Zoledronic Acid Add-on Therapy for Standard-Risk Ewing Sarcoma Patients in the Ewing 2008R1 Trial.

PURPOSE: The phase III, open-label, prospective, multicenter, randomized Ewing 2008R1 trial (EudraCT2008-003658-13) was conducted in 12 countries to evaluate the effect of zoledronic acid (ZOL) maintenance therapy compared with no add-on regarding event-free survival (EFS, primary endpoint) and overall survival (OS) in standard-risk Ewing sarcoma (EWS). PATIENTS AND METHODS: Eligible patients had localized EWS with either good histologic response to induction chemotherapy and/or small tumors (<200 mL). Patients received six cycles of VIDE induction and eight cycles of VAI (male) or eight cycles of VAC (female) consolidation. ZOL treatment started parallel to the sixth consolidation cycle. Randomization was stratified by tumor site (pelvis/other). The two-sided adaptive inverse-normal four-stage design (planned sample size 448 patients, significance level 5%, power 80%) was changed after the first interim analysis using the Müller-Schäfer method. RESULTS: Between April 2010 and November 2018, 284 patients were randomized (142 ZOL/142 no add-on). With a median follow-up of 3.9 years, EFS was not significantly different between ZOL and no add-on group in the adaptive design (HR, 0.74; 95% CI, 0.43-1.28, P = 0.27, intention-to-treat). Three-year EFS rates were 84.0% (95% CI, 77.7%-90.8%) for ZOL vs. 81.7% (95% CI, 75.2%-88.8%) for no add-on. Results were similar in the per-protocol collective. OS was not different between groups. The 3-year OS was 92.8% (95% CI, 88.4%-97.5%) for ZOL and 94.6% (95% CI, 90.9%-98.6%) for no add-on. Noticeable more renal, neurologic, and gastrointestinal toxicities were observed for ZOL (P < 0.05). Severe renal toxicities occurred more often in the ZOL arm (P = 0.003). CONCLUSIONS: In patients with standard-risk localized EWS, there is no additional benefit from maintenance treatment with ZOL.

Interdisciplinarity in Diagnostics of Bone Lesions. / Interdisziplinarität in der Diagnosefindung häufiger Knochenläsionen im klinischen Alltag.

INTRODUCTION: Due to substantial advances in all medical disciplines, interdisciplinary cooperation is of major relevance in modern medicine. Given the rarity of benign and malignant bone tumours, diagnosis and therapy of these lesions is especially challenging. Focusing on typical cases, it is the aim of this article to illustrate the necessity of interdisciplinary cooperation. METHODS: The scope of this article is to highlight the particular significance of interdisciplinarity in the diagnosis of bone tumours. To this end, we illustrate the interdisciplinary approach in typical clinical cases. RESULTS AND DISCUSSION: The article demonstrates that a combined clinico-radiological approach is essential in the diagnosis of leave-me-alone lesions, and it underlines the essential role of an interdisciplinary correlation of clinical context, radiology and pathology in the interpretation of bone tumour biopsies. It documents the experience that all clinical aspects and diagnostic findings need to be synoptically integrated in a joint interdisciplinary tumour board to eventually find the correct diagnosis. CONCLUSION: It is generally accepted that the diagnosis of a bone tumour can often not be made by the pathologist alone but essentially requires interdisciplinary cooperation.

[Bone tumours-What's new in the 2020 WHO classification and beyond]. / Knochentumoren ­ Neues in und jenseits der WHO-Klassifikation 2020.

The recent WHO classification of Bone Tumours (2020) has introduced several changes. Conceptionally, small round cell sarcomas are now summarized in a distinct chapter, acknowledging their occurrence in both, bone and soft tissue. In the light of new molecular findings some diagnostic categories, such as fibrohistiocytic tumors, have been abandoned, and a few new entities have been added to the classification. Finally, systematic changes were made with regard to the terminology employed in the classification of chondrogenic tumours, and modifications have been made with respect to the biological potential of some lesions. This article summarizes the major changes made, underscoring the elementary role of an interdisciplinary approach in the diagnosis and management of bone lesions.

