Combined treatment by octreotide and everolimus: Octreotide enhances inhibitory effect of everolimus in aggressive meningiomas.

Treatment for recurrent and aggressive meningiomas remains an unmet medical need in neuro-oncology, and chemotherapy exhibits limited clinical activity, if any. Merlin expression, encoded by the NF2 gene, is lost in a majority of meningiomas, and merlin is a negative regulator of mTORC1. The sst2 somatostatin receptor, targeted by octreotide, is highly expressed in meningiomas. To investigate new therapeutic strategies, we evaluated the activity of everolimus (mTOR inhibitor), BKM-120 and BEZ-235 (new Pi3K/Akt/mTOR inhibitors), octreotide and a combined treatment (octreotide plus everolimus), on cell proliferation, signaling pathways, and cell cycle proteins, respectively. The in vitro study was conducted on human meningioma primary cells extracted from fresh tumors, allowing the assessment of somatostatin analogs at the concentration levels used in patients. The results were correlated to WHO grades. Further, everolimus decreased cell viability of human meningiomas, but concomitantly, induced Akt activation, reducing the antiproliferative effect of the drug. The new Pi3K inhibitors were not more active than everolimus alone, limiting their clinical relevance. In contrast, a clear cooperative inhibitory effect of octreotide and everolimus was observed on cell proliferation in all tested meningiomas, including WHO grades II-III. Octreotide not only reversed everolimus-induced Akt phosphorylation but also displayed additive and complementary effects with everolimus on downstream proteins involved in translation (4EB-P1), and controlling cell cycle (p27Kip1 and cyclin D1). We have demonstrated a co-operative action between everolimus and octreotide on cell proliferation in human meningiomas, including aggressive ones, establishing the basis for a clinical trial.

Circumferential management of unstable thoracolumbar fractures using an anterior expandable cage, as an alternative to an iliac crest graft, combined with a posterior screw fixation: results of a series of 85 patients.

OBJECT: The optimal management of unstable thoracolumbar fractures remains unclear. The objective of the present study was to evaluate the results of using an expandable prosthetic vertebral body cage (EPVBC) in the management of unstable thoracolumbar fractures. METHODS: Eighty-five patients with unstable T7-L4 thoracolumbar fractures underwent implantation of an EPVBC via an anterior approach combined with posterior fixation. Long-term functional outcomes, including visual analog scale and Oswestry disability index scores, were evaluated. RESULTS: In a mean follow-up period of 16 months, anterior fixation led to a significant increase in vertebral body height, with an average gain of 19%. However, the vertebral regional kyphosis angle was not significantly increased by anterior fixation alone. No significant difference was found between early postoperative, 3-month, and 1-year postoperative regional kyphosis angle and vertebral body height. Postoperative impaction of the prosthetic cage in adjacent endplates was observed in 35% of the cases, without worsening at last follow-up. Complete fusion was observed at 1 year postoperatively and no cases of infections or revisions were observed in relation to the anterior approach. CONCLUSIONS: The use of EPVBCs for unstable thoracolumbar fractures is safe and effective in providing long-term vertebral body height restoration and kyphosis correction, with a moderate surgical and sepsis risk. Anterior cage implantation is an alternative to iliac bone graft fusion and is a viable option in association with a posterior approach, in a single operation without additional risks.

Percutaneous kyphoplasty and pedicle screw fixation for the management of thoraco-lumbar burst fractures.

The study design includes prospective evaluation of percutaneous osteosynthesis associated with cement kyphoplasty on 18 patients. The objective of the study is to assess the efficacy of a percutaneous method of treating burst vertebral fractures in patients without neurological deficits. Even if burst fractures are frequent, no therapeutic agreement is available at the moment. We report in this study the results at 2 years with a percutaneous approach for the treatment of burst fractures. 18 patients were included in this study. All the patients had burst vertebral fractures classified type A3 on the Magerl scale, between levels T9 and L2. The patients' mean age was 53 years (range 22-78 years) and the neurological examination was normal. A percutaneous approach was systematically used and a kyphoplasty was performed via the transpedicular pathway associated with percutaneous short-segment pedicle screw osteosynthesis. The patients' follow-up included CT scan analysis, measurement of vertebral height recovery and local kyphosis, and clinical pain assessments. With this surgical approach, the mean vertebral height was improved by 25% and a mean improvement of 11.28 degrees in the local kyphotic angle was obtained. 3 months after the operation, none of the patients were taking class II analgesics. The mean duration of their hospital stay was 4.5 days (range 3-7 days) and the mean follow-up period was 26 months (range 17-30 months). No significant changes in the results obtained were observed at the end of the follow-up period. Minimally invasive methods of treating burst vertebral fractures can be performed via the percutaneous pathway. This approach gives similar vertebral height recovery and kyphosis correction rates to those obtained with open surgery. It provides a short hospital stay, however, and might therefore constitute a useful alternative to open surgical methods.

Successful treatment of a giant isolated cerebral mucormycotic (zygomycotic) abscess using endