Impact of Single Center Treatment on Ewing Sarcoma 10-Year Long Term Survival Rates.

PURPOSE OF THE STUDY Ewing sarcomas (ES) are the second most common solid malignant bone tumors in both, children and adolescents, and systemic chemotherapy protocols were established during the last 3 decades which proved to be a successful approach in addition to local treatment. The purpose of the present study is (i) to provide survival rates and prognostic factors for patients with ES which received treatment in a single center and (ii) to compare data with results of multicenter studies. MATERIALS AND METHODS Patients (n = 38) were treated by the same surgeon whereas surgery was combined with radiotherapy in 55.3% of the patients (n = 21). Median age at diagnosis was 17.5 years (4.7-60) and the median follow-up time for all patients was 8.2 years (9.8 years for survivors, 3.2 years for non-survivors). RESULTS The survival rate for metastasis free sarcoma decreases from 90.5% to 50% for patients diagnosed with disseminated disease stage. Patients with a good response to chemotherapy survived in 83.3% of the cases. In addition, a higher OS was found for patients younger than 15 years (82.4%) when compared to patients older than 15 years (73.3%). In contrast, multicenter studies reported lower survival rates for metastasis free (~60%) and metastasis stages (< 40%). DISCUSSION The survival rates in the present single center study are higher than the rates reported from multi-center studies although same chemotherapy protocols were used and no substantially difference are apparent for patient population. CONCLUSIONS Based on the present data we re-emphasize that patients with Ewing sarcoma receive appropriate treatment in a large and qualified center particularly considering the survival rates. In addition, our data underline that a close collaboration between the oncological team and the experienced surgeon is crucial for patient's care. Key words: Ewing sarcoma, survival rate, single center, prognostic factors, chemotherapy, surgery, multi center, single center.

High-Resolution Ultrasound Including Contrast-Enhanced Ultrasound (CEUS) for the Detection of Gas Formation during Aspergillus Fumigatus Infection in Mice.

PURPOSE: A. fumigatus infections represent a major threat for patients with a suppressed immune system. Early diagnosis is of importance for a favorable outcome but appears to be difficult due to limited diagnostic procedures. Here we investigated the sensitivity of high-resolution ultrasound (HRU) for the detection of A. fumigatus infection in the liver. MATERIALS AND METHODS: BALB/c mice were intravenously infected with A. fumigatus and monitored by HRU, Doppler sonography (CCDS), contrast-enhanced ultrasound (CEUS), and real-time strain color-coded elastography (CCE) using a multi-frequency probe (6 - 15 MHz). Contrast media bolus injection of sulfur-hexafluoride micro-bubbles was applied and digital cine-loops from the arterial phase, as well as the portal venous phase up to the late phase of the whole liver were analyzed. All data were correlated to the histopathological findings. RESULTS: Using HRU and CEUS, a sonic shadow was detected in all infected animals. All Aspergillus-infected nodes from 3 - 6 mm in the liver showed a shadow with rim enhancement and no intranodal enhancement when using CEUS. A. fumigatus infection was confirmed by CFU assessment and histopathological analysis. Granulomas were not associated with shadowing on B-mode. In contrast, granulomas with a diameter above 5 mm and a higher stiffness in CCE generated particularly an arterial rim enhancement and portal venous washout without contrast media uptake in the late phase. In addition, CEUS was able to define dynamic capillary microvascularization of infected liver areas. CONCLUSION: Liver lesions associated with A. fumigatus infection can be detected in mice when combined with CEUS and CCE in vivo.

Sonoelastography can be used to monitor the restoration of Achilles tendon elasticity after injury.

