Surgery is the mainstay of treatment for localized soft tissue sarcomas (STS). The curative treatment highly depends on complete tumor resection, as positive margins are associated with local recurrence (LR) and prognosis. However, determining the tumor margin during surgery is challenging. Real-time tumor-specific imaging can facilitate complete resection by visualizing tumor tissue during surgery. Unfortunately, STS specific tracers are presently not clinically available. In this review, STS-associated cell surface-expressed biomarkers, which are currently already clinically targeted with monoclonal antibodies for therapeutic purposes, are evaluated for their use in near-infrared fluorescence (NIRF) imaging of STS. Clinically targeted biomarkers in STS were extracted from clinical trial registers and a PubMed search was performed. Data on biomarker characteristics, sample size, percentage of biomarker-positive STS samples, pattern of biomarker expression, biomarker internalization features, and previous applications of the biomarker in imaging were extracted. The biomarkers were ranked utilizing a previously described scoring system. Eleven cell surface-expressed biomarkers were identified from which 7 were selected as potential biomarkers for NIRF imaging: TEM1, VEGFR-1, EGFR, VEGFR-2, IGF-1R, PDGFRα, and CD40. Promising biomarkers in common and aggressive STS subtypes are TEM1 for myxofibrosarcoma, TEM1, and PDGFRα for undifferentiated soft tissue sarcoma and EGFR for synovial sarcoma.
Background Shoulder injections for conditions such as adhesive capsulitis are commonly performed and can be administered through image-based or landmark-based injection approaches. Ultrasound-guided injections are widely used and accurate because ultrasound allows real-time visualization of the needle and injected contrast. Landmark-based injections would be advantageous, if they were accurate, because they would save the time and expense associated with ultrasound. However, few prospective studies have compared well-described landmark-based shoulder injection techniques without ultrasound. Question/purpose Using anatomic landmarks, and without using ultrasound, is the accuracy of glenohumeral injection for adhesive capsulitis greater via the posterior approach or via a new anterior approach? Methods Between 2018 and 2020, we treated 108 patients potentially eligible for adhesive capsulitis treatment. These patients had clinical symptoms of aggravating shoulder pain with a duration of less than 4 months and passively impaired, painful glenohumeral ROM. Due to the exclusion of patients with other shoulder conditions (full-thickness rotator cuff ruptures and posttraumatic stiffness), 95 patients received an injection in this sequential, prospective, comparative study. Between 2018 and 2019, 41 patients (17 males and 24 females; mean age 52 ± 5 years; mean BMI 24 ± 3 kg/m2) were injected through the posterior approach, with the acromion as the anatomical landmark, during the first part of the study period. After that, between 2019 and 2020, 54 patients (20 males and 34 females; mean age 54 ± 4 years; mean BMI 23 ± 3 kg/m2) received an injection through a new anterior approach, with the acromioclavicular joint as the anatomic landmark, during the second part of the study period. Injections via both approaches were administered by two experienced shoulder specialists (both with more than 10 years of experience). Both specialists had experience with the posterior approach before this study, and neither had previous training with the new anterior approach. Injections contained a corticosteroid, local anaesthetic, and contrast medium. Radiographs were taken within 20 minutes after the injection, and a radiologist blinded to the technique determined accuracy. Accurate injections were defined as having contrast fluid limited to the glenohumeral joint, while inaccurate injections displayed leakage of contrast fluid into the soft tissue or subacromial space. All of the enrolled patients were analyzed. Results In the group with the posterior approach, the accuracy was 78% (32 of 41) in contrast to 94% (51 of 54, odds ratio 0.21 [95% CI 0.05 to 0.83]; p = 0.03) in patients with the new anterior approach. Conclusion The new anterior approach without the use of ultrasound was more accurate than the posterior approach. In fact, it was nearly as accurate as previously published ultrasound-guided approaches. We recommend using the new anterior approach for intraarticular glenohumeral injections instead of ultrasound-guided injections because it will save time and costs associated with ultrasound. Still, the clinical effects (anxiety, pain, functional outcome, and adverse events) of the new anterior approach should be compared with ultrasound-guided injections in a randomized study. Level of Evidence Level II, therapeutic study.
Sarcomas are a rare heterogeneous group of malignant neoplasms of mesenchymal origin which represent approximately 13% of all cancers in pediatric patients. The most prevalent pediatric bone sarcomas are osteosarcoma (OS) and Ewing sarcoma (ES). Rhabdomyosarcoma (RMS) is the most frequently occurring pediatric soft tissue sarcoma. The median age of OS and ES is approximately 17 years, so this disease is also commonly seen in adults while non-pleiomorphic RMS is rare in the adult population. The mainstay of all treatment regimens is multimodal treatment containing chemotherapy, surgical resection, and sometimes (neo)adjuvant radiotherapy. A clear resection margin improves both local control and overall survival and should be the goal during surgery with a curative intent. Real-time intraoperative fluorescence-guided imaging could facilitate complete resections by visualizing tumor tissue during surgery. This review evaluates whether non-targeted and targeted fluorescence-guided surgery (FGS) could be beneficial for pediatric OS, ES, and RMS patients. Necessities for clinical implementation, current literature, and the positive as well as negative aspects of non-targeted FGS using the NIR dye Indocyanine Green (ICG) were evaluated. In addition, we provide an overview of targets that could potentially be used for FGS in OS, ES, and RMS. Then, due to the time- and cost-efficient translational perspective, we elaborate on the use of antibody-based tracers as well as their disadvantages and alternatives. Finally, we conclude with recommendations for the experiments needed before FGS can be implemented for pediatric OS, ES, and RMS patients.
Carbon-fiber (CF) plates are a promising alternative to metal plates. However, reported experience in orthopaedic oncology remains limited. The aim of this study was to identify complications of patients with bone tumors treated with CF plates. Between February 2015 and May 2021, 13 centers retrospectively registered patients with bone tumors that were reconstructed using CF plates. Complications were identified, and timing and etiology of complications were noted. Similar complications were tabulated and classified based on mechanical, non-mechanical and paediatric complications. Mechanical complications included: (1) aseptic loosening or graft-host non-union, and (2) structural complications. Non-mechanical complications included: (3) soft tissue complications, (4) infection and (5) tumor progression. Specific paediatric complications included (6) growth arrest resulting in longitudinal or angular deformity. Ninety-six patients were included with a median follow-up time of 35 months. In total, 22 (23%) patients had complications. Mechanical complications included: 1 (1%) aseptic loosening, 2 (2%) non-unions, and 7 (7%) structural complications. Non-mechanical complications included 1 (1%) soft tissue complication, 4 (4%) infections and 5 (5%) tumor progressions. Paediatric complications occurred in 2 (2%) patients. This study suggests CF plates are safe to use in demanding reconstructions after bone tumor resections, presenting a seemingly low complication profile.
Introduction: Myxofibrosarcoma (MFS) is the most common soft-tissue sarcoma subtype in elderly patients. Local recurrence (LR) remains a major concern as the lack of intraoperative guidance and an infiltrative growth pattern with long, slender tails hamper surgeons’ ability to achieve adequate resection margins for MFS. Fluorescence-guided surgery (FGS) could overcome this concern by delineating tumor tissue during surgery. One of the most important steps to successful FGS is to define a tumor-specific biomarker that is highly overexpressed in tumor tissue while low or absent in adjacent healthy tissue. The aim of this study is to evaluate the expression of eight previously selected promising biomarkers for FGS in MFS tissue samples with adjacent healthy tissue using immunohistochemistry (IHC). Methods: The following eight biomarkers were stained in seventeen paraffin-embedded MFS samples: tumor endothelial marker-1 (TEM-1, also known as endosialin/CD248), vascular endothelial growth factor receptor-1 (VEGFR-1, also known as Flt-1), vascular endothelial growth factor receptor-2 (VEGFR-2, also known as Flk1), vascular endothelial growth factor-A (VEGF-A), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), platelet derived growth factor receptor-α (PDGFR-α), and cluster of differentiation 40 (CD40, also known as TNFRSF5). A pathologist specializing in sarcoma annotated the margin between the tumor and adjacent healthy tissue in each MFS tissue sample. Subsequently, we used an objective IHC scoring method to assess and compare the difference in staining intensity between the tumor and adjacent healthy tissue, which is crucial for the use of FGS. Results: TEM-1, VEGF-A, and PDGFR-α stained all MFS tumors, while the other biomarkers did not show expression in all MFS tumors. Ultimately, TEM-1 was identified as the most suitable biomarker for FGS in MFS based on higher tumor-to-background (TBR) staining intensity compared to VEGF-A and PDGFR-α, regardless of preoperative therapy. Conclusion: TEM-1-targeted FGS tracers should be further investigated to optimize MFS treatment.
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