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Gynecological cancer is a term referring to malignancies that typically involve ovarian, cervical, uterine, vaginal, and vulvar cancer. Combined, these cancers represent major causes of morbidity and mortality in women with a heavy socioeconomic impact. MiRNAs are small non-coding RNAs that are intensively studied in the field of cancer and changes in them have been linked to a variety of processes involved in cancer that range from tumorigenesis to prognosis and metastatic potential. This review aims to summarize the existing literature that has linked miRNAs with each of the female malignancies as potential biomarkers in diagnosis (circulating miRNAs), in tumor histology and prognosis (as tissue biomarkers), and for local (lymph node) and distant metastatic disease.

The detection of HPV infection and microbial colonization in cervical lesions is currently done through PCR-based viral or bacterial DNA amplification. Our objective was to develop a methodology to expand the metaproteomic landscape of cervical disease and determine if protein biomarkers from both human and microbes could be detected in distinct cervical samples. This would lead to the development of multi-species proteomics, which includes protein-based lateral flow diagnostics that can define patterns of microbes and/or human proteins relevant to disease status. In this study, we collected both non-frozen tissue biopsy and exfoliative non-fixed cytology samples to assess the consistency of detecting human proteomic signatures between the cytology and biopsy samples. Our results show that proteomics using biopsies or cytologies can detect both human and microbial organisms. Across patients, Lumican and Galectin-1 were most highly expressed human proteins in the tissue biopsy, whilst IL-36 and IL-1RA were most highly expressed human proteins in the cytology. We also used mass spectrometry to assess microbial proteomes known to reside based on prior 16S rRNA gene signatures. Lactobacillus spp. was the most highly expressed proteome in patient samples and specific abundant Lactobacillus proteins were identified. These methodological approaches can be used in future metaproteomic clinical studies to interrogate the vaginal human and microbiome structure and metabolic diversity in cytologies or biopsies from the same patients who have pre-invasive cervical intraepithelial neoplasia, invasive cervical cancer, as well as in healthy controls to assess how human and pathogenic proteins may correlate with disease presence and severity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To assess the effect of hysteroscopic polypectomy on the in vitro fertilization (IVF) results in infertile women with at least one prior negative IVF outcome. Methods: This retrospective cohort study included women who had attended the "2nd Department of Obstetrics and Gynecology of the National and Kapodistrian University of Athens" and "Iaso" Maternity Hospital from October 2019 to January 2023 for infertility treatment. The medical records of 345 women aged 18-45 years old without abnormal findings in hysterosalpingography (HSG) and with at least one previous failed IVF procedure were analyzed. The male factor was excluded, as well as a prior hysteroscopic removal of polyps. In 67 women, polyps were suspected during initial two-dimensional ultrasound (2D-US) examination. The final sample of the study comprised 40 patients, in which endometrial polyps were removed by hysteroscopy with the use of resectoscope. All patients underwent ovarian stimulation and IVF in the consecutive cycle using a short GnRh antagonist protocol. Main Results: After hysteroscopic polypectomy, 29 (72.5%) out of 40 patients had a positive pregnancy result: 26 (65%) clinical and 3 (7.5%) biochemical pregnancies were documented. There was a statistically significant difference between the number of clinical pregnancies before and after polypectomy ( p < 0.001), as well as between the total number of pregnancies ( p < 0.001). Secondary Results : Women with positive outcome were significantly younger and had significantly lower FSH levels ( p < 0.007). They also had significantly higher AMH ( p < 0.009) and peak estradiol levels ( p < 0.013) and yielded more M II oocytes ( p < 0.009) and embryos ( p < 0.002). Conclusions: Hysteroscopic polypectomy in women with a suspected endometrial polyp using 2D ultrasound and a history of prior failed IVF attempt improves IVF outcomes in terms of the clinical and total number of pregnancies.

Introduction: Endometriosis, defined as the presence of endometrial glands and stroma outside the uterine cavity, mainly affects the pelvic viscera and peritoneum. Endometriosis can also occur at sites of surgical incisions on the abdominal wall, mainly in women with a history of cesarean section (CS). The incidence of abdominal wall endometriosis after CS reaches 1%. Clinical suspicion, along with imaging, plays a crucial role in diagnosis. The preferred treatment involves extensive surgical excision with clear margins, ensuring a definitive diagnosis through histopathology examination., Case Presentation: This case report is of a 44-year-old woman with a history of two CS procedures who developed pain and pigmentation at the incisional site one year after the last CS. Thirteen years after the surgical excision of an abdominal wall endometriosis (AWE) mass, followed by hormone therapy, she presented in our hospital with worsening pain for further management. Pelvic MRI findings were consistent with AWE. During surgery, the abdominal wall endometriosis foci were removed, and the defect in the aponeurosis was repaired using a dual-sided mesh in a tension-free procedure., Conclusion: Although AWE is a rare condition, we foresee an increase in cases because of the ever-increasing CS rates and the important association between AWE and CS. Healthcare practitioners should remain vigilant for this condition in women of reproductive age who exhibit cyclic pain, a palpable mass in the abdomen, and a background of previous uterine surgeries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Triantafyllidou, Mili, Kalampokas, Vlahos and Kalampokas.)

Antiphospholipid syndrome is an autoimmune disorder which is characterized by the presence of heterogeneous antiphospholipid antibodies. There is an evidence on antiphospholipid (aPL) antibodies related to thromboembolic events in cancer patients. In fact, the thrombotic complications in patients with malignancy occur at a rather high frequency, compared to other risk factors. In parallel with standard therapies available, there is need of case-by-case monitoring of each patient and the introduction of new therapies and need for more clinical trials which will address many questions for the optimal management of patients. This paper presents a basic review of the literature on the aPL antibodies associated with cardiovascular disease and cancer, as well as its complications, which are reported so far in the bibliography., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Conjoined twins represent a rare type of monoamniotic twins. Ultrasound assessment during the first trimester can facilitate the diagnosis, however further assessment by colour Doppler studies, 3D imaging, fetal echocardiography and fetal magnetic resonance imaging (MRI) is usually required in order to determine the specific fetal abnormalities and to guide appropriate pregnancy management. This case report presents a rare case of conjoined twins complicating a dichorionic-diamniotic triplet pregnancy, achieved after intracytoplasmic sperm injection (ICSI) and blastocyst transfer. A 44-year-old woman was referred for chorionicity determination to our Fetal Medicine Centre due to suspicion of conjoined twins in a triplet pregnancy. Ultrasound assessment at 11 weeks demonstrated a dichorionic triplet pregnancy which was also complicated by a rare type of conjoined twins (thoracoomphalopagus) and after a successful embryo reduction a neonate of 2200 g was delivered by caesarean section at term. The accurate diagnosis and early detection of conjoined twins by a fetal medicine specialist is crucial, especially as far as multiple pregnancies with three or more fetuses are concerned.

