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The aim of this study was to evaluate the diagnostic accuracy and efficiency of p16/ki-67 dual stain in the identification of CIN2+ lesions, in Greek women with ASCUS or LSIL cytology. A total of 200 women, 20 to 60 years old, were enrolled in the study. All samples were cytologically evaluated and performed for p16/ki-67 and high-risk HPV (HR-HPV) test. All patients were referred to colposcopy for biopsy and histological evaluation. Three cervical cancer (CC) screening strategies were designed and the total direct medical costs of the procedures during our clinical trial were evaluated, from a healthcare perspective. HPV 16 as expected was the most common HR-HPV type followed by HPV 31 and HPV 51. The risk for CIN2+ was significantly higher in HPV 16/18 positive cases. p16/ki-67 demonstrated a high sensitivity for CIN2+ identification in both ASCUS and LSIL groups (90.4% and 95%, respectively). HR-HPV test with sensitivity 52.3% and 65.5%, as well as colposcopy with sensitivity 14.3% and 36% respectively in ASCUS and LSIL group, showed inferior results compared to p16/ki-67. The specificity of p16/ki-67 for ASCUS and LSIL was 97.2% and 95.2% respectively, inferior only to colposcopy: 100% and 100%, lacking however statistical significance. HR-HPV test instead, presented the lowest specificity: 76.4% and 71.4% respectively in comparison to the other two methods. From a healthcare perspective, the costs and benefits of the tests implementation for the annual screening and triaging, in three CC screening strategies, were also calculated and discussed. The results of the study indicate that p16/ki-67 is a safe and rapid assay that could be used to detect CIN2+ among women with mild cervical lesions, presenting both high sensitivity and specificity and could minimize the psychological and economic burden of HPV screening.

BackgroundLymph node metastasis is a principal prognostic factor for the treatment of endometrial cancer. Added value of para-aortic lymphadenectomy to only pelvic lymphadenectomy for intermediate/high-risk endometrial cancer patients remains controversial.ObjectiveA systematic review and meta-analysis was performed to assess the impact of combined pelvic and para-aortic lymph node dissection (PPALND) compared to only pelvic lymph node dissection (PLND) on survival outcomes of intermediate and/or high-risk patients.Study designThe systematic review and meta-analysis adhered to the PRISMA guidelines for meta-analyses of interventional studies. Pubmed, Scopus, EMBASE and Cochrane were searched up to April 20, 2018. Included studies were those comparing high-risk endometrial cancer patients that had performed pelvic and para-aortic lymph node dissection (PPALND) vs. only pelvic lymph node dissection (PLND) apart from standard procedure (total hysterectomy with bilateral salpingo-oophorectomy, TAHBSO). Primary outcomes of the study were overall survival and disease-free survival rates. Methodological quality of the included studies was assessed using the ROBINS-I tool. Overall quality of the evidence for the primary and secondary outcomes was evaluated as per GRADE guideline using the GRADE pro GD tool.ResultsThere were 13 studies identified with 7349 patients included. All studies were retrospective observational as no RCTs or prospective studies adhering to inclusion criteria were retrieved. Combined pelvic and para-aortic lymphadenectomy was associated with 46% decreased risk for death (HR 0.54, 95% CI 0.35–0.83, I2 = 62.1%) and 49% decreased risk for recurrence (HR 0.51, 95% CI 0.28–0.93). It was also associated with increased 5-year OS rate (RR 1.13, 95% CI 1.04–0.24, I2 = 57.3%) and increased 5-year DFS rate (RR 1.23, 95% CI 1.14–1.31, I2 = 85.5) compared with only pelvic lymphadenectomy.ConclusionCombined pelvic and para-aortic lymphadenectomy is associated with improved survival outcomes compared with only pelvic lymphadenectomy in women with intermediate/high-risk endometrial cancers. Further prospective studies should be performed.

