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.

Programmed Death Ligand 1: Unveiling its Impact on Endometrial Carcinogenesis.

Endometrial cancer is a commonly diagnosed gynecological malignancy presenting an increasing incidence worldwide. The immune response plays a crucial role in the mechanisms underlying carcinogenesis and the progression of tumors. In recent times, there has been a discernible surge in the acknowledgment of the importance of programmed death ligand 1 (PDL1) in evading the immunological response of the host and promoting the growth of malignancies. The primary aim of this review is to consolidate the existing corpus of evidence pertaining to the role of PDL1 in the etiology and progression of endometrial cancer and investigate the molecular mechanisms involved in the expression of PDL1 in cells impacted by endometrial cancer. Finally, the association between PDL1 expression and clinical outcomes, as well as the potential therapeutic uses of targeting the PDL1 pathway are being analyzed.

Differences in cervical length during the second trimester among normal weight, overweight and obese women: A systematic review and meta-analysis.

Objective: Maternal obesity has been previously linked to increased risk of preterm birth; however, the actual pathophysiology behind this observation remains unknown. Cervical length seems to differentiate among overweight, obese and extremely obese patients, compared to normal weight women. However, to date the actual association between body mass index and cervical length remains unknown. In this systematic review, accumulated evidence is presented to help establish clinical implementations and research perspectives. Methods: We searched Medline, Scopus, the Cochrane Central Register of Controlled Trials CENTRAL, Google Scholar, and Clinicaltrials.gov databases from inception till February 2023. Observational studies that reported on women undergone ultrasound assessment of their cervical length during pregnancy were included, when there was data regarding their body mass index. Statistical meta-analysis was performed with RStudio. The quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). Results: Overall, 20 studies were included in this systematic review and 12 in the meta-analysis. Compared to women with normal weight, underweight women were not associated with increased risk of CL < 15 mm or < 30 mm and their mean CL was comparable (MD -1.51; 95% CI -3.07, 0.05). Overweight women were found to have greater cervical length compared to women with normal weight (MD 1.87; 95% CI 0.52, 3.23) and had a lower risk of CL < 30 mm (OR 0.65; 95% CI 0.47, 0.90). Conclusion: Further research into whether BMI is associated with cervical length in pregnant women is deemed necessary, with large, well-designed, prospective cohort studies with matched control group.

MicroRNAs Can Influence Ovarian Cancer Progression by Dysregulating Integrin Activity.

Ovarian cancer is a deadly disease that affects thousands of women worldwide. Integrins, transmembrane receptors that mediate cell adhesion and signaling, play important roles in ovarian cancer progression, metastasis, and drug resistance. Dysregulated expression of integrins is implicated in various cellular processes, such as cell migration, invasion, and proliferation. Emerging evidence suggests that microRNAs (miRNAs) can regulate integrin expression and function, thus affecting various physiological and pathological processes, including ovarian cancer. In this article, we review the current understanding of integrin-mediated cellular processes in ovarian cancer and the roles of miRNAs in regulating integrins. We also discuss the therapeutic potential of targeting miRNAs that regulate integrins for the treatment of ovarian cancer. Targeting miRNAs that regulate integrins or downstream signaling pathways of integrins may provide novel therapeutic strategies for inhibiting integrin-mediated ovarian cancer progression.

Bladder Cancer during Pregnancy: A Review of the Literature.

Bladder malignancy represents the fourth most common cancer in men and the eighth in women in the western world. Women under 75 years of age have a risk of 0.5-1% of developing bladder cancer. The diagnosis usually occurs between 65 and 70 years of age, whereas the mortality rate for women varies from 0.5 to 4 per 100,000 every year. Nulliparous women present a greater risk than women who have given birth. The risk is further decreased when parity increases. Theoretically, hormonal changes occurring during pregnancy play a protective role. Smoking and occupational exposure to specific chemicals are the most common risk factors of bladder cancer. Other risk factors such as chronic urinary tract inflammation, cyclophosphamide, radiotherapy, and familial correlation have been reported. The aim of this review is to highlight a rare combination, which is the co-existence of bladder malignancy and pregnancy. We present thirteen different cases of women who were diagnosed with malignant bladder tumors during their pregnancy. A review of the literature was conducted, focusing on the unspecific symptoms, possible diagnostic tools, and suitable treatment modalities. The management of bladder cancer in pregnancy is a challenging process. The fragile balance between the possible complications of pregnancy and maternal health is yet to be discussed.

sFLT1, PlGF, the sFLT1/PlGF Ratio and Their Association with Pre-Eclampsia in Twin Pregnancies-A Review of the Literature.

