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.

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.

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.

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.

Enhanced Recovery Protocols in Urogynecologic and Pelvic Floor Reconstructive Surgery: A Systematic Review and Meta-Analysis.

IMPORTANCE: The implementation of Enhanced Recovery After Surgery (ERAS) protocols may optimize the clinical outcome of surgical patients, by reducing the length of hospital stay (LOS) and improving the quality of recovery. OBJECTIVE: This study aims to evaluate the impact of ERAS protocols in the intraoperative and postoperative course of patients undergoing pelvic floor reconstructive surgery. METHODS: A systematic search of PubMed/MEDLINE, Embase, and the Cochrane Library was conducted up to January 2022, using the Systematic Reviews and Meta-analyses guidelines. Search terms, such as ERAS, urogynecology, sacrocolpopexy were tailored to each database as necessary. Statistical analysis was performed using the RevMan 5.4 software. Confidence intervals (CI) were set at 95%. Mean difference and risk ratio were used in the analysis, and the results were calculated using the random effect model. RESULTS: Six studies that reported outcomes of 1,153 women were included. The ERAS protocols were implemented in 553 women, whereas the remaining 600 received standard perioperative care. A significantly shorter LOS (mean difference, -16.17 hours; 95% CI, -24.07 to -8.26 hours; P < 0.0001) and a higher proportion of patients discharged within 24 hours postoperatively was observed in ERAS patients compared with non-ERAS controls (risk ratio, 3.08; 95% CI, 2.00-4.75; P < 0.00001). Operative time, estimated blood loss, complications, and readmission rates did not differ between the 2 groups. CONCLUSIONS: Our analysis showed that ERAS protocols have a favorable impact on the perioperative course of urogynecologic populations. More research is required to determine those key components of ERAS protocols, specifically applicable and more beneficial to women with pelvic floor disorders.

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.

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.

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.

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 Prognostic Role and Significance of Dll4 and Toll-like Receptors in Cancer Development.

The Notch signaling pathway regulates the development of embryonic and tissue homeostasis of various types of cells. It also controls cell proliferation, variation, fate and cell death because it emits short-range messages to nearby cells. The pathway plays an important role in the pathophysiology of various malignancies, controlling cancer creation. It also limits cancer development by adjusting preserved angiogenesis and cellular programs. One of the Notch signaling ligands (in mammals) is Delta-like ligand 4 (Dll4), which plays a significant role in the overall malignancies' advancement. Particularly, sequencing Notch gene mutations, including those of Dll4, have been detected in many types of cancers portraying information on the growth of particular gynecological types of tumors. The current research article examines the background theory that implies the ability of Dll4 in the development of endometrial and other cancer types, and the probable therapeutic results of Dll4 inhibition.

Basic principles of molecular biology of cancer cell-Molecular cancer indicators.

Molecular biology of cancer cell is a domain of medical science that is rapidly growing in our days. Knowing the ways and paths that cancer cells follow is crucial to the prevention of cancer itself. Central role to these paths, concerning the cell cycle and the process of apoptosis, has the protein p53. The whole mechanism of the cell cycle is activated by the action of various mitogens, such as growth factors, hormones and cytokines. Carcinogenesis involves alterations of genes (proto-oncogenes and tumor suppressor genes), which encode proteins of the signal transduction. Many of the damages that lead to carcinogenesis may be due to the lack of repressive signals for cell division, but also to the absence of the sensitivity of cells to repressive signals. The cell has mechanisms of receiving apoptotic-antitumor signals and mechanisms of execution of these instructions. A percentage of cancers (4-8%) are etiologically linked to germ (stem) cells mutations and occur at an increased frequency in families (hereditary cancers). Substantial progress in understanding the mechanisms of carcinogenesis, filtration and metastasis of cancer has highlighted the key role of specific genes, primarily oncogenes and tumor suppressor genes.

Primary Fallopian Tube Cancer in an 89-Year-Old Patient.

