Background/Aim: This study aimed to examine the immunohistochemical expression of Inositol-Requiring Enzyme 1 Alpha (IRE1) and Protein Kinase R-like ER Kinase (PERK) immunoreactivity scores (IRS) as emerging biomarkers on key clinicopathologic features and survival outcomes in endometrial cancer (EC). Patients and Methods: Immunoreactive scores (IRS) for IRE1 and PERK were assessed in tumor samples from 73 EC survivors and compared with 20 benign endometrial controls. Associations between IRS values and clinicopathological variables were analyzed. Overall survival (OS) and disease-free survival (DFS) were evaluated using univariable and multivariable Cox proportional hazards models adjusted for age, FIGO stage, and tumor grade. Results: IRE1-IRS and PERK-IRS were significantly higher in EC survivors compared to controls (p=0.015 and p<0.001, respectively) and PERK-IRS was higher in non-endometrioid than endometrioid tumors (p=0.017). EC survivors undergoing laparotomy exhibited higher PERK-IRS than those treated laparoscopically (p=0.009). Neither IRE1-IRS nor PERK-IRS was associated with OS or DFS, except for a negative association of high vs. low IRE1-IRS score and DFS in the unadjusted model (p=0.026) but not in the adjusted one. Conclusion: IRE1 and PERK expression is up-regulated in endometrial cancer and correlates with selected clinicopathological features, particularly those linked to aggressive disease. However, neither marker demonstrated independent prognostic value for survival outcomes. Further studies are warranted to clarify the role of ER stress pathways in EC biology and their potential implications for risk stratification and targeted therapy.

BACKGROUND/AIM:Placenta accreta spectrum (PAS) is characterized by abnormal placental adherence/invasion at a scarred implantation bed. Endoplasmic reticulum (ER) stress signaling via inositol-requiring enzyme 1 (IRE1) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) shapes trophoblast behavior, but its interface-specific role in PAS is unclear. We evaluated IRE1 and PERK immunoreactivity in extravillous trophoblast (EVT) subsets to test associations with PAS severity and maternal outcomes. PATIENTS AND METHODS:In a retrospective series from a tertiary center, cesarean hysterectomy specimens for PAS and gestational age-matched cesarean controls were analyzed. Immunohistochemistry for IRE1 and PERK was performed on basal plate regions, with semiquantitative immunoreactivity score (IRS:0-12) recorded for EVT subtypes. Associations with clinicopathological parameters and with negative controls were examined with bivariate analyses. RESULTS:IRE1 expression showed no significant associations with clinicopathological parameters. PERK IRS was significantly higher in PAS obstetrical hysterectomy specimens than in controls (mean 9.40±1.96 vs. 4.17±1.52; p<0.001). Across PAS subtypes (accreta/increta/percreta), PERK-IRS varied numerically but not significantly. Within PAS, PERK-IRS was negatively associated with maternal complications (p=0.035). CONCLUSION:PERK-IRS was elevated at the stressed implantation interface in PAS relative to normal placentation, while IRE1 showed no clear differential signal with the current assay. Paradoxically, within PAS, lower local PERK-IRS signal correlated with complications, suggesting that the magnitude/timing of PERK engagement may influence operative risk. Larger studies incorporating activation-specific markers are warranted to refine biological stratification and prognostication in PAS.

Background: Breast cancer (BC) remains one of the leading causes of cancer-related deaths worldwide, with early detection being essential for improving survival rates, treatment outcomes, and preventive women's healthcare strategies. Artificial Intelligence (AI), particularly deep learning (DL) and machine learning (ML) algorithms, has emerged as a promising tool for improving the accuracy and efficiency of BC diagnosis. This systematic review explores the role of AI in early BC detection and its implications for preventive and patient-centered women's healthcare. Methods: A comprehensive search was conducted in PubMed and Scopus for studies published between January 2015 and December 2025, following PRISMA guidelines. The search strategy included combinations of MeSH terms and free-text keywords related to artificial intelligence, machine learning, deep learning, BC screening, mammography, magnetic resonance imaging (MRI), ultrasound, and BC detection. Eleven studies involving approximately 148,170 participants were included. Methodological quality was assessed according to study design. Results: AI-driven diagnostic systems demonstrated improved accuracy, sensitivity, specificity, and efficiency compared with conventional approaches. AI applications in mammography and ultrasound reduced radiologists' workload and healthcare costs while enhancing cancer detection rates, particularly in women with high breast density. AI models also showed potential in identifying metastases and predicting clinical outcomes, supporting more efficient patient management and follow-up care. Conclusions: AI-based tools represent a promising advancement in BC detection and screening efficiency. Their integration into BC screening programs may strengthen preventive women's healthcare services and improve patient outcomes. However, further large-scale clinical validation and real-world implementation studies are required before widespread clinical implementation.

Mismatch repair deficiency (MMRd) is a critical biomarker in endometrial cancer (EC) for prognostication, Lynch syndrome screening, and immunotherapy eligibility. This study aimed to determine the prevalence of MMRd and its correlation with clinicopathological characteristics in EC. This prospective observational cohort included 93 patients with EC undergoing primary surgical treatment, managed as per the European Society of Gynaecological Oncology (ESGO) guidelines. MLH1, PMS2, MSH2, and MSH6 expression was assessed through immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded hysterectomy specimens. Associations between mismatch repair (MMR) status and histology, grade, lymphovascular space invasion (LVSI), myometrial invasion, FIGO 2023 stage, nodal status, recurrence, and survival were analyzed. The median age was 66 years. Most tumors were endometrioid (86%), 29% were grade 3, 45.2% showed deep myometrial invasion, and 23.7% had substantial LVSI. MMRd was identified in 41.9% of cases, with MLH1 and PMS2 loss being most frequent, and was significantly associated with endometrioid histology (p = 0.027) and deep myometrial invasion (p = 0.011). No significant correlations were found with grade, LVSI, FIGO stage, nodal involvement, recurrence, or overall survival. Routine MMR assessment may refine risk stratification and guide individualized treatment decisions.

Background: Persistent human papillomavirus (HPV) can cause low- or high-grade cervical lesions, which may progress to cervical cancer. This prospective, multicenter, real-world study assessed the effectiveness, tolerability and safety of a Coriolus versicolor-based vaginal gel for the regression of HPV-related low-grade cervical lesions in routine Greek practice. Methods: PAPILOBS-GR is a multicenter, open-label, non-interventional, prospective observational, non-comparative study conducted across 45 sites in Greece. Women aged ≥18 years with ASCUS/LSIL cytology and concordant colposcopy were enrolled. Participants received Coriolus versicolor-based vaginal gel for six months. A second 6-month cycle was offered if needed. The primary endpoint was lesion regression. Secondary endpoints included HPV clearance, patient satisfaction, biopsy evolution, tolerability, and safety. Results: Of 524 enrolled patients (mean age: 34.4 ± 10.0 years; 40.5% HR-HPV), 494 (94.3%) completed the study. Overall, 75.9% achieved lesion regression (72.1% at 6 months and 34.0% at 12 months). HPV clearance occurred in 72.0% overall (68.1% at 6 months and 50.0% at 12 months). Exploratory comparisons showed generally consistent effectiveness across subgroups, including women with HR-HPV, those aged >40 years, and vaccinated participants. No significant differences in clinical endpoints were observed in association with age or vaccination status. Among 22 patients with baseline and 12-month biopsies, 59.1% showed histological improvement. Satisfaction scores exceeded 8/10 at 6- and 12-month follow-ups. Only two non-serious possibly product-related adverse events were reported. Conclusions: Coriolus versicolor-based vaginal gel was associated with high rates of lesion regression and excellent tolerability, reinforcing previous clinical findings and supporting its potential role as an adjunctive approach during watchful waiting for HPV-positive low-grade cervical lesions.

Uterine leiomyomas are common benign tumors, whereas "giant" leiomyomas occupying most of the abdominal cavity are now uncommon and can pose diagnostic and operative challenges. We present the case of a 45-year-old woman with progressive abdominal distension and long-standing menorrhagia. Computed tomography demonstrated a massive uterine fundal mass consistent with a giant subserosal leiomyoma and a separate right adnexal cystic lesion. The patient underwent elective midline laparotomy and total abdominal hysterectomy with bilateral salpingo-oophorectomy. The ovarian cyst was removed intact without capsular rupture, and peritoneal washings were obtained. Estimated blood loss was 80 mL. Postoperative recovery followed an enhanced recovery after surgery (ERAS) pathway, enabling discharge on postoperative day four. Final histopathology confirmed a giant subserosal leiomyoma measuring 44 × 38 × 30 cm and revealed an occult clear cell carcinoma confined to the ovarian cyst (FIGO stage IA), with negative peritoneal cytology. Completion staging surgery and adjuvant-treatment discussion were recommended at a multidisciplinary tumor board; however, the patient declined further extensive surgery and was referred to medical oncology for adjuvant management and close surveillance. This case highlights the complexity of removal in giant uterine tumors, careful handling of adnexal cysts to avoid intraoperative rupture, and the feasibility of ERAS-based recovery.

