynch syndrome, one of the most common genetic syndromes predisposing to cancer, is associated with a series of malignant conditions, among which the most frequent is colorectal cancer, but gynecologic cancers (especially endometrial) are also quite common. Despite the significant progress made in understanding this condition over time, there are still aspects in managing this condition that have not demonstrated clear benefits. This article aims to summarize the recommendations of international societies and present the latest developments in managing Lynch syndrome, focusing on gynecologic cancer screening and possible prevention strategies. Advances in genetic testing procedures and discoveries related to the association between oncological pathology frequency and the affected pathogenic variant type will probably lead to personalized medicine focused on the individual patient in the coming years. Although various screening methods for gynecological cancers in patients with Lynch syndrome have been used over time, they have not shown significant survival benefits. This highlights the need for studying and implementing new screening and diagnostic methods, which have been under investigation in recent years and are mentioned in this article.

The Role of ROR1 in Chemoresistance and EMT in Endometrial Cancer Cells

Background and Objectives: Receptor tyrosine kinase-like orphan receptor type 1 (ROR1) plays a critical role in embryogenesis and is overexpressed in many malignant cells. These characteristics allow ROR1 to be a potential new target for cancer treatment. The aim of this study was to investigate the role of ROR1 through in vitro experiments in endometrial cancer cell lines. Materials and Methods: ROR1 expression was identified in endometrial cancer cell lines using Western blot and RT-qPCR. The effects of ROR1 on cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) markers were analyzed in two endometrial cancer cell lines (HEC-1 and SNU-539) using either ROR1 silencing or overexpression. Additionally, chemoresistance was examined by identifying MDR1 expression and IC50 level of paclitaxel. Results: The ROR1 protein and mRNA were highly expressed in SNU-539 and HEC-1 cells. High ROR1 expression resulted in a significant increase in cell proliferation, migration, and invasion. It also resulted in a change of EMT markers expression, a decrease in E-cadherin expression, and an increase in Snail expression. Moreover, cells with ROR1 overexpression had a higher IC50 of paclitaxel and significantly increased MDR1 expression. Conclusions: These in vitro experiments showed that ROR1 is responsible for EMT and chemoresistance in endometrial cancer cell lines. Targeting ROR1 can inhibit cancer metastasis and may be a potential treatment method for patients with endometrial cancer who exhibit chemoresistance.

Fertility Preservation in Endometrial Cancer—Treatment and Molecular Aspects

Endometrial cancer is one of the most common gynecological malignancies worldwide; incidences are rising, with 417,367 new cases registered in 2020. Of these, the proportion of women that are of reproductive age is around 4–14% and the number is increasing. Thus, in addition to oncological therapy and safety, the preservation of fertility plays a central role in therapeutic strategies. Molecular genetic patient data provide a robust supplementary benefit that improves primary risk assessment and can help design personalized treatment options to curtail over- and undertreatment and contribute to fertility preserving strategies. The aim of our review is to provide an overview of the latest significant recommendations in the diagnosis and therapy of endometrial cancer during reproductive age. In this paper the most recent groundbreaking molecular discoveries in endometrial cancer are highlighted and discussed as an opportunity to enhance the prognostic and therapy options in this special patient collective.

Hereditary Women’s Cancer: Management and Risk-Reducing Surgery

Hereditary women’s syndromes due to inherited mutations result in an elevated risk of developing gynecological cancers over the lifetime of affected carriers. The BRCA 1 and 2 mutations, Lynch syndrome (LS), and mutations in rare hereditary syndromes increase this risk and require more effective management of these patients based on surveillance and prophylactic surgery. Patients need counseling regarding risk-reducing surgery (RRS) and the time required to perform it, considering the adverse effects of premenopausal surgery and the hormonal effect on quality of life, bone density, sexual activity, and cardiological and vascular diseases. Risk-reducing salpingo-oophorectomy (RRSO) is the gold standard for BRCA-mutated patients. An open question is that of endometrial cancer (EC) risk in patients with BRCA1/2 mutation to justify prophylactic hysterectomy during RRSO surgical procedures. RRS provides a 90–95% risk reduction for ovarian and breast cancer in women who are mutation carriers, but the role of prophylactic hysterectomy is underinvestigated in this setting of patients. In this review, we evaluate the management of the most common hereditary syndromes and the benefits of risk-reducing surgery, particularly exploring the role of prophylactic hysterectomy.

Loss of Expression of Antiangiogenic Protein FKBPL in Endometrioid Endometrial Carcinoma: Implications for Clinical Practice

Background and Objectives: FK506 binding protein like (FKBPL) is a member of the immunophilin family, with anti-angiogenic effects capable of inhibiting the migration of endothelial cells and blood vessel formation. Its role as an inhibitor of tumor growth and angiogenesis has previously been shown in studies with breast and ovarian cancer. The role of FKBPL in angiogenesis, growth, and carcinogenesis of endometrioid endometrial carcinoma (EEC) is still largely unknown. The aim of this study was to examine the expression of FKBPL in EEC and benign endometrial hyperplasia (BEH) and its correlation with the expression of vascular endothelial factor-A (VEGF-A) and estrogen receptor alpha (ERα). Materials and Methods: Specimens from 89 patients with EEC and 40 patients with BEH, as well as histological, clinical, and demographic data, were obtained from the Clinical Hospital Centre Zemun, Belgrade, Serbia over a 10-year period (2010–2020). Immunohistochemical staining of the tissue was performed for FKBPL, VEGF-A, and ERα. Slides were analyzed blind by two pathologists, who measured the intensity of FKBPL and VEGF-A expression and used the Allred score to determine the level of ERα expression. Results: Immunohistochemical analysis showed moderate to high intensity of FKBPL expression in 97.5% (n = 39) of samples of BEH, and low or no expression in 93.3% (n = 83) of cases of EEC. FKBPL staining showed a high positive predictive value (98.8%) and a high negative predictive value for malignant diagnosis (86.7%). The difference in FKBPL expression between EEC and BEH was statistically significant (p < 0.001), showing a decrease in intensity and loss of expression in malignant tissues of the endometrium. FKBPL expression was positively correlated with ERα expression (intensity, percentage and high Allred score values) and negatively correlated with the expression of VEGF-A (p < 0.05 for all). Conclusions: FKBPL protein expression demonstrated a significant decrease in FKBPL in EEC in comparison to BEH tissue, with a high predictive value for malignancy. FKBPL might be emerging as a significant protein with antiangiogenic and antineoplastic effects, showing great promise for the diagnostic and therapeutic applications of its therapeutic derivatives in gynecological oncology.

Isolated Spleen Metastases of Endometrial Cancer: A Case Report

Background: Isolated splenic metastases from endometrial cancer, which is a relatively common malignancy, are extremely rare findings; to date, only 14 cases have been reported in the literature. Case Summary: We report a patient with isolated splenic metastases of endometrial cancer 3 years after radical surgery of the primary tumor. The patient was successfully treated by splenectomy and six cycles of paclitaxel. Fifty months after splenectomy, she was alive and well, and with no evidence of disease. Conclusion: Isolated spleen metastasis of endometrial cancer is very rare. Radical surgery and adjuvant therapy may offer excellent long-term survival.

Brain Metastases from Gynecologic Malignancies

Background and Objectives: To present a series of brain metastases from gynecologic primaries and provide a summary of the relevant literature. Materials and Methods: We retrospectively review 18 patients with histologically confirmed brain metastases from gynecologic primaries and summarize the largest series of relative reports. Results: Six brain metastases were of endometrial primary and 12 of ovarian primary. In 3 cases (16.7%), diagnosis of brain metastases was made at presentation of the gynecologic primary; in the others, median time to development of brain metastasis was 34 (range, 6–115) months. Median survival after brain metastasis diagnosis was 5 (range, 1–89) months. Favorable prognostic factors were better performance status (p = 0.04) and, marginally, smaller metastasis size (p = 0.06). No differences in brain metastases between endometrial and ovarian primaries were found, except for the time interval from primary to brain metastases diagnosis, which was shorter for endometrial tumors (p = 0.05). A comprehensive summary of previous studies is provided. Conclusions: Performance status and smaller brain metastases size are good prognostic factors. Endometrial cancer brain metastases develop earlier than ovarian cancer brain metastases.

Risk of More Advanced Lesions at Hysterectomy after Initial Diagnosis of Non-Atypical Endometrial Hyperplasia in Patients with Postmenopausal Bleeding and Oral Anticoagulant Treatment

Background and Objectives: Endometrial hyperplasia (EH) is a precursor lesion to endometrial cancer (EC), and when cellular atypia is present, in 40% of cases, they are diagnosed with EC on hysterectomy. Usually, EH is clinically manifested by uterine bleeding. In patients with oral anticoagulant therapy (OAT), the uterus is the second most common source of bleeding. The aim of the study was to show that uterine bleeding in postmenopausal patients undergoing OAT may reveal precancerous endometrial lesions with atypia, or neoplastic lesions in patients with an initial diagnosis of endometrial hyperplasia without atypia (non-atypical endometrial hyperplasia, NAEH) on dilation and curettage (D&C). We will be able to estimate the risk of a postmenopausal female patient with uterine bleeding during an OAT to have a precancerous endometrial lesion. Materials and Methods: The subjects of the study were 173 female patients with uterine bleeding, who have had total hysterectomy with bilateral salpingoovarectomy, of whom 99 underwent an OAT. There were 101 female patients initially diagnosed with NAEH, of which 60 did not have anticoagulant treatment (mean age 57.36 ± 6.51) and 41 had anticoagulant treatment (mean age 60.39 ± 7.35) (p = 0.006). From the pathology diagnosis moment, the surgery was performed at 42.09 ± 14.54 days in patients without OAT and after 35.39 ± 11.29 days in those who received such treatment (p = 0.724). Results: Initial diagnosis of NAEH established at D&C was changed at the final diagnosis after hysterectomy in EH with cellular atypia (atypical endometrial hyperplasia AEH) or EC in 18.18% of patients without OAT, and in 40.54% of patients who received this treatment. Conclusions: Based on a logistic regression model, it is estimated that female patients with an initial histopathological diagnosis of NAEH and who underwent OAT have, on average, 4.85 times greater odds (OR = 4.85, 95% CI 1.79–14.06) than the others of being identified postoperatively with more advanced lesions.

Insights into the Two Most Common Cancers of Primitive Gut-Derived Structures and Their Microbial Connections

The gastrointestinal and respiratory systems are closely linked in different ways, including from the embryological, anatomical, cellular, and physiological angles. The highest number (and various types) of microorganisms live in the large intestine/colon, and constitute the normal microbiota in healthy people. Adverse alterations of the microbiota or dysbiosis can lead to chronic inflammation. If this detrimental condition persists, a sequence of pathological events can occur, such as inflammatory bowel disease, dysplasia or premalignant changes, and finally, cancer. One of the most commonly identified bacteria in both inflammatory bowel disease and colon cancer is Escherichia coli. On the other hand, patients with inflammatory bowel disease are at risk of several other diseases—both intestinal (such as malnutrition and intestinal obstruction, besides cancer) and extraintestinal (such as arthritis, bronchiectasis, and cancer risk). Cancers of the lung and colon are the two most common malignancies occurring worldwide (except for female breast cancer). Like the bacterial role in colon cancer, many studies have shown a link between chronic Chlamydia pneumoniae infection and lung cancer. However, in colon cancer, genotoxic colibactin-producing E. coli belonging to the B2 phylogroup may promote tumorigenesis. Furthermore, E. coli is believed to play an important role in the dissemination of cancer cells from the primary colonic site. Currently, seven enteric pathogenic E. coli subtypes have been described. Conversely, three Chlamydiae can cause infections in humans (C. trachomatis may increase the risk of cervical and ovarian cancers). Nonetheless, striking genomic plasticity and genetic modifications allow E. coli to constantly adjust to the surrounding environment. Consequently, E. coli becomes resistant to antibiotics and difficult to manage. To solve this problem, scientists are thinking of utilizing suitable lytic bacteriophages (viruses that infect and kill bacteria). Several bacteriophages of E. coli and Chlamydia species are being evaluated for this purpose.

HbA1c as a Key Metabolic Marker in Predicting Myomectomy Requirement in Women with Uterine Fibroids: A Machine Learning Study

Background and Objectives: Uterine fibroids are common benign tumors that frequently require surgical management, particularly myomectomy, in women of reproductive age. Metabolic dysfunction and insulin resistance have been implicated in fibroid biology; however, the clinical relevance of glycated hemoglobin (HbA1c) in predicting myomectomy requirement remains unclear. This study aimed to evaluate the predictive role of HbA1c for myomectomy requirement in women with uterine fibroids using conventional statistical analyses and machine learning-based models under real-world clinical decision-making conditions. Materials and Methods: This study evaluated data from a retrospective multicenter cohort comprising 618 women with a diagnosis of uterine fibroids. Patients were stratified according to myomectomy status (performed vs. not performed). Comparative analyses, univariate and multivariate logistic regression, and machine learning modeling were conducted using demographic, laboratory, hormonal, and fibroid-related variables. A total of 155 machine learning models were trained, and the top 20 models with the highest accuracy were evaluated. Blinded concordance analysis was conducted on 50 independent, anonymized cases evaluated by a gynecologist who was blinded to the study data. Results: Patients undergoing myomectomy (38.5%) had significantly higher HbA1c levels than non-surgical patients (5.57 ± 0.32 vs. 5.03 ± 0.61, p < 0.001). HbA1c showed a strong association with myomectomy requirement in univariate analysis (OR 0.026, 95% CI 0.012–0.055) but lost significance in multivariate models, while ferritin remained independently associated. Machine learning models incorporating HbA1c, ferritin, hormonal, and fibroid parameters achieved accuracies between 0.99 and 1.00. Blinded concordance analysis demonstrated 94% concordance between model predictions and expert clinical judgment. Conclusions: HbA1c is a valuable integrative marker in predicting myomectomy requirement when evaluated within multidimensional machine learning frameworks, although its independent effect is confounded by iron-related parameters. These findings support the use of HbA1c as part of a comprehensive decision-support approach in uterine fibroid management.

An AI-Driven Clinical Decision Support Model Based on Anemia and Fibroid Parameters to Guide Surgical Decision-Making

Background and Objectives: This study aimed to identify the clinical factors associated with the need for surgical intervention in women with uterine fibroids (UFs) and develop a data-driven clinical decision helper algorithm. By comparing hematologic and fibroid characteristics and prospectively assessing clinical concordance with the model predictions, we sought to create an objective tool for surgical decision-making. Materials and Methods: This retrospective study enrolled 618 women with UFs who were evaluated at three participating hospitals. Of these, 238 (38.5%) underwent surgery. Comparative statistical analyses were conducted between patients who underwent myomectomy and those who did not. Machine learning (ML) models were trained to predict myomectomy necessity. A clinical concordance assessment was conducted using 50 cases that were evaluated in real time by a gynecologist blinded to both the clinical outcomes and the model outputs. Agreement between clinical assessment and algorithm-based predictions was subsequently evaluated. Results: Hemoglobin and ferritin concentrations were significantly reduced in the surgery group compared with the non-surgery group (p < 0.001). ML analyses integrating fibroid characteristics with anemia-related markers identified support vector ML models as the most accurate classifiers. Ferritin-based models achieved accuracies of 98–99% and near-perfect ROC–AUC values. ML models combining UF number or volume with ferritin demonstrated the highest precision, sensitivity, and F1-scores. Clinical concordance analysis showed 98% agreement with the blinded gynecologist, with only one borderline discordant case. Conclusions: This decision helper algorithm provides a highly accurate and objective tool for predicting surgical necessity in patients with UFs. Anemia status and fibroid characteristics were the strongest predictors. By reducing subjective variability and closely reflecting expert reasoning, the model offers a practical framework for integration into routine gynecologic decision-making.

A Simple Eco-Friendly HPLC-PDA Method for the Simultaneous Determination of Paclitaxel and Seliciclib in Plasma Samples for Assessing Their Pharmacodynamics and Pharmacokinetics in Combination Therapy for Uterine Sarcoma

Background/Objectives: Uterine sarcoma, a rare cancer originating in the smooth muscle of the uterus, exhibits high rates of recurrence and metastasis. It represents one of the most challenging types of cancer due to its chemorefractory nature, showing little response to conventional chemotherapy methods and displaying a relative survival rate of 30–40%. A potentially promising approach for treating uterine sarcoma involves combination therapy with paclitaxel (PAC), a microtubule-targeting agent, and seliciclib (SEL), a cyclin-dependent kinase inhibitor. SEL has been identified as a drug that can enhance the effectiveness of PAC through synergistic effects. To further refine this treatment strategy, an efficient analytical tool capable of simultaneously measuring the concentrations of PAC and SEL in blood plasma is needed. This tool would make it easier to study the pharmacokinetic interactions of potential drugs and assist in monitoring therapy when administering this combination treatment. Regrettably, a method meeting these specific requirements has not been documented in the existing literature. Methods: This article introduces the first HPLC technique employing a PDA detector to concurrently measure PAC and SEL levels in plasma. The methodology underwent validation in accordance with the ICH standards for validating bioanalytical methods. Results: The method exhibited linearity in the concentrations ranging from 0.8 to 100 µg mL−1 for both PAC and SEL. The limits of quantification were determined and found to be 1.34 and 1.25 µg mL−1 for PAC and SEL, respectively. All the other validation criteria conformed to the ICH validation standards. The HPLC-PDA method was successfully employed to quantify both PAC and SEL in plasma samples with a high level of reliability (in terms of accuracy and precision). The eco-friendliness of the approach was verified using three thorough assessments. This technique serves as a valuable asset in establishing the correct dosage and administration schedule for the combined treatment involving PAC and SEL, ensuring the desired therapeutic effects and safety in managing uterine sarcoma. Conclusions: The proposed HPLC-PDA method is the first reliable and eco-friendly method developed to simultaneously determine PAC and SEL in high-throughput plasma samples in clinical laboratories.

Uterine Leiomyomas with Specific Histology Features of Two Fumarate Hydratase/Succinate Dehydrogenase-Deficient Tumors: A Double Case Report

Background and Objectives: Mutations in succinate dehydrogenase (SDH) and fumarate hydratase (FH) give rise to various familial cancer syndromes, with these alterations being characteristic of certain types of histomorphologically specific leiomyomas that hold significant predictive value. Materials and Methods: This study presents two cases of uterine leiomyomas exhibiting rare histomorphological and genetic characteristics, which are crucial for prognosis and further treatment. Results: Distinct histopathological features such as marked nuclear atypia, intracellular eosinophilic globules, and abnormal intratumoral vessels raise suspicion for specific leiomyoma subtypes, which carry predictive significance for additional hereditary cancer syndromes. Immunohistochemical analysis confirmed FH/SDH deficiency in both patients, who underwent careful follow-up. Conclusions: This study describes two cases involving unusual leiomyomas, the histopathological characteristics of which may easily go unrecognized. These features hold predictive significance because their specific mutations point to additional hereditary cancer syndromes, highlighting the need for further examinations.

Heterotopic Tubal Choriocarcinoma Coexistent with a Viable Intrauterine Pregnancy: A Case Report

Background and Objectives: Choriocarcinoma is an aggressive oncological disease that manifests as trophoblast tissue proliferation. The vast majority of primary lesions affect the uterus, with primarily extrauterine lesions being a rarity. Choriocarcinoma with an ongoing pregnancy is extremely rare because fetuses usually do not survive the third trimester. Case Report: We present a case of heterotopic tubal choriocarcinoma coexisting with a viable intrauterine pregnancy. A 30-year-old, 39-week pregnant woman (gravida 2, para 2) came to our hospital complaining of acute upper abdominal pain. During routine prenatal screening in the first trimester, no pathological ultrasound findings were detected. Similar abdominal pain episodes had been recorded at 18, 27, and 32 weeks of gestation, when patient was hospitalized for examination and observation, but the cause of symptoms at that time of gestation remained unclear. The patient underwent an emergency caesarean section due to severe abdominal pain and fetal compromise. She delivered a live male infant. During the surgery, around 1000 mL of blood clots were evacuated, and the excision of the right fallopian tube and masses, as well as the control of significant blood loss was performed. Postoperative serum beta-hCG was elevated to 139 482 IU/L, while imaging studies showed no metastasis. The histological examination of the excised tissue samples confirmed a diagnosis of tubal choriocarcinoma. With a FIGO score of 8, the patient received three courses of the EP/EMA regimen. After more than a year, the patient showed no radiographic signs of distant metastasis and is now in complete remission. Conclusions: This case highlights the diagnostic complexity of such extremely rare scenarios. Even though such cases are rare, it demonstrates the necessity for improved diagnostic measures to enhance patient outcomes in similar clinical situations.

Cervical Cancer Screening: Histologic Outcomes of HPV-Negative HSIL/ASC-H Cytology in a Tertiary Referral Cohort in Northern Thailand

Background and Objectives: Cotesting combines cervical cytology and HPV testing and usually identifies HSIL/ASC-H in association with HPV positivity; however, a small subset shows discordant results with high-grade cytology but negative HPV testing. We evaluated the clinicopathologic significance and histologic outcomes of HPV-negative HSIL or ASC-H cytology in a tertiary referral setting. Materials and Methods: We retrospectively reviewed women referred to a tertiary colposcopy unit (January 2019–October 2025) with HPV-negative HSIL or ASC-H on cotesting. Clinical findings, colposcopy, histology, excisional procedures, and follow-up were abstracted. Cytology and histology were reviewed by an expert gynecologic pathologist, and p16 immunohistochemistry was performed in all cases. Results: Among 92 women with HSIL/ASC-H cytology who underwent cotesting, 84 were HPV-positive (35 HSIL, 49 ASC-H). Eight cases (8.7%) remained HPV-negative after cytology review: 2/37 (5.4%) HSIL and 6/55 (10.9%) ASC-H. On histology, 4/8 (50%) had HSIL (CIN3) and 4/8 had LSIL; all CIN3 cases showed diffuse block-type p16 positivity. Two of six HPV-negative ASC-H cases (33.3%) were CIN3. One patient had persistent high-grade disease requiring two excisional procedures during follow-up. Conclusions: HPV-negative HSIL/ASC-H cytology is uncommon but associated with a substantial risk of CIN3. The consistent p16 positivity in tissue-confirmed HSIL supports HPV-attributable disease and suggests that most discordant cases reflect false-negative HPV testing rather than HPV-independent pathology. High-grade cytology should prompt colposcopic evaluation regardless of HPV status, and management should not be de-escalated solely on the basis of a negative HPV test.

Targeting Ovarian Neoplasms: Subtypes and Therapeutic Options

The ovary, as the primary organ responsible for reproduction and new life, plays a central role in female development, maturation, and health. Neoplasms arising from the ovary and its associated tissues exhibit substantial heterogeneity in their histopathological and molecular profiles, many of which remain poorly understood. This review aims to summarize recent advances in the understanding of genetic alterations underlying ovarian neoplasms and to explore therapeutic strategies informed by molecular biomarkers and tumor microenvironmental factors. A comprehensive literature search was performed, focusing on genomic alterations, biomarker-guided therapies, and tumor microenvironmental modulation in ovarian cancers. Emphasis was placed on studies addressing lipid mediator pathways and their roles in immune regulation and therapeutic response. Based on diagnostic classifications, recurrent alterations in TP53, MYC, PIK3CA, and KRAS are consistently observed across epithelial and germ cell ovarian tumors, whereas non-epithelial subtypes such as sex cord–stromal tumors (SCSTs) and small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT), are predominantly associated with ARID1A and SMARCA4 mutations, respectively. These findings highlight distinct pathogenic mechanisms linked to specific genetic alterations and reveal potential therapeutic vulnerabilities. Moreover, lipid metabolism has been closely implicated in immune surveillance through STING signaling cascades within innate immune cells, suggesting that lipid mediators and their associated genes may represent promising therapeutic targets in ovarian cancers (OCs). Targeting lipid mediators could be particularly effective in relapsed OCs, as modulating innate immune cells within the tumor microenvironment (TME) may enhance immune surveillance and improve antitumor responses. Integrating genetic and microenvironmental insights offers a promising direction for developing more effective and personalized therapeutic strategies in OC.

An AI-Driven Clinical Decision Support Framework Utilizing Female Sex Hormone Parameters for Surgical Decision Guidance in Uterine Fibroid Management

Background and Objective: Changes in female sex hormone levels are closely linked to the development and progression of uterine fibroids (UFs). Clinical approaches to fibroid management vary according to guidelines and depend on patient symptoms, fibroid size, and clinician judgment. Despite available diagnostic tools, surgical decisions remain largely subjective. With the advancement of artificial intelligence (AI) and clinical decision support technologies, clinical experience can now be transferred into data-driven computational models trained with hormone-based parameters. To develop a clinical decision support algorithm that predicts surgical necessity for uterine fibroids by integrating fibroid characteristics and female sex hormone levels. Methods: This multicenter study included 618 women with UFs who presented to three hospitals; 238 underwent surgery. Statistical analyses and artificial intelligence-based modeling were performed to compare surgical and non-surgical groups. Training was conducted with each hormone—follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), prolactin (PRL), and anti-Müllerian hormone (AMH)—and with 126 input combinations including hormonal and morphological variables. Five supervised learning algorithms—support vector machine, decision tree, random forest, and k-nearest neighbors—were applied, resulting in 630 trained models. In addition to this retrospective development phase, a prospective validation was conducted in which 20 independent clinical cases were evaluated in real time by a gynecologist blinded to both the model predictions and the surgical outcomes. Agreement between the clinician’s assessments and the model outputs was measured. Results: FSH, LH, and PRL levels were significantly lower in the surgery group (p < 0.001, 0.009, and <0.001, respectively), while E2 and AMH were higher (p = 0.012 and 0.001). Fibroid volume was also greater among surgical cases (90.8 cc vs. 73.1 cc, p < 0.001). The random forest model using LH, FSH, E2, and AMH achieved the highest accuracy of 91 percent. In the external validation phase, the model’s predictions matched the blinded gynecologist’s decisions in 18 of 20 cases, corresponding to a 90% concordance rate. The two discordant cases were later identified as borderline scenarios with clinically ambiguous surgical indications. Conclusions: The decision support algorithm integrating hormonal and fibroid parameters offers an objective and data-driven approach to predicting surgical necessity in women with UFs. Beyond its strong internal performance metrics, the model demonstrated a high level of clinical concordance during external validation, achieving a 90% agreement rate with an independent, blinded gynecologist. This alignment underscores the model’s practical reliability and its potential to reduce subjective variability in surgical decision-making. By providing a reproducible and clinically consistent framework, the proposed AI-based system represents a meaningful advancement toward the validated integration of computational decision tools into routine gynecological practice.

The “Undefined and Ignored Normal Tissue” Bulboclitoral Complex in Locally Advanced Cervical Cancer Treated with Definitive Radiochemotherapy: Is It Not the Organ at Risk?

Background and Objectives: The bulboclitoral complex (BCC) is an essential organ for female sexual health. However, it is not defined as an organ at risk in any guideline defining target volumes in radiotherapy of gynecological cancers, and there is no information about dose constraint. Materials and Methods: Simulation computed tomography scans of 20 patients diagnosed with locally advanced cervical cancer were used retrospectively. The volumetric modulated arc therapy treatment plan with a total dose of 45 Gy in 25 fractions was created using the planning target volume (PTV)-standard, which was created without considering the BCC, and the PTV-BCC spared, which were contoured and included in the optimization. Bulboclitoral complex doses in PTV-standard and PTV-BCC spared plans were compared using the paired simple t test. Results: Median BCC volume was 17.6 cm3 (11.20–25.50). Bulboclitoral complex maximum dose (Dmax) was median 49.07 Gy (48.49–50.25) and 28.81 Gy (18.14–44.61) in the PTV-standard and PTV-BCC spared plans, respectively, and the BCC Dmax was statistically significantly lower in the PTV-BCC spared plan (p < 0.001). When comparing BCC percentage of volume receiving 45 Gy (V45), the median values for PTV-standard and PTV-BCC spared plans were 37.5% (13.3–82.6) and 0%, respectively (p ≤ 0.001). Conclusions: The bulboclitoral complex can be dosimetrically protected from radiation by contouring and optimizing it as an organ at risk in the radiotherapy plan. The clinical effects of protecting the BCC from radiation as an organ at risk on sexual health need to be investigated.

Perspectives from Hysterectomy Specimens on the Hidden Malignancy Risk in HSIL Patients with Surgical Margin Continuity

Background and Objectives: We aim to examine the histopathological results following hysterectomy performed due to insufficient cervical tissue in patients diagnosed with high-grade squamous intraepithelial lesions (HSILs) who underwent the loop electrosurgical excision procedure (LEEP) and cold-knife conisation (CKC) and exhibited continuity at the surgical margin and residual disease. Materials and Methods: Thirty-four patients who underwent hysterectomy due to insufficient cervical tissue and had HSILs at the surgical margin were included in this study. The following information was analysed: age, body mass index (BMI), parity, menopausal status (premenopausal/postmenopausal), smoking history, smear result, HPV result, colposcopic cervical biopsy result, transformation zone information, LEEP+Endocervical Curettage (ECC) histopathological result, CKC+ECC histopathological result, hysterectomy material histopathological result, presence or absence of cervical glandular involvement, and presence or absence of residual lesions in the hysterectomy material. Results: The mean (±SD) age of the study cohort was 46.7 ± 8.3 years, the mean BMI was 27.4 ± 2.3 kg/m2, and the mean parity was 2.5 ± 0.7. According to the results of the hysterectomy performed on these 34 patients, in whom Cervical Intraepithelial Neoplasia 3 (CIN3) continuity at the surgical margin and the inability to perform re-excision were determined, 8 patients (23.5%) had CIN2, 19 patients (55.9%) had CIN3, 3 patients (8.8%) had adenocarcinoma in situ, and 4 patients (11.8%) had squamous cell carcinoma (SCC). Histopathological examinations of the hysterectomy specimens revealed negative surgical margins in all patients, while glandular involvement was present in 13 patients (34.2%). Conclusions: It should be borne in mind that patients with HSILs showing continuity at the surgical margin may have an underlying squamous cell carcinoma. These patients should be carefully evaluated for hysterectomy if they do not have sufficient cervical tissue for repeat excisional procedures.

Comprehensive Genomic Characterization of 102 Cervical Adenocarcinoma Tumors

Background and Objectives: Cervical adenocarcinoma (CAC) is a histologically distinct subtype of cervical cancer with a rising incidence in many regions. While the roles of key driver mutations are known, a comprehensive understanding of its genomic landscape, particularly variations across different populations and tumor stages, remains incomplete. This study aims to characterize the somatic genomic landscape of CAC by identifying recurrent mutations, copy number alterations (CNAs), and patterns of co-occurrence, with a focus on variations across racial groups and between primary and metastatic tumors. Materials and Methods: We conducted a comprehensive genomic analysis of 102 tumor samples from 99 patients diagnosed with cervical adenocarcinoma using data from the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database. Results: The most frequently mutated genes were PIK3CA (25.5%), TP53 (21.6%), ARID1A (20.6%), and KRAS (16.7%). Significant amplification of ERBB2 was also observed (n = 3; 4.83%). Our analysis revealed notable genomic disparities across racial groups, with TP53 mutations being significantly more frequent in White patients compared to Asian and Black patients (p = 0.0236). Furthermore, we identified significant co-occurrence between mutations in KRAS and MSH2 (p = 0.011) as well as ATM and STK11 (p = 0.037). In comparing tumor types, mutations in BCL6 were found to be significantly enriched in metastatic samples. Conclusions: This study validates the primary drivers of cervical adenocarcinoma and reveals novel findings, including notable racial disparities in TP53 mutation frequency and unique patterns of co-occurring mutations. These findings highlight the genomic heterogeneity of the disease and suggest that ancestry and tumor evolution may influence its molecular pathogenesis, offering potential avenues for the development of targeted therapies and personalized biomarkers.

Relationship Between Population Density, Availability of Gynecological Services, and Cervical Cancer Incidence and Mortality Across Administrative Units in Serbia and Bosnia and Herzegovina During 2016–2020

Background and Objectives: Burden of cervical cancer in Central and Eastern Europe is higher than in other parts of Europe. We analyzed cervical cancer epidemiology in Serbia and Bosnia and Herzegovina (the Federation of Bosnia and Herzegovina and the Republic of Srpska) from January 2016 to December 2020, exploring the role of available sociodemographic factors and healthcare service parameters on incidence and mortality rates, using an ecological approach based on aggregated data. Materials and Methods: Incidence and mortality rates are standardized using the method of direct standardization with the World-ASR-W. Administrative units are grouped by tertiles of incidence and mortality to explore sociodemographic factors and healthcare parameters across these groups. Results: Average age-standardized incidence rates of cervical cancer per 100,000 females were 19.28 in Serbia, 12.48 in the Federation of Bosnia and Herzegovina, and 22.44 in the Republic of Srpska. Mortality rates per 100,000 females were 6.67, 5.22, and 4.56 in Serbia, the Federation of Bosnia and Herzegovina, and the Republic of Srpska, respectively. Several parameters of sociodemographics and health service usage differed significantly across units grouped by tertiles based on incidence level, i.e., female population ≥ 15 years old (p = 0.028), population density (p = 0.046), percent of gynecologists in the primary healthcare (p = 0.041), number of gynecologists per 10,000 females ≥ 15 years (p = 0.007), and the area-to-gynecologist ratio (p = 0.010). A moderate negative correlation was found between incidence and population density (rho = −0.465, p = 0.017), and a moderate positive correlation between incidence and area-to-gynecologist ratio (rho = 0.534, p = 0.005). Conclusions: Cervical cancer remains a leading cause of cancer among women in developing countries. Implementing tailored activities, such as educational programs, preventive services, and investments in healthcare infrastructure, particularly at the administrative units’ level, can help in reducing health disparities and improving health outcomes.

Expression of Core Hippo Pathway Proteins in Cervical Cancer and Their Association with Clinicopathologic Parameters

Background: The Hippo signaling pathway, a highly conserved regulatory cascade, regulates tissue homeostasis, organ size, and tumor suppression. Dysregulation of this pathway contributes to oncogenesis in various human malignancies; however, its clinicopathologic relevance in cervical cancer has not been completely elucidated. Therefore, this study aimed to investigate the expression patterns of key Hippo pathway proteins and analyze their associations with tumor behavior and clinicopathologic features in cervical carcinoma. Materials and Methods: Ninety-nine cervical cancer specimens obtained from hysterectomies performed at Gyeongsang National University Hospital (2012–2019) were retrospectively analyzed. Immunohistochemical staining for Yes-associated protein (YAP), phosphorylated YAP (p-YAP), mammalian sterile-20-like kinase-1 (MST1), and large tumor suppressor kinase-1 (LATS1) was performed on tissue microarrays. Chi-square or Fisher’s exact tests and logistic regression were employed for assessing associations between marker expression and clinicopathologic variables. Functional validation was conducted via small interfering RNA-mediated YAP knockdown in Caski cervical cancer cells, with reverse transcription-polymerase chain reaction, Western blotting, and wound-healing assays assessing YAP suppression and cell migration. Results: YAP and p-YAP were expressed in 71.8% and 62.6% of tumors, respectively; MST1 in 82.8%; and LATS1 in 22.2%. YAP and p-YAP overexpression was correlated with larger tumor size (p = 0.013 and p = 0.011) and higher International Federation of Gynecology and Obstetrics stage (p = 0.007 and p < 0.001). YAP and p-YAP expression was positively correlated (odds ratio, 4.34; 95% confidence interval, 1.70–11.61). MST1 or LATS1 expression demonstrated no significant associations. In vitro, YAP silencing decreased mRNA and protein expression levels and significantly impaired cell migration, supporting its role in tumor aggressiveness. Conclusions: YAP and p-YAP overexpression are associated with advanced stage and larger tumor size in cervical cancer, indicating Hippo pathway dysregulation. YAP functional suppression attenuated migratory capacity, highlighting YAP as a promising prognostic biomarker and therapeutic target.

The Vaginal Microbiota, Human Papillomavirus, and Cervical Dysplasia—A Review

Background and Objectives: The relationship between the vaginal microbiota, human papillomavirus infection (HPV), and cervical precancerous lesions is a critical area of research, as it influences both the progression of HPV-related diseases and potential treatment strategies. New evidence suggests that Lactobacillus crispatus dominance in the microbiota may protect against HPV persistence and speed the elimination of HPV. This study aims to explore the relationship between the vaginal microbiota composition and HPV infection, focusing on the impact of these factors on the development of cervical precancerous lesions. Materials and Methods: A comprehensive literature review was conducted using the PubMed database, focusing on studies that analyzed the association between the vaginal microbiota and HPV infection in the context of cervical dysplasia. This study was primarily based on clinical data on HPV integration in women with low-grade squamous intraepithelial lesions (LSILs), high-grade squamous intraepithelial lesions (HSILs), and cervical cancer. Results: Different types of vaginal microbiota communities (CSTs) have different pathogenic or protective potential. Healthy women predominantly exhibited CST I, with Lactobacillus crispatus as the dominant microorganism. CST IV, associated with increased anaerobic bacteria, was most common in HSIL and cervical cancer patients. Statistical analysis revealed that bacterial vaginosis (BV) was significantly associated with HPV persistence, with studies reporting a 1.8–3.4-fold increased risk (p < 0.05) of persistent HR-HPV infection in BV-positive women. Conclusions: Our literature review suggests that the composition of the vaginal microbiota can modulate the local immune response, the expression of viral oncogenes, and the integrity of the epithelial barrier. Furthermore, certain bacterial genes or metabolic pathways can be associated with a favorable or unfavorable outcome of the disease. Analysis of the vaginal microbiota could serve as an additional risk assessment tool, helping to distinguish between regressing and progressive precancerous conditions.

Hydatidiform Mole with Coexisting Normal Pregnancy: A Systematic Review and Individual Participant Data Meta-Analysis

Background and Objectives: This study aimed to evaluate obstetric, neonatal, and oncologic outcomes of pregnancies complicated by a hydatidiform mole coexisting with a live fetus (HMCF) carried beyond viability, and to assess the impact of delivery mode on outcomes. Materials and Methods: A systematic review and individual participant data meta-analysis included HMCF cases progressing beyond 23 weeks. Obstetric and neonatal outcomes, delivery patterns, and oncologic risks were analyzed. Results: Among 118 pregnancies complicated by HMFC (124 newborns), most were complete moles (87%). Median delivery occurred at 31.6 weeks, with over half before 32 weeks. Common complications included vaginal bleeding (59%), preeclampsia (30%), and hyperthyroidism (18%). Cesarean delivery was performed in 79% of cases, often for mole-related factors, but was not associated with reduced maternal or oncologic risk. Neonatal deaths occurred exclusively in infants delivered ≤32 weeks, highlighting extreme prematurity as the key determinant of survival. Severe preeclampsia was strongly linked to earlier delivery. Conclusions: With close monitoring, continuation of HMCF pregnancies is possible. Neonatal mortality is mainly driven by prematurity, which appears to be an indirect consequence of HMFC through the development of mola-associated complications. Cesarean section does not appear to improve maternal and oncologic outcomes. Vaginal delivery can be considered when no standard contraindications exist.

Interplay Between Immune Microenvironment CD8+ Tumor-Infiltrating Lymphocytes and PDL-1 Expression as Prognostic Markers in Invasive Cervical Squamous Cell Carcinoma

Background: Cervical cancer remains a major cause of cancer-related morbidity and mortality worldwide, with limited therapeutic options for advanced disease. As we better understand the fine mechanisms involved in the interaction between tumor cells and the tumor microenvironment, new paths and opportunities will emerge. Recent evidence highlights the prognostic and predictive roles of immune checkpoint markers and tumor-infiltrating lymphocytes (TILs), especially CD8+ TILs, in shaping treatment outcomes. Objectives: This study investigated the immunohistochemical expression of PD-L1 and CD8+ TILs in 48 newly diagnosed, treatment-naive cervical cancer cases and analyzed their associations with clinicopathological features and survival outcomes. Results: In our cohort, we observed that PD-L1 positivity was identified in 68.8% of cases, most frequently in advanced FIGO stages and in tumors with lympho-vascular invasion or with a high proliferation rate evaluated by the Ki-67 index. High levels of intra-tumoral CD8+ TILs were observed in 52.1% of cases and correlated positively with stromal TILs, lower proliferation rates, and absence of vascular invasion. A significant inverse relationship was found between PD-L1 expression and the density of CD8+ TILs (p = 0.047). Survival analysis showed that patients exhibiting a “cold” immunophenotype with low levels of CD8+ TILs and PD-L1-positive tumors had worse outcomes, while high levels of CD8+ TILs played a protective role. Conclusions: Our study highlights the importance of the immunohistochemical assessment of PD-L1 and CD8+ TILs biomarkers, which have a complementary inter-relationship and have a significant prognostic impact on cervical squamous cell carcinoma. PD-L1 positivity marks aggressive disease features, while higher intra-tumoral CD8+ TIL density is protective. Their combined evaluation may improve patient stratification and inform immunotherapy strategies.

Currently Available Treatment Modalities for Uterine Fibroids

Uterine fibroids (leiomyomas and myomas) are the most common benign gynecological condition in patients presenting with abnormal uterine bleeding, pelvic masses causing pressure or pain, infertility and obstetric complications. Almost a third of women with fibroids need treatment due to symptoms. Objectives: In this review we present all currently available treatment modalities for uterine fibroids. Methods: An extensive search for the available data regarding surgical, medical and other treatment options for uterine fibroids was conducted. Review: Nowadays, treatment for fibroids is intended to control symptoms while preserving future fertility. The choice of treatment depends on the patient’s age and fertility and the number, size and location of the fibroids. Current management strategies mainly involve surgical interventions (hysterectomy and myomectomy hysteroscopy, laparoscopy or laparotomy). Other surgical and non-surgical minimally invasive techniques include interventions performed under radiologic or ultrasound guidance (uterine artery embolization and occlusion, myolysis, magnetic resonance-guided focused ultrasound surgery, radiofrequency ablation of fibroids and endometrial ablation). Medical treatment options for fibroids are still restricted and available medications (progestogens, combined oral contraceptives andgonadotropin-releasing hormone agonists and antagonists) are generally used for short-term treatment of fibroid-induced bleeding. Recently, it was shown that SPRMs could be administered intermittently long-term with good results on bleeding and fibroid size reduction. Novel medical treatments are still under investigation but with promising results. Conclusions: Treatment of fibroids must be individualized based on the presence and severity of symptoms and the patient’s desire for definitive treatment or fertility preservation.

The Value of the Naples Prognostic Score at Diagnosis as a Predictor of Cervical Cancer Progression

Background and Objectives: The Naples prognostic score (NPS), which incorporates inflammatory and nutritional indicators, is increasingly used as a prognostic score for various malignancies. Nonetheless, few studies have specifically evaluated the NPS as a prognostic factor for cervical cancer. This study aimed to assess the value of NPS at diagnosis as a predictor of cancer progression. Materials and Methods: This study included patients diagnosed with cervical cancer at Korea University Anam Hospital from January 2019 to December 2023. Patients with incomplete data or those who were lost to follow-up were excluded. The NPS was calculated based on laboratory results at the time of diagnosis, categorizing patients into the low-NPS group (NPS 0–1) and high-NPS group (NPS ≥ 2). Survival analysis was performed using the Kaplan–Meier method and log-rank test. Univariate and multivariate Cox proportional hazards models were used to identify independent prognostic factors. Results: Out of 178 patients, 98 and 80 were categorized into the low-NPS and high-NPS groups, respectively. Kaplan–Meier survival analysis showed that the high-NPS group had significantly lower disease-free survival (DFS) (p < 0.001) and overall survival (OS) (p = 0.02) rates than the low-NPS group. Multivariate Cox regression analysis identified the NPS as an independent prognostic factor for DFS (adjusted hazard ratio, 1.98; p = 0.017), but not for OS. Conclusions: This study demonstrated that the NPS measured at diagnosis may serve as a useful independent prognostic factor for cancer progression in patients with cervical cancer.

Editorial for Special Issue “Diagnosis and Treatment of Cervical Cancer”

Cervical cancer remains one of the most significant gynecologic malignancies worldwide, particularly impacting women in their reproductive years [...]

“Pre-Treatment“ and “Post-Treatment” Systemic Inflammatory Markers: Is There Any Prognostic Role for Metastatic Cervical Cancer on Bevacizumab Containing Treatment?

Background and Objectives: Despite developments in cervical cancer (CC) treatment, an advanced stage is a poor prognostic factor. Cervical cancer is an immunogenic tumor in which viruses, like HPV, play a role in carcinogenesis. Therefore, systemic inflammatory markers (SIMs) may have prognostic value. Most studies on SIMs focus on the early stage by evaluating pretreatment levels. This study aims to evaluate the prognostic and predictive values of both pretreatment and post-treatment parameters at the advanced stage, as well as treatment efficacy after progression with first-line treatment. Materials and Methods: A total of 133 advanced-stage CC patients with progression on first-line platin–paclitaxel and bevacizumab were evaluated retrospectively. Demographic and histopathological characteristics were recorded along with treatment details. Pre-treatment baseline blood parameters and post-treatment follow-up values were recorded to calculate SIMs as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammatory response index (SIRI). Results: Median values for SIMs were accepted as cut-off values. Post-treatment values demonstrated stronger predictive power, with pre-treatment SIRI and NLR being significant only in univariate analysis, but not in multivariate analysis. High post-treatment SIRI (>2.1) was correlated with shorter overall survival (OS) and considered a poor prognostic factor. High post-treatment SIRI (>2.1), -SII (>746), and -PLR (>197) emerged as independent prognostic factors for progression-free survival (PFS). Their prognostic values were clearer in the whole population and the metachronous metastatic subgroup. Rechallenge of platinum-based chemotherapy was an option for those who had at least 6 months of PFS with first-line platinum-based chemotherapy. Bevacizumab addition to single-agent or combination regimens led to improved ORR as well. Conclusions: Post-treatment SIRI is a promising prognostic factor for OS, while post-treatment SIRI, SII, and PLR may serve as convenient SIMs for PFS. Platinum-based combination chemotherapy reinduction is a feasible second-line treatment strategy, especially with the addition of bevacizumab.

Lower Urinary Tract Symptoms in Uterine Myoma: A Systematic Review and Meta-Analysis

Background and Objectives: Lower urinary tract symptoms (LUTSs) are prevalent among patients with uterine myoma (UM); however, these health issues have not been systematically evaluated. To address this research gap, this systematic review and meta-analysis synthesizes existing findings on the prevalence estimates and odds ratios for LUTSs in patients with UM. Materials and Methods: A systematic literature search using PubMed and Embase was conducted for articles published between 1 January 2000 and 24 September 2023. The search and review processes followed the PRISMA and MOOSE guidelines. This study was registered in PROSPERO (CRD42023474156). Data on the prevalence and odds ratios of LUTSs—including storage symptoms (frequency, urgency, nocturia), voiding symptoms, and urinary incontinence (UI) subtypes such as stress incontinence (SUI), urgency urinary incontinence (UUI), and mixed urinary incontinence (MUI)—were extracted. Pooled prevalence estimates and odds ratios were calculated using random-effects meta-analysis. Subgroup analyses and univariate meta-regression were conducted to examine associations with age, BMI, parity, WHO region, and risk of bias. The impact of UM size was assessed using standardized mean differences. Results: Of the 572 articles screened, 20 met the inclusion criteria. The overall pooled prevalence of LUTSs in UM patients was 49% (95% CI, 26–72%), with substantial heterogeneity across studies (I2 = 99.8%). The pooled prevalence for urinary frequency, urgency, nocturia, voiding dysfunction, and overall UI, SUI, UUI, and MUI ranged from 15% to 54%. SUI and UUI were significantly associated with UM (OR = 2.0, 95% CI: 1.2–3.3; OR = 1.5, 95% CI: 1.1–2.0, respectively). Hysterectomy was not associated with an improvement in overactive bladder (OAB) symptoms (OR = 1.9, 95% CI: 0.6–5.7). A larger UM size was not linked to worsening LUTS. Fourteen studies (70%) had some concerns about the risk of bias, while six studies (30%) had a low risk of bias. Egger’s test showed no significant publication bias (p = 0.19). Conclusions: Approximately half of patients with UM experience LUTSs or UI. The findings emphasize the need to consider urinary symptoms in UM management. Further research is warranted to reduce heterogeneity and explore treatment-specific outcomes.

A Minimally Invasive Treatment Approach for Early-Stage Uterine Cervical Cancer: The Impact of the LACC Trial and a Literature Review

Background and Objectives: Recent studies have supported the non-inferiority of the minimally invasive treatment approach over the open approach. However, they have also underlined its inferiority regarding its oncological results, while preserving the short-term benefits. The direct effects of these results were represented by indication changes in international guidelines on the application of minimally invasive surgery for treating early-stage cervical cancer. Material and metods: Herein, a literature review, including studies between 1992 and 2017, was performed. Results: The results show that the studies published during this period supported the non-inferiority of the minimally invasive treatment approach for early-stage cervical cancer compared with the open approach. However, the studies included were unicentric, non-randomized and relied on a reduced number of patients. The results of the Laparoscopic Approach to Cervical Cancer [LACC] trial could not have been considered, since only studies published between 1992 and 2017 were included. This trial firmly supported the advantages of the minimally invasive approach in treating early-stage cervical cancer. The literature published after 2018 highlighted the necessity for new clinical studies, randomized and prospective ones, to cover the defects of this study and to verify (or not) its results. Conclusions: the studies published after 2018 mainly focused on the deficiencies of the LACC trial and also on developing new methods that could improve this surgical technique, thus enhancing the safety of the minimally invasive approach in treating early-stage cervical cancer. However, none of the included studies succeeded to provide enough evidence to oppose the results obtained in the LACC trial. Therefore, in order to clarify the state of this surgical approach, the results of three ongoing randomized clinical trials are expected.

Reproductive Outcomes in Young Women with Early-Stage Cervical Cancer Greater than 2 cm Undergoing Fertility-Sparing Treatment: A Systematic Review

Background and Objectives: Despite advancements in detection and treatment, cervical cancer remains a significant health concern, particularly among young women of reproductive age. Limited data exists in the literature regarding fertility-sparing treatment (FST) of cervical cancers with tumor sizes greater than 2 cm. The objective of this systematic review was to evaluate the reproductive outcomes of women diagnosed with cervical cancer greater than 2 cm who underwent FST. Materials and Methods: A comprehensive search of the literature was carried out on the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), the Health Technology Assessment Database, and Web of Science. Only original studies (retrospective or prospective) that reported reproductive outcomes of patients with cervical cancer >2 cm were considered eligible for inclusion in this systematic review (CRD42024521964). Studies describing only the oncologic outcomes, involving FST for cervical cancers less than 2 cm in size, and case reports were excluded. Results: Seventeen papers that met the abovementioned inclusion criteria were included in the present systematic review. In total, 443 patients with a cervical cancer larger than 2 cm were included in this systematic review. Eighty pregnancies occurred, with 24 miscarriages and 54 live births. Conclusions: FST appears to be a viable option for women of childbearing age diagnosed with cervical cancer larger than 2 cm. However, careful consideration is advised in interpreting these encouraging results, as they are subject to limitations, such as variability in study designs and potential biases. In addition, reproductive outcomes should be further cross-referenced with oncologic outcomes to clarify the potential risk–benefit ratio. It is critical to conduct further research using standardized approaches and larger participant groups to strengthen the validity of the conclusions drawn.

Heart Failure Associated with Giant Uterine Leiomyoma: A Case Report

Heart failure impairs the heart’s pumping ability and triggers catecholamine production as an adaptive mechanism. Uterine leiomyomas are common tumors of the female reproductive tract. Their growth is promoted by dysregulated angiogenesis and gonadal steroid hormones. Although uterine leiomyomas share risk factors with most cardiovascular diseases, their relationship with heart failure has not been well described. Herein, we present the case of a 45-year-old woman with heart failure who visited the emergency department, where we incidentally discovered a giant uterine leiomyoma. The patient was admitted with progressive dyspnea and abdominal distension. Echocardiography revealed an enlarged right ventricle and a decreased systolic function. Computed tomography revealed cardiomegaly with bilateral pleural effusions and a tumor measuring 18.0 × 12.0 cm in the abdominal cavity with massive ascites. A diagnosis of heart failure in conjunction with a uterine leiomyoma was established, which prompted the prescription and adjustment of heart failure medications according to the patient’s clinical presentation. Three weeks later, given the persistent symptoms of bilateral lower extremities pitting edema and abdominal distension, a total hysterectomy was performed. Postoperatively, echocardiography revealed marked improvement in her heart failure. The patient was discharged in a stable clinical and hemodynamic conditions, and reported good physical condition at the 4-month follow-up. Growth factors and the compression effect of uterine leiomyomas may predispose patients to heart failure and exacerbate its deterioration. Although reports of fibroid-related heart failure are rare, uterine leiomyomas should be considered a potential cause of refractory heart failure. Nevertheless, a direct association requires a longer follow-up period.

Predictors of Infused Distending Fluid Volume in Hysteroscopic Myomectomy

Background and Objectives: The use of a bipolar resectoscope has become popular due to the lower risk of hyponatremia. However, gynecologists might overlook the risk of water intoxication. Water intoxication is associated with the infusion of distending fluid. We were interested in the prediction of the infused distending fluid volume in the era of bipolar hysteroscopy. Thus, the aim of this study was to identify the predictors of the infused distending fluid volume for hysteroscopic myomectomy. Materials and Methods: All consecutive women who underwent monopolar (n = 45) or bipolar (n = 137) hysteroscopic myomectomy were reviewed. Results: Myoma diameter (cm, coefficient = 680 mL, 95% confidence interval (CI) = 334–1025 mL, p <0.001) and bipolar hysteroscopy (coefficient = 1629 mL, 95% CI = 507–2752 mL, p = 0.005) were independent predictors of infused distending fluid volume. A myoma diameter ≥4.0 cm was the optimal cutoff value to predict the presence of >5000 mL of infused distending fluid. One woman in the bipolar group developed life-threatening water intoxication. Conclusions: Myoma diameter is associated with an increase in infused distending fluid volume, especially for myomas ≥4 cm. Meticulous monitoring of the infused distension fluid volume is still crucial to avoid fluid overload during bipolar hysteroscopic myomectomy.

The Clinical Course of the Late Toxicity of Definitive Radiotherapy in Cervical Cancer

Background and Objectives: This study aimed to investigate the clinical course and characteristics of late toxicity over time following the completion of definitive radiotherapy (RT) in patients with cervical cancer. Materials and Methods: We retrospectively reviewed the medical records of 60 patients with cervical cancer who underwent pelvic external beam radiotherapy followed by intracavitary brachytherapy. Late toxicity was assessed for the lower gastrointestinal (GI) tract and bladder organ at 6, 12, 24, 36, and >36 months post-RT. We examined the onset and prevalence of late toxicity at each time point. Clinical remission and interventions for managing late toxicity were also investigated. Results: The peak onset of lower GI toxicity occurred 12 months after RT completion, with a median symptom duration of 9.9 months (range, 0.1–26.3 months), and exhibited its highest prevalence rate of 15.5% at 24 months post-RT. Most GI toxicities developed and resolved within three years post-RT, with a prevalence rate of 8.1% at three years, followed by a decreasing trend. Bladder toxicity first peaked at 24 months post-RT and continued to occur beyond 36 months, showing the re-increasing pattern in the prevalence rate after 36 months (23.5%). In terms of clinical remission, 66.7% of lower GI toxicities (12 of 18 patients) and 60% of bladder toxicities (9 of 15 patients) achieved complete remission by the last follow-up date. Conclusions: Late toxicities of the GI and bladder following definitive RT in cervical cancer are partially reversible and exhibit distinct patterns of onset and prevalence over time. A systematic follow-up strategy should be established for the early detection and timely intervention of late toxicity by understanding these clinical courses.