The incidence of endometrial cancer (EC) is rising and healthcare professionals need to be informed about the latest data on the constant developments in the field of its management. With particular interest in the classification and management of EC, we surveyed current literature, national and international data, and guidelines, as well as the latest studies to present the most recent data regarding the management of EC. It became evident that despite the consensus on low-risk EC, there are still controversies surrounding the management of high-risk EC, especially regarding the role of sentinel lymph node biopsy (SLNB). Our aim is to present the old and new perspectives in the management of EC, the different available surgical routes, the possible desire for fertility preservation, the role of adjuvant therapies and the focus on the advantages and the limitations of the implementation of SLNB in therapeutic strategies. It became evident throughout our search and based on literature data that minimally invasive surgery (MIS) leads to satisfying outcomes, thus becoming gradually the preferred route of surgery, while SLNB could provide essential information and guidance about the overall management needed in cases of both low-risk and high-risk EC.

Cancer during childhood and adolescence remains a major public health issue, affecting a significant portion of this age group. Although newer anti-cancer treatments have improved survival rates, this comes at a cost in terms of gonadotoxic effects. As a result, the preservation of fertility is important. Ovarian tissue cryopreservation, one of the newest methods, has some advantages, especially for prepubertal patients: no need for ovarian stimulation, thus, no further risk for estrogen-sensitive cancer types, and preservation of more and better-quality primordial follicles of the ovarian cortex. The most frequent indications include treatment with alkylating agents, ovarian-focused radiotherapy, leukemias, lymphomas, brain and neurological tumors, as well as Turner syndrome and benign hemoglobinopathies. An expected survival exceeding 5 years, the absence of systematic disease and an overall risk of premature ovarian insufficiency over 50% are among the criteria that need to be fulfilled in order for a patient to undertake this method. Orthotopic transplantation is more frequently used, since it can allow both live birth and the recovery of endocrine function. Reimplantation of malignant cells is always a major risk and should always be taken into consideration. Histological analysis, as well as immunohistochemical and molecular methods, are needed in order to improve the search for malignant cells before transplantation. Ovarian tissue cryopreservation appears to be a method with specific benefits, indications and risks which can be an important tool in terms of preserving fertility in younger women.

We present two cases of family members (first cousins) with short extremities caused by a novel variant of COL2A1 gene (NM&#95;001844.5). Case 1 description: A 29-year-old woman presented in her first pregnancy for a second trimester anomaly scan at 23 weeks of gestation. Fetal long bones were measured below the third centile for gestational age. Follow-up scans revealed fetal long bone growth deceleration. Initial genetic work-up was negative and the rest of the maternal follow-up was unremarkable. A male baby weighing 3180 g was delivered at 39 weeks and 4 days of gestation. Case 2 description: A 33-year-old pregnant woman presented for a routine second trimester anomaly scan at 20 weeks and 4 days of gestation. All fetal measurements were appropriate for the gestational age. The routine growth scan performed at 32 weeks showed fetal long bone measurements below the third centile for gestational age, while the follow-up growth scan at 36 weeks and 4 days of gestation revealed consistent, below the third centile, fetal long bone growth. Given that the fetuses of these two cases were related (first cousins), whole exome sequencing (WES) was performed on Case 2. WES revealed a novel heterozygous missense variant c.1132G>A (p. Gly378Ser) of COL2A1 gene (NM&#95;001844.5). Subsequently, targeted genetic sequencing for the variant was performed on Case 1 and the same novel variant was found. Targeted sequencing revealed the same variant in the mother of Case 1 and the father of Case 2 (siblings). A female baby weighing 3200 g was delivered at 40 weeks and 4 days of gestation.

Interstitial and cornual pregnancies are dangerous, yet rare, forms of ectopic pregnancy, accounting for 2%-4% of all ectopic pregnancies. A 38-year-old female, para 1, gravida 3 had undergone another in vitro fertilisation (IVF) cycle (a salpingectomy performed elsewhere for treating a hydrosalpinx before a previous IVF attempt). Duration of pregnancy is 6 weeks and 5 days, a transvaginal ultrasound revealed an embryo with a positive foetal heartbeat, located in the left cornuum. As no conservative treatment option could be followed, we proceeded with laparoscopic removal of ectopic pregnancy through cornual resection. Since a specific surgical methodology has not yet been established, presenting more step-by-step surgical approaches that can be used in clinical practice is of high importance. We present a step-by-step surgical approach that we have implemented in cases of cornual pregnancy in our department., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Human Reproductive Sciences.)

Background: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare congenital syndrome characterized by uterovaginal agenesis. Most patients are diagnosed during adolescence, when body image and sexual identity are shaped. Our main objective was to investigate how MRKH syndrome affects psychology, quality of life (QoL), and the sexual life of patients compared with non-affected individuals., Methods: Original peer-reviewed research papers examining psychological outcomes, QoL, and sexual function of MRKH patients were searched in PubMed. Titles, abstracts, and full text from potentially eligible records were reviewed by two independent reviewers. Case reports and papers published not in English were excluded., Results: Our search identified 63 records, of which 20 were included: 10 examined psychological and psychosocial outcomes, 14 examined sexual function outcomes, and 6 examined QoL outcomes. Results may be affected by selection bias and confounding due to differences between MRKH patients and controls., Conclusions: MRKH could be associated with a higher prevalence of anxiety and depression symptoms and social insecurity compared with women of a similar age without the condition. MRKH could also be associated with greater pain and discomfort during sexual intercourse and limitations in arousal, lubrication, and orgasm. MRKH patients more commonly experience impairment of mental-health-related QoL, but physical-health-related QoL is not affected.