Twin pregnancies demonstrate a 2-3-fold higher chance of developing PE compared to singletons, and recent evidence has demonstrated that the sFLT1/PIGF ratio is strongly associated with PE, adverse pregnancy outcomes, as well as imminent deliveries due to PE complications. The primary objective of this systematic review was to summarise the available data on the levels of sFLT1, PlGF and their ratios in twin pregnancies and to investigate their association with the development of PE, adverse pregnancy outcomes and the timing of the delivery. A systematic search of Ovid Embase, Web of Science, Science Direct, PubMed, Ovid Medline, Google Scholar and CINAHL was carried out. sFLT1 levels and the sFLT1/PIGF ratio appeared higher in twins compared to singleton pregnancies, especially in the third trimester, while PlGF levels appeared higher up until the third trimester, with their values showing no difference or being even lower than in singletons thereafter. The sFLT1/PIGF ratio has been reported to be an independent marker of adverse outcomes related to pre-eclampsia and is associated with the mean time until delivery in an inverse manner. Further research is required in order to establish the optimal sFLT1/PIGF cut-off values and to stratify the risk of adverse outcomes in twin pregnancies.

Liver replacement therapy with extracorporeal blood purification techniques current knowledge and future directions.

Clinically, it is highly challenging to promote recovery in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). Despite recent advances in understanding the underlying mechanisms of ALF and ACLF, standard medical therapy remains the primary therapeutic approach. Liver transplantation (LT) is considered the last option, and in several cases, it is the only intervention that can be lifesaving. Unfortunately, this intervention is limited by organ donation shortage or exclusion criteria such that not all patients in need can receive a transplant. Another option is to restore impaired liver function with artificial extracorporeal blood purification systems. The first such systems were developed at the end of the 20th century, providing solutions as bridging therapy, either for liver recovery or LT. They enhance the elimination of metabolites and substances that accumulate due to compromised liver function. In addition, they aid in clearance of molecules released during acute liver decompensation, which can initiate an excessive inflammatory response in these patients causing hepatic encephalopathy, multiple-organ failure, and other complications of liver failure. As compared to renal replacement therapies, we have been unsuccessful in using artificial extracorporeal blood purification systems to completely replace liver function despite the outstanding technological evolution of these systems. Extracting middle to high-molecular-weight and hydrophobic/protein-bound molecules remains extremely challenging. The majority of the currently available systems include a combination of methods that cleanse different ranges and types of molecules and toxins. Furthermore, conventional methods such as plasma exchange are being re-evaluated, and novel adsorption filters are increasingly being used for liver indications. These strategies are very promising for the treatment of liver failure. Nevertheless, the best method, system, or device has not been developed yet, and its probability of getting developed in the near future is also low. Furthermore, little is known about the effects of liver support systems on the overall and transplant-free survival of these patients, and further investigation using randomized controlled trials and meta-analyses is needed. This review presents the most popular extracorporeal blood purification techniques for liver replacement therapy. It focuses on general principles of their function, and on evidence regarding their effectiveness in detoxification and in supporting patients with ALF and ACLF. In addition, we have outlined the basic advantages and disadvantages of each system.

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.

Intrauterine Growth Restriction Due to Gestational Diabetes: From Pathophysiology to Diagnosis and Management.

Intrauterine growth restriction (IUGR) represents a condition where the fetal weight is less than the 10th percentile for gestational age, or the estimated fetal weight is lower than expected based on gestational age. IUGR can be caused by various factors such as maternal, placental or fetal factors and can lead to various complications for both the fetus and the mother, including fetal distress, stillbirth, preterm delivery, and maternal hypertension. Women with gestational diabetes are at an increased risk of developing IUGR. This article reviews the different aspects of gestational diabetes in addition to IUGR, the diagnostic methods available for IUGR detection, including ultrasound and Doppler studies, discusses the management strategies for women with IUGR and gestational diabetes and analyzes the importance of early detection and timely intervention to improve pregnancy outcomes.

