Systemic Metal Ion Concentrations in Patients With Hip and Knee Megaprostheses: A Prospective Cohort Study.

Background: Local tissue and serum metal ions have been shown to be elevated in some metal-on-metal and metal-on-polyethylene joint replacements. Local elevations have been linked to adverse local tissue reactions in some patients, and systemic elevation has been less commonly implicated cardiac and neurologic issues. Using a prospective study design, we aimed to identify the changes in serum metal ion levels after hip or knee megaprosthesis reconstruction. Furthermore, we will evaluate the occurrence of adverse effects and complications, possibly linked to metal ion elevation. Methods: Fourteen consecutive patients receiving a Modular Universal Tumor Revision System megaprosthesis were enrolled. Blood samples were collected preoperatively and postoperatively to determine the serum ion concentrations of aluminum, chromium, cobalt, and silver. To evaluate the safety of the megaprostheses and the subsequently possible related (elevated) serum metal ion concentrations, all adverse effects and complications were registered until last outpatient clinic visit at the time of this study. Results: Compared to the preoperative median serum concentrations, the postoperative median serum concentrations of chromium, silver, and cobalt increased 11-fold, 62-fold, and 64-fold, respectively. The median serum concentration of aluminum increased with 16%. Elevations were primarily noted in patients with knee prostheses. Eight patients had no adverse effects or complications during the period between preoperative and postoperative blood sampling. One adverse effect directly related to the serum metal ion concentrations, namely argyria, was observed. Conclusions: This study documents significantly elevated concentrations of the metal ions, but only one adverse effect directly related to the metal ion concentrations was observed. Future studies are needed to further assess the impact of elevated metal ion levels after megaprostheses, specifically knee implants, which are metal-on-metal.

What Do We Know about Survival in Skeletally Premature Children Aged 0 to 10 Years with Ewing Sarcoma? A Multicenter 10-Year Follow-Up Study in 60 Patients.

(1) Background: Younger age has been associated with better overall survival (OS) in Ewing sarcoma (ES), especially under the age of 10. The favorable survival in younger patients underlines the need for minimizing treatment burden and late sequelae. Our study aimed at describing clinical characteristics, treatment and outcome of a cohort of ES patients aged 0−10. (2) Methods: In this retrospective multicenter study, all consecutive ES patients aged 0−10, treated in four sarcoma centers in the Netherlands (n = 33) and one in Spain (n = 27) between 1982 and 2008, with a minimum follow-up of 10 years, were included. OS, local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) were calculated. Potential factors of influence on OS (risk and protective factors) were analyzed. (3) Results: 60 patients with median follow-up 13.03 years were included. All patients were treated with chemotherapy in combination with local treatment, being surgery alone in 30 (50%) patients, radiotherapy (RT) alone in 12 (20%) patients or surgery plus RT in 18 (30%) patients (12 pre- and 6 postoperative). Limb salvage was achieved in 93% of patients. The 10-OS, -LRFS and -DMFS are 81% (95% CI: 71−91%), 89% (95% CI: 85−93%) and 81% (95% CI: 71−91%), respectively. Six patients developed LR, of which two developed subsequent DM; all had axial ES (pelvis, spine or chest wall), and these patients all died. Ten patients developed DM; eight died due to progressive disease, and two are currently in remission, both with pulmonary metastasis only. Negative or wide resection margin was significantly associated with better OS. Age < 6 years, tumor volume < 200 mL, absence of metastatic disease and treatment after 2000 showed trends towards better OS. Two patients developed secondary malignancy; both had chemotherapy combined with definitive RT for local treatment. (4) Conclusions: Overall survival of these youngest patients with ES was very good. Limb salvage surgery was achieved in >90% of patients. Wide resection margin was the only factor significantly associated with better survival.

Candidate Biomarkers for Specific Intraoperative Near-Infrared Imaging of Soft Tissue Sarcomas: A Systematic Review.

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.

Can Navigation Improve the Ability to Achieve Tumor-free Margins in Pelvic and Sacral Primary Bone Sarcoma Resections? A Historically Controlled Study.

