Dopamine receptors D1 and D2 show prognostic significance and potential therapeutic applications for endometrial cancer patients.

OBJECTIVE: Catecholaminergic signaling has been a target for therapy in different type of cancers. In this work, we characterized the ADRß2, DRD1 and DRD2 expression in healthy tissue and endometrial tumors to evaluate their prognostic significance in endometrial cancer (EC), unraveling their possible application as an antitumor therapy. METHODS: 109 EC patients were included. The expression of the ADRß2, DRD1 and DRD2 proteins was evaluated by immunohistochemistry and univariate and multivariate analysis to assess their association with clinic-pathological and outcome variables. Finally, HEC1A and AN3CA EC cell lines were exposed to different concentrations of selective dopaminergic agents alone or in combination to study their effects on cellular viability. RESULTS: ADRß2 protein expression was not associated with clinico-pathological parameters or prognosis. DRD1 protein expression was reduced in tumors samples but showed a significant inverse association with tumor size and stage. DRD2 protein expression was significantly associated with non-endometrioid EC, high grade tumors, tumor size, worse disease-free survival (HR = 3.47 (95%CI:1.35-8.88)) and overall survival (HR = 2.98 (95%CI:1.40-6.34)). The DRD1 agonist fenoldopam showed a reduction of cellular viability in HEC1A and AN3CA cells. The exposure to domperidone, a DRD2 antagonist, significantly reduced cell viability compared to the control. Finally, DRD1 agonism and DRD2 antagonism combination induced a significant reduction in cell viability of the AN3CA cells compared to monotherapy, close to being an additive response than a synergistic effect (CI of 1.1 at 0.5% Fa). CONCLUSION: DRD1 and DRD2 expression levels showed a significant association with clinico-pathological parameters. Both the combined activation of DRD1 and blockage of DRD2 may form an innovative strategy to inhibit tumor growth in EC.

Impact of Laparoscopic Prolapse Repair in the Levator Hiatus Area.

STUDY OBJECTIVE: To determine whether laparoscopic surgery by sacrocolpopexy or sacrocervicopexy with posterior mesh attachment to levator ani to treat pelvic organ prolapse reduces the levator hiatus area, as measured by transperineal 3- and 4-dimensional ultrasound. The secondary objective was to assess the risk factors for prolapse recurrence. DESIGN: This is a prospective cohort study. SETTING: A university tertiary hospital. PATIENTS: Women with symptomatic apical prolapse at a high risk of recurrence were included. High risk of recurrence was defined as age <60 years and levator injury (avulsion and/or ballooning) or stage III-IV prolapse Pelvic Organ Prolapse Quantification. INTERVENTIONS: Women were treated with laparoscopic sacrocolpopexy or sacrocervicopexy. MEASUREMENTS AND MAIN RESULTS: Women underwent clinical examination according to assessment by the Pelvic Organ Prolapse Quantification system and transperineal ultrasound for the levator hiatus area at Valsalva. We collected demographic, clinical, and ultrasound data before surgery from clinical records and performed a comparative analysis of the levator hiatus areas before and after surgery and univariate and multivariate analyses of the risk factors for recurrence. Among the 30 women who enrolled, the levator hiatus area at Valsalva decreased significantly after surgery by an average of 4.68 cm2 (p = .028). However, despite a recurrence rate of 13.3%, we found no risk factors associated with recurrence in either the univariate or the multivariate analyses. CONCLUSION: Laparoscopic surgery by sacrocolpopexy or sacrocervicopexy for pelvic organ prolapse with mesh posterior attachment to levator ani significantly reduces the levator hiatus area measured by transperineal ultrasound. Further large-scale studies will be needed to confirm our results and identify risk factors for recurrence.

Congenital Cytomegalovirus Awareness and Knowledge among Health Professionals and Pregnant Women: An Action towards Prevention.

