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Homologous recombination deficiency (HRD) is a key biomarker associated with increased sensitivity to PARP inhibitors (PARPi) in advanced epithelial ovarian cancer. Accurate identification of HRD status is essential for selecting patients most likely to benefit from these therapies. Current diagnostic approaches combine sequencing to detect mutations in homologous recombination repair genes—particularly BRCA1 and BRCA2—with genome-wide analysis of structural genomic alterations indicative of HRD. This review briefly outlines the biological basis of HRD and its clinical significance and then focuses on currently available assays for HRD assessment. We compare their molecular strategies, including the use of targeted gene panels and genomic instability metrics such as loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions. The review also highlights the strengths and limitations of each platform and discusses their role in guiding clinical decision-making. Challenges related to dynamic tumor evolution and the interpretation of HRD status in recurrent disease settings are also addressed.

Transvaginal ultrasound (TVUS) represents an accurate and noninvasive technique to investigate endometrial thickness (ET) in the early diagnosis of endometrial cancer (EC). In the literature, for maximum ET there is no consensus on the cutoff value for normal ET in postmenopause for either symptomatic or asymptomatic women. Most patients with EC present with postmenopausal bleeding (PMB) and in these patients is necessary to perform TVUS to evaluate ET as an indicator for endometrial biopsy. On the contrary, if ET is incidentally detected in postmenopausal patients without bleeding, endometrial sampling for a postmenopausal woman without bleeding should not be routinely performed, although it is estimated that up to 15% of EC occurs in women without vaginal bleeding. The aim of our review was to give clinicians necessary and useful knowledge on the role of TVUS and ET for early detection of EC in their daily routine practice. Based on the most important studies in the literature, we summarized that in premenopausal woman with abnormal uterine bleeding, an optimal cutoff for ET has not yet been established. For postmenopausal women with PMB, at low risk, and ET <4 mm, a follow-up scan could be offered, and for women with ET ≥4 mm, office hysteroscopy-guided endometrial sampling is recommended independently of ET results. On the other hand, in postmenopausal women with PMB and at high risk of EC, office hysteroscopy-guided endometrial sampling is necessary. In postmenopausal women without PMB and ET ≥4 mm, arbitrary endometrial sampling is not recommended, but evaluated case by case based on risk factors. In conclusion, there is broad consensus on the importance of TVUS and the need for further investigation based on risk factors of EC.

Background/Objectives: Cancer immunotherapy through the use of PD-1/PD-L1 inhibitors have shown significant promise in endometrial carcinoma (EC), particularly in tumors with microsatellite instability (MSI) or mismatch repair deficiency (dMMR), present in approximately 30% of cases. This review evaluated PD-L1 and PD-1 expression as potential biomarkers for immunotherapy response in EC, focusing on their relationship with MSI status. Methods: A systematic review, adhering to PRISMA guidelines, analyzed studies from MEDLINE and Embase until February 2023 on PD-1/PD-L1 expression in EC stratified by MSI status, including diverse study designs but excluding conference abstracts, with independent screening, data extraction, and additional reference checks to ensure comprehensive coverage. Results: A systematic analysis of 10 studies found that PD-L1 expression was more frequently expressed in MSI tumors (49%) compared to microsatellite-stable tumors (MSS) (33.5%), while PD-1 was expressed in 58% of MSI cases and 48% of MSS cases. Despite these findings, the prognostic value of PD-L1/PD-1 remains uncertain, with conflicting results regarding their association with survival outcomes. PD-L1 expression varied across molecular subtypes, being highest in POLE-mutated tumors (76.56%) and serous carcinomas (73%). Differences in PD-L1 expression between primary and metastatic sites were also noted, complicating its use as a biomarker. Conclusions: The assessment of PD-L1 expression in EC could represent a valuable option for selecting patients who may benefit from immune checkpoint inhibitors (ICI), including those in the MSS cohort, thereby ensuring a more tailored and personalized treatment strategy.