Background/Objectives: Molecular classification has become integral to endometrial cancer (EC) management, with mismatch repair deficiency (dMMR) representing a key biomarker for prognostication, Lynch syndrome screening, and immunotherapy eligibility. However, reported dMMR rates and their associations with histopathological features remain variable. This study aimed to determine the prevalence of dMMR and its correlation with clinicopathological characteristics in early-stage EC. Methods: In this prospective observational cohort study, 93 patients with early-stage EC undergoing primary surgical treatment between September 2022 and December 2025 were included. All patients were managed according to European Society of Gynaecological Oncology (ESGO) guidelines. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded hysterectomy specimens to assess MLH1, PMS2, MSH2, and MSH6 expression. dMMR was defined as complete or subclonal loss of nuclear staining in ≥1 protein, while proficient MMR (pMMR) required preserved (> 90%) expression of all four proteins. Associations between MMR status and histology, grade, lymphovascular space invasion (LVSI), depth of myometrial invasion, FIGO 2023 stage, nodal status, recurrence, and survival were analyzed. Results: Median age was 66 years (range 35–86). Most tumors were endometrioid (86%), 27.9% were grade 3, 44% demonstrated deep myometrial invasion, and 23.6% showed substantial LVSI. dMMR was identified in 41.9% (39/93) of cases. MLH1 (38.0%) and PMS2 (39.8%) loss were most frequent, whereas MSH2 (3.2%) and MSH6 (4.3%) loss was uncommon. dMMR was significantly associated with endometrioid histology (p = 0.03) and deep myometrial invasion (p = 0.011). No significant correlations were observed with tumor grade, LVSI, FIGO stage, nodal involvement, recurrence, or overall survival during follow-up. Conclusions: dMMR was detected in approximately 40% of early-stage ECs and was significantly associated with endometrioid histology and deep myometrial invasion. Routine assessment of MMR status may refine risk stratification and support individualized therapeutic decision-making. Further studies with longer follow-up are warranted to clarify its prognostic impact.

Viral carcinogenesis as a causative mechanism of breast cancer has been intensively researched during the last decades. The role of Epstein-Barr virus (EBV) and Bovine Leukemia virus (BLV) in breast oncogenesis has been investigated in a plethora of studies, but with conflicting results. The aim of this systematic review and meta-analysis was to compare the frequency of molecular detection of the EBV genome and BLV genome between women with breast cancer and women without malignant breast tumors. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, SCOPUS, Cochrane CENTRAL and ClinicalTrials.gov were searched up to 20 May 2024. Included studies were those comparing the frequency of molecular detection of the EBV and/or BLV genome in breast tissue specimens with polymerase chain reaction (PCR) methods between patients with breast cancer and women without breast malignancies. The primary outcomes of the study were the frequency of molecular detection of the EBV genome and BLV genome. Methodological quality of included studies was assessed using the Newcastle-Ottawa Scale. A total of 29 studies met the selection criteria and were included in this meta-analysis; 19 studies reported results for molecular detection of the EBV genome, 9 studies for detection of the BLV genome and 1 study for detection of genomic material of both viruses. The frequency of molecular detection of viral genomes was significantly higher in patients with breast cancer, compared to women with healthy breasts or benign breast diseases, regarding both EBV (OR: 3.041, 95% CI: 1.791 to 5.164, p < 0.0001) and BLV (OR: 3.459, 95% CI: 2.118 to 5.650, p < 0.0001). The frequency of molecular detection of EBV and BLV genomes is higher, in a statistically significant manner, in patients with breast cancer compared to women without breast malignancies. The presence of these viral factors in breast tissue could imply their potential contribution in breast carcinogenesis, but is not sufficient to establish it, and the molecular detection of their genomes could be potentially exploited in the future for preventive, diagnostic and therapeutic purposes. Further studies are required to thoroughly investigate and establish a causal relationship between EBV and BLV infection and breast carcinogenesis, as well as to support the use of viral genome molecular detection in clinical settings for the management of breast cancer patients.

