Enhancing Ovarian Tumor Diagnosis: Performance of Convolutional Neural Networks in Classifying Ovarian Masses Using Ultrasound Images.

Background/Objectives: This study aims to create a strong binary classifier and evaluate the performance of pre-trained convolutional neural networks (CNNs) to effectively distinguish between benign and malignant ovarian tumors from still ultrasound images. Methods: The dataset consisted of 3510 ultrasound images from 585 women with ovarian tumors, 390 benign and 195 malignant, that were classified by experts and verified by histopathology. A 20% to80% split for training and validation was applied within a k-fold cross-validation framework, ensuring comprehensive utilization of the dataset. The final classifier was an aggregate of three pre-trained CNNs (VGG16, ResNet50, and InceptionNet), with experimentation focusing on the aggregation weights and decision threshold probability for the classification of each mass. Results: The aggregate model outperformed all individual models, achieving an average sensitivity of 96.5% and specificity of 88.1% compared to the subjective assessment's (SA) 95.9% sensitivity and 93.9% specificity. All the above results were calculated at a decision threshold probability of 0.2. Notably, misclassifications made by the model were similar to those made by SA. Conclusions: CNNs and AI-assisted image analysis can enhance the diagnosis and aid ultrasonographers with less experience by minimizing errors. Further research is needed to fine-tune CNNs and validate their performance in diverse clinical settings, potentially leading to even higher sensitivity and overall accuracy.

Diaphragmatic stripping in epithelial ovarian cancer at first diagnosis: Impact on morbidity and survival outcomes.

OBJECTIVES: Diaphragmatic stripping is a standard procedure that is performed in a significant proportion of patients undergoing surgical cytoreduction for advanced ovarian cancer. The objective of the present study is to evaluate morbidity and survival outcomes among patients offered diaphragmatic surgery for primary diagnosed optimally resected ovarian cancer. STUDY DESIGN: We conducted a retrospective cohort study, identifying patients that were offered surgery between 2016 and 2021 for primary diagnosis of ovarian cancer. Cases that had diaphragmatic stripping or partial diaphragmatic resection were selected and compared to cases that did not require this procedure. Kaplan-Meier and Cox-regression analyses were applied to evaluate survival outcomes. RESULTS: Overall, 61 patients that had diaphragmatic stripping were identified. Severe postoperative complications (Clavien-Dindo 3 + ) were noted in 19 patients (31 %). Survival analyses denoted that the stage of the disease at the time of diagnosis, as well as the timing of the surgical procedure (PDS vs IDS) and the completion of tumor debulking were factors that significantly affected the recurrence free and overall survival of patients. Severe postoperative morbidity was a significant predictor of the overall survival. Multivariate cox-regression analysis that was adjusted for the stage of the disease revealed that preoperative pleural effusion, optimal (compared to complete) tumor resection and the occurrence of postoperative complications significantly affected the overall survival of patients. Compared to patients that did not have diaphragmatic surgery, patients submitted to diaphragmatic stripping or resection had improved progression free and overall survival rates, irrespective of the stage of the disease at diagnosis or the adequacy of resection status. CONCLUSIONS: Diaphragmatic surgery is feasible in advanced ovarian cancer patients with acceptable morbidity that mainly refers to postoperative pleural effusion. Its positive impact on patients' survival requires further investigation.

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.

Application of Biomarkers in Obese Infertile Women: A Genetic Tool for a Personalized Treatment.

