Perivascular epithelioid cell tumor of the uterus: Report of two cases and mini-review of the literature

AbstractIntroductionPerivascular Epithelioid Cell tumor (PEComa) is a rare neoplasm of mesenchymal origin, with the uterus being the most common site of appearance, regarding the female genital tract.Case reportWe present two cases of PEComas of the uterus in patients aged 57 and 42-years-old, presented to our department with palpable abdominal masses and abnormal vaginal bleeding. During follow up period, both patients are free of recurrent disease one and two years after surgery, respectively, without receiving any adjuvant treatment.ConclusionsPEComa of the female gynecological tract is a rare entity presenting with variable symptoms and different prognosis for each individual case. The diagnosis is based on histopathology and immunohistochemistry reports and the optimal treatment is the surgical resection of the tumor

Καλλιέργεια ωοθυλακίων πριν τον σχηματισμό του άντρου (preantral) επίμυων, με την προσθήκη ινοβλαστών (fibroblasts) και καλλιεργητικού μέσου από εμβρυϊκά βλαστικά κύτταρα αμνιακού υγρού: Μελέτη με μορφολογικά κριτήρια και με γενετικούς biomarkers της in vitro ωρίμανσης και γονιμοποίησης και της ανάπτυξης των προεμβρύων μέχρι το στάδιο της βλαστοκύστης

