Glioblastoma is one of the deadliest malignancies and is virtually incurable. Accumulating evidence indicates that a small population of cells with a stem-like phenotype is the major culprit of tumor recurrence. Enhanced DNA repair capacity and expression of stemness marker genes are the main characteristics of these cells. Elimination of this population might delay or prevent tumor recurrence following radiochemotherapy. The aim of this study was to analyze whether interference with the Hedgehog signaling (Hh) pathway or combined Hh/Notch blockade using small-molecule inhibitors can efficiently target these cancer stem cells and sensitize them to therapy. Using tumor sphere lines and primary patient-derived glioma cultures we demonstrate that the Hh pathway inhibitor GANT61 (GANT) and the arsenic trioxide (ATO)-mediated Hh/Notch inhibition are capable to synergistically induce cell death in combination with the natural anticancer agent (−)-Gossypol (Gos). Only ATO in combination with Gos also strongly decreased stemness marker expression and prevented sphere formation and recovery. These synergistic effects were associated with distinct proteomic changes indicating diminished DNA repair and markedly reduced stemness. Finally, using an organotypic brain slice transplantation model, we show that combined ATO/Gos treatment elicits strong growth inhibition or even complete elimination of tumors. Collectively, our data show for the first time that ATO and Gos, two drugs that can be used in the clinic, represent a promising targeted therapy approach for the synergistic elimination of glioma stem-like cells.

Glioblastoma (GBM) still presents as one of the most aggressive tumours in the brain, which despite enormous research efforts, remains incurable today. As many theories evolve around the persistent recurrence of this malignancy, the assumption of a small population of cells with a stem-like phenotype remains a key driver of its infiltrative nature. In this article, we research Chordin-like 1 (CHRDL1), a secreted protein, as a potential key regulator of the glioma stem-like cell (GSC) phenotype. It has been shown that CHRDL1 antagonizes the function of bone morphogenic protein 4 (BMP4), which induces GSC differentiation and, hence, reduces tumorigenicity. We, therefore, employed two previously described GSCs spheroid cultures and depleted them of CHRDL1 using the stable transduction of a CHRDL1-targeting shRNA. We show with in vitro cell-based assays (MTT, limiting dilution, and sphere formation assays), Western blots, irradiation procedures, and quantitative real-time PCR that the depletion of the secreted BMP4 antagonist CHRDL1 prominently decreases functional and molecular stemness traits resulting in enhanced radiation sensitivity. As a result, we postulate CHRDL1 as an enforcer of stemness in GSCs and find additional evidence that high CHRDL1 expression might also serve as a marker protein to determine BMP4 susceptibility.

Introduction: Capsular contracture most often leads to implant revision surgery for aesthetic or reconstructive purposes. However, little is known about which operation is chosen when revision surgery has to be performed. We performed analysis of revision indications and performed revision surgery considering implant removal or replacement and additional surgical procedures. To our knowledge, this study presents the largest German single-center analysis regarding implant revision surgery after the onset of complications. Methods: Retrospective 10-year data analysis of a single-center population undergoing breast implant revision surgery. Results: Capsular contracture was the most frequent finding before reoperation, both removal and replacement (p < 0.05). It was linked to longer duration of in situ implant placement (p < 0.05) and more frequently in reconstructive patients (p < 0.05). Implant replacement was performed more often before definite implant removal for reconstructive patients (p < 0.05). Mean duration of in situ implant placement before definite removal was lower for reconstructive patients (p = 0.005). Overall reconstructive patients were older than aesthetic patients (p < 0.05). After implant removal, 61.7% of aesthetic patients chose to undergo mastopexy, 54.7% of reconstructive patients opted for autologous breast reconstruction, and 25.4% did not choose an additional surgical procedure after implant removal. Conclusion: Significant differences are observed for reconstructive and aesthetic patients regarding indication leading to revision surgery, time of revision surgery, and the type of performed revision surgery itself. After implant removal, more than 60% of aesthetic patients undergo mastopexy, more than half of reconstructive patients choose autologous breast reconstruction, and over a quarter of patients choose no additional surgical procedures.

(1) Background: Protruding ears are the most common auricular malformation affecting approximately 5% of the population. One common factor leading to auricular protrusion is a deficiency or total absence of the antihelix. A technique first described by Gottfried Lemperle in 2003 attempts cartilage thinning, folding, and fixation by non-absorbable mattress sutures after ventral skin incision along the ventral helical rim. (2) Methods: Retrospective analysis of patient records was performed for otoplasties according to this technique, performed between 1985 and 2014 at Agaplesion Markus Hospital in Frankfurt, Germany. All recorded complications were examined. (3) Results: A total of 912 single otoplasties were performed according to this technique from 1985 to 2014. Overall complications included 26% minor complications not requiring further surgery and 11% major complications leading to revision surgery. Within those requiring revision surgery, the most common reason was recurrence of auricular protrusion (5%), followed by suture granulomas (5%) and hematomas (2%). (4) Conclusions: Lemperle’s otoplasty technique addresses the open thinning and shaping of the antihelix through a ventral incision along the helix to prevent irregularities and possible ridges. Results show a low complication rate comparable to data found in published studies. This technique is easy to perform, safe, and avoids often seen contour irregularities of the antihelix compared to techniques with a posterior approach.

Zusammenfassung: Hintergrund Die Mastektomie ist essenzieller Bestandteil der geschlechtsangleichenden Operationen in der Gruppe Frau-zu-Mann(FM)-transidenter Patienten. Einschlägige Studien zeigen eine hohe Patientenzufriedenheit in dieser Kohorte, allerdings etablierte sich bisher kein standardisiertes Verfahren zur Evaluation der Effektivität. Methoden Anhand des etablierten Breast-Q-Fragebogens entwickelten wir eine modifizierte Version unter Berücksichtigung spezifischer Fragestellungen hinsichtlich FM-transidenter Patienten. Demnach erfolgte die Anpassung aller Fragen, welche gezielt die Physiologie von Cis-Frauen adressieren. Im Sinne eines „One-Group Post-Test Only“-Designs kontaktierten wir Patienten nach stattgehabter Mastektomie im Zeitraum von 1991 bis 2017 und evaluierten die Ergebnisse des Fragebogens von insgesamt 28 Patienten. Letzterer beinhaltet 57 Fragen hinsichtlich der grundlegenden Zufriedenheit mit der Brustregion, ebenso wie spezifische Fragen zur Zufriedenheit mit dem Mamillen-Areola-Komplex und hinterfragt Themen wie Erwartungen, Selbstbewusstsein, Sexualleben und Bedauern nach erfolgter Mastektomie. Ergebnisse Insgesamt zeigte sich ein hohes Maß an Patientenzufriedenheit nach stattgehabter Mastektomie. Alle befragten Patienten würden den Eingriff wiederholen und nur wenige äußerten Bedauern. Konklusion Die Mastektomie spielt eine entscheidende Rolle hinsichtlich geschlechtsangleichender Eingriffe bei Trans-Männern und zeigt eine hohe postoperative Zufriedenheit als Ausdruck einer Lebensqualitätsverbesserung.

Received: 07 September 2021 Accepted: 27 September 2021 Publication Date: 07 December 2021 (online) © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany