Eric Lodewijk Staals

Introduction: Symptomatic avascular necrosis of the knee in young patients represents a therapeutic challenge. We present two cases of patients with bilateral massive osteonecrosis and advanced femoral chondropathy treated with bilateral femoral resurfacing. Conclusion: Prosthetic resurfacing of the distal femur in symptomatic osteonecrosis may represent a bone‐sparing technique for young patients, specifically targeting the pathological compartments. It allows for a rapid return to normal activity, reduces pain, and may delay the need for total knee replacement.

Diffuse type tenosynovial giant cell tumor (D-TGCT) of the knee presents with stiffness, pain and swelling with surgery being the mainstay treatment. However, the literature lacks data on clinical course of range of motion, pain (ROM), and swelling after open synovectomy for D-TGCT. Therefore, this study aims to evaluate clinical course after open anterior synovectomy. A retrospective analysis was conducted on 214 patients treated for TGCT at our Institutions between 2010 and 2023. 51 patients with anterior knee D-TGCT who underwent open anterior synovectomy were included. Pre- and postoperative assessments included ROM, pain (VAS scale), and reported swelling. The mean knee flexion increased from 100° (SD 14.28) preoperatively to 131.8° (12.64) at 12 months post-surgery. Knee extension remained stable, ranging from 178.4° preoperatively to 179.2° at the final follow-up. Pain decreased from a mean of 5.0 (SD 2.8) preoperatively to 0.5 (SD 0.7) at 12 months. Swelling was initially reported in 90.4% of patients, with 95.74% of them showing improvement at six months, and 100% at 12 months. Open anterior synovectomy effectively improves knee function, pain, swelling in patients with anterior knee D-TGCT, although functional recovery may take up to 6–12 months.

Background: Treating bone sarcomas in young children, particularly in the proximal femur, is challenging because of the need to preserve growth potential, maintain joint function, and conserve bone for future revisions. In 1997, we introduced a new technique combining a vascularized fibula that preserved the proximal epiphysis to substitute for the femoral head and physis with a massive bone allograft aimed at providing a supportive scaffold for the autograft during growth. This approach initially showed promising results in both anatomic and functional restoration, but because it was a complex operation, we believed that longer term follow-up of this procedure would be helpful to judge its value as a potential reconstructive option. Questions/purposes: (1) What proportion of patients achieved allograft union; what proportion exhibited radiologic signs of vitality in the vascularized fibula, demonstrating bone growth and remodeling; what proportion avoided revision surgery; and what complications were observed with this technique? (2) What were the observed outcome scores using the Musculoskeletal Tumor Society (MSTS) score? (3) What was the status of the hip after treatment? Methods: Between 1997 and 2010, a total of 14 patients who were 6 years old or younger underwent resection of the proximal femur for a bone sarcoma in two sarcoma centers. Six patients were treated with a vascularized fibular autograft plus bulk allograft reconstruction. The median (range) length of the proximal femur resection was 13 (11 to 14) cm. During the period in question, we generally performed the vascularized fibular autograft plus bulk allograft when the acetabular diameter was < 36 mm. None of those who had the fibula autograft plus bulk allograft reconstruction were lost to follow-up before 2 years without meeting a study endpoint (revision, reoperation) or died prior to 2 years with implants intact. All six patients in the original group had either a follow-up of at least 14 years or had met a study endpoint (revision, reoperation) before that minimum surveillance duration; these patients were the focus of the current study. We noted that two patients had follow-up periods of 20 and 27 years but have not been seen in the last 5 years; they were included for survivorship analysis purposes, yet we emphasize that we cannot ascertain their current status. The median (range) follow-up was 17 (14 to 27) years. Results: Six of six patients achieved allograft union, while five of six underwent reoperations, and four of six had the graft removed as part of a revision procedure at a median (range) of 19 (7 to 40) months. Only one patient maintained the original reconstruction after 27 years, despite an epiphysiolysis that occurred 56 months after surgery, which was corrected surgically. The other five patients experienced a complication of the reconstruction at a median (range) onset at 19 (7 to 40) months after surgery. Two of the six patients had a common peroneal nerve palsy at the harvested site. Allograft union was observed a median of 8 months from the index procedure. All patients presented residual limb length discrepancy ranging from 1 to 7 cm. The median (range) MSTS score before any revision was 38% (33% to 93%). Four of the six patients underwent removal of the biological reconstruction and were reconstructed by other methods. They displayed a median (range) MSTS functional score of 88% (73% to 93%) at most recent follow-up. One of the six patients showed progressive diaphyseal hypertrophy, growth, and remodeling of the epiphysis, along with integration with the allograft, and had a final limb length discrepancy of -1 cm. The vascularized fibular epiphysis was enlarged and remodeled to provide a new femoral head and grew similar to the physis of the native femoral head in this one patient. Conclusion: Biological reconstruction using a vascularized fibula and bone allograft in young patients with proximal femur sarcoma was not a durable solution for most patients, and it resulted in frequent unplanned reoperations and revisions. Only one of six patients in this small series had a reconstruction that lasted into adulthood. Even though this was a small group of patients, the poor survival of the construct, the frequent complications, and the unpredictable results associated with it led us to discontinue its use in favor of prosthetic replacement. Level of Evidence: Level IV, therapeutic study.