Boswellic Acid Enhances Gemcitabine’s Inhibition of Hypoxia-Driven Angiogenesis in Human Endometrial Cancer

Background and Objectives: Endometrial carcinoma is among the most common gynecological malignancies, with recurrence and chemoresistance remaining major clinical challenges. This study aimed to evaluate the combined effects of Boswellic acid (BA), a natural pentacyclic triterpene, and Gemcitabine (GEM), a nucleoside analog chemotherapeutic, on hypoxia, angiogenesis, and apoptosis in human endometrial cancer cells. Materials and Methods: ECC-1 cells were treated with BA, GEM, or their combination under normoxic and hypoxic conditions. Cell viability (MTT assay); nuclear morphology (NucBlue staining); cell cycle distribution (PI flow cytometry); angiogenesis (VEGF ELISA expression); apoptosis (Caspase-3/7 activity; Bax; Bcl-2 expression); inflammatory cytokines (IL-1β; IL-6; TNF-α); and gene ontology enrichment were analyzed. Results: Both BA and GEM reduced cell viability in a dose- and time-dependent manner, with the combination producing synergistic cytotoxicity and lower IC50 values. Hypoxia enhanced drug sensitivity, particularly in combination therapy. BA and GEM significantly suppressed HIF-1α and VEGF expression, with maximal inhibition observed in the combination group. Apoptotic induction was confirmed by increased Bax and Caspase-3 and decreased Bcl-2 expression, together with elevated Caspase-3/7, -8, and -9 activity. Pro-inflammatory cytokine levels were markedly reduced, and gene ontology analysis revealed enrichment of apoptotic, anti-proliferative, and anti-angiogenic pathways. Conclusions: BA + GEM combination synergistically suppresses hypoxia-driven angiogenesis and promotes apoptosis in endometrial cancer cells. These findings support its potential as an adjuvant therapeutic approach, warranting further preclinical and clinical validation.

Cold Knife Versus Carbon Dioxide for the Treatment of Preinvasive Cervical Lesion

Background and Objectives: Cervical cancer (CC) represents a significant health concern worldwide, particularly for younger women. Cold knife (CK) conization and carbon dioxide (CO2) laser conization are two techniques commonly used to remove pre-invasive lesions, offering a potential curative intent in cases of incidental diagnosis of CC. This study aimed to assess the clinical implications and pathological outcomes of CK vs. CO2 laser conization for pre-invasive lesions. Materials and Methods: We retrospectively analyzed women who underwent CO2 or CK conization for high-grade preinvasive lesions (CIN2/3, CIS and AIS) between 2010 and 2022. Patient demographics, surgical details and pathological outcomes were collected. Pregnancy outcomes, including composite adverse obstetric rates, and oncological follow-up data, were also obtained. Results: In all, 1270 women were included; of them, 1225 (96.5%) underwent CO2, and 45 (3.5%) underwent CK conization. Overall, the rate of positive endocervical or deep margins was lower with CO2 laser compared to CK (4.3% vs. 13.3%, p = 0.015). Incidental CC was diagnosed in 56 (4.4%) patients, with 35 (62.5%) squamous and 21 (46.6%) adenocarcinomas. In a multivariate regression model, the relative risk for positive endocervical or deep margins is significantly greater in cases of incidental diagnosis of CC (p < 0.01). In cases of incidental diagnosis of CC, we found that the probabilities of having either positive endocervical or deep margins after CO2 laser or CK conization are similar, with a higher risk in case of adenocarcinoma lesion. Among women with CC, 42 (75%) opted for radical treatment, while 14 (25%) underwent a follow-up. Only one woman (7.1%) in the follow-up group, who had undergone CK conization, experienced a composite adverse obstetric outcome. No recurrences were observed after a median follow-up of 53 months. Conclusions: CO2 laser conization achieved a lower positive margin rate overall. CK and CO2 conization appear to be equivalent oncological options for incidental CC.

Cardiovascular Mortality in Ovarian Cancer Patients: An Analysis of Patient Characteristics Using the SEER Database

Background and Objectives: Cardiovascular disease (CVD) is a major contributor to the high mortality rate among individuals with ovarian cancer. Nevertheless, there is limited understanding regarding the specific patient attributes that might impact the risk of CVD in this group. Materials and Methods: A retrospective cohort study was performed using the SEER database to analyze primary ovarian cancer cases from 2000 to 2019. Multivariable logistic regression analysis was employed to identify patient characteristics linked to cardiovascular mortality. Results: The cohort included 41,930 cases of patients who were alive, 54,829 cases of cancer-related deaths, 3003 cases of cardiovascular-related deaths, and 10,238 cases with other causes of death. Poorly differentiated cancer cells and distant metastasis were associated with a higher risk of cardiovascular mortality. Logistic regression analysis identified age, year of diagnosis, race, laterality, and staging as significant risk factors for cardiovascular cause of death. The risk of cardiovascular cause of death was lower in patients aged 31–60 and higher in those aged over 60 years old, and the risk also increased with a later year of diagnosis. Patients who were not white were at a higher risk of cardiovascular cause of death. Additionally, bilateral ovarian cancer and distant staging disease were linked to elevated risks of cardiovascular cause of death. Conclusion: Cardiovascular mortality is a significant concern in ovarian cancer patients, and several patient characteristics are associated with an increased risk. Our study suggests that targeted interventions to improve cardiovascular health in high-risk patients, such as those with comorbidities or an advanced stage at diagnosis, may improve survival in this population.

Impact of Smoking on Cervical Histopathological Changes in High-Risk HPV-Positive Women: A Matched Case–Control Study

Background and Objectives: The aims of this study were to assess the impact of smoking on cervical histopathology in women with high-risk HPV types 16 and 18 (the most common types) utilizing comprehensive clinical data and to conduct a risk analysis based on smoking pack-years. Materials and Methods: Between 2022 and 2024, 1048 high-risk HPV-positive women aged 25 to 65 years were categorized into two groups: smokers and non-smokers. Data acquired from a histopathological examination of samples collected during a colposcopic evaluation of these women were compared individually regarding clinical and demographic factors, specifically age, gravida, parity, and alcohol consumption. Subsequently, the impact of prolonged and excessive smoking on histopathological cellular changes was assessed in women with the same characteristics. A case–control study was performed on 312 smokers and 312 non-smokers following mutual matching. Results: The women were matched one-to-one regarding gravida, parity, and alcohol consumption. Subsequently, they were paired within a ±2-year age range. The mean age of the smoker group was 47.1 ± 8.8, while that of the non-smoker group was 47.2 ± 8.5 (p: 0.904). In all cases of high-risk HPV positivity, the rate of normal cervical cytological results was 14% in women who smoked and 29% in women who did not smoke. The LGSIL, HGSIL, ASC-H, and AGC-NOS rates were elevated in the smoker group, and a statistically significant difference was observed between the two groups in terms of abnormal cervical cytological results (p < 0.001). After a colposcopic biopsy, the smoker group exhibited higher rates of HGSILs, LGSILs, AGC-NOS, and CIS pathological lesions (28% vs. 23%), whereas the non-smoker group exhibited higher rates of chronic cervicitis (23% vs. 16%). However, no statistically significant difference was found between the two groups (p: 0.092). In a comparison of endocervical curettage (ECC) samples, it was observed that the HGSIL, CIS, and AGC-FN rates in the smoker group were almost the same as those in the non-smoker group. However, the LGSIL histopathology results (32% vs. 18%) were higher, and the rate of negativity with no pathology was higher in the non-smoker group (72% vs. 59%). A statistically significant difference in ECC histopathology was noted between the two groups (p < 0.001). An ROC analysis conducted between smoking pack-years and the colposcopic and endocervical curettage biopsy results revealed that the cutoff value for the colposcopic abnormal histopathological results increased, with 40% sensitivity and 76% specificity above 20 pack-years (AUC: 0.592 and p: 0.025). Additionally, the abnormal histopathology rates for endocervical curettage exhibited 81% sensitivity and 32% specificity above 13 pack-years (AUC: 0.586 and p: 0.008). The rate of abnormalities in the colposcopic biopsy results was 2.19 times higher for individuals with over 20 pack-years, and the rate of abnormalities in the ECC results was 2.08 times higher for those with over 13 pack-years; additionally, statistically significant results were obtained (p-values of 0.027 and 0.008, respectively). Conclusions: The most important cause of neoplastic changes in the cervix uteri is high-risk HPV infection, with evidence indicating that prolonged excessive smoking significantly exacerbates the persistence and progression of HPV infection, thereby influencing neoplastic changes in the cervix uteri. It is crucial for women to cease smoking in order to eradicate HPV infection from the body.

Temporal Changes in Incidence Rates of the Most Common Gynecological Cancers in the Female Population in Central Serbia

Background and Objectives: There were 1,335,503 newly diagnosed cases of the most common gynecological cancers in women (cervical, uterine and ovarian cancer) worldwide in 2020. The main objective of this paper was to assess temporal changes in incidence rates of the most common gynecological cancers and to determine the age group with the greatest increase in incidence in the Serbian female population in the period 2003–2018. Material and Methods: Trends and annual percentage change (APC) of the incidence rate with corresponding 95% confidence intervals (CI) were calculated by Joinpoint regression analysis. The trend was considered to be significantly increasing (positive change) or decreasing (negative change) when the p-value was below 0.05 (p < 0.05). Results: The total number of newly registered cancer cases from 2003 to 2018 was 35,799. There was a significant increase of age standardized rate (ASR) for all cancer incidences in women from 2012 to 2018 with APC 6.9% (95% CI from 0.9 to 13.3, p = 0.028) and for uterine cancer during the 2014–2018 period with APC of 16.8% (95% CI: from 4.0 to 31.1, p = 0.014), as well as for ovarian cancer incidence in the 2012–2018 period with APC of 12.1% (95% CI: from 6.7 to 17.8, p < 0.001). A non-significant decrease of ASRs of incidence for cervical cancer was determined from 2003 to 2015 with APC of −0.22% (95% CI: from −3.4 to 3.1, p = 0.887) and a non-significant increase of ASRs incidence from 2015 to 2018 with APC of 14.21% (95% CI: from −13.3 to 50.5, p = 0.311). The most common gynecological cancers were present in all age groups and only ovarian cancer was registered in the youngest age group (0–4 years). Cervical cancer showed a typical increase after the age of 30, with peak incidence in women aged 40–44 and 65–69 years. The increased incidence trend regarding age for cervical cancer (y = 1.3966x + 0.3765, R2 = 0.3395), uterine cancer (y = 1.7963x − 5.4688, R2 = 0.5063) and ovarian cancer (y = 1.0791x − 0.8245, R2 = 0.5317) is statistically significant. Conclusion: Based on our presented results, a significant increase of incidence trend for the most common gynecological cancers in the Serbian female population from 2012 to 2018 was determined. There has been a significant increase in the incidence of uterine cancer from 2014 up to 2018, as well as for ovarian cancer from 2012 up to 2018, while cervical cancer showed a non-significant decrease of incidence trend from 2003 until 2015 and then a non-significant increase. In women below 20 years of age, ovarian cancer was significantly more prevalent, while cervical cancer was significantly more prevalent in the age groups 20–39 and 40–59 years. In the age group of 60–79, uterine cancer had a significantly higher incidence than the other two cancers. Measures of primary prevention, such as vaccination of children against Human Papilloma Virus and screening measures of secondary prevention, for the female population aged 25 to 64 years of age are needed, as well as educating females about healthy lifestyles via media and social networks to help prevent the most common gynecological cancers.

New Perspectives in Therapeutic Vaccines for HPV: A Critical Review

Human Papillomavirus is the main cause of cervical cancer, including squamous cell carcinoma of the oropharynx, anus, rectum, penis, vagina, and vulva. In recent years, considerable effort has been made to control HPV-induced diseases using either prophylactic or therapeutic approaches. A critical review of the literature about the therapeutic Human Papillomavirus vaccine was performed to analyze its efficacy in the treatment of female lower genital tract lesions and its possible perspective application in clinical practice. The most important medical databases were consulted, and all papers published from 2000 until 2021 were considered. We retrieved a group of seven papers, reporting the role of anti HPV therapeutic vaccines against the L2 protein in the order of their efficacy and safety in female lower genital tract disease. In addition, the immune response due to vaccine administration was evaluated. The development of therapeutic vaccines represents an interesting challenge for the treatment of HPV infection of the lower genital tract. Literature data underline that the L2 protein may be an interesting and promising target in the development of therapeutic HPV vaccines, but the possible strengths and the unclear longevity of L2 immune responses are factors to be considered before clinical use.

Metastatic Patterns of Malignant Germ Cell Tumors Vary by Histologic Subtype and Primary Site

Background and Objectives: Malignant germ cell tumors (GCTs) are rare but clinically significant neoplasms arising in gonadal and extragonadal sites. Malignant GCTs, divided into seminomatous and non-seminomatous subtypes, show diverse biological behavior. Although molecular studies have advanced understanding of their origins and genetic features, little is known about metastatic patterns due to their rarity and generally favorable outcomes. This study aimed to describe metastatic patterns of malignant GCTs across primary sites and histologic subtypes using population-based database. Materials and Methods: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) program for patients diagnosed with malignant GCTs between 2010 and 2022. Cases were stratified by primary site (testis, ovary, mediastinum), age group (<8 years vs. ≥8 years), and histologic subtype. Metastatic patterns were assessed using both overall and organotropic metastasis rates, and differences between groups were evaluated descriptively using appropriate statistical tests. Results: A total of 32,015 malignant GCTs were identified, comprising 93.0% testicular, 5.6% ovarian, and 1.4% mediastinal tumors. In patients aged ≥8 years, ovarian tumors tended to show generally lower lymph node and distant metastasis rates. In contrast, mediastinal tumors appeared to have the highest distant metastasis rates. Organotropic analysis suggested distinct subtype- and site-specific differences. For seminoma/dysgerminoma, the organotropic metastasis pattern was generally consistent across different primary sites, whereas the other subtypes showed variable organotropic metastasis rates depending on the primary site. Conclusions: The metastatic patterns of GCTs appear to differ by histologic subtype and primary site. These findings suggest that both subtype and site of origin should be considered when assessing metastatic risk and may provide a framework for improved risk stratification in clinical practice.

The Influence of Circulating Immune Cell and CA125 Dynamics on Neoadjuvant Therapy Selection for Advanced Ovarian Cancer

Background and Objectives: Ovarian cancer, including tubal and peritoneal cancer, is the third most common gynecological cancer and the leading cause of death from gynecological malignancies in developed countries. This study explores the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in determining the optimal duration of neoadjuvant chemotherapy (NACT) for advanced ovarian cancer. It also investigates the correlation between NLR dynamics and the KELIM score, a chemosensitivity marker, to enhance individualized therapeutic strategies. Materials and Methods: A total of 79 patients underwent NACT followed by interval debulking surgery (IDS) or palliative care. The data collected included demographic information, tumor characteristics, treatment modalities, and laboratory parameters. The baseline NLR (NLR-T0) and post-therapeutic NLR (NLR-T1) were calculated, and their variation (NLR∆) was analyzed. The KELIM score was determined using CA-125 values. Results: Patients with a high baseline NLR (≥2.5) had significantly worse progression-free survival (PFS) and overall survival (OS) compared to those with a low NLR (<2.5). A negative NLR∆ was associated with poorer PFS and OS. The KELIM score indicated a more effective treatment response, with higher scores correlating with better outcomes. The majority of patients achieved R0 resection, and those with favorable KELIM scores showed improved survival rates. Conclusions: The NLR is a valuable prognostic marker for assessing treatment response and guiding NACT duration in advanced ovarian cancer.

Unique Case of Rare Non-Neural Granular Cell Tumor of the Rectus Abdominis Muscle

Background and Objectives: Our report contributes a unique case of a non-neural GCT occurring in an unusual location, with its development during pregnancy adding to its rarity. Materials and Methods: Granular cell tumors (GCTs), also known as Abrikossoff’s tumors, are rare neoplasms of Schwann cell origin with predominantly benign behavior. We present a case of a 29-year-old female with a non-neural variant of a GCT discovered incidentally during a cesarean section, situated on the posterior surface of the rectus abdominis muscle. Results: Histologically, the tumor exhibited features consistent with a benign non-neural GCT, confirmed through an immunohistochemical analysis. Despite the atypical presentation and challenging surgical removal due to prior scarring, the patient experienced no postoperative complications and showed no signs of recurrence during follow-up. Conclusions: This case highlights the importance of considering GCTs in differential diagnoses, particularly in unusual anatomical locations, and underscores the favorable prognosis associated with timely surgical intervention.

Histopathologic and Preneoplastic Changes in Tubal Ligation Materials

Background and Objectives: To investigate histopathological changes and serous carcinoma precursors such as secretory cell outgrowths (SCOUTs) and p53 signature in the bilateral tubal ligation (BTL) materials used during cesarean section (S/C). Materials and Methods: In total, 138 patients underwent S/C and tubal sterilization (TS) between October 2020 and May 2021 at Konya City Hospital. Patients’ data were obtained from the hospital’s system. All data and findings were investigated and statistically evaluated. Results: The mean age was 34.62 years (22–44), the mean gravity was 4.89 (2–15) and the mean parity was 3.46 (1–10). In total, 5.79% SCOUT, 7.24% atypia and 9.42% p53 signatures were observed. Significant correlations were shown between the epithelial cell lineage and age between Ki-67, SCOUT, and gravity; between the Ki-67 results and gravity and parity; and between the p53 score and age. Conclusions: TS is a common, safe, and effective method worldwide. Today, BTL is increasing along with increasing S/C ratios. In addition to the reduced risk of ovarian cancers with ligation alone, precursor lesions such as hyperplasia, SCOUT, p53 signature, and STIL/Serous tubal intraepithelial carcinoma (STIC) are encountered in the ampulla materials obtained. Considering the low rates of re-anastomosis, tubal excision may be recommended instead of ligation in women of relatively higher gravity and age.

Can MRI Accurately Diagnose and Stage Endometrial Adenocarcinoma?

Background and Objectives: Endometrial carcinoma is one of the most common gynecological cancers, and benign lesions such as endometrial hyperplasia, polyps, adenomyosis and leiomyomas should be included in the differential diagnosis. Magnetic resonance imaging has an important role in evaluating endometrial cancer and assessing the depth of myometrial invasion, and it closely correlates with the prognosis of the patient. The purpose of this study is to evaluate the MRI semiology of the endometrial carcinomas that mimic benign lesions, the main factors that may affect the correct diagnosis and the feasibility of magnetic resonance imaging to evaluate the depth of the myometrial invasion of endometrial cancer. Materials and Methods: This is a retrospective analysis of 45 patients that underwent MRI examinations and the lesions were pathologically diagnosed as endometrial carcinoma after surgical resection. This study evaluated the staging accuracy of T2-weighted imaging, diffusion-weighted imaging (DWI), ADC mapping and T1-weighted imaging with fat saturation before and after gadolinium injection. Results: In 36 of the 45 cases, the MRI of the lesion showed the characteristics of endometrial cancer and the diagnosis was certain. Nine lesions (20%) were described as unequivocal and had unspecific MR appearance. In eight of the nine cases (89%), the histopathologic report revealed the presence of leiomyomas and two of these cases (22%) were also associated with adenomyosis. The cause of underestimation in these patients was coexisting lesions exhibiting heterogenous intensity and contrast enhancement, which made it difficult to detect the margins of the lesions. The depth of the myometrial invasion was underestimated in nine cases and overestimated in three cases. The staging accuracy with MRI was 74%. There was a significant correlation between MR imaging and histopathologic finding in the assessment of myometrial invasion (p < 0.001). Cervical extension was noted in eight cases (18%), but was missed on MR imaging in two patients and overstaged in none. Six of them were associated with myometrial invasion in more than 50% of the thickness. There was a significant correlation between MR imaging and histopathologic finding in the assessment of cervical extension (p < 0.001). Conclusions: Our data confirm the high accuracy of MRI in the diagnosis and local staging of endometrial carcinoma. The information provided by MRI has an important role in planning the treatment and the prognosis of the patients.

Improvement of Cancer Care—Analysis of ESGO Quality Indicators for the Surgical Treatment of Endometrial Cancer in Slovenian and Croatian Gynaecologic Oncology Departments

Background and Objectives: This study aims to analyze ESGO quality indicators for the surgical treatment of endometrial cancer patients at two gynecologic oncology departments in Slovenia and Croatia, providing insights for improving cancer care. Materials and Methods: We conducted a retrospective analysis of clinical data to evaluate ESGO quality indicators for surgical treatment of endometrial cancer patients from 2020 to 2022. ESGO quality indicators were calculated, and the results were discussed to formulate suggestions for enhancing cancer care. Institutional review board approval was obtained for the analysis. Results: The analysis reveals that the Slovenian Department for Gynecology and Breast Oncology in Maribor achieved compliance with 24 out of 26 quality indicators, while the Department of Obstetrics and Gynecology in Rijeka met 18 out of 26. The disparity may be partly attributed to Maribor’s status as an ESGO-accredited center in training since 2014, which facilitates more rapid updates in care practices. Conclusions: Based on our findings and epidemiological data, we recommend several actions to enhance cancer care in both countries: (a) advance initiatives for the centralization of care (2 to 3 centers in Slovenia and 5 to 6 in Croatia), (b) implement a national system for the prospective measurement of quality indicators, and (c) pursue center accreditation and gynecologist certification in subspecialty care by international societies such as ESGO, given the small size of both countries. Our results confirm that the analysis of ESGO quality indicators is a viable method for all stakeholders involved in enhancing cancer care.

Carcinosarcoma of the Endometrium—Pathology, Molecular Landscape and Novel Therapeutic Approaches

Endometrial carcinosarcoma (ECS) is a rare and aggressive histological subtype of endometrial cancer that is associated with a dismal prognosis. It is a biphasic metaplastic carcinoma with a monoclonal origin comprising epithelial and mesenchymal components. The ECS originates from the epithelial components of the tumor, which undergoes an epithelial-to-mesenchymal transition. Approximately half of patients are diagnosed at the early stage of the disease, whereas the other half are diagnosed at the advanced stage. More than one-third of women present with metastatic lymph nodes, and approximately 10% will have distant metastases. Therefore, ECS is the deadliest type of endometrial cancer compared to other high-grade endometrial carcinomas. Surgical resection with adjuvant therapy remains the standard of care in most cases. The rarity of this disease hinders conducting prospective clinical trials to establish the optimal treatment regimens and increase overall survival. There are no specific guidelines for managing these rare and aggressive tumors despite the increasing interest in ECS in the gynecologic oncology community. The present review focuses on all new insights into ECS regarding its epidemiology, pathology, prognosis, and treatment. Furthermore, the molecular characteristics and new treatment regimens for primary (early and advanced stages) and recurrent ECS are discussed in detail.

Sentinel Lymph Node Dissection—Novelty, Trend, or a Paradigm Shift in Surgical Decision-Making for Early Cervical Cancer?

Cervical cancer remains the fourth most common malignancy among women worldwide, with over 600,000 new cases and approximately 350,000 deaths in 2022. Lymph node (LN) status is a critical prognostic factor, and in 2018, the International Federation of Gynecology and Obstetrics (FIGO) revised its staging system to include regional LN metastases, underscoring the importance of accurate nodal assessment. Sentinel lymph node biopsy (SLNB) has emerged as a minimally invasive alternative to systematic pelvic lymphadenectomy in early-stage disease, aiming to shorten operative time, reduce healthcare costs, and minimize treatment-related morbidity. This review synthesizes current evidence on SLNB in early-stage cervical cancer, including its diagnostic accuracy, optimal techniques, cost-effectiveness, and remaining clinical challenges. Data from prospective trials and meta-analyses demonstrate that SLNB provides high detection rates, especially with bilateral mapping and the use of advanced tracers such as indocyanine green. Ultrastaging further improves the detection of micrometastases and isolated tumor cells, refining adjuvant therapy decisions. Compared to full lymphadenectomy, SLNB significantly decreases intraoperative blood loss, operative time, and postoperative complications—most notably, lymphedema—while maintaining equivalent disease-free and overall survival. International guidelines now endorse SLNB for appropriately selected patients with early-stage cervical cancer (tumor size < 4 cm, negative preoperative imaging). However, variations persist between European and U.S. recommendations regarding its role as a standalone procedure. Future research must address protocol standardization, the prognostic relevance of low-volume metastases, and factors influencing mapping success. Overall, SLNB represents a paradigm shift toward more individualized, evidence-based surgical management of early-stage cervical cancer.

Bmi-1 Immunohistochemical Expression in Endometrial Carcinoma is Correlated with Prognostic Activity

Background and objectives: B-lymphoma Mo-MLV insertion region 1 (Bmi-1) is a stem cell factor that is overexpressed in various human cancer tissues. It has been implicated in cancer cell proliferation, cell invasion, distant metastasis, and chemosensitivity, and is associated with patient survival. Several reports have also identified Bmi-1 protein overexpression in endometrial carcinoma; however, the relationship between Bmi-1 expression and its significance as a clinicopathological parameter is still insufficiently understood. Accordingly, the present study aimed to clarify whether immunohistochemical staining for Bmi-1 in human endometrial carcinoma and normal endometrial tissues can be used as a prognostic and cell proliferation marker. Materials and Methods: Bmi-1 expression was assessed in endometrioid carcinoma (grade 1–3) and normal endometrial tissues (in the proliferative and secretory phases) by immunohistochemistry; protein expression was evaluated using the nuclear labeling index (%) in the hot spot. Furthermore, we examined other independent prognostic and proliferation markers, including the protein levels of Ki-67, p53, and cyclin A utilizing semi-serial sections of endometrial carcinoma tissues. Results: The expression of the Bmi-1 protein was significantly higher in all grades of endometrial carcinoma than in the secretory phase of normal tissues. Moreover, Bmi-1 levels tended to be higher in G2 and G3 tissues than in G1 tissue, without reaching significance. Bmi-1 expression showed no notable differences among International Federation of Gynecology and Obstetrics (FIGO) stages in endometrial carcinoma. Furthermore, we observed a significant positive relationship between Bmi-1 and Ki-67, cyclin A, or p53 by Spearman’s rank correlation test, implying that high Bmi-1 expression can be an independent prognostic marker in endometrial carcinoma. Conclusions: Our study suggests that Bmi-1 levels in endometrial carcinoma tissues may be useful as a reliable proliferation and prognostic biomarker. Recently, the promise of anti-Bmi-1 strategies for the treatment of endometrial carcinoma has been detected. Our results provide fundamental data regarding this anti-Bmi-1 strategy.

Prevalence of Carcinogenic Genotypes of HPV-Infected Women in a Ten-Year Period (2014–2023) in Vojvodina, Serbia

Background and Objectives: Human papillomavirus (HPV) infection and its etiological role in the development of cervical cancer are well established. The cervical cancer mortality rate in Serbia is one of the highest among European countries, and this cancer is the second-leading cause of death in Serbian women aged from 15 to 44. Materials and Methods: This retrospective study was conducted at the Institute of Public Health of Vojvodina. A total of 10,062 cervical specimens from Serbian women were collected and HPV tested in ten years. The study patients were divided into five age groups. HPV genotype testing was performed using a commercial kit to detect 14 high-risk (HR) HPV genotypes. Additionally, cervix cytology data have been available for patients tested in 2022 and 2023. Results: An overall positive rate was found in 43.3% of patients (4356/10,062). A single HPV infection (62.1%) was the main infection pattern. The most frequent HR HPV genotypes were HPV 16, 31, 52, 56, 39, and 51, comprising 62.3% of the detected genotypes, including multiple infections. A significant difference was noted in the HPV prevalence across the different age groups, with a bimodal distribution of HPV infection. The highest prevalence was recorded in the age group ≤ 30 and those after 61 years. Women diagnosed with high-grade squamous intraepithelial lesions (HSIL) were significantly older compared to others. HR HPV is the most prevalent in patients with HSIL cytological findings (76.5%). The most common type, according to age-specific distribution and cytological findings, was HR HPV 16. Conclusions: This study provides comprehensive data on HR HPV distribution among Serbian women, which can serve as a basis for subsequent monitoring of genotypic distribution. It is particularly significant considering they are missing in the updated ICO/IARC Report for Serbia, and the cervical cancer mortality rate in Serbia is one of the highest among European countries.

