Effects of herbal compounds on various aspects of endometriosis treatment: a systematic review.

OBJECTIVE: Endometriosis means the presence of tissue similar to normal endometrium outside the uterus. Although surgical, hormonal, and analgesic treatment relieves symptoms and improves fertility, it is associated with side effects and a high recurrence rate. Alternative medicines like medicinal plants have been used for the treatment of chronic diseases. Given the global importance of endometriosis as a chronic disease affecting over 15% of all women in their fertile period, this systematic review aimed to give a comprehensive view of research on medicinal plants. MATERIALS AND METHODS: Comprehensive searches were performed on three databases, including PubMed/MEDLINE, Web of Science Core Collection (Indexes = SCI-EXPANDED, SSCI, A, and HCI Timespan), and Scopus, to identify papers published until June 2023. Keywords, such as "Endometriosis" and "Herbal Medicine", were used to search. A manual search of valid journals followed by a manual search of the references of the retrieved full-text articles was performed. All retrieved articles were imported into a database into Endnote X9. Articles that did not meet the inclusion criteria were excluded from the study, and the full texts of all the articles that met the inclusion criteria were assessed. Studies that evaluated the effects of herbal compounds on various aspects of endometriosis treatment were included in the review. RESULTS: In total, 11 studies were included in the present study. The evidence showed that in addition to safety, drugs available alongside treatments could play an effective role in improving the symptoms associated with endometriosis. In this study, the positive results of using Chinese treatments were reported in aspects such as fertility rate, pain, endometriosis recurrence rate, quality of life, sexual function, CA-125 level, and menopause symptoms. CONCLUSIONS: A wide range of preclinical and clinical studies evaluated the effectiveness and safety of medicinal plants in the treatment of endometriosis symptoms. Thus, alternative treatments for endometriosis with no or low side effects should be included in the holistic treatment of endometriosis upfront. However, there is still a need for well-designed trials to investigate standard interventions and specific and safe doses of herbal medicines.

Overexpression of the orphan nuclear receptor NR2F6 is associated with improved survival across molecular subgroups in endometrial cancer patients.

INTRODUCTION: NR2F6 (nuclear receptor subfamily 2 group F member 6, also called Ear-2) is known to be an orphan nuclear receptor that has been characterized as an intracellular immune checkpoint in effector T cells and, therefore, may control tumor development and growth. The prognostic impact of NR2F6 in endometrial cancers is evaluated in this study. MATERIALS AND METHODS: Expression analysis of NR2F6 in 142 endometrial cancer patients was performed by immunohistochemistry of primary paraffin­embedded tumor samples. Staining intensity of positive tumor cells was automatically assessed semi-quantitatively, and results were correlated with clinicopathological characteristics and survival. RESULTS: Forty five of 116 evaluable samples (38.8%) showed an overexpression of NR2F6. This leads to an improvement of the overall survival (OS) and progression-free survival (PFS). In NR2F6-positive patients, the estimated mean OS was 156.9 months (95% confidence interval (CI) 143.1-170.7) compared to 106.2 months in NR2F6-negative patients (95% CI 86.2-126.3; p = 0.022). The estimated PFS differed by 63 months (152 months (95% CI 135.7-168.4) vs. 88.3 months (95% CI 68.5-108.0), p = 0.002). Furthermore, we found significant associations between NR2F6 positivity, MMR status, and PD1 status. A multivariate analysis suggests NR2F6 to be an independent factor influencing the OS (p = 0.03). CONCLUSION: In this study, we could demonstrate that there is a longer progression-free and overall survival for NR2F6-positive patients with endometrial cancer. We conclude that NR2F6 might play an essential role in endometrial cancers. Further studies are required to validate its prognostic impact.

Influence of the second stage of labor on maternal and neonatal outcomes in vaginal births after caesarean section: a multicenter study in Germany.

