Search Results (16)

This study aimed to identify unique characteristics in the peripheral blood mononuclear cells (PBMCs) of endometriosis patients and develop a non-invasive early diagnostic tool. Using single-cell RNA sequencing (scRNA-seq), we constructed the first single-cell atlas of PBMCs from endometriosis patients based on 107,964 cells and 25,847 genes. Within CD16⁺ monocytes, we discovered JUP as a dysregulated gene. To assess its diagnostic potential, we measured peritoneal fluid (PF) and serum JUP levels in a large cohort of 199 patients including 20 women with ovarian cancer (OC). JUP was barely detectable in PF but was significantly elevated in the serum of patients with endometriosis and OC, with levels 1.33 and 2.34 times higher than controls, respectively. Additionally, JUP was found in conditioned culture media of CD14⁺/CD16⁺ monocytes aligning with our scRNA-seq data. Serum JUP levels correlated with endometriosis severity and endometrioma presence but were unaffected by dysmenorrhea, menstrual cycle, or adenomyosis. When combined with CA125 (cancer antigen 125) JUP enhanced the specificity of endometriosis diagnosis from 89.13% (CA125 measured alone) to 100%. While sensitivity remains a challenge at 19%, our results suggest that JUP’s potential to enhance diagnostic accuracy warrants additional investigation. Furthermore, employing serum JUP as a stratification marker unlocked the potential to identify additional endometriosis-related genes, offering novel insights into disease pathogenesis. Full article

Background/Objectives: Adenomyosis is a debilitating gynecologic condition that affects both multiparous older women and nulliparous younger women, inducing a variety of symptoms such as dysmenorrhea, menorrhagia, and infertility. Thermal ablation techniques are new procedures that have been proposed for the treatment of adenomyosis. They include high-intensity focused ultrasound (HIFU), percutaneous microwave ablation (PMWA), and radiofrequency ablation (RFA). Because thermal ablation techniques are minimally invasive or noninvasive, fertility is not impaired while symptoms improve. In addition, hospital stays and financial costs are generally reduced, increasing the interest in these alternative management options. Methods: In this narrative review, we conducted a thorough literature search of PubMed/Medline from the database inception to September 2022. In our search, we focused on noninvasive treatment methods such as HIFU ablation, RFA ablation, and PMWA as well as adenomyosis-specific terms and noninvasive techniques (ultrasonography, ultrasound, or magnetic resonance imaging). The queries were a combination of MeSH terms and keywords. The search was limited to the English language. Abstracts were screened according to their content, and relevant articles were selected. Results: Overall, the results showed that the above-mentioned ablation techniques are effective and safe in providing adenomyosis treatment. Lesion size and uterus volume are reduced, leading to considerable symptom alleviation with all three methods. Positive results concerning safety and fertility preservation have been described as well. Conclusions: Nonetheless, more research is required in this field to compare the efficacy and safety of different ablation techniques with traditional therapies. Such research will help improve these procedures and their associated decision-making processes. Full article

Lynch syndrome is an inherited tumor syndrome caused by a pathogenic germline variant in DNA mismatch repair genes. As the leading cause of hereditary endometrial cancer, international guidelines recommend universal screening in women with endometrial cancer. However, testing for Lynch syndrome is not yet well established in clinical practice. The aim of this study was to evaluate adherence to our Lynch syndrome screening algorithm. A retrospective, single-center cohort study was conducted of all endometrial cancer patients undergoing surgical treatment at the Bern University Hospital, Switzerland, between 2017 and 2022. Adherence to immunohistochemical analysis of mismatch repair status, and, if indicated, to MLH1 promoter hypermethylation and to genetic counseling and testing was assessed. Of all 331 endometrial cancer patients, 102 (30.8%) were mismatch repair-deficient and 3 (0.9%) patients were diagnosed with Lynch syndrome. Overall screening adherence was 78.2%, with a notable improvement over the six years from 61.4% to 90.6%. A major reason for non-adherence was lack of provider recommendation for testing, with advanced patient age as a potential patient risk factor. Simplification of the algorithm through standardized reflex screening was recommended to provide optimal medical care for those affected and to allow for cascading testing of at-risk relatives. Full article