Ovarian Cancer—Insights into Platinum Resistance and Overcoming It

Ovarian cancer is the most lethal gynecologic malignancy. Platinum-based chemotherapy is the backbone of treatment for ovarian cancer, and although the majority of patients initially have a platinum-sensitive disease, through multiple recurrences, they will acquire resistance. Platinum-resistant recurrent ovarian cancer has a poor prognosis and few treatment options with limited efficacy. Resistance to platinum compounds is a complex process involving multiple mechanisms pertaining not only to the tumoral cell but also to the tumoral microenvironment. In this review, we discuss the molecular mechanism involved in ovarian cancer cells’ resistance to platinum-based chemotherapy, focusing on the alteration of drug influx and efflux pathways, DNA repair, the dysregulation of epigenetic modulation, and the involvement of the tumoral microenvironment in the acquisition of the platinum-resistant phenotype. Furthermore, we review promising alternative treatment approaches that may improve these patients’ poor prognosis, discussing current strategies, novel combinations, and therapeutic agents.

Mininvasive Cytoreduction Surgery plus HIPEC for Epithelial Ovarian Cancer: A Systematic Review

Background and objectives: The Gold-Standard treatment for Advanced Epithelial Ovarian Cancer remains cytoreductive surgery followed by systemic chemotherapy. Surgery can be performed either by an open or minimally invasive approach (MIS), although the former remains the most widely used approach. Recently, Van Driel et al. proved that adding 100 mg/m2 of Cisplatin in Hyperthermic Intraperitoneal Chemotherapy (HIPEC) at Interval Debulking Surgery (IDS) gives a disease-free survival (DFS) advantage. Similarly, Gueli-Alletti et al. demonstrated how the MIS approach is feasible and safe in IDS. Moreover, Petrillo et al. reported pharmacokinetic profiles with a higher chemotherapy concentration in patients undergoing HIPEC after MIS compared with the open approach. Therefore, the following review investigates the oncological and clinical safety consequences of the association between MIS and HIPEC. Methods: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched the PubMed and Scopus databases in April 2022. Studies containing data about oncological and safety outcomes were included. We registered the Review to the PROSPERO site for meta-analysis with protocol number CRD42022329503. Results: Five studies fulfilled inclusion criteria. 42 patients were included in the review from three different Gynecological Oncological referral centers. The systematic review highlighted a Recurrence Rate ranging between 0 and 100%, with a 3-year Platinum-Free Survival between 10 and 70%. The most common HIPEC drug was Cisplatin, used at concentrations between 75 and 100 mg/m2 and at an average temperature of 42 °C, for 60 to 90 min. Only 1 Acute Kidney Insufficiency has been reported. Conclusions: The scarcity of clinical trials focusing on a direct comparison between MIS and the open approach followed by HIPEC in EOC treatment does not make it possible to identify an oncological advantage between these two techniques. However, the safety profiles shown are highly reassuring.

Circulating CD4+ Treg, CD8+ Treg, and CD3+ γδ T Cell Subpopulations in Ovarian Cancer

Background and Objectives: Regulatory T cells (Tregs) are usually enriched in ovarian cancer (OC), and their immunosuppressive function plays a key role in tumorigenesis and progression. We mainly explored the phenotypical characterization of Treg-related markers on αβ and γδ T cell subsets in patients with OC. Materials and Methods: Thirty-six untreated patients with OC at the Women’s Hospital of Nanjing Medical University from September 2019 to August 2021 were enrolled. Phenotypical characterization of Tregs-related markers were detected by flow cytometry (FCM). Enzyme-linked immunosorbent assay was used to detect the levels of carbohydrate antigen (CA125) and transforming growth factor β (TGF-β). The level of human epididymis protein 4 (HE4) was detected by electrochemiluminescence immunoassay. Results: Circulating CD4+ Tregs, CD8+ Tregs, and CD3+γδ T cell subpopulations from OC patients have elevated Foxp3, CD25, CD122, Vδ1, and reduced CD28 expression compared to benign ovarian tumor (BOT) patients and healthy controls (HC). The upregulation of Foxp3 and Vδ1 and the downregulation of CD28 were highly specific for maintaining the immunosuppression function of CD4+ Tregs, CD3+γδ T cells, and CD8+ Tregs in OC patients. These Treg subpopulations were able to discriminate OC from BOT and HC. The levels of CA125, HE4, and TGF-β were increased in OC patients. A significant positive correlation between Treg subpopulations and CA125, HE4, and TGF-β was revealed. Conclusions: Proportions of CD4+ Tregs, CD8+ Tregs, and CD3+γδ T cell subsets were significantly increased in OC patients and were positively correlated with FIGO stage/metastasis status, CA125, HE4, and TGF-β. These indicators have the potential to be used as immunosurveillance biomarkers for OC.

The Impact of Patient Characteristics, Risk Factors, and Surgical Intervention on Survival in a Cohort of Patients Undergoing Neoadjuvant Treatment for Cervical Cancer

Introduction: Cervical cancer is among the most frequent types of neoplasia worldwide and remains the fourth leading cause of cancer death in women, a fact that raises the necessity for further development of therapeutic strategies. NCCN guidelines recommend radiation therapy with or without chemotherapy as the gold standard for locally advanced cervical cancer. Also, some studies claim that performing surgery after chemo-radiation therapy does not necessarily improve the therapeutic outcome. This study aims to determine the impact of the risk factors, various characteristics, and surgical treatment for patients in different stages of the disease on survival rate. Material and methods: Our study started as a retrospective, observational, unicentric one, carried out on a cohort of 96 patients diagnosed with cervical cancer from the surgical department of the Bucharest Oncological Institute, followed from 1 January 2019 for a period of 3 years. After the registration of the initial parameters, however, the study became prospective, as the patients were closely monitored through periodical check-ups. The end-point of the study is either the death of the participants or reaching the end of the follow-up period, and, therefore, we divided the cohort into two subgroups: the ones who survived after three years and the ones who did not. All 96 patients, with disease stages ranging from IA2 to IIIB, underwent radio-chemotherapy followed by adjuvant surgery. Results: Among the 96 patients, 45 (46%) presented residual tumor after radio-chemotherapy. Five patients (5%) presented positive resection margins at the post-operative histopathological examination. The presence of residual tumor, the FIGO stage post-radiotherapy, positive resection margins, and lympho-vascular and stromal invasions differed significantly between the subgroups, being more represented in the subgroup that reached the end-point. Variables correlated with the worst survival in Kaplan–Meier were the pelvic lymph node involvement—50% at three years (p—0.015)—and the positive resection margins—only 20% at three years (p < 0.001). The univariate Cox model identified as mortality-associated risk factors the same parameters as above, but also the intraoperative stage III FIGO (p < 0.001; HR 9.412; CI: 2.713 to 32.648) and the presence of post-radiotherapy adenopathy (p—0.031; HR: 3.915; CI: 1.136 to 13.487) identified through imagistic methods. The independent predictors of the overall survival rate identified were the positive resection margins (p—0.002; HR: 6.646; CI 2.0 to 22.084) and the post-radiotherapy stage III FIGO (p—0.003; HR: 13.886; CI: 2.456 to 78.506). Conclusions: The most important predictor factors of survival rate are the positive resection margins and the FIGO stage after radiotherapy. According to the NCCN guidelines in stages considered advanced (beyond stages IB3, IIA2), the standard treatment is neoadjuvant chemoradiotherapy. In our study, with radical surgery after neoadjuvant therapy, 46% of patients presented residual tumor at the intraoperative histopathological examination, a fact that makes the surgical intervention an important step in completing the treatment of these patients. In addition, based on the patient’s features/comorbidities and the clinical response to chemotherapy/radiotherapy, surgeons could carefully tailor the extent of radical surgery, thus resulting in a personalized surgical approach for each patient. However, a potential limitation can be represented by the relatively small number of patients (96) and the unicentric nature of our study.

The Inhibitory Effect of KerraTM, KSTM, and MinozaTM on Human Papillomavirus Infection and Cervical Cancer

Background and Objectives: Cervical cancer is one of the most common types of frequently found cancers in Thailand. One of the causative agents is the infection of the high-risk human papillomavirus (HPV) type 16 and 18. Traditional medicines are rich sources of bioactive compounds which are a valuable source for the development of novel cancer therapies. In this study, the therapeutic effects of 3 traditional medicines, KerraTM, KSTM, and MinozaTM, were studied on HeLa and CaSki cells. Materials and Methods: The effects of KerraTM, KSTM, and MinozaTM on cancer cells were evaluated through cytotoxicity and cell death assays. The infection assay using HPV-16 pseudovirus was also carried out. Results: All traditional medicines efficiently suppressed cell growths of HeLa and CaSki, with KerraTM being the most potent anticancer agent followed by KSTM and MinozaTM. KerraTM at 158 µg/mL and 261 µg/mL significantly increases the percentage inhibition of the HPV-16 pseudovirus infection in a pre-attachment step in a dose-dependent manner, while KSTM at 261 µg/mL efficiently inhibited viral infection in both pre-attachment and adsorption steps. However, KerraTM, KSTM, and MinozaTM at subtoxic concentrations could not reduce the viral E6 mRNA expressions of HPV-16 and HPV-18. Cell death assay by acridine orange/ethidium bromide showed that KerraTM increased population of dead cells in dose-dependent manner in both CaSki and HeLa. The percentage of secondary necrosis in KerraTM-treated CaSki was higher than that of HeLa cells, while the percentage of late apoptotic cells in HeLa was higher than that of CaSki, indicating that HeLa was more susceptible to KerraTM than CaSki. For KSTM and MinozaTM, these extracts at 250 µg/mL promoted autophagy over cell death. At 500 µg/mL, the percentage of dead cells in KerraTM was higher than that of KSTM and MinozaTM. Conclusions: KerraTM is a potent traditional medicine for promoting cancer cell death. KerraTM is possibly useful in the prevention and treatment of cervical cancer. Further investigation will be carried out to gain a better understanding of the biochemical mechanism and the pharmacological activity underlying this effect.

Bioinformatic Analysis for Influential Core Gene Identification and Prognostic Significance in Advanced Serous Ovarian Carcinoma

Background and objectives: Ovarian cancer is one of the leading causes of death among women worldwide. Most newly diagnosed ovarian cancer patients are diagnosed in advanced stages of the disease. Despite various treatments, most patients with advanced stage ovarian cancer, including serous ovarian cancer (the most common subtype of ovarian cancer), experience recurrence, which is associated with extremely poor prognoses. In the present study, we aimed to identify core genes involved in ovarian cancer and their associated molecular mechanisms, as well as to investigate related clinicopathological implications in ovarian cancer. Materials and methods: Three gene expression cohorts (GSE14407, GSE36668, and GSE38666) were obtained from the Gene Expression Omnibus databases to explore potential therapeutic biomarkers for ovarian cancer. Nine up-regulated and six down-regulated genes were screened. Three publicly available gene expression datasets (GSE14407, GSE36668, and GSE38666) were analyzed. Results: A total of 14 differently expressed genes (DEGs) were identified, among which nine genes were upregulated (BIRC5, CDCA3, CENPF, KIF4A, NCAPG, RRM2, UBE2C, VEGFA, and NR2F6) and were found to be significantly enriched in cell cycle regulation by gene ontology analysis. Further protein–protein interaction network analysis revealed seven hub genes among these DEGs. Moreover, Kaplan–Meier survival analysis showed that a higher expression of CDCA3 and UBE2C was associated with poor overall patient survival regardless of tumor stage and a higher tumor histologic grade. Conclusion: Altogether, our study suggests that CDCA3 and UBE2C may be valuable biomarkers for predicting the outcome of patients with advanced serous ovarian cancer.

Recent Advances and Adaptive Strategies in Image Guidance for Cervical Cancer Radiotherapy

The standard of care for locally advanced cervical cancer is external beam radiotherapy (EBRT) with simultaneous chemotherapy followed by an internal radiation boost. New imaging methods such as positron-emission tomography and magnetic resonance imaging have been implemented into daily practice for better tumor delineation in radiotherapy planning. The method of delivering radiation has changed with technical advances in qualitative imaging and treatment delivery. Image-guided radiotherapy (IGRT) plays an important role in minimizing treatment toxicity of pelvic radiation and provides a superior conformality for sparing the organs at risk (OARs) such as bone marrow, bowel, rectum, and bladder. Similarly, three-dimensional image-guided adaptive brachytherapy (3D-IGABT) with computed tomography (CT) or magnetic resonance imaging (MRI) has been reported to improve target coverage and reduce the dose to normal tissues. Brachytherapy is a complementary part of radiotherapy treatment for cervical cancer and, over the past 20 years, 3D-image-based brachytherapy has rapidly evolved and established itself as the gold standard. With new techniques and adaptive treatment in cervical cancer, the concept of personalized medicine is introduced with an enhanced comprehension of the therapeutic index not only in terms of volume (three-dimensional) but during treatment too (four-dimensional). Current data show promising results with integrated IGRT and IGABT in clinical practice and, therefore, better local control and overall survival while reducing treatment-related morbidity. This review gives an overview of the substantial impact that occurred in the progress of image-guided adaptive external beam radiotherapy and brachytherapy.

Characteristics of Women Seeking Cervical Cancer Cytology Screening in a Private Health Facility

Background and Objectives: Over 80% of cervical cancer cases in sub-Saharan Africa are detected at late stages, predominantly due to the lack or inaccessibility of prevention services. Public health facilities in Ethiopia offer free cervical cancer screening for eligible women. Besides the public health facilities, private providers also offer a variety of screening services at the patients’ expense. As the overall cervical cancer screening uptake in Ethiopia is still far below the 90% WHO target, coordination between all actors of the health system is key. This includes a close cooperation between the public and private sectors to combine the advantages of both to the benefit of all patients as well as media campaigns and community involvement to promote the self-initiation of screening. Materials and Methods: To gain insights into the utilization of cervical cancer screening in the private health sector, we conducted an institution-based cross-sectional study at Arsho medical laboratories in Addis Ababa. Every woman who came there for cervical cancer screening between 1 May and 30 June 2020 was asked to participate in a questionnaire-based, face-to-face interview about their socio-demographic background, cervical cancer screening experience and self-initiation of screening. A total of 274 women participated in the interviews. We further assessed the reproductive status of the patients, their risk factors for cervical cancer, source of information about the screening and barriers to cervical cancer screening. Results: The ages of the participants ranged between 20–49 years. The majority (over 70%) were married. A total of 37.6% reported self-initiating the screening. More than three-quarters of all interviewed women reported mostly using the private health care sector for all kinds of health services. Conclusions: While the Ethiopian government efforts on scaling up cervical cancer screening focus mainly on public health facilities, the private sector often does not get as much attention from policy makers. Efforts should be made to extend the government’s interest in cervical cancer screening and implementation research to the private healthcare sector.

Expression of Vascular Endothelial Growth Factor-A (VEGF-A) in Adenocarcinoma and Squamous Cell Cervical Cancer and Its Impact on Disease Progression: Single Institution Experience

Background and Objectives: The aim of this retrospective study was to determine the difference in VEGF-A expression in adenocarcinoma and squamous cell cervical cancer and to show the influence of VEGF-A expression on clinical, pathological, and therapeutic prognostic factors on the outcome of treatment and the survival of patients. Materials and Methods: The study included patients with cervical cancer who were treated in the period from 1 January 2010 to 31 December 2021 at the Clinic for Gynecology and Obstetrics, University Hospital Centre, Osijek. The researchers conducted a retrospective analysis of data from patients’ medical history, along with the pathohistological findings and oncologist findings. The study included 66 patients with cervical cancer (divided into two subgroups of 33 with adenocarcinoma or squamous cell cervical cancer). Diagnosis was based on the pathohistological status and FIGO staging. VEGF-A expression was significantly higher in adenocarcinoma. Subjects with a higher expression of VEGF-A had a significantly higher rate of disease progression and a higher possibility for lethal outcome. Results: Statistically significant prognostic factors in bivariate analysis in predicting a negative treatment outcome were: older age, greater depth of stromal invasion, FIGO IIB stage, chemotherapy, and positive lymph nodes. In the multivariate analysis, age and positive lymph nodes were shown to be significant predictors for a negative treatment outcome. Conclusions: VEGF-A has shown to be statistically more expressed in adenocarcinoma, which correlates with disease progression, but not statistically significant in multivariate regression analysis as an independent prognostic factor for poor survival of the subjects.

Cervical Cancer and Human Papillomavirus Awareness among Women in Antigua and Barbuda

Background and objectives: Cervical cancer is the fourth leading cause of cancer-related deaths in women. Human papilloma virus (HPV) is known to cause cervical cancer. The incidence and mortality of cervical cancer has drastically reduced due to effective vaccination against HPV in developed countries. The projected rise in cervical cancer cases in Latin American and Caribbean countries necessitates a study to evaluate awareness about HPV, cervical cancer, the HPV vaccine, and prevention among women in Antigua and Barbuda. Materials and methods: This was an observational, cross-sectional study. The participants were women aged between 18 and 65 years, residing in Antigua and Barbuda. The study was conducted over the period of February to April 2023. After taking informed consent electronically, sociodemographic and behavioral data was collected through questionnaires sent out as links and QR-codes and were analyzed by QualtricsXM. The association between the demographic groups and awareness about HPV, cervical cancer, the HPV vaccine, and prevention was analyzed by a Chi-square test. Results: In total, 467 women were included in the study. The percentage of participants aware of HPV was 91.6% (n = 412). A total of 70.7% (n = 318) and 56.7% (n = 255) women were aware that cervical cancer is caused by HPV and is sexually transmitted, respectively. Although 70.6% (n = 315) of participants were aware that the vaccine protects against HPV, only 12.8% (n = 57) were vaccinated. Of the participants, 49.7% (n = 192) were willing to get vaccinated. The percentage of participants aware of the Papanicolaou (Pap) smear procedure was 98.9% (n = 435) and 87.8% (n = 382) had a Pap smear within the last 10 years while 12.2% (n = 53) never had a Pap smear screening. The willingness to know more information about HPV and the HPV vaccine among the participants was 77% (n = 335). Conclusions: The overall awareness among women in Antigua and Barbuda about HPV, cervical cancer, the HPV vaccine, and prevention was high. We recommend a national health education program and vaccine drive to complement our findings.

Re-Irradiation with Intensity-Modulated Radiation Therapy for the Treatment of Recurrent Cervical Cancer in the Pelvis: An Analysis of Outcomes and Toxicity

Background and Objectives: Treatment options for most patients with recurrent cervical cancer within the previously irradiated field are limited. This study aimed to investigate the feasibility and safety of re-irradiation using intensity-modulated radiation therapy (IMRT) for patients with cervical cancer who experienced intrapelvic recurrence. Materials and Methods: We retrospectively analyzed 22 patients with recurrent cervical cancer who were treated with re-irradiation for intrapelvic recurrence using IMRT between July 2006 and July 2020. The irradiation dose and volume were determined based on the range considered safe for the tumor size, location, and previous irradiation dose. Results: The median follow-up period was 15 months (range: 3–120) and the overall response rate was 63.6%. Of the symptomatic patients, 90% experienced symptom relief after treatment. The 1- and 2-year local progression-free survival (LPFS) rates were 36.8% and 30.7%, respectively, whereas the 1- and 2-year overall survival (OS) rates were 68.2% and 25.0%, respectively. Multivariate analysis revealed that the interval between irradiations and gross tumor volume (GTV) were significant prognostic factors for LPFS. The response to re-irradiation showed borderline statistical significance for LPFS. The GTV and response to re-irradiation were also independent prognostic factors for OS. Grade 3 late toxicities were observed in 4 (18.2%) of the 22 patients. Recto- or vesico-vaginal fistula occurred in four patients. The irradiation dose was associated with fistula formation with borderline significance. Conclusions: Re-irradiation using IMRT is a safe and effective treatment strategy for patients with recurrent cervical cancer who previously received RT. Interval between irradiations, tumor size, response to re-irradiation, and radiation dose were the main factors affecting efficacy and safety.

Challenges in the Diagnosis and Individualized Treatment of Cervical Cancer

Cervical cancer is still the fourth most common cancer in women throughout the world; an estimated 604,000 new cases were observed in 2020. Better knowledge of its pathogenesis, gained in recent years, has introduced new preventive and diagnostic approaches. Knowledge of its pathogenesis has made it possible to provide individualized surgical and drug treatment. In industrialized countries, cervical cancer has become a less frequent tumor entity due to the accessibility of the human papilloma virus vaccination, systematic preventive programs/early detection programs, health care infrastructure and the availability of effective therapy options. Nevertheless, globally, neither mortality nor morbidity has been significantly reduced over the past 10 years, and therapy approaches differ widely. The aim of this review is to address recent advances in the prevention, diagnostic investigation and treatment of cervical cancer globally, focusing on advances in Germany, with a view toward providing an updated overview for clinicians. The following aspects are addressed in detail: (a) the prevalence and causes of cervical cancer, (b) diagnostic tools using imaging techniques, cytology and pathology, (c) pathomechanisms and clinical symptoms of cervical cancer and (d) different treatment approaches (pharmacological, surgical and others) and their impact on outcomes.

Performance of the IOTA ADNEX Model on Selected Group of Patients with Borderline Ovarian Tumours

Background and objectives: ultrasound is considered to be the primary tool for preoperative assessment of ovarian masses; however, the discrimination of borderline ovarian tumours (BOTs) is challenging, and depends highly on the experience of the sonographer. The Assessment of Different NEoplasias in the adneXa (ADNEX) model is considered to be a valuable diagnostic tool for preoperative assessment of ovarian masses; however, its performance for BOTs has not been widely studied, due to the low prevalence of these tumours. The aim of this study was to evaluate the performance of ADNEX model for preoperative diagnosis of BOTs. Methods: retrospective analysis of preoperative ultrasound datasets of patients diagnosed with BOTs on the final histology after performed surgery was done at a tertiary oncogynaecology centre during the period of 2012–2018. Results: 85 patients were included in the study. The performance of ADNEX model based on absolute risk (AR) improved with the selection of a more inclusive cut-off value, varying from 47 (60.3%) correctly classified cases of BOTs, with the selected cut-off of 20%, up to 67 (85.9%) correctly classified cases of BOTs with the cut-off value of 3%. When relative risk (RR) was used to classify the tumours, 59 (75.6%) cases were identified correctly. Forty (70.2%) cases of serous and 16 (72.7%) cases of mucinous BOTs were identified when AR with a 10% cut-off value was applied, compared to 44 (77.2%) and 15 (68.2%) cases of serous and mucinous BOTs, correctly classified by RR. The addition of Ca125 improved the performance of ADNEX model for all BOTs in general, and for different subtypes of BOTs. However, the differences were insignificant. Conclusions: The International Ovarian Tumour Analysis (IOTA) ADNEX model performs well in discriminating BOTs from other ovarian tumours irrespective of the subtype. The calculation based on RR or AR with the cut-off value of at least 10% should be used when evaluating for BOTs.

Early-Stage Ovarian Malignancy Score versus Risk of Malignancy Indices: Accuracy and Clinical Utility for Preoperative Diagnosis of Women with Adnexal Masses

Background and objectives: To compare the diagnostic accuracy and clinical utility of the Early-stage Ovarian Malignancy (EOM) score with the Risk of Malignancy Index (RMI) in the presurgical assessment of women presenting with adnexal masses. Materials and Methods: A secondary analysis was carried out in a retrospective cohort of women who presented with an adnexal mass and were scheduled for surgery at Phrapokklao Hospital between September 2013 and December 2017. The clinical characteristics, ultrasonographic features of the masses, and preoperative CA-125 levels were recorded. The EOM and the RMI score were calculated and compared in terms of accuracy and clinical utility. Decision curve analysis (DCA), which examined the net benefit (NB) of applying the EOM and the RMI in practice at a range of threshold probabilities, was presented. Results: In this study, data from 270 patients were analyzed. Fifty-four (20.0%) women in the sample had early-stage ovarian cancer. All four RMI versions demonstrated a lower sensitivity for the detection of patients with early-stage ovarian cancer compared to an EOM score ≥ 15. An EOM ≥ 15 resulted in a higher proportion of net true positive or NB than all versions of the RMIs from a threshold probability of 5% to 30%. Conclusions: It also showed a higher capability to reduce the number of inappropriate referrals than the RMIs at a threshold probability between 5% and 30%. The EOM score showed higher diagnostic sensitivity and has the potential to be clinically more useful than the RMIs to triage women who present with adnexal masses for referral to oncologic gynecologists. Further external validation is required to support our findings.

BRCA Genes and Related Cancers: A Meta-Analysis from Epidemiological Cohort Studies

Background and Objectives:BRCA1 and BRCA2 are genes located in different chromosomes that are disproportionately associated with hereditary breast and ovarian cancer syndrome. Their association with other cancers remains to be explored. Materials and Methods: We systematically reviewed cohort studies to explore the association of BRCA 1 and BRCA2 with various cancers except lung cancer. We searched PubMed, Medline (EBSCOhost) and relevant articles published up to 10 May 2021. The odds ratio, standardised morbidity rate and cancer-specific standardised incidence ratio were pooled together as relative risk (RR) estimates. Results: Twelve studies were included for analysis. BRCA mutation increased pancreatic and uterine cancers by around 3–5- and 1.5-fold, respectively. BRCA mutation did not increase brain cancer; colorectal cancer; prostate, bladder and kidney cancer; cervical cancer; or malignant melanoma. BRCA2 increased gastric cancer with RR = 2.15 (1.98–2.33). Conclusion: The meta-analysis results can provide clinicians and relevant families with information regarding increased specific cancer risk in BRCA1 and BRCA2 mutation carriers.

The Risk of Para-Aortic Lymph Node Metastases in Apparent Early Stage Ovarian Cancer

Background and objectives: To identify the risk factors for para-aortic lymph node metastases in cases with presumed early stage ovarian cancer. Materials and methods: Between 2014 and 2019, 48 patients with apparent early stage ovarian cancer were submitted to surgery. In all cases, pelvic and para-aortic lymph node dissection was performed for staging purposes. Results: Among the 48 cases we identified nine cases with positive pelvic lymph nodes and 11 cases with positive para-aortic lymph nodes. The positivity of the retrieved lymph nodes was significantly correlated with the histopathological subtype represented by serous histology (p = 0.02), as well as with the degree of differentiation (p = 0.004). Conclusions: Patients with serous ovarian carcinomas in association with a poorer degree of differentiation are at risk of associated lymph node metastases even in presumed early stages of the disease. Therefore, lymph node dissection should be performed in such cases in order to provide adequate staging and tailoring of further treatment.

Secondary Amenorrhea and Infertility Due to an Inhibin B Producing Granulosa Cell Tumor of the Ovary. A Rare Case Report and Literature Review

Granulosa cell tumor of the ovary (GCT) is a rare ovarian tumor with nonspecific symptoms. Studies reported that GCT are usually secreting estrogens and inhibins, especially inhibin B. It is considered that, in premenopausal women, irregular menses or secondary amenorrhea may be an early symptom of GCT and, in postmenopausal women, the most common manifestation is vaginal bleeding. Additionally, endometrial abnormalities can be associated due to estrogenic secretion. At reproductive age, high levels of inhibin, lead to low levels of FSH and secondary amenorrhea causing infertility. At times, increased levels of LH in women with GCT are observed and the pathogenesis is still unclear. Therefore, inhibin B level can differentiate GCT from other causes of secondary amenorrhea. We report the case of a 26-year-old nulliparous, women who presented in our clinic with secondary infertility lasting longer than 2 years, secondary amenorrhea, polycystic ovarian syndrome, and suspicion of right ovarian endometrioma on CT scan. The ultrasound examination revealed that the right ovary was transformed in an anechoic mass with increased peripheral vascularity having a volume of 10 cm3. This patient had high serum levels of inhibin B and LH but normal levels of FSH and estradiol. The preliminary diagnosis of granulosa cell tumor of the ovary was made. After counseling, the informed consent for treatment was obtained and the patient agreed to undergo surgery. An uneventful laparoscopy was performed with right oophorectomy and multiple peritoneal sampling. The histological diagnosis confirmed adult GCT limited to right ovary, with negative peritoneal biopsies (FIGO IA). After surgery the patient recovered fully and had normal menstrual cycles with normal serum levels of hormones. Two months later she conceived spontaneously and had an uneventful pregnancy. In conclusion, for cases with secondary amenorrhea, the evaluation of inhibin B level is essential. Elevated inhibin B level may be a sign for the presence of an unsuspected tumor. With early diagnosis and treatment, the prognosis is generally good and the fertility may be preserved, especially in young patients with GCT.

Proton Beam Therapy in Gynecological Cancers: A Systematic Review of Indications, Complications, and Limitations

Background and Objectives: Gynecological cancers frequently require radiation therapy (RT) in primary, adjuvant, or salvage settings. However, photon-based RT is associated with non-negligible toxicity, and treatment of pelvic recurrences after prior irradiation remains challenging. Proton beam therapy (PBT), due to its favorable dose distribution and reduced exposure of organs at risk (OARs), has emerged as a potential alternative, particularly in re-irradiation scenarios. Despite its expanding use in other malignancies, evidence supporting PBT in gynecologic cancers remains limited. This systematic review aims to investigate the use of PBT in gynecological cancers and its associated complications. Materials and Methods: This systematic review was conducted according to PRISMA guidelines and registered in PROSPERO. A comprehensive search (2000–2025) identified studies investigating PBT in gynecologic cancers. Eligible designs included randomized trials and prospective and retrospective series. Reported adverse events were categorized as GI, GU, or other, and only grade ≥3 CT-CAE complications were considered. Results: Of 580 records screened, 9 studies comprising 232 patients met inclusion criteria. Most patients were treated for endometrial (n = 147) or cervical (n = 75) cancer; 90 received chemotherapy. Overall, severe toxicity occurred in 15.2% of patients. GI complications ranged from 0–14% and GU from 0–33%. Complication rates were lowest in adjuvant or de novo treatment series (0–10%), whereas re-irradiation cohorts showed higher rates (up to 33% GU). Comparative studies suggested a possible advantage of PBT over IMRT, particularly for GI toxicity, though data remain limited. Conclusions: Severe GI and GU toxicity after PBT in gynecologic cancers appears infrequent, particularly in primary and adjuvant settings, though re-irradiation remains challenging. Current evidence is restricted to small and heterogeneous studies. Ongoing phase II trials will provide prospective data to clarify feasibility, toxicity, and long-term outcomes. Until then, PBT in gynecologic oncology should be regarded as investigational.

Therapeutic Strategies for Ovarian Cancer in Point of HGF/c-MET Targeting

Ovarian cancer is the fifth leading cause of cancer deaths in women and is regarded as one of the most difficult cancers to treat. Currently, studies are being conducted to develop therapeutic agents for effective treatment of ovarian cancer. In this review, we explain the properties of the hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (c-MET) and how the signaling pathway of HGF/c-MET is activated in different cancers and involved in tumorigenesis and metastasis of ovarian cancer. We present the findings of clinical studies using small chemicals or antibodies targeting HGF/c-MET signaling in various cancer types, particularly in ovarian cancer. We also discuss that HGF/c-MET-targeted therapy, when combined with chemo drugs, could be an effective strategy for ovarian cancer therapeutics.

Segmental Renal Infarction Associated with Accessory Renal Arteries After Para-Aortic Lymphadenectomy in Gynecologic Malignancies

Background and Objectives: The causes and clinical outcomes of renal perfusion abnormalities occurring after para-aortic lymphadenectomy (PANDx) for gynecologic malignancies are unknown. We investigated the potential involvement of accessory renal artery (ARA) obstruction in their development by reassessing perioperative contrast-enhanced computed tomography (CECT). Materials and Methods: This retrospective study investigated a clinical database to identify urinary contrast defects using CECT in all patients who had undergone PANDx between January 2020 and December 2024. The perfusion defects in the kidney detected by CECT were extracted by a gynecologic oncologist and evaluated by a radiologist and urologist for suspected obstruction of ARAs. Results: Postoperative renal contrast defects were observed in 3.8% (6/157) of patients. Renal parenchymal fibrosis, cortical atrophy, and parenchymal thinning were observed as universal findings in all patients showing renal contrast defects. In five of the six cases, ARAs supplying the infarcted renal segments were identified on preoperative CECT, and arterial obstruction was confirmed on postoperative imaging. The remaining case was considered to be latent pyelonephritis. All five patients underwent laparotomy, and preoperative CECT failed to detect ARAs. The median resected para-aortic lymph node was 23 nodes (range: 15–33) in five patients, showing no statistically significant difference compared to patients without perfusion abnormalities (p = 0.19). Postoperative serum creatinine levels remained stable. Conclusions: ARA obstruction appears to be a risk factor for segmental renal infarction after para-aortic lymphadenectomy in gynecological malignancies; however, the clinical impact on urinary function may be limited. Awareness of this potential complication is essential for gynecologic oncologists performing PANDx.

The Role of Medical Therapies in the Management of Cervical Intraepithelial Neoplasia: A Narrative Review

Cervical cancer and its precursors (cervical intraepithelial neoplasia (CIN)) represent a current major public health concern. Currently, the treatment of choice for patients with HSILs (high-grade intraepithelial lesions) is surgical treatment—LEEP or cold-knife conization—except for in pregnant women, where it may have significant future consequences. In this paper, we aim to review the current evidence regarding the efficacy of non-surgical approaches for CINs. Therefore, we searched Google Scholar and PubMed for papers on CIN treatments; 91 studies published in English were included in the analysis. The results of the reviewed studies were variable depending on the agent and methodology used. Overall, the remission rates of CIN II ranged from 43 to 93%. However, for some agents, the results were contradictory. Once topical agents have been proven to be effective, they could be used as an alternative to surgical methods in treating HPV-associated CIN, with fewer adverse effects. The use of local agents could allow for more personalized treatments for patients with CINs. Future directions were also sought.

A Preliminary Investigation into the Use of Cannabis Suppositories and Online Mindful Compassion for Improving Sexual Function Among Women Following Gynaecological Cancer Treatment

Background and Objectives: The impact of gynaecological cancer and its treatments on sexual intimacy can be profound on female sexuality. However, very few registered clinical trials have addressed sexual intimacy among this cohort. Materials and Methods: This preliminary randomised control trial (RCT) and content analysis assessed the effectiveness of a brief online mindful compassion group intervention adjunct with cannabis suppositories. Eighty-three participants aged between 18 and 50+ years who were at least six months post-cancer treatment were randomly allocated to one of four groups, depending on whether they were already using cannabis suppositories. These included a cannabis-only group (CO), a mindful-compassion group (MC), a combined mindful-compassion and cannabis suppositories group (COCM) and a care-as-usual group (CAU). Measurements of sexual function, sexual self-efficacy, mindful compassion, well-being and quality of life were taken at weeks 0, 4 and 12. Results: Sexual function, including arousal, lubrication and orgasms, improved for both the MC p = 0.002 and COCM p ≤ 0.001 groups; in addition, sexual pain was reduced in the COCM p = 0.008 and CO p ≤ 0.001 groups compared to the CAU and MC groups, where p ≥ 0.05. Feedback suggested that cannabis mediated the effects of mindful compassion and supported well-being, sexual self-efficacy, and quality of life. Participants also voiced a preference for cannabis suppositories when using dilators as part of their treatment and the use of sex toys instead of dilators, suggesting that dilators had negatively impacted their sexuality. Conclusions: These preliminary and exploratory outcomes look promising and provide a foundation for future research to develop varied healthcare options to improve mental health service delivery and quality of life for this cohort.

Factors Associated with Para-Aortic Lymph Node Metastasis in High-Risk Endometrial Cancer

Background and Objectives: Para-aortic lymph node involvement is a key prognostic factor in high-risk endometrial cancer. This study aimed to identify factors associated with para-aortic lymph node metastasis and to assess their predictive value for surgical decision-making. Materials and Methods: A retrospective analysis was conducted on 81 patients with high-risk endometrial cancer who underwent systematic pelvic and para-aortic lymphadenectomy between January 2015 and December 2024. Factors evaluated included histologic subtype, lymphovascular space invasion (LVSI), cervical stromal involvement, depth of myometrial invasion, and tumor diameter. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of para-aortic metastasis. Receiver operating characteristic (ROC) analysis was used to determine the optimal tumor size threshold. Results: Para-aortic lymph node metastasis was identified in 21.0% of patients, and isolated para-aortic metastasis was observed in 2.5%. In univariate analysis, pelvic lymph node positivity, LVSI, cervical stromal invasion, deep myometrial invasion, and tumor size ≥ 3.55 cm were significantly associated with para-aortic spread. Multivariate analysis revealed that pelvic lymph node positivity was the only independent predictor (OR 39.0; 95% CI 5.06–301.46; p < 0.001). Conclusions: Pelvic lymph node status serves as a strong and independent predictor of para-aortic metastasis in high-risk endometrial cancer. A tumor diameter greater than 3.5 cm may also indicate an increased risk of para-aortic spread. These findings suggest that selective and individualized para-aortic assessment strategies may be considered to improve staging accuracy and optimize surgical planning in this patient population.

The Feasibility of Sentinel Lymph-Node, Mapped with Indocyanine Green, Biopsy in Endometrial Cancer Patients: A Prospective Study

Background and objectives. Systematic pelvic lymphadenectomy (LND) is an essential part of lymph-node status evaluation in endometrial cancer (EC) patients to tailor the adjuvant treatment. However, it is associated with the post-operative lymphatic complications and does not improve the outcomes of the disease. Indocyanine green (ICG) mapped sentinel lymph-node biopsy (SLB) has recently been introduced into the clinical practice as an alternative for the surgical lymph-node evaluation in EC patients with the potential to decrease LND related complications. The aim of our study was to evaluate the feasibility of ICG mapped SLB in low, intermediate, and high-risk EC patients in a center with no previous experience on endoscopic SLB procedure. Materials and Methods: The prospective study was performed. 170 patients with histologically confirmed EC were included. Sentinel lymph-nodes (SLs) were mapped with ICG dye and removed ahead of the total laparoscopic hysterectomy. Low-risk patients received only SLB, while SLB and LND were performed for intermediate and high-risk patients. Results: The overall detection rate of SLs was 88.8%. Bilateral mapping was achieved in 68.2% of the patients. The overall detection rate for low-risk patients was 93.7%, 85.0% for the intermediate-risk group, and 100% for high-risk patients (p = 0.232). The most common anatomical sites of SLs were the external iliac (45.8% on the right and 46.6% on the left) and obturator regions (20.9% and 25.6%, respectively). Positive lymph-nodes were found in 8 (4.7%) patients. The sensitivity of SLB was 75.0% and negative predictive value (NPV)—97.2%. Conclusions: Even in the center with no previous experience, sentinel lymph-node biopsy using ICG mapping is feasible. However, the favorable outcomes might be associated with the learning process of newly established method.

Primary Fallopian Tube Carcinoma Presenting with a Massive Inguinal Tumor: A Case Report and Literature Review

Primary fallopian tube carcinoma (PFTC) has characteristics similar to those of ovarian carcinoma. The typical course of PFTC metastasis includes peritoneal dissemination and pelvic and paraaortic lymph node metastasis, while inguinal lymph node metastasis is rare. Moreover, the initial presentation of PFTC with an inguinal tumor is extremely rare. A 77-year-old postmenopausal woman presented with a massive 12-cm inguinal subcutaneous tumor. After tumor resection, histopathological and immunohistochemical analysis showed that the tumor was a high-grade serous carcinoma of gynecological origin. Subsequent surgery for total hysterectomy with bilateral salpingo-oophorectomy revealed that the tumor developed in the fallopian tube. She received adjuvant chemotherapy with carboplatin and paclitaxel, followed by maintenance therapy with niraparib. There has been no recurrence or metastasis 9 months after the second surgery. We reviewed the literature for cases of PFTC and ovarian carcinoma that initially presented with an inguinal tumor. In compliance with the Preferred Reporting Items for Systematic Reviews guidelines, a systematic literature search was performed through 31 January 2022 using the PubMed and Google scholar databases and identified 14 cases. In half of them, it was difficult to identify the primary site using preoperative imaging modalities. Disease recurrence occurred in two cases; thus, the prognosis of this type of PFTC appears to be good.

Uterine Mesenchymal Tumors: Updates on Pathology, Molecular Landscape, and Therapeutics

Background: Mesenchymal uterine tumors are a diverse group of neoplasms with varying biological potential. Many of these neoplasms can have overlapping morphologic similarities, which, in some instances, render their diagnosis and categorization thorough histomorphologic examination inconclusive. In the last decade, an exponential amount of molecular data aiming to more accurately characterize and, consequently, treat these tumors have accumulated. Objective: The goal of this narrative review is to provide a pathologic review, a genetic update, and to know the new therapeutic avenues of primary uterine mesenchymal neoplasms.

Total Exenteration En Bloc with a Nephrectomy for Locally Advanced Cervical Cancer Invading a Pelvic Kidney—A Case Report and Literature Review

Introduction: Extended pelvic resection might be the option of choice in patients presenting locally advanced cervical cancer. However, the possibility of a co-existence of an ectopic, pelvic kidney that is invaded by such a tumor is extremely rare. Case Presentation: A 54-year-old female patient, diagnosed with locally advanced cervical cancer in the presence of a pelvic kidney, was submitted to surgery with curative intent. A large, abscessed cervical tumor invading the urinary bladder and the rectum was found, so a total exenteration was planned. Intraoperatively, tumor invasion of the left kidney, which was found in an ectopic, pelvic position was also encountered; therefore, total pelvic exenteration in association with a left nephrectomy was successfully performed. Conclusions: The presence of an ectopic, pelvic disposition of the kidney makes it susceptible to be invaded by locally advanced pelvic tumors; in such cases, a nephrectomy might also be needed.

Uncommon Metastasis of Ovarian Dysgerminoma: A Case Report and Review of the Literature

Ovarian malignant germ cell tumors (OMGCT) represent less than 10% of all ovarian tumors. Dysgerminoma is the most common malignant primitive germ cell tumor in young women, known for its curability and low propensity to invade and metastasize when diagnosed early. Herein, we report an unusual type of ovarian dysgerminoma (OD) metastasis with a brief review of the literature, lacking similar reported cases. To our knowledge, although there are several case reports of dysgerminoma metastases with variable anatomic location and presentation, vaginal metastasis has not been previously described. The local or systemic relapse together with local and distant metastasis is considered as an independent predictor of poor survival in patients with OD. In light of the absence of mutations status, our patient successfully responded to therapy. Currently, the patient remains in clinical remission. A specific follow-up plan is ongoing knowing that ovarian dysgerminomas tend to recur most often in the first 2–3 years after treatment.

Pan-Cancer Analysis Reveals PPRC1 as a Novel Prognostic Biomarker in Ovarian Cancer and Hepatocellular Carcinoma

Background and Objectives: As is well understood, peroxisome proliferator-activated receptor gamma cofactor-related 1 (PPRC1) plays a central role in the transcriptional control of the mitochondrial biogenesis and oxidative phosphorylation (OXPHOS) process, yet its critical role in pan-cancer remains unclear. Materials and Methods: In this paper, the expression levels of PPRC1 in different tumor tissues and corresponding adjacent normal tissues were analyzed based on four databases: The Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), The Cancer Genome Atlas (TCGA), and Tumor Immune Estimation Resource (TIMER). Meanwhile, the prognostic value of PPRC1 was inferred using Kaplan–Meier plotter and forest-plot studies. In addition, the correlation between PPRC1 expression and tumor immune cell infiltration, immune checkpoints, and the tumor-stemness index was analyzed using TCGA and TIMER databases. Results: According to our findings, the expression level of PPRC1 was found to be different in different cancer types and there was a positive correlation between PPRC1 expression and prognosis in several tumor types. In addition, PPRC1 expression was found to be significantly correlated with immune cell infiltration, immune checkpoints, and the tumor-stemness index in both ovarian and hepatocellular carcinoma. Conclusions: PPRC1 demonstrated promising potential as a novel biomarker in pan-cancer due to its potential association with immune cell infiltration, expression of immune checkpoints, and the tumor-stemness index.

Meigs Syndrome and Elevated CA-125: Case Report and Literature Review of an Unusual Presentation Mimicking Ovarian Cancer

Background and Objectives: Meigs syndrome is represented by a benign adnexal tumor, ascites, and hydrothorax. Even though the ovarian mass is often characterized by a fibroma-like origin, cancer antigen-125 (CA-125) serum levels could be elevated as in the development of ovarian cancer. Here, we present the case of a patient with Meigs syndrome and increased CA-125. Materials and Methods: We performed systematic research for articles including similar cases in PubMed, EMBASE, and Scopus in February 2023, adopting the string of idioms: “Meigs syndrome AND Cancer antigen 125”, and following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Eligible records were 25. Hydrothorax was right-sided in 10 cases over 25; left-sided in two patients over 25. Concerning ascites, two patients showed more than 6 L of ascitic fluid, whereas three patients had 6 L or less. CA-125 elevation ranged from 149 IU/mL to 3803 IU/mL. Adnexal mass histotypes were: struma ovarii (12 cases), thecomas (two cases), fibrothecomas (five cases), fibromas (five cases), and one sclerosing stromal tumor (SST). Conclusions: In postmenopausal women with elevated CA-125 serum levels and an adnexal mass suspicious for malignancy at ultrasound (US), ascites and pleural effusion, surgery, and histopathological examination are necessary. MS is a diagnostic option, with an excellent prognosis after exeresis of the mass.

Assessing the Level of Knowledge and Experience Regarding Cervical Cancer Prevention and Screening among Roma Women in Romania

Background and Objectives: Romania ranks among the countries with a particularly high rate of mortality that can be prevented through prevention programs, screening, early detection, and prompt care. Cervical cancer (CC) is a major cause of these preventable deaths, affecting individuals from marginalized and rural regions, as well as the Roma population. The purpose of this article was to identify accurate and consistent information about the Roma population on the risk of CC, as well as the importance of understanding the causes of the disease and awareness of the available prevention methods. Materials and Methods: A cross-sectional study was conducted using a self-administered questionnaire applied only to Roma women in Romania. Results: We enrolled 759 patients in this study. These were divided into two groups: Group 1 comprised 289 (38.1%) women who had been tested for HPV infection, while Group 2 included 470 (61.9%) women who had never been tested for HPV infection. Characterization of women in Group 1: mostly aged between 25 and 54 years, with high school education, married, who started sexual activity under the age of 18 years, with only one sexual partner, and had over five pregnancies. Regarding contraceptive methods, 35.7% of women do not know or use any contraceptive method, and 32.2% use hormonal contraceptives. Two thirds of the women tested had heard of HPV, and 19.7% were vaccinated against HPV with at least 2–3 doses. A percentage of 8.7 had a diagnosis of CC, compared to those who were not tested (p-0.0001), whereas 63% of the tested women did not know much about CC, as opposed to 85.7% of the group of untested women. Conclusions: Cervical cancer (CC) continues to be a public health concern in Romania, particularly among vulnerable groups. Promoting campaigns to raise awareness for HPV vaccination and CC screening are necessary to reduce the associated mortality and morbidity.

Trends in Mortality Rates of Corpus Uteri and Ovarian Cancer in Lithuania, 1987–2016

Background: The corpus uteri and ovarian cancers burden in Lithuania has remained high. The aim of this study was to investigate time trends in mortality rates of corpus uteri and ovarian cancer in Lithuania across age groups and time periods over a 30-year time span. Materials and Methods: Data on numbers of deaths from corpus uteri cancer during the period 1987–2016 and ovarian cancer during the period 1993–2016 were obtained from the WHO mortality database. Trends in age-standardized mortality rates (ASR, world standard), and age-specific rates were analyzed by calculating annual percentage change using Joinpoint regression. In addition, age–period–cohort analysis was performed for each cancer type. Results: Mortality from corpus uteri cancer decreased by −1.2% (95% CI: −1.8; −0.7) annually from 1987 to 2016. Decrease was most pronounced in youngest age group of 40–49 years; annual percentage change was −2.4 (95% CI: −4.0; −0.9). Mortality rates for ovarian cancers decreased by −1.2% (95% CI: −1.6; −0.8) annually from 1993 to 2016. Corpus uteri and ovarian cancer ASRs in 2016 were 3.5/100,000 and 7.4/100,000, respectively. The age–period–cohort analysis suggests that temporal trends in corpus uteri cancer mortality rates could be attributed to period and cohort effects. Conclusion: A reduction in mortality rate was observed for corpus uteri and ovarian cancer over the entire study period. Similar decreasing pattern for corpus uteri and ovarian cancer mortality indicate effect of shared factors.

IL-6 597A/G (rs1800797) and 174G/C (rs1800795) Gene Polymorphisms in the Development of Cervical Cancer in Lithuanian Women

Our study aimed to evaluate the distribution of genotypes and allele frequencies of IL-6 597A/G (rs1800797) and 174G/C (rs1800795) polymorphisms in HPV infected and uninfected healthy women and cervical cancer patients. A PCR based Multiplex HPV genotyping test kit was used for in vitro detection and differentiation of high risk HPV genotypes. Genotyping of two polymorphisms, IL-6 597A/G (rs1800797) and 174G/C (rs1800795), was performed using the KASP genotyping assay kit. Cervical cancer patients were more likely to be HPV positive than control patients. Allele C of IL-6 rs1800795 was associated with a higher risk of cervical cancer by 2.26-fold and genotype CC by 5.37-fold. Genotype CC of IL-6 rs1800795 was more frequent in the HPV positive group compared with the HPV negative group (p = 0.002). Allele G of IL-6 rs1800797 was more frequently found in women with HPV16/HPV18 compared to other HPV types (p = 0.045). Women with AA genotypes of IL-6 rs1800797 were less frequently infected with HPV16/HPV18 compared to other HPV types (p = 0.045). The major finding of the study is the significant association of C allele and CC genotype of IL-6 1800795 gene with cervical cancer in the Lithuanian population. Genotype CC of IL-6 rs1800795 has a significant association with HPV infection as well.

Cervical Cancer Prevention in the Era of the COVID-19 Pandemic

Background and Objectives: Cervical cancer (CC) is the fourth most common cause of cancer-related morbidity and mortality among women worldwide. CC prevention is based on screening and HPV vaccination. The COVID-19 pandemic has caused difficulties in implementing CC-preventative measures. The aim of this study was to collect data on the implementation of CC prophylaxis in Poland provided by public and private health care with a particular focus on the impact of the COVID-19 pandemic and attempt to estimate the level of CC-screening implementation by 2026 under public and private health care. Materials and Methods: Data on the implementation of privately funded (2016–2021) and publicly funded (2014–2021) CC-preventative measures in Poland were examined. The Prophet algorithm, which positions itself as an automatic forecasting procedure and represents a local Bayesian structural time-series model, was used to predict data. The correlation test statistic was based on Pearson’s product moment correlation coefficient and follows a t distribution. An asymptotic confidence interval was given based on Fisher’s Z transform. Results: In 2021, a significantly higher population screening coverage was observed in private health care (71.91%) than in the public system (12.6%). Our estimation assumes that the adverse downward trend of population coverage (pap smear CC screening) in the public system will continue to 5.02% and in the private health system to 67.92% in 2026. Correlation analysis showed that with the increase in the sum of HPV tests and LBC, the percentage of Pap smear coverage in the private healthcare sector decreases r = −0.62, p = 0.260 df = 3, CI = [−0.97, 0.57]. The amount of HPV vaccinations provided in private health care is steadily increasing. Immunization coverage of the population of girls aged 9–18 years under private health care at the end of the observation period was 4.3% (2021). Conclusions: It is necessary to reorganize the public CC-screening system in Poland based on a uniform reporting system for tests performed in both public and private health care using the model of action proposed by us. We recommend the introduction of a national free HPV vaccination program funded by the government and implemented in public and private health care facilities.

Ultrasound Assessment of Adnexal Pathology: Standardized Methods and Different Levels of Experience

Background and objectives: An expert’s subjective assessment is still the most reliable evaluation of adnexal pathology, thus raising the need for methods less dependent on the examiner’s experience. The aim of this study was to evaluate the performance of standardized methods when applied by examiners with different levels of experience and to suggest the most suitable method for less-experienced gynecologists. Materials and methods: This single-center retrospective study included 50 cases of histologically proven first-time benign or malignant adnexal pathology. Three examiners evaluated the same transvaginal ultrasound images: an expert (level III), a 4th year resident in gynecology (level I), and a final year medical student after basic training (labeled as level 0). The assessment methods included subjective evaluation, Simple Rules (SR) with and without algorithm, ADNEX and Gynecologic Imaging Reporting and Data System (GI-RADS) models. Sensitivity, specificity, accuracy, positive and negative predictive values with 95% confidence interval were calculated. Results: Out of 50 cases, 33 (66%) were benign and 17 (34%) were malignant adnexal masses. Using only SR, level III could classify 48 (96%), level I—41 (82%) and level 0—40 (80%) adnexal lesions. Using SR and algorithm, the performance improved the most for all levels and yielded sensitivity and specificity of 100% for level III, 100% and 97% for level I, 94.4% and 100% for level 0, respectively. Compared to subjective assessment, ADNEX lowered the accuracy of level III evaluation from 97.9% to 88% and GI-RADS had no impact. ADNEX and GI-RADS improved the sensitivity up to 100% for the less experienced; however, the specificity and accuracy were notably decreased. Conclusions: SR and SR+ algorithm have the most potential to improve not only sensitivity, but also specificity and accuracy, irrespective of the experience level. ADNEX and GI-RADS can yield sensitivity of 100%; however, the accuracy is decreased.

Gestational Trophoblastic Disease: Diagnostic and Therapeutic Updates in Light of Recent Evidence: A Literature Review

Background/objectives: Gestational trophoblastic diseases (GTDs) are rare premalignant and malignant conditions characterized by abnormal proliferation of trophoblastic tissue. They are often asymptomatic but may present with vaginal bleeding. GTDs include hydatidiform moles and gestational trophoblastic neoplasms (GTNs). Current research aims to improve diagnostic tools and treatment strategies to reduce cancer risk and improve survival. Increasing attention is being paid to immunotherapy and treatment personalization, with the goal of minimizing long-term side effects and enhancing quality of life. Less toxic therapies are ideal for low-risk patients to reduce drug-related toxicity. Materials and Methods: A narrative review was conducted to analyze studies from the last twenty years on the diagnosis, staging, and treatment of GTDs. Sources included PubMed, Scopus, and Cochrane Library, using keywords such as “trophoblastic disease,” “hydatidiform mole,” and “gestational trophoblastic neoplasia.” Results: In recent years, the clinical management of gestational trophoblastic disease (GTD) has made significant progress through diagnostic, prognostic, and therapeutic innovations. More sensitive imaging techniques and serial monitoring of serum β-hCG now allow early diagnosis of hydatidiform mole and gestational trophoblastic neoplasia (GTN), reducing the risk of complications and metastasis. Conclusions: In the last decade, GTD management has improved significantly, with better diagnostic techniques, standardized staging, and more effective treatments. However, challenges persist, including relapse management, long-term monitoring, and psychological support. Early diagnosis is key, with ultrasound being essential for detecting abnormalities in the first weeks of pregnancy. Staging follows FIGO and WHO criteria, considering hCG levels and metastasis. This review highlights recent advances in diagnostic tools, emerging therapies—including immunotherapy—and the need for personalized, less toxic treatment approaches to improve patient outcomes.

Effect of the HDAC Inhibitor on Histone Acetylation and Methyltransferases in A2780 Ovarian Cancer Cells

Background andObjective: Epigenetic modifications are believed to play a significant role in the development of cancer progression, growth, differentiation, and cell death. One of the most popular histone deacetylases inhibitors (HDACIs), suberoylanilide hydroxamic acid (SAHA), also known as Vorinostat, can directly activate p21WAF1/CIP1 gene transcription through hyperacetylation of histones by a p53 independent mechanism. In the present investigation, we evaluated the correlation between histone modifications and DNA methyltransferase enzyme levels following SAHA treatments in A2780 ovarian cancer cells. Materials and Methods: Acetylation of histones and methyltransferases levels were analyzed using RT2 profiler PCR array, immunoblotting, and immunofluorescence methods in 2D and 3D cell culture systems. Results: The inhibition of histone deacetylases (HDAC) activities by SAHA can reduce DNA methyl transferases / histone methyl transferases (DNMTs/HMTs) levels through induction of hyperacetylation of histones. Immunofluorescence analysis of cells growing in monolayers and spheroids revealed significant up-regulation of histone acetylation preceding the above-described changes. Conclusions: Our results depict an interesting interplay between histone hyperacetylation and a decrease in methyltransferase levels in ovarian cancer cells, which may have a positive impact on the overall outcomes of cancer treatment.

Neoadjuvant Chemotherapy in Advanced Stage Endometrial Cancer: A Systematic Review and Meta-Analysis

Background and Objectives: Endometrial cancer is the most common gynecological malignancy in developed countries and is becoming increasingly prevalent. Early diagnosis and treatment may lead to lower rates of morbidity and mortality. The aim of the present meta-analysis is to investigate whether neoadjuvant chemotherapy (NACT) can enhance resectability, reduce tumor burden, and ultimately improve survival rates compared to primary surgery in patients with advanced endometrial cancer. Materials and Methods: All studies that examined the impact of NACT on survival outcomes of patients with advanced endometrial cancer were eligible for inclusion, including randomized and non-randomized interventional studies. Studies were identified by searching MEDLINE (1945–2024), Scopus (1941–2024), Google Scholar (2004–2024) and ClinicalTrials.gov (2000–2024). Data was selected and extracted by two reviewers based on the PRISMA guidelines. Results: Five retrospective studies with a cumulative total of 8658 patients were included. No statistically significant difference in overall survival was observed between patients who received NACT and those who underwent primary surgery (HR 0.91, 95% CI 0.79–1.04). NACT was associated with some perioperative advantages, though these did not translate into a survival benefit. Conclusions: The currently available evidence, which is limited to retrospective studies with significant heterogeneity, suggests that NACT does not confer a survival advantage over primary debulking surgery in advanced endometrial cancer. These findings should be considered hypothesis-generating, underscoring the need for prospective trials. NACT may still be a reasonable option for selected subgroups, such as frail patients, those with extensive peritoneal disease, or cases in which complete cytoreduction is unlikely with upfront surgery.

Does Retroperitoneal vNOTES Sentinel Lymph Node Mapping Represent a Feasible Staging Option in Presumed Early-Stage Endometrial Cancer?

Background and Objectives: Sentinel lymph node (SLN) mapping is an established alternative to systematic lymphadenectomy for early-stage endometrial cancer (EC). While retroperitoneal vNOTES affords direct access to pelvic nodes without abdominal incisions, data regarding its oncologic validity remain sparse. This study evaluates the SLN detection rates, perioperative outcomes, and 12-month oncologic outcomes oncologic results of retroperitoneal vNOTES mapping in presumed early-stage EC. Materials and Methods: This single-center retrospective cohort study analyzed consecutive patients undergoing retroperitoneal vNOTES staging (hysterectomy, BSO, and SLN mapping) for presumed EC between February 2023 and January 2024. Eligible patients had radiologically uterine-confined disease and were candidates for transvaginal surgery. Following cervical methylene blue injection, SLN mapping was executed via the retroperitoneal vNOTES route. Mapped and suspicious nodes were excised, with side-specific lymphadenectomy performed for failed mapping per algorithm. While perioperative outcomes were assessed for the full cohort, oncologic analyses (FIGO 2023 staging, nodal metastasis) were restricted to patients with confirmed carcinoma. Results: Of 98 patients (median age 54; BMI 31 kg/m2), final pathology confirmed carcinoma in 78 (73 endometrioid, 5 serous) and EIN in 20. Bilateral SLN mapping succeeded in 87.8% (86/98), necessitating side-specific lymphadenectomy in the remaining 12.2%. The obturator fossa was the predominant nodal basin (43.9%). Within the carcinoma cohort (n = 78), 57.7% were Grade 1 and 74.4% FIGO Stage I. Nodal metastases (FIGO IIIC1) were identified in 12.8% (10/78), all prompting adjuvant therapy. At a median follow-up of 12 months, no disease recurrences were observed. The complication rate was 6.1% (5.1% Clavien–Dindo ≥ III), with no conversions required. At 12-month follow-up, no recurrences were detected, though the absence of systematic lymphadenectomy precluded formal sensitivity analysis. Conclusions: Retroperitoneal vNOTES represents a feasible and safe strategy for SLN mapping in early-stage EC, demonstrating high bilateral detection with minimal morbidity. However, reliance on methylene blue and limited follow-up necessitate caution. Broader implementation requires validation through prospective, comparative trials utilizing indocyanine green and long-term oncologic surveillance.

Early Postoperative Albumin and Neutrophil Dynamics for Risk Stratification After Cytoreductive Surgery in Ovarian Cancer: A Retrospective Multicenter Cohort Study

Background and Objectives: Serum albumin is a widely available and inexpensive biomarker that reflects nutritional status and physiological reserve. Hypoalbuminemia has been linked to poor postoperative outcomes in surgical oncology; however, its role in predicting early complications after cytoreductive surgery for ovarian cancer, as well as the potential contribution of systemic inflammatory indices in nutritionally preserved patients, remains incompletely understood. This study aimed to evaluate the predictive value of early postoperative serum albumin for early surgical complications and to explore whether inflammatory indices could offer additional prognostic information in patients with adequate albumin levels. Materials and Methods: We conducted a retrospective observational cohort study including patients undergoing cytoreductive surgery for ovarian cancer at two Italian tertiary referral centers between July 2023 and December 2025. Postoperative serum albumin was measured on the first postoperative day. Systemic inflammatory parameters were assessed using perioperative changes in neutrophils and composite indices. Early postoperative complications occurring within 30 days were recorded. Multivariable logistic regression analyses were performed, and subgroup analyses were conducted in patients with postoperative albumin ≥3 g/dL. Receiver operating characteristic (ROC) analysis was used to identify an optimal cutoff for significant inflammatory predictors. Results: A total of 121 patients were included, of whom 30 developed early postoperative complications. Patients with complications had significantly lower postoperative albumin levels than those without complications (median 2.75 vs. 3.09 g/dL; p < 0.001). In multivariable analysis, lower postoperative albumin independently predicted early complications (OR 0.26, 95% CI 0.06–0.86). In the subgroup of patients with preserved albumin levels (≥3 g/dL), a smaller postoperative neutrophil decline independently predicted complications (OR 1.56, 95% CI 1.12–2.70). A neutrophil drop cutoff of −1.15 × 103/dL showed good specificity (81.5%) and high negative predictive value (95.7%). Conclusions: Early postoperative serum albumin is a strong predictor of early surgical complications after cytoreductive surgery for ovarian cancer. In patients with preserved nutritional status, dynamic neutrophil changes provide additional prognostic information. Incorporating low-cost metabolic and inflammatory biomarkers may enhance early postoperative risk stratification and support more personalized patient management.

HER3 and FOLR1 Expression as Actionable Targets in High-Grade Serous Ovarian Carcinoma: Prognostic and Therapeutic Implications

Background and Objectives: High-grade serous ovarian carcinoma (HGSC) is characterized by aggressive tumor behavior, frequent recurrence, and limited long-term survival. Despite the established clinicopathological prognostic factors, significant heterogeneity in clinical outcomes persists, highlighting the need for biologically relevant molecular biomarkers. HER3 and folate receptor alpha (FOLR1) have promising prognostic biomarkers in ovarian cancer; however, the combined biological and prognostic impact of these two molecules has not yet been clearly demonstrated. Materials and Methods: This retrospective observational study included 66 patients with histopathologically confirmed HGSC. The immunohistochemical expression of HER3 and FOLR1 was evaluated using a standardized immunoreactivity scoring system. Associations with clinicopathological features were analyzed, and survival outcomes were analyzed using Kaplan–Meier analysis and Cox proportional hazards regression models. Results: High HER3 expression was significantly associated with distant metastasis and was identified as an independent adverse prognostic factor for both overall survival (OS) and progression-free survival (PFS). FOLR1 expression was associated with OS in univariate analysis, but did not retain independent prognostic significance in multivariate models. A moderate yet statistically significant positive correlation between HER3 and FOLR1 expression was observed, suggesting a potential association between proliferative signaling and metabolic pathways that may warrant further mechanistic investigation. Conclusions: Our findings demonstrate that HER3 is a robust prognostic biomarker in HGSC and support a biologically relevant HER3–FOLR1 interaction contributing to tumor aggressiveness. These results provide a translational rationale for combined biomarker assessment and for the development of HER3- and FOLR1-targeted therapeutic strategies, particularly antibody–drug conjugates, for HGSC.

The Hidden Cost of Delay: Post-Pandemic Evolution of Advanced Ovarian Cancer Profiles

Background and Objectives: High-grade serous ovarian carcinoma (HGSOC) remains the most lethal gynecologic malignancy, with outcomes heavily dependent on early diagnosis and timely multimodal treatment. The COVID-19 pandemic profoundly disrupted oncologic care, leading to diagnostic delays, modified treatment algorithms, and deferred surgeries. This study aimed to assess how these disruptions influenced disease presentation, surgical complexity, and postoperative outcomes during the pandemic and post-pandemic periods in a Romanian tertiary oncology center. Materials and Methods: A retrospective, single-center cohort analysis was conducted on 112 patients with histologically confirmed HGSOC who underwent surgical treatment between 26 February 2020 and 25 February 2024. The cohort was divided into two equal groups: a pandemic cohort (2020–2022) and a post-pandemic cohort (2022–2024). Clinical, pathological, and therapeutic parameters were compared, including FIGO and T staging, surgical duration, ICU admissions, and treatment intervals. Results: The post-pandemic period was marked by a significant rise in advanced-stage presentations (FIGO IV: 17.8% vs. 33.9%, p = 0.003), peritoneal carcinomatosis (58.9% vs. 82.1%, p = 0.004), and multiorgan invasion (7.1% vs. 16.0%, p = 0.039). Mean operative time increased significantly post-pandemic (94.0 ± 36.3 vs. 123.5 ± 52.5 min, p = 0.003), as did ICU admissions (35.7% vs. 60.7%, p = 0.002). While the number of neoadjuvant and adjuvant chemotherapy cycles remained consistent between cohorts, a greater surgical complexity and longer postoperative recovery characterized the post-pandemic cases, suggesting cumulative disease progression and increased treatment demands. Conclusions: The findings indicate an association between the post-pandemic period and more advanced disease profiles at presentation, as well as increased surgical complexity, highlighting potential long-term effects of healthcare disruption. These results highlight the necessity for resilient cancer care systems emphasizing early detection, multidisciplinary coordination, and adaptive treatment models to mitigate future systemic disruptions and preserve survival outcomes in women with HGSOC.

The Role of Lymph Node Downstaging Following Neoadjuvant Treatment in a Group of Patients with Advanced Stage Cervical Cancer

Background and Objectives: Cervical cancer is the fourth most frequent type of neoplasia in women. It is most commonly caused by the persistent infection with high-risk strands of human papillomavirus (hrHPV). Its incidence increases rapidly from age 25 when routine HPV screening starts and then decreases at the age of 45. This reflects both the diagnosis of prevalent cases at first-time screening and the likely peak of HPV exposure in early adulthood. For early stages, the treatment offers the possibility of fertility preservation.. However, in more advanced stages, the treatment is restricted to concomitant chemo-radiotherapy, combined, in very selected cases with surgical intervention. After the neoadjuvant treatment, an imagistic re-evaluation of the patients is carried out to analyze if the stage of the disease remained the same or suffered a downstaging. Lymph node downstaging following neoadjuvant treatment is regarded as an indubitable prognostic factor for predicting disease recurrence and survival in patients with advanced cervical cancer. This study aims to ascertain the important survival role of radiotherapy in the downstaging of the disease and of lymphadenectomy in the control of lymph node invasion for patients with advanced-stage cervical cancer. Material and Methods: We describe the outcome of patients with cervical cancer in stage IIIC1 FIGO treated at Bucharest Oncological Institute. All patients received radiotherapy and two-thirds received concomitant chemotherapy. A surgical intervention consisting of type C radical hysterectomy with radical pelvic lymphadenectomy was performed six to eight weeks after the end of the neoadjuvant treatment. Results: The McNemar test demonstrated the regression of lymphadenopathies after neoadjuvant treatment—p: <0.001. However, the persistence of adenopathies was not related to the dose of irradiation (p: 0.61), the number of sessions of radiotherapy (p: 0.80), or the chemotherapy (p: 0.44). Also, there were no significant differences between the adenopathies reported by imagistic methods and those identified during surgical intervention—p: 0.62. The overall survival evaluated using Kaplan-Meier curves is dependent on the post-radiotherapy FIGO stage—p: 0.002 and on the lymph node status evaluated during surgical intervention—p: 0.04. The risk factors associated with an increased risk of death were represented by a low preoperative hemoglobin level (p: 0.003) and by the advanced FIGO stage determined during surgical intervention (p-value: 0.006 for stage IIIA and 0.01 for stage IIIC1). In the multivariate Cox model, the independent predictor of survival was the preoperative hemoglobin level (p: 0.004, HR 0.535, CI: 0.347 to 0.823). Out of a total of 33 patients with neoadjuvant treatment, 22 survived until the end of the study, all 33 responded to the treatment in varying degrees, but in 3 of them, tumor cells were found in the lymph nodes during the intraoperative histopathological examination. Conclusions: For advanced cervical cancer patients, radical surgery after neoadjuvant treatment may be associated with a better survival rate. Further research is needed to identify all the causes that lead to the persistence of adenopathies in certain patients, to decrease the FIGO stage after surgical intervention, and, therefore, to lower the risk of death. Also, it is mandatory to correctly evaluate and treat the anemia, as it seems to be an independent predictor factor for mortality.

Impact of SARS-CoV-2 Pandemic on the Diagnosis of Cervical Cancer and Precursor Lesions—A Single-Center Retrospective Study

Background and Objectives: Our aim was to perform a retrospective analysis of the volume of cervical screening tests, the number of patients treated with an excision method, and the incidence of invasive and non-invasive cervical during a pandemic and pre-pandemic period of 24 months. Materials and Methods: The study compared 404 patients who underwent cervical cone biopsy for cervical cancer. The study examined patients’ specimens based on histopathological characteristics and categorized cervical lesions based on pap smear. Results: There was a statistically significant age difference between the two study periods. The mean difference was 32 years before the pandemic and 35 years during the pandemic (p-value > 0.05). The biggest patient loss ratio identified by age group was in the 50–59-year group, with a 14.53% loss in the pre-pandemic period and a 9.1% loss in the pandemic period. In the pandemic period, patients from rural areas presented in the clinical trial with a lower rate of 39.52% (83 patients) vs. 60.47% (127 patients) in urban areas. A higher percentage of patients experiencing cervicorrhagia as a clinical manifestation in the pandemic period vs. the pre-pandemic period, with an increase in more severe lesions in the pandemic period, had a statistical significance of 8% more newly diagnosed compared to the pre-pandemic period. Conclusions: The addressability of the patients during the COVID period was not affected in a drastic way in our study. We encountered a decrease in appointments in the age group of 50–59 years and a decrease in patients with rural residence. In our study, we found an increase in cervical bleeding as a reason for consultation in the pandemic period with a higher lesion degree, both on a pap smear and on a cervical biopsy.

A Novel Notch-Related Gene Signature for Prognosis and Immune Response Prediction in Ovarian Cancer

Background and Objectives: Notch is a fascinating signaling pathway. It is extensively involved in tumor growth, cancer stem cells, metastasis, and treatment resistance and plays important roles in metabolic regulation, tumor microenvironment, and tumor immunity. However, the role of Notch in ovarian cancer (OC) has yet to be fully understood. Therefore, this study systematically described the expression, mutation, and copy number variation of genes in the Notch signaling pathway in OC and evaluated the relationship between gene mutation and Overall Survival (OS) prognosis. Materials and Methods: Notch risk score (NTRS) was established by univariate Cox regression analysis combined with Lasso regression analysis, and the efficacy of NTRS in predicting prognosis and immunotherapy response in patients with OC was verified. We further assessed the correlations of NTRS with clinical features, immune infiltration level, immune checkpoint expression, and immune characteristics. Additionally, differential expression and functions of the fourteen signature genes were confirmed via vitro assays. Results: The results showed that Notch genes (NTGs) were markedly differentiated between tumor and normal tissues, which may help to explain the high heterogeneity in the biological characteristics and therapeutic outcomes of human OC. A Notch risk (NTR) prognostic model based on 11 key NTGs was successfully constructed. Tumors with high Notch risk scores (NTRS) were independently associated with shorter overall survival and poorer immunotherapy outcomes. We further assessed the correlations of NTRS with immune characteristics. The results showed that NTGs play a key role in regulating the tumor immune microenvironment. Additionally, we validated the baseline and induced expressions of 14 prognosis-related NTGs in our own OC samples. In vitro assays confirmed that the knockdown of NCOR2 and APH1B and overexpression of HEY2 and SKP2 could inhibit the proliferation, invasion, and migration of OC cells. Conclusions: These findings emphasize that Notch multilayer changes are associated with the prognosis of patients with OC and the characteristics of immune cell infiltration. Our predictive signature may predict the prognosis and immunotherapy response of OC patients in an independent manner. NCOR2, APH1B, HEY2, and SKP2 may more prominently represent important indicators to improve patient prognosis.

Expression of Inflammation Depending on the Stage of Cervical Cancer

Background and Objectives: Cervical cancer (CC) remains a major public health problem, ranking as the fourth most common cause of cancer incidence and mortality in women globally. The development of CC is believed to be closely related to chronic inflammation. Thus, we aimed to evaluate the expression of systemic inflammation in patients with CC and to determine the threshold prognostic value of the systemic inflammation markers for CC and its advanced stage. Materials and Methods: 182 participants were recruited: 94 histology-proven patient with CC and 88 healthy women with NILM confirmed by liquid-based cytology test. The pre-treatment serum concentrations of cytokines, including IFN-β, IFN-γ, IL-1β, IL-2, IL-6, IL-10, IL-12p70, LCN2, TREM-1, and TNF-α, were determined for all study patients. Results: The odds ratio (OR) of having IL-6 concentration >17.4 pg/mL in the CC group compared to control patients was 11.4 (95% CI: 4.897–26.684); that of having TREM-1 concentration >355.6 pg/mL was 5.9 (95% CI: 2.257–15.767); and that of having LCN2 concentration >23,721.5 pg/mL was 3.4 (95% CI: 1.455–8.166). The odds ratio (OR) of having IL-6 concentration >28.7 pg/mL in advanced-stage CC (III–IV stage) compared to early-stage CC (I–II stage) was 2.921 (95% CI: 1.06–8.045), and that of having LCN2 concentration >25,640.0 pg/mL was 4.815 (95% CI: 1.78–13.026). Conclusions: The pre-treatment serum inflammation markers IL-6, TREM-1, and LCN2 at specified levels could be used as predictors of cervical cancer, and IL-6 and LCN2 as predictors of an increased chance of advanced-stage (III–IV stages) cervical cancer. Patients with cervical cancer had expressed systemic inflammation, and expression of inflammation elevated the chance of having CC and advanced-stage disease.

The Role of β1 Integrin/CD29 as a Potential Prognostic Factor for the Risk of Progression to Cervical Carcinoma in HPV-Associated Lesions

Background and Objectives: Available evidence reports the overexpression of β1 integrin in dysplastic rather than normal cervical tissue. We aimed to evaluate the involvement of β1 (CD29) integrin in the progressive pathogenesis of cervical intraepithelial neoplasia (CIN). Materials and Methods: From January 2019 to December 2021, we prospectively enrolled women undergoing a colposcopy with a cervical biopsy for abnormal cervical cytology and/or undefined cytology with a positive HPV DNA test and women with relapsing cervical inflammatory disorders. Based on the histopathological results, women were divided into four groups: group A (CIN1), group B (CIN2), group C (CIN3), and group D (no CIN diagnosis) as a control group. Subsequently, cytofluorimetry and immunohistochemical analysis (based on the identified positive cell ratios as follows: ≤10%, negative; 10–25%, 1+ (weak); 25–50%, 2+ (medium); ≥50%, and 3+ (high)) for β1 integrin were carried out. Results: In total, 154 women were included. The average fluorescence intensity in the four groups was 2.35 ± 1.37, 2.73 ± 1.56, 3.09 ± 1.56, and 2.13 ± 1.25 UA from groups A to D, respectively; this figure was significantly different for CIN3 (group C) women relative to the other groups (p = 0.0132). Higher β1 integrin/CD29 concentrations in the CIN groups with HR-HPV 16 and 18 were also detected (p = 0.0292, 0.0367, and 0.0357 respectively for CIN3, CIN2, and CIN1). Immunohistochemistry analysis showed higher results for the CIN3 group compared to controls and all the other groups (p < 0.001). Conclusions: β1/CD29 integrin expression increased with CIN grade, and it was significantly higher in CIN3 lesions. This could be used as a promising screening tool to identify women prone to developing high-grade cervical lesions. However, additional evidence is needed to strengthen these findings.

Reflections on Postpartum Hysterectomy as a Possible Complication of Cesarean Myomectomy: A Long Debate

Uterine fibroids are common benign tumors found in fertile women. Numerous obstetrical issues, such as dystocia during labor, fetal hypotrophy, a ruptured amniotic sac, early labor, low-birth-weight newborns, etc., are associated with fibrous pregnant uteri. Cesarean myomectomy is not a common procedure because of the possibility of postpartum hysterectomy or a potentially lethal hemorrhage. For the chosen topic, we present two instances of emergency postpartum hysterectomies following cesarean myomectomy. After a cesarean myomectomy, two women experienced a perioperative hemorrhage that required a postpartum hysterectomy without a salpingo-oophorectomy. A postpartum hysterectomy was required in every instance due to the failure of additional hemostatic techniques to control the bleeding after the cesarean myomectomy. In every case, the location and number of fibroids—rather than their size—were the primary factors leading to the postpartum hysterectomy. In order to ensure that the patient is safe and that the advantages outweigh the dangers, the current trends in cesarean myomectomy include aiming to conduct the procedure either electively or when it offers an opportunity. The treatment is still up for debate because it is unknown how dangerous a second hysterectomy is for people who have had a cesarean myomectomy.

Cesarean Myomectomy: Reflections on Clinical and Surgical Controversies between a New Trans-Decidual Technique vs. Traditional Method

Up to 70–80% of women of reproductive age may be affected with the most common uterine tumors, known as fibroids or myomas. These benign tumors are the second most prevalent cause of surgery among premenopausal women. Predictions show that the occurrence of myomas in pregnancy will increase, and that the risk of having myomas during pregnancy increases with advanced maternal age. Although most women with fibroids do not experience any symptoms during pregnancy, up to 30% of women experience problems during pregnancy, childbirth, and the puerperium. The viability of myoma excision during cesarean surgery (CS) is a contentious issue raised by the rising incidence of myomas in pregnancy and CS rates. A new surgical procedure for removing fibroids using a trans-endometrial approach, which involves making an incision through the decidua itself, has put into doubt the long-standing practice of cesarean myomectomy (CM) with a trans-serosal approach. Some authors have recently advocated for this last approach, highlighting its advantages and potential uses in real-world situations. The purpose of this paper is to critique the present approach to cesarean myomectomy by analyzing the clinical and surgical distinctions between the two approaches and providing illustrations of the CM methods.

Evaluation of Changes in Circulating Cell-Free DNA as an Early Predictor of Response to Chemoradiation in Rectal Cancer—A Pilot Study

Background and Objectives: The objective of this study was to investigate quantitative changes in cell-free DNA (cfDNA) found in the bloodstream of patients with locally advanced rectal cancer who received neoadjuvant long-course chemoradiation, assuming a change in DNA fragments release during therapeutic stress. Materials and Methods: This was a prospective observational study that involved 49 patients who had three distinct pathologies requiring neoadjuvant chemoradiation: 18 patients with breast cancer, 18 patients with cervical cancer, and 13 patients with rectal cancer. Both breast cancer and cervical cancer patients were used as a control groups. Breast cancer patients were used as a control group as irradiation targeted healthy tissue after the tumor resection (R0), while cervical cancer patients were used as a control group to evaluate the effect of chemoradiation regarding cfDNA in a different setting (squamous cell carcinomas) and a different tumor burden. Rectal cancer patients were the study group, and were prospectively evaluated for a correlation between fragmentation of cfDNA and late response to chemoradiation. Blood samples were collected before the initiation of treatment and after the fifth radiation dose delivery. cfDNA was quantified in peripheral blood and compared with the patients’ clinicopathological characteristics and tumor volume. Conclusion: Thirteen patients with locally advanced rectal cancer (T3/T4/N+/M0) were included in the study, and all of them had their samples analyzed. Eight were male (61.54%) and five were female (38.46%), with an average age of 70.85 years. Most of the patients had cT3 (53.85%) or cT4 (46.15%) tumors, and 92.31% had positive lymph nodes (N2–3). Of the thirteen patients, only six underwent surgery, and one of them achieved a pathological complete response (pCR). The mean size of the tumor was 122.60 mm3 [35.33–662.60 mm3]. No significant correlation was found between cfDNA, tumor volume, and tumor regression grade. cfDNA does not seem to predict response to neoadjuvant chemoradiotherapy and it is not correlated to tumor volume or tumor regression grade.

The Efficiency of a Uterine Isthmus Tourniquet in Minimizing Blood Loss during a Myomectomy—A Prospective Study

Background and Objectives: The objective of this study was to assess the effectiveness of using a peri-cervical tourniquet in reducing blood loss during a laparoscopic myomectomy. Materials and Methods: This prospective study evaluated the impact of performing a concomitant tourniquet placement during a laparoscopic myomectomy (LM). A total of 60 patients were randomly allocated to one of two groups: 30 patients who underwent an LM with a tourniquet placement (the TLM group) and 30 patients who benefited from a standard LM (the SLM group). This study’s main objective was to evaluate the impact of tourniquet use on perioperative blood loss, which is quantified as the difference in the pre- and postoperative hemoglobin levels (Delta Hb) and the postoperative blood transfusion rate. Results: The mean Delta Hb was statistically lower in the TLM group compared to the SLM group: 1.38 g/dL vs. 2.41 g/dL (p < 0.001). The rate of postoperative iron perfusion in the TLM group was significantly lower compared to the SLM group (4 vs. 13 patients; p = 0.02). All four patients that required a blood transfusion were from the SLM group. On average, the peri-cervical tourniquet fastening time was 10.62 min (between 7 and 15 min), with no significant impact on the overall operative time: 98.50 min for the TLM group compared to 94.66 min for the SLM group. Conclusions: Fastening a tourniquet during a laparoscopic myomectomy is a valuable technique to effectively control intraoperative bleeding and enhance surgical outcomes.