High-Dose Treosulfan and Melphalan as Consolidation Therapy Versus Standard Therapy for High-Risk (Metastatic) Ewing Sarcoma.

PURPOSE: Ewing 2008R3 was conducted in 12 countries and evaluated the effect of treosulfan and melphalan high-dose chemotherapy (TreoMel-HDT) followed by reinfusion of autologous hematopoietic stem cells on event-free survival (EFS) and overall survival in high-risk Ewing sarcoma (EWS). METHODS: Phase III, open-label, prospective, multicenter, randomized controlled clinical trial. Eligible patients had disseminated EWS with metastases to bone and/or other sites, excluding patients with only pulmonary metastases. Patients received six cycles of vincristine, ifosfamide, doxorubicin, and etoposide induction and eight cycles of vincristine, actinomycin D, and cyclophosphamide consolidation therapy. Patients were randomly assigned to receive additional TreoMel-HDT or no further treatment (control). The random assignment was stratified by number of bone metastases (1, 2-5, and > 5). The one-sided adaptive-inverse-normal-4-stage-design was changed after the first interim analysis via Müller-Schäfer method. RESULTS: Between 2009 and 2018, 109 patients were randomly assigned, and 55 received TreoMel-HDT. With a median follow-up of 3.3 years, there was no significant difference in EFS between TreoMel-HDT and control in the adaptive design (hazard ratio [HR] 0.85; 95% CI, 0.55 to 1.32, intention-to-treat). Three-year EFS was 20.9% (95% CI, 11.5 to 37.9) in TreoMel-HDT and 19.2% (95% CI, 10.8 to 34.4) in control patients. The results were similar in the per-protocol collective. Males treated with TreoMel-HDT had better EFS compared with controls: median 1.0 years (95% CI, 0.8 to 2.2) versus 0.6 years (95% CI, 0.5 to 0.9); P = .035; HR 0.52 (0.28 to 0.97). Patients age < 14 years benefited from TreoMel-HDT with a 3-years EFS of 39.3% (95% CI, 20.4 to 75.8%) versus 9% (95% CI, 2.4 to 34); P = .016; HR 0.40 (0.19 to 0.87). These effects were similar in the per-protocol collective. This observation is supported by comparable results from the nonrandomized trial EE99R3. CONCLUSION: In patients with very high-risk EWS, additional TreoMel-HDT was of no benefit for the entire cohort of patients. TreoMel-HDT may be of benefit for children age < 14 years.

Recurrent CTNNB1 mutations in craniofacial osteomas.

Osteoma is a benign bone forming tumor predominantly arising on the surface of craniofacial bones. While the vast majority of osteomas develops sporadically, a small subset of cases is associated with Gardner syndrome, a phenotypic variant of familial adenomatous polyposis caused by mutations in the APC gene resulting in aberrant activation of WNT/ß-catenin signaling. In a sequencing analysis on a cohort of sporadic, non-syndromal osteomas, we identified hotspot mutations in the CTNNB1 gene (encoding ß-catenin) in 22 of 36 cases (61.1%), harbouring allelic frequencies ranging from 0.04 to 0.53, with the known S45P variant representing the most frequent alteration. Based on NanoString multiplex expression profiling performed in a subset of cases, CTNNB1-mutated osteomas segregated in a defined "WNT-cluster", substantiating functionality of CTNNB1 mutations which are associated with ß-catenin stabilization. Our findings for the first time convincingly show that osteomas represent genetically-driven neoplasms and provide evidence that aberrant WNT/ß-catenin signaling plays a fundamental role in their pathogenesis, in line with the well-known function of WNT/ß-catenin in osteogenesis. Our study contributes to a better understanding of the molecular pathogenesis underlying osteoma development and establishes a helpful diagnostic molecular marker for morphologically challenging cases.

