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We read, with great interest, two recent articles by Castellucci and al [...]

Abstract Aim of the study was to evaluate the diagnostic performance and feasibility of transabdominal ultrasound shear wave elastography (SWE) in assessing sonoelastographic features of the uterus. Twenty-seven premenopausal women were enrolled between 2021 and 2022. Transabdominal SWE measured myometrial stiffness in various uterine segments. Additionally, tissue stiffness of the quadriceps femoris muscle and autochthonous back muscle was measured. Statistical analysis employed non-parametric tests, t test, and a robust mixed linear model. Stiffness values of the uterus and the two investigated muscle types exhibited a similar spectrum: 6.38 ± 2.59 kPa (median 5.61 kPa; range 2.76–11.31 kPa) for the uterine myometrium, 7.22 ± 1.24 kPa (6.82 kPa; 5.11–9.39 kPa) for the quadriceps femoris musle, and 7.43 ± 2.73 kPa (7.41 kPa; 3.10–13.73 kPa) for the autochthonous back muscle. A tendency for significant differences in myometrial stiffness was observed concerning the type of labor mode (mean stiffness of 9.17 ± 1.35 kPa after vaginal birth vs. 3.83 ± 1.35 kPa after Caesarian section, p = 0.01). No significant differences in myometrial stiffness were observed concerning age, BMI, previous pregnancies, uterine flexion and menstrual cycle phase. Transabdominal SWE of uterine stiffness seems to be a fast and practicable method in a clinical setting. Uterine stiffness appears to be largely independent of various factors, except for the mode of delivery. However, further studies are needed to validate these results.

Background and Purpose: To investigate the effect of topical non-invasive physical plasma (NIPP), a volatile mix generated out of ambient air, on prevention of acute radiation dermatitis (RD) during and after whole-breast irradiation (WBI). Materials and Methods: Lateral and medial breast halves were randomised within each patient to receive either 120 s of NIPP or sham treatment daily during WBI. Standard skin care with urea lotion was applied to the whole breast. Blinded acute skin toxicity was assessed weekly for each breast half separately and included clinician- (CTCAE) and patient-reported (modified RISRAS), and objective (spectrophotometry) assessments. As an additional external control, a comparable standard of care (SoC) patient collective from a previous prospective trial was used. Results: Sixty-four patients were included. There were no significant differences between breast halves. Post-hoc comparison with a similar SoC control collective revealed OR = 0.28 (95% CI 0.11–0.76; p = 0.014) for grade ≥ 2 RD upon WBI completion, along with less hyperpigmentation (p

Abstract Background Inducible T cell costimulator ICOS is an emerging target in immuno-oncology. The aim of this study was to investigate the epigenetic regulation of ICOS in melanoma by DNA methylation. Methods We comprehensively investigate ICOS DNA methylation of specific CpG sites and expression pattern within the melanoma microenvironment with regard to immune correlates, differentiation, clinical outcomes, and immune checkpoint blockade (ICB) response. Results Our study revealed a sequence-contextual CpG methylation pattern consistent with an epigenetically regulated gene. We found a cell type-specific methylation pattern and locus-specific correlations and associations of CpG methylation with ICOS mRNA expression, immune infiltration, melanoma differentiation, prognosis, and response to ICB. High ICOS mRNA expression was identified as a surrogate for enriched immune cell infiltration and was associated with favorable overall survival (OS) in non-ICB-treated patients and predicted response and a prolonged progression-free survival (PFS) following ICB therapy initiation. ICOS hypomethylation, however, significantly correlated with poor OS in non-ICB patients but predicted higher response and prolonged PFS and OS in ICB-treated patients. Moreover, we observed cytoplasmic and sporadically nuclear tumor cell-intrinsic ICOS protein expression. Tumor cell-intrinsic ICOS protein and mRNA expression was inducible by pharmacological demethylation with decitabine. Conclusion Our study identified ICOS DNA methylation and mRNA expression as promising prognostic and predictive biomarkers for immunotherapy in melanoma and points towards a hitherto undescribed role of ICOS in tumor cells.