This study investigates links between CART and leptin gene expression, FSH receptor Asn680Ser polymorphism, and reproductive hormones in morbidly obese patients under 40 years old, facing infertility, and undergoing bariatric surgery. A total of 29 women were included in this study. A hormonal profile along with detection of CART and leptin gene expression was evaluated before and after bariatric surgery. Additionally, the presence or absence of Asn680Ser of the FSHR gene was studied. Following bariatric surgery, a mean reduction in BMI (16.03 kg/m2) was observed in all women. FSH levels preoperatively varied significantly among genotypes, with medians of 8.1, 9.5, and 10.3 for individuals without polymorphism, heterozygotes, and homozygotes, respectively (p = 0.0408). Post surgery, marginal differences in FSH levels were observed (5.8, 7.1, and 8.2, respectively) (p = 0.0356). E2 and LH levels exhibited no significant genotype-based differences pre and post surgery. Presurgical E2 levels were 29.6, 29.8, and 29.6, respectively (p = 0.91634), while postsurgical levels were 51.2, 47.8, and 47 (p = 0.7720). LH levels followed similar patterns. Our findings highlight bariatric surgery's positive impact on BMI reduction and its potential connection to genetic markers, hormones, and infertility. This suggests personalized treatments and offers a valuable genetic tool for better fertility outcomes in obese individuals.

Splenectomy as Part of Maximal-Effort Cytoreductive Surgery in Advanced Epithelial Ovarian Cancer.

INTRODUCTION: A splenectomy is frequently performed during debulking surgery for advanced ovarian cancer. Its impact on perioperative and survival outcomes remains questionable as current evidence is conflicting. In the present study, we sought to determine the factors that affect survival rates in ovarian cancer patients that undergo a splenectomy as part of maximal-effort cytoreduction. PATIENTS AND METHODS: A retrospective chart review was conducted that included all epithelial ovarian cancer patients that had surgical cytoreduction for advanced epithelial ovarian cancer. Differences among splenectomized and non splenectomized patients were evaluated as well as the impact of known risk factors on survival outcomes of splenectomized patients. RESULTS: Overall, 245 patients were identified and 223 were included in the present series, of whom 91 had a splenectomy. Recurrence rates as well as death rates were comparable among splenectomized and non-splenectomized patients; however, both the disease-free survival (log-rank = 0.001), as well as the overall survival of splenectomized patients (log-rank = 0.006), was shorter. Thrombotic events as well as rates of pulmonary embolism were comparable. Sepsis was more common among splenectomized patients. The site of splenic metastases did not influence patients' survival. Among splenectomized patients, those offered primary debulking had longer progression-free survival (log-rank = 0.042), although their overall survival did not differ compared to patients submitted to interval debulking. Complete debulking significantly improved the overall survival compared to optimal debulking (log-rank = 0.047). Splenectomized patients that developed sepsis had worse overall survival (log-rank = 0.005). DISCUSSION: The findings of our study support the feasibility of splenectomy in advanced epithelial ovarian cancer; however, its impact on patients' survival is considerable. Therefore, every effort should be made to avoid splenic injury which will result in unintended splenectomy for non-oncological reasons.

Preventing postpartum hemorrhage: A network meta-analysis on routes of administration of uterotonics.

1. OBJECTIVE: To perform a network meta-analysis to specify the route of administration that maximises the effectiveness of each of the available prophylactic uterotonics without increasing the risk for side effects. 2. DATA SOURCES: Literature searches on 12th September 2022 included: CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. The reference lists of the retrieved study records were also searched. 3. STUDY ELIGIBILITY CRITERIA: Population: Randomized controlled trials involving women in the third stage of labour after a vaginal or caesarean delivery in hospital or community settings. INTERVENTIONS: Systemically administered prophylactic uterotonics of any route and dose for primary postpartum hemorrhage prevention. Comparison: Any other prophylactic uterotonic, or a different route or dose of a given uterotonic, or placebo, or no treatment. Outcomes (primary): postpartum hemorrhage ≥ 500 mL and ≥ 1000 mL. 4. STUDY APPRAISAL AND SYNTHESIS METHODS: Risk of bias and trustworthiness assessments were performed, according to Cochrane's guidance. Direct, indirect and network meta-analyses were conducted, and results were summarized either as risk ratio or mean difference with 95% confidence intervals for dichotomous and continuous outcomes, respectively. The certainty of generated evidence was assessed according to the GRADE approach. Cumulative probabilities were calculated and the surface under the cumulative ranking curve was used to create a ranking of the available drugs. 5. RESULTS: One hundred eighty-one studies involving 122,867 randomised women were included. Most studies were conducted in hospital settings in lower-middle income countries and involved women delivering vaginally. When compared with intramuscular oxytocin, carbetocin (RR 0.58, 95 % CI 0.40-0.84) and oxytocin (RR 0.75, 95 % CI 0.59-0.97) by an intravenous bolus, and intramuscular ergometrine plus oxytocin combination (RR 0.71, 95 % CI 0.56-0.91) are probably more effective in preventing primary postpartum hemorrhage. Intramuscularly administered oxytocin and carbetocin by an intravenous bolus have a favourable side effects profile. 6. CONCLUSIONS: Generated evidence was generally moderate and global inconsistency was low. Carbetocin and oxytocin by an intravenous bolus, and intramuscular ergometrine plus oxytocin combination are probably the top uterotonics for primary postpartum hemorrhage prevention. Large scale studies exploring different routes of administration for available prophylactic uterotonics, and women's views should be conducted.

Maternal and neonatal outcomes following magnesium sulfate in the setting of chorioamnionitis: a meta-analysis.

PURPOSE: Magnesium sulfate (MgSO4) has been widely used in obstetrics as a mean to help decrease maternal and neonatal morbidity in various antenatal pathology. As a factor, it seems to regulate immunity and can, thus, predispose to infectious morbidity. To date, it remains unknown if its administration can increase the risk of chorioamnionitis. In the present meta-analysis, we sought to accumulate the available evidence. METHODS: We systematically searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL, and Google Scholar databases in our primary search along with the reference lists of electronically retrieved full-text papers. RESULTS: Eight studies were included that investigated the incidence of chorioamnionitis among parturient that received MgSO4 and control patients. Magnesium sulfate was administered in 3229 women and 3330 women served as controls as they did not receive MgSO4. The meta-analysis of data revealed that there was no association between the administration of magnesium sulfate and the incidence of chorioamnionitis (OR 0.98, 95% CI 0.73, 1.32). Rucker's analysis revealed that small studies did not significantly influence the statistical significance of this finding (OR 1.12, 95% CI 0.82, 1.53). Trial sequential analysis revealed that the required number to safely interpret the primary outcome was not reached. Two studies evaluated the impact of MgSO4 in neonates delivered in the setting of chorioamnionitis. Neither of these indicated the presence of a beneficial effect in neonatal morbidity, including the risk of cerebral palsy, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, stillbirth, or neonatal death. CONCLUSION: Current evidence indicates that magnesium sulfate is not associated with an increased risk of maternal chorioamnionitis. However, it should be noted that its effect on neonatal outcomes of offspring born in the setting of chorioamnionitis might be subtle if any, although the available evidence is very limited.

N-Terminal Pro-B Type Natriuretic Peptide as a Predictive Biomarker of Bronchopulmonary Dysplasia or Death Due to Bronchopulmonary Dysplasia in Preterm Neonates: A Systematic Review and Meta-Analysis.