Bowel preparation traditionally refers to the removal of bowel contents via mechanical cleansing measures. Although it has been a common practice for more than 70 years, its use is based mostly on expert opinion rather than solid evidence. Mechanical bowel preparation in minimally invasive and vaginal gynecologic surgery is strongly debated, since many studies have not confirmed its effectiveness, neither in reducing postoperative infectious morbidity nor in improving surgeons’ performance. A comprehensive search of Medline/PubMed and the Cochrane Library Database was conducted, for related articles up to June 2019, including terms such as “mechanical bowel preparation,” “vaginal surgery,” “minimally invasive,” and “gynecology.” We aimed to determine the best practice regarding bowel preparation before these surgical approaches. In previous studies, bowel preparation was evaluated only via mechanical measures. The identified randomized trials in laparoscopic approach and in vaginal surgery were 8 and 4, respectively. Most of them compare different types of preparation, with patients being separated into groups of oral laxatives, rectal measures (enema), low residue diet, and fasting. The outcomes of interest are the quality of the surgical field, postoperative infectious complications, length of hospital stay, and patients’ comfort during the whole procedure. The results are almost identical regardless of the procedure’s type. Routine administration of bowel preparation seems to offer no advantage to any of the objectives mentioned above. Taking into consideration the fact that in most gynecologic cases there is minimal probability of bowel intraluminal entry and, thus, low surgical site infection rates, most scientific societies have issued guidelines against the use of any bowel preparation regimen before laparoscopic or vaginal surgery. Nonetheless, surgeons still do not use a specific pattern and continue ordering them. However, according to recent evidence, preoperative bowel preparation of any type should be omitted prior to minimally invasive and vaginal gynecologic surgeries.

Background/Objectives: Cytoreduction status is a critical prognostic factor in ovarian cancer, yet preoperative selection of patients suitable for primary debulking surgery and accurate prediction of surgical outcome remain challenging. This study aimed to evaluate the prognostic ability of MRI-based Fagotti score and Peritoneal Cancer Index (PCI) for predicting resectability of peritoneal disease in ovarian cancer patients. Methods: This was a prospective single-center observational study. Patients with suspected primary ovarian cancer who underwent preoperative MRI of the abdomen and pelvis with a dedicated protocol were considered. MRI-based Fagotti score and PCI were determined by two readers independently, using a combination of T2W, Diffusion-Weighted Imaging (DWI), and contrast-enhanced T1W sequences. In cases of discordance, a third radiologist reviewed the scans and consensus was reached. ROC analysis and logistic regression were used to evaluate prognostic performance. The reference standard to predict resectability was optimal cytoreduction defined as residual disease ≤1 cm. Results: Forty-six women with epithelial ovarian cancer (mean age 56.3 ± 2.6 years) who underwent preoperative MRI, followed by laparoscopy and/or laparotomy, were included in the study. Both MRI-based Fagotti score and PCI showed high predictive value for predicting resectability (AUC 0.92 and 0.94, respectively). Optimal cut-offs were ≤6 for Fagotti score and ≤20 for PCI. Patients with scores below these thresholds had >60-fold (Fagotti) and >100-fold (PCI) increased odds for successful primary cytoreduction (p < 0.001). Conclusions: MRI-based Fagotti score and PCI may serve as powerful noninvasive predictors of surgical outcome in ovarian cancer. MRI may reliably guide treatment decisions, reducing unnecessary laparotomies and optimizing patient selection.

Background/Objectives: Cervical cancer (CC) is the fourth most common gynecologic malignancy, disproportionately affecting women in low- and middle-income countries. Despite the effectiveness of HPV vaccination and screening strategies, CC poses a major global health issue, accounting for approximately 94% of annual deaths. Τhis review aims to summarize the current evidence regarding adjuvant treatment indications for surgically treated cervical cancer patients and identify areas where further research is required. Methods: After a literature search, a comprehensive review of the existing guidelines, clinical trials, and cohort studies related to cervical cancer treatment was conducted, focusing on the role of adjuvant therapy in patients classified as at low, intermediate, and high risk for recurrence, who may require no further treatment. Results: Adjuvant therapy is generally unnecessary for low-risk patients, while high-risk patients with lymph node invasion, parametrial involvement, or large tumor size require chemoradiation (CRT). Ιntermediate-risk patients fall into a grey zone, where the necessity of adjuvant therapy is still debatable. Guidelines emphasize the need for individualization in treatment strategies, since, based on the published studies, careful surgery alone and observation can provide similar outcomes to adjuvant therapy. Conclusions: This review emphasizes that achieving monotherapy remains pivotal to optimize outcomes and minimize overtreatment. Definitive adjuvant treatment is indicated for high-risk cases, and intermediate-risk patients may benefit from careful observation following adequate surgical intervention, pointing out the necessity of well-designed clinical trials.