Objective structured clinical examination (OSCE) is a well-known assessment method to evaluate clinical skills and competence in healthcare. Following the recently reformed National Competence-Based Catalog of Learning Objectives in Medicine, the implementation of this assessment method in the training program for medical students is now obligatory in Germany. This major change requires a reorganization not only of the training programs but also of the students themselves and the way they learn. We performed a poll evaluating the students’ opinions regarding these major changes and the implementation of the OSCE with a new training program. To implement this assessment method and to evaluate the OSCE, Kern’s six-step approach comprising (1) problem identification and general needs assessment, (2) needs assessment of the targeted learners, (3) goals and objectives, (4) educational strategies, (5) implementation, and (6) evaluation and feedback was applied. To evaluate and gather feedback, a poll was used to analyze the student’s opinions regarding OSCE in gynecology and obstetrics and OSCE in general, in addition to the regular analysis of the students’ results. To reform the educational strategy, a two-step approach was developed: First, the students completed the regular training program and a written examination, and second, they participated in a 1-week clerkship, in small group teaching, and in the OSCE. The OSCE stations were developed primarily based on the National Competence-Based Catalog and the German Catalog of Learning Objectives in Medicine, as well as on the feedback of experts reflecting their expectations for physicians beginning their careers. The students performed well in the OSCE and gave positive feedback regarding this examination method. Furthermore, they welcomed the upcoming changes by considering OSCE a valuable assessment tool, and they showed appreciation for the two-step approach by supporting the combination of an OSCE and a written examination. Thus, this article presents the implementation of an OSCE and a strategy for the adaptation of the curriculum to fulfill the new OSCE requirements and—to our knowledge—reveals students’ primary opinions regarding the changes in their medical training program for the first time.

IntroductionComplete macroscopic cytoreduction represents the most important prognostic parameter for overall survival in ovarian cancer. This dogma remains tenacious despite significant improvements in adjuvant systemic treatment. Hence, optimization of surgical therapy is an overarching goal to improve patients’ outcomes. In this context, intraoperative tumor-specific imaging might facilitate optimized cytoreduction. In neurosurgery, intraoperative 5-aminolevulinic acid (5-ALA) guided imaging is applied in clinical routine to assess surgical resection margins. Here, we report the case of a patient with ovarian cancer in whom intraoperative 5-ALA tumor visualization led to optimized complete cytoreduction.ObjectiveIntraoperative administration of 5-ALA led to improved complete cytoreduction by identification and resection of additional ovarian cancer tumor manifestations.CaseThe 39-year-old patient, Jehovah`s witness, presented to our department with a left sided ovarian mass, suspicious of ovarian cancer, based on clinical examination, sonographic suspicious features and a CA12-5 elevation. The patient’s medical history and family history was unremarkable. Preoperative CT imaging of the thorax and abdomen showed no pathology besides the adnexal mass. Surgery was performed by a midline laparotomy with hysterectomy, bilateral adnexectomy, pelvic peritonectomy, omentectomy, ureterolysis, diaphragm stripping, adhesiolysis and the collection of peritoneal and rectal samples. Intraoperative 5-ALA imaging using a dedicated excitation and detection loupe system (Reveal, DVI) led to tumor detection at the diaphragm, the omentum and the rectum that was not detectable by palpation and visualization using white light. The pathology results revealed that the 5-ALA positive samples (diaphragm, rectum and omentum) obtained by intraoperative 5-ALA were positive for ovarian cancer.ConclusionIntraoperative administration of 5-ALA represents a promising approach to improve complete cytoreduction in ovarian cancer surgery thereby improving clinical outcomes. Hence, further research and clinical trials are required to investigate the potential of intraoperative 5-ALA imaging in ovarian cancer debulking surgery and its impact on long-term clinical outcomes.

Key points Deep learning methods enable accurate segmentation of the uterus in T2-weighted MRI. Automatic uterine volumetry is possible in patients with and without leiomyomas. Automated volumetry enables an objective assessment of response to high-intensity focused ultrasound therapy.