The aim of this systematic review and meta-analysis is to examine the association between exposure to preeclampsia during pregnancy and the occurrence of cerebral palsy in offspring. For this reason, the authors searched PubMed/Medline, EMBASE, and Google Scholar databases (end-of-search: 22 November 2021) and identified the most relevant studies. Then, a meta-analysis of all the eligible studies was performed. Subgroup and meta-regression analyses by study design, degree of adjustment, and geographical region were also conducted. A total of 10 studies were finally included, and no statistical significance was noted in the association between preeclampsia and cerebral palsy (pooled OR = 1.16, 95% CI: 0.77-1.74). The subgroup of studies that provided adjusted odds ratios for any variable except for gestational age showed a statistically significant association (pooled OR = 1.62, 95% CI: 1.36-1.93), whereas the association dissipated in studies also adjusting for gestational age (pooled OR = 1.63, 95% CI: 0.48-5.50). In conclusion, it seems that preeclampsia is not associated with cerebral palsy independently of gestational age; however, further research is needed to shed light on this topic.

Malignant disease complicates pregnancy in up to 1 per 1,000-2,000 cases. Pregnancy itself does not constitute a predisposing factor for malignancy. Management and treatment of patients suffering from a malignancy during pregnancy still represents a challenge in everyday clinical practice. Recent advances in imaging, diagnostic and overall treatment modalities have tailored the management of patients, specifically those who wish to maintain the pregnancy. The aim of this review was to provide clinicians with concise information on the management of the most common malignancies during pregnancy. We performed a review of the current literature including review articles, original research articles and guidelines, which are used for the management of the most common malignancies during pregnancy. Breast, cervical and ovarian malignant tumours are the most common during pregnancy. However, the overall outcome and survival per stage for these cancers do not appear to be influenced by pregnancy. Ethical, emotional and treatment dilemmas may be encountered during treatment planning. Individualization of treatment planning should be made by a multidisciplinary team but the final decision rests with the parents., Competing Interests: The Authors have no conflicts of interest to declare in relation to this study., (Copyright 2021, International Institute of Anticancer Research.)

Purpose: To assess the recurrence pattern and survival in women treated with definitive chemoradiotherapy for cervical cancer., Methods: A retrospective cohort study of women FIGO (2012) stage IB2 to IVA from the Grampian region of Scotland between February 2000 and March 2011. These women were followed up until April 2018., Results: A total of 121 eligible women allocated with mean age at treatment 50.59 years (SD = 13.98, range 22-82). Tumours staged: IB2: n = 24 (19.8%), II: n = 45 (37.2%), III: n = 43 (35.5%) and IVA: n = 7 (5.8%). Two (1.7%) women had no available data. Fifty-five (45.5%) women had recurrence after treatment, and 51 (42.15%) women died from the disease. The sites of recurrence were as follows: central pelvic only (n = 4, 7.27%), pelvic and distant (n = 39, 70.91%) and distant only (n = 12, 21.82%) with median time from end of treatment to first recurrence 44 months (range 2-98), 26 months (range 1-146) and 22 months (range 3-66) respectively. 5-and 8-year overall survival was 76.0% (95% CI: 68.8%-84.0%) and 64.4% (95% CI: 56.4%-73.5%) respectively., Conclusions: Though overall survival is better than with radiotherapy alone, recurrence occurs up to 10 years after treatment. This raises the issues of how to reduce late recurrence and the appropriateness of current follow-up protocols., (© 2020 John Wiley & Sons Ltd.)

Objective: One of the most common challenges in everyday clinical practice of gynecological oncology is to identify the type and the primary origin of a tumor. This is a crucial step in the management, treatment, prognosis, and survival of patients suffering from a gynecological malignancy. Immunohistochemistry has been widely adopted over the last three decades in pathology laboratories all over the world. Recent advances in our understanding of the differentiation of gynecological tumors based on immunohistochemical expression have resulted in use of immunohistochemistry as a major diagnostic tool in gynecology, for precise tumor classification. More recently, advances in molecular pathology, have taken this disease sub-classification further resulting in more effective personalised treatment regimens. The aim of this review is to provide clinicians with up to date information on the various immunohistochemical and molecular tests used in the diagnosis of gynecological malignancies of the female genital tract and an understanding of how to interpret them., Methods: We performed a review of the current literature including review articles, original research articles, and guidelines on various immunohistochemical markers and molecular techniques which are used for the differential diagnosis of gynecologic malignancies., Conclusions: Immunohistochemistry is useful as an objective means for improved diagnostic reproducibility, accuracy, and precise classification in cases where the diagnosis with histochemical stains is inconclusive, providing a more reliable estimate of clinical outcomes. The diagnosis, in some cases, can be further refined by the use of molecular techniques leading to personalised medical treatments., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To assess the incidence of endometrial cancer after endometrial ablation or resection (EA/R) for menorrhagia., Method: The present retrospective observational cohort study included women who underwent EA/R for menorrhagia at Aberdeen Royal Infirmary between February 1, 1990 and December 31, 1997. Follow-up data until 2015 were examined. To assess risk of endometrial cancer, each woman was matched by age to the annual observed incidence of endometrial cancer in northeast Scotland for each year from the date of EA/R until 2015., Results: During the 7-year study period, 901 eligible women (mean age 42.3 ± 5.7 years; range 26-50 years) underwent EA/R. Of these patients, 204 (22.6%) subsequently had a hysterectomy for reasons other than endometrial cancer, and 695 (77.1%) did not. The overall incidence of endometrial cancer was 0.2% (2/901); the risk of developing endometrial cancer after EA/R was calculated as 11.1 per 100 000 women years. The mean expected incidence for all women and the subgroup with no hysterectomy was estimated to be 26.5 and 35.6 occurrences per 100 000 women years, respectively. The observed incidence was significantly lower versus the mean expected risk for both groups (P<0.001)., Conclusion: The findings indicate that the risk of endometrial cancer could be significantly reduced but not eliminated by EA/R., (© 2018 International Federation of Gynecology and Obstetrics.)