INTRODUCTION: Cytomegalovirus (CMV) is a major cause of childhood disabilities, and consensus recommendations emphasize the importance of hygienic measures to reduce perinatal infection. Our study aimed to evaluate the level of awareness about CMV among health professionals and pregnant women. METHODS: We submitted a 20-item online survey regarding CMV perinatal infection to all obstetricians and midwives in Catalonia (Spain) and a 7-item lay version of the questionnaire to 700 pregnant women. Levels of knowledge were compared among groups. RESULTS: Of the 1,449 health professionals approached, 338 surveys were answered. 72% of professionals considered CMV a relevant problem. 47% of obstetricians and 28% of midwives (p ≤ 0.001) routinely informed pregnant women, and less than half knew the risk of fetal transmission. We observed significant differences in knowledge between obstetricians and midwives concerning the risks of recurrent infections, risk of transmission, and risk of severe infection (60.7% vs. 45.6%, p = 0.006 and 50.6% vs. 22.5%, p ≤ 0.001); and regarding maternal and neonatal symptoms and newborn sequelae (23% vs. 8.8%, p ≤ 0.001). Of the 700 women approached, we obtained a response rate of 72%. Only 23% had previously heard about CMV, 22% identified transmission routes, and 15% preventive measures. Compared to women without risk factors for CMV infection, women at greater risk had heard more about CMV (mothers of children <3 years: 36% vs. 20%, p < 0.001; occupational exposure: 43% vs. 20%, p ≤ 0.001) and had received more information (mothers of children <3 years: 18% vs. 9.5%, p ≤ 0.001; occupational exposure: 23% vs. 9.3%, p = 0.001). CONCLUSION: Health care professionals have limited knowledge about CMV and may fail to enforce preventive measures. While pregnant women have limited awareness about CMV infection, they recognize the need for information. Health campaigns should be promoted to enhance awareness about this perinatal infection.

Prevalence of levator ani avulsion in a multicenter study (PAMELA study).

PURPOSE: The objective is to determine the prevalence of levator ani muscle (LAM) avulsion using four-dimensional ultrasound in primiparous women after vaginal delivery and according to delivery mode. METHODS: This prospective, multicenter study included 322 women evaluated at 6-12 months postpartum by four-dimensional transperineal ultrasound to identify levator ani muscle avulsion. The researcher who performed the ultrasound was blinded to all clinical data. Meaningful data about the birth were also recorded: mode of delivery, mother's age and body mass index, duration of second stage, episiotomy, perineal tearing, anesthesia, assistant, head circumference and fetal weight. RESULTS: 303 volumes were valid for evaluation. The overall prevalence of levator ani muscle avulsion was 18.8% (95% CI 14.4-23.2%). In our multivariate analysis, only mode of delivery reached statistical significance as a risk factor for levator ani muscle avulsion (p < 0.001). The prevalence according to the different modes of delivery was 7.8% in spontaneous delivery, 28.8% in vacuum-assisted and 51.1% in forceps-assisted delivery. Compared with spontaneous delivery, the OR for LAM avulsion was 12.31 with forceps (CI 95% 5.65-26.80) and 4.78 with vacuum-assisted delivery (CI 95% 2.15-10.63). CONCLUSIONS: Levator ani avulsion during vaginal delivery in primiparous women occurs in nearly one in every five deliveries. Delivery mode is a significant and modifiable intrapartum risk factor for this lesion. The incidence is lower in spontaneous delivery and significantly increases when an instrument is used to assist delivery, especially forceps.

Strict versus Liberal Use of Sentinel Node Biopsy in Breast Cancer Surgery: Any Clinical Outcome Differences? A 20-Year Clinical Experience.

Introduction: As applied to early breast cancer (BC) patients, sentinel node biopsy (SNB) has undergone major changes over the years, especially concerning the widening of indication criteria or skipping systematic axillary lymph node dissection (ALND) after a positive SN. We aimed to ascertain whether a strict versus a more liberal use of SNB resulted in different clinical outcomes in our clinical experience. Methods: We studied consecutive BC patients undergoing SNB between January 1, 2000, and March 31, 2020. There were 1,587 patients and 1,634 SNB procedures. Cases were divided into two study groups: the "strict" SNB group (unifocal tumors up to 35 mm in which ALND was always performed for a positive SN, amounting to 1,183 SNBs), and the "liberal" SNB group (extended tumor size up to selected T3 cases, as well as multifocal or bilateral disease, and patients with previous contralateral BC, not always followed by ALND after a positive SN, amounting to 451 SNBs). Patients were closely followed up to the end of the study. Results: Clinico-pathological variables were strikingly different between study groups, with the liberal group showing a higher risk profile. Cox regression analysis for disease recurrence did not show significant differences in axillary, lymph node, or locoregional recurrence rates or distant relapse. There were no differences in survival between groups. Conclusion: It seems reasonable to adopt the liberal SNB approach, as the goal of surgical management in early BC patients must be attaining optimal locoregional disease control, no matter the differences in distant metastatic spread rates across different BC risk profiles.