Fallopian tube cancer is an extremely rare gynecological condition, accounting for just 1 to 2% of all female tract malignancies. The mean age of diagnosis is similar to that of ovarian cancer, between 60 and 75 years, but it can affect a wide spectrum of ages. Advanced age and family history of ovarian and breast cancer are the main risk factors, since they are associated with increased incidence of this uncommon entity. In this study, we report a rare case of an elderly, 89-year-old patient that presented to our clinic due to vaginal bleeding.

Cervical Twin Heterotopic Pregnancy: Overview of Ectopic Pregnancies and Scanning Detection Algorithm.

Background: Ectopic pregnancy is the leading cause of gestation-related deaths during the first trimester. Cervical twin heterotopic pregnancies, when ectopic, constitute a small and rare part of gynecological surgery. Case Presentation: A 30-year-old pregnant woman (gravida 3, para 2) presented with mild pain in the lower abdomen and traces of bleeding per vaginum for three days. Transvaginal ultrasonography revealed a balloon-shaped cervical canal with a visible gestational sac measuring 3.5 × 3.9 cm. A second gestational sac was seen in the uterine cavity. The measurements of the gestational sacs corresponded to 7 + 4 weeks' pregnancy. A decision for medical abortion with mifepristone and misoprostol was made. However, due to an incomplete abortion and continuous bleeding, a curettage was performed. Conclusions: Spontaneous heterotopic pregnancy with the ectopic pregnancy located in the cervix is an extremely rare clinical condition requiring urgent treatment in order to reduce maternal mortality and morbidity and preserve fertility.

Breast Cancer Apoptosis and the Therapeutic Role of Luteolin.

Breast cancer represents one of the three most common gynecological cancers, with each subtype having distinct risk profile and treatment strategies. Optimal therapy for each case depends not only on tumor subtype and cancer stage, but also on patient preferences. Thus, the final therapeutic choice seems complicated to be reached. In addition, frequent relapses and the aesthetic effects have led to the search for more effective and less invasive methods. Surgical interventions have become less complex and new hormonal and chemotherapeutic drugs are established, that promise great results, either combined to surgical treatment or used exclusively. Luteolin is a representative of natural flavonoid that has proven to modulate various signaling pathways involved in cancer development. Recent data demonstrate that luteolin induces apoptotic cell death via antioxidant activity, acting as an anticancer agent against various types of human malignancies including breast cancer. The aim of this review is to summarize latest data considering the therapeutic role of luteolin in breast cancer.

A Potential Pathogenic Link Between Cancer of Female Reproductive System and Infertile Women Treated With Assisted Reproduction Techniques.

Prevention and treatment of infertility remains a priority for developed countries where a large proportion of women undergo in vitro fertilization (IVF) after ovarian stimulation. Latest data suggest that, in the USA alone, almost eight million women of fertile age will have sought medical advice for fertility problems by 2025. However, over the last years, attention has been increasingly focused, and questions have risen, on the long-term health effects in women who underwent assisted reproductive technologies (ARTs). Since the emergence of ART, reports highlight a possible connection of ovarian stimulation and several types of gynaecological cancer, including ovarian, endometrial and cervical types, but due to limited scientific evidence, such a speculation is still under investigation. The objective of this review is to summarize the latest data of ovarian hyperstimulation and IVF, associated with the risk of gynecological tract cancer development.

Gynecological Benignities Causing Obstructive Uropathy. Review of the Literature.

BACKGROUND/AIM: Obstructive uropathy is defined the clinical entity that is characterized by changing the structural and functional feature of the urinary system due to interruption of normal urinary runoff. Gynecological benignities could rarely cause obstructive uropathy. Material and Methods: In this study the incidence and the severity of obstructive uropathy caused by gynecological benignities, was investigated. Additionally, we examined the spectrum of the contigent therapeutical procedures, in order to contend with this severe clinical entity, as well as the dangerous for life complication of urosepsis. Results: Gynecological benignities can cause obstructive uropathy. These conditions are rarely faced, composing a challenging problem for physicians. In the spectrum of these conditions are included adnexal masses, leiomyomas, pelvic inflammatory disease and endometriosis. Conclusions: Obstructive uropathy due to gynecological benignities is a very rare, difficult and challenging condition and physicians should always consider the existence of uropathy in such cases.