BACKGROUND: The American College of Obstetricians and Gynecologists (ACOG) introduced a new standard of care in 2014, extending the duration of the second stage of labor in order to reduce caesarean delivery (CD) rates and its severe complications. The aim of the present study is to evaluate success rates of trial of labor after caesarean section (TOLAC), as well as maternal and neonatal outcomes after the establishment of the recent guidelines. METHODS: A retrospective study was performed at two large departments in Germany from January 2008 to January 2018. Patients undergoing TOLAC were divided into two groups. Group I (958 patients) was constituted before the establishment of the current guidelines, and Group II (588 patients) after the establishment of the guidelines. A subgroup analysis was performed to compare neonatal outcomes after successful TOLAC and operative vaginal delivery with those after failed TOLAC and secondary CD. RESULTS: The success rate of vaginal births after cesarean section (VBAC) fell from 66.4% in Group I to 55.8% in Group II (p < 0.001). The median duration of the second stage of labor was statistically significantly longer in Group II than in Group I (79.3 ± 61.9 vs. 69.3 ± 58.2 min) for patients without previous vaginal birth. The incidence of operative vaginal delivery decreased from Group I to Group II (9.6% vs. 6.8%). The incidence of third- and fourth-degree perineal lacerations, blood loss and emergency CD were similar in the two groups. Concerning the neonatal outcome, our groups did not differ significantly in regard of rates of umbilical artery cord pH < 7.1 (p = 0.108), the 5-min Apgar scores below 7 (p = 0.224) and intubation (p = 0.547). However, the transfer rates to the neonatal care unit were significantly higher in Group II than in Group I (p < 0.001). Neonatal outcomes did not differ significantly in the subgroup analysis. CONCLUSION: Extending the second stage of labor does not necessarily result in more vaginal births after TOLAC. Maternal and neonatal outcomes were similar in both groups. Further studies will be needed to evaluate the role of operative vaginal delivery and the duration of the second stage of labor in TOLAC.

Sphingosine-kinase-1 expression is associated with improved overall survival in high-grade serous ovarian cancer.

PURPOSE: Sphingosine-kinase-1 (SPHK1) is a key enzyme of sphingolipid metabolism which is involved in ovarian cancer pathogenesis, progression and mechanisms of drug resistance. It is overexpressed in a variety of cancer subtypes. We investigated SPHK1 expression as a prognostic factor in epithelial ovarian cancer patients. METHODS: Expression analysis of SPHK1 was performed on formalin-fixed paraffin-embedded tissue from 1005 ovarian cancer patients with different histological subtypes using immunohistochemistry. Staining intensity of positive tumor cells was assessed semi-quantitatively, and results were correlated with clinicopathological characteristics and survival. RESULTS: In our ovarian cancer collective, high levels of SPHK1 expression correlated significantly with complete surgical tumor resection (p = 0.002) and lower FIGO stage (p = 0.04). Progression-free and overall survival were further significantly longer in patients with high-grade serous ovarian cancer and overexpression of SPHK1 (p = 0.002 and p = 0.006, respectively). CONCLUSION: Our data identify high levels of SPHK1 expression as a potential favorable prognostic marker in ovarian cancer patients.

An unprecedented occult non-communicating rudimentary uterine horn treated with laparoscopic excision and preservation of both fallopian tubes: a case report and review of the literature.

BACKGROUND: Müllerian duct anomalies are congenital malformations of the female genital tract and may be of various types. For decades they have been classified according to the American Society of Reproductive Medicine, which mentions unicornuate uterine malformations as the second subgroup. They result from the arrested development of one of the Müllerian ducts and appear in approximately 1/1000 women. These anomalies are usually diagnosed in the second decade of life, because they tend to remain asymptomatic until adolescence and their initial symptoms may vary. Patients present with symptoms such as dysmenorrhea, infertility, and chronic or acute abdominal pain. CASE PRESENTATION: We report on a 21-year-old Caucasian German patient who suffered from dysmenorrhea for 7 years. After a transvaginal ultrasound and magnetic resonance tomography of the pelvis was performed, the patient underwent a diagnostic hysteroscopy and operative laparoscopy, and was finally diagnosed with a Müllerian duct anomaly presenting with a non-communicating rudimentary uterine horn. The left tube arose directly in orthotopic location from the cornua of uterus, with no connection to the rudimentary uterine horn or structure. CONCLUSION: The anatomic features of this case have not been reported previously and were not consistent with any existing classification. More cases are needed in order to confirm our hypothesis. Gynecologists should always consider Müllerian anomalies as an important differential diagnosis in young patients with abdominal pain.

Incidence of unexpected uterine malignancies after electromechanical power morcellation: a retrospective multicenter analysis in Germany.

PURPOSE: During the last decade, electromechanical power morcellation (EMM) was more frequently used but it may be associated with the dissemination of occult malignancies. The aim of the present study was to determine the frequency of unexpected uterine malignancies after EMM. METHODS: This retrospective study consisted of patients who were treated at three departments of Gynecology in Germany from 2008 to 2017. We identified women who underwent an operation with the use of EMM. Clinical records, risk factors, and the outcomes of the patients were reviewed. RESULTS: We performed an analysis of 1683 patients who had undergone laparoscopic supracervical hysterectomy (LASH), total hysterectomy, or myomectomy (LM) (48.6%, 8.4%, and 43.0%, respectively). Unexpected malignancies were detected in 4 of 1683 patients (0.24%). In all cases, the malignancy proved to be a sarcoma and was detected after LASH. All patients with occult sarcomas were older than 45 years and the most common (75%) risk factor was the appearance of a solitary tumor. The patients underwent secondary laparotomy for complete oncological staging, and no histological dissemination of the sarcoma was registered. Two patients had a recurrence. At the final follow-up investigation all four patients were in good general health. CONCLUSION: Occult malignancies are liable to spread after EMM, although the overall risk of being diagnosed with an occult malignancy and the risk of dissemination appear to be low. Once the preoperative diagnostic investigation has yielded no suspicious findings, laparoscopic morcellation may be considered a safe method, especially LM in patients of reproductive age.