BackgroundTo evaluate the expression of programmed cell death-ligand 1 (PD-L1) and CD8 in high-grade endometrial carcinomas and relate it to several clinicopathological parameters.MethodsOne hundred and one (101) patients with high-grade endometrial carcinomas who were completely surgically staged were included in this study. PD-L1 and CD8 + expression was evaluated by immunohistochemistry.ResultsIn our cohort, 47 women (46.5%) had endometrioid carcinomas and 54 patients (53.5%) were diagnosed with non-endometrioid cancers. In endometrioid carcinomas, there was a significantly higher rate of positivity for PD-L1 expression (p = 0.042) and of intraepithelial CD8 + cell counts (p = 0.004) as opposed to non-endometrioid cancers. There were no significant relationships with any of the other clinicopathological features under study. Univariate and multivariate analysis revealed that only high intraepithelial CD8 + counts (p = 0.01) was associated with longer progression-free survival. Tumors positive for PD-L1 and high intraepithelial CD8 expression were mainly of endometrioid histology, whilst PD-L1-positive/CD8 low and PD-L1-negative/CD8 low tumors were mostly non-endometrioid carcinomas (p = 0.01). PD-L1 negative/CD8 high tumors had the longest progression-free survival (p = 0.032).ConclusionsIn grade 3 endometrial carcinomas, both of endometrioid and non-endometrioid type, high intraepithelial CD8 + counts represent an independent favorable prognostic factor and when related to PD-L1-negative tumors, a longer progression-free survival can be predicted. Immunotherapy could probably be considered for PD-L1-positive/CD8 + high tumors, which were mostly of endometrioid histology.

Background/Objectives: Bisphenols (BPs) and especially bisphenol S (BPS), an analog of bisphenol A (BPA), are widely used and induce oxidative stress, resulting in the inhibition of cell proliferation and induction of apoptosis which all are crucial for reproduction, the progression of pregnancy, and fertility. The present study integrates trophoblastic cells as an in vitro model to provide evidence and investigate the molecular interactions regarding placenta-related pregnancy complications after cytotoxic exposure to BPS. Methods: Human endometrial epithelial adenocarcinoma Ishikawa cell lines and trophoblastic cells were cultured. Cells obtained from the cultures were divided into plates and incubated for 24 h with different concentrations of bisphenol S (BPS). Cell viability was measured using the Countess Automated Cell Counter and the viability of Ishikawa cells was assessed after 48 h and for trophoblasts after 24 h. The effect of siRNA on NANOG expression was evaluated using qRT-PCR. Quantification of DNMT and NANOG was performed by qPCR and the G6PD gene was used as an internal control. Results: Real-time PCR results showed that the expression of the DNMT1 gene varies depending on the concentration of BPS in trophoblastic cells. In Ishikawa cell lines, real-time PCR results showed that DNMT1 gene expression was higher due to cell increase, but the measured fold change did not differ significantly. Data analysis indicated a statistically significant difference between CpDNMT1 in trophoblasts with and without BPS, where higher values were observed in the case of BPS presence (p = 0.019). The largest difference was observed between CpDNMT1 trophoblasts without BPS and CpDNMT1 Ishikawa with BPS (p < 0.001). Silencing the NANOG gene resulted in a reduced expression of DNMT1, while the G6PD gene was still detected. Conclusions: The results of this study highlight the cytotoxic effects of BPS and consequently its effect on trophoblast viability. The results of NANOG-DNMT1 gene expression related to BPS exposure reinforces our understanding of EDC-induced placental dysfunction.

