Exosomes - Spectacular role in reproduction.

Exosomes are nano-sized structures that are found in semen, epididymal -fluid, endometrium, as well as in follicular fluid. They are responsible for transporting bioactive cargo- proteins, lipids, and nucleic acids. Exosomes have been proven to influence processes in both female and male reproductive systems, including gametogenesis, acrosomal reaction, sperm capacitation, and embryo implantation in the endometrium. Exosomes are made of the same particles as the cells they come from and are secreted by normal and pathological cells. Therefore, exosomes can reflect the physiological state of cells. Moreover, due to the transportation of biomolecules, they participate in intercellular communication and can be used as biomarkers of many diseases, including ovarian, endometrial and prostate cancer. Identification of exosomes as biomarkers could contribute to a better understanding of genital dysfunction and fertility disorders.

Baby Wet Wipes: An Unusual Culprit of Lymphomatoid Contact Dermatitis Mimicking Mycosis Fungoides.

ABSTRACT: Lymphomatoid contact dermatitis (LCD) is a rare, benign pseudolymphoma with clinicopathologic features of both allergic contact dermatitis and cutaneous T-cell lymphoma (CTCL). In this article, we report a fascinating case of LCD secondary to chronic baby wet wipe use with clinical features of allergic contact dermatitis and histopathologic changes of mycosis fungoides, a subtype of CTCL. We argue that LCD should be added to the list of mimickers of mycosis fungoides, a subtype of CTCL.

A Systematic Review of Anogenital Distance and Gynecological Disorders: Endometriosis and Polycystic Ovary Syndrome.

Background and Aim: Anogenital distance (AGD) can serve as a life-long indicator of androgen action in gestational weeks 8-14. AGD has been used as an important tool to investigate the exposure to endocrine-disrupting compounds in newborns and in individuals with male reproductive disorder. Endometriosis and polycystic ovary syndrome (PCOS) are two common gynecological disorders and both are related to prenatal androgen levels. Therefore, we performed a systematic review to evaluate the relationships of AGD with these gynecological disorders. Methods: PubMed, Web of Science, and Embase were searched for published studies up to January 25, 2021. No language restriction was implemented. Results: Ten studies were included in this review. Five focused on women with endometriosis, and six investigated women with PCOS. According to these studies, PCOS patients had longer AGD than controls, while endometriosis patients had shorter AGD than controls. In conclusion, this study provides a detailed and accurate review of the associations of AGD with endometriosis and PCOS. Conclusion: The current findings indicate the longer AGD was related to PCOS and shorter AGD was related to endometriosis. However, further well-designed studies are needed to corroborate the current findings.

Ischemia-modified albumin in gynecology.

Background: Ischemia-modified albumin (IMA) is an oxidative stress marker used to assess the presence and severity of oxidative stress. This marker was first used for early diagnosis of myocardial ischemia. Materials & methods: A variety of IMA studies were carried out to show the effect of oxidative stress on gynecological disorders. Conclusion: This analysis summarizes the literature by conducting electronic research on the relationship between IMA and gynecological disorders.

"I have had an exceedingly beautiful life" The Jewish gynecopathologist Robert Meyer (1864-1947) and his extraordinary response to Nazi repression.

The Jewish scientist Robert Meyer received worldwide professional recognition as a pioneer gynecopathologist. Before his death, he wrote a memoir in which he gave an entirely positive assessment of his life. The latter, however, is at odds with the fact that he was disenfranchised by the National Socialists and driven into emigration. But even before Hitler's seizure of power, he had to cope with several strokes in private as well as in professional life. This article takes these apparent inconsistencies as an occasion for a fundamental analysis of Robert Meyer's life and work. Special attention is paid to his scientific achievements, but also to repressive experiences in the Third Reich, the background of his emigration and his specific handling of these adversities. Various archival documents, Meyer's memoirs, and other contemporary writings by and about Robert Meyer and about the development of the field of gynecopathology serve as central sources. The study concludes that Meyer made fundamental contributions to the embryology of the vagina, ovarian tumors, cancer diagnosis, endometriosis, and genital and fetal abnormalities. Despite his scientific merits, he was never granted a regular professorship - mainly, because he was professionally caught between two stools (gynecology and pathology), but also due to low career ambition. Nevertheless, thanks to influential supporters, he was able to hold out in Germany until 1939, when he emigrated to the United States. Meyer considered his life "beautiful" despite many misfortunes because he defined happiness in life primarily in terms of fulfilling personal relationships and was willing to accept life as it comes. In addition, he found distraction and fulfillment in his scientific work.