Fast Leak-Proof, Intraumbilical, Single-Incision Laparoscopic Ovarian Cystectomy for Huge Ovarian Masses: “Hybrid Cystectomy and Reimplantation” Method

Background and Objectives: To introduce a new technique for fast leakage-proof, intraumbilical, single-incision laparoscopic ovarian cystectomy for huge ovarian masses (>10 cm) Materials and Methods: Seven consecutive, reproductive-aged women, including three adolescents, with huge ovarian masses (mature cystic teratoma, n = 4; endometrioma, n = 2; and mucinous cystadenoma, n = 1) who underwent transumbilical single-incision ovarian cystectomy with the new “hybrid cystectomy and reimplantation” method were included. The procedure was: (1) trans-umbilical single-incision laparoscopy; (2) inspection of the pelvic cavity and placing the mass in a laparoscopic endo-bag for cystic content leakage prevention; (3) in-bag resection using cold scissors and minimal cauterization of the cystectomy site; (4) in-bag tissue extraction; (5) rapid extracorporeal cystectomy with traction without electrocautery; (6) re-insertion of the retrieved ovarian cortex intracorporeally through the single port, and (7) intracorporeal suture of the retrieved tissue to the in situ ovary. Results: The mean patient age was 24.71 ± 6.56 (range 17–37) years and the mean maximal diameter of the masses was 17.71 ± 2.86 (range 13–22) cm. There was no case of unintended intracorporeal cyst rupture and no need for copious irrigation for washing and suctioning the leaked mass content. The mean total operating time was 76.42 ± 6.39 (range 65–85) min, the total volume of saline used for irrigation was 814.28 ± 331.35 (range 500–1500) mL, and the estimated blood loss was 107.14 ± 47.72 (range 50–200) mL. There were no perioperative complications. All patients except the two endometriosis patients had regular, normal menstruation. Conclusions: Our preliminary findings were encouraging in terms of the safety and efficiency of the new method. Future trials need to elucidate the benefits of this method in terms of fertility preservation.

Current Therapeutic Approaches in Cervical Cancer Based on the Stage of the Disease: Is There Room for Improvement?

Cervical cancer continues to be among the most common malignancies in women, and in recent decades, important measures have been taken to reduce its incidence. The first and most important steps to achieve this goal are oriented toward prevention through screening programs and vaccination, mainly against oncogenic human papillomavirus (HPV) strains 16 and 18. The therapeutic approach is based on the diagnosis and treatment guidelines for cervical cancer, which establish for each stage (FIGO, TNM) specific conduct. These guidelines summarize quite precisely the elements of therapeutic practice, but, in some places, they leave optional variants based on which nuanced approaches could be established. Adherence to these guidelines, which include the performing of minor or major surgery, with or without chemotherapy and radiation therapy, combined with advanced imaging investigations, has been able to lead to a substantial increase in survival. The purpose of this literature review is to discuss the diagnosis and treatment options in cervical cancer depending on the histological type, FIGO staging, and patient performance index, taking into account the hospital resources available in middle-income countries (percentage of gross domestic product allocated to health services around 5.5%, in the case of Romania).

PD-L1 Expression in Different Segments and Histological Types of Ovarian Cancer According to Lymphocytic Infiltrate

Background and Objectives: Ovarian cancer is the leading cause of death among gynecological tumors. PD-1/PD-L1 immunoregulatory mechanism is activated in ovarian cancers. Lymphocyte infiltration is a significant factor that affects its expression. We analyzed the correlation between localization of lymphocytic infiltrate and PD-L1 expression in epithelial ovarian tumors. Materials and Methods: PD-L1 expression was analyzed in 328 subjects, 122 with epithelial ovarian carcinoma, 42 with atypical proliferative tumor, and 164 with benign epithelial ovarian tumor. Expression in central and invasive tumor parts in epithelial ovarian carcinoma was combined with the most pronounced lymphocyte reaction. Immunohistochemical analysis was performed using the tissue microarray and correlated with a set of histopathology parameters. Results: PD-L1 expression was most prominent in epithelial ovarian carcinoma with different levels of expression observed between invasive and central tumor segments. A high level of PD-L1 expression on tumor cells was more frequently present in the invasive than in the central tumor parts (p < 0.001) only in high-grade serous ovarian carcinoma (HGSC). There was no significant correlation between peritumoral lymphocytic infiltrate and PD-L1 expression regardless of tumor segment. In the central tumor parts of HGSC, there was a correlation of intratumoral lymphocytic infiltrate with a higher level of PD-L1 expression (p = 0.003). Conclusions: The most prominent PD-L1 expression was observed in the invasive tumor parts of HGSC. Only the central parts of the HGSC exhibited significant PD-L1 expression in association with considerable intratumoral lymphocytic infiltrate.

Expectations and Challenges of First-Line Maintenance Therapy for Advanced Ovarian Cancer

The incidence of ovarian cancer, which has had a poor prognosis, is increasing annually. Currently, the prognosis is expected to improve with the use of molecular-targeted drugs and immune checkpoint inhibitors as maintenance therapies after the first-line chemotherapy. The GOG218 and ICON7 studies reported the usefulness of bevacizumab and the SOLO-1 and PRIMA (A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Niraparib Maintenance Treatment in Patients With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy) studies have reported the usefulness of olaparib and niraparib, respectively. The ATHENA study investigating the usefulness of rucaparib is currently ongoing. Although clinical studies of immune checkpoint inhibitors are lagging in the field of gynecology, many clinical studies using programmed death cell-1 (PD-1) and PD-1 ligand 1 (PD-L1) antibodies are currently ongoing. Some biomarkers have been identified for molecular-targeted drugs, but none have been identified for immune checkpoint inhibitors, which is a challenge that should be addressed in the future.

Primary Vaginal Mucinous Adenocarcinoma of Intestinal Type—Clinical, Radiological and Morphological Aspects

Background and Objectives: Neoplasms of the vagina are rare and account for 1–2% of all tumors of the female reproductive system. Primary neoplasms of the vagina are most often carcinomas originating from squamous or glandular epithelium. Of the primary glandular tumors, clear cell, endometrioid, and serous adenocarcinomas are the most common types, while mucinous and mesonephric types are very rare. Mucinous adenocarcinoma is histologically subclassified into endocervical and intestinal types. We add to the existing literature another case of an extremely rare gynecological neoplasm—primary vaginal mucinous adenocarcinoma (PVMAC) intestinal type associated with vaginal villous adenoma with high-grade dysplasia. We discuss the clinical, radiological and morphological features of this rare entity. Materials and Methods: We report a case of a 59-year-old woman with PVMAC intestinal type associated with vaginal villous adenoma with high-grade dysplasia. The patient was evaluated with a gynecological exam, and biopsy, curettage and tumor excision were performed. The positron emission tomography-computed tomography (PET/CT) scan, at the level of the pelvis, supported the primary location of the disease. Histological and immunohistochemical methods were applied. Results: The gynecological examination of the vagina revealed an exophytic polypoid mass with a diameter of 3 cm, located on the posterior wall, in the area of introitus vaginae. The PET/CT scan revealed a hypermetabolic malignant formation involving the vagina and anal canal, without evidence of pelvic and inguinal lymphadenopathy, and also, it excluded disease at sites other than the vagina. The histological and immunohistochemical investigations, as well as the clinical and radiological data, lent support to the diagnosis “primary vaginal mucinous adenocarcinoma intestinal type”. Conclusions: PVMAC intestinal type is a rare gynecological pathology, which presents a serious challenge for oncogynecologists, radiologists and pathologists.

Advanced Ovarian Cancer during Pregnancy. Tumour Evolution Analysis and Treatment Approach

Background: The possible presence of malignant adnexal mass should be considered during pregnancy. For this reason, it is important to keep in mind such possibility while performing routine obstetric ultrasounds to diagnose asymptomatic ovarian cancer in the early stages. Case presentation: 27-year-old pregnant patient with a known adnexal tumour occurring at week 20 and enlarged supraclavicular lymph nodes of 3 cm size who was diagnosed with metastases from low-grade papillary serous ovarian carcinoma. The patient, obstetricians, neonatologists and oncologists agreed on initiating neoadjuvant chemotherapy and performing an elective C-section at week 34. She gave birth to a female infant weighing 2040 g who is currently in good health, and continues receiving follow-up care by a medical oncologist. Conclusions. An early diagnosis of gynaecologic malignancies during pregnancy is of critical importance because, although they are very rare, managing and treating carcinomas at an early stage allow us to increase maternal and fetal well-being and to offer more alternatives to our patients.

Survival and Chemosensitivity in Advanced High Grade Serous Epithelial Ovarian Cancer Patients with and without a BRCA Germline Mutation: More Evidence for Shifting the Paradigm towards Complete Surgical Cytoreduction

Background and Objectives: Approximately 10–15% of high-grade serous ovarian cancer (HGSOC) cases are related to BRCA germline mutations. Better survival rates and increased chemosensitivity are reported in patients with a BRCA 1/2 germline mutation. However, the FIGO stage and histopathological entity may have been confounding factors. This study aimed to compare chemotherapy response and survival between patients with and without a BRCA 1/2 germline mutation in advanced HGSOC receiving neoadjuvant chemotherapy (NACT). Materials and Methods: A cohort of BRCA-tested advanced HGSOC patients undergoing cytoreductive surgery following NACT was analyzed for chemotherapy response and survival. Neoadjuvant chemotherapy served as a vehicle to assess chemotherapy response on biochemical (CA125), histopathological (CRS), biological (dissemination), and surgical (residual disease) levels. Univariate and multivariate analyses for chemotherapy response and survival were utilized. Results: Thirty-nine out of 168 patients had a BRCA ½ germline mutation. No differences in histopathological chemotherapy response between the patients with and without a BRCA ½ germline mutation were observed. Survival in the groups of patients was comparable Irrespective of the BRCA status, CRS 2 and 3 (HR 7.496, 95% CI 2.523–22.27, p < 0.001 & HR 4.069, 95% CI 1.388–11.93, p = 0.011), and complete surgical cytoreduction (p = 0.017) were independent parameters for a favored overall survival. Conclusions: HGSOC patients with or without BRCA ½ germline mutations, who had cytoreductive surgery, showed comparable chemotherapy responses and subsequent survival. Irrespective of BRCA status, advanced-stage HGSOC patients have a superior prognosis with complete surgical cytoreduction and good histopathological response to chemotherapy.

High-Grade Endometrioid Stromal Sarcoma of the Ovary: Malignant Transformation of Ovarian Mature Cystic Teratoma

We report an extremely rare case of ovarian high-grade endometrioid stromal sarcoma arising from a mature cystic teratoma with clinicopathologic features, and then we briefly review the pertinent literature. A 62-year-old nulliparous woman presented with lower abdominal pain that had begun 6 months earlier. Magnetic resonance imaging showed two adnexal masses with fat components, which suggested that they were mature cystic teratomas. The eccentric thick rim of the left mass showed irregular invasion of the uterus, which was suggestive of malignancy. Positron emission tomography/computed tomography demonstrated high fluorodeoxyglucose uptake in the corresponding area. The patient underwent debulking cytoreductive surgery. The diagnosis was of an International Federation of Obstetrics and Gynecology stage IIIC high-grade endometrioid stromal sarcoma arising from a mature cystic teratoma. After surgery, the patient received adjuvant chemotherapy with three courses of doxorubicin regimen. The cancer recurred 3 months after surgery, and the patient died of progressive disease. It might be helpful for clinicians to be aware of this rare disease and the poor prognosis when it is at an advanced stage.

Cytochrome 4Z1 Expression Connotes Unfavorable Prognosis in Ovarian Cancers

Background and Objective: Ovarian cancer is a leading cause of death in females. Since its treatment is challenging and causes severe side effects, novel therapies are urgently needed. One of the potential enzymes implicated in the progression of cancers is Cytochrome 4Z1 (CYP4Z1). Its expression in ovarian cancer remains unknown. Therefore, the current study aims to assess CYP4Z1 expression in different subtypes of ovarian cancers. Materials and Methods: Immunohistochemistry was used to characterize CYP4Z1 expression in 192 cases of ovarian cancers along with eight normal ovarian tissues. The enzyme’s association with various clinicopathological characteristics and survival was determined. Results: CYP4Z1 was strongly expressed in 79% of ovarian cancers, compared to negative expression in normal ovarian samples. Importantly, significantly high CYP4Z1 expres-sion was determined in patients with advanced-stage cancer and a high depth of invasion (p < 0.05). Surprisingly, CYP4Z1 expression was significantly associated with a low patient survival rate. Univariate analysis revealed that patient survival was strongly associated with CYP4Z1 expression, tumor stage, depth of invasion, and lymph node metastasis (p < 0.05). Multivariate analysis showed that only CYP4Z1 expression was significantly associated with patient survival (p < 0.05). Conclusions: CYP4Z1 expression is correlated with shorter patient survival and has been identified as an independent indicator of a poor prognosis for ovarian cancer patients.

Scar-Free Laparoscopy in BRCA-Mutated Women

Background and Objectives: BRCA 1 and 2 mutations have a cumulative risk of developing ovarian cancer at 70 years of 41% and 15%, respectively, while a cumulative risk of breast cancer by 80 years of age was 72% for BRCA1 mutation carriers and 69% for BRCA2 mutation carriers. The NCCN recommends risk-reducing salpingo-oophorectomy (RRSO), typically between 35 and 40 years, and upon completion of childbearing in BRCA1 mutation, while it is reasonable to delay RRSO for management of ovarian cancer risk until age 40–45 years in patients with BRCA2. In recent years there have been two main lines of evolution in laparoscopy. The former concerning the development of a single-site laparoscopic and the latter concerning the miniaturisation of laparoscopic instruments (mini/micro-laparoscopy). Materials and Methods: In this case report, we show our experience in prophylactic adnexectomy, on a mutated-BRCA patient, using the MiniLap® percutaneous surgical system. Results: This type of technique is safe and effective and does not require a particular learning curve compared to single-port laparoscopy. Conclusions: The considerable aesthetic advantage of the scars, we believe, albeit to a lesser extent, is useful to find in these patients burdened by an important stress load.

Impact of Activation of EGFL7 within Microenvironment of High Grade Ovarian Serous Carcinoma on Infiltration of CD4+ and CD8+ Lymphocytes

Background: It has been demonstrated that Egfl7 promotes tumor cell escape from immunity by downregulating the activation of tumor blood vessels. Aim: to analyze mRNA expression of EGFL7 within the tumor microenvironment of high-grade ovarian serous carcinoma and its association with a number of intraepithelial CD4+/CD8+ lymphocytes and ICAM-1 expression. Methods: qPCR analysis of EGFL7 mRNA in cancer cells and adjacent stromal endothelium microdissected from formalin-fixed paraffin-embedded tumors of 59 high-grade ovarian serous carcinoma patients, was performed. Infiltration of intraepithelial lymphocytes (CD4+/CD8+) and expression of ICAM-1 were evaluated by immunohistochemistry and compared between tumors with different statuses of EGFL7 expression. Results: EGFL7 was expressed in cancer cells (9/59, 15.25%), endothelium (8/59, 13.56%), or both cancer cells and adjacent endothelium (4/59, 6.78%). ICAM-1 was expressed on cancer cells (47/59, 79.66%), stromal endothelium (46/59, 77.97%), or both epithelium and endothelium (40 of 59, 67.8%). EGFL7-positivity of cancer cells and endothelium was associated with lower intraepithelial inflow of CD4+ (p = 0.022 and p = 0.029, respectively) and CD8+ lymphocytes (p = 0.004 and p = 0.031, respectively) but impact neither epithelial nor endothelial ICAM-1 expression (p = 0.098 and p = 0.119, respectively). The patients’ median follow-up was 23.83 months (range 1.07–78.07). Lack of prognostic significance of EGFL7-status and ICAM-1 expression was notified. Conclusion: EGFL7 is activated in the cancer cells as frequently as in the endothelium of human high-grade ovarian serous carcinoma. Activation of EGFL7 in cancer cells and/or endothelial cells could negatively impact diapedesis regardless of localization.

Bevacizumab with Chemotherapy as a First-Line Treatment for Advanced Ovarian Cancer in a Serbian Cohort

Background and Objectives: For stage IIIb–IV ovarian cancer, bevacizumab-containing treatment is considered the standard of care. The purpose of this study was to evaluate the efficacy of bevacizumab in combination with carboplatin and paclitaxel as a first-line treatment for advanced ovarian cancer. Materials and Methods: Eligible patients had stage IIIc–IV ovarian cancer according to the International Federation of Gynecology and Obstetrics with no clinical signs or symptoms of gastrointestinal obstruction or a history of abdominal fistulae, gastrointestinal perforation, or intra-abdominal abscess or evidence of rectosigmoid involvement by pelvic examination, bowel involvement on computed tomography, or clinical symptoms of bowel obstruction in the previous 6 months. After debulking surgery, the patients received 175 mg/m2 paclitaxel and carboplatin (AUC 6) for the first six cycles and 7.5 mg/kg bevacizumab every three weeks up to 17 cycles until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was progression-free survival. The secondary endpoint was overall survival. Results: Between April 2017 and March 2020, 35 patients began study treatment. Bevacizumab was administered at 7.5 mg/kg in all the patients and for more than 7.5 months in 70% of them. The median progression-free survival was 20 months (95% CI: 16–23). The median overall survival was not reached. Conclusions: This was, to our knowledge, the first trial in Serbia to show progression-free survival and overall survival of combination regimens in advanced ovarian cancer. Based on the observed progression-free survival, bevacizumab combined with chemotherapy should be considered as a standard option in advanced ovarian cancer.

Effects of Icodextrin Solution (Adept®) on Ovarian Cancer Cell Proliferation in an In Vitro Model

Background and objective: Anti-adhesion barriers are currently used during ovarian cancer surgery to decrease adhesion-related morbidity. Adept® (4% icodextrin) solution, a liquid anti-adhesion material, has been widely used during gynecologic surgeries, though the risk of this barrier for oncologic surgery is controversial. The aim of this study was to determine the effect of Adept® solution on the proliferation of ovarian cancer cells. Materials and methods: We assessed the dose- and time-dependent effects of icodextrin on the growth and proliferation of OVCAR-3 and A2780 human ovarian tumor cell lines in vitro. Cell growth was determined by cell number counting. Expressions of cell cycle-regulation proteins (cyclin D1 and cyclin B1) were determined using Western blot analysis. Results: Adept® did not significantly increase ovarian cancer cell growth when tested at various concentrations (0, 1, 5, 10, 15, and 20%, equal to 0, 0.04, 0.2, 0.4, 0.6 and 0.8% icodextrin) and different time points (1–3 days) compared to control cells. Moreover, the protein levels of cyclin D1 and B1 were not overexpression-elevated in icodextrin-treated ovarian cancer cells, either with an increasing concentration or with an increasing treated time. These results demonstrated that Adept® does not activate the growth or proliferation of ovarian cancer cells in either a dose- or time-dependent manner. Conclusions: This study supports the use of Adept® solution as a safe anti-adhesion barrier for ovarian cancer surgery, though further in vivo studies are necessary.

Acute Presentation of Large Size Clear Cell Ovarian Carcinoma as Double Torsed Ovarian Tumor

We report a 46-year-old patient who presented to the emergency department with complaints of acute abdominal pain, nausea, and vomiting. An abdominal CT scan revealed a large (207 × 155 × 182 mm) thin-walled inhomogeneous tumor connected to the uterus and right ovary. Emergency surgery laparotomy was performed. Inside the abdominal cavity, a 30 × 30 cm heterogenous, dark blue tumor in the right adnexa area, torsed two times, weighing 3700 g was found. Histological examination revealed right ovary clear cell carcinoma. We emphasize the rare nature of the histology and presentation of this case report. Ovarian clear cell carcinomas are relatively rare malignancies, presenting in 5 to 10% of ovarian malignant tumors in the west.

The Preventive Effect of Dietary Antioxidants on Cervical Cancer Development

Cervical cancer results from a continuous process, starting from a normal cervical epithelium after human papillomavirus (HPV) infection and progressing to cervical intraepithelial neoplasia (CIN), before finally developing into invasive squamous carcinoma (ISC). In recent decades, dietary antioxidants, such as vitamins, have received much attention in relation to cancer prevention. We reviewed the relevant literature to investigate the dietary and nutrient intake on cervical cancer. The intake of vitamins A and D and carotenoids may inhibit early cervical cancer development. The intake of folate may prevent or inhibit HPV infection rom progressing to various grades of CIN. The intake of vitamins C and E may widely inhibit the process of cervical cancer development. Polyphenols are often used in cases of cervical cancer in combination chemotherapy and radiation therapy. Regarding nutrients, different antioxidants may have differing abilities to intervene in the natural history of cervical diseases associated with HPV infection. Regarding foods, the intake of both vegetables and fruits containing multiple vitamins may widely suppress cervical cancer development. Most previous papers have described epidemiological studies. Thus, further research using in vitro and in vivo approaches will be needed to clarify the effects of the dietary and nutrient intake in detail.

Comparison of Postoperative Adjuvant Chemotherapy and Concurrent Chemoradiotherapy for FIGO2018 Stage IIIC1 Cervical Cancer: A Retrospective Study

Background and Objectives: In October 2018, the International Federation of Gynecology and Obstetrics (FIGO) revised its classification of advanced stages of cervical cancer. The main points of the classification are as follows: stage IIIC is newly established; pelvic lymph node metastasis is stage IIIC1; and para-aortic lymph node metastasis is stage IIIC2. Currently, in Japan, radical hysterectomy is performed in advanced stages IA2 to IIB of FIGO2014, and concurrent chemoradiotherapy (CCRT) is recommended for patients with positive lymph nodes. However, the efficacy of CCRT is not always satisfactory. The aim of this study was to compare postoperative adjuvant chemotherapy (CT) and postoperative CCRT in stage IIIC1 patients. Materials and Methods: Of the 40 patients who had undergone a radical hysterectomy at Iwate Medical University between January 2011 and December 2016 and were pathologically diagnosed as having positive pelvic lymph nodes, 21 patients in the adjuvant CT group and 19 patients in the postoperative CCRT group were compared. Results: The 5 year survival rates were 77.9% in the CT group and 74.7% in the CCRT group, with no significant difference. There was no significant difference in overall survival or progression-free survival between the two groups. There was no significant difference between CT and CCRT in postoperative adjuvant therapy in the new classification IIIC1 stage. Conclusions: The results of the prospective Japanese Gynecologic Oncology Group (JGOG) 1082 study are pending, but the present results suggest that CT may be a treatment option in rural areas where radiotherapy facilities are limited.

Clinical and Prognostic Significance of TZAP Expression in Cervical Cancer

Background and Objectives: Telomeric zinc finger-associated protein (TZAP) is a telomere-associated factor that was previously called ZBTB48. This protein binds preferentially to long telomeres, competing with telomeric repeat factors 1 and 2. Genetic changes in TZAP may be associated with cancer pathogenesis; however, this relationship has not yet been elucidated for any type of cancer. In this study, we aimed to examine the clinicopathologic and prognostic value of TZAP expression in cervical cancer (CC). Materials and Methods: The data were extracted from The Cancer Genome Atlas cohorts by OncoLnc (21 cancer types, 7700 cancers). The prognostic value of TZAP for different stages of 264 CCs was examined using survival analysis. Results: The TZAP expression did not differ significantly between CC and normal matched tissues. Age, cancer stage, and viral infection were not associated with TZAP expression. Survival analysis revealed a shorter overall survival in CC patients with a lower TZAP expression (χ2 = 3.62, p = 0.057). The prognostic value of TZAP expression was greater in patients with N1 stage CC (χ2 = 5.64, p = 0.018). Conclusion: TZAP expression is a possible prognostic marker for CC, especially stage N1 CC.

Multiple Rare Primary Malignancies: A Mixed Squamous Neuroendocrine Adenocarcinoma of the Cervix, Metastasized Carcinosarcoma and Extramammary Vulvar Paget’s Disease Case Report

The occurrence of more than one primary malignant tumor in a single patient is rare. Multiple primary malignancies can pose difficulties in differential diagnosis between primary tumors and metastasis. Here, we present a case report with multiple primary malignancies. The patient is a 45-year-old female who was diagnosed with cervical mixed squamous neuroendocrine adenocarcinoma, metastasized carcinosarcoma and extramammary vulvar Paget’s disease. The patient was first diagnosed with a microinvasive squamous cervical carcinoma in situ. After a few months, the amputation of a small residual tumor and histological evaluation revealed an IA1-stage poorly differentiated (G3) mixed squamous and neuroendocrine cervical adenocarcinoma. After two years, the disease had progressed and biopsies from altered sites were taken. Histological diagnosis from an ulcerated vulvar region revealed extramammary vulvar Paget’s disease. A biopsy from vagina polyp revealed an earlier diagnosed mixed squamous and neuroendocrine cervical adenocarcinoma. However, histological diagnosis from an inguinal lymph node biopsy was unexpected and revealed carcinosarcoma. It indicated either the development of another primary malignancy, or an unusual spread of metastasis. Clinical presentation as well as diagnostic and treatment challenges are discussed in this case report. This case report shows that multiple primary malignancy cases are difficult to manage both for clinicians and the patient because the therapeutic options can become limited. This complex case was managed by a multidisciplinary team.

Cervical Cancer Mortality in Romania: Trends, Regional and Rural–Urban Inequalities, and Policy Implications

Background and Objectives: Despite being largely preventable, cervical cancer mortality still remains an important public health problem globally, in Europe, and in Romania. The European Union member states are urged to implement systematic, population-based screenings for cervical cancer, but the programs developed by the countries remain very heterogeneous. This study aimed to investigate the differences in cervix cancer mortality between Romania and EU and within Romania over the last two decades and to reveal the major sources of inequalities and the policy implications. Materials and Methods: We analyzed the number of deaths and the mortality rates by cervical cancer, standardized using the direct method, over two decades (2001–2016 for the EU, and 2001–2019 for the national and sub-national analyses). Trends, mortality reduction over the years, and mortality differences at the beginning and end of the time interval have been calculated for the EU and Romania, at national and sub-national levels (rural–urban and regions). Results: Our results revealed differences in cervical cancer mortality between Romania and EU and within Romania (among regions and rural–urban areas). These differences used to be very high in the past and are still persisting. Conclusions: The country should revisit its national cervical cancer screening program, which has been implemented for many years, but with a very limited participation rate. Due to the similar problems existing in Central-Eastern Europe, targeted support from the EU for the members from this geographical area could contribute to the minimization of differences in cervical cancer mortality among the EU members.

Cervical Cancer and Human Papillomavirus Awareness among Women in Saudi Arabia

Background and Objectives: Cervical cancer (CC) is the eighth most common cancer among Saudi women of all ages. With limited national data, we aimed to evaluate the public awareness of cervical cancer, CC risk factors, HPV infection, and HPV vaccines in different regions of Saudi Arabia. Materials and Methods: This was a survey-based cross-sectional study that encompassed 564 Saudi women over a period of a month. A self-administrated questionnaire was distributed through different social media platforms. Results: The collected data included sociodemographic variables and questions assessing awareness of CC, and the attitudes toward CC screening and human papillomavirus (HPV) vaccination. Most respondents were aware of CC (84.0%), although their primary source of information was the internet. However, only 45 females (8.0%) had a history of cervical screening. Furthermore, most females did not know that HPV was transmitted sexually (78.9%), or that it caused genital warts (81.7%) and CC (81.9%). Regarding the HPV vaccine, 100 females (17.7%) had heard about it, but only 11 (2.0%) took the vaccine, although more than half of the respondents (54.1%) were willing to take the vaccine after being informed about it. Conclusions: We noticed a remarkable lack of awareness among the respondents regarding HPV’s clinical implications; and the HPV vaccine, and its importance and availability. The main source of information for most of the Saudi women in this study was the internet, which may be an unreliable source, or provide misleading information that may delay screening or discourage vaccination. Thus, organized campaigns by the Ministry of Health or other health-advocating agencies, in addition to screening and vaccination programs, are strongly encouraged.