Large Cyst of Skene Gland: A Rare Perineum Mass.

Objective In this report we present a rare case of a large cyst of Skene gland in a female patient with a palpable vaginal mass persisting for at least 2 years. Case Report A 67-year-old female admitted to the department of urology due to the presence of "a vaginal mass" for the past 2 years. A cyst of Skene's duct was suspected based on clinical manifestation and findings of magnetic resonance imaging showing an extensive cyst formation in the upper vaginal area and anterior to the urethra. Based on these findings, a decision for surgical removement of the cyst was made. The cyst was incised, drained, and marsupialized. The postoperative recovery was uneventful, and the patient was discharged on the second postoperative day. Conclusion High clinical suspicion is important to reach this rare diagnosis. Partial excision and marsupialization of the cyst is a simple procedure with low morbidity, without recurrence, and excellent results.

Maternal Infection and Preterm Birth: From Molecular Basis to Clinical Implications.

As the leading cause of neonatal morbidity and mortality, preterm birth is recognized as a major public health concern around the world. The purpose of this review is to analyze the connection between infections and premature birth. Spontaneous preterm birth is commonly associated with intrauterine infection/inflammation. The overproduction of prostaglandins caused by the inflammation associated with an infection could lead to uterine contractions, contributing to preterm delivery. Many pathogens, particularly Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Gardnerella vaginalis, Ureaplasma urealyticum, Mycoplasma hominis, Actinomyces, Candida spp., and Streptococcus spp. have been related with premature delivery, chorioamnionitis, and sepsis of the neonate. Further research regarding the prevention of preterm delivery is required in order to develop effective preventive methods with the aim of reducing neonatal morbidity.

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.

Inflammatory Molecules Responsible for Length Shortening and Preterm Birth.

It is estimated that inflammation at the placental-maternal interface is directly responsible for or contributes to the development of 50% of all premature deliveries. Chorioamnionitis, also known as the premature rupture of the amniotic membrane in the mother, is the root cause of persistent inflammation that preterm newborns experience. Beyond contributing to the onset of early labor, inflammation is a critical element in advancing several conditions in neonates, including necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia, intraventricular hemorrhage, retinopathy of prematurity and periventricular leukomalacia. Notably, the immune systems of preterm infants are not fully developed; immune defense mechanisms and immunosuppression (tolerance) have a delicate balance that is easily upset in this patient category. As a result, premature infants are exposed to different antigens from elements such as hospital-specific microbes, artificial devices, medications, food antigens and hypoxia/hyperoxia. This has detrimental implications for preterm deliveries of less than 28 weeks because they have not yet evolved the mechanisms to tolerate maternal and self-antigens.

Portal Vein Thrombosis after C-Section in a Patient with Polycythemia Vera (PV) Due to Pregnancy and Iron Deficiency Anemia (IDA).

Polycythemia vera (PV) is one of the three main classic disorders of Philadelphia-negative myeloproliferative neoplasms (MPNs), with the other two being essential thrombocythemia (ET) and primary myelofibrosis (PMF). PV may develop (15%) in women of childbearing age (15-45 years), with an anticipated rate of roughly 0.3 per 100,000 people, although maintaining a male to female ratio predominance of about 2:1 and a peak prevalence in the sixth and seventh decades of life. Without always being presented with its actual clinical manifestations due to pregnancy itself, and most commonly due to iron deficiency, PV can be frequently missed and therefore belatedly diagnosed. We describe the case of a primipara woman in her 40s, without risk factors for thrombosis, who developed a portal vein occlusion 1.5 month postpartum after C-section and who had a delayed diagnosis of PV.

Pregnancy and COVID-19.