Organoids of the female reproductive tract.

Healthy functioning of the female reproductive tract (FRT) depends on balanced and dynamic regulation by hormones during the menstrual cycle, pregnancy and childbirth. The mucosal epithelial lining of different regions of the FRT-ovaries, fallopian tubes, uterus, cervix and vagina-facilitates the selective transport of gametes and successful transfer of the zygote to the uterus where it implants and pregnancy takes place. It also prevents pathogen entry. Recent developments in three-dimensional (3D) organoid systems from the FRT now provide crucial experimental models that recapitulate the cellular heterogeneity and physiological, anatomical and functional properties of the organ in vitro. In this review, we summarise the state of the art on organoids generated from different regions of the FRT. We discuss the potential applications of these powerful in vitro models to study normal physiology, fertility, infections, diseases, drug discovery and personalised medicine.

Gynecological, reproductive and sexual outcomes after uterine artery embolization for post-partum haemorrage.

In this case control study, long-term gynecological, reproductive and sexual outcomes after uterine artery embolization (UAE) for postpartum hemorrhage (PPH) were evaluated. The study was performed in a single referral hospital for PPH in Lausanne from 2003 to 2013. Each woman whose delivery was complicated by PPH and treated by UAE was included, and compared to a control group of women whose delivery was uncomplicated. Cases were matched by maternal age, parity, ethnicity, year and mode of delivery, birth weight and gestational age in a 1-3 ratio. A total of 77 patients treated by UAE for PPH were identified in our obstetrical database. Among them, 63 were included and compared to 189 matched patients (no PPH). The mean interval time between UAE and this study was 8.1 years. Time to menstrual cycle recovery after delivery (3.9 vs 5.6 months, p = 0.66), spotting (7.9% vs 7.2%, p = 0.49), dysmenorrhea (25.4% vs 22.2%, p = 0.60) and amenorrhea (14.3% vs 12.2%, p = 0.66) were similar between the two groups. There was no difference in the FSFI score between the groups (23.2 ± 0.6 vs 23.8 ± 0.4; p = 0.41). However, the interval time to subsequent pregnancy was longer for patients after UAE than the control group (35 vs 18 months, p = 0.002). In case of pregnancy desire, the success rate was lower after UAE compared to controls (55% vs 93.5%, p < 0.001). The rate of PPH was higher in those with previous PPH (6.6% vs 36.4%, p = 0.010). Patients treated by UAE for PPH did not report higher rates of gynecological symptoms or sexual dysfunction compared to patients with uneventful deliveries. The inter-pregnancy interval was increased and the success rate was reduced. In subsequent pregnancies, a higher rate of PPH was observed in those that underwent UAE.

Review of 189 Consecutive Female Genital Skin and Mucosal Biopsies Submitted to an Academic Dermatopathology Practice.

OBJECTIVES: To describe consecutive vulvar biopsy cases and to create an educational template for pathology trainees and practicing pathologists. METHODS: We reviewed 189 consecutive biopsies from the female genital area skin and mucosa. We classified them based on etiologies and examined limited clinical information. RESULTS: We classified diagnoses as squamous intraepithelial neoplasia (21.5%), melanocytic neoplasia (17.9%), lichenoid dermatoses (15.9%), nonlichenoid dermatoses (11.3%), infectious (6.2%), reparative (4.6%), or miscellaneous (22.6%). The miscellaneous diagnoses included common entities (polyps and cysts) and rarer entities (calcinosis cutis, adnexal neoplasms, or basal cell carcinoma) and nonspecific descriptive diagnoses. Clinicians most often included the actual diagnosis in their differential for melanocytic lesions (83%) and least often for inflammatory lesions (32%). However, some cases included a clinical description without a differential diagnosis (14%) or no helpful clinical information (4%). The distribution of whether correct diagnoses were included in the clinical differential was similar between submitting physicians and midlevel providers. CONCLUSIONS: Understanding squamous and melanocytic pathology and the various lichenoid and other inflammatory diagnoses is critical for signing out female genital tract skin pathology. The cases examined in this report can serve as an educational template for trainees and practicing pathologists.

Evaluating sensitivity and specificity of handheld point-of-care ultrasound testing for gynecologic pathology: a pilot study for use in low resource settings.