BACKGROUND: Emerging evidence suggests the clinical utility of N terminal pro B type natriuretic peptide (NT-proBNP) in multiple cardiac and pulmonary abnormalities both in adult and pediatric populations. To date, however, there is no consensus regarding its efficacy for the prediction and severity of bronchopulmonary dysplasia in premature neonates. The objective of the present meta-analysis was to determine differences in NT-proBNP among neonates that develop BPD or die from BPD and to evaluate if there is relative information on the diagnostic accuracy of the method. METHODS: We conducted a systematic search according to the PRISMA guidelines and looked into Medline (1966-2023), Scopus (2004-2023), Clinicaltrials.gov (2008-2023), EMBASE (1980-2023), Cochrane Central Register of Controlled Trials CENTRAL (1999-2022) and Google Scholar (2004-2023) together with the reference lists from included studies. The potential risk of bias encountered in our study was evaluated using the QUADAS -2 tool. Finally, a total of 9 studies met the eligibility criteria, comprising 1319 newborns, from which 397 developed BPD and 922 were unaffected controls. RESULTS: The results retrieved from our meta-analysis showed that newborns suffering from BPD had notably elevated NT-proBNP levels after birth when compared with healthy neonates (SMD 2.57, 95% CI 0.41, 4.72). The summary effect of the AUC meta-analysis showed that NT-proBNP was very accurate in detecting neonates at risk of developing severe BPD or dying from the disease (AUC -0.16, 95% CI -0.23, -0.08). No studies reported data relevant to the sensitivity and/or specificity of the method in diagnosing BPD. CONCLUSION: Serum NT-proBNP levels represent a potential future biomarker with great diagnostic validity for the prediction of BPD complicating preterm deliveries. The limited amount of studies included and the significant variations in cutoff values and timing of measurement still restrict the application of NT-proBNP as an established clinical biomarker for BPD. The design of larger prospective studies will provide a more representative number of participants and will address the discrepancies in existing literature.

Evaluation of IOTA-ADNEX Model and Simple Rules for Identifying Adnexal Masses by Operators with Varying Levels of Expertise: A Single-Center Diagnostic Accuracy Study.

Objectives The discrimination of ovarian lesions presents a significant problem in everyday clinical practice with ultrasonography appearing to be the most effective diagnostic technique. The aim of our study was to externally evaluate the performance of different diagnostic models when applied by examiners with various levels of experience. Methods This was a diagnostic accuracy study including women who were admitted for adnexal masses, between July 2018 and April 2021, to a Greek tertiary oncology center. Preoperatively sonographic data were evaluated by an expert gynecologist, a 6 th and a 1 st year gynecology resident, who applied the International Ovarian Tumor Analysis (IOTA) Simple Rules (SR) and Assessment of Different NEoplasias in the adneXa (ADNEX) model to discriminate between benign and malignant ovarian tumors. The explant pathology report was used as the reference diagnosis. Kappa statistics were used for the investigation of the level of agreement between the examined systems and the raters. Results We included 66 women, 39 with benign and 27 with malignant ovarian tumors. ADNEX (with and without "CA-125") had high sensitivity (96-100%) when applied by all raters but a rather low specificity (36%) when applied by the 1st year resident. SR could not be applied in 6% to 17% of the cases. It had slightly lower sensitivity, higher specificity, and higher overall accuracy, especially when applied by the 1st year resident (61% vs. 92%), compared to ADNEX. Conclusion Both ADNEX and SR can be utilized for screening in non-oncology centers since they offer high sensitivity even when used by less experienced examiners. In the hands of inexperienced examiners, SR appears to be the best model for assessing ovarian lesions.

Advantages and Limitations of Ultrasound as a Screening Test for Ovarian Cancer.

Ovarian cancer (OC) is the seventh most common malignancy diagnosed among women, the eighth leading cause of cancer mortality globally, and the most common cause of death among all gynecological cancers. Even though recent advances in technology have allowed for more accurate radiological and laboratory diagnostic tests, approximately 60% of OC cases are diagnosed at an advanced stage. Given the high mortality rate of advanced stages of OC, early diagnosis remains the main prognostic factor. Our aim is to focus on the sonographic challenges in ovarian cancer screening and to highlight the importance of sonographic evaluation, the crucial role of the operator΄s experience, possible limitations in visibility, emphasizing the importance and the necessity of quality assurance protocols that health workers have to follow and finally increasing the positive predictive value. We also analyzed how ultrasound can be combined with biomarkers (ex. CA-125) so as to increase the sensitivity of early-stage OC detection or, in addition to the gold standard examination, the CT (Computed tomography) scan in OC follow-up. Improvements in the performance and consistency of ultrasound screening could reduce the need for repeated examinations and, mainly, ensure diagnostic accuracy. Finally, we refer to new very promising techniques such as liquid biopsies. Future attempts in order to improve screening should focus on the identification of features that are unique to OC and that are present in early-stage tumors.

Ovarian Cancer and Glutamine Metabolism.

Cancer cells are known to have a distinct metabolic profile and to exhibit significant changes in a variety of metabolic mechanisms compared to normal cells, particularly glycolysis and glutaminolysis, in order to cover their increased energy requirements. There is mounting evidence that there is a link between glutamine metabolism and the proliferation of cancer cells, demonstrating that glutamine metabolism is a vital mechanism for all cellular processes, including the development of cancer. Detailed knowledge regarding its degree of engagement in numerous biological processes across distinct cancer types is still lacking, despite the fact that such knowledge is necessary for comprehending the differentiating characteristics of many forms of cancer. This review aims to examine data on glutamine metabolism and ovarian cancer and identify possible therapeutic targets for ovarian cancer treatment.

Prenatal Identification of a Novel Mutation in the MCPH1 Gene Associated with Autosomal Recessive Primary Microcephaly (MCPH) Using Next Generation Sequencing (NGS): A Case Report and Review of the Literature.

BACKGROUND: MCPH1 is known as the microcephalin gene (OMIM: *607117), of which the encoding protein is a basic regulator of chromosome condensation (BCRT-BRCA1 C-terminus). The microcephalin protein is made up of three BCRT domains and conserved tandem repeats of interacting phospho-peptides. There is a strong connection between mutations of the MCPH1 gene and reduced brain growth. Specifically, individuals with such mutations have underdeveloped brains, varying levels of mental retardation, delayed speech and poor language skills. METHODS: In this article, a family with two affected fetuses presenting a mutation of the MCPH1 gene is reported. During the first trimester ultrasound of the second pregnancy, the measure of nuchal translucency was increased (NT = 3.1 mm) and, therefore, the risk for chromosomal abnormalities was high. Chorionic villi sampling (CVS) was then performed. Afterwards, fetal karyotyping and Next Generation Sequencing were carried out. Afterwards, NGS was also performed in a preserved sample of the first fetus which was terminated due to microcephaly. RESULTS: In this case, the fetuses had a novel homozygous mutation of the MCPH1 gene (c.348del). Their parents were heterozygous for the mutation. The fetuses showed severe microcephaly. Because of the splice sites in introns, this mutation causes the forming of dysfunctional proteins which lack crucial domains of the C-terminus. CONCLUSION: Our findings portray an association between the new MCPH1 mutation (c.348del) and the clinical features of autosomal recessive primary microcephaly (MCPH), contributing to a broader spectrum related to these pathologies. To our knowledge, this is the first prenatal diagnosis of MCPH due to a novel MCPH1 mutation.

Cancer Treatment and Immunotherapy during Pregnancy.

BACKGROUND/AIM: Immunotherapy has, in recent years, witnessed an expansion in its indications for the treatment of cancer. Coupled with the fact that, nowadays, even more women choose to postpone parenthood, thus increasing their chances of having some kind of malignancy during pregnancy, more and more women are eligible for receiving immunotherapy during this period of their lives. The cases of cancer diagnosed during pregnancy is an ever-increasing trend nowadays. MATERIALS AND METHODS: The oncologists and clinicians treating women often face a range of ethical and therapeutic dilemmas due to the particularity of the patient's conditions. The primary concern is the protection of the mother, firstly, and then the fetus (through adjustments to the various treatment regimens) if possible. RESULTS AND CONCLUSIONS: Oncological drugs, radiation therapy, surgery, or a combination of all the above methods are selected, depending on the case. In this project, we studied the oncology drugs used for various types of gestational cancer, their appropriateness and timing, as well as their possible effects on the parent and embryo upon their administration. Various studies have shown that the administration of oncological drugs should be postponed until at least after the first trimester of pregnancy.