BACKGROUND: Anatomic and surgical complexity make pelvic and sacral bone sarcoma resections challenging. Positive surgical margins are more likely to occur in patients with pelvic and sacral bone sarcomas than in those with extremity sarcomas and are associated with an increased likelihood of local recurrence. Intraoperative navigation techniques have been proposed to improve surgical accuracy in achieving negative margins, but available evidence is limited to experimental (laboratory) studies and small patient series. Only one small historically controlled study is available. Because we have experience with both approaches, we wanted to assess whether navigation improves our ability to achieve negative resection margins. QUESTIONS/PURPOSES: Are navigated resections for pelvic and sacral primary bone sarcomas better able to achieve adequate surgical margins than nonnavigated resections? METHODS: Thirty-six patients with pelvic or sacral sarcomas treated with intraoperative navigation were retrospectively compared with 34 patients undergoing resections without navigation. All patients underwent resections between 2000 and 2017 with the intention to achieve a wide margin. Patients in the navigation group underwent surgery between 2008 and 2017; during this period, all resections of pelvic and sacral primary bone sarcomas with the intention to achieve a wide margin were navigation-assisted by either CT fluoroscopy or intraoperative CT. Patients in the control group underwent surgery before 2008 (when navigation was unavailable at our institution), to avoid selection bias. We did not attempt to match patients to controls. Nonnavigated resections were performed by two senior orthopaedic surgeons (with 10 years and > 25 years of experience). Navigated resections were performed by a senior orthopaedic surgeon with much experience in surgical navigation. The primary outcome was the bone and soft-tissue surgical margin achieved, classified by a modified Enneking system. Wide margins (≥ 2 mm) and wide-contaminated margins, in which the tumor or its pseudocapsule was exposed intraoperatively but further tissue was removed to achieve wide margins, were considered adequate; marginal (0-2 mm) and intralesional margins were considered inadequate. RESULTS: Adequate bone margins were achieved in more patients in the navigated group than in the nonnavigation group (29 of 36 patients [81%] versus 17 of 34 [50%]; odds ratio, 4.14 [95% CI, 1.43-12.01]; p = 0.007). With the numbers available, we found no difference in our ability to achieve adequate soft-tissue margins between the navigation and nonnavigation group (18 of 36 patients [50%] versus 18 of 34 [54%]; odds ratio, 0.89 [95% CI, 0.35-2.27]; p = 0.995). CONCLUSIONS: Intraoperative guidance techniques improved our ability to achieve negative bony margins when performing surgical resections in patients with pelvic and sacral primary bone sarcomas. Achieving adequate soft-tissue margins remains a challenge, and these margins do not appear to be influenced by navigation. Larger studies are needed to confirm our results, and longer followup of these patients is needed to determine if the use of navigation will improve survival or the risk of local recurrence. LEVEL OF EVIDENCE: Level III, therapeutic study.

A Cadaveric Comparative Study on the Surgical Accuracy of Freehand, Computer Navigation, and Patient-Specific Instruments in Joint-Preserving Bone Tumor Resections.

Orthopedic oncologic surgery requires preservation of a functioning limb at the essence of achieving safe margins. With most bone sarcomas arising from the metaphyseal region, in close proximity to joints, joint-salvage surgery can be challenging. Intraoperative guidance techniques like computer-assisted surgery (CAS) and patient-specific instrumentation (PSI) could assist in achieving higher surgical accuracy. This study investigates the surgical accuracy of freehand, CAS- and PSI-assisted joint-preserving tumor resections and tests whether integration of CAS with PSI (CAS + PSI) can further improve accuracy. CT scans of 16 simulated tumors around the knee in four human cadavers were performed and imported into engineering software (MIMICS) for 3D planning of multiplanar joint-preserving resections. The planned resections were transferred to the navigation system and/or used for PSI design. Location accuracy (LA), entry and exit points of all 56 planes, and resection time were measured by postprocedural CT. Both CAS + PSI- and PSI-assisted techniques could reproduce planned resections with a mean LA of less than 2 mm. There was no statistical difference in LA between CAS + PSI and PSI resections (p=0.92), but both CAS + PSI and PSI showed a significantly higher LA compared to CAS (p=0.042 and p=0.034, respectively). PSI-assisted resections were faster compared to CAS + PSI (p < 0.001) and CAS (p < 0.001). Adding CAS to PSI did improve the exit points, however not significantly. In conclusion, PSI showed the best overall surgical accuracy and is fastest and easy to use. CAS could be used as an intraoperative quality control tool for PSI, and integration of CAS with PSI is possible but did not improve surgical accuracy. Both CAS and PSI seem complementary in improving surgical accuracy and are not mutually exclusive. Image-based techniques like CAS and PSI are superior over freehand resection. Surgeons should choose the technique most suitable based on the patient and tumor specifics.

Introducing fluorescence guided surgery into orthopedic oncology: A systematic review of candidate protein targets for Ewing sarcoma.

Ewing sarcoma (ES), an aggressive bone and soft-tissue tumor, is treated with chemotherapy, radiotherapy, and surgery. Intra-operative distinction between healthy and tumorous tissue is of paramount importance but challenging, especially after chemotherapy and at complex anatomical locations. Near infrared (NIR) fluorescence-guided surgery (FGS) is able to facilitate the determination of tumor boundaries intra-operatively, improving complete resection and therefore survival. This review evaluates potential ES-specific proteins from the literature as targets for NIR FGS.