Osteosarcoma and Ewing sarcoma are bone tumors mostly diagnosed in children, adolescents, and young adults. Despite multimodal therapy, morbidity is high and survival rates remain low, especially in the metastatic disease setting. Trials investigating targeted therapies and immunotherapies have not been groundbreaking. Better understanding of biological subgroups, the role of the tumor immune microenvironment, factors that promote metastasis, and clinical biomarkers of prognosis and drug response are required to make progress. A prerequisite to achieve desired success is a thorough, systematic, and clinically linked biological analysis of patient samples, but disease rarity and tissue processing challenges such as logistics and infrastructure have contributed to a lack of relevant samples for clinical care and research. There is a need for a Europe-wide framework to be implemented for the adequate and minimal sampling, processing, storage, and analysis of patient samples. Two international panels of scientists, clinicians, and patient and parent advocates have formed the Fight Osteosarcoma Through European Research consortium and the Euro Ewing Consortium. The consortia shared their expertise and institutional practices to formulate new guidelines. We report new reference standards for adequate and minimally required sampling (time points, diagnostic samples, and liquid biopsy tubes), handling, and biobanking to enable advanced biological studies in bone sarcoma. We describe standards for analysis and annotation to drive collaboration and data harmonization with practical, legal, and ethical considerations. This position paper provides comprehensive guidelines that should become the new standards of care that will accelerate scientific progress, promote collaboration, and improve outcomes.

The objective of this study was to determine the efficacy of the PRECICE 2^® nail in the treatment of lower limb length discrepancy in patients with a history of bone tumors. This study reports on outcomes, complications, and the safety of the PRECICE 2 limb lengthening nail in a cohort of pediatric patients with limb length discrepancy after surgery for bone tumors. Seventeen patients were treated with intramedullary magnetic nails. The average patient age at the time of surgery was 19 (range 11–32). The PRECICE 2 nail was used on 14 femurs (6 retrograde and 8 anterograde) and 3 tibias. The average consolidation time was 141 days (range 50–360) with a mean CI of 31 ± 12 days/cm. The ASAMI bone score showed 14 (82%) excellent results, 1 (6%) good result, and 2 (12%) poor results. The ASAMI functional score showed 13 (84.6%) excellent results, 3 (11.5%) good results, and 1 (3.8%) fair result. Patients treated with chemotherapy for bone cancer did not show any increase in distraction time or consolidation time. A total of 3 (17%) problems, 1 obstacle (5.5%), and 1 complication (5.5%) were encountered in our case series. The PRECICE 2 nail allows for effective and accurate lengthening preserving the range of motion in patients treated for bone tumors.

Introduction: Aneurysmal bone cyst (ABC) is a lytic benign bone lesion representing about 1% of all primary bone tumors. Method to treat ABC's have developed over time. The standard of care cure for ABC has been curettage with or without bone grafting of the defect but is burdened by recurrence rates of approximately 25%–31%. Based on the assumption that ABCs usually supplied by one or more pathological feeding arteries, selective arterial embolization has been described as an adjuvant preoperative procedure to reduce intra‐operative hemorrhage, and as primary treatment for lesions in difficult surgical access. In the current study, we therefore asked whether (1) a single or a repeat selective arterial embolization (SAE) for treating ABCs would produce comparable healing rates compared with curettage and bone grafting; (2) evaluated the relationship of recurrence in relation to the site of the cyst, the age, and gender of the patients; and (3) the two techniques differ in term of long‐term complication.Material and Methods: We retrospectively reviewed 265 patients who underwent curettage and bone grafting or SAE performed at our institute from 1994 to 2018. The diagnosis of ABC was always established with percutaneous CT‐guided biopsy or open biopsy. Patients were followed clinically with plain radiographs or CT scan at 3, 6, 9, and 12 months then annually in the absence of symptoms. Treatment success was determined evaluating pre‐ and postprocedural imaging according to Chang classification.Results: Two hundred and nineteen were treated with curettage and bone grafting (curettage group), and 46 with SAE Group. Of the 219 patients treated with Curettage and bone grafting (curettage group), 165 out of 219 (75.3%) experienced bone healing, while local recurrence was observed in 54 cases (24.7%) after 12 months on average (range: 3–120 months) from surgery. After the first SAE, bone ossification was seen in 27 (58.7%), without needing any further treatment. Eleven recurred patients were treated with SAE (four patients need two while seven need three SAE to heal), and eight patients with curettage and bone grafting. Thirty‐eight out of 46 (82%) patients experienced bone ossification regardless the number of SAE. The overall rate of local recurrence for all patients was 26.7%. SAE group presented a lower complication rate (6%) where two patients experienced skin necrosis, and one limb‐length discrepancies (2% of all cohort).Discussion: The use of SAE is an attractive option to treat ABC as it combines on one hand a lower complication rate than curettage and bone grafting, on the other it can be carried out in case of nonresectable ABCs, significantly reducing the size of viable ABC lesions, fostering bone remodeling and mineralization, and most importantly, significantly improving the patient's quality of life.

This retrospective study reports on the treatment of chronic osteomyelitis with local debridement combined with PerOssal^®. The diagnosis of chronic osteomyelitis was confirmed in all cases and classified according to the Cierny–Mader (C-M) classification. The primary outcome was the eradication of infection at a minimum of one year after surgery. A total of 93 patients (median age: 40 years) were included. The most represented sites were the femur (24, 25.8%) and tibia (52, 55.9%). Twenty-six patients (28.0%) had significant local or systemic comorbidities (C-M Class B hosts). According to anatomic type, 31 cases were type I, 13 type II, 21 type III and 28 type IV. Vancomycin was added to PerOssal^® in most cases (80, 86.0%). In 24 (25.8%) cases, Vancomycin and Rifampicin were combined. In 32 (34.4%) cases, intraoperative cultures were negative. Staphylococcus aureus was isolated in 39 (63.9%) patients, and Gram-negative bacteria were isolated in 12 cases. The median follow-up was 21 months (range 12–84). A total of 21 (22.6%) patients developed an infection recurrence (IR) after a median follow-up of 11 months (range: 1–47). PerOssal^® holds several practical advantages compared to other bone void fillers. Thus, due to its good biocompatibility and sufficient antibiotic release, it represents a viable adjuvant treatment in chronic osteomyelitis.