Background: SLN mapping has emerged as a standard of care in endometrial cancer due to its high sensitivity and significant reduction in morbidity. Although lymphovascular space invasion (LVSI) is a known risk factor for lymph node metastasis and recurrence, evidence on the reliability of SLN mapping in LVSI-positive patients is scarce. The aim of this study was to determine the impact of LVSI on the diagnostic performance of SLN mapping. Methods: This retrospective cohort study included patients with endometrial cancer who underwent primary surgical treatment at the Bern University Hospital, Switzerland, between 2012 and 2022. Results: LVSI was present in 22% of patients and was significantly associated with lymph node metastasis (p < 0.001) and recurrence (p < 0.001). In node-negative patients with only SLN mapping performed, LVSI was an independent predictor of recurrence during multivariable Cox regression analysis (p = 0.036). The negative predictive value of SLN mapping was 91.5% and was significantly lower in tumors with LVSI (75.0%) compared to LVSI-negative tumors (95.6%, p = 0.004). Conclusion: The presence of LVSI was significantly associated with worse oncological outcomes. LVSI was an independent predictor of recurrence in node-negative patients with only SLN mapping performed. Furthermore, the negative predictive value of SLN mapping was significantly lower in LVSI-positive tumors. Full article

Identifying tissue-specific molecular signatures of active regulatory elements is critical to understanding gene regulatory mechanisms. In this study, transcription start sites (TSS) and enhancers were identified using Cap analysis of gene expression (CAGE) across endometrial stromal cell (ESC) samples obtained from women with (n = 4) and without endometriosis (n = 4). ESC TSSs and enhancers were compared to those reported in other tissue and cell types in FANTOM5 and were integrated with RNA-seq and ATAC-seq data from the same samples for regulatory activity and network analyses. CAGE tag count differences between women with and without endometriosis were statistically tested and tags within close proximity to genetic variants associated with endometriosis risk were identified. Over 90% of tag clusters mapping to promoters were observed in cells and tissues in FANTOM5. However, some potential cell-type-specific promoters and enhancers were also observed. Regions of open chromatin identified using ATAC-seq provided further evidence of the active transcriptional regions identified by CAGE. Despite the small sample number, there was evidence of differences associated with endometriosis at 210 consensus clusters, including IGFBP5, CALD1 and OXTR. ESC TSSs were also located within loci associated with endometriosis risk from genome-wide association studies. This study provides novel evidence of transcriptional differences in endometrial stromal cells associated with endometriosis and provides a valuable cell-type specific resource of active TSSs and enhancers in endometrial stromal cells. Full article

Adenomyosis is a common benign gynecologic condition characterized by ectopic endometrial glands and stroma in the myometrium causing pain (dysmenorrhea) and abnormal uterine bleeding. New interventional techniques have been introduced over recent years. This study evaluates the treatment success and side effects of radiofrequency ablation. An electronic literature search in the PubMed, Scopus, and ScienceDirect databases was carried out on the outcomes of pain reduction and, secondarily, on abnormal uterine bleeding, reintervention, reproductive outcome, imaging outcome, and complications. There was a mean decrease in dysmenorrhea pain scores by −63.4 ± 9.0% at 12 months. Data on other outcome parameters were sparse. No major complications were reported. Radiofrequency ablation represents a promising minimally invasive and organ-preserving treatment in patients with symptomatic adenomyosis. It is associated with clinically meaningful improvement of adenomyosis-related pain in the short term. Full article

Introduction: Gynecological sarcomas are rare malignant tumors with an incidence of 1.5–3/100,000 and are 3–9% of all malignant uterine tumors. The preoperative differentiation between sarcoma and myoma becomes increasingly important with the development of minimally invasive treatments for myomas, as this means undertreatment for sarcoma. There are currently no reliable laboratory tests or imaging-characteristics to detect sarcomas. The objective of this article is to gain an overview of sarcoma US/MRI characteristics and assess their accuracy for preoperative diagnosis. Methods: A systematic literature review was performed and 12 studies on ultrasound and 21 studies on MRI were included. Results: For the ultrasound, these key features were gathered: solid tumor > 8 cm, unsharp borders, heterogeneous echogenicity, no acoustic shadowing, rich vascularization, and cystic changes within. For the MRI, these key features were gathered: irregular borders; heterogeneous; high signal on T2WI intensity; and hemorrhagic and necrotic changes, with central non-enhancement, hyperintensity on DWI, and low values for ADC. Conclusions: These features are supported by the current literature. In retrospective analyses, the ultrasound did not show a sufficient accuracy for diagnosing sarcoma preoperatively and could also not differentiate between the different subtypes. The MRI showed mixed results: various studies achieved high sensitivities in their analysis, when combining multiple characteristics. Overall, these findings need further verification in prospective studies with larger study populations. Full article