Accuracy of frozen section at early clinical stage of endometrioid endometrial cancer: a retrospective analysis in Germany.

PURPOSE: The aim of this study was to estimate the accuracy of intra-operative frozen section (FS) diagnosis during hysterectomy for early-stage endometrial cancer (EC). METHODS: At the Department of Obstetrics and Gynecology, University of Luebeck, between 2009 and 2014, the intra-operative FS pathology of 164 patients with pre-operative endometrial curettage, showing G1 or G2 endometrioid EC at an early clinical stage (FIGO I-II), was compared retrospectively with the final paraffin section reports. The accuracy of myometrial invasion (MI) in all patients and separately in stage FIGO I patients was calculated and the under- or overtreatment of the patients was analyzed. A subgroup analysis was performed focusing on the percentage of inadequate staging by FS with clinical consequences. RESULTS: Concordance of FS and final pathology results in terms of FIGO stage was 85.2%, with an under-diagnosis rate of 14% and an over-diagnosis rate of 0.8%. The subgroup analysis rate of patients who were inappropriately operated using FS was 6.6%, while 3.3% underwent a secondary operation. The overall accuracy of FS in predicting MI was 93.3% and in patients with stage FIGO I, 92.7%. Sensitivity, specificity, PPV and NPV were 98.25%, 89.06%, 88.89% and 98.28%, respectively, and in stage FIGO I, 98.25%, 84.62%, 90.32% and 97.06%, respectively. CONCLUSION: The authors consider that intra-operative FS is a reliable diagnostic method to identify the clinical stage of EC and especially MI, to determine the necessity of lymphadenectomy. Further development of diagnostic techniques is essential to maximize diagnostic accuracy.

Effectiveness of sublingual use of 400 mcg prostaglandin E1 for first trimester surgical abortion according to parity: a retrospective study.

AIM: The aim of this paper was to evaluate the effectiveness of sublingual use of misoprostol in women undergoing first trimester surgical abortion. Special consideration was given in a sub-group analysis according to parity. METHODS: A retrospective study was conducted, enrolling patients during 2006-2009. Pregnancies less than 12 weeks of gestation were exclusively included. Our sample was divided in: group 1, in which we included women who had received 400 mcg of misoprostol sublingually two hours before surgical abortion and group 2, with no use of misoprostol. Cervical dilatation and estimated blood loss (EBL) were compared between the two groups. Moreover, a sub-group analysis of the former parameters was made separately in nulliparous and multiparous women. RESULTS: Out of 79 patients included, 48 (60.75%) received misoprostol, while 31 (39.25%) did not. Cervical dilatation was significantly higher in group 1 (6.4±2.1 mm vs. 4.7±1.7 mm in group 2, P=0.001), while EBL was significantly lower in the same group (105.0±22.1 mL vs. 120.3±24.2 mL for group 2, P=0.005). Concerning the sub-analysis, cervical dilatation was significantly increased and EBL was significantly lower in multiparous receiving misoprostol comparing with those who did not (P=0.001 and P=0.002, respectively). However, the same parameters did not differ significantly between the two sub-groups of nulliparous women. CONCLUSION: Sublingual administration of 400mcg misoprostol is effective concerning cervical ripening and EBL in women undergoing first trimester surgical abortion. According to the results of the present clinical trial prostaglandin E1 is more effective in multiparous group of women.

Biomarkers in pre-eclampsia: a novel approach to early detection of the disease.

Pre-eclampsia is a unique disorder of human pregnancy with a great impact on maternal and perinatal morbidity and mortality worldwide and especially in developing countries. The aetiology is still unknown and the pathophysiology of the disease is the subject of extensive investigation. Recently, much of the interest of the investigators for the prediction of pre-eclampsia has been aimed at measurable manifestations of abnormal placentation, endothelial dysfunction and feto-maternal unit perfusion. Biomarkers constitute a novel approach to an early detection of the disease. Low maternal serum levels of PAPP-A and PP13 early in pregnancy are predictive for emerging pre-eclampsia. On the other hand, increased levels of homocysteine, ADMA, sEng, leptin and sFlt-1 in the 1st trimester, signal the onset of the disease later in pregnancy. After the onset of pre-eclampsia, increased serum levels of PAPP-A, ADMA, homocysteine and sFlt-1 are associated with the severity of the disease. The identification of biomarkers which can contribute to the early detection of pre-eclampsia is essential. It could then be possible to apply better surveillance and treatment protocols in such patients.