Abstract Uterine fibroids are the most common benign uterine tumors and can cause various severe symptoms as abnormal menstrual bleeding or pelvic pain. Therefore, the primary objective in the treatment of uterine fibroids is a sufficient symptom relief. Ultrasound (US)-guided High-intensity focused ultrasound (HIFU) is an effective non-invasive treatment strategy for ablation of uterine fibroids that can achieve a significant tumor volume reduction. The aim of the study is to evaluate if US-guided HIFU treatment can reduce fibroid-associated symptoms leading to an improvement of health-related quality of life. Fifty-five women with symptomatic uterine fibroids underwent US-guided HIFU ablation. Clinical evaluation was performed on the basis of the Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) at baseline, 6 weeks, 3, 6, 9 and 12 months after HIFU. Imaging follow-up included contrast-enhanced ultrasound (CEUS) and contrast-enhanced MRI. A significant reduction of the Symptom Severity Scale (SSS) was observed between 6 weeks and 12 months after HIFU (49.9 ± 19.4 at baseline vs. 42.2 ± 20.1 at 6 weeks and 23.6 ± 12.7 at 12 months after treatment, p

The pandemic effects are still being perceived on the worldwide economy and economic growth is projected to slow in 2022 and 2023 compared to 2021. In this "bad" environment, the war in Ukraine severely affected European countries' economies and all world economies as a domino effect. This paper investigates public sector performance in European countries in recent literature by analyzing 2018-2022 published scientific papers. We perform science mapping by using the VOSviewer software to identify networks between keywords and authors. Our results reveal that strong links exist between keywords occurrence, authors' networks, but also between countries and institutions.

Abstract Background Vulvar squamous cell carcinoma (VSCC) is an uncommon gynecologic malignancy but with an increasing incidence in recent years. Etiologically, VSCC is classified into two subtypes: HPV-dependent and HPV-independent. Localized VSCC is treated surgically and/or with radiation therapy, but for advanced, metastatic or recurrent disease, therapeutic options are still limited. N6-methyladenosine (m6A) is the most prevalent post-transcriptional messenger RNA (mRNA) modification and involved in many physiological processes. The group of m6A proteins can be further divided into: ‚writers’ (METTL3, METTL4, METTL14, WTAP, KIAA1429), ‚erasers’ (FTO, ALKBH5), and ‚readers’ (HNRNPA2B1, HNRNPC, YTHDC1, YTHDF1-3). Dysregulated m6A modification is implicated in carcinogenesis, progression, metastatic spread, and drug resistance across various cancer entities. Up to date, however, only little is known regarding the role of m6A in VSCC. Methods Here, we comprehensively investigated protein expression levels of a diverse set of m6A writers, readers and erasers by applying immunohistochemical staining in 126 patients with primary VSCC. Results In the entire study cohort, dominated by HPV-independent tumors, m6A protein expression was not associated with clinical outcome. However, we identified enhanced protein expression levels of the ‚writers’ METTL3, METTL14 and the ‚reader’ YTHDC1 as poor prognostic markers in the 23 patients with HPV-dependent VSCC. Conclusion Our study suggests dysregulated m6A modification in HPV-associated VSCC.