Objective: In United Kingdom., test of cure after treatment of any grade of cervical intraepithelial neoplasia (CIN) incorporates high-risk human papillomavirus (Hr-HPV) test and cytology at 6-month follow-up. The aims of the study were to determine the rate of recurrent CIN in women who are Hr-HPV positive and cytology negative and to explore possible associated risk factors., Methods: A retrospective observational cohort study was performed in women treated for any grade CIN between 2010 and 2015 from a regional population, who were Hr-HPV positive and cytology negative at first follow-up., Results: A total of 2729 women were identified as treated for any grade CIN, and 213 (7.8%) were re-referred to colposcopy having Hr-HPV-positive test and negative cytology at test of cure. Their mean age was 31.56 years (range = 19-62 years). The mean time of follow-up per woman was 30.50 months (range = 2-63 months). At colposcopy, 171 (80.3%) had colposcopy examination only and 42 women (19.7%) had a biopsy. Twenty-four cases (11.3%) of CIN were identified of which 4 (1.9%) were CIN 2/3. Eleven women (5.2%) in total had a repeat treatment. Five women (2.3%) had biopsy-proven CIN 2/3 within 12-months after treatment. No cases of CIN 3+ after negative colposcopy were identified during the follow-up period., Conclusions: The incorporation of Hr-HPV testing yielded a very small number of women with residual CIN within 12 months of treatment. Our results suggest that women who are Hr-HPV positive and cytology negative after treatment of CIN with normal and adequate colposcopy could be discharged to routine recall if confirmed by larger national data.

Background: Primary small cell ovarian cancer of pulmonary type (SCCOPT) is a rare aggressive ovarian tumour with an incidence of <1%, usually occurring in perimenopausal or postmenopausal women and known to have a poor prognosis. Current treatment is platinum based but has not resulted in long term survival., Case Presentation: We report a case of a 77-year old Caucasian woman who presented initially with a one-week history of abdominal discomfort with raised inflammatory markers and Ca125 of 50 μ/ml. Calcium levels were normal. She underwent primary debulking surgery, and histology showed a tumour comprising areas of classical small-cell carcinoma morphology. 6 cycles of adjuvant chemotherapy with carboplatin was offered. Relapsed/progressive disease was noted after 3 months of chemotherapy and patient died 7 months after treatment completion., Conclusions: SCCOPT is a rare aggressive malignancy with majority of the women having an overall survival of 2 years. There is no clear consensus for the diagnosis and optimal treatment.

Background/aim: Ovarian cancer (OC) has a high mortality rate and usually presents late in advanced stage, which poses challenges to management. Better understanding of the disease biology and application of radical surgery (RS) to achieve no visible residual tumor, alongside with chemotherapy, may lead to longer survival amongst these patients. Our purpose was to examine the demographic characteristics, surgical morbidity and outcomes of patients undergoing RS for OC., Materials and Methods: A retrospective cohort study of women undertaking surgery for OC between February 2014 and September 2016 in Aberdeen Royal Infirmary., Results: A total of 121 women had surgery for OC of whom 78 (64.5%) were stage II and above. Of these, 40 (51.3%) women had primary and 38 (48.7%) had interval debulking surgery with 42 (53.8%) having radical surgery. The most common procedures that were performed as part of RS included rectosigmoid resection (n=20, 47.6%), small bowel resection (n=10, 23.8%), splenectomy (n=9, 21.4%). Morbidity outcomes included blood loss >1.5 lt. (n=14, 33.3%), hospitalization >7days (n=31, 73.8%), sepsis (n=8, 19%). There was no short-term mortality. Debulking outcomes were: no macroscopic residual disease (n=36, 85.7%), ≤10 mm disease (n=2, 4.8%), and ≥10 mm disease (n=3, 7.1%)., Conclusion: Our findings support the practise where RS for OC can be offered to selected patients, with good surgery outcomes and low morbidity rates., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: Endometrial cancer is increasingly prevalent in western societies and affects mainly postmenopausal women; notably incidence rates have been rising by 1.9% per year on average since 2005. Although the early-stage endometrial cancer can be effectively managed with surgery, more advanced stages of the disease require multimodality treatment with varying results. In recent years, endometrial cancer has been extensively studied at the molecular level in an attempt to develop effective therapies. Recently, a family of compounds that alter epigenetic expression, namely histone deacetylase inhibitors, have shown promise as possible therapeutic agents in endometrial cancer. The present review aims to discuss the therapeutic potential of these agents., Materials and Methods: This literature review was performed using the MEDLINE database; the search terms histone, deacetylase, inhibitors, endometrial, targeted therapies for endometrial cancer were employed to identify relevant studies. We only reviewed English language publications and also considered studies that were not entirely focused on endometrial cancer. Ultimately, sixty-four articles published until January 2018 were incorporated into our review., Results: Studies in cell cultures have demonstrated that histone deacetylase inhibitors exert their antineoplastic activity by promoting expression of p21WAF1 and p27KIP1, cyclin-dependent kinase inhibitors, that have important roles in cell cycle regulation; importantly, the transcription of specific genes (e.g., E-cadherin, PTEN) that are commonly silenced in endometrial cancer is also enhanced. In addition to these abstracts effects, novel compounds with histone deacetylase inhibitor activity (e.g., scriptaid, trichostatin, entinostat) have also demonstrated significant antineoplastic activity both in vitro and in vivo, by liming tumor growth, inducing apoptosis, inhibiting angiogenesis and potentiating the effects of chemotherapy., Conclusions: The applications of histone deacetylase inhibitors in endometrial cancer appear promising; nonetheless, additional trials are necessary to establish the therapeutic role, clinical utility, and safety of these promising compounds.

Objective: To estimate the incidence of hysterectomy following endometrial resection or endometrial ablation (ERA)., Methods: The present retrospective study enrolled women who underwent ERA for benign heavy menstrual bleeding (HMB) at Aberdeen Royal Infirmary, UK, between February 1, 1990, and December 31, 1997; follow-up data to the end of 2015 were included from the pathology laboratory report system from the single pathology laboratory in the region. Data were compared between patients who did or did not require a hysterectomy after ERA., Results: There were 901 patients who underwent ERA for HMB during the study period. The mean age of patients was 42.3 ± 5.7 years; of the patients included, 206 (22.9%) women underwent hysterectomy and these patients had a mean age of 40.1 years. Of the patients who had hysterectomies, 155 (75.2%) did so in the first 5 years following ERA, 31 (15.0%) did within 6-10 years, 11 (5.3%) did within 11-15 years, and 9 (4.4%) did within 16-20 years. In total, 51 (24.8%) of these patients had hysterectomies within 6-25 years of ERA., Conclusions: A significant majority of women who underwent ERA for HMB did not require hysterectomy up to 25 years after the procedure., (© 2017 International Federation of Gynecology and Obstetrics.)

