It is time to implement molecular classification in endometrial cancer.

A huge effort has been done in redefining endometrial cancer (EC) risk classes in the last decade. However, known prognostic factors (FIGO staging and grading, biomolecular classification and ESMO-ESGO-ESTRO risk classes stratification) are not able to predict outcomes and especially recurrences. Biomolecular classification has helped in re-classifying patients for a more appropriate adjuvant treatment and clinical studies suggest that currently used molecular classification improves the risk assessment of women with EC, however, it does not clearly explain differences in recurrence profiles. Furthermore, a lack of evidence appears in EC guidelines. Here, we summarize the main concepts why molecular classification is not enough in the management of endometrial cancer, by highlighting some promising innovative examples in scientific literature studies with a clinical potential significant impact.

Endometriosis and Adolescence: The Impact of Dysmenorrhea.

Endometriosis affects approximately 10% of premenopausal women worldwide. Despite its impact on quality of life, the delay in diagnosing this chronic disease is well known. Many patients with endometriosis report having suffered from dysmenorrhea and chronic pelvic pain in adolescence or at a young age. However, this painful symptom is often highly underestimated and considered a normal and transient symptom in young women. The real prevalence of endometriosis in adolescence remains uncertain. Some authors recently described at least one ultrasound feature of endometriosis in 13.3% of a general population of adolescent girls, which increased to 35.3% in young girls with severe dysmenorrhea. Dysmenorrhea is classified as primary dysmenorrhea or secondary dysmenorrhea. Primary dysmenorrhea is defined as a menstrual pain without organic disease, while secondary dysmenorrhea is defined as a menstrual pain associated with organic pelvic pathology. Since endometriosis represents the main cause of secondary dysmenorrhea in adolescents and young women, it is important to determine whether the patient has primary dysmenorrhea or additional suggestive symptoms related to endometriosis. Endometriosis in adolescent patients is a challenging problem with clinical and pathological differences compared with its presentation in premenopausal women. Adolescents and young women with dysmenorrhea and painful symptoms that suggest endometriosis should be referred to dedicated endometriosis centers for an early diagnosis and appropriate medical and surgical management. This paper aims to describe the role of dysmenorrhea in adolescents and the management of these young patients to confirm or exclude endometriosis.

Towards reproducible research in recurrent pregnancy loss immunology: Learning from cancer microenvironment deconvolution.

The most recent international guidelines regarding recurrent pregnancy loss (RPL) exclude most of the immunological tests recommended for RPL since they do not reach an evidence-based level. Comparisons for metanalysis and systematic reviews are limited by the ambiguity in terms of RPL definition, etiological and risk factors, diagnostic work-up, and treatments applied. Therefore, cohort heterogeneity, the inadequacy of numerosity, and the quality of data confirm a not standardized research quality in the RPL field, especially for immunological background, for which potential research application remains confined in a separate single biological layer. Innovative sequencing technologies and databases have proved to play a significant role in the exploration and validation of cancer research in the context of dataset quality and bioinformatics tools. In this article, we will investigate how bioinformatics tools born for large-scale cancer immunological research could revolutionize RPL immunological research but are limited by the nature of current RPL datasets.

Transvaginal ultrasound evaluation of the pelvis and symptoms after laparoscopic partial cystectomy for bladder endometriosis

Objective: To evaluate transvaginal sonography (TVS) findings after laparoscopic partial cystectomy for bladder endometriosis and to correlate postsurgical ultrasound findings with symptoms. Material and Methods: A retrospective study including women who underwent laparoscopic partial cystectomy for bladder endometriosis. Within 12 months after surgery, TVS examination was conducted in all patients to evaluate the bladder morphology, and the presence of any postsurgical sonographic findings of the pelvis. Painful symptoms were assessed using a visual analogue scale. Results: A total of 40 women were included. At the follow-up visit, 25 patients were receiving medical treatment while 15 had declined post-surgical therapy and had tried to conceive. The presence of bladder deep-infiltrating endometriosis (DIE) was found in nine (22.5%), fibrotic thickening of the bladder wall was found in 15 (37.5%), and normal bladder morphology was observed in 16 (40%). There was a correlation between anterior adenomyosis and bladder DIE, and fibrotic thickening of the bladder. Patients with TVS signs of bladder DIE and anterior adenomyosis suffered more dysmenorrhea and dysuria than patients with normal bladder. Conclusion: Post-operative TVS can detect the alteration of pelvis and could explain the causes of the persistence of symptoms.