This systematic review and meta-analysis investigates the association of first-line poly(adenosine diphosphate-ribose) polymerase inhibitor (PARP inhibitor) maintenance therapy with efficacy and safety outcomes among patients with advanced-stage epithelial ovarian cancer. QuestionWhat is the association of first-line poly(adenosine diphosphate-ribose) polymerase inhibitor (PARP inhibitor) maintenance therapy with survival outcomes in epithelial ovarian cancer, and how do outcomes vary across regimens and subgroups?FindingsIn this meta-analysis of 7 randomized clinical trials among 4013 patients with advanced-stage epithelial ovarian cancer responding to first-line platinum-based chemotherapy, progression-free survival improved in most subgroups but not in homologous recombination-proficient tumors, and no subgroup demonstrated a statistically significant overall survival benefit. Efficacy and toxic effects varied across agents.MeaningThis study found that first-line PARP inhibitor maintenance therapy was associated with a progression-free survival benefit in many patient populations; however, the lack of overall survival benefit, increased toxic effects, and variability across subgroups and regimens, suggest that treatment should be individualized. ImportanceFirst-line maintenance therapy with poly(adenosine diphosphate-ribose) polymerase inhibitors (PARP inhibitors) after platinum-based chemotherapy improves progression-free survival (PFS) in advanced epithelial ovarian cancer (EOC), particularly in patients with BRCA-variant or homologous recombination-deficient tumors. However, overall survival (OS) benefits remain uncertain, and toxic effect profiles emphasize the need for optimized patient and agent selection.ObjectiveTo evaluate the efficacy and safety of first-line PARP inhibitor maintenance therapy compared with chemotherapy alone in advanced-stage EOC, with subgroup analyses by BRCA and HRD status, up-front or interval surgery, chemotherapy response, and residual disease.Data sourcesMedline, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from database inception to August 19, 2024.Study SelectionRandomized clinical trials and prospective 2-arm studies evaluating PARP inhibitor maintenance therapy in patients with advanced-stage EOC responding to first-line platinum-based chemotherapy were included.Data Extraction and SynthesisThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline was followed in reporting this study. Data were independently extracted by 2 reviewers. Random-effects models were used for meta-analysis. Risk of bias was assessed with Cochrane risk of bias and certainty of evidence with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.Main Outcomes and MeasuresPrimary outcomes were PFS and OS; secondary outcomes included high-grade adverse events.ResultsA total of 7 randomized clinical trials with 4013 patients with advanced-stage epithelial ovarian cancer responding to first-line platinum-based chemotherapy were included. PARP inhibitor maintenance was associated with improved PFS in the overall population (hazard ratio [HR], 0.57; 95% CI, 0.46-0.70; high certainty) and in all molecular subgroups except the homologous recombination proficient group (BRCA variant: HR, 0.40; 95% CI, 0.35-0.45; BRCA wild type: HR, 0.62; 95% CI, 0.44-0.86; homologous recombination deficient: HR, 0.44; 95% CI, 0.39-0.50; all high certainty). PFS benefits were consistent across surgical timing, chemotherapy responses, and residual disease; for example, surgical timing had HRs of 0.51 (95% CI, 0.31-0.84) for neoadjuvant chemotherapy and 0.54 (95% CI, 0.36-0.81) for primary cytoreductive surgery (all high certainty). No molecular subgroup showed a statistically significant OS improvement (high to low certainty). High-grade adverse events were more common in the PARP inhibitor group (HR, 2.40; 95% CI, 1.16-4.93; high certainty). Observed treatment efficacy and toxic effects varied across PARP inhibitor regimens; for example, the risk ratio for any recurrence or death in the overall study group ranged from 0.53 (95% CI, 0.40-0.70) for senaparib to 0.83 (95% CI, 0.68-1.00) for olaparib, while the risk ratio for high-grade adverse events ranged from 1.15 (95% CI, 0.64-2.06) for veliparib to 4.73 (95% CI, 2.77-8.07) for niraparib.Conclusions and RelevanceIn this study, no subgroup showed an association between first-line PARP inhibitor maintenance therapy in advanced-stage EOC and improved OS, and findings suggest that the consistency of associated PFS benefits may vary, particularly in homologous recombination proficient and BRCA wild type tumors. Variability in efficacy and toxic effects across subgroups and PARP inhibitor regimens underscores the importance of individualized treatment decisions.