COVID-19 Incidence and Mortality in Patients Operated on for Breast Cancer. Comparison with the General Population.

BACKGROUND: Breast Cancer (BC) remains the most diagnosed malignancy and the most common cause of cancer-related mortality in women worldwide. Covid-19 mortality in BC patients has been linked to comorbid conditions rather than to cancer treatment itself, although this was not confirmed by a meta-analysis. Also, during Covid-19 outbreaks, a great deal of health care resources is reassigned to critical Covid-19 patients. PATIENTS AND METHODS: During 5 consecutive trimesters (from 1/12/2020 to 31/3/2021) 2511 BC patients older than 20 years from our institution were surveyed. 1043 of them had received a Covid test and these made our study group, which was conveniently compared with the Covid-19 tested background feminine Catalan population. RESULTS: 13.1% of our patients presented with a positive Covid-19 test, whereas confirmed COVID-19 infection amounted to 7.1% of the feminine Catalan tested population. The COVID-19-specific mortality rate was 11.7% (16/137) in the study group, which compares with a 4.7% rate for the overall population. Most deaths occurred in patients over 70. CONCLUSION: Three clinical factors were significantly associated with Covid-19 mortality in BC, namely lack of hormone therapy, distant metastases, and BC dwelling in nursing homes. BC patients are at a higher risk of Covid-19 infection and mortality in comparison with the reference group without BC.

Neural plasticity of the uterus: New targets for endometrial cancer?

Endometrial carcinoma is the most common gynecological malignancy in Western countries and is expected to increase in the following years because of the high index of obesity in the population. Recently, neural signaling has been recognized as part of the tumor microenvironment, playing an active role in tumor progression and invasion of different solid tumor types. The uterus stands out for the physiological plasticity of its peripheral nerves due to cyclic remodeling brought on by estrogen and progesterone hormones throughout the reproductive cycle. Therefore, a precise understanding of nerve-cancer crosstalk and the contribution of the organ-intrinsic neuroplasticity, mediated by estrogen and progesterone, of the uterine is urgently needed. The development of new and innovative medicines for patients with endometrial cancer would increase their quality of life and health. This review compiles information on the architecture and function of autonomous uterine neural innervations and the influence of hormone-dependent nerves in normal uterus and tumor progression. It also explores new therapeutic possibilities for endometrial cancer using these endocrine and neural advantages.

Pregnancy in Pateints With Exstrophy-Epispadias Complex: Are Higher Rates of Complications and Spontaneous Abortion Inevitable?

OBJECTIVE: To report on the characteristics of pregnancy in female patients with EEC (exstrophy-epispadias complex), determining in particular whether they are at higher risk of spontaneous abortion or complications. MATERIALS AND METHOD: Fifty patients diagnosed with EEC and treated in a reference center for this pathology were reviewed. Those with an incomplete medical history were excluded, leaving a total of 37 women with a median follow-up of 26 years (1-48 years). The outcome measurements were successful pregnancies, miscarriages, urological, gynecological and obstetric complications, impaired renal function, newborn characteristics, and postpartum urogynecological complications. Descriptive statistics was used. RESULTS: Eight patients achieved 17 pregnancies (88.2% spontaneous). Of these pregnancies, 10 (58.8%) were successful, while 7 (41.2%) terminated in miscarriages. Urinary tract infection (UTI) was the most frequent complication (41.6%) and intestinal occlusion was the most severe. A total of 62.5% of the patients presented genital prolapses after pregnancies. A total of 85.7% of patients were dry during the follow-up after their pregnancies. No newborn presented EEC or any other type of malformation. Our study has the limitation of being a retrospective review of a very heterogeneous and small group of patients. CONCLUSION: EEC patients can achieve spontaneous pregnancies but have an increased risk of miscarriage. For this reason, monitoring and control by a specialized and integrated multidisciplinary team is required to minimize complications.