PURPOSE: The aim of the current study was to evaluate an ultrasound approach for depicting elastic recovery after stem cell application on injured Achilles tendons. MATERIALS AND METHODS: A rabbit Achilles tendon injury model was used and randomized hind limbs received an extracellular matrix either with autologous mesenchymal stem cells (group 2, n = 6) or without (group 3, n = 6). The cells were harvested from the rabbits' nuchal fat body. Untreated Achilles tendons (group 1, n = 6) served as controls. Specimens were harvested after 8 weeks and analyzed longitudinally for elasticity using a high resolution 6-15 MHz matrix linear probe. For each tendon, real-time color-coded sonoelastography sequences were recorded for 20 seconds and 10 color histogram frames were obtained. Defined regions of interest (ROIs) were placed on the injury (n = 3) and on the adjacent uninjured tendon tissue (n = 3). In total, 180 measurements were obtained for semi-quantitative analysis. RESULTS: Repeated measures ANOVA demonstrated a higher elasticity for the stem cell-seeded matrix (group 2) in comparison to the unseeded matrix (group 3) (p < 0.001). No significant difference was found between the injured tendon tissue treated with stem cell-seeded matrix (group 2) and the uninjured Achilles tendons (group 1) (p > 0.05). Moreover, no differences were found between the measurements at different points in time (p > 0.05). CONCLUSION: Our results indicate that autologous mesenchymal stem cell application successfully restores the mechanical properties of injured tendon tissue. Furthermore, sonoelastography makes it possible to monitor the elasticity of injured Achilles tendons.

Contrast enhanced ultrasound (CEUS) and time intensity curve (TIC) analysis in compartment syndrome: first results.

OBJECTIVE: Purpose of this study was to monitor changes of microcirculation in acute compartment syndrome using contrast enhanced ultrasound (CEUS) and to assess the modified perfusion with a special quantification software. METHODS: 8 patients with trauma of the lower limb or the upper extremity were enrolled after acute compartment syndrome was diagnosed clinically and by intracompartmental pressure measurement. The qualitative analysis of the corresponding compartment was assessed using B-scan mode and CEUS simultaneously. CEUS was performed using a multifrequence probe (6-9 MHz, LOGIQ E9 GE) after a i.v. bolus injection of 2 × 2.4 ml contrast agent (SonoVue(®), Bracco, Italy). Digital raw data were stored as cine loops up to 2 minutes. Retrospectively semiquantitative perfusion analysis was performed using time intensity curve analysis and the quantification software QONTRAST(®). RESULTS: 6 out of 8 patients had to be operated due to clinical symptoms and to a pressure perfusion gradient lower than 30 mm Hg. 2 out of 8 were treated conservatively. In all patients haematomas were seen in B-scan mode. No necrosis could be detected. In the TIC analysis low levels of time to peak (20.0 ± 12.1) and area under the curve (118.4 ± 87.8) were observed in acute compartment syndrome. Similarly results have been obtained using the perfusions parameter PEAK (11.1 ± 5.7), time to PEAK (14.7 ± 9.7), regional blood volume (257.1 ± 192.6), and regional blood flow (12.1 ± 6.5) in QONTRAST(®) perfusion software. CONCLUSION: CEUS may be capable of differing between acute compartment syndrome and imminent compartment syndrome.

Evaluation of hyperbaric oxygen therapy for free flaps using planar optical oxygen sensors. Preliminary results.

OBJECTIVES: This study was designed to determine if a) hyperbaric oxygen increases the tissue oxygenation of free flaps and b) verification of this effect is possible by using a recently validated and innovative method for two-dimensional pO2 measurement (Luminescence lifetime imaging = LLI). METHODS: Six patients with a free parascapular flap transplanted to the lower limb received hyperbaric oxygen (HBOT) therapy. The HBOT regimen consisted of treatment over 90 minutes with 100% O2 (FiO2 1.0) at 240 kPa (Marx-Schema). The transcutaneous oxygen partial pressure (ptcO2) was measured over the entire flap with the use of luminescence lifetime imaging (LLI) before and 30, 60, 120 minutes after treatment. The LLI is based on the oxygen dependent quenching of phosphorescence of the indicator dye platinum (II)-octaethyl-porphyrin implemented in a polystyrene sensor foil. RESULTS: In all six free flaps we could find a significant increase of tissue oxygen over the entire flap in form of increased R-values as well as subsequently calculated absolute ptcO2 values over a period of 120 min after hyperbaric therapy. The ptcO2 values increased significantly from 42.59 ± 1.11 Torr before to 81.14 ± 5.95 Torr after hyperbaric treatment (p < 0.001). Even after 2 hours the ptcO2 values were significantly higher (83.45 ± 13.80 Torr) compared with values prior to HBOT (p < 0.006). CONCLUSIONS: The findings of this study demonstrated an increase of oxygen supply over the entire flap after hyperbaric oxygen therapy.

TTP (time to PEAK) and RBV (regional blood volume) as valuable parameters to detect early flap failure.