BACKGROUND: Point-of-care ultrasound (POC-US) is a diagnostic test conducted at the site of patient care with direct interpretation by the clinician, providing immediate results. POC-US for gynecologic application is not well characterized by current literature yet has the potential to increase access in limited resource settings. We compared the diagnostics of three POC-US devices for gynecologic (GYN) pathology and then performed evaluation of sensitivity and specificity of a single best POC-US device for intended use in a low resource setting. METHODS: This is prospective, pilot descriptive study of 60 subjects. In part 1, comparison of three POC-US devices was performed. Twenty subjects underwent POC-US with three test units [GE Vscan (Vscan), Sonosite Iviz (Iviz), Philips Lumify (Lumify)] followed by diagnostic ultrasound (Dx-US) for reference imaging. Image quality and correlation for devices was scored by blinded reviewers and quantitative measurements of GYN pathology were compared. In part 2, forty subjects underwent POC-US validation with the highest scoring device (Lumify) and Dx-US for reference imaging. Concordance of POC-US operator-interpreted diagnosis with reference imaging interpretation were assessed by Cohen's unweighted kappa coefficient. Accuracy and agreement of POC-US were assessed by linear regression and Bland-Altman plot analysis. Sensitivity and specificity of POC-US for gynecologic pathologies were calculated. RESULTS: In aggregate qualitative measurements, Lumify and Iviz units performed superiorly to Vscan. There was no statistically significant difference in quantitative measurements between devices, but a trend towards lower mean error was seen for Lumify and Iviz as compared to Vscan. Lumify device had highest overall scoring and was selected for further testing. In validation comparison of Lumify to Dx-US, no statistically significant differences were found for measurements of endometrium, uterus, ovaries, adnexal pathology, or leiomyomata, (P < 0.02) with excellent agreement in operator-interpreted diagnosis (Kappa > 0.7). Sensitivity and specificity of detecting pathology was 80-100% with PPV and NPV 76-100%. CONCLUSION: Among three POC-US devices, Lumify and Iviz devices show highest potential for successful application to clinical gynecologic ultrasound. Clinician-performed POC-US has high diagnostic accuracy, sensitivity, and specificity for basic GYN anatomy and pathology. POC-US is an acceptable and feasible diagnostic tool with potential for future application in a low resource setting to increase access to ultrasound.

Report of the National Cancer Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development-sponsored workshop: gynecology and women's health-benign conditions and cancer.

The Division of Cancer Prevention and the Division of Cancer Biology at the National Cancer Institute and the Gynecologic Health and Disease Branch in the National Institute of Child Health and Human Development organized a workshop in April 2019 to explore current insights into the progression of gynecologic cancers from benign conditions. Working groups were formed based on 3 gynecologic disease types: (1) Endometriosis or Endometrial Cancer and Endometrial-Associated Ovarian Cancer, (2) Uterine Fibroids (Leiomyoma) or Leiomyosarcoma, and (3) Adenomyosis or Adenocarcinoma. In this report, we highlight the key questions and current challenges that emerged from the working group discussions and present potential research opportunities that may advance our understanding of the progression of gynecologic benign conditions to cancer.

Simulation-based clinical learning for the third year medical student: Effectiveness of transabdominal and transvaginal ultrasound for elucidation of OB/GYN scenarios.

PURPOSE: Point-of-care ultrasound (POCUS) is gaining recognition as a teaching modality that acts as an integrative learning tool during medical student transition to clinical rotations. This study aimed to determine if the use of ultrasound simulation enhances understanding of Obstetrical and Gynecological (Ob/Gyn) anatomy and pathology in third-year medical students (M3), and if M3 students found the simulator useful. METHODS: M3 students taking the OB/Gyn clerkship were invited to participate. Baseline knowledge of pelvic ultrasound anatomy and pathology was assessed with a multiple-choice question test. Participants received a one-hour OB/Gyn ultrasound simulation training session. A post-test assessed knowledge after the intervention. Survey data was collected regarding learning styles and learner satisfaction. RESULTS: Following simulator-based training, the median correct number of responses to the knowledge questions increased from 11 of 18 to 14 of 18 correct (P < .001). Statistically significant increases were also observed in comfort level with OB/GYN ultrasound (P < .001). All 68 students answered that the ultrasound simulator was helpful and enjoyed using the simulator. CONCLUSIONS: This study suggests that ultrasound simulators are useful for improvement in knowledge, comfort level, and ability to identify pathology in Ob/Gyn scenarios in M3 students.