The conventiol-trans bronchial needle aspiration (c-TB) has been the first procedure for sampling hilar/mediastil lymph node for the diagnosis/staging of lung cancer. In the last decade the endobronchial ultrasound trans bronchial needle aspiration (EBUS-TB) was introduced in clinical practice and became the first-choice exam in diagnosis and staging of lung cancer. The aim of this study was to compare the diagnostic accuracy (DA), sensitivity and adequacy of c-TB and EBUS-TB. It was a retrospective and observatiol multicenter study. The first endpoint was diagnostic accuracy of EBUS-TB versus c-TB. The secondary end-points were sensitivity and adequacy. Two hundred and nine consecutive patients underwent the procedure, 99 EBUS-TB and 110 c-TB. When lymph nodes with short axis <2 cm the diagnostic accuracy for correct diagnosis was 94.2% in EBUS-TB group and 89.7% in c-TB group (p=0.01); the sample adequacy was 70.3% and 42%, respectively (p=0.01); the sensitivity was 93% (95% CI, 82-98%) and 86.4% (95% CI, 67.6-95.6%), respectively (p=0.002). In lymph nodes with short axis ‰¥2 cm the diagnostic accuracy was 95.7% in EBUS-TB group and 93% in c-TB group (p=0.939); the sample adequacy was 68.7% and 68.3%, respectively (p=0.889); the sensitivity was 95.1% (95% CI, 83-99%) and 92.1%, respectively (95% CI, 78.7-97.7%) (p=0.898). The EBUS-TB in patients with lymph nodes size <2 cm presented a statistically significant difference in the DA, adequacy and sensitivity compared to c-TB procedure, while there were no significant differences in the DA, adequacy and sensitivity between EBUS-TB and c-TB in patients with lymph node size ‰¥2 cm. The results of our study indicated that the EBUS-TB should be the first-choice procedure for the diagnosis/staging in lung cancer patients with lymph node size <2 cm. In patients with lymph node size ‰¥2 cm, instead, both procedures can be used for the diagnosis/staging of lung cancer.

The sedation plays an important role in the endobronchial ultrasound transbronchial needle aspiration (EBUS-TB) procedure. The sedation can be Minimal (anxiolysis), Moderate (conscious sedation) or Deep. The ACCP guidelines suggest that moderate or deep sedation (DS) is an acceptable approach. In fact, several studies compare moderate versusdeep sedation, but no study has been carried out to compare deep sedation versusminimal. We carried out a retrospective study to compare the Deep versusMinimal sedation (MiS) in patients undergoing EBUS-TB. The primary end point was the diagnostic accuracy. The secondary end points were adequacy and sensitivity. We evaluated the LN size sampling, procedural time, complications and patient tolerance. Thirty-six patients underwent EBUS-TB, 16 under DS and 20 under MiS. The overall diagnostic accuracy for correct diagnosis was 92.9% in DS group and 94.1% in MiS group (p=0.554). Sample adequacy,defined as the percentage of patients with a specific diagnosis by EBUS-TB, was 87.5% (14 of 16) and 85% (17 of 20) for the DS group and MiS group, respectively, (p=0.788); the sensitivity was 92.9% in the DS group (95% CI, 73-100%) and 92.9% in the MiS group (95% CI, 77-100%) (p=0.463). There were no major complications in either group. Minor complications were 4 in MiS and 1 in DS (p=0.355). The patients in the MiS group recalled the procedure more often compared to the other group (p=0.041). The majority of the patients would agree to undergo the same procedure again in the future in both groups (p=0.766). In our experience EBUS-TB performed under MiS has comparable accuracy, adequacy, sensitivity, complications and patient satisfaction to DS, even if the sample was small. Future prospective multicenter studies are needed to confirm our results.

Lateral episiotomy is a widely used procedure, although it is rarely mentioned in the literature and its effects on the pelvic floor are largely unexplored. The purpose of this study is to evaluate the impact of lateral episiotomy on the incidence of urinary incontinence (UI) after vaginal delivery in primiparas. The study design is a prospective cohort study. The primiparas were divided into two groups. The first group consisted of women who gave birth with lateral episiotomy, while the second group included women who gave birth with an intact perineum or with perineal tears of first and second degree. Assessments of UI were performed at 5 and 8 months after childbirth using the International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) questionnaire followed by the stress test. The results revealed no significant differences ( > 0.05) in emergence of stress urinary incontinence (SUI) between the groups at the two time points. There were no statistically significant differences in overall rate of UI, urge urinary incontinence (UUI), or mixed urinary incontinence according to the ICIQ-SF questionnaire. The overall incontinence rate on the first examination was 24% in the episiotomy group and 36% in the perineal laceration group, although the difference was not statistically significant ( = 0.064). On the second examination, rates were similar and without a statistically significant difference. Lateral episiotomy has a neutral effect on the onset of UI in primiparous women in the first year after delivery.

