Molecular Insights in Uterine Leiomyosarcoma: A Systematic Review.

Uterine fibroids (UFs) are the most common benign tumors of female genital diseases, unlike uterine leiomyosarcoma (LMS), a rare and aggressive uterine cancer. This narrative review aims to discuss the biology and diagnosis of LMS and, at the same time, their differential diagnosis, in order to distinguish the biological and molecular origins. The authors performed a Medline and PubMed search for the years 1990-2022 using a combination of keywords on the topics to highlight the many genes and proteins involved in the pathogenesis of LMS. The mutation of these genes, in addition to the altered expression and functions of their enzymes, are potentially biomarkers of uterine LMS. Thus, the use of this molecular and protein information could favor differential diagnosis and personalized therapy based on the molecular characteristics of LMS tissue, leading to timely diagnoses and potential better outcomes for patients.

Glutathione Transferase P1: Potential Therapeutic Target in Ovarian Cancer.

Chemotherapy resistance of ovarian cancer, regarded as the most lethal malignant gynecological disease, can be explained by several mechanisms, including increased activity of efflux transporters leading to decreased intracellular drug accumulation, increased efflux of the therapeutic agents from the cell by multidrug-resistance-associated protein (MRP1), enhanced DNA repair, altered apoptotic pathways, silencing of a number of genes, as well as drug inactivation, especially by glutathione transferase P1 (GSTP1). Indeed, GSTP1 has been recognized as the major enzyme responsible for the conversion of drugs most commonly used to treat metastatic ovarian cancer into less effective forms. Furthermore, GSTP1 may even be responsible for chemoresistance of non-GST substrate drugs by mechanisms such as interaction with efflux transporters or different signaling molecules involved in regulation of apoptosis. Recently, microRNAs (miRNAs) have been identified as important gene regulators in ovarian cancer, which are able to target GST-mediated drug metabolism in order to regulate drug resistance. So far, miR-186 and miR-133b have been associated with reduced ovarian cancer drug resistance by silencing the expression of the drug-resistance-related proteins, GSTP1 and MDR1. Unfortunately, sometimes miRNAs might even enhance the drug resistance in ovarian cancer, as shown for miR-130b. Therefore, chemoresistance in ovarian cancer treatment represents a very complex process, but strategies that influence GSTP1 expression in ovarian cancer as a therapeutic target, as well as miRNAs affecting GSTP1 expression, seem to represent promising predictors of chemotherapeutic response in ovarian cancer, while at the same time represent potential targets to overcome chemoresistance in the future.

Neurological outcomes of antenatal corticosteroid therapy.

AIM OF THE STUDY: The aim of the study was to investigate whether antenatal corticosteroid therapy (ACST) could impact neurological condition, as assessed through muscular tone, of prematurely born infants. METHODS: All 82 patients at risk of preterm delivery treated and delivered over 12 months were divided into two equal groups regarding the use of ACST. The investigated parameters were pregnancy complications, biophysical profile, Apgar score, gestational age of delivery and all postpartum complications. Neurological development and muscular tone were evaluated at the 1st, 3rd, 6th and 12th months of life using Vojta's method, which classifies muscular tone as good, hypotonic or hypertonic. RESULTS: After therapy, infants from the treated and control groups differed in biophysical profile, Apgar score, length of intensive care, occurrence of respiratory distress syndrome and intraventricular haemorrhage. During the follow-up, significantly more infants from the ACST group had good muscular tone when compared with those from the control group. Regression analysis showed that ASCT can significantly impact an infant's muscular tone. Still, the week of delivery and the complications such as diabetes mellitus, intrauterine growth restriction and respiratory distress syndrome, could change the association of ACST and infants' muscular tone. CONCLUSION: ACST was associated with the positive neurological outcomes of prematurely born infants when assessed through their muscular tone.

A Rare Case of Epithelioid Trophoblastic Tumor Presenting as Hematoma of a Caesarean Scar in the Lower Uterine Segment.

Epitheliod trophoblastic tumor (ETT) account for only 1-2% of all the cases of gestational trophoblastic neoplasia (GTN), with a reported mortality rate of 10-24%. ETT is derived from chorionic type intermediate trophoblastic cells, which appears to be the reason for the only slightly elevated ßhCG levels in these patients. We present a case of a 42-year-old patient who was admitted to the clinic eight months after Caesarean delivery, for irregular vaginal bleed with normal values of beta-human chorionic gonadotropin (ßhCG). A 6 × 5 cm hematoma was evacuated from the isthmic uterine segment during the operation, and the histopathological exam of the tissue surrounding the hematoma revealed ETT. There were no metastatic lesions on the thoracal, abdominal, and pelvic CT. The second ultrasonographic exam revealed tumefaction of 5 cm at the site from the previous surgical procedure. Color Doppler imaging revealed no central nor peripheral blood flow. The patient underwent a total abdominal hysterectomy with bilateral adnexectomy without adjuvant chemotherapy. This appears to be one of the shortest intervals from the anteceded gestational event until the diagnosis of this tumor, along with the absence of the significant ultrasonographic feature of the ETT-peripheral Doppler signal pattern. We underline that, even with normal values of ßhCG, irregular vaginal bleeding following the antecedent gestational event should always arouse suspicion of GTN.