The aim of the present study was to investigate the impact of anastrozole and letrozole supplementation following surgically induced menopause on bone metabolism and biomechanical properties. A total of 45 Wistar rats underwent ovariectomy and were then randomly allocated to receive no treatment, anastrozole or letrozole. At 2 and 4 months following the initiation of the present study, the serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were determined, and the animals were sacrificed at the end of the 4-month period to assess the biomechanical properties of the femoral bones. The applied force and the deflection of the central section were recorded during the test. Taking advantage of these quantities, the fracture force, the stiffness of the bone and the energy absorbed until fracture were determined. At 2 months following the initiation of the experimental protocol, the mean OPG levels were significantly increased in the control group compared with the anastrozole-treated group (P<0.01). Similarly, RANKL levels were significantly increased in the control rats compared with the anastrozole-treated animals (P<0.001) and animals that received letrozole (P<0.05). Notably, these trends were not observed at the end of the experiment (4 months). A biomechanical study of the femoral bones revealed significantly decreased stiffness among animals that received anastrozole (P<0.05) and letrozole (P<0.01) compared with their control counterparts. The results of the present study indicate that treatment with anastrozole and letrozole significantly increases the levels of OPG and RANKL in bone, an effect that appears to be directly associated with the biomechanical properties of bones.

Triple-negative breast cancer (TNBC) lacks expression of estrogen receptor (ER), progesterone receptor (PR) and HER2 gene. It comprises approximately 15-20% of breast cancers (BCs). Unfortunately, TNBC's treatment continues to be a clinical problem because of its relatively poor prognosis, its aggressiveness and the lack of targeted therapies, leaving chemotherapy as the mainstay of treatment. It is essential to find new therapies against TNBC, in order to surpass the resistance and the invasiveness of already existing therapies. Given the fact that epigenetic processes control both the initiation and progression of TNBC, there is an increasing interest in the mechanisms, molecules and signaling pathways that participate at the epigenetic modulation of genes expressed in carcinogenesis. The acetylation of histone proteins provokes the transcription of genes involved in cell growth, and the expression of histone deacetylases (HDACs) is frequently up-regulated in many malignancies. Unfortunately, in the field of BC, HDAC inhibitors have shown limited effect as single agents. Nevertheless, their use in combination with kinase inhibitors, autophagy inhibitors, ionizing radiation, or two HDAC inhibitors together is currently being evaluated. HDAC inhibitors such as suberoylanilidehydroxamic acid (SAHA), sodium butyrate, mocetinostat, panobinostat, entinostat, YCW1 and N-(2-hydroxyphenyl)-2-propylpentanamide have shown promising therapeutic outcomes against TNBC, especially when they are used in combination with other anticancer agents. More studies concerning HDAC inhibitors in breast carcinomas along with a more accurate understanding of the TNBC's pathobiology are required for the possible identification of new therapeutic strategies., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: Local anesthetics combined with opioids are commonly used in labor epidural analgesic schemes. This study investigated if the addition of fentanyl to epidural ropivacaine can affect cervical dilation and progress of vaginal delivery., Methods: Sixty-two nulliparous parturients were randomized to receive epidurally 8 ml ropivacaine 0.2% combined with fentanyl 20 μg (F/R-group, n = 31) or with normal saline 0.4 ml (R-group, n = 31), every hour. Rescue doses of 5 ml ropivacaine 0.2% were also administered. Measurements were performed every 60 min until full cervical dilation. The primary end-point was the time to reach 10-cm cervical dilation. Secondary outcomes were Bishop scores, mode of delivery, total ropivacaine dose, pain, and satisfaction scores (numerical scale, 0-10)., Results: Data from 60 parturients (29 in the F/R and 31 in the R-group) were analyzed. The F/R-group had 26 vaginal deliveries (four instrumentally assisted), and three cesarean deliveries. The R-group had 27 vaginal deliveries (six instrumentally assisted) and 4 cesarean deliveries. Time to 10-cm cervical dilation did not differ between the groups (4 ± 2.4 h in the F/R-group vs 4.4 ± 2.1 h in the R-group, p = .341). The number of women remaining in the study every hour until full cervical dilation and Bishop scores for a 4-h period did not differ between the groups (p = .617). Total ropivacaine dose was comparable between the groups, but the F/R-group reported significantly lower pain (p = .01) and higher satisfaction scores (p = .001)., Conclusions: The addition of fentanyl to ropivacaine 0.2% solution did not affect cervical dilation and progress of the first stage of labor, but improved both analgesia and satisfaction.

Malignant melanoma of the vagina is a rare, aggressive malignancy of poor prognosis. It principally affects post-menopausal women, with a mean age of 57 years, and the factors that contribute to its appearance are not well known. The first case of primary malignant vaginal melanoma was reported in 1887 and modern literature has noted about 500 cases, globally. Vaginal melanomas constitute 0.3% of all malignant melanomas and fewer than 3% of all vaginal carcinomas. To date there is no clear consensus regarding treatment. An early, accurate diagnosis and prompt investigation is essential in reaching appropriate treatment decisions. We present a clinical case of primary vaginal melanoma and review the literature briefly, presenting the current treatment plans and updates of this rare gynecological malignancy. Considerations, epidemiology, associated risk factors, response to therapy and expected outcome are also discussed., Conclusion: Primary malignant vaginal melanoma is a rare but aggressive melanoma that affects women in their 6th and 7th decade of life. The tumor appears as a dark node or spindle but can also be amelanotic. The size of the tumor is indicative of the prognostic factors. Surgery seems to be the only efficient treatment. Postoperative adjuvant therapy might help in preventing recurrence of the tumor. The survival rate is largely dependent on nodal and distant metastasis of the disease after initial tumor resection. There is a dire need to form a proper therapeutic regime to control this disease., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

