Auswirkungen auf das Peritoneum durch Wasserstrahlanwendung - Experimentelle Untersuchungen mit Argonplasma

In dieser Studie wurde der Gewebeeffekt der Hybrid-Argonplasma-Koagulation (HybridAPC) am Rattenperitoneum untersucht. Bei diesem Instrument wird die monopolare Hochfrequenz-Koagulationstechnik der Argonplasma-Koagulation (APC) mit einer Wasserstrahl-Unterspritzung (mit physiologischer Kochsalzlösung) kombiniert. Vor Koagulation kann mit demselben Instrument ein Wasserkissen ins Gewebe eingebracht werden. Durch diese Maßnahme kann das Ausmaß des thermischen Schadens besser kontrolliert und tiefere Gewebeschichten geschont werden. Da bis Dato noch keine Studie den Effekt einer Gewebeunterspritzung vor Koagulation am Peritoneum untersucht, sollte dies in der vorliegenden Studie unter Anwendung der HybridAPC erfolgen. Methoden: Die Untersuchung der unterschiedlichen Gewebeeffekte erfolgte an 24 weiblichen Wistar-Ratten unter Allgemeinanästhesie. Auf der einen Seite der Bauchwand erfolgte nur eine Unterspritzung des Peritoneums um die alleinigen Auswirkungen der Unterspritzung auf das Gewebe zu prüfen. Auf der anderen Seite wurde nach Unterspritzung mit APC punktuell koaguliert. Pro Tier wurden mit jeder Behandlungsart zwei Läsionen gesetzt. Am 10. postoperativen Tag erfolgte die Euthanasierung der Tiere mit Evaluation der Adhäsionen und anschließender histopathologischer Auswertung des behandelten Gewebes (Second Look). Hierbei wurden folgende Parameter untersucht: Eindringtiefe der Wasserstrahl-Unterspritzung, Ausmaß des thermischen Schadens bei Koagulation, Grad der akuten und chronischen Entzündungsreaktion, Auftreten von Fremdkörperreaktionen und Karbonisation. Ergebnisse: Bei alleiniger Gewebeunterspritzung mit Kochsalzlösung konnte keine Adhäsion im Bereich der während der Operation traumatisierten Areale festgestellt werden. Bei 15% der Herde zeigte sich jedoch eine geringe chronische Entzündung. Die Schicht in welcher sich das Wasserkissen intraoperativ befand, konnte beim Second Look histologisch nicht mehr festgestellt werden. Die Anwendung der HybridAPC führte histologisch zu einer thermischen Schädigung der oberflächlichen Gewebeschichten mit einer Eindringtiefe von 329 ± 123 μm bei einem Energieeintrag von 106 ± 10,7 J. Im Bereich der 44 HybridAPC Läsionen konnte postoperativ nur eine Adhäsion (Grad 2) beobachtet werden. Schlussfolgerung: Die Ergebnisse der Studie legen nahe, dass die alleinige Unterspritzung des Peritoneums der Ratte mit physiologischer Kochsalzlösung einen geringen traumatischen und adhäsiogenen Reiz für das Gewebe darstellt. Durch die Unterspritzung des Gewebes vor Koagulation konnte die Tiefe des thermischen Schadens signifikant reduziert werden und auch die Varianz der Tiefe der thermischen Schädigung (im Vergleich zu vorausgegangen Studie der Arbeitsgruppe mit der konventionellen APC) am Rattenperitoneum vermindert werden. Nach Anwendung der HybridAPC bildeten sich signifikant weniger Adhäsionen im Bereich der Koagulationsareale als im Vergleich zur konventionellen APC aus

Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial

Background Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. Methods In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Results Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58–1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen. Conclusions No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences

Identification of a novel tumor microenvironment prognostic signature for advanced-stage serous ovarian cancer

(1) Background: The tumor microenvironment is involved in the growth and proliferation of malignant tumors and in the process of resistance towards systemic and targeted therapies. A correlation between the gene expression profile of the tumor microenvironment and the prognosis of ovarian cancer patients is already known. (2) Methods: Based on data from The Cancer Genome Atlas (379 RNA sequencing samples), we constructed a prognostic 11-gene signature (SNRPA1, CCL19, CXCL11, CDC5L, APCDD1, LPAR2, PI3, PLEKHF1, CCDC80, CPXM1 and CTAG2) for Fédération Internationale de Gynécologie et d’Obstétrique stage III and IV serous ovarian cancer through lasso regression. (3) Results: The established risk score was able to predict the 1-, 3- and 5-year prognoses more accurately than previously known models. (4) Conclusions: We were able to confirm the predictive power of this model when we applied it to cervical and urothelial cancer, supporting its pan-cancer usability. We found that immune checkpoint genes correlate negatively with a higher risk score. Based on this information, we used our risk score to predict the biological response of cancer samples to an anti-programmed death ligand 1 immunotherapy, which could be useful for future clinical studies on immunotherapy in ovarian cancer