Integrated Bioinformatics Investigation of Novel Biomarkers of Uterine Leiomyosarcoma Diagnosis and Outcome.

Uterine leiomyosarcomas (uLMS) have a poor prognosis and a high percentage of recurrent disease. Bioinformatics has become an integral element in rare cancer studies by overcoming the inability to collect a large enough study population. This study aimed to investigate and highlight crucial genes, pathways, miRNAs, and transcriptional factors (TF) on uLMS samples from five Gene Expression Omnibus datasets and The Cancer Genome Atlas Sarcoma study. Forty-one common differentially expressed genes (DEGs) were enriched and annotated by the DAVID software. With protein-protein interaction (PPI) network analysis, we selected ten hub genes that were validated with the TNMplotter web tool. We used the USCS Xena browser for survival analysis. We also predicted TF-gene and miRNA-gene regulatory networks along with potential drug molecules. TYMS and TK1 correlated with overall survival in uLMS patients. Finally, our results propose further validation of hub genes (TYMS and TK1), miR-26b-5p, and Sp1 as biomarkers of pathogenesis, prognosis, and differentiation of uLMS. Regarding the aggressive behavior and poor prognosis of uLMS, with the lack of standard therapeutic regimens, in our opinion, the results of our study provide enough evidence for further investigation of the molecular basis of uLMS occurrence and its implication in the diagnosis and therapy of this rare gynecological malignancy.

Psychosexual outcomes in women of reproductive age at more than two-years from excisional cervical treatment - a cross-sectional study.

Purpose: To investigate the long-term psychosexual outcomes in women following excisional cervical treatment. Materials and methods: Women with cold-knife conization (CKC) or large loop excision of the transformation zone (LLETZ) treatment were interviewed after a follow-up colposcopy visit. Their demographics, treatment and psychosexual characteristics were recorded. Results: One hundred and forty six women with a mean age of 35.2 ± 5.4 years underwent either LLETZ (68.5%) or CKC (31.5%) treatment within 4.7 ± 2.7 years (range: 2-15) before the interview. 27.4% of women were less interested in sexual intercourse following treatment in comparison with their interest before. Those women with less interest in sexual intercourse after treatment had higher anxiety and depression scores and were more worried about disease progression. Women with post-treatment complications were at risk of less interest in sexual intercourse and of greater anxiety and depression. Women with abnormal smears at follow-up were at risk of greater anxiety. The type of treatment and grade of dysplasia did not affect their interest in sexual intercourse or the anxiety and depression scores. Conclusions: Approximately, one-third of women at more than two years post-treatment may suffer from less interest in sexual intercourse, have relatively greater anxiety and depression, and might still be concerned about the possibility of disease progression.

Cesarean myomectomy trends and controversies: an appraisal.

OBJECTIVE: Although the first report on cesarean myomectomy (CM) was a century ago, the management of a myomectomy during a cesarean section (CS) remains controversial. The objective of this study is to provide the latest data on this topic regarding the techniques and complications of CM. METHODS: The authors consulted the most important scientific databases investigating the indications and contraindications for CM, the operational techniques, benefits and complications. RESULTS: CM provides the benefits of two surgeries in one laparotomy, avoiding the risks of repeated anesthesia and relaparotomy. Nevertheless, in some patients, CM may be associated with increased morbidity and, in such cases, an interval myomectomy might be a safer option. Myomas compromising fetal extraction and uterine incision and/or suturing should be preferably enucleated during CS. CM is generally considered relatively safe in cases of anterior wall myomas, subserous and pedunculated myomas, particularly if a myomectomy is feasible without additional hysterotomy. Multiple myomas, deep intramural, fundal and cornual myomas and posterior uterine wall myomas are associated with more surgical complications during CM. CONCLUSIONS: With increasing reports in favor of CM, the risk-benefit ratio should be still evaluated with randomized controlled trials, in order to achieve more data on CM.

Electric shock in pregnancy: a review.

OBJECTIVE: The effect of gestational age and other factors that could influence the outcome of an electric shock in pregnancy have not been defined yet. Objective of this study is to provide reliable data on medical issues linked to electric shock in pregnancy. METHODS: Authors consulted the most important scientific databases investigating reactions to electric shock in pregnancy, analyzing mechanism of electric shock, gestational age at the time of injury, the post-shock complications, interval from injury to delivery and fetal and maternal outcome. RESULTS: The spectrum of electrical injuries in pregnancy ranges from transient unpleasant sensation with no effect on the fetus to sudden maternal and fetal death. The clinical presentation of the fetal injury may manifest immediately or even postnataly. Reported outcomes include spontaneous abortion, placental abruption, cardiac arrhythmias, fetal burn and intrauterine fetal death. If the pregnancy is continued, decreased fetal movements and asphyxia, pathological fetal heart patterns, intrauterine fetal growth retardation, damage to the fetal central nervous system and oligoamnios can occur. CONCLUSIONS: More large prospective observational studies are necessary for a proper insight into the expected outcomes of the electric shock in pregnancy as well as for a final definition of monitoring procedures of such pregnancies.