[High risk pregnancy in patients with extrophy-epispadia complex: Uro-gynecological characteristics and management.] / Embarazo de alto riesgo en pacientes con complejo extrofia-epispadias: características uro-ginecológicas y manejo.

OBJECTIVE: The exstrophy-epispadias complex (EEC) ranges from distal epispadias to cloacal exstrophy, with serious repercussions on the quality of life of patients. However, reconstructive surgery offers the opportunity to reach adulthood and consider motherhood.The objective of this work is to assess the uro-gynecological characteristics and the risks that pregnant women have with EEC. MATERIALS AND METHOD: Retrospective study of 50 patients diagnosed with EEC and treated in a reference center for this pathology, born between 1968 and 2000. Their medical records were reviewed and all demographic, pathological and gynecological data were collected. RESULTS: 37 patients have the inclusion criteria and of these 8 achieved 17 pregnancies (90% spontaneous and 10% through IVF). 10 were successful (50% at term) and 7 were abortions, 87.5% of which were in the first trimester. Urinary tract infection (UTI) was the most frequent complication (41.6%) and the most severe was intestinal occlusion. None of the patients presented renal function impairment during the gestation or dilation of the pathological upper urinary tract (UUT). 62.5% of the patients presented genital prolapses after pregnancies, 80% of which were grade III and IV. 87.5% were dry in the follow-up after their pregnancies. CONCLUSION: Pregnancy in the EEC patients is high risk and it is crucial that the follow-up is carried out by a specialized and integrated multidisciplinary team to minimize complications.

OBJETIVO: El complejo extrofia-epispadias (CEE) abarca desde las epispadias distales hasta la extrofia de cloaca, con serias repercusiones en la calidad de vida de los pacientes; sin embargo, la cirugía reconstructiva ofrece la oportunidad de llegar a la edad adulta y plantearse la maternidad. El objetivo de este trabajo es valorar las características uro-ginecológicas y los riesgos que presentan las gestantes con CEE. MATERIALES Y MÉTODO: Estudio retrospectivo de 50 pacientes diagnosticadas de CEE y tratadas en un centro de referencia para esta patología, nacidas entre 1968 y 2000. Se revisaron sus historias clínicas y se recogieron todos los datos demográficos, patológicos  y ginecológicos. RESULTADOS: 37 pacientes cumplían los criterios de inclusión y de estas 8 lograron 17 embarazos (90% espontáneos y 10% mediante FIV). 10 fueron exitosos (50% a término) y 7 fueron abortos, 87,5% de los cuales fueron en el primer trimestre. La infección urinaria (ITU) fue la complicación más frecuente (41,6%) y la más severa fue la oclusión intestinal. Ninguna de las pacientes presentó deterioro de la función renal durante la gestación o dilatación del tracto urinario superior (TUS) patológica. 62,5% de las pacientes presentaron prolapsos genitales posteriores a los embarazos, 80% de los cuales fueron grado III y IV. 87,5% se encontraban secas en el seguimiento posterior a sus embarazos. CONCLUSIÓN: El embarazo en el CEE es de alto riesgo y es crucial que el seguimiento sea llevado a cabo por un equipo multidisciplinar especializado e integrado para minimizar las complicaciones.

[The fibroid as clinical problem]. / El mioma como problema clínico.

Uterine fibroids are the most common benign tumours that affect women of reproductive age and they represent the main indication for surgery for benign uterine pathology. In 25% of cases, they become clinically apparent, causing heavy menstrual bleeding, pelvic pain and/or infertility. Therefore, fibroids have a notable impact on the economic costs for the health system and also on the quality of life of the women they afflict. Although MRI is the most precise technique to diagnose fibroids, ultrasound remains the most cost-effective method. Surgery has been the treatment of choice for years, and several minimally invasive procedures have recently been developed. There are a wide variety of conservative medical treatment options, which are continually expanding. Research on the biology of these tumours can lead to new therapeutic options for the management of fibroids as we better understand the role that growth factors and genetic mutations play in them.