With a lifetime risk estimated to be one in eight in industrialized countries, breast cancer is the most frequent type of cancer among women worldwide. Patients are often treated with anti-estrogens, but it is common that some tumors develop resistance to therapy. The causation and progression of cancer is controlled by epigenetic processes, so there is an ongoing interest in research into mechanisms, genes and signaling pathways associating carcinogenesis with epigenetic modulation of gene expression. Given the fact that histone deacetylases (HDACs) have a great impact on chromatin remodeling and epigenetics, their inhibitors have become a very interesting field of research., Aim: This review focused on the use of HDAC inhibitors as anticancer treatment and explains the mechanisms of therapeutic effects on breast cancer. We anticipate further clinical benefits of this new class of drugs, both as single agents and in combination therapy. Molecules such as suberoylanilide hydroxamic acid, trichostatin A, suberoylbis-hydroxamic acid, panobinostat, entinostat, valproic acid, sodium butyrate, SK7041, FTY720, N-(2-hydroxyphenyl)-2-propylpentanamide, Scriptaid, YCW1, santacruzamate A and ferrocenyl have shown promising antitumor effects against breast cancer. HDAC inhibitors consists an attractive field for targeted therapy against breast cancer. Future therapeutic strategies will include combination of HDAC inhibitors and chemotherapy or other inhibitors, in order to target multiple oncogenic signaling pathways. More trials are needed., (Copyright© 2017 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Ulipristal acetate (UA), a selective progesterone modulator, has been approved for short-term therapy for symptomatic fibroids. We decided to undertake a systematic review of the best available evidence and draw a more definitive conclusion regarding the efficacy of UA for the management of uterine fibroids. The outcomes included symptomatic relief, quality of life-related parameters, reduction in fibroid size, side effects and recurrence rate. We included four randomised controlled trials which consisted of three trials which compared UA with placebo, and one trial compared it with gonadotropin-releasing hormone analogues for symptomatic relief. The three trials comparing UA with placebo reported significant improvement in symptoms related to excessive uterine bleeding as evidenced by the attainment of amenorrhea or reduction in pictorial blood assessment chart. However, due to the heterogeneity of the available data, a meta-analysis was possible only for one the outcomes - attainment of amenorrhea which indicated improvement in symptoms [57.88 (19.81-169.16); p < 0.00001]. The improved quality of life parameters and reduction in fibroid size was noted in the UA group. With regards to adverse events, even though the three included studies reported increased non-physiological endometrial-related changes following UA, these changes reverted back to normal within 6 months. Short-term use of UA seems to be an effective and safe method of treating uterine fibroids.

Background: Endometriosis is a common, estrogen-dependent, gynecological disease, which is defined as the presence of endometrial tissue outside the uterine cavity. Current data have associated endometriosis with specific malignancies, including ovarian and breast cancer., Purpose: The purpose of our study is to summarize and present published literature providing evidence regarding the possible relationship between endometriosis and breast cancer., Methods: Pubmed and Scopus databases were searched systematically for studies that sought to identify a potential association of endometriosis and breast cancer. 15 relevant articles were retrieved and included in the present review., Results: A small number of observational studies have shown a correlation of endometriosis and breast cancer. Other studies found that the risk of breast cancer increases with age. The scenario of an early interruption of the inflammatory process, derived from endometriosis, by oophorectomy and a possible consequent decrease in the risk of breast cancer has also been proposed. The hypothesis that both conditions could be related through common mutations on BRAC1 and BRAC2 genes has also been investigated., Conclusion: The available published evidence is inconclusive. Further studies are needed to evaluate the association of endometriosis and breast cancer and the possible pathogenetic pathways that relate the two disorders.

Introduction: Compared to laparotomy, laparoscopy has many benefits for patients, such as shorter recovery and lower morbidity rates. Port site metastases after laparoscopic approach in the treatment of gynecologic malignancies are uncommon. The purpose of this review is to identify and summarize possible risk factors for port-site metastases in patients undergoing laparoscopic surgery in the ambit of gynecologic oncology., Discussion: The precise incidence of port-site metastases is not well known because many patients are not followed-up during the whole postoperative period. Possible risk factors that can increase the risk of port-site metastases can be the presence of large masses in the abdomen, especially in the presence of concomitant ascites and in patients treated for ovarian carcinomas. Different theories have been postulated in order to explain the development of port site metastases during laparoscopy for oncological patients., Conclusions: Patient selection is an essential factor that can influence the incidence of port site metastases in gynecological patients. Robust data regarding port site metastases in gynecologic oncology are needed.

An ectopic pregnancy is defined as cesarean scar pregnancy (CSP) when the products of conception are implanted within the myometrium in the area of a cesarean section scar. CSP can be a life-threatening condition and to date there is no clear consensus for CSP management. A medical approach joining high treatment rates with fertility preservation could be a safer and less invasive method of therapy.We present a case of CSP with a viable embryo that was successfully treated with a novel medical therapy combining multidose methotrexate (MTX) and mifepristone.No further additional invasive procedure was required since pregnancy products were dissolved and no major complications were experienced.Multidose MTX and mifepristone can be considered a safe and effective treatment for CSP.

The most frequent ovarian germ cell tumors are mature cystic teratomas (MCTs), composing 10-25% of all ovarian neoplasms. MCTs have the potential of undergoing malignant transformation, typically in postmenopausal women, with a frequency of 0.17-3%, with squamous cell carcinoma being the most common malignant tumor arising from MCT. We present the rare clinical entity of a squamous cell carcinoma arising from a mature cystic teratoma in a 56-year-old premenopausal woman as well as diagnostic and therapeutic route followed.

Within the last decades, the percentage of diagnosed cervical cancer in women of reproductive age has increased. The possibility of diagnosing small cervical tumors (< or = twocm) in childbearing age, can be explained due to the fact that many women, are aware of the benefits of Pap smear or colposcopy examination. Many demand a more conservative policy to handle such lesions in order to have an uneventful pregnancy in the near future.