Ένας από τους βασικότερους παράγοντες για την επιτυχή κατάληξη ενός πρωτοκόλλου υποβοηθούμενης αναπαραγωγής είναι η άρτια ωρίμανση των ωοθυλακίων, προκειμένου αυτά να γονιμοποιηθούν in vitro και στη συνέχεια να εμφυτευτούν στη μήτρα. Αυτό επιτυγχάνεται με πρωτόκολλα πρόκλησης πολλαπλής ωοθυλακιορρηξίας, τα οποία βασίζονται στη λήψη φαρμάκων, κυρίως ανασυνδυασμένων γοναδοτροπινών, από μέρους των γυναικών, προκειμένου να γίνει διέγερση των ωοθηκών και αυτές με τη σειρά τους να παράξουν έναν σημαντικό αριθμό ωαρίων, κατάλληλων για γονιμοποίηση. Όμως, ο ορατός κίνδυνος των ανεπιθύμητων ενεργειών, όπως το σύνδρομο υπερδιέγερσης των ωοθηκών (Ovarian Hyperstimulation Syndrome – OHSS), έχει στρέψει τους ειδικούς στην υποβοηθούμενη αναπαραγωγή στην αυξανόμενη εφαρμογή προτοκόλλων με ελάχιστη ή και καθόλου διέγερση των ωοθηκών. Υπό αυτό το πρίσμα, η επιστημονική κοινότητα που ασχολείται με την ανθρώπινη αναπαραγωγή, τα τελευταία χρόνια έχει αφοσιωθεί στην ανεύρεση μεθόδων ωρίμασνης των ωοθυλακίων με την όσο το δυνατόν λιγότερη χρήση φαρμάκων. Μια τέτοια μέθοδος η οποία φαίνεται να απασχολεί έντονα τους ερευνητές είναι η ανάπτυξη και ωρίμανση των ωοθυλακίων σε περιβάλλον εργαστηρίου, εκτός ανθρώπινου οργανισμού. Η προσπάθεια αυτή απαιτεί την ανάπτυξη καλλιεργητικών μέσων, εμπλουτισμένων με ορμόνες και αυξητικούς παράγοντες για την ομάλή ωρίμανση των ωοθυλακίων. Άλλωστε, το ιδανικό καλλιεργητικό μέσο είναι εκείνο, μέσα στο οποίο ένα ωοθυλάκιο μπορεί, ξεκινώντας από το στάδιο του αρχέγονου ωοθυλακίου να αναπτυχθεί ως το Γραφιανό ωοθυλάκιο, με άρτια ανατομική και λειτουργική δομή. Ως τώρα, αυτό έχει πραγματοποιηθεί μόνο στον επίμυ από τους Eppig και Ο’ Brien το 1996. Ο σκοπός της παρούσας μελέτης είναι η διερεύνηση της προσθήκης ινοβλαστών (fibroblasts) και υπερκείμενου καλλιεργητικού μέσου από εμβρυϊκά βλαστικά κύτταρα (stem cells) στην καλλιέργεια ωοθυλακίων πριν τον σχηματισμό του άντρου (preantral) επίμυων. Αξιολογήθηκε με μορφολογικά κριτήρια η in vitro ωρίμανση και γονιμοποίηση αυτών, καθώς και η ανάπτυξη των προεμβρύων μέχρι το στάδιο της βλαστοκύστης. Με το πειραματικό πρωτόκολλο που εφαρμόστηκε, συλλέγησαν δεδομένα από 105 επίμυες. Συγκεκριμένα, χρησιμοποιήθηκαν από 21 επίμυες στην ομάδα ελέγχου, στις ομάδες SAF1, SAF5 και SAF10, όπως και στην ομάδα FIB. Συνολικά, 4514 προκοιλοτικά ωοθυλάκια συλλέγησαν και κατανεμήθηκαν τυχαία στις προαναφερθείσες 5 ομάδες. Αναλυτικά, 1080, 1122, 1190, 1115 και 1197 ωοθυλάκια κατανεμήθηκαν στις ομάδες ελέγχου, SAF1, SAF5, SAF10 και FIB, αντίστοιχα. Στατιστικά σημαντικές διαφορές μεταξύ των ώριμων ωοθυλακίων παρατηρήθηκαν υπέρ της ομάδας FIB (p<0.001) συγκριτικά με την ομάδα ελέγχου αλλά και με τις ομάδες SAF1, SAF5 και SAF10. Στατιστικά σημαντικές διαφορές παρατηρήθηκαν μέσω του Krusakl Wallis H Test στην πρώιμη εμβρυϊκή ανάπτυξη, στα στάδια των 2-, 4-, 8-κυττάρων, καθώς και στο στάδιο μοριδίου-βλαστοκύστης. Περαιτέρω ανάλυση έδειξε πως η ομάδα FIB εμφάνισε στατιστικά σημαντικά υψηλότερο ποσοστό 2-κυττάρων, 4-κυττάρων, 8-κυττάρων και μοριδίου-βλαστοκύστης (p<0.001, p<0.001, p=0.01, p=0.04, αντίστοιχα) or SAF1 (p<0.001, p<0.001, p<0.001. p=0.01, αντίστοιχα) or SAF5 (p<0.001, p<0.001, p=0.002, p=0.02, αντίσχτοιχα) or SAF10 (p<0.001, p<0.001, p<0.001, p=0.02, αντίστοιχα). Η τεχνική της in vitro ανάπτυξης των ωοθυλακίων αποτελεί έναν αναπτυσσόμενο τομέα μελέτης, μέσω του οποίου μπορούμε να αποκομίσουμε σημαντικές πληροφορίες σχετικά με τη διαδικασία της ωοθυλακιογένεσης. Η διενέργεια περαιτέρω μελετών στα έμβρυα που προκύπτουν από αυτή τη διαδικασία κρίνεται ως απαραίτητη, ώστε να αναζητηθούν τυχόν γονιδιακές βλάβες, πριν οι τεχνικές αυτές εφαρμοστούν στον άνθρωπο. Με βάση τα δεδομένα αυτά, το πεδίο της έρευνας στην ωοθυλακική ανάπτυξη αποτελεί μια σημαντική πρόκληση για το μέλλον.During the past years, research community has turned its eye to try and unravel the mysteries that control the stimulation of oocyte growth and development. There have been a great number of studies and experiments with the purpose to explain the mechanisms that govern oocyte development in vitro. Small follicles, isolated from the ovary and cultured in vitro, have the ability to achieve an extraordinary degree of further development, reaching substantial growth, oocyte maturation and ovulation. Inside the basement membrane that surrounds the follicle, the cells interact through numerous mechanisms, such as gap junctions, which enable the follicle to operate as a functional unit. Follicles are created when primary oocytes are enveloped by a single layer of Granulosa Cells. Granulosa cells are essential for the oocyte’s survival, hence the oocyte itself promotes their proliferation. While the follicle grows and becomes antral, subpopulations of granulosa cells can be distinguished according to their location, density and response to gonadotropins and epidermal growth factor (EGF). Surrounding the basement membrane, other cell lines begin to form the theca interna and externa layers. Oocytes from the preantral stage of follicle development require extended periods of growth in vitro, in order to achieve developmental competence. They consist of an oocyte arrested in prophase of meiosis I, enveloped by layers of granulosa and theca cells. This long journey ends with the ovulation of a mature metaphase II oocyte. A detailed knowledge of follicle and oocyte development in vivo is