Evidence indicates that SARS-CoV-2 infection increases the likelihood of adverse pregnancy outcomes. Modifications in the circulatory, pulmonary, hormonal, and immunological pathways induced by pregnancy render pregnant women as a high-risk group. A growing body of research shows that SARS-CoV-2 infection during pregnancy is connected to a number of maternal complications, including pneumonia and intensive care unit (ICU) hospitalization. Miscarriages, stillbirth, preterm labor, as well as pre-eclampsia and intrauterine growth restriction are also among the most often documented fetal implications, particularly among expecting women who have significant COVID-19 symptoms, often affecting the timing and route of delivery. Thus, prevention of infection and pharmacological treatment options should aim to minimize the aforementioned risks and ameliorate maternal, obstetric and fetal/neonatal outcomes.

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.

Neurodevelopmental Outcomes of Pregnancies Resulting from Assisted Reproduction: A Review of the Literature.

The term infertility is defined as the lack of conception within 1 year of unprotected intercourse. It affects more than 80 million individuals worldwide. It is estimated that 10-15% of couples of reproductive age are challenged by reproductive issues. Assisted reproduction techniques (ART) are responsible for more than 4% of live births. Our aim is to review the research on neurodevelopmental outcomes of newborns born after the implementation of assisted reproduction methods compared to those conceived naturally. We conducted a comprehensive search of the PubMed, Crossref and Google Scholar electronic databases for related articles up to June 2022 using the PRISMA guidelines. Our research revealed a large number of long term follow-up studies between 2 and 18 years of age, with comparable developmental outcomes. Many studies compared the effects of different infertility treatments against natural conception. The review of the literature revealed that ART is safe, as the majority of studies showed no effect on the neurodevelopmental outcomes of the offspring. In most cases when such an effect was observed, it could be attributed to confounding factors such as subfertility, multiple pregnancies and gestational age at delivery. Finally, the increase in the prevalence of neurodevelopmental disorders after ART, as described in studies with statistically significant results, is predominantly marginal, and given the low incidence of neurodevelopmental disorders in the general population, its clinical significance is debatable.

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.

Primary Cervical Carcinosarcoma: Report of a Rare Case.

Background Carcinosarcomas are malignant mixed Müllerian tumors (MMMT), containing both epithelial and mesenchymal components. Carcinosarcomas of the uterine cervix comprise an extremely rare histopathological entity, with less than 150 cases reported in the literature to date. Materials and Methods A 79-year-old postmenopausal female patient was referred to our gynecological department due to a pelvic mass and vaginal bleeding. A cervical curettage was performed and the histological report revealed a malignant neoplasm with high cellularity consisting of two components; the first was a chondrosarcoma and the latter a adenocarcinoma. A diagnosis of MMMT was confirmed through immunohistochemical (IHC) staining. Neoadjuvant chemotherapy and radiotherapy were implemented, and a year later the patient underwent a radical hysterectomy and oncological pelvic lymph node dissection. She remains disease-free 12 months postoperatively. Conclusion Primary cervical carcinosarcomas are extremely rare tumors demonstrating a bipartite profile. Preoperative diagnosis with appropriate immunochemistry testing of this rare entity is crucial to decision making.

When the endometrioid adenocarcinoma and the endometrial stromal sarcoma meet: A report of an extremely rare case.

Introduction: Collision tumors are characterized by the coexistence of two adjacent, but histologically distinct tumors. This entity can occur between tumors originating from the same organ or between metastases from other sites. Case presentation: A 49-year-old postmenopausal female with abnormal vaginal bleeding and abdominal pain was diagnosed with two coexistent tumors, a grade 1 endometrioid carcinoma and a pT2 undifferentiated stromal sarcoma (USS). On the first time, the patient underwent a total abdominal hysterectomy with bilateral salpingo-oopherectomy and one month later, she was diagnosed with recurrence. Then, a second surgical excision of the recurrent tumor was performed including exploratory laparotomy and anterior pelvic exenteration. She had an uneventful postoperative period, but unfortunately a month following the second operation she passed away. Conclusion: We aim to raise awareness of these rare synchronous malignancies and highlight the importance of having a broad differential diagnosis in a patient presenting with abnormal vaginal bleeding. Further studies with larger patient populations are needed to shed light in etiology and pathogenesis of the concurrence of two malignancies with different embryological origin in the same organ, in order to optimize management of these patients.