Primary fallopian tube carcinoma (PFTC) is an uncommon gynecologic tumor, responsible for 0.14% to 1.8% of genital malignancies, with a mean incidence of 3.6 per million women per annum. The factors that contribute to its appearance are not well-known. Overall survival percentages for patients with PFTC are generally low. Although the preoperative diagnosis rarely occurs and it is usually first confirmed by the pathologist, an earlier diagnosis occurs with early clinical manifestation and prompt investigation leading to better prognosis. Both PFTC and epithelial ovarian cancer (EOC) are treated with similar surgical and chemotherapy methods. The authors report a case of a patient with bilateral high grade serous carcinoma of the fallopian tube, whose initial presentation was bilateral cystic adnexal masses and serosanguinous discharge, with no other pelvic involvement. This article also reviews in brief and presents updates of this rare gynecological malignancy.

Homeopathy has been used in the past for treating a broad aspect of diseases. In gynecology, its use remains limited. Taking under consideration its clinical aspects, the authors attempted to use it for treating female sub fertility problems. With this study, the authors present five cases of female infertility treated successfully with the use of homeopathic treatment in a large obstetrics-gynecology Hospital in Athens.

Tuberous sclerosis (TS) or tuberous sclerosis complex (TSC), also known as Bourneville disease or Bourneville-Pringle disease, is an autosomal dominant disorder classically characterized by the presence of hamartomatous growths in multiple organs. A combination of symptoms may include seizures, developmental delay, behavioral problems, skin abnormalities, and lung and kidney diseases. The authors present a case of a 18 year-old female patient with a history of TS, epileptic episodes, mental retardation, and papillary formations in multiple organs located at the abdominal, axillary, cervical, facial, and genital region.

The needs of the uterus and the fetus for the provision of nutrients and oxygen, supplied by the blood flow, are understandably extremely high, with the circulatory system playing the most important role in this action. Abnormal vascular growth and transformation that create a high vessel resistance network have been associated with various pregnancy pathologies, including miscarriage, small for gestational age (SGA) fetuses with or without preeclampsia and intrauterine growth restriction (IUGR). Placental growth factor (PlGF) has a major role in vasculogenesis and angiogenesis in human placenta. Low concentrations of PlGF and high concentrations of its inhibitor-soluble Fms-like tyrosine kinase-1 (sFlt-1) are linked with impaired angiogenesis and placental development, leading to the above pregnancy complications. The activity of vascular endothelial growth factor (VEGF), which is the most potent of all angiogenic mediators, is partly modulated by PlGF. Although the mechanisms via which PlGF exerts its various effects are still under investigation, we herein discuss the known actions exerted by this major mediator together with its results on fetal growth.

Primary fallopian tube carcinoma (PFTC) is a rare gynaecological tumour that accounts for 0.14-1.8% of genital malignancies. The most common age of occurrence is between 40 and 65 years, and the mean age is 55 years. The factors that contribute to its appearance are not well known. Population studies show that the mean incidence of PFTC is 3.6 per million women per annum. Overall survival percentages for patients with PFTC are generally low, in the range of 22-57%. Pre-operative diagnosis is rare and PFTC is usually confirmed by a pathologist, but earlier diagnosis with early clinical manifestation and prompt investigation improves the prognosis. Both PFTC and epithelial ovarian cancer (EOC) are treated with similar surgical and chemotherapy methods. Studies have shown that the prognosis for PFTC is worse than that for EOC or other primary gynaecological tumours. This article reviews and presents the current updates of this rare gynaecological malignancy., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Operative laparoscopy compared with laparotomy has been established as the gold standard surgical approach in treating ovarian cysts. However, the safety of a laparoscopic cystectomy has been questioned in what has to do with the subsequent damage to the ovarian reserve of the operated ovary. One of the best available methods to determine ovarian reserve, due to its biochemical and pathological characteristics is anti-Mullerian hormone (AMH). With this study, we are reviewing currently available studies examining the effect laparoscopic operations have on AMH levels.

One of the most serious complications of assisted reproduction techniques is ovarian hyperstimulation syndrome (OHSS). OHSS not only increases morbidity and mortality in IFV cycles, but also causes significant other problems, as cancelled in vitro fertilization (IVF) cycles, prolonged hospitalization, causing emotional and sociofinancial consequences. Several treatments for OHSS have been proposed and among these Cabergoline (Cb2). Despite the above-mentioned beneficial effect, Cb2 has not been widely used in everyday's clinical practice. With our study, we try to review all studies with strong evidence examining Cb2 use for OHSS prevention.

Purpose: The objective of this study was to evaluate the effect oftamoxifen on the endometrium of45 postmenopausal women with breast cancer, as evidenced by hysteroscopic, ultrasound, histological methods, and by immunohistochemical investigation of the expression of Bcl-2 and Ki67., Materials and Methods: Forty-five postmenopausal women with breast cancer (ER and/or PgR positive) undergoing tamoxifen therapy for six to 48 months, were selected from the files of the 2nd Department of Obstetrics and Gynecology, University of Athens Aretaieion Hospital, among a total of 120 patients treated from 2004-2009., Results: The ultrasound findings during the follow-up period revealed 18 cases of thickened endometrium, 14 cases of suspected polyps, one case with accumulation of endometrial fluid, and 12 cases of heterogeneous endometrial echo texture. The patients had undergone hysteroscopy because of thickened endometrium (18/45 patients), postmenopausal bleeding (14/45 patients), and polyps (13/45 patients). The endometrial tissue samples were examined in the Pathology Department of Aretaieion Hospital and showed in 23 cases with adenomatous endometrial polyps, 15 cases with endometrial cystic atrophy, two cases with adenomatous hyperplasia, and five cases with mucosal endometrial adhesions. Immunohistochemical investigation of Bcl-2 and KJ67 expression was undertaken on paraffin blocks and showed elevated expression in the cases with endometrial polyps and hyperplasia, in contrast to atrophic endometria., Conclusion: Long-term tamoxifen therapy of postmenopausal women with breast cancer is associated with uterine pathology. Ultrasonography alone is useful in asymptomatic patients selecting cases with increased endometrial thickness for further investigation. Hysteroscopy is an accurate method for diagnosing endometrial disease because it provides a direct view of the uterine cavity, reveals focal lesions, and enables targeted biopsies to be performed at the same time. Pathological findings show elevated expression of Ki67 and Bcl-2 in hyperplastic endometria and adenomatous polyps, consistent with an elevated glandular cell proliferation due to tamoxifen effect.