BACKGROUND: Free flap transplantation is used more and more frequently in order to cover extensive wound defects. The basic prerequisite for successful flap salvage after flap failure is a short time interval from failure until revision. For this reason many different flap monitoring systems have been tested over the last years. OBJECTIVE: The aim of the experiment was to detect critical capillary perfusion using contrast enhanced ultrasound. Quantitative analysis should be performed by a special perfusion software (QONTRAST; Bracco, Italy) appraising digital raw data of contrast enhanced ultrasound (CEUS). Additionally diverse risk factors for free flap transplantation were determined. METHODS: Thirty-one patients were examined after free flap transplantation during the first 72 hours after operation. CEUS was performed with a linear transducer (6-9 MHz, LOGIQ E9/GE) and a bolus injection of 2.4 ml of contrast agent (SonoVue, Bracco, Italy). Operation and examination were performed by either an experienced plastic surgeon or an experienced ultrasound examiner. Depth dependent capillary perfusion was analysed and quantitative perfusions analysis was performed using the perfusions software QONTRAST (Bracco, Italy). Eleven revisions had to be performed: 7 due to haematoma and 4 due to superficial necrosis. RESULTS: Reduced capillary perfusion was seen in all 11 complications using CEUS. Significant difference comparing the no complication and the complication group was observed using TTP (time to PEAK) and RBV (regional blood volume) quantitative analysis. Mean RBV was 922.1 ± 150.9 in the no complication and 303.0 ± 53.9 in the complication group (p = 0.001). Mean TTP was 37.6 ± 3.8 in the no complication and 21.3 ± 3.4 in the complication group (p = 0.006). Tendency to higher complication rate was seen in older male patients with vascular or malignant primary disease. CONCLUSION: In this clinical trial, capillary perfusion after free flap transplantation as well as detection of vascular complications was demonstrated using CEUS. Quantitative perfusions analysis could be performed and flap viability could be assessed easily.

Assessment of bone microcirculation by contrast-enhanced ultrasound (CEUS) and [18F]-positron emission tomography/computed tomography in free osseous and osseocutaneus flaps for mandibular reconstruction: preliminary results.

PURPOSE: Postsurgical evaluation of bone microcirculation in osseous and osseocutaneus free flaps by contrast enhanced ultrasound (CEUS) with time intensity curve (TIC) analysis and [18F]-positron emission tomography/computed tomography (Fluoride-PET/CT). PATIENTS AND METHODS: 10 patients with osseous or osseocutaneus microvascular flaps were evaluated with CEUS. Ultrasound was carried out by an experienced examiner with a high resolution linear probe (6-9 MHz, LOGIQ E9, GE) after intravenous bolus injection of 2.4 ml SonoVue® (BRACCO, Germany). Time intensity curves (TIC) in selected regions of interest (ROI) were analyzed and compared with the evaluation of [18F]-positron emission tomography/computed tomography and the clinical course for at least 2 month. RESULTS: 9/10 patients showed evidence for soft tissue and osseous microcirculation of the transplants in CEUS correlating with the clinical course. The soft tissue parts of the transplant showed a mean value of 84% (range 51-98%) and the bone parts a mean value of 39% (range 11-75%) for the Area under the curve (AuC) compared with the AuC for the anastomotic vessel region. Mean values for time to peak (TTP) were 27,1 sec (range 8.7-52.0 sec) for the anastomotic vessels, 29.3 sec (range 7.9-62.0 sec) for the soft tissue of and 32.0 sec (range 7.4-69.0 sec) for the transplant bone. In 1/10 patients flap failure occurred, after denudation the bone was left as an avascular transplant. AuC showed a mean value of 0.5 % for the bone region compared with the vessel region. Fluoride-PET/CT assessed bone vitality in 7 patients as "good" in 1 patient as "uncertain" and in 1 patient as "poor". CEUS assessment was corresponding with Fluoride-PET/CT in 4 patients, clinical assessment in 6 patients. CONCLUSION: Fluoride-PET/CT is a valuable tool to make an indirect statement about the perfusion of the transplanted bone and was used as control in this study. CEUS is a new and promising method for the evaluation of microcirculation of buried free microvascular bone grafts and the osseous part of osseocutaneous flaps and may be used for a steady monitoring in the first postoperative days.