Genital verruciform xanthoma: lessons from a contemporary multi-institutional series.

AIMS: Verruciform xanthoma (VX) is an uncommon lesion, seen in the oral mucosa and rarely occurring at cutaneous genital sites. Reports of exceptional VX presentations dominate the literature; herein, we assess the clinical and histological features of a cohort of routine, consecutive cases. METHODS AND RESULTS: Clinicopathological features of genital VXs from four academic centres were reviewed. A cohort of 25 lesions from 24 patients (22 male, two female; median age = 62 years), occurred on the scrotum (84%), penis (8%) and perineum/vulva (8%). VX was never suspected clinically; considerations ranged from fibroepithelial polyps to squamous cell carcinoma. Classic diagnostic criteria were present at least focally in each lesion, including verrucous architecture, prominent wedge-shaped parakeratosis extending between exophytic epidermal projections and neutrophils in the stratum corneum. Xanthomatous cells were present in all cases, but scattered to rare in 24%. CONCLUSIONS: Consecutive genital VXs reliably exhibited classic histopathological features, although the essential finding of xanthomatous cells may be scarce. Our comparison to meta-analyses of published cases found relatively fewer penile and vulvar examples. Additionally, the median age was older than in published series, which have emphasised syndromic associations.

Histeroscopía quirúrgica: experiencia, resultados y complicaciones según clasificación Clavien-Dindo / Surgical hysteroscopy: experience, results and complications according to Clavien-Dindo classification

OBJETIVO: Describir y analizar la experiencia clínica, resultados y complicaciones según Clavien-Dindo de las histeroscopías quirúrgicas realizadas en pabellón. MÉTODOS: Estudio descriptivo retrospectivo de las histeroscopías quirúrgicas realizadas entre el 1 de enero de 2012 y 1 de enero de 2018 en el Hospital Clínico de la Universidad de Chile. RESULTADOS: Hubo 613 histeroscopías quirúrgicas en el período analizado, de las cuales 593 cumplieron con los requisitos para incluirse en este estudio. Las indicaciones para realizar el procedimiento fueron: pólipo endometrial (56,3%), miomas uterinos (22,1%), sangrado uterino anormal (4,3%) y otras (17,7%). Hubo un 89,2% de concordancia entre el diagnóstico intraoperatorio y el estudio histopatológico. Se pesquisaron 11 hiperplasias endometriales sin atipías, 3 con atipías y 10 neoplasias malignas. Cabe destacar que, del total de pólipos resecados, hubo 8 casos (2,5%) con potencial malignidad (atipías o neoplasia maligna). Según la clasificación Clavien Dindo, hubo 22 complicaciones intraoperatorias (3,7%) grado I o II, cuyo diagnóstico fue realizado en el acto quirúrgico. No hubo complicaciones grado III o más (severas, con reintervención). CONCLUSIÓN: La tasa de éxito, correlación histeroscópica - anatomopatológica final y complicaciones fue similar a lo publicado en la literatura disponible. El diagnóstico intraoperatorio de la lesión y su reparación en el mismo acto quirúrgico, disminuye el riesgo de morbimortalidad de las pacientes, haciéndolo similar al de una paciente sin complicación. Utilizar la clasificación Clavien Dindo para evaluar las complicaciones nos permitirá en adelante, objetivar, mejorar aspectos del procedimiento quirúrgico y plantear estrategias de prevención y manejo de dichos eventos adversos.

OBJECTIVE: To describe and analyze the clinical experience, results and complications according to Clavien-Dindo of surgical hysteroscopies performed in the ward. METHODS: Retrospective descriptive study of surgical hysteroscopies performed between January 1, 2012 and January 1, 2018 at the Hospital Clinico of the University of Chile. RESULTS: There were 613 surgical hysteroscopies in the analyzed period of which 593 fulfilled the requirements to be included in this study. The indications to perform the procedure were: endometrial polyp (56.3%), uterine fibroids (22.1%), abnormal uterine bleeding (4.3%) and others (17.7%). There was an 89.2% agreement between the intraoperative diagnosis and the histopathological study. Eleven endometrial hyperplasias without atypia, 3 with atypia and 10 malignant neoplasms were investigated. It should be noted that, of the total of resected polyps, there were 8 cases (2.5%) with potential malignancy (atypia or malignant neoplasm). According to the Clavien Dindo classification, there were 22 intraoperative complications (3.7%) grade I or II, the diagnosis of which was made during surgery. There were no grade III or more complications (severe, with reoperation). CONCLUSION: The success rate, final hysteroscopic-pathological correlation and complications was similar to that published in the available literature. The intraoperative diagnosis of the lesion and its repair in the same surgical act, reduces the risk of morbidity and mortality of the patients, making it similar to that of a patient without complication. Using the Clavien Dindo classification to assess complications will henceforth allow us to objectify, improve aspects of the surgical procedure and propose strategies for the prevention and management of such adverse events.