Background and Objectives: This study aims to evaluate the relevance of urethral pressure profile (UPP) measurements in the diagnosis of urodynamic stress incontinence (USI) in women with stress and mixed urinary incontinence (SUI and MUI). Materials and Methods: A cross-sectional chart review was used. All patients who had urodynamic studies (UDSs) in the urogynecology unit of an academic hospital over the last 6 months and complained of SUI or MUI were analyzed. Clinical examination included prolapse grading with the POP-Q system. The presenting symptoms, initial diagnosis before UDS, and results from flow studies—cystometrography (CMG), which included a 1-3-5 cough test at 300–350 mL bladder filling, and urethral pressure profilometry (UPP)—were recorded. p < 0.05 was considered significant in all statistical comparison tests; receiver operator characteristic (ROC) curves were also used to determine the best predictor of SUI diagnosis. Results: In total, 57 women were included in this study, with a mean age of 60.7 (±9.3). Upon UDS, 28 women (49.1%) demonstrated USI (Group 1), while 29 women (50.9%) did not demonstrate USI (Group 2). No differences between the two groups were noted during free uroflowmetry and the filling phase of CMG. However, the women in Group 2 had a significantly lower MUCP, FUL, and post-void residual after pressure flow compared to the women in Group 1 (p = 0.038, 0.003, and 0.04, respectively, upon Student’s t test for independent parameters). The ROC analysis indicated that when using MUCP and FUL for the diagnosis of USI, the AUCs are 0.663 (0.525–0.782) and 0.756 (0.623–0.861), respectively. Conclusions: By exhibiting correlations between low MUCP/FUL and USI, UPP appears to be a valid test for USI. The value of UPP in diagnosing USI in those with SUI and MUI appears to be clinically important. Further studies are needed in non-SUI patients, in addition to SUI subgroups and various incontinence treatment groups.

OBJECTIVE:Placental site trophoblastic tumor (PSTT) is a rare pathologic entity of gestational trophoblastic neoplasia. The main objective of the present manuscript is to summarize current evidence regarding the possibility of fertility-sparing management. METHODS:A systematic review of the literature was conducted to evaluate the efficacy, oncological safety, and fertility-preservation outcomes in patients with PSTT undergoing fertility-sparing management. PubMed, Scopus, and Cochrane Library were searched to identify proper articles. Eligibility criteria included all prospective or retrospective cohorts reporting conservative management of PSTT. Primary outcomes were the rate of recurrence and fertility outcome. Secondary outcomes concerned the type of conservative management. RESULTS:Overall, 16 articles were retrieved including a total of 63 patients. The mean age was 28.3 years (range; 21-37) and the mean serum beta-human chorionic gonadotropin was 17,251.9 IU/L (range; <0.1 to 430,290 IU/L). Regarding the antecedent pregnancy, 41.3% (26 cases) were full-term pregnancies, and 30.2% (19 cases) were abortions. Most cases were International Federation of Gynecology and Obstetrics stage I (73%). The overall recurrence rate of disease was 13.8% (8 of 63 patients) with these patients all treated with hysterectomy after recurrence. There were overall 23 full-term pregnancies reported, indicating a 36.5% fertility rate per patient, while 2 pregnancies are still ongoing at the time of publication. CONCLUSIONS:Fertility-sparing management of patients with PSTT is feasible and oncologically safe, with 36.5% fertility outcomes.

The use of post-operative drainage has been a topic of debate for several years. While the trend has increasingly shifted toward avoiding routine drainage, opinions on its necessity remain divided. The main objective of this comprehensive review is to effectively summarize and present the current knowledge and up-to-date evidence on the role of prophylactic drainage in women undergoing obstetric, oncological, or other types of gynecological surgical procedures in terms of the indications, post-operative surgical infections, morbidity recovery, post-operative complications and outcomes. Prophylactic drainage does not seem to decrease morbidity in cases of lymphadenectomy and radical hysterectomy. Debulking surgery does not necessitate prophylactic drainage in the majority of cases; however, its usage should be individualized based on the surgical complexity. Conflicting evidence exists regarding drains’ effectiveness in preventing anastomotic leakage, with high rates of re-operation and abscess formation noted. Despite the fact that vaginal drains may help with hematoma and infectious morbidity, the overall benefit of vaginal and peritoneal drains in preventing post-operative morbidity is questionable. Finally, negative pressure wound therapy may reduce surgical site infection rates in patients undergoing cytoreductive surgery for ovarian cancer. Although there is still a great need for further investigation, the topic has been covered adequately by many prospective trials and the international guidelines have provided clear suggestions to guide physicians in clinical practice. However, need for individualization and personalized strategies is well emphasized by the published evidence in an effort to balance the benefits and risks of drainage usage determined by the type of surgery and patient status.