Ewing Sarcoma-Diagnosis, Treatment, Clinical Challenges and Future Perspectives.

Ewing sarcoma, a highly aggressive bone and soft-tissue cancer, is considered a prime example of the paradigms of a translocation-positive sarcoma: a genetically rather simple disease with a specific and neomorphic-potential therapeutic target, whose oncogenic role was irrefutably defined decades ago. This is a disease that by definition has micrometastatic disease at diagnosis and a dismal prognosis for patients with macrometastatic or recurrent disease. International collaborations have defined the current standard of care in prospective studies, delivering multiple cycles of systemic therapy combined with local treatment; both are associated with significant morbidity that may result in strong psychological and physical burden for survivors. Nevertheless, the combination of non-directed chemotherapeutics and ever-evolving local modalities nowadays achieve a realistic chance of cure for the majority of patients with Ewing sarcoma. In this review, we focus on the current standard of diagnosis and treatment while attempting to answer some of the most pressing questions in clinical practice. In addition, this review provides scientific answers to clinical phenomena and occasionally defines the resulting translational studies needed to overcome the hurdle of treatment-associated morbidities and, most importantly, non-survival.

Pain in survivors of Ewing sarcoma: Prevalence, associated factors and prediction of recurrence.

BACKGROUND: While the prognosis of patients with Ewing sarcoma (EwS) is improving, little is known about the frequency of pain and its risk factors in survivors of EwS. This study aims to analyse the prevalence and risk factors of pain and its predictive value for recurrence. PATIENTS AND METHODS: In patients with remission after treatment of EwS, frequency and characteristics of pain within the first 5 years of follow up were assessed retrospectively. RESULTS: Of 80 patients, 37 (46%) presented with at least one episode of pain. Chronic pain (>3 months) was observed in 10 patients (13%). Experience of at least one episode of pain was associated with prior combined local treatment (surgery and radiation compared to surgery alone; odds ratio [OR] 5.83, 95% confidence interval [CI] 1.43-34.9, P = .007). A total of 59 episodes of pain were observed, including 47 acute and 12 chronic episodes. Lower limb pain accounted for 46% (27/59) of all episodes of pain, and was associated with primary tumour of the pelvis or lower extremity (OR 4.29, 95% CI 1.18-18.21, P = .025), which represented 64% (51/80) of all EwS. The positive predictive value of pain for recurrence was only 12%. CONCLUSION: Pain is a common problem in survivors of EwS, which mostly affects the lower extremity, and should be regularly assessed. Interventions to reduce pain may be particularly important in patients with combined local treatment with surgery and radiation, who seem to be at considerably increased risk for pain. Patients presenting with pain should be examined for recurrence.

[The importance of radiology in bone sarcoma diagnostics : Initial and advanced diagnostics]. / Stellenwert der Radiologie in der Diagnostik der Knochensarkome : Initiale und weiterführende Diagnostik.

BACKGROUND: Reliable diagnostic assessment of malignant bone lesions remains a challenge in all the medical disciplines involved. The high incidence of benign (mainly pediatric) bone lesions needs to be distinguished from the rare malignant counterparts. If clinical presentation and patient history are unable to exclude a malignant tumour, adequate imaging of the affected region is necessary. OBJECTIVES: This article focuses on giving implementable advice in dealing with problems and questions arising in the diagnostic process of treating patients with suspected or confirmed bone sarcoma. Also, follow-up recommendations from a radiological point of view are presented. METHODS: Review and discussion of relevant literature against personal experiences in the medical imaging of patients with bone sarcomas. RESULTS: Interpretation of projection radiographic images usually succeeds in assessing a bone tumour's dignity by evaluating periosteal reaction, the formation of a tumour matrix and consideration of the Lodwick classification. A current adaptation of the classic Lodwick classification incorporates diagnostic possibilities of more recent imaging techniques (magnetic resonance imaging (MRI), positron emission tomography (PET)) and is presented in this article. Plain radiographs are superseded by MRI as the primary imaging performed when depicting bone lesions with increasing frequency. The role of MRI in terms of primary diagnostics, staging, planning of biopsy tracts and tumour resections, evaluation of treatment response and follow-up are discussed. All diagnostic imaging techniques, including whole-body imaging methods, relevant in the diagnosis and therapy of bone sarcomas are presented in the sequence in which they appear during treatment. CONCLUSIONS: Radiological imaging and expertise are important pillars in diagnosis and treatment of bone sarcomas. A variety of complementing imaging techniques provide a treatment-relevant basis significant for all medical disciplines involved.