Abstract Background Estrogen-related receptor α (ERRα) has been reported to play a critical role in endometrial cancer (EC) progression. However, the underlying mechanism of ERRα-mediated lipid reprogramming in EC remains elusive. The transcription factor EB (TFEB)-ERRα axis induces lipid reprogramming to promote progression of EC was explored in this study. Methods TFEB and ERRα were analyzed and validated by RNA-sequencing data from the Cancer Genome Atlas (TCGA). The TFEB-ERRα axis was assessed by dual-luciferase reporter and chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR). The mechanism was investigated using loss-of-function and gain-of-function assays in vitro. Lipidomics and proteomics were performed to identify the TFEB-ERRα-related lipid metabolism pathway. Pseudopods were observed by scanning electron microscope. Furthermore, immunohistochemistry and lipidomics were performed in clinical tissue samples to validate the ERRα-related lipids. Results TFEB and ERRα were highly expressed in EC patients and correlated to EC progression. ERRα is the direct target of TFEB to mediate EC lipid metabolism. TFEB-ERRα axis mainly affected glycerophospholipids (GPs) and significantly elevated the ratio of phosphatidylcholine (PC)/sphingomyelin (SM), which indicated the enhanced membrane fluidity. TFEB-ERRα axis induced the mitochondria specific phosphatidylglycerol (PG) (18:1/22:6) + H increasing. The lipid reprogramming was mainly related to mitochondrial function though combining lipidomics and proteomics. The maximum oxygen consumption rate (OCR), ATP and lipid-related genes acc, fasn, and acadm were found to be positively correlated with TFEB/ERRα. TFEB-ERRα axis enhanced generation of pseudopodia to increase the invasiveness. Mechanistically, our functional assays indicated that TFEB promoted EC cell migration in an ERRα-dependent manner via EMT signaling. Consistent with the in vitro, higher PC (18:1/18:2) + HCOO was found in EC patients, and those with higher TFEB/ERRα had deeper myometrial invasion and lower serum HDL levels. Importantly, PC (18:1/18:2) + HCOO was an independent risk factor positively related to ERRα for lymph node metastasis. Conclusion Lipid reprogramming induced by the TFEB-ERRα axis increases unsaturated fatty acid (UFA)-containing PCs, PG, PC/SM and pseudopodia, which enhance membrane fluidity via EMT signaling to promote EC progression. PG (18:1/22:6) + H induced by TFEB-ERRα axis was involved in tumorigenesis and PC (18:1/18:2) + HCOO was the ERRα-dependent lipid to mediate EC metastasis.

Abstract Little is known about the specific anaesthesiological and multidisciplinary management of high-intensity focused ultrasound (HIFU) in uterine fibroids. This observational single-center study is the first reporting on an interdisciplinary approach to optimize outcome following ultrasound (US)-guided HIFU in German-speaking countries. A sample of forty patients with symptomatic uterine fibroids was treated by HIFU. Relevant treatment parameters such as total treatment time for intervention, anaesthesia, and sonication time as well as total energy, body temperature, peri-interventional medication and complications were analyzed. Interventional variables did not correlate significantly either with opioid dose or with body temperature. The average fibroid volume reduction rate was 37.8% ± 23.5%, 48.5% ± 22.0% and 70.2% ± 25.5% after 3, 6 and 12 months, respectively. No major anaesthesiological complications occurred apart from an epileptic seizure prior to HIFU treatment in one patient. Peri-procedural hyperthermia (> 37.5 °C) occurred in two patients. Post-procedural two patients experienced a sciatic nerve irritation up to one year; one patient with very large treated fibroid experienced strong short-lasting post-procedural pain. There were two complication-free pregnancies of HIFU-treated patients. Multidisciplinary management is crucial to optimize safety and outcome of US-guided HIFU for uterine fibroids. Peri-procedural pain and temperature management are critical points where an adequate collaboration between anesthesiologist and interventionalist is mandatory.

Abstract Background Prior research has shown that around 5%–7% of patients in breast cancer centers in Germany participate in the discussion of their own case within a multidisciplinary tumor conference (MTC). The PINTU study is one of the first to research this practice. The objective is to describe (a) how patient participation in MTCs is implemented, (b) what is the role of patients, and (c) how patients experience MTCs. Methods MTCs in six breast and gynecological cancer centers in North Rhine‐Westphalia, Germany, with and without patient participation, are studied prospectively by (non)participatory, structured observation. Breast and gynecological cancer patients completed surveys before, directly after, and 4 weeks after MTC participation. Data are analyzed descriptively. Results Case discussions of a sample of n = 317 patients (n = 95 with MTC participation and n = 222 without) were observed. Survey data were obtained from n = 242 patients (n = 87 and n = 155). Observational data showed heterogeneity in the ways MTC participation was practiced. Among participating patients, 89% had the opportunity to express their opinion and 61% were involved in decision‐making. Whereas most patients reported positive experiences and would recommend participation, some had negative experiences and regretted participating. Conclusions Due to a lack of recommendations, hospitals implement patient participation in MTCs in many different ways. So far, it is unknown which setting and procedures of MTC participation are beneficial for patients. However, existing evidence on communication in cancer care together with this exploratory study's findings can build the basis for developing recommendations for hospitals that invite their patients to MTCs. Clinical trial registration number German Clinical Trials Register Nr. DRKS00012552.