Effects of matcha tea extract on cell viability and peroxisome proliferator-activated receptor γ expression on T47D breast cancer cells

PURPOSE: In the following work, we investigated the nuclear peroxisome proliferator-activated receptor gamma (PPARγ)-dependent proliferation behavior of breast cancer cells after stimulation with matcha green tea extract (MTE). METHODS: T47D cells were stimulated with MTE at concentrations of 5, 10 and 50 µg/ml. Cell viability was assessed using a WST-1 assay after an incubation time of 72 h. PPARγ expression was quantified at the gene level by real-time polymerase chain reaction (PCR). A western blot (WB) was carried out for the qualitative assessment of the expression behavior of on a protein level. RESULTS: The WST-1 test showed a significant inhibition of viability in T47D cells after 72 h at 5, 10 and 50 µg/ml. The PCR showed an overexpression of PPARγ in T47D cells in all concentrations. At the concentration of 50 µg/ml the expression was significantly increased (p < 0.05). The WB demonstrated a significant quantitative increase of PPARγ at protein level with MTE concentrations of 10 and 50 µg/ml. In addition, there was a negative correlation between the overexpression of PPAR γ and the inhibition of proliferation. CONCLUSION: MTE decreases the cell viability of T47D cells and furthermore leads to an overexpression of PPARγ on protein and mRNA level

Cytoplasmic Localization of RXRα Determines Outcome in Breast Cancer

International audienceThe aim of this retrospective study was to assess the prognostic value of cytoplasmic versus nuclear RXRα expression in breast cancer (BC) tissue samples and to correlate the results with clinicopathological parameters. In 319 BC patients, the expression of RXRα was evaluated via immunohistochemistry. Prognosis-determining aspects were calculated through uni- and multivariate analyses. Correlation analysis revealed a trend association with nuclear RXRα expression regarding an improved overall survival (OS) (p = 0.078), whereas cytoplasmic RXRα expression was significantly correlated with a poor outcomes in terms of both OS (p = 0.038) and disease-free survival (DFS) (p = 0.037). Strengthening these results, cytoplasmic RXRα was found to be an independent marker for DFS (p = 0.023), when adjusted to clinicopathological parameters, whereas nuclear RXRα expression was positively associated with lower TNM-staging, i.e., pT (p = 0.01), pN (p = 0.029) and pM (p = 0.001). Additionally, cytoplasmic RXRα expression was positively associated with a higher histopathological tumor grading (p = 0.02). Cytoplasmic RXRα was also found to be a negative prognosticator for Her-2neu-negative and triple-negative patients. Altogether, these findings support the hypothesis that the subcellular localization of RXRα plays an important role in carcinogenesis and the prognosis of BC. The expression of cytoplasmic RXRα is correlated with a more aggressive course of the disease, whereas nuclear RXRα expression appears to be a protective factor. These data may help to identify high-risk BC subgroups in order to find possible specific options in targeted tumor therapy

Trends among patients with endometriosis over a 7-year period and the impact of the COVID-19 pandemic: experience from an academic high-level endometriosis centre in Germany

PURPOSE: Endometriosis is known to be an underestimated disease. Lately the awareness of the disease seems to have improved. Aim of this analysis is to provide an overview of the development of treatment of patients diagnosed with endometriosis. This includes a special scope on implications of the COVID-19 pandemic since in multiple settings postponed treatments resulting in negative impact on prognosis were reported. MATERIALS AND METHODS: We analysed the development of numbers of patients treated for endometriosis in an academic centre within a 7-year period, 01/2015–12/2021, performing a systematic analysis of ICD-10-Codes from our computer system used in clinical routine. RESULTS: Treatment numbers increased over the past 7 years, i.e., 239 treated cases in 2015 vs. 679 in 2021. Following restrictions for outpatient evaluation and surgical capacity at our centre, during COVID-19 pandemic the numbers of treated patients were reduced, especially in the first lockdown period (03/22/2020–05/05/2020 vs. same period in 2019: outpatient clinic (9 vs. 36; p < 0.001), patients surgically treated (27 vs. 52; p < 0,001)). The comparison of 2020 to 2019 showed a reduction in April 2020 of − 37% in outpatient department and up to − 90% for surgically treated patients. Comparing to 2019, we found a reduction of surgical interventions in 2020 by − 9% and an increase by 83% in 2021. CONCLUSIONS: Raising numbers of patients treated for endometriosis point to a new awareness for the disease. After the decline during the lockdown period numbers raised again, leading to a delay, but not an omission of treatment. A certified endometriosis centre with established and well-organized structures is required to improve not only treatment results but also quality of life of those affected