The Significance of Peritoneal Washing as a Prognostic Indicator for Ovarian Cancer Patients.

BACKGROUND/AIM: During ovarian cancer (OC) debulking surgery, the surgeon can examine the peritoneal cavity for malignant cancer cells with peritoneal washing (PW) cytology. The goal of this study was to examine the significance of peritoneal washing as a prognostic indicator for ovarian cancer patients. PATIENTS AND METHODS: Information considering the prognostic factors of OC and their impact in PW's result was collected, compared, and combined. RESULTS: Omental metastasis, tumor type, tumor invasion, tumor size, tumor grade/ stage, tumor's cytoreduction, and recurrence affect both the peritoneal washing result and the patient's prognosis. The correlation that most of the above factors have with a positive PW and dismal prognosis, led us to the assumption that PW has a significance as a prognostic indicator. CONCLUSION: The significance of PW as a prognostic indicator remains an assumption.

p16/Ki-67 Dual Staining Is a Reliable Biomarker for Risk Stratification for Patients With Borderline/Mild Cytology in Cervical Cancer Screening.

BACKGROUND/AIM: To evaluate p16/Ki-67 dual-staining performance for detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in the management of women with minor cervical abnormalities. PATIENTS AND METHODS: All 759 enrolled patients were tested for cytology, high-risk human papillomavirus (HR-HPV) and dual p16/Ki-67 staining. RESULTS: Positivity rates for HR-HPV and dual staining increased as dysplasia was worsened from non-CIN (37.6% and 0%) to CIN1 (62.5% and 1.6%) and CIN2+ (98.7% and 97.3%), respectively. HPV18 and HPV16 exhibited the highest odds ratios (53.16 and 11.31) in the CIN2+ group. Both p16/Ki-67 dual staining and HR-HPV presented similar sensitivities (97.3% and 98.7%, respectively) for CIN2+ detection. Dual staining specificity, however, was 99.3%, significantly higher compared to HR-HPV testing (52.2%). The utility of dual staining was evaluated in different screening strategies and appeared to reduce the number of colposcopies required for the detection of CIN2+ cases. CONCLUSION: p16/Ki-67 dual-staining cytology is a surrogate triage biomarker in cytology-based screening programs, with high performance for efficient risk stratification of women with mild cervical abnormalities.

A Brief Overview of Oncogenes and Signal Transduction Pathways in Gynecological Cancer.

Gynecological cancer is the cancer that originates in the female reproductive system. According to the anatomical location of the cancer, it is distinguished into cervical, uterine, vaginal, ovarian, and vulvar cancer. Oncogenes and tumor catalytic genes play a key role in the genesis and development of gynecological cancer. This article presents the signaling pathways and expression of oncogenes that take place in the carcinogenesis of the female reproductive system.

The p16/ki-67 assay is a safe, effective and rapid approach to triage women with mild cervical lesions.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The Conundrum of Prematurity and Pregnancy Outcomes after Fertility Sparing Treatment Modalities for Early Stage Cervical Cancer: A Systematic Review of the Literature.

Advances in modern medicine have allowed patients with early stage cervical cancer (stages Ia - IIai) to preserve their fertility with oncologic efficacy comparable to previous radical treatments. A variety of conservative-fertility sparing procedures, also known as Fertility Sparing Surgeries (FSS) have been proposed. The present review aimed to provide the current evidence on obstetric outcomes and the prematurity rates as well as to discuss the management modalities of these high-risk pregnancies. Our review of the literature included 3042 women with early cervical cancer, of whom 2838 underwent FSS (204 excluded for oncologic reasons). Almost half of these patients attempted to become pregnant and about two thirds of them achieved at least one pregnancy either spontaneously or with the help of Assisted Reproduction Technologies. Data revealed that 63.9% of these pregnancies resulted in live births, whereas 37.6% of them were preterm. The main cause of preterm births in this subpopulation is the postoperative cervical length restriction that consequently leads to cervical incompetence and ascending infections that eventually lead to (clinical or subclinical) chorioamnionitis. Radical operations such as ART, VRT and MIRT presented with higher prematurity rates. The lack of standardized protocols for the management of pregnancies after FSS precluded reaching to firm results with regards to the efficacy of them in achieving favourable obstetrical outcomes. Further large volume studies are warranted with the intent to acquire standardized guidelines for pregnancies achieved after FSS for early stage cervical cancer.

