Utilization of a genetically modified muscle flap for local BMP-2 production and its effects on bone healing: a histomorphometric and radiological study in a rat model

Aim of the study We developed an experimental rat model to explore the possibility of enhancing the healing of critical-size bone defects. The aim of this study was to demonstrate the feasibility of this concept by achieving high local BMP-2 expression via a transduced muscle flap that would facilitate bony union while minimizing systemic sequelae. Methods The transduction potential of the adenoviral vector encoding for BMP-2 was tested in different cell lines in vitro. In vivo experiments consisted of harvesting a pedicled quadriceps femoris muscle flap with subsequent creation of a critical-size defect in the left femur in Sprague-Dawley rats. Next, the pedicled muscle flap was perfused with high titers of Ad.BMP-2 and Ad.GFP virus, respectively. Twelve animals were divided into three groups comparing the effects of Ad.BMP-2 transduction to Ad.GFP and placebo. Bone healing was monitored radiologically with subsequent histological analysis post-mortem. Results The feasibility of this concept was demonstrated by successful transduction in vitro and in vivo as evidenced by a marked increase of BMP-2 expression. The three examined groups only showed minor difference regarding bone regeneration; however, one complete bridging of the defect was observed in the Ad.BMP-2 group. No evidence of systemic viral contamination was noted. Conclusions A marked increase of local BMP-2 expression (without untoward systemic sequelae) was detected. However, bone healing was not found to be significantly enhanced, possibly due to the small sample size of the study

Combination therapy with Olaratumab/doxorubicin in advanced or metastatic soft tissue sarcoma -a single-Centre experience

BACKGROUND: The antibody targeting platelet-derived growth factor receptor alpha (PDGFRA), olaratumab, was approved in 2016 for metastatic soft tissue sarcoma (STS) in combination with doxorubicin based on promising results of a phase Ib/II trial by the Food and Drug Administration (FDA). However, recently the phase III ANNOUNCE trial could not confirm the additional value of olaratumab in this context. METHODS: Here, in a retrospective analysis we share our single-centre experience with olaratumab/doxorubicin in STS by including n = 32 patients treated with olaratumab/doxorubicin between 2016 and 2019. RESULTS: Median progression-free survival (PFS) in the overall cohort was 3.1 months (range 0.6-16.2). A response [complete remission (CR), partial remission (PR) or stable disease (SD)] was seen in n = 11 (34%) cases, whereas n = 21 (66%) patients showed progressive disease (PD). In n = 9 patients surgery was performed subsequently in an individual therapeutic approach. Out of n = 5 patients receiving additional regional hyperthermia, n = 3 achieved PR or SD. CONCLUSIONS: This single-centre experience does also not support the promising phase Ib/II results for olaratumab/doxorubicin in STS. However, our findings do not preclude that olaratumab combination therapy could be valuable in a neoadjuvant setting. This warrants further exploration also taking into account the heterogeneous nature of STS

Comorbidities rather than older age define outcome in adult patients with tumors of the Ewing sarcoma family

BACKGROUND: Ewing family of tumors (EFT) is rarely diagnosed in patients (pts) over the age of 18 years (years), and data on the clinical course and the outcome of adult EFT pts is sparse. METHODS: In this retrospective analysis, we summarize our experience with adult EFT pts. From 2002 to 2020, we identified 71 pts of whom 58 were evaluable for the final analysis. RESULTS: Median age was 31 years (18-90 years). Pts presented with skeletal (n = 26), and extra-skeletal primary disease (n =32). Tumor size was ≥8 cm in 20 pts and 19 pts were metastasized at first diagnosis. Between the age groups (≤25 vs. 26-40 vs. ≥41 years) we observed differences of Charlson comorbidity index (CCI), tumor origin, as well as type and number of therapy cycles. Overall, median overall survival (OS) was 79 months (95% confidence interval, CI; 28.5-131.4 months), and median progression-free survival (PFS) 34 months (95% CI; 21.4-45.8 months). We observed a poorer outcome (OS, PFS) in older pts. This could be in part due to differences in treatment intensity and the CCI (<3 vs. ≥3; hazard ratio, HR 0.334, 95% CI 0.15-0.72, p = 0.006). In addition, tumor stage had a significant impact on PFS (localized vs. metastasized stage: HR 0.403, 95% CI 0.18-0.87, p = 0.021). CONCLUSIONS: Our data confirms the feasibility of intensive treatment regimens in adult EFT pts. While in our cohort outcome was influenced by age, due to differences in treatment intensity, CCI, and tumor stage, larger studies are warranted to further explore optimized treatment protocols in adult EFT pts

Impact of a specialised palliative care intervention in patients with advanced soft tissue sarcoma - a single-centre retrospective analysis