Ultrasound Findings of Adenomyosis in Adolescents: Type and Grade of the Disease.

STUDY OBJECTIVE: To evaluate the ultrasound features, types, and degrees of adenomyosis among adolescents and to correlate these findings with clinical symptoms DESIGN: A retrospective observational study. SETTING: Gynecological ultrasound units from January 2014 to June 2020. PATIENTS: A total of 43 adolescents (aged 12-20 years) who were diagnosed as having adenomyosis at a pelvic ultrasound examination. INTERVENTIONS: Ultrasound features and location and type of adenomyosis within the uterus were evaluated on stored 2-dimensional images and videos and 3-dimensional volumes. Adenomyosis was classified as mild, moderate, and severe according to the extension of the disease in the uterus as described in our previous published classification. MEASUREMENTS AND MAIN RESULTS: Adenomyotic features recorded among our population were myometrial hyperechoic areas, uterine wall asymmetry, intramyometrial cystic areas, and some types of junctional zone alterations. The posterior uterine wall (58%) and the outer myometrial layer (93%) were mostly affected. In 44% of adolescents (19/43) with adenomyosis, at least 1 location of pelvic endometriosis was documented. Dysmenorrhea was the most commonly reported symptoms (88%), and it was associated with adenomyosis of the outer myometrium, myometrial hyperechoic areas, uterine wall asymmetry, and intramyometrial cystic areas. Adolescents with dyspareunia showed diffuse adenomyosis (9/9 patients) including both the inner and outer myometrium (7/9 patients) and in the posterior wall (7/9 patients). Heavy menstrual bleeding was associated with diffuse adenomyosis (18/23 patients) mostly of the outer myometrium (22/23 patients). Scoring system showed predominantly mild disease and no severe adenomyosis was found. Adolescents with diffuse adenomyosis were significantly older and showed a high percentage of heavy menstrual bleeding compared with those with the focal disease of the inner myometrium. CONCLUSION: This study shows that adenomyosis is not only a pathology of adult life, but it involves young patients mostly in a mild-to-moderate form and is associated with typical painful symptoms. In adolescents, the diagnosis of adenomyosis is feasible through a noninvasive way with ultrasound and a proper management can be set.

Oral administration of Lactobacillus crispatus M247 to papillomavirus-infected women: results of a preliminary, uncontrolled, open trial.

BACKGROUND: Vaginal microbiotas can be clustered into five different possible categories (CST I to V), according to their bacterial dominance. In CST I, the dominance of Lactobacillus crispatus seems to correlate with better vaginal health and with a lower incidence of sine causa infertility, preterm delivery, bacterial vaginosis, and viral (including human papillomavirus; HPV) infection. According to the same method of classifying the vaginal microbiome, CST IV (non-Lactobacillus-dominated) demonstrates a higher incidence of disorders. METHODS: In an open, non-controlled study, we enrolled 35 HPV-positive women who mostly (N.=24) demonstrated CST IV status, with the other individuals categorized as having either CST III (N.=10) or CST II (N.=1) microbiotas. RESULTS: After 90 days of oral treatment with a probiotic (L. crispatus M247) we observed a reduction of approximately 70% in HPV positivity and a significant change in CST status with 94% of women now classified as CST I. CONCLUSIONS: Despite the limitations of our study, it is the first demonstration that it is possible to intervene orally with an L. crispatus probiotic to bring about a change in CST status and, in parallel, increased HPV clearance.

