Introduction Aneurysmal bone cysts (ABCs) are expansive and destructive lesions positive for osteoclast markers, resembling benign giant cell tumors (GCTs). Treatment options include surgical resection, curettage and cavity filling, embolization, injection of fibrosing agents, or radiotherapy. Particularly in children and adolescents with spinal ABCs, these options may be unsatisfactory, and innovative forms of treatment are needed. Denosumab is a human monoclonal antibody that inhibits osteoclast function by blocking the cytokine receptor activator of the nuclear factor-kappa B ligand. Satisfactory results with denosumab in treating GCTs and immunohistochemical similarities suggest that it may also have positive effects on ABCs. Methods and ResultsThis report is the first description of the therapeutic use of denosumab in two patients with spinal ABCs. Two boys (aged 8 and 11) had recurrent ABCs at C5 after surgery with intralesional tumor resection. Treatment options were discussed by the interdisciplinary tumor board. Arterial embolization was attempted, but failed due to an absence of appropriate afferent arteries. After the families had received extensive information and provided written consent, denosumab therapy was initiated as an individualized treatment, despite the absence as yet of scientific evidence. After the start of denosumab therapy, both patients recovered from pain and neurologic symptoms significantly and are now in a healthy condition with no severe side effects. Magnetic resonance imaging check-ups after 2 or 4 months of denosumab treatment, respectively, showed tumor regression in both patients. Discussion Longer follow-up and clinical studies are warranted to establish the value of denosumab in the treatment of ABCs.

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Conventional lumbar microdiscectomy requires subperiosteal dissection of the muscular and tendineous insertions from the midline structures. This prospective, randomized, single center trial aimed to compare a blunt splitting transmuscular approach to the interlaminar window with the subperiosteal microsurgical technique. Two experienced surgeons performed first time lumbar microdiscectomy on 125 patients. The type of approach and retractor used was randomized and both patients and evaluator were blinded to it. In 59 patients a speculumcounter-retractor was inserted through a subperiosteal (SP) route and in 66 patients an expandable tubular retractor was introduced via a transmuscular (TM) approach. In both groups the mean age was 51 years, the male gender prevalent (61%) and the distribution of the operated levels was similar. The outcome measures were VAS for back and leg pain, ODI and the postoperative analgesic consumption was scored by the WHO 3-class protocol. A postsurgical VAS (0-1) was defined as excellent, VAS (2-4) as satisfactory result. In this study the patients scored from 1 to 3 points daily according to the class of drugs taken.Furthermore, a 1/3 point (class 1), 2/3 point (class 2) and 1 point (class 3) was added for each on-demand drug intake. Recovery from radicular pain was excellent (SP 68%, TM 76%) or satisfactory (SP 23%, TM 21%). Recovery from back pain was excellent (SP 58%, TM 59%) or satisfactory (SP 37%, TM 37%). Postoperative mean improvement ODI was: SP 29% and TM 31%. Postoperative mean analgesic intake: SP 4.8 points, TM 2.6 points (P = 0.03). Lumbar microdiscectomy improves pain and ODI irrespective of the type of approach and retractor used. However, the postsurgical analgesic consumption is significantly less if a tubular retractor is inserted via a transmuscular approach.

Scatter factor/hepatocyte growth factor (SF/HGF) is a pleiotropic cytokine that has been implicated in glioma invasion and angiogenesis. The SF/HGF receptor, MET, has been found to be expressed in neoplastic astrocytes as well as in endothelial cells of the tumor vasculature. Both SF/HGF and MET expression have also been described to correlate with the malignancy grade of human gliomas. However, most glioblastoma cell lines lack SF/HGF expression, raising the question of the cellular origin of SF/HGF in vivo. Using in situ hybridization, we analyzed glioblastomas, anaplastic astrocytomas, diffuse astrocytomas, pilocytic astrocytomas, and normal brain for the expression of SF/HGF mRNA. We detected strong SF/HGF expression by the majority of the tumor cells and by vascular endothelial cells in all glioblastoma specimens analyzed. Combined use of in situ hybridization with fluorescence immunohistochemistry confirmed the astrocytic origin of the SF/HGF-expressiong cells. In contrast, CD68-immunoreactive microglia/macrophages, as well as vascular smooth muscle cells reactive to alpha-smooth muscle actin, lacked SF/HGF expression. In anaplastic, diffuse, and pilocytic astrocytomas, SF/HGF expression was confined to a subset of tumor cells, and signals were less intense than in glioblastomas. In addition, we detected SF/HGF mRNA in cortical neurons. SF/HGF expression was not up regulated around necroses or at tumor margins. MET immunoreactivity was observed in GFAP-expressing astrocytic tumor cells and endothelial cells as well as in a subset of microglia/macrophages. We conclude that in vivo, both autocrine and paracrine stimulation of tumor cells and endothelium through the SF/HGF-MET system are likely to contribute to tumor invasion and angiogenesis. Lack of SF/HGF expression by most cultured glioblastoma cells is not representative of the in vivo situation and most likely represents a culture artifact.

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Level IV-retrospective nonrandomized objective study.

Summary of background data The skeletal system is affected in up to 60% of patients with neurofibromatosis type 1. The most commonly observed entities are spinal deformities and tibial dysplasia. Early recognition of radiologic osseous dystrophy signs is of utmost importance because worsening of the deformities without treatment is commonly observed and surgical intervention is often necessary. Due to the relative rarity and the heterogenic presentation of the disease, evidence regarding the best surgical strategy is still lacking. Purpose To report our experience with the treatment of skeletal manifestations in pediatric patients with (neurofibromatosis type 1) NF-1 and to present the results with our treatment protocols. Materials and methods This is a retrospective, single expert center study on children with spinal deformities and tibial dysplasia associated with NF-1 treated between 2006 and 2020 in a tertiary referral institution. Results Spinal deformity: Thirty-three patients (n = 33) were included. Mean age at index surgery was 9.8 years. In 30 patients (91%), the deformity was localized in the thoracic and/or lumbar spine, and in 3 patients (9%), there was isolated involvement of the cervical spine. Eleven patients (33%) received definitive spinal fusion as an index procedure and 22 (67%) were treated by means of “growth-preserving” spinal surgery. Halo-gravity traction before index surgery was applied in 11 patients (33%). Progression of deformity was stopped in all patients and a mean curve correction of 60% (range 23–98%) was achieved. Mechanical problems with instrumentation requiring revision surgery were observed in 55% of the patients treated by growth-preserving techniques and in none of the patients treated by definitive fusion. One patient (3%) developed a late incomplete paraplegia due to a progressive kyphotic deformity. Tibial dysplasia: The study group comprised of 14 patients. In 5 of them (36%) pathological fractures were present on initial presentation. In the remaining 9 patients (64%), anterior tibial bowing without fracture was observed initially. Four of them (n = 4, 28%) subsequently developed a pathologic fracture despite brace treatment. Surgical treatment was indicated in 89% of the children with pathological fractures. This involved resection of the pseudarthrosis, autologous bone grafting, and intramedullary nailing combined with external fixation in some of the cases. In 50% of the patients, bone morphogenic protein was used “off-label” in order to promote union. Healing of the pseudarthrosis was achieved in all of the cases and occurred between 5 to 13 months after the index surgical intervention. Four of the patients treated surgically needed more than one surgical intervention in order to achieve union; one patient had a re-fracture. All patients had a good functional result at last follow-up. Conclusion Early surgical intervention is recommended for the treatment dystrophic spinal deformity in children with NF-1. Good and sustainable curve correction without relevant thoracic growth inhibition can be achieved with growth-preserving techniques alone or in combination with short spinal fusion at the apex of the curve. Preoperative halo-gravity traction is a safe and very effective tool for the correction of severe and rigid deformity in order to avoid neurologic injury. Fracture union in tibial dysplasia with satisfactory functional results can be obtained in over 80% of the children by means of surgical resection of the pseudarthrosis, intramedullary nailing, and bone grafting. Wearing a brace until skeletal maturity is achieved is mandatory in order to minimize the risk of re-fracture.