BACKGROUND: Soft tissue sarcomas (STS) account for less than 1% of all malignancies. Approximately 50% of the patients develop metastases with limited survival in the course of their disease. For those patients, palliative treatment aiming at symptom relief and improvement of quality of life is most important. However, data on symptom burden and palliative intervention are limited in STS patients. AIM: Our study evaluates the effectiveness of a palliative care intervention on symptom relief and quality of life in STS patients. DESIGN/SETTING: We retrospectively analysed 53 inpatient visits of 34 patients with advanced STS, admitted to our palliative care unit between 2012 and 2018. Symptom burden was measured with a standardised base assessment questionnaire at admission and discharge. RESULTS: Median disease duration before admission was 24 months, 85% of patients had metastases. The predominant indication for admission was pain, weakness and fatigue. Palliative care intervention led to a significant reduction of pain: median NRS for acute pain was reduced from 3 to 1 (p < 0.001), pain within the last 24 h from 5 to 2 (p < 0.001) and of the median MIDOS symptom score: 18 to 13 (p < 0.001). Also, the median stress level, according to the distress thermometer, was reduced significantly: 7.5 to 5 (p = 0.027). CONCLUSIONS: Our data underline that specialised palliative care intervention leads to significant symptom relief in patients with advanced STS. Further efforts should aim for an early integration of palliative care in these patients focusing primarily on the identification of subjects at high risk for severe symptomatic disease

State of the art - Status quo of plastic and reconstructive surgery from the view point of hand surgery

Modern plastic-reconstructive surgery, much like hand surgery, represents a young and fast-developing surgical discipline. The principles of plastic surgery originate in the developmental stages of surgery and have considerable influence on hand surgery. Microsurgery, free or pedicled transfer of tissue, peripheral nerve surgery, plexus surgery, tendon transfers, arthroplasty, vascularized bone transfers, or toe to thumb transplants, are all performed while considering plastic surgical principles and represent just a part of plastic surgical techniques which are daily applied in hand-surgical routine. They emphasize the intimate relationship and the mutual influence between the two disciplines. The future of plastic surgery is likely to include composite tissue allotransplantation, flap prefabrication, virtual surgical planning, application of growth factors to influence bone growth, fracture healing, angiogenesis, tendon healing or wound healing. Furthermore, the field of tissue engineering is likely to introduce novel materials, such as nerve conduits. All of the above may have direct influence on hand surgery and, therefore, the future of plastic and hand surgery is at least as intricately intertwined as was their past. They will remain related through the characteristics that led to their development: innovation, creativity, diversity and the search for individualized solutions.Die moderne plastisch-rekonstruktive Chirurgie stellt, wie die Handchirurgie, eine junge, sich rasch entwickelnde, chirurgische Disziplin dar. Die Prinzipien der modernen plastischen Chirurgie haben ihren Ursprung in den Entwicklungsstufen der Chirurgie und seit je her ihren Einfluss auf die Entwicklung der Handchirurgie. Die Mikrochirurgie, der freie oder gestielte Gewebetransfer, die peripheren Nervenchirurgie, die Plexuschirurgie, die motorischen Ersatzplastiken, die Gelenkplastiken unter Berücksichtigung plastisch chirurgischer Prinzipien, die vaskularisierten Knochentransplantate und der Zehentransfer als Daumen- oder Fingerersatz stellen nur eine Teilmenge der im handchirurgischen Alltag zur Anwendung kommenden plastisch chirurgischen Verfahren dar. Sie unterstreichen die enge Verwandtschaft und den intensiven gegenseitigen Einfluss. Die Zukunftsfelder der Plastischen Chirurgie beinhalten neben dem Gebiet der Allotransplantation gemischter Gewebseinheiten (CTA), die Lappen-Präfabrikation zur Individualisierung der operativen Lösungen, die Funktion und Anwendung von Wachstumsfaktoren zur Beeinflussung von Knochenwachstum, Frakturkonsolidierung, Angiogenese, Sehnenheilung oder Wundheilung, sowie das Gebiet des Tissue Engineering, der Erschließung und Anwendung von Ersatzmaterialien, wie Nervenconduits und der virtuellen Operationsplanung.Nahezu alle diese Felder werden möglicherweise besondere Auswirkungen auf die Handchirurgie haben. Die Zukunft der Plastischen Chirurgie und Handchirurgie sind untrennbar mit einander verbunden. Sie können in den Eigenschaften, die zu ihrer Entstehung geführt haben, der Innovationsfähigkeit und Kreativität sowie der Vielfältigkeit und Individualität ihrer Problemlösungen gefunden werden

Standortbestimmung – Status quo der plastisch-rekonstruktiven Chirurgie aus der Sicht der Handchirurgie

Modern plastic-reconstructive surgery, much like hand surgery, repres a young and fast-developing surgical discipline. The principles of plastic surgery originate in the developmental stages of surgery and have considerable influence on hand surgery. Microsurgery, free or pedicled transfer of tissue, peripheral nerve surgery, plexus surgery, tendon transfers, arthroplasty, vascularized bone transfers, or toe to thumb transplants, are all performed while considering plastic surgical principles and represent just a part of plastic surgical techniques which are daily applied in hand-surgical routine. They emphasize the intimate relationship and the mutual influence between the two disciplines. The future of plastic surgery is likely to include composite tissue allotransplantation, flap prefabrication, virtual surgical planning, application of growth factors to influence bone growth, fracture healing, angiogenesis, tendon healing or wound healing. Furthermore, the field of tissue engineering is likely to introduce novel materials, such as nerve conduits. All of the above may have direct influence on hand surgery and, therefore, the future of plastic and hand surgery is at least as intricately intertwined as was their past. They will remain related through the characteristics that led to their development: innovation, creativity, diversity and the search for individualized solutions