Therapeutic Efficacy of a Coriolus versicolor-Based Vaginal Gel in Women with Cervical Uterine High-Risk HPV Infection: A Retrospective Observational Study.

INTRODUCTION: A Coriolus versicolor-based vaginal gel is available for treating women with cervical uterine high-risk human papillomavirus (HPV) infection through re-epithelizing and re-balancing microbiota actions. METHODS: A longitudinal retrospective observational study was performed to evaluate efficacy and safety of the gel. Women treated with Coriolus versicolor-based vaginal gel were compared with women not treated with the gel. Both groups were monitored for HPV infection by an HPV DNA test, Pap smear (cytology) and colposcopy at baseline and after 6 months. RESULTS: Overall, 183 high-risk HPV positive women were enrolled (97 treated and 86 controls). After 6 months, the HPV DNA test became negative in 67.0% versus 37.2% of treated and controls, respectively (p < 0.0001). Furthermore, 76.1% versus 40.8% registered a colposcopy improvement (p = 0.0005) and 60.4% versus 40.8% showed a remission (p = 0.05), for treated versus controls, respectively. Regarding to cytology, 78.5% of treated versus 37.7% of controls registered an improvement, while 70.8% of treated versus 34.8% of controls had a remission (p < 0.0001 for both variables). At multivariate analyses adjusted for age, smoking habit, and use of estroprogestinic pill, compared to controls, women treated with the gel showed a significantly higher likelihood to experience the clearence of HPV DNA (OR 4.81; 95% 2.43-9.53), and remission at colposcopy (OR 2.30; 95% 1.00-5.31), and cytology (OR 5.13; 95% 2.40-10.96) at 6 months. No adverse event was reported during the follow-up. CONCLUSIONS: The use of a Coriolus versicolor-based vaginal gel in high-risk HPV patients is safe and effective based on all examined tests.

Transvaginal Ultrasound Findings After Laparoscopic Rectosigmoid Segmental Resection for Deep Infiltrating Endometriosis.

OBJECTIVES: To evaluate transvaginal ultrasound (TVUS) findings in patients who underwent segmental rectosigmoid resection for deep infiltrating endometriosis (DIE) and to correlate postsurgical ultrasound findings with symptoms. METHODS: A retrospective study including 50 premenopausal women with bowel endometriosis who underwent segmental rectosigmoid resection was conducted. Within 12 months after surgery, a TVUS examination was conducted in all patients to evaluate the presence of postsurgical endometriosis locations and symptoms, including dysmenorrhea, dyspareunia, dysuria, dyschezia, and chronic pelvic pain. Pelvic pain was assessed in all women by a visual analog scale. RESULTS: At the follow-up 32 of 50 patients were receiving medical treatment, whereas 18 women declined postsurgical medical therapy and tried to conceive. A high percentage of adhesions (90%) was found. A negative sliding sign (a simple diagnostic sign that can be performed during a TVUS examination, consisting of gentle pressure applied by both the vaginal transducer and the examiner's hand on the abdomen; if the uterus does not glide freely along with the rectum and posterior fornix, the sign is considered negative, and adhesions can be suspected) was found in 29 (58%) women and was associated with bowel symptoms. Recurrence of posterior DIE was found in 9 cases (18%) and endometriomas in 8 cases (16%). Adenomyosis was observed in 80% of women and was present in all symptomatic patients. CONCLUSIONS: After rectosigmoid segmental resection patients with DIE may continue to be symptomatic, and postoperative TVUS may reveal foci of disease or pelvic adhesions. Moreover, adenomyosis could be linked to symptoms experienced during follow up. Women should be aware that painful symptoms and alterations of pelvic organs could still be present after surgery and be detectable by TVUS.

Adolescence and endometriosis: symptoms, ultrasound signs and early diagnosis.

OBJECTIVE: To evaluate the ultrasonographic presence of different forms of endometriosis and the associated clinical symptoms in adolescent women. DESIGN: Retrospective observational study. SETTING: University hospital. PATIENT(S): Two hundred and seventy women aged 12-20 years referred to the gynecologic ultrasound unit from January 2014 to June 2019. INTERVENTION(S): Two-dimensional, three-dimensional, and power Doppler ultrasound (US) pelvic examination (transvaginal or transrectal in pre-sexually active adolescents) were performed in all included adolescents. Medical history was collected for each patient before the scan. MAIN OUTCOME MEASURE(S): All possible locations of endometriosis evaluated and recorded using a dedicated ultrasound mapping sheet and severity of painful symptoms evaluated through a visual analogue scale (VAS). RESULT(S): Dysmenorrhea was detected in 147 (54.4%) of 270 patients and heavy menstrual bleeding in 76 (28.1%) of 270. At least one ultrasound feature of endometriosis was identified in 36 (13.3%) of 270 cases. Ovarian endometriomas were found in 22 (11%) patients, adenomyosis in 16 (5.2%), and deep infiltrating endometriosis (DIE) in 10 (3.7%). Ultrasound signs of endometriosis were found in 21% of adolescents who reported dysmenorrhea and 33% with dyspareunia. The presence of DIE at ultrasound was associated with bowel symptoms in 33% of patients and associated with dyspareunia in 25% of patients. CONCLUSION(S): The detection rate of pelvic endometriotic lesions at ultrasound was 13%. The rates of dysmenorrhea, dyspareunia and heavy menstrual bleeding in adolescents with endometriosis ultrasound signs were statistically significantly higher compared with those without. In patients with dysmenorrhea, the detection rate of pelvic endometriosis at ultrasound increased to 20%. Professionals involved with teens should be aware of the clinical presentation of endometriosis to reduce the delay between the onset of symptoms and the diagnosis, referring these young women to dedicated centers.

Lockdown of Breast Cancer Screening for COVID-19: Possible Scenario.

BACKGROUND/AIM: Coronavirus disease is spreading worldwide. Due to fast transmission and high fatality rate drastic emergency restrictions were issued. During the lockdown, only urgent medical services are guaranteed. All non-urgent services, as breast cancer (BC) screening, are temporarily suspended. The potential of breast cancer screening programs in increasing the survival rate and decreasing the mortality rate has been widely confirmed. Suspension could lead to worse outcomes for breast cancer patients. Our study aimed to analyse the data and provide estimates regarding the temporary BC screening suspension. PATIENTS AND METHODS: Data regarding breast cancer and respective screening programs were achieved through literature research and analysis. RESULTS: Considering three different scenarios with respect to the lockdown's impact on breast cancer screening, we estimate that approximately 10,000 patients could have a missed diagnosis during these 3 months. Considering a 6-month period, as suggested by the Imperial college model, the number of patients who will not receive a diagnosis will rise to 16,000. CONCLUSION: Breast cancer screening should be resumed as soon as possible in order to avoid further breast cancer missed diagnosis and reduce the impact of delayed diagnosis.

A rare case of vulvar superficial myofibroblastoma associated with ambigous and unusual differential diagnosis.

•Superficial myofibroblastoma of the Labia Majora.•Differential diagnosis between vulvar superficial myofibroblastoma and cyst/hydrocele of Nuck duct.•Differential diagnosis between vulvar superficial myofibroblastoma and inguinal/crural hernia.

Erratum to "Uterine Tumor Resembling Ovarian Sex Cord Tumors Type II with Vaginal Vault Recurrence".

[This corrects the article DOI: 10.1155/2019/5231219.].

Pregnancy-Related Complications in Women with Recurrent Pregnancy Loss: A Prospective Cohort Study.

The aim of this prospective cohort study was to determine whether women with recurrent pregnancy loss (RPL) have an increased risk of pregnancy complications compared to normal pregnant women. A total of 1092 singleton pregnancies were followed, 431 in women with RPL and 661 in normal healthy women. The prevalence of the following complications was observed: threatened miscarriage, miscarriage, cervical insufficiency, chromosomal/genetic abnormalities, fetal anomalies, oligohydramnios, polyhydramnios, fetal growth restriction, intrauterine fetal death, gestational diabetes mellitus (GDM), preeclampsia, placenta previa, abruptio placentae, pregnancy-related liver disorders, and preterm premature rupture of the membranes. The odds ratio and 95% CI for each pregnancy complication considered were determined by comparing women with RPL and normal healthy women. Women with RPL had an overall rate of pregnancy complications higher than normal women (OR = 4.37; 95% CI: 3.353-5.714; p < 0.0001). Their risk was increased for nearly all the conditions considered. They also had an increased risk of multiple concomitant pregnancy complications (OR = 4.64; 95% CI: 3.10-6.94, p < 0.0001). Considering only women with RPL, women with ≥3 losses had a higher risk of pregnancy complications than women with two losses (OR = 1.269; 95% CI: 1.112-2.386, p < 0.02). No differences were found in the overall risk of pregnancy complications according to the type, explained or unexplained, of RPL. Women with secondary RPL had an increased risk of GDM than women with primary RPL. Pregnancy in women with RPL should be considered at high risk.

First-trimester trophoblasts obtained by chorionic villus sampling maintain tolerogenic and proteomic features in successful pregnancies despite a history of unexplained recurrent pregnancy loss.

PROBLEM: While there are several known causes for recurrent pregnancy loss (RPL), about 50% are unexplained (uRPL), and in these cases, an aberrant immune regulation seems to be involved. Although fetally derived trophoblast cells have a key role in immune regulation, it is difficult to study their immune function during pregnancy, and it is not known whether trophoblast function may be an inherent aberration in uRPL or whether it is associated with the outcome of the current pregnancy. METHOD OF STUDY: Chorionic villus sampling (CVS) was performed for clinical indications at 12 weeks of gestation. Superfluous materials, divided in small explants, were cultured for 20-24 hours, and supernatants (conditioned medium) were collected from 36 women with singleton normal pregnancies, of whom 9 women had a history of RPL. The secreted immune protein profile was measured by proximity extension assay, and the conditioned medium was further used in functional ex vivo models to assess ability to polarize blood monocytes and CD4+ T cells into immune regulatory phenotypes, as detected by flow cytometry. RESULTS: Conditioned medium from chorionic villi, human fetally derived placental tissue, was able to induce a decidual-type of M2-like macrophages, as well as an expansion of Treg cells ex vivo, both in women with uRPL and in control women. The preserved immunological properties were confirmed by a maintained immune protein profile in RPL compared with controls. CONCLUSION: Trophoblasts in an ex vivo model maintain tolerogenic and proteomic profile features in successful pregnancies, despite a previous history of RPL.

Tor Vergata University-Hospital in the Beginning of COVID-19-Era: Experience and Recommendation for Breast Cancer Patients.

COVID-19 has been officially declared as a pandemic by the WHO. Italy was the first European country to be strongly affected by this outbreak. All elective and health promotion activities were reduced. Accordingly, Italian Breast Units and breast cancer (BC) screening programs scaled down significantly their activities. The aim of this study was to evaluate measures that could potentially reduce the clinical impact of COVID-19 on BC patients. Temporary recommendations are needed that could assist specialists in preventing COVID-19 infection and optimizing resources for diagnosis and treatment of BC patients.

Endometrial Cancer Immune Escape Mechanisms: Let Us Learn From the Fetal-Maternal Interface.

The immune escape mechanisms at the base of tumor progression in endometrial cancer mimic immune tolerance mechanisms occurring at the maternal-fetal interface. The biological and immunological processes behind the maternal-fetal interface are finely tuned in time and space during embryo implantation and subsequent pregnancy stages; conversely, those behind cancer progression are often aberrant. The environment composition at the maternal-fetal interface parallels the pro-tumor microenvironment identified in many cancers, pointing to the possibility for the use of the maternal-fetal interface as a model to depict immune therapeutic targets in cancer. The framework of cancer environment signatures involved in immune adaptations, precisely timed in cancer progression, could reveal a specific "immune clock" in endometrial cancer, which might guide clinicians in patient risk class assessment, diagnostic workup, management, surgical and therapeutic approach, and surveillance strategies. Here, we review studies approaching this hypothesis, focusing on what is known so far about oncofetal similarities in immunity with the idea to individualize personalized immunotherapy targets, through the downregulation of the immune escape stage or the reactivation of the pro-inflammatory processes suppressed by the tumor.