Background/Objectives: This study evaluates the diagnostic performance of DNA methylation testing, alone and in combination with cervical cytology, for high-grade squamous intraepithelial lesion (HSIL) detection. Methods: A prospective study was conducted on 170 high-risk HPV (hr-HPV)-positive women. DNA methylation (QIAsure®) and cervical cytology were performed prior to cervical large loop excision of the transformation zone (LLETZ). Sensitivity, specificity, and area under the curve (AUC) metrics were calculated, including stratified analyses for HPV16/18 and other hr-HPV genotypes. Results: DNA methylation alone achieved a sensitivity of 69.7%, specificity of 79%, and an AUC of 0.796 for HSIL detection. The combination of cervical cytology and DNA methylation improved sensitivity to 94.7%, specificity to 76.3%, and AUC to 0.860. Stratification by HPV genotype revealed that in HPV16/18-positive cases, DNA methylation alone reached an AUC of 0.790, while the combination with cytology significantly enhanced performance to 0.917. DNA methylation alone demonstrated an AUC of 0.744 for other hr-HPV types, and the combined approach achieved an AUC of 0.849. Specificity for the combined approach was notably higher in HPV16/18-positive women (88.9%) than in other hr-HPV cases (72.4%), whereas the sensitivity of the combined approach was significantly higher in both groups (94.5% vs. 95%, respectively). Conclusions: The integration of DNA methylation with cervical cytology significantly enhances diagnostic accuracy for CIN2+ lesions, especially in HPV16/18-positive cases. However, the comparatively lower AUC and specificity observed in other hrHPV types suggest the need for further optimization to enhance accuracy in non-16/18 infections. These findings support the integration of methylation-based testing with cytology as a valuable triage strategy for improving cervical cancer screening and patient management.

Background Uterine sarcomas consist a heterogeneous group of mesenchymal gynecological malignancies with unclear therapeutic recommendations and unspecific but poor prognosis, since they usually metastasize and tend to recur very often, even in early stages. Methods We retrospectively analyzed all female patients with uterine sarcomas treated in our institution over the last 17 years. Clinico-pathological data, treatments and outcomes were recorded. Kaplan-Meier curves were plotted and time-to-event analyses were estimated using Cox regression. Results Data were retrieved from 61 women with a median age of 53 (range: 27–78) years, at diagnosis. Fifty-one patients were diagnosed with leiomyosarcoma (LMS), 3 with high grade endometrial stromal sarcoma (ESS), 5 with undifferentiated uterine sarcoma (UUS), 1 with Ewing sarcoma (ES) and 1 with Rhabdomyosarcoma (RS). 24 cases had stage I, 7 stage II, 14 stage III and 16 stage IV disease. Median disease-free survival (DFS) in adjuvant approach was 18.83 months, and median overall survival (OS) 31.07 months. High mitotic count (> 15 mitoses) was significantly associated with worse OS ( P  < 0.001) and worse DFS ( P  = 0.028). Conclusions Mitotic count appears to be independent prognostic factor while further insights are needed to improve adjuvant and palliative treatment of uterine sarcomas.

Endometriosis is a common benign gynecological condition defined as the presence of endometrial tissue in tissues outside the uterine cavity. Apart from the common sites of endometriosis, rare sites other have also been reported including the liver, the thoracic cavity, the muscles, nerves, and more rarely in a patent Nuck canal. We aim to evaluate the clinical presentation, diagnostic features, and management of the Nuck endometriosis. A meticulous search of three electronic databases was performed until May 2020 for articles reporting cases of Nuck endometriosis. A total of 36 patients from 20 studies were analyzed. Median age of patients was 36 years with 33 women being of reproductive age. A right-sided lesion was identified in 30 cases (83.3%), while all patients suffer from a groin mass with cyclic pain in a proportion of 22%. All the patients finally underwent surgery for investigation of the lesion and fixation of the defect. Five cases of malignancy were detected at final pathology. All of them were alive with a median reported overall survival of 37 months. Nuck endometriosis should be included in the differential diagnosis of female patients with groin swelling. An evaluation by a gynecologist is important when endometriosis is suspected.