of outmost importance, in order to create an ideal environment for the growth of follicles and oocytes in vitro. In vitro growth cultures are very sensitive and extremely vulnerable. Therefore, it is crucial for the culture to be supplemented with nutrients, electrolytes, antioxidants, amino acids, energy substrates, vitamins and growth factors in order to achieve viability and growth. On the other hand, it is essential to remove waste products that could jeopardize the process. Since the last decade, amniotic fluid stem cell cultures are considered to be a potential provider of an environment that could prove useful in the process of in vitro growth of preantral follicles. The amniotic fluid is a unique source of different populations of stem cells (mesenchymal, hematopoietic, trophoblastic) and, possibly, of more primitive stem cells. Human amniotic fluid contains a cell population positive for mesenchymal markers (CD90, CD105, CD73 and CD166). With the use of reverse transcriptase polymerase chain reaction, flow cytometric and immunocytochemical analyses, it has been established that human amniotic fluid consists of a distinct cell population that expresses Deleted in Azoospermia-Like (DAZL) gene, C-kit, SSEA-4 and Oct-4. These findings indicate the plasticity of amniotic fluid stem cells and their potential use as a multipotent cell source for regenerative somatic cell therapy. Their differentiation potential into cells of all three embryonic germ cell layers along with a high proliferation rate are clear advantages over most known adult stem cell sources. Based on these characteristics, amniotic fluid cells seem to represent an intermediate stage between embryonic stem cells and lineage-restricted adult progenitor cells. It has been established that cellular interactions between ovarian germ-line and somatic cell components are beneficial for follicular development, while there are compounds derived from somatic cells that favor the growth of preantral follicles. Data have shown that amniotic fluid derived mesenchymal stem cells proliferate significantly faster in culture than immunocytochemically comparable cells derived from fetal or adult subcutaneous connective tissue. The present randomized controlled study aimed to assess the in vitro growth of mouse preantral follicles in an environment that is mainly used for the culture of amniotic fluid stem cells and fibroblasts lines. Specifically, in vitro growth of mouse preantral follicles cultured in 1%, 5% and 10% supernatant from amniotic fluid (SAF) stem cells and in fibroblasts derived from amniotic fluid (FIB) were compared to those cultured in a basic culture medium. In addition, we aimed to evaluate which of these culture mediums provided the higher number of mature follicles, 2-, 4- and 8-cells and morulas/blastocysts embryo stages. Data from 105 mouse were collected (21 in the control group, 21 in the F1 group, 21 in the F10 group, 21 in the F5 group and 21 in the FIB group). In total, 4514 preantral follicles were collected and randomly distributed in the five experimental groups. In particular, 1080, 1122, 1190 and 1115 follicles and 1197 were assigned to control, SAF1, SAF5, SAF10 and FIB respectively. Abnormally distributed data were found for the 2-cells, 4-cells, 8-cells and MB stages of embryos. Outliers were not found in any of the searched variances. Differences between groups using Welch ANOVA or Kruskal Wallis H Test are presented in Table 1. Statistically significant difference between mature follicles were detected by the Welch ANOVA (F(4)=31.2, p<0.001, partial eta squared 0.6). Tuckey post-hoc revealed that mature oocytes were significantly more in the FIB group (p<0.001) compared to control, SAF1, SAF5 and SAF10 group (Table 1). Statistically significant difference was detected for the 2-, 4-, 8-cells and MB between groups by the Kruskal Wallis H Test. Pairwise post-hoc comparisons revealed that FIB group had significantly higher number of 2-cells, 4-cells, 8-cells and MB compared to control (p<0.001, p<0.001, p=0.01, p=0.04, respectively) or SAF1 (p<0.001, p<0.001, p<0.001. p=0.01, respectively) or SAF5 (p<0.001, p<0.001, p=0.002, p=0.02, respectively) or SAF10 (p<0.001, p<0.001, p<0.001, p=0.02, respectively). The process of in vitro growth of preantral follicles has not left the experimental stage, at least not yet. The challenge to develop technologies in the laboratory, that could lead from a follicle containing a prophase I oocyte to a metaphase II one, capable of ovulation and fertilization could lead to a scientific breakthrough. Combined with the advances in cryopreservation and IVM, could be a tremendous help for young patients to preserve their fertility, being able to store their own germ cells before abdominal surgery or aggressive chemo- and/or radiotherapy, which is known to partially or completely destroy their follicular reserve. Fertility preservation in young patients with cancer is a novel therapeutic approach that is gaining more ground by the gynecologic oncology experts. A few years ago, this notion would be out of the question. But as science progresses to minimal invasive and personalized treatment and cancer patients are now of significantly younger age than the previous decades, it is now considered malpractice not to offer up-to-date fertility preservation alternatives