PurposeThe most important prognostic factor for survival in ovarian cancer patients is complete cytoreduction. The preoperative prediction of suboptimal cytoreduction, considered as any residual disease at the end of surgery, could prevent futile surgery and morbidity. Here, we aimed to identify markers in the preoperative abdominal CT scans of an unselected cohort of patients with ovarian cancer that are predictive of incomplete cytoreduction.MethodsThis is a single-institution retrospective analysis of 105 epithelial ovarian cancer (EOC) patients treated with surgical cytoreduction between 2010 and 2020. Twenty-two variables on preoperative abdominal CT scans were compared to the intraoperative macroscopic findings by Fisher’s exact test. Parameters with a significant correlation between intraoperative findings and imaging were analyzed by multivariate binary logistic regression analysis regarding the surgical outcome of complete versus incomplete cytoreduction.ResultsComplete cytoreduction (CC), indicated by the absence of macroscopic residual disease, was achieved in 79 (75.2%) of 105 patients and 46 (63.9%) of 72 International Federation of Gynecology and Obstetrics (FIGO) stage III and IV patients. Twenty patients (19%) were incompletely cytoreduced due to miliary carcinomatosis of the small bowel, and six patients (5.7%) had various locations of residual disease. Thirteen variables showed a significant correlation between imaging and surgical findings. Large-volume ascites, absence of numerically increased small lymph nodes at the mesenteric root, and carcinomatosis of the transverse colon in FIGO stage III and IV patients decreased the rate of CC to 26.7% in the multivariate analysis.ConclusionLarge-volume ascites, the absence of numerically increased small lymph nodes at the mesenteric root, and carcinomatosis of the transverse colon are markers in preoperative CT scans predicting a low chance for complete cytoreduction in unselected ovarian cancer patients in a real-world setting.

Introduction To evaluate treatment response of uterine fibroids after ultrasound guided high-intensity focused ultrasound (USgHIFU) with a special focus on fibroid size and characterization based on Funaki classification scheme, as well as clinical response to treatment of leading fibroid-associated symptoms. Materials and methods Uterine fibroids treated by USgHIFU were assigned to Funaki type 1–3 based on T2-w-MRI. Differences in size, non-perfused volume ratio (NPVR) and volume reduction over time were determined using T1-/T2-w MRI sequences and contrast-enhanced sonography. Treatment effects on three leading fibroid-associated symptoms were also evaluated. Measurements were compared by mixed model, Bland–Altman’s plot and Spearman’s correlation. Results In this prospective single-center study, 35 patients with 44 symptomatic uterine fibroids were treated by USgHIFU (n = 22, n = 12 and n = 10 assigned to Funaki type 1, 2 and 3, respectively). NPVRs of Funaki type 1 and 2 fibroids were significantly higher compared to type 3 (p = .0023). A significant fibroid shrinkage was observed independent of Funaki type compared to baseline: 38.8 ± 26.9%, 46.7 ± 30.3% and 54.5 ± 29.3% at 3, 6 and 12 months, respectively (each p

Introduction High-intensity focused ultrasound (HIFU) is an innovative noninvasive procedure for local ablation of different benign and malignant tumors. Preliminary data of animal studies suggest an ablation-associated immune response after HIFU that is induced by cell necrosis and release of intracellular components. The aim of this study is to evaluate if a HIFU-induced early sterile inflammatory reaction is initiated after ablation of uterine fibroids (UF) and pancreatic carcinoma (PaC) which might contribute to the therapeutic effect. Material and methods A hundred patients with PaC and 30 patients with UF underwent US-guided HIFU treatment. Serum markers of inflammation (leukocytes, CRP, IL-6) and LDH in both collectives as well as tumor markers CA 19-9, CEA and CYFRA in PaC patients were determined in sub-cohorts before and directly after HIFU (0, 2, 5 and 20 h post-ablation) as well as at 3, 6, 9 and 12 months follow-up. Peri-/post interventional imaging included contrast-enhanced MRI of both cohorts and an additional CT scan of PaC patients. Results An early post-ablation inflammatory response was observed in both groups with a significant increase of leukocytes, CRP and LDH within the first 20 h after HIFU. Interestingly, IL-6 was increased at 20 h after HIFU in PaC patients. A significant reduction of tumor volumes was observed during one year follow-up (p