Anatomic shape variants of extremitas sternalis claviculae as collected from sternoclavicular thin-slice CT-studies of 2820 male borderline-adults.

Within medical age assessment practice, the indicator "medial clavicular ossification" constitutes crucial evidence capable of excluding age minority "beyond reasonable doubt" concerning age-disputed individuals doubtfully claiming children's rights during legal procedures. Yet, one of its characteristics affects the morphological variability including a fair amount of downright peculiar appearances. As a result, inexperienced examiners are tempted to classify actually not-assessable formations according to the two established developmental typologies of Schmeling et al. and Kellinghaus et al. being at the same time the most frequent systemic error of age-related clavicular taxation. Since a respective overview appears missing, the study extracts not-assessable shape variants of the medial collar bone from a large sample of 2820 male borderline-adults as seen from thin-slice, sternoclavicular computed tomography. The two already highlighted configurations "more than one, medial, secondary ossification centres" and "medial metaphyseal concavity" are found as the most commonly encountered features impeding reliable delineation of staging criteria. In accordance with previous literature, it is emphasized that "qualified" rating of extremitas sternalis claviculae within age assessment practice presupposes "knowledge about the diversity of [its] anatomic shape variants."

Activating mutations in the MAP-kinase pathway define non-ossifying fibroma of bone.

Non-ossifying fibroma (NOF), which occasionally results in pathologic fracture, is considered the most common benign and self-limiting lesion of the growing skeleton. By DNA sequencing we have identified hotspot KRAS, FGFR1 and NF1 mutations in 48 of 59 patients (81.4%) with NOF, at allele frequencies ranging from 0.04 to 0.61. Our findings define NOF as a genetically driven neoplasm caused in most cases by activated MAP-kinase signalling. Interestingly, this driving force either diminishes over time or at least is not sufficient to prevent autonomous regression and resolution. Beyond its contribution to a better understanding of the molecular pathogenesis of NOF, this study adds another benign lesion to the spectrum of KRAS- and MAP-kinase signalling-driven tumours. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Impact of the Interdisciplinary Tumor Board of the Cooperative Ewing Sarcoma Study Group on local therapy and overall survival of Ewing sarcoma patients after induction therapy.

BACKGROUND: The Interdisciplinary Tumor Board (ITB) of the Cooperative Ewing Sarcoma Study (CESS) Group was investigated to assess its impact on the overall survival (OAS) of Ewing sarcoma (EwS) patients. The ITB functions as a reference center for the international institutions participating in the clinical trials of the CESS group, but is also available internationally to patients who have not been treated within an appropriate clinical trial. The value of tumor boards in terms of benefit for the patients and the health care system in general is not well documented and is also the subject of controversial discussions. A review of the representative literature is included. METHODS: Data were analyzed from 481 patients who had been registered into the European Ewing Tumor Working Initiative of National Groups (EURO E.W.I.N.G.-99) clinical trial via the CESS data center between 2006 and 2009; this included 331 patients with localized disease and another 150 individuals with metastases at diagnosis. Median follow-up time was 3.2 years. RESULTS: Improved OAS was observed for patients with metastases who had received recommendations from the ITB compared with those who had not received recommendations. In patients with localized disease, a recommendation from the ITB had no influence on OAS. CONCLUSION: As a reference center for a rare disease, recommendations from our ITB impacted local therapy and led to higher OAS in patients with metastatic disease. To our knowledge, this is the first analysis that examines the value of a reference tumor board on a rare disease.