Human Chorionic Gonadotropin: The Pregnancy Hormone and More

To thoroughly review the uses of human chorionic gonadotropin (hCG) related to the process of reproduction and also assess new, non-traditional theories. Review of the international literature and research studies. hCG and its receptor, LH/CGR, are expressed in numerous sites of the reproductive tract, both in gonadal and extra-goanadal tissues, promoting oocyte maturation, fertilization, implantation and early embryo development. Moreover, hCG seems to have a potential role as an anti-rejection agent in solid organ transplantation. Future research needs to focus extensively on the functions of hCG and its receptor LH/CGR, in an effort to reveal known, as well as unknown clinical potentials

Pyoderma Gangrenosum of the breast: A case report study

INTRODUCTION: Pyoderma gangrenosum (PG) of the breast is a rare and rapidly spreading disease, which usually co-exists with severe underlying systemic conditions. PG often presents secondary to breast surgery with skin lesions and signs of infection, even though it is a non-infectious, necrotizing dermatological entity. PRESENTATION OF CASE: We present a case of de novo unilateral breast PG in 37-year-old woman, with a clear medical history whatsoever. The patient was treated with corticosteroids and, in a two-month follow up, presents with nearly no signs of PG. DISCUSSION: PG of the breast presents with atypical clinical signs and is characterized by an exclusion based diagnosis. It often mimics inflammation but is resistant to antibiotics. CONCLUSION: The optimal treatment for PG is systemic use of corticosteroids and surgical debridement of the necrotic tissue, while the timely onset of the therapeutic approach is of outmost importance. (C) 2017 The Author(s). Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd

Detection of High-Grade Cervical Intraepithelial Neoplasia by Electrical Impedance Spectroscopy in Women Diagnosed with Low-Grade Cervical Intraepithelial Neoplasia in Cytology