Placental Mesenchymal Dysplasia: Ultrasound Characteristics and Diagnostic Pitfalls.

Placental mesenchymal dysplasia (PMD) is a rare, benign developmental anomaly with a reported prevalence of 0.02% (Arizawa and Nakayama, 2002). It is characterized by placentomegaly with multiple cystic lesions of the stem villi and vascular anomalies (Pawoo and Heller, 2014). Early detection of PMD has been described during routine prenatal ultrasound (Vaisbuch et al., 2009). The sonographic characteristics of PMD include increased placental thickness and multiple cystic areas within the placenta with either an absence of blood flow or with low venous Doppler signals (Vaisbuch et al., 2009). The differential diagnosis of multicystic placental lesions with the presence of a live fetus include partial molar pregnancy, multiple hematomas, chorioangioma Beckwith-Wiedemann syndrome and PMD. Chorioangiomas are well circumscribed masses within the placenta and they are characterized by the presence of a single feeding vessel with the same pulse rate as the umbilical cord (Zalel et al., 2002). Invasive prenatal testing is required for the exclusion of partial molar pregnancy and Beckwith-Wiedemann Syndrome (Vaisbuch et al., 2009). Definitive diagnosis of PMD is based on the pathologic examination of the placenta. Histology reveals aneurysm or dilated blood vessels that may be thrombosed. The stem villi are edematous and enlarged with thick-walled vessels, without trophoblastic proliferation (Pawoo and Heller, 2014). This case report highlights the significance of the early detection of PMD, illustrates the pitfalls in differential diagnosis and provides valuable insights regarding PMD management in a clinical setting.

Efficacy and safety of colistin loading dose: a meta-analysis.

OBJECTIVES: Colistin represents a polypeptide used for the treatment of MDR microorganisms, although the optimal dosing strategy is under investigation. The present meta-analysis aims to determine whether the administration of a colistin loading dose in patients receiving high-dose maintenance regimens changes the rates of treatment success and the risk of nephrotoxicity. METHODS: Medline, Scopus, CENTRAL, Clinicaltrials.gov and Google Scholar were systematically searched from inception to 18 November 2019. Studies were considered eligible if they reported clinical outcomes among patients receiving high-dose colistin therapy with and without the administration of a loading dose. Meta-analysis was performed by fitting a random-effects model. RESULTS: Eight (three prospective and five retrospective cohort) studies were included, comprising 1115 patients. The administration of a colistin loading dose was associated with significantly higher microbiological [risk ratio (RR) = 1.23, 95% CI = 1.10-1.39] but not clinical (RR = 1.04, 95% CI = 0.87-1.24) success. No significant associations were calculated for nephrotoxicity (RR = 1.31, 95% CI = 0.90-1.91) and mortality (RR = 1.03, 95% CI = 0.82-1.29) risk. The results remained stable after adjustments for small sample size, credibility ceilings, publication bias and risk of bias. CONCLUSIONS: Observational evidence suggests that the administration of a colistin loading dose in patients receiving high maintenance dosage regimens is significantly associated with higher rates of microbiological response, but does not change clinical cure, mortality or nephrotoxicity risk. The dosing regimen that would provide the optimal balance between treatment efficacy and safety needs to be determined by future randomized controlled trials.