Forensic age assessment by 3.0T MRI of the knee: proposal of a new MRI classification of ossification stages.

PURPOSE: To explore the possibility of determining majority via a morphology-based examination of the epiphyseal-diaphyseal fusion by 3.0 T magnetic resonance imaging (MRI), a prospective cross-sectional study developing and applying a new stage classification was conducted. MATERIALS AND METHODS: 344 male and 350 female volunteers of German nationality between the ages of 12-24 years were scanned between May 2013 and June 2015. A 3.0 T MRI scanner was used, acquiring a T1-weighted (T1-w) turbo spin-echo sequence (TSE) and a T2-weighted (T2-w) TSE sequence with fat suppression by spectral pre-saturation with inversion recovery (SPIR). The gathered information was sifted and a five-stage classification was formulated as a hypothesis. The images were then assessed using this classification. The relevant statistics were defined, the intra- and interobserver agreements were determined, and the differences between the sexes were analysed. RESULTS: The application of the new classification made it possible to correctly assess majority in both sexes by the examination of the epiphyses of the knee joint. The intra- and interobserver agreement levels were very good (κ > 0.80). The Mann-Whitney-U Test implied significant sex-related differences for most stages. CONCLUSION: Applying the presented MRI classification, it is possible to determine the completion of the 18th year of life in either sex by 3.0 T MRI of the knee joint. KEY POINTS: • Based on prospective referential data a new MRI classification was formulated. • The setting allows assessment of the age of an individual's skeletal development. • The classification scheme allows the reliable determination of majority in both sexes. • The staging shows a high reproducibility for instructed and trained professional personnel. • The proposed classification is likely to be adaptable to other long bone epiphyses.

Recurrence of Ewing sarcoma: Is detection by imaging follow-up protocol associated with survival advantage?

BACKGROUND: The Cooperative Ewing Sarcoma Study and the Late Effects Surveillance System of the Society for Paediatric Oncology and Haematology recommend a structured follow-up imaging protocol (FUIP) for patients with Ewing sarcoma (EwS) with decreasing frequency of imaging over the first 5 years. The present study aims to assess the effectiveness of the FUIP for EwS patients regarding survival after relapse. PATIENTS AND METHODS: A retrospective multicenter analysis on 160 eligible patients with EwS recurrence was performed. Potential survival differences following recurrence diagnosis between patients with protocol-detected and symptomatic relapse were investigated using the Kaplan-Meier method. Additional subgroup analyses were performed on the relapse type. Overall survival (OS) was calculated from diagnosis of relapse to last follow-up or death. RESULTS: In the multicenter analysis, recurrence was detected by FUIP in 77 of 160 patients (48%) and due to symptoms in 83 patients (52%). Regarding the entire study population, OS was significantly superior in patients with protocol-detected relapse compared to patients with symptomatic relapse (median, 2.4 vs. 1.2 years; P < 0.001). In the subgroup analyses, patients whose lung recurrences were detected by the FUIP experienced longer survival after recurrence than those whose recurrences were detected symptomatically (P = 0.023). In the 83 symptomatic patients, pain was the most prevalent symptom of relapse (72%). CONCLUSION: FUIP may benefit survival in EwS relapse, especially in lung recurrence. Pain was the leading symptom of relapse.

Impact of helmet use in equestrian-related traumatic brain injury: a matched-pairs analysis.

PURPOSE: Traumatic brain injury is an important health concern in equestrian sports. Nevertheless, the use of safety helmets, especially in recreational riding, is reported to be rare. The purpose of this study was to perform the first matched-pairs analysis of traumatic brain injury with regard to the use of helmets. MATERIALS AND METHODS: In a multicenter retrospective database analysis 40 patients (mean age: 35 ± 17.13 years; 34 female & 6 male) were combined in 20 matched pairs based on age group, gender and trauma mechanism. Admission trauma computed tomography was qualitatively analyzed for the presence or absence of fractures or intracranial hemorrhage. Quantitatively, in patients with intracranial hemorrhage dedicated volumetry of the blood volume was performed. Odds ratio and relative risk were calculated for the endpoints fractures and intracranial hemorrhage. Crude risk ratio and lesion volume differences between helmeted and unhelmeted riders were compared. RESULTS: Concerning skull fractures, in this cohort 6 patients (85.7% of all patients with fractures) did not wear a helmet and only one (14.3%) wore a helmet (p = .068).and fractures were considered more complex in the unhelmeted subgroup. Intracranial hemorrhage occurred significantly more often in the unhelmeted subgroup (10 vs. 2; p = .008). Moreover, the total lesion volume with 19.31 ± 23.93ml in the unhelmeted subgroup, presenting with intracranial hemorrhage, was significantly higher than in the control group (0.65 ± 0.35ml; p = .002). Odds ratios were 9 for intracranial hemorrhage (p = .014) and 8.14 for skull fractures without helmet (p = .09). Altogether, the relative risk for intracranial bleeding for unhelmeted riders was 5-fold higher and the relative risk reduction was 96% by wearing a safety helmet. CONCLUSIONS: Under consideration of comparable trauma mechanisms, horseback riders that do not wear a safety helmet are at risk to suffer significantly more severe brain injury than helmeted riders. Therefore, safety helmets are recommendable for all horseback riders.

Intraindividual incongruences of medially ossifying clavicles in borderline adults as seen from thin-slice CT studies of 2595 male persons.

In the past, numerous studies have documented the possibility of intraindividual differing appearances of the paired age-marker "medial clavicular ossification" in borderline adults. However, the extent of the divergences is rarely mentioned. Against that the article describes this phenomenon from a large sample of 2595 male persons by means of thin-slice CT imaging of the sternoclavicular regions. For determining the ossification stage of the medial clavicles, the two accepted classifications by Schmeling et al. (five main stages) and Kellinghaus et al. (six substages) were applied and buildings deviating from that labelled as atypical "norm variants". The longstanding observation could be confirmed that intraindividual stage discrepancies of this age indicator are generally moderate and do not exceed one main stage or two substages of the respective classifications. It is concluded that stage determination should be scrutinized, if a dissimilarity seems to show larger differences.

Forensic age estimation by magnetic resonance imaging of the knee: the definite relevance in bony fusion of the distal femoral- and the proximal tibial epiphyses using closest-to-bone T1 TSE sequence.

OBJECTIVES: To clarify the relevance of the bony fusion of the distal femoral and the proximal tibial epiphyses by means of magnetic resonance imaging (MRI), a prospective cross-sectional cohort study was performed with a special focus on a reliable determination of the 14th, 16th and 18th years of life. METHODS: We scanned 658 German volunteers in the age bracket 12-24 years using a 3.0 T MR-scanner and utilising a T1 turbo spin-echo sequence representing true bone anatomy. Minimum, maximum, mean ± standard deviation and median with lower and upper quartiles were defined. Intra- and interobserver agreements were determined (Cohen's kappa). The statistical relevance of sex-related differences was analysed (Mann-Whitney U test, p < 0.05, exact, two-sided). RESULTS: The bony fusion took place before the 18th year of life in both epiphyses. The Mann-Whitney U test results imply significant sex-related differences for most stages. For both epiphyses, the intra observer (κ femur 0.961; tibia 0.971) and interobserver (κ femur 0.941; tibia 0.951) agreement levels were very good. CONCLUSION: The 14th and the 16th years of life can be determined in both sexes, but the completion of the 18th year of life cannot solely be determined by the bony fusion, as depicted by closest-to-bone MRI. KEY POINTS: • Forensic age estimation by means of MRI of the knee is feasible. • MRI provides data about the ossification process without using ionising radiation. • The method allows the determination of the 14th and 16th years of life. • The bony fusion is not suitable as the sole indicator of majority. • The chosen classification is easy to use for specially trained professional personnel.

Comparison of imaging planes during CT-based evaluation of clavicular ossification: a multi-center study.

Determining the ossification stage of the medial clavicular epiphysis by computed tomography represents the currently recommended methodology for the question of whether a living individual has completed the 18th or 21st year of life. In the present study, thin-slice CT scans of 1078 sternoclavicular joints were reconstructed in axial and coronal image series and evaluated according to the two classification systems established for age diagnostics using the clavicle. Both image series (axial and coronal) were analyzed separately. When comparing the results of axial and coronal view, a different ossification stage was found in 35.6% of the clavicles. The results suggest an influence of the imaging plane on the process of stage determination. In order to further approximate the three-dimensional and asymmetrical structure of the epiphyseal ossification center, the usage of at least two different reformation types may be recommended. In practice, only those reference studies should be applied which exactly employed the same number and orientations of the reformation types that are going to be used in the respective routine case.

Ewing sarcoma during follow-up.

AIM: To evaluate the performance of a prospectively defined follow-up imaging protocol that includes FDG-PET(/CT) to detect tumour recurrence in Ewing sarcoma (EwS) before becoming symptomatic. METHODS: Imaging results and clinical data during follow-up were retrospectively analysed from all patients treated successfully within the EURO E.W.I.N.G. 99 trial at the University Hospital Münster, Germany. All patients received follow-up imaging according to a comprehensive protocol that included regular X-ray, CT, MRI, bone scan and PET(/CT), albeit not all on the same day and with varying intervals for the different modalities. RESULTS: 80 of 105 patients underwent follow-up at our institution after complete remission. 30 patients had recurrent tumour during the follow-up period of 3.6 years on average. 19 recurrences (63%) were detected by scheduled imaging before the advent of clinical symptoms. The majority of these recurrences (8 out of 19; 42%) was detected first by PET/ CT (and confirmed with additional imaging thereafter), even though the total number of PET/CTs was comparatively low (138) and PET/CT was not systematically scheduled before other imaging techniques. Recurrences detected by bone scan were also detectable by PET. CONCLUSIONS: The implemented follow-up protocol was effective in the detection of EwS recurrence before the advent of symptoms. Most cases of those detected before onset of symptoms were detected by PET/CT first. This hybrid imaging modality should therefore be considered in the routine follow-up of EwS patients, as is standard in our hospital. In combination with PET, low-dose chest CT seems to be sufficient in the detection of small pulmonary nodules.

Single-Site Cannulation Venovenous Extracorporeal CO2 Removal as Bridge to Lung Volume Reduction Surgery in End-Stage Lung Emphysema.

Lung volume reduction surgery (LVRS) is an important treatment option for end-stage lung emphysema in carefully selected patients. Here, we first describe the application of low-flow venovenous extracorporeal CO2 removal (LFVV-ECCO2R) as bridge to LVRS in patients with end-stage lung emphysema experiencing severe hypercapnia caused by acute failure of the breathing pump. Between March and October 2015, n = 4 patients received single-site LFVV-ECCO2R as bridge to LVRS. Indication for extracorporeal lung support was severe hypercapnia with respiratory acidosis and acute breathing pump failure. Two patients required continuous mechanical ventilation over a temporary tracheostomy and were bed ridden. The other two patients were nearly immobile because of severe dyspnea at rest. Length of preoperative ECCO2R was 14 (1-42) days. All patients underwent unilateral LVRS. Anatomical resection of the right (n = 3) or left (n = 1) upper lobe was performed. Postoperatively, both patients with previous mechanical ventilatory support were successfully weaned. ECCO2R in patients with end-stage lung emphysema experiencing severe hypercapnia caused by acute breathing pump failure is a safe and effective bridging tool to LVRS. In such patients, radical surgery leads to a significant improvement of the performance status and furthermore facilitates respiratory weaning from mechanical ventilation.