The Role of Chemokines in Cervical Cancers

Both clinical-pathological and experimental studies have shown that chemokines play a key role in activating the immune checkpoint modulator in cervical cancer progression and are associated with prognosis in tumor cell proliferation, invasion, angiogenesis, chemoresistance, and immunosuppression. Therefore, a clear understanding of chemokines and immune checkpoint modulators is essential for the treatment of this disease. This review discusses the origins and categories of chemokines and the mechanisms that are responsible for activating immune checkpoints in cervical dysplasia and cancer, chemokines as biomarkers, and therapy development that targets immune checkpoints in cervical cancer research.

Students’ Knowledge about Cervical Cancer Prevention in Poland

Background and Objectives: In Poland, the rates of morbidity and mortality due to cervical cancer are amongst the highest in Europe. A significant percentage of newly diagnosed cases of cervical cancer are at an advanced stage. Unfortunately, only about 20% of Polish women take part in cervical cancer screening. The aim of the study was to assess students’ knowledge of cervical cancer risk factors and prevention. Materials and Methods: The study was provided to Polish students from various universities and faculties between May 2020 and November 2020. The questionnaire was designed specifically for this study and was validated. The chi-square test was used to compare the responses between subgroups. Results: The study was carried out on a group of 995 students (80.6% women, 19% men, 0.4% no data), (average age 21.9 years). Most students knew that the main risk factor for cervical cancer is human papillomavirus (HPV) infection (82% of all responders; 86% of medical students; 73% of non-medical students; p < 0.001). Only 40% of students knew that in Poland the Population Prevention and Early Diagnosis Program is carried out on women aged 25–59 years every three years. Most students correctly indicated that cervical cancer screening in Poland is performed using cervical cytology and were familiar with the basis of cytology. Only 57% of students knew that there are no specific early symptoms of cervical cancer. A total of 78% of all respondents knew that HPV vaccination reduces the risk of cervical cancer. Medical students and students who are sexually active demonstrated a better knowledge of cervical cancer. Conclusions: The Polish students had some knowledge of cervical cancer risk factors and primary and secondary prevention. Significantly better knowledge was demonstrated by medical students. Some efforts should be made to ensure that young people, who are not associated with medicine are better educated about cervical cancer in order to reduce the overall incidence and improve early detection rates.

Prognostic Significance of Immune Checkpoint Markers in Prognosis of Grade 3 Endometrioid Carcinoma

Background and Objectives: Uterine FIGO grade 3 endometrioid carcinoma (EC) is an uncommon but aggressive subtype of endometrial cancer with limited biomarker data to guide prognosis and management. This study aimed to evaluate the prognostic significance of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) expression in tumor tissue (TT) and tumor microenvironment (TME). Materials and Methods: We retrospectively analyzed tumor samples from 53 patients with FIGO grade 3 EC. Immunohistochemistry was performed to assess PD-1 and PD-L1 expression in TT and TME. Clinicopathological data including age, stage, lymph node invasion (LNI), lymphovascular space invasion (LVSI), depth of myometrial invasion (MI), adjuvant therapy, and survival outcomes were collected. Survival analyses were conducted using Kaplan–Meier and Cox proportional hazards models. Results: PD-1 expression was identified in 34% of TT and 41.5% of TME, while PD-L1 was expressed in 22.6% of TT and 34% of TME. Except for PD-1 in TME, positive expression of these immune checkpoint molecules correlated with significantly shorter survival (log-rank p < 0.05) outcomes. In univariate analysis, PD-1 and PD-L1 expression in TT, deep MI, LNI and LVSI were associated with adverse outcomes. Multivariate analysis confirmed PD-1 and PD-L1 positivity in TT as independent prognostic factors (PD-1: HR 3.2, 95% CI 1.4–7.0; PD-L1: HR 3.3, 95% CI 1.4–7.8). Patients with concurrent PD-1 and PD-L1 expression in TT showed the poorest overall survival, suggesting a cumulative negative effect. Conclusions: PD-1 and PD-L1 expression in tumor tissue are independent predictors of poor prognosis in FIGO grade 3 EC. These findings support their role as clinically relevant biomarkers and potential therapeutic targets. Incorporating checkpoint evaluation into routine pathological assessment could improve prognostic accuracy and guide treatment strategies, particularly in high-risk patients who might benefit from immunotherapy approaches.

Papillary Squamotransitional Cell Carcinoma of the Uterine Cervix with Atypical Presentation: A Case Report with a Literature Review

Introduction: Cervical cancer is the fourth most prevalent malignancy and the fourth leading cause of cancer-related death in women around the world. Histologically, squamous cell carcinoma (SCC) is the most common form of cervical cancer. SCC has several subtypes, and one of the rarest is papillary squamotransitional cell carcinoma (PSCC). In general, PSCC is believed to have a similar course and prognosis to typical SCC, with a high risk of late metastasis and recurrence. Case report: We discuss the case of a 45-year-old patient diagnosed with PSCC who was admitted to our department in December 2021. The clinical manifestations were pelvic discomfort and lymphadenopathy throughout the body. On admission, all laboratory values, with the exception of C-Reactive Protein (CRP) at 22.35 mg/L and hemoglobin (HGB) at 87.0 g/L, were normal. The clinical and ultrasound examination revealed a painful formation with indistinct borders in the right portion of the small pelvis. Following dilation and curettage, a Tru-Cut biopsy of the inguinal lymph nodes was performed. The investigation histologically indicated PSCC. MRI of the small pelvis showed an endophytic tumor in the cervix with dimensions of 35/26 mm and provided data for bilateral parametrial infiltration; a hetero-intensive tumor originating from the right ovary and involving small intestinal loops measuring 90/58 mm; and generalized lymphadenopathy and peritoneal metastases in the pouch of Douglass. The FIGO classification for the tumor was IVB. The patient was subsequently referred for chemotherapy by the tumor board’s decision. Discussion: Despite the generally good prognosis of SCC, PSCC is a rare and aggressive subtype. It is usually diagnosed at an advanced stage and has a poor prognosis. Conclusions: PSCC is a rare subtype of SCC, and its diagnosis and treatment are challenging.

Laparoscopic Radical Trachelectomy after Neoadjuvant Chemotherapy for Fertility Preservation in Early-Stage Bulky Cervical Cancer: A Case Report and Literature Review

Management of early-stage cervical cancer (CC) in young women often faces challenges to preserve fertility, as well as to achieve an adequate oncological outcome. Although existing evidence supports a fertility-sparing treatment in the case of tumors <2 cm in diameter, the approach is less clear in bulky early-stage CC. In addition, the outcomes of radical trachelectomy performed by minimally invasive techniques are also highly debatable. Highlighting the high incidences of young women with early-stage CC, the lack of sufficient data raises considerable hindrances towards the proper counseling of this vulnerable patient group. In this report, a case of a young woman with bulky early-stage CC with a strong desire to preserve fertility is presented. A satisfactory oncological outcome was achieved after neoadjuvant chemotherapy followed by laparoscopic radical trachelectomy. Ongoing prospective trials are expected to provide stronger evidence on this topic.

Curious Case of Superfitial Spreading Cervical Squamocellular Carcinoma with Adnexal Involvement

Background and Objectives: Cervical squamous cell carcinoma (SCC) usually showed an infiltrative growth pattern into endocervical stroma. In rare cases, SCC spreads superficially as an intraepithelial lesion to proximal uterine segments, and more rarely, involves invasive and more aggressive behavior on secondary sites. Materials and Methods: In this study, we present the case of an interesting form of cervical SCC growth and we discuss the possible reasons for that presentation. Results: After clinical examination and repeated histomorphological analysis, we found remarkable cervical epithelial dysplasia (a high-grade squamous intraepithelial lesion—H-SIL). A histopathology report after conization and hysterectomy showed squamocellular carcinoma with microinvasive focuses. Interestingly, squamocellular carcinoma was found in the proximal uterine and adnexal structure, as well as intraepithelial and microinvasive lesions. Conclusions: Our study described a rare presentation of primary cervical SCC with unusual adnexal involvement. This pattern of tumor growth should be especially considered for patients who are proposed for sparing surgical procedures. A detailed and multidisciplinary approach for every patient is very important because unpredictable cases are present. However, they are rare.

The Oncological Implication of Sentinel Lymph Node in Early Cervical Cancer: A Meta-Analysis of Oncological Outcomes and Type of Recurrences

Background and Objectives: Pelvic lymphadenectomy has been associated with radical hysterectomy for the treatment of early Cervical Cancer (ECC) since 1905. However, some complications are related to this technique, such as lymphedema and nerve damage. In addition, its clinical role is controversial. For this reason, the sentinel lymph node (SLN) has found increasing use in clinical practice over time. Oncologic safety, however, is debated, and there is no clear evidence in the literature regarding this. Therefore, our meta-analysis aims to schematically analyze the current scientific evidence to investigate the non-inferiority of SLN versus PLND regarding oncologic outcomes. Materials and Methods: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched the PubMed and Scopus databases in June 2022 since their early first publications. We made no restrictions on the country. We considered only studies entirely published in English. We included studies containing Disease-Free Survival (DFS), Overall Survival (OS), Recurrence Rate (RR), and site of recurrence data. We used comparative studies for meta-analysis. We registered this meta-analysis to the PROSPERO site for meta-analysis with protocol number CRD42022316650. Results: Twelve studies fulfilled inclusion criteria. The four comparative studies were enrolled in meta-analysis. Patients were analyzed concerning Sentinel Lymph Node Biopsy (SLN) and compared with Bilateral Pelvic Systematic Lymphadenectomy (PLND) in early-stage Cervical Cancer (ECC). Meta-analysis highlighted no differences in oncological safety between these two techniques, both in DFS and OS. Moreover, most of the sites of recurrences in the SLN group seemed not to be correlated with missed lymphadenectomy. Conclusions: Data in the literature do not seem to show clear oncologic inferiority of SLN over PLND. On the contrary, the higher detection rate of positive lymph nodes and the predominance of no lymph node recurrences give hope that this technique may equal PLND in oncologic terms, improving its morbidity profile.

Comparison of Breast Cancer and Cervical Cancer in Uzbekistan and Korea: The First Report of The Uzbekistan–Korea Oncology Consortium

In general, as a country’s economy, education level, and life expectancy increase, the incidence of cancer increases. This is because the peak incidence of cancer occurs in individuals in their 70s and 80s, and the health proportion of non-communicable diseases increases with the development of the living environment. Changes in diet, lifestyle and enhanced methods of detection contribute to an increase in cancer incidence as well. Recently, Uzbekistan has grown rapidly, and its incidence of cancer is also increasing. In the health management of cancer, not only treatment but also the identification and prevention of causes and effective screening should be considered. South Korea has a common ethnicity with Uzbekistan and has successfully performed national screening for seven major cancers over the past 20 years. The 5-year survival rate after cancer diagnosis in Korea was only 42.9% 20 years ago, but recently it has improved to 70.7%. We formed an advisory consortium in which oncologists from Uzbekistan and Korea could cooperate for cancer management in Uzbekistan. This advisory consortium intends to present the necessary considerations and recommendations for cancer management in Uzbekistan by examining the literature and cancer statistics of Uzbekistan and South Korea. In addition to the overall analysis, we identified and reviewed the major cancers with high morbidity in three categories in Uzbekistan: gynecological cancer (breast and cervical cancer), cancer common in men (lung and liver cancer), and gastrointestinal cancer (stomach and colorectal cancer). This review covers the general cancer statistics of Uzbekistan and a detailed review of gynecological cancer between two countries, and relevant recommendations.

Assessment of Sexual Dysfunction in Cervical Cancer Patients after Different Treatment Modality: A Systematic Review

Background and Objectives: Cervical cancer is a leading cause of mortality among women. Chemo-radiation followed by interventional radiotherapy (IRT) is the standard of care for stage IB–IVA FIGO. Several studies have shown that image-guided adaptive IRT resulted in excellent local and pelvic control, but it is associated with vaginal toxicity and intercourse problems. The purpose of this review is to evaluate the dysfunctions of the sexual sphere in patients with cervical cancer undergoing different cervix cancer treatments. Materials and Methods: We performed a comprehensive literature search using Pub med, Scopus and Cochrane to identify all the full articles evaluating the dysfunctions of the sexual sphere. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. Results: One thousand three hundred fifty-six women included in five studies published from 2016 to 2022 were analyzed. The median age was 50 years (range 46–56 years). The median follow-up was 12 months (range 0–60). Cervical cancer diagnosis and treatment (radiotherapy, chemotherapy and surgery) negatively affected sexual intercourse. Sexual symptoms such as fibrosis, strictures, decreased elasticity and depth and mucosal atrophy promote sexual dysfunction by causing frigidity, lack of lubrication, arousal, orgasm and libido and dyspareunia. Conclusions: Physical, physiological and social factors all contribute to the modification of the sexual sphere. Cervical cancer survivors who were irradiated have lower sexual and vaginal function than the normal population. Although there are cures for reducing discomfort, effective communication about sexual dysfunctions following treatment is essential.

HPV and HIV Coinfection in Women from a Southeast Region of Romania—PICOPIV Study

Background and Objectives: Romania faces one of the highest cervical cancer burdens in Europe though it is a preventable cancer through population screening by cytology and human papillomavirus (HPV) detection. Also, it has one of the highest incidences of human immunodeficiency virus (HIV) infection. HPV and HIV coinfection are frequently encountered. The aim of study was to establish the prevalence of HPV infection among HIV-positive women in Southeast Region of Romania, to genotype high risk HPV types -and to correlate the results with clinical data and cytological cervical lesions. Materials and Methods: 40 HIV-positive women were screened for HPV types and for cytological cervical lesions. The findings were evaluated in correlation with CD4 cell counts, HIV viral load, age at first sexual intercourse, number of sexual partners, vaginal candidiasis, and Gardnerella using statistical methods. Results: 19/40 (47.5%) women were positive for HPV types, 63.15% infected with single HPV type and 36.85% with multiple HPV types. The most frequent types were type: 31 (42.1%), 56 (31.57%), 53 (15.78%). On cytology, 34 (85%) women were found with NILM of which 38.23% were HPV-positive. Fifteen percent of women had abnormal cytology (three ASC-US, three LSIL), and all of them were HPV-positive. Through analyzing the value of CD4 count, women with CD4 count ≤ 200 cells/μL were found to be significantly more likely to be infected with HPV; meanwhile there was no correlation between the detection of HPV types and HIV viral load. Candida or Gardnerella were more often associated with HIV-positive women with HPV, than in women without HPV. Conclusions: Infection with HPV types is common among HIV-positive women in the Southeast Region of Romania and it is associated with age at the beginning of sexual life, number of sexual partners, CD4 value, vaginal candidiasis, and Gardnerella infection.

Echinacea angustifolia and Echinacea purpurea Supplementation Combined with Vaginal Hyaluronic Acid to Boost the Remission of Cervical Low-Grade Squamous Intraepithelial Lesions (L-SILs): A Randomized Controlled Trial

Background and Objectives: Echinacea angustifolia and purpurea have known immunomodulatory effects which boost viral clearance, including HPV infection. However, evidence regarding the improvement due to Echinacea-based supplements of cervical HPV-related pathologies is still lacking. The aim of this study is to evaluate the efficacy of Echinacea supplementation on the remission of cervical low-grade squamous intraepithelial lesions (L-SIL). Materials and Methods: A single-blind 1:1:1 parallel randomized controlled trial was conducted at the Colposcopy Unit of a tertiary care referral center. Reproductive-aged women were allocated either to (a) an oral supplement based on Echinacea extracts plus vaginal hyaluronic acid-based soft gel capsules, (b) the Echinacea supplement alone, or (c) vaginal hyaluronic acid-based soft gel capsules alone for 3 months. The primary outcome was the regression of cervical intraepithelial neoplasia (CIN)-1 for each treatment arm at 3, 6 and 12 months after the diagnosis. Secondary outcomes included changes in the epithelialization, pap smear, colposcopic parameters, histological reports, and vaginal health indexes (VHI) in the study groups. Results: 153 women (52 for arm A, 50 for arm B and 51 for arm C) completed the follow-up and were included in the analysis. There were no significant differences in both primary and secondary outcomes for the three groups after 3 months. At the 6-month follow-up, the number of persistent CIN-1 diagnoses was significantly lower in arm A (15/51), rather than in arm B (23/48, p = 0.03) and C (27/49, p = 0.03). Similarly, the same effect was seen after 12 months for treatment A (5/51) relative to B (15/48, p = 0.03) and C (14/48, p = 0.03). Colposcopic, histological and vaginal parameters were all significantly improved at 6 and 12 months for arm A relative to B and C, while no beneficial effects were seen after 3 months. Conclusions: Echinacea extracts supplementation in women with L-SIL/CIN-1 significantly boosts HPV lesion clearance, reducing the overall amount of diagnosis, histological, colposcopic and vaginal parameters after 6 and 12 months. However, a limited sample size reduces the quality of evaluated evidence, emphasizing the need for additional studies to validate these findings.

Retrospective Comparison of Laparoscopic versus Open Radical Hysterectomy for Early-Stage Cervical Cancer in a Single Tertiary Care Institution from Lithuania between 2009 and 2019

Background and Objectives: A great debate within the academic arena was evoked by the LACC study, giving rise to doubt regarding the oncological outcomes of the laparoscopic approach for early-stage cervical cancer. This encouraged us to conduct a retrospective analysis of CC treatment surgical approaches applied to the patients at tertiary level Vilnius University Hospital Santaros Clinics, Vilnius, Lithuania, between 2009 and 2019. Materials and Methods: The retrospective study was carried out to evaluate the outcomes after 28 laparoscopic and 62 laparotomic radical hysterectomies for early cervical cancer in a single tertiary care institution performed during the period 2009–2019. For statistical analysis of patients’ parameters, SPSS v. 17.0 was applied, together with the Kaplan–Meier method with a long-rank test and the Cox proportional hazard regression model used for bi-variate analysis determining OS outcomes between MIS and open-surgery groups. Results: After computing data with the Cox regression model, there was no significant difference of the 36-months overall survival between laparoscopy and laparotomy groups, as opposed to the LACC study. Conclusions: Our tertiary institution faces a considerable challenge, and we acknowledge the limitations of the study and also feel a responsibility to follow the latest guidelines. Currently, it appears that the most substantial attention should be focused on the cessation of uterine manipulator use as well as laparoscopic technique learning curves.

Cervical Intraepithelial Neoplasia Grade 3 in a HPV-Vaccinated Patient: A Case Report

Persistent infection with human papillomavirus (HPV) causes almost all cervical precancerous lesions and cancers. Bivalent, quadrivalent, and nonavalent HPV vaccines effectively prevent high-grade cervical intraepithelial neoplasia (CIN3). The effectiveness of HPV vaccination against CIN3 is 97–100% in HPV-naïve populations and 44–61% in the overall population. Although HPV vaccination has substantially reduced the incidence of cervical cancers, several cases of precancerous cervical lesions in HPV-vaccinated patients have been reported. We report the clinical case of a 19-year-old woman whose first Pap smear was diagnosed as a high-grade squamous intraepithelial lesion (HSIL) after quadrivalent HPV vaccination. Colposcopy and cervical biopsy were performed, revealing HSIL/CIN3. Our multidisciplinary team decided to take a conservative approach with follow-up visits with cervical biopsies of this young patient. After six months, spontaneous regression of high-grade cervical dysplasia was observed. Although HPV immunization has shown to be extremely effective in preventing a high proportion of cervical precancerous lesions and cervical cancers, HPV vaccines do not protect against all oncogenic high-risk HPV genotypes. Consequently, healthcare providers must encourage HPV-vaccinated women to still regularly attend national cervical screening programs.

CD74 and HLA-DRA in Cervical Carcinogenesis: Potential Targets for Antitumour Therapy

Background and Objectives: Abnormal expressions of CD74 and human leukocyte antigen-DR alpha (HLA-DRA) have been reported in various cancers, though their roles in cervical cancer remain unclear. This study aimed to evaluate the gene and protein expressions of CD74 and HLA-DRA in the progression from normal cervix to precancerous cervical intraepithelial neoplasia (CIN) and finally to squamous cell carcinoma (SCC). Materials and Methods: The gene expression profiles of CD74 and HLA-DRA were determined in formalin-fixed paraffin-embedded tissues, with three samples each from normal cervixes, human papillomavirus type 16/18-positive, low-grade CIN (LGCIN), high-grade CIN (HGCIN), and squamous cell carcinoma (SCC) using Human Transcriptome Array 2.0. Immunohistochemical expression of the proteins was semi-quantitatively assessed in another cohort of tissue microarray samples comprising 7 normal cervix cases, 10 LGCIN, 10 HGCIN, and 95 SCC. Results: The transcriptomics profile and proteins’ expression demonstrated similar trends of upregulation of CD74 and HLA-DRA from normal cervix to CIN and highest in SCC. There was a significant difference in both proteins’ expression between the histological groups (p = 0.0001). CD74 and HLA-DRA expressions were significantly associated with CIN grade (p = 0.001 and p = 0.030, respectively) but not with the subjects’ age or SCC stage. Further analysis revealed a positive correlation between CD74 and HLA-DRA proteins. Conclusions: CD74 appears to promote cervical carcinogenesis via oncogenic signalling mechanisms and may serve as a potential antitumour target. Additionally, the upregulation of HLA-DRA, often associated with stronger immunogenicity, could be a promising biomarker for developing immunotherapies.

Minimally Invasive Surgery and Recurrence Risk in Borderline Ovarian Tumours: A 10-Year Cohort Analysis

Background and Objectives: Borderline ovarian tumours (BOTs) predominantly affect women of reproductive age. Following concerns about minimally invasive surgery (MIS) in cervical cancer, the oncological safety of the surgical approach in BOTs requires evaluation, particularly in fertility-sparing procedures where clinical implications are greatest. This study aimed to assess whether MIS is associated with increased recurrence risk in BOTs, with stratified analysis by fertility-sparing status based on a pre-specified hypothesis of differential effects. Materials and Methods: Single-centre cohort study of 91 BOT patients treated at Nottingham City Hospital Cancer Centre between 2014–2023. The primary outcome was progression-free survival comparing MIS versus open surgical approaches. Results: Minimally invasive surgery was associated with higher observed recurrence compared to open surgery (5/25 [20.0%, 95% CI: 6.8–40.7%] vs. 3/66 [4.5%, 95% CI: 0.9–12.7%], absolute risk difference 15.5% [95% CI: 2.1–28.9%]; unadjusted HR 5.29, 95% CI: 1.26–22.17; p = 0.022). Conclusions: This study identifies an association between minimally invasive surgery and higher recurrence in borderline ovarian tumours, particularly in fertility-sparing procedures. While based on small numbers necessitating cautious interpretation, the consistency across analytical approaches, substantial magnitude of observed differences, and biological plausibility warrant validation in larger cohorts to inform surgical counselling.

Minimally Invasive Surgery in the Management of Advanced Epithelial Ovarian Cancer: A Comprehensive Analysis of Current Evidence and Clinical Applications

Background and Objectives: Advanced epithelial ovarian cancer (AEOC) often requires extensive cytoreductive surgery. Minimally invasive surgery (MIS), especially diagnostic laparoscopy, is increasingly used to assess resectability and guide treatment. This review aimed to evaluate the evidence on MIS in AEOC, focusing on its diagnostic and therapeutic roles in primary and interval debulking surgery (PDS and IDS), and its impact on perioperative and oncologic outcomes. Materials and Methods: A structured literature review was performed using PubMed, MEDLINE, Embase, Scopus, and the Cochrane Library, including studies published between January 2000 and June 2025. Eligible studies involved laparoscopic or minimally invasive cytoreduction in PDS or IDS, reporting surgical feasibility, perioperative results, and oncologic outcomes. Data were synthesized qualitatively due to heterogeneity across studies. Results: Observational studies indicate that diagnostic laparoscopy predicts resectability, reduces futile laparotomies, and improves patient selection for primary surgery. In selected patients, non-randomized cohorts of laparoscopic PDS report R0 resection rates up to 95%, with low morbidity and short hospital stays. In IDS after neoadjuvant chemotherapy, MIS has been associated with reduced blood loss, fewer complications, and faster postoperative recovery, while showing progression-free and overall survival comparable to laparotomy in retrospective series. Conversion to open surgery was generally reported in fewer than 10% of cases when stringent selection criteria were applied. Conclusions: Diagnostic laparoscopy is a valuable tool for accurate preoperative evaluation and surgical planning in EOC. MIS, particularly for IDS, appears to offer reduced morbidity and equivalent survival outcomes when performed in experienced centers, whereas its application in PDS remains investigational and should be reserved for highly selected cases. These conclusions are limited by the predominance of retrospective evidence and the heterogeneity in patient selection and surgical expertise.

Clinical and Prognostic Relevance of BRIP1 Expression in Colorectal Cancer: Evidence from TCGA and Korean Cohorts

Background and Objectives: BRCA1-interacting protein C-terminal helicase 1 (BRIP1) encodes a member of the RecQ DEAH helicase family and interacts with the BRCT repeats of breast cancer type 1 (BRCA1). It also participates in DNA damage repair and tumor suppression; thus, its mutations may be associated with an increased risk of several cancers, including fallopian tube and ovarian cancer. Recent research has explored whether BRIP1 dysregulation also contributes to the development and progression of other malignancies. This study investigated the clinical and prognostic value of BRIP1 in colorectal cancer (CRC). Materials and Methods: We first analyzed The Cancer Genome Atlas (TCGA) dataset to evaluate the prognostic significance of BRIP1 mRNA expression in CRC. BRIP1 expression was subsequently examined in tumor tissues from 60 CRC patients, and its associations with clinicopathological characteristics and clinical outcomes were assessed. Results: In rectal cancer, a higher BRIP1 expression was associated with younger age. In colon cancer, BRIP1 expression was correlated with gender, lymphatic invasion, carcinoembryonic antigen (CEA) level, pathological stage, M stage, N stage, microsatellite instability (MSI) status, and anatomical tumor location. Survival analysis showed that low BRIP1 expression was associated with poorer overall survival in both rectal and colon cancers significantly. In CRC patient tissues, lower BRIP1 expression was further related to elevated CEA levels and unfavorable clinical outcomes. Lower BRIP1 mRNA expression is significantly associated with aggressive clinicopathological features and poor prognosis in CRC. Conclusions: BRIP1 may serve as a promising biomarker for risk stratification and a potential therapeutic target in the management of CRC.

Evaluating Comorbidity Scores in Geriatric Ovarian Cancer: A Retrospective Cohort Analysis

Background and Objectives: This study aimed to comparatively evaluate the association of commonly used comorbidity scores with survival, mortality, and recurrence in ovarian cancer patients aged 50 years and above. Materials and Methods: In this single-center, retrospective study, 130 female patients diagnosed between 2017 and 2024 who had received systemic therapy and had complete medical records were included. Comorbidity scores—including the Charlson Comorbidity Index (CCI), Cumulative Illness Rating Scale-Geriatric (CIRS-G), Adult Comorbidity Evaluation-27 (ACE-27), Elixhauser Comorbidity Index, Index of Coexistent Disease (ICED), and Functional Comorbidity Index (FCI)—were calculated for each patient. Survival analyses were conducted using the Kaplan–Meier method and Cox regression modeling. The prognostic accuracy of comorbidity scores was assessed via receiver operating characteristic (ROC) curve analysis. Results: Patients with higher CCI scores had significantly shorter survival, and CCI was identified as an independent prognostic factor in multivariate analysis. While other comorbidity scores were associated with overall survival in univariate analyses, they lost statistical significance in multivariate models. Patients with a higher comorbidity burden experienced more frequent disease recurrence and shorter time to recurrence. Conclusions: Comorbidity burden is a key clinical determinant of survival and disease trajectory in older patients with ovarian cancer. The CCI demonstrated the highest prognostic accuracy in this population and may serve as a valuable tool in individualized treatment planning. Integration of comorbidity-based assessments into standard decision-making processes is recommended in geriatric oncology practice.