Prevalence of endosalpingiosis and other benign gynecologic lesions.

Endosalpingiosis, traditionally regarded as an incidental pathological finding, was recently reported to have an association with gynecologic malignancies. To determine the prevalence of endosalpingiosis, we evaluated all benign appearing adnexal lesions using the Sectioning and Extensively Examining-Fimbria (SEE-Fim) protocol, and queried the pathology database for the presence of endosalpingiosis, gynecologic malignancy, endometriosis, Walthard nests, and paratubal cysts. Using the SEE-Fim protocol, the prevalence of endosalpingiosis, endometriosis, Walthard nests, and paratubal cysts were 22%, 45%, 33%, and 42% respectively, substantially higher than previously reported. All lesions were observed to increase with age except endometriosis which increased until menopause then decreased dramatically. Among specimens including ovarian tissue, the prevalence of implantation of at least one lesion type was ubiquitous in patients age 51 and older (93%). The clinical significance of endosalpingiosis should be a continued area of research with larger trials assessing prevalence, factors affecting incidence, and association with malignancy. Our findings contribute to elucidating the origin of ectopic lesions and gynecologic disease risk.

Expert consensus from the Italian Society for Colposcopy and Cervico-Vaginal Pathology (SICPCV) for colposcopy and outpatient surgery of the lower genital tract during the COVID-19 pandemic.

In the context of the COVID-19 pandemic, patients need to be evaluated within 2-4 weeks in the following cases: cytology result of "squamous cell carcinoma," "atypical glandular cells, favor neoplastic," "endocervical adenocarcinoma in situ," or "adenocarcinoma"; histopathological diagnosis of suspected invasion from cervical/vaginal biopsy, or invasive disease after a cervical excision procedure, vaginal excision, or vulvar biopsy/excision; sudden onset of strongly suggestive symptoms for malignancy. Digital imaging technologies represent an important opportunity during the COVID-19 pandemic to share colposcopic images with reference centers, with the aim of avoiding any concentration of patients. All patients must undergo screening for COVID-19 exposure and should wear a surgical mask. A high-efficiency filter smoke evacuation system is mandatory to remove surgical smoke. Electrosurgical instruments should be set at the lowest possible power and not be used for long continuous periods to reduce the amount of surgical smoke. The following personal protective equipment should be used: sterile fluid-repellant surgical gloves, an underlying pair of gloves, eye protection, FFP3 mask, surgical cap, and gown. The colposcope should be protected by a disposable transparent cover. A protective lens that must be disinfected after each use should be applied. The use of a video colposcope should be preferred.

Biological therapy in genital psoriasis in women.

Genital psoriasis (GenPs) is a frequent manifestation of psoriasis, causing distress, especially in women. We prospectively studied a population of 74 psoriatic women with severe and generalized psoriasis eligible to biologic therapy, to examine which biologic therapy is more effective on GenPs and to study possible associations between PASI severity and GenPs. Overall, 25/74 (34%) had GenPs: 6 received Ixekizumab, 7 Ustekinumab, 8 Adalimumab, 2 Secukinumab, 1 Etanercept, 1 Certolizumab. Therapies were administered based on PASI severity, independently from the presence of GenPs. Side effects, PASI score, sPGA-G scale for GenPs were recorded at time 0 and after 6 month of therapy. The mean sPGA-G scale value was 2.8 before treatment. After biologic therapy, all patients except one, improved of at least one point. Mostly, patients treated with anti-IL17 (Secukinumab, Ixekizumab) and anti-IL12/23 (Ustekinumab) improved. Mean PASI ranged from 10 to 16.3 before treatment. After 6 months of therapy, 4 anti-TNFα patients, 6 anti-IL17 and 1 anti-IL12/23, reached PASI 90. At time 0, no correlation between PASI and sPGA-G was visible (Pearson r = 0.10, p = .620). From our data, GenPs apparently responds favorably to IL17A inhibitors, but further studies, based on larger numbers of patients, are needed.