Verrucous carcinoma of the female genital tract is a rare lesion, primarily affecting postmenopausal women. We present a 78-year-old patient with verrucous carcinoma of the vulva, who was admitted to the "Aretaieion" Athens University Hospital. She had complained of vulvar itching during the last two years without visiting a specialist doctor.

Purpose: To evaluate the efficacy of misoprostol administrated vaginally on cervical priming and its complications prior to diagnostic or operative hysteroscopy in women who have undergone at least one cesarean section and who have never delivered vaginally before and/or had other transcervical procedure., Methods: A total of 55 patients undergoing hysteroscopy for various intra-uterine lesions were included in this study and were randomly allocated to two groups finally. Thirty patients in the study group were given 200 μg misoprostol vaginally 12 h before the procedure, whereas 25 patients in the control group did not receive any cervical priming. The countered outcome included the cervical width detected with Hegar dilatators and complication rates., Results: Mean cervical width was greater in the study group (6.6 ± 1.3) than in the control group (5.1 ± 0.9). Complications and failure rates were lower in the study group., Conclusion: Application of 200 μg misoprostol vaginally 12 h before hysteroscopy softens the cervix, reduces cervical resistance and consequently the need for cervical dilatation, with only mild side effects.

Background: We investigated the associations between second trimester amniotic fluid (AF) levels of human adiponectin and placental growth factor (PLGF) in small for gestational age (SGA), large for gestational age (LGA) and appropriate for gestational age (AGA) fetuses., Materials and Methods: Adiponectin and PLGF levels were determined by enzyme immunoassay in AF of 21 SGA, 13 LGA and 44 AGA fetuses between 15-22 weeks of gestation, derived from pregnant women who underwent amniocentesis., Results: Adiponectin and PLGF levels were detectable in AF. Median (25th-75th percentile) adiponectin levels were 16.1 (10.9-32.3) ng/ml in SGA, 19.5 (15.1-30.9) ng/ml in AGA, and 18.2 (14.7-30.8) ng/ml in LGA fetuses. Median (25th-75th percentile) PLGF levels were 24.2 (19.9-34.9) pg/nl in SGA, 26.4 (20.9-33.8) pg/ml in AGA and 33.5 (21.8-40.4) pg/ml in LGA fetuses. The differences were not statistically significant. Nevertheless, indication of differentiation of levels existed when SGA and LGA fetuses in the extremes of distribution were considered. Specifically, very severely SGA fetuses (≤2.5th percentile) tended to have high levels of adiponectin and reduced levels of PLGF in AF., Conclusion: This is the first study presenting adiponectin and PLGF concentrations in early second trimester amniotic fluid in AGA, SGA and LGA fetuses. The altered concentrations of adiponectin and PLGF in very severely SGA fetuses possibly result from the growth-promoting effect of these factors through the metabolic route and the vascular integrity of the placenta, respectively.

Purpose: To assess the diagnostic value of transvaginal sonography (TVS) measurement of the endometrium compared to hysteroscopic findings and histopathologic reports in order to facilitate clinical management in asymptomatic postmenopausal women with thickened endometrium., Methods: During the period between January 2000 and December 2008, a retrospective analysis was performed including cases of women who were preoperatively diagnosed with a sonographically thickened endometrium, while asymptomatic, and therefore underwent hysteroscopic and fractionated dilatation and curettage (D & C) under general anesthesia at the Second Department of Obstetrics and Gynecology at Aretaieion Hospital in Athens, Greece. In the present study we compare US, hysteroscopic and pathologic findings., Results: The mean age of the patients ranged between 54-74 years (mean age 65.2 +/- 6.8 years). In 108 cases, sonographically measured endometrial thickness ranged between 5 and 10 mm. In 59 cases, endometrial thickness ranged between 11 and 15 mm, whereas in 22 cases, between 16 and 20 mm and finally, in 13 cases endometrial thickness was more than 20 mm. Hysteroscopic examination revealed endometrial polyps in 161 cases, focal hyperplastic lesions in 28 cases, complete hyperplastic lesions in five cases while atrophy was found in five and cancer in three cases, respectively. Pathological results of the samples taken after hysteroscopy are as follows: in 169 cases (83.67%) in women with asymptomatic abnormal endometrial thickness, an endometrial polyp was present. Endometrial thickness in these cases patients was 10.9 +/- 7.5 mm. In patients with focal hyperplasia (22 cases), endometrial thickness was 7.2 +/- 0.5 mm but in patients with complete hyperplasia (5 cases) endometrial thickness was higher (12.3 +/- 5.1 mm). Finally, in three cases with endometrial carcinoma endometrial thickness was 15.5 +/- 7.8 mm. Six cases out of 28 described in our study were diagnosed as focal hyperplasia and two out of five cases as complete hyperplasia, whereas histological reports classified these cases as endometrial polyps. The other histological diagnoses confirmed hysteroscopic findings and thus provided the same results., Conclusions: We recommend hysteroscopy to follow gynecological TVS when a thickened endometrium is found in asyptomatic postmenopausal women for better diagnostic and, in a later stage, therapeutic efficacy.

Purpose: To evaluate the effect of the presence of endometrial polyps (EP) on pregnancy rates and how polypectomy could affect pregnancy rates in women scheduled for intrauterine insemination (IUI)., Methods: The study included patients who had attended the Second Department of Obstetrics and Gynecology of the University of Athens from April 2003 to October 2008 for infertility treatment and were candidates for IUI. In these women the presence of an endometrial polyp had been already diagnosed during the infertility evaluation. The study group consisted of 86 women who, following the diagnosis of endometrial polyp, had agreed to have the polyps removed hysteroscopically prior to the IUI. The control group consisted of 85 women, who despite the fact that the presence of an endometrial polyp had been previously diagnosed and its removal suggested, elected not to have the polyp removed. We used statistical analysis to check what effect the removal of the polyp had on the total number of pregnancies., Results: There was a statistically significant difference in cumulative pregnancy rates between the two groups. The group that underwent polyp removal had higher pregnancy rates as compared to the one that the polyps were left intact., Conclusions: We propose that hysteroscopic polypectomy of any size appears to improve fertility in women with otherwise unexplained infertility.