AimThis study aims to evaluate the incidence of postoperative ileus (POI) following cytoreductive surgery in epithelial ovarian cancer (EOC) patients and its impact on anastomotic leakage occurrence and postoperative complications.MethodsA total of 357 surgeries were performed on 346 ovarian cancer patients between 1/2010 and 12/2020 at our institution. The postoperative course regarding paralytic ileus, anastomotic leakage, and postoperative complications was analyzed by Fisher's exact test and through ordinal logistic regression.ResultsA total of 233 patients (65.3%) returned to normal gastrointestinal functions within 3 days after surgery. A total of 123 patients (34.5%) developed POI. There were 199 anastomoses in 165 patients and 24 leakages (12.1%). Postoperative antibiotics (p 0.001), stoma creation (p 0.0001), and early start of laxatives (p 0.0048) significantly decreased POI, while anastomoses in general (p 0.0465) and especially low anastomoses (p 0.0143) showed increased POI rates. Intraoperative positive fluid excess >5,000 cc was associated with a higher risk for POI (p 0.0063), anastomotic leakage (p 0.0254), and severe complications (p 0.0012).ConclusionPostoperative antibiotics, an early start with laxatives, and stoma creation were associated with reduced POI rates. Patients with anastomoses showed an increased risk for POI. Severe complications, anastomotic leakages, and POI were more common in the case of intraoperative fluid balance exceeding 5,000 cc.

Abstract Minimally invasive surgery (MIS) has become the standard approach in early stage cervical cancer (ECC). However, the recently published “LACC” trial and even others could show inferior PFS and OS of MIS compared to open radical hysterectomy. The results led to a widespread debate about the best surgical approach in ECC. The present survey aimed to get first insights after publication. NOGGO and AGE conducted a nationwide digital survey among 186 Gynecological Cancer Centers. Descriptive statistics and t-tests were performed using SPSS. A majority of the centers were of high expertise and/or experience in treatment of ECC and were highly aware of the LACC trial results. Trial quality and scientific value were rated as very good/good. However, still 40% would not change the standard of care to open surgery. Centers with higher volume and participating in clinical trials were more likely to change. This survey represents insights after the surprising results of recently published trials towards the surgical approach of ECC. There still seems to be a high need of future trials and possible explanations for the unexpected worse outcomes in the MIS group.

Recently, biomedical research has increasingly investigated physical plasma as an innovative therapeutic approach with a number of therapeutic biomedical effects. It is known from radiation and chemotherapy that these applications can lead to the induction and activation of primarily cytoprotective heat shock proteins (HSP). HSP protect cells and tissues from physical, (bio)chemical, and physiological stress and, ultimately, along with other mechanisms, govern resistance and treatment failure. These mechanisms are well known and comparatively well studied in drug therapy. For therapies in the field of physical plasma medicine, however, extremely little data are available to date. In this review article, we provide an overview of the current studies on the interaction of physical plasma with the cellular HSP system.

Due to a vast influx in the secretory phase of the menstrual cycle, leukocytes represent 40–50% of the decidua at the time of implantation. Their importance for the implantation, maintenance of pregnancy, and parturition are known yet not fully understood. Thus, in idiopathic infertility, decidual immune-related factors are speculated to be the cause. In this review, the immune cell functions in the decidua were summarized, and clinical diagnostics, as well as interventions, were discussed. There is a rising number of commercially available diagnostic tools. However, the intervention options are still limited and/or poorly studied. In order for us to make big steps towards the proper use of reproductive immunology findings, we need to understand the mechanisms and especially support translational research.