The Tenosynovial giant cell tumor Observational Platform Project (TOPP) registry is an international prospective study that ­previously described the impact of diffuse-type tenosynovial giant cell tumour (D-TGCT) on patient-reported outcomes (PROs) from a baseline snapshot. This analysis describes the impact of D-TGCT at 2-year follow-up based on treatment strategies. TOPP was conducted at 12 sites (EU: 10; US: 2). Captured PRO measurements assessed at baseline, 1-year, and 2-year follow-ups were Brief Pain Inventory (BPI), Pain Interference, BPI Pain Severity, Worst Pain, EQ-5D-5L, Worst Stiffness, and ­Patient-Reported Outcomes Measurement Information System. Treatment interventions were no current/planned treatment (Off-Treatment) and systemic treatment/surgery (On-Treatment). A total of 176 patients (mean age: 43.5 years) were included in the full analysis set. For patients without active treatment strategy ­(Off-Treatment) at baseline (n = 79), BPI Pain Interference (1.00 vs. 2.86) and BPI Pain Severity scores (1.50 vs. 3.00) were numerically favorable in patients remaining Off-Treatment compared with those who switched to an active treatment strategy at year 1. From 1-year to 2-year ­follow-ups, patients who remained Off-Treatment had better BPI Pain Interference (0.57 vs. 2.57) and Worst Pain (2.0 vs. 4.5) scores compared with patients who switched to an alternative treatment strategy. In addition, EQ-5D VAS scores (80.0 vs. 65.0) were higher in patients who remained ­Off-Treatment between 1-year and 2-year follow-ups compared with patients who changed treatment strategy. For patients receiving systemic treatment at baseline, numerically favorable scores were seen in patients remaining on systemic therapy at 1-year follow-up: BPI Pain Interference (2.79 vs. 5.93), BPI Pain Severity (3.63 vs. 6.38), Worst Pain (4.5 vs. 7.5), and Worst Stiffness (4.0 vs. 7.5). From 1-year to 2-year follow-up, EQ-5D VAS scores (77.5 vs. 65.0) were higher in patients who changed from systemic treatment to a different treatment strategy. These findings highlight the impact D-TGCT has on patient quality of life, and how treatment strategies may be influenced by these outcome measures. (ClinicalTrials.gov number: NCT02948088)

Background and Objectives: Diffuse‐tenosynovial giant cell tumor (D‐TGCT) is a rare, locally aggressive, typically benign neoplasm affecting mainly large joints, representing a wide clinical spectrum. We provide a picture of the treatment journey of D‐TGCT patients as a 2‐year observational follow‐up. Methods: The TGCT Observational Platform Project registry was a multinational, multicenter, prospective observational study at tertiary sarcoma centers spanning seven European countries and two US sites. Histologically confirmed D‐TGCT patients were categorized as either those who remained on initial treatment strategy (determined at baseline visit) or those who changed treatment strategy with specific changes documented (e.g., systemic treatment to surgery) at the 1‐year and/or 2‐year follow‐up visits. Results: A total of 176 patients were assessed, mean diagnosis age was 38.4 ( SD ± 14.6) years; most patients had a knee tumor (120/176, 68.2%). For the 2‐year observation period, most patients (75.5%) remained on the baseline treatment strategy throughout, 54/79 patients (68.4%) remained no treatment, 30/45 patients (66.7%) remained systemic treatment, 39/39 patients (100%) remained surgery. Those who changed treatment strategy utilized multimodal treatment options. Conclusions: This is the first prospectively collected analysis to describe D‐TGCT patient treatments over an extended follow‐up and demonstrates the need for multidisciplinary teams to determine an optimal treatment strategy.

Background: Giant cell tumors of bone (GCTB) are osteolytic tumors. Denosumab, a RANK-L inhibitor, is approved for GCTB. Data on serum bone turnover marker (sBTM) changes are lacking. We present a phase II correlative study on sBTMs in GCTB patients treated with denosumab. Methods: All GCTB patients receiving denosumab within a multicentre, open-label, phase 2 study were enrolled. Serum levels of carboxyterminal-crosslinked-telopeptide of type I collagen (s-CTX), alkaline phosphatase (ALP), bone-alkaline phosphatase (bALP), parathyroid hormone (sPTH), and osteocalcin (OCN) were prospectively assessed (baseline, T0, 3 months, T1, 6 months, T2). The primary endpoint was assessment of sBTM changes after denosumab; the secondary endpoints were disease-free survival (DFS) and sBTM correlation. Results: In 54 cases, sBTMs decreased during denosumab treatment except for sPTH. With a median follow-up of 59 months, 3-year DFS was 65% (%CI 52–79), with a significantly worse outcome for patients with high (≥500 UI/mL) s-CTX at baseline, as compared to low s-CTX (p = 0.0512; p = 0.0589). Conclusion: Denosumab induces ALP/OCN and s-CTX reduction. High baseline s-CTX identifies a group of patients at higher risk of progression of the disease.