The authors attempt to address the importance of timely detection and management of cervical intraepithelial neoplasia (CIN) to prevent cervical cancer. The study focused on the potential of electrical impedance spectroscopy (EIS) as an adjunct to colposcopy, aiming to enhance the accuracy of identifying high-grade cervical lesions. Colposcopy, a widely used technique, exhibited variable sensitivity in detecting high-grade lesions, which relies on the expertise of the operator. The study’s primary objective is to evaluate the effectiveness of combining colposcopy with EIS in detecting high-grade cervical lesions among patients initially diagnosed with low-grade CIN based on cytology. We employed a cross-sectional observational design, recruiting 101 women with abnormal cervical cytology results. The participants underwent colposcopy with acetic acid and subsequent EIS using the ZedScan device. The ZedScan results are categorized into color-coded probability levels, with red indicating the highest likelihood of high-grade squamous intraepithelial lesions (HSIL) occurrence. Results revealed that ZedScan exhibits a sensitivity rate of 89.5% and a specificity rate of 84% for detecting high-grade lesions. Colposcopy, on the other hand, recorded a sensitivity rate of 85.5% and a specificity rate of 92%. The agreement rate between ZedScan and biopsy is 79.2%, as indicated by a kappa coefficient of 0.71, while the agreement rate between colposcopy and biopsy is 74.3%, with a kappa coefficient of 0.71

LH receptor gene expression in cumulus cells in women entering an ART program

Luteinizing hormone (LH) exerts its actions through its receptor (LHR), which is mainly expressed in theca cells and to a lesser extent in oocytes, granulosa and cumulus cells. The aim of the present study was the investigation of a possible correlation between LHR gene and LHR splice variants expression in cumulus cells and ovarian response as well as ART outcome. Forty patients undergoing ICSI treatment for male factor infertility underwent a long luteal GnRH-agonist downregulation protocol with a fixed 5-day rLH pre-treatment prior to rFSH stimulation and samples of cumulus cells were collected on the day of egg collection. RNA extraction and cDNA preparation was followed by LHR gene expression investigation through real-time PCR. Furthermore, cumulus cells were investigated for the detection of LHR splice variants using reverse transcription PCR. Concerning LHR expression in cumulus cells, a statistically significant negative association was observed with the duration of ovarian stimulation (odds ratio = 0.23, = 0.012). Interestingly, 6 over 7 women who fell pregnant expressed at least two specific types of LHR splice variants (735 bp, 621 bp), while only 1 out of 19 women that did not express any splice variant achieved a pregnancy. Consequently, the present study provide a step towards a new role of LHR gene expression profiling as a biomarker in the prediction of ovarian response at least in terms of duration of stimulation and also a tentative role of LHR splice variants expression in the prediction of pregnancy success

What Has Changed in the Management of Uterine Serous Carcinomas? Two Decades of Experience

Uterine serous carcinoma accounts for 3–10% of endometrial cancers, but it is the most lethal histopathological subtype. The molecular characterization of endometrial carcinomas has allowed novel therapeutic approaches for these patients. We undertook a retrospective analysis of patients with uterine serous carcinomas treated in our hospital within the last two decades to identify possible changes in their management. The patients and their characteristics were evenly distributed across the two decades. Treatment modalities did not change significantly throughout this period. After adjuvant treatment, patients’ median disease-free survival was 42.07 months (95% CI: 20.28–63.85), and it did not differ significantly between the two decades (p = 0.059). The median overall survival was 47.51 months (95% Cl: 32.18–62.83), and it significantly favored the first decade’s patients (p = 0.024). In patients with de novo metastatic or recurrent disease, median progression-free survival was 7.8 months (95% Cl: 5.81–9.93), whereas both the median progression-free survival and the median overall survival of these patients did not show any significant improvement during the examined time period. Overall, the results of our study explore the minor changes in respect of uterine serous carcinoma’s treatment over the last two decades, which are reflected in the survival outcomes of these patients and consequently underline the critical need for therapeutic advances in the near future