Soft Tissue Sarcomas of the Arm – Oncosurgical and Reconstructive Principles within a Multimodal, Interdisciplinary Setting

Soft tissue sarcomas of the upper extremity represent a severe threat for the patient and a difficult task for the treatment team. Due to the complex anatomy of the arm, most sarcomas involve valuable functional structures. Nonetheless, a large portion of the patients can be treated in a limb-sparing manner, and surgery is the mainstay of local tumor control. This review gives an overview of the disease entities and their epidemiology, on necessary patient work-up, staging, and imaging modalities, as well as the importance of interdisciplinary decision-making. The surgical therapies and principles of tumor excision are outlined, as well as reconstructive options. Furthermore, adjuvant treatments are discussed with a special focus on the various application techniques for radiation therapy. In spite of established treatment algorithms, each case is an individual challenge and individually tailored therapy is required. This aspect is illustrated by presenting three comprehensive cases demonstrating useful strategies. A summary of the relevant literature is given

Evidence for Gender-Specific Transcriptional Profiles of Nigral Dopamine Neurons in Parkinson Disease

Epidemiological data suggest that the male gender is one of the risks factors for the development of Parkinson Disease (PD). Also, differences in the clinical manifestation and the course of PD have been observed between males and females. However, little is known about the molecular aspects underlying gender-specificity in PD. To address this issue, we determined the gene expression profiles of male and female dopamine (DA) neurons in sporadic PD.We analyzed Affymetrix-based microarrays on laser microdissected DA neurons from postmortem brains of sporadic PD patients and age-matched controls across genders. Pathway enrichment demonstrated that major cellular pathways involved in PD pathogenesis showed different patterns of deregulation between males and females with more prominent downregulation of genes related to oxidative phosphorylation, apoptosis, synaptic transmission and transmission of nerve impulse in the male population. In addition, we found upregulation of gene products for metabolic processes and mitochondrial energy consumption in the age-matched male control neurons. On the single cell level, selected data validation using quantitative Real-Time (qRT)-PCR was consistent with microarray raw data and supported some of the observations from data analysis.On the molecular level, our results provide evidence that the expression profiles of aged normal and PD midbrain DA neurons are gender-specific. The observed differences in the expression profiles suggest a disease bias of the male gender, which could be in concordance with clinical observations that the male gender represents a risk factor for sporadic PD. Validation of gene expression by qRT-PCR supported the microarray results, but also pointed to several caveats involved in data interpretation

Repeated chest wall reconstruction after resection of a sternal chondroid chordoma with long-term postoperative infection of the reconstructive material

We present the case of a 23-year-old man with a chondroid chordoma of the sternum. The patient underwent chest wall resection, followed by stabilization using a sandwich graft of Prolene mesh and methylmethacrylate, covered with bilateral pedicled musculus pectoralis flaps. After adjuvant radiotherapy and 2 years of follow-up, the patient developed a graft-associated infection. We removed the allogeneic material and the encapsulated abscess, and the wound was conditioned through negative wound pressure therapy. This time, wound closure and chest wall stabilization were achieved with a Prolene mesh covered by a free anterolateral thigh flap. This case demonstrates the importance of carefully considering the material for chest wall stabilization and establishing multidisciplinary cooperation

Evaluation of a Novel Thiol–Norbornene-Functionalized Gelatin Hydrogel for Bioprinting of Mesenchymal Stem Cells

Introduction: Three-dimensional bioprinting can be considered as an advancement of the classical tissue engineering concept. For bioprinting, cells have to be dispersed in hydrogels. Recently, a novel semi-synthetic thiolene hydrogel system based on norbornene-functionalized gelatin (GelNB) and thiolated gelatin (GelS) was described that resulted in the photoclick hydrogel GelNB/GelS. In this study, we evaluated the printability and biocompatibility of this hydrogel system towards adipose-tissue-derived mesenchymal stem cells (ASCs). Methods: GelNB/GelS was synthesized with three different crosslinking densities (low, medium and high), resulting in different mechanical properties with moduli of elasticity between 206 Pa and 1383 Pa. These hydrogels were tested for their biocompatibility towards ASCs in terms of their viability, proliferation and differentiation. The extrusion-based bioprinting of ASCs in GelNB/GelS-high was performed to manufacture three-dimensional cubic constructs. Results: All three hydrogels supported the viability, proliferation and chondrogenic differentiation of ASCs to a similar extent. The adipogenic differentiation of ASCs was better supported by the softer hydrogel (GelNB/GelS-low), whereas the osteogenic differentiation was more pronounced in the harder hydrogel (GelNB/GelS-high), indicating that the differentiation fate of ASCs can be influenced via the adaption of the mechanical properties of the GelNB/GelS system. After the ex vivo chondrogenic differentiation and subcutaneous implantation of the bioprinted construct into immunocompromised mice, the production of negatively charged sulfated proteoglycans could be observed with only minimal inflammatory signs in the implanted material. Conclusions: Our results indicate that the GelNB/GelS hydrogels are very well suited for the bioprinting of ASCs and may represent attractive hydrogels for subsequent in vivo tissue engineering applications

Molekulare Mechanismen der Interaktion zwischen Osteoblasten und Endothelzellen und deren Bedeutung für die Gewebezüchtung des Knochens

Hintergrund. Das führende Problem in der Knochenersatzforschung ist die Vaskularisation der eingesetzten Konstrukte, und das gemeinsame Ziel unserer Arbeiten ist es, molekulare Faktoren mit sowohl proangiogenetischer als auch proosteogener Wirkung zu identifizieren. Die Kokultivierung von Osteoblasten (OBs) und Endothelzellen (ECs) wirkt sich osteoinduktiv und pro-proliferativ auf die Osteoblasten, ebenfalls werden die Proliferation der Endothelzellen und die Ausbildung von Gefäßen angeregt.Material und Methoden. Die Veränderungen im Transkriptom und Proteom der ECs und der OBs wurden mittels mRNA Microarrays und mittels Massenspektrometrie untersucht. Die Ergebnisse wurden durch rt-qPCR und durch ELISA verifiziert. Um molekulare Mechanismen der Interaktion zwischen OBs und ECs zu untersuchen wurden mRNA-bindenden Proteine per Biotin-Pulldown Experimente und die microRNAs per miRNA Microarrays verwendet. Ergebnisse. Die Transkriptom- und Proteomanalysen ergaben wiederholt, dass die Kokultivierung stets zu einer Hochregulation der Komponenten der Extrazellulärmatrix führt. Der Biotin-Pulldown Versuch ergab, dass die Stabilität der osteoblastären Alkalischen Phosphatase durch Bindung an Vimentin, ein Intermediärfilament, erhöht wird. Die miRNA Versuche zeigten die Bedeutung der angiogenen miRNA-126 in der Biologie der Osteoblasten. Diskussion. Die Ergebnisse belegen wiederholt die Bedeutung der Extrazellulärmatrix in der Interaktion der ECs und OBs. Diese Beobachtungen haben Bedeutung für die Herstellung der Knochenersatzkonstrukte. Insbesondere die Herstellung per 3D Biodruck ermöglicht heute die gezielte Besiedlung der Konstrukte mit Komponenten der Extrazellulärmatrix, was zu einer verbesserten angio- und osteogenen Leistung des Konstruktes in-vivo führen kann