Endometriosis is a common gynaecological condition characterised by the growth of endometrial tissue outside the uterus and is associated with pain and infertility. Currently, the gold standard for endometriosis diagnosis is laparoscopic excision and histological identification of endometrial epithelial and stromal cells. There is, however, currently no known association between the histological appearance, size, morphology, or subtype of endometriosis and disease prognosis. In this study, we used histopathological software to identify and quantify the number of endometrial epithelial and stromal cells within excised endometriotic lesions and assess the relationship between the cell contents and lesion subtypes. Prior to surgery for suspected endometriosis, patients provided menstrual and abdominal pain and dyspareunia scores. Endometriotic lesions removed during laparoscopic surgery were collected and prepared for immunohistochemistry from 26 patients. Endometrial epithelial and stromal cells were identified with Cytokeratin and CD10 antibodies, respectively. Whole slide sections were digitised and the QuPath software was trained to automatically detect and count epithelial and stromal cells across the whole section. Using this classifier, we identified a significantly larger number of strongly labelled CD10 stromal cells (p = 0.0477) in deeply infiltrating lesions (99,970 ± 2962) compared to superficial lesions (2456 ± 859). We found the ratio of epithelial to stromal cells was inverted in deeply infiltrating endometriosis lesions compared to superficial peritoneal and endometrioma lesions and we subsequently identified a correlation between total endometrial cells and abdominal pain (p = 0.0005) when counted via the automated software. Incorporating histological software into current standard diagnostic pipelines may improve endometriosis diagnosis and provide prognostic information in regards to severity and symptoms and eventually provide the potential to personalise adjuvant treatment decisions. Full article

Global biodiversity decline is continuing largely unabated. The International Union for Conservation of Nature (IUCN) Red List of Threatened Species (hereafter, Red List) provides us with the gold standard for assessments, but taxonomic coverage, especially for invertebrates and fungi, remains very low. Many players contribute to the Red List knowledge base, especially IUCN Red List partners, IUCN-led assessment projects, and the Specialist Groups and Red List Authorities (RLA) of the IUCN Species Survival Commission. However, it is vital that we develop the next generation of contributors and bring in new, diverse voices to build capacity and to sustain the huge assessment effort required to fill data gaps. Here, we discuss a recently established partner network to build additional capacity for species assessments, by linking academia directly into the assessment processes run by Specialist Groups and RLAs. We aim to increase Red List “literacy” amongst potential future conservationists and help students to increase publication output, form professional networks, and develop writing and research skills. Professors can build Red List learning into their teaching and offer Red Listing opportunities to students as assignments or research projects that directly contribute to the Red List. We discuss the opportunities presented by the approach, especially for underrepresented species groups, and the challenges that remain. Full article

Higher cesarean section rates and better ultrasound diagnostics have led to a more frequent diagnosis of isthmocele, a cesarean scar defect. Sometimes, endometriosis is found in the isthmocele, but simultaneous extrauterine endometriosis and endometriosis in the isthmocele have not yet been reported. Additionally, the surgical technique to repair the isthmocele is the subject of ongoing controversy. The aim of this study is to analyze a possible correlation between uterine scar (isthmocele) endometriosis and extrauterine endometriosis and to investigate the outcome of laparoscopic isthmocele resection in the rendezvous technique. In this single-center retrospective study, we included 83 women of reproductive age with symptomatic isthmocele undergoing laparoscopic isthmocele repair in rendezvous technique from 2004 to 2020 at the University of Bern. We collected data on patient and surgical characteristics as well as on postoperative outcomes (symptoms, further pregnancy, and pregnancy outcomes) retrospectively. We analyzed and compared these data for patients with and without endometriosis. Endometriosis was diagnosed during surgery in 22 out of 83 operated patients (26.5%). Diagnosis of isthmocele endometriosis (n = 9, 11%) was significantly higher in patients with extrauterine endometriosis (n = 6, p = 0.004). While the duration of surgery was significantly longer for patients with endometriosis (p = 0.006), the groups did not differ with regard to blood loss or complications. In addition, both groups showed similar indications for isthmocele repair (infertility, abnormal uterine bleeding, or dysmenorrhea). Surgery significantly improved abnormal uterine bleeding (χ² p < 0.001), dysmenorrhea (χ², p = 0.03), and infertility (χ², p < 0.001). Regardless of the presence of endometriosis, 25 of 40 (63%) infertile patients became pregnant after surgery. In one out of eight pregnancies, however, we observed scar complications during pregnancy such as uterine scar pregnancy (n = 3), uterine scar dehiscence (n = 3), and placenta previa (n = 1). Endometriosis is a non-negligible intraoperative finding in patients with symptomatic isthmocele. The laparoscopic approach in the rendezvous technique is safe and effective. Therefore, this method should be recommended, especially in women with secondary infertility, and preoperatively simultaneous endometriosis resection should be discussed with the patient. In follow-up, postoperative pregnancies have to be monitored with care. Full article

(1) Background: The aim of this study was to evaluate the impact of endometriosis on postoperative pain following laparoscopic hysterectomy; (2) Methods: A total of 214 women who underwent a laparoscopic hysterectomy between January 2013 and October 2017 were divided into four subgroups as follows: (1) endometriosis with chronic pain before the surgery (n = 57); (2) pain-free endometriosis (n = 50); (3) pain before the surgery without endometriosis (n = 40); (4) absence of both preoperative pain and endometriosis (n = 67). Postoperative pain was compared by using Visual Analog Scale (VAS) scores and by tracking the use of painkillers during the day of surgery and the first two postoperative days; (3) Results: Women with chronic pain before the surgery reported higher VAS scores during the first postoperative days, while the use of analgesics was similar across the groups. There was no difference in the postoperative pain when comparing endometriosis patients to non-endometriosis patients; (4) Conclusions: Women with chronic pelvic pain demonstrated increased postoperative pain after laparoscopic hysterectomy, which was independent of the presence or severity of endometriosis. The increased VAS scores did not, however, translate into equally greater use of painkillers, possibly due to the standardised protocols of analgesia in the immediate postoperative period. These findings support the need for careful postsurgical pain management in patients with pain identified as an indication for hysterectomy, independent of the extent of the surgery or underlying diagnosis. Full article

Background: use of fibrin sealants following pelvic, paraaortic, and inguinal lymphadenectomy may reduce lymphatic morbidity. The aim of this meta-analysis is to evaluate if this finding applies to the axillary lymphadenectomy. Methods: randomized trials evaluating the efficacy of fibrin sealants in reducing axillary lymphatic complications were included. Lymphocele, drainage output, surgical-site complications, and hospital stay were considered as outcomes. Results: twenty-three randomized studies, including patients undergoing axillary lymphadenectomy for breast cancer, melanoma, and Hodgkin’s disease, were included. Fibrin sealants did not affect axillary lymphocele incidence nor the surgical site complications. Drainage output, days with drainage, and hospital stay were reduced when fibrin sealants were applied (p < 0.0001, p < 0.005, p = 0.008). Conclusion: fibrin sealants after axillary dissection reduce the total axillary drainage output, the duration of drainage, and the hospital stay. No effects on the incidence of postoperative lymphocele and surgical site complications rate are found. Full article

Recurrence of endometriosis after surgery constitutes a serious challenge. Whether there is an evolution of lesion subtypes with each recurrence and whether certain lesions subtypes tend to recur faster than others is not adequately addressed. Medical records of all patients who underwent surgery for endometriosis between 1997 and 2018 in the Department of Gynecology and Obstetrics, University of Bern, were reviewed. Inclusion criteria was surgically confirmed endometriosis recurrence, defined as a subsequent surgery for endometriosis after a previous complete surgical excision of endometriosis lesions. Three subtypes of endometriosis were defined: superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA), and deep infiltrating endometriosis (DIE). Time to recurrence and variation in endometriosis subtype between the first and recurrent surgeries were the primary outcome measures. Out of the 322 patients with recurrent surgery that were identified, for 234 of them, the endometriosis subtype at first surgery was confirmed and classified (SUP = 56, OMA = 124, DIE = 54). No statistically significant difference was found for time to recurrence between lesion subtypes. SUP compared to the other groups had a higher possibility of presenting with SUP at recurrence (Odds Ratio (OR): 3.65, 95% confidence interval (CI): 1.74–7.51) and OMA compared to the other groups had a higher possibility of presenting with OMA at recurrence (OR: 3.72, 95% CI: 2.04–6.74). Nevertheless, a large number of SUP patients subsequently presented with OMA (10/56: 17.9%) or DIE (27/56: 48.2%) lesions at recurrence. Similarly, a large number of OMA patients subsequently presented with DIE (49/124: 39.5%) lesions at recurrence. In conclusion, although SUP and OMA patients compared to the others are more likely to present with the same subtype at recurrence, increasing lesion subtype severity occurs in a substantial proportion of patients. Time to recurrence is independent from the lesion subtype at first surgery. Full article

Rivers are important ecosystems under continuous anthropogenic stresses. The hyporheic zone is a ubiquitous, reactive interface between the main channel and its surrounding sediments along the river network. We elaborate on the main physical, biological, and biogeochemical drivers and processes within the hyporheic zone that have been studied by multiple scientific disciplines for almost half a century. These previous efforts have shown that the hyporheic zone is a modulator for most metabolic stream processes and serves as a refuge and habitat for a diverse range of aquatic organisms. It also exerts a major control on river water quality by increasing the contact time with reactive environments, which in turn results in retention and transformation of nutrients, trace organic compounds, fine suspended particles, and microplastics, among others. The paper showcases the critical importance of hyporheic zones, both from a scientific and an applied perspective, and their role in ecosystem services to answer the question of the manuscript title. It identifies major research gaps in our understanding of hyporheic processes. In conclusion, we highlight the potential of hyporheic restoration to efficiently manage and reactivate ecosystem functions and services in river corridors. Full article