Introduction/BackgroundEpithelial ovarian cancer (EOC), notably high-grade serous EOC (HGS-EOC), is a prevalent and lethal cancer in women. Despite the efficacy of initial treatment involving primary surgical cytoreduction and platinum-based chemotherapy, high relapse rates contribute to poor outcomes. This study leverages single-cell RNA-Seq data to delve into gene expression, immune signatures, and pathways, providing insights into the tumor microenvironment (TME) and immune profile of HGS-EOC.MethodologyThe single-cell RNA-Seq patient cohort comprises 35 samples from 15 patients, collected pre and post neoadjuvant chemotherapy (NACT) at specific sites: the primary site (ovary or nearby tissues), omentum (the most invaded membrane), and peritoneum (the second most invaded). The procedure involves dissociating fresh samples, conducting flow cytometry analysis with a panel of antibodies, and employing Illumina Next-Seq 2000 for single-cell RNA sequencing, carried out by co-investigators at Humanitas Clinical Institute, MilanResultsPreliminary results from analyzing a complete patient, encompassing a primary sample pre-NACT and three metastatic sites post-NACT, indicate a higher prevalence of the stromal component in metastatic samples compared to the primary site. Dimensionality reduction techniques and the ESTIMATE package are utilized to assess TME composition, deriving tumor, immune, and stromal scores from gene expression profiles.ConclusionThe findings underscore the pivotal role of the TME, particularly the stromal component, in tumor progression. While these initial results highlight distinctions in cell composition between primary and metastatic sites, further analyses with additional samples are imperative for a comprehensive understanding of cell behavior throughout disease progression.DisclosuresNoneAbstract 483 Figure 1

Immunotherapy, particularly the use of immune checkpoint inhibitors (ICIs), has shown limited efficacy in treating ovarian cancer (OC), possibly due to diverse T cell infiltration patterns in the tumor microenvironment. This review explores how neoadjuvant chemotherapy (NACT) impacts the immune landscape of OC, focusing on tumor-infiltrating lymphocytes (TILs), PD-1/PD-L1 expression, and their clinical implications. A comprehensive literature search across four databases yielded nine relevant studies. These studies evaluated stromal (sTILs) and intra-epithelial (ieTILs) TILs before and after NACT. sTIL responses varied, impacting prognostic outcomes, and ieTILs increased in some patients without clear survival associations. PD-L1 expression after NACT correlated with improved overall survival (OS), and increases in granzyme B+ and PD-1 correlated with longer progression-free survival (PFS). Remarkably, reduced FoxP3+ TILs post-NACT correlated with better prognosis. NACT often increases sTIL/ieTIL and CD8+ subpopulations, but their correlation with improved PFS and OS varies. Upregulation of co-inhibitory molecules, notably PD-L1, suggests an immunosuppressive response to chemotherapy. Ongoing trials exploring neoadjuvant ICIs and chemotherapy offer promise for advancing OC treatment. Standardized measurements assessing TIL density, location, and heterogeneity are crucial for addressing genetic complexity and immunological heterogeneity in OC.

(1) Background: In 2018 FIGO reclassified tumors confined to the cervix larger than 4 cm as stage IB3. Although concurrent CTRT has been the standard of care and surgery the alternative, optimal management remains controversial due to the lack of direct comparison between surgery and CTRT. (2) Methods: This prospective observational study investigated the efficacy, safety and oncologic outcomes of nerve-sparing laparoscopic radical hysterectomy (nsLRH) for FIGO stage IB3 cervical cancer patients (IB3). From 2009 to 2023, IB3 patients underwent laparoscopic pelvic lymphadenectomies with frozen section analysis, followed by a nsLRH if the lymph nodes were tumor-free. No uterine manipulator was used and the vaginal cuff was sealed before retrieving the specimen. Intermediate-risk patients were under close observation without adjuvant therapy. Outcomes were monitored until 2023. (3) Results: During the study period, 74 IB3 patients were treated. Sixty-eight (91.9%) underwent a nsLRH. A complete resection with negative margins was achieved in all cases. At a median of 68 months of follow-up, the disease-free survival (DFS) rate was 89.7% and the overall survival (OS) rate was 93.1%. The overall complication rate was 23.5% and there were no grade 4–5 complications. (4) Conclusions: In patients with IB3 cervical cancer, a nsLRH is safe and effective. While awaiting the results from ongoing randomized trials, these findings support nsLRH as a viable treatment.

This study provides a comprehensive overview of the role of immunotherapy in the treatment of mismatch repair-deficient (MMRd) endometrial carcinomas. Immunotherapy has emerged as a transformative approach in the treatment of MMRd due to the high mutation rate and subsequent PD-1/PD-L1 overexpression seen in these tumors. This review analyzes the current landscape of existing randomized clinical trials, highlighting the efficacy of immune checkpoint inhibitors (ICIs) like pembrolizumab, avelumab, and dostarlimab. Additionally, the focus extends to the potential of combined therapeutic strategies, such as the integration of ICIs with targeted agents, while also exploring the application of immunotherapy in non-traditional settings beyond advanced or recurrent disease. This includes emerging roles in the adjuvant and neoadjuvant contexts to prevent recurrence and target early-stage disease. These findings underscore the importance of tailoring treatments based on the molecular characteristics of each tumor and paving the way for future advancements in the field of gynecologic oncology. Despite promising results, this article acknowledges the necessity of further research to refine patient selection criteria and explore combination strategies that can overcome resistance mechanisms.