Time-to-Pregnancy in Women with Unexplained Recurrent Pregnancy Loss: A Controlled Study.

To determine whether differences are present in the time-to-pregnancy (TTP) between women with unexplained recurrent pregnancy loss (uRPL) and control women, in this case-control, retrospective study, carried out in tertiary university hospitals, the TTP, defined as the months needed to reach pregnancy from when the woman started to try to conceive, was determined in 512 women, 207 of which were diagnosed as having uRPL and 305 were normal healthy control women. The specific TTPs for each pregnancy, stratified by order of pregnancy occurrence, were also determined. Pregnancy rates by time were calculated by using the Kaplan-Meier method to construct the survival curves. The age at which the pregnancies occurred was determined. Comparisons were carried out between women with uRPL and controls. Overall, 1192 pregnancies occurred and were analyzed. Mean TTP in uRPL women was shorter than in controls (P < 0.001) when all the pregnancies were considered. Similarly, it was shorter in the first, second, third, and fifth pregnancy. The pregnancy rates of uRPL women were shorter than that of control women for the first three pregnancies, for which the numbers of subjects allowed the comparisons to be made. These findings were observed despite maternal age of uRPL women was higher than that of control women. TTP is shorter in uRPL than in normal women. This finding clinically supports to the hypothesis that women with uRPL could be, at least in early stages of pregnancy, more fertile or receptive toward the implanting embryo than healthy women.

Uterine and placental blood flow indexes and antinuclear autoantibodies in unexplained recurrent pregnancy loss: should they be investigated in pregnancy as correlated potential factors? A retrospective study.

BACKGROUND: The potential role of antinuclear antibodies (ANA) in recurrent pregnancy loss (RPL) pathogenesis is still debated, although some evidences suggest that they could affect pregnancy outcome, leading to a higher miscarriage rate in these patients. A hypothesized mechanism is through changes in uterine flow in pre-conceptional stage, by modifying endometrial receptivity in RPL. However, scant data are available, in pregnancy, about their role in RPL placental perfusion, also in relation to its potential treatments, such as low molecular weight heparin (LMWH). The aim of this study is to retrospectively further investigate the correlation between two-dimensional (2D) and three-dimensional (3D) uterine and placental flow indexes and the presence or the absence of ANA in women with unexplained RPL (uRPL), treated or not treated with LMWH. METHODS: 2D Doppler measurement of pulsatility index (PI) of the uterine arteries and 3D ultrasonography determination of vascularization index (VI), flow index (FI) and vascularization flow index (VFI) was carried out with the aid of the virtual organ computer-aided analysis (VOCAL) technique in LMWH treated (n 24) and not treated-uRPL patients (n 20) and in the relative control group (n 27), each group divided in ANA+ and ANA- subgroups. Serum assay for the presence of ANA was performed in all women. RESULTS: No differences were found in PI, VFI and VI values, by comparing the different groups. A difference in VI values was found for ANA- patients between RPL women not treated with LMWH and the treated ones (p = 0,01), which have lower VI values and similar to controls. By considering only ANA- treated and not treated RPL patients, the ROC curve shows an area of 0,80 and at the VI cut-off of 11,08 a sensitivity of 85% and a specificity of 67%. CONCLUSIONS: LMWH could exert a potential beneficial effect in restoring the physiological blood flow supply in terms of VI in uRPL ANA- status, suggesting to include ANA and VI investigations in the RPL diagnostic algorithm in a research context, since further studies are needed to clarify this challenging hypothesis in order to try to ameliorate ANA and abnormal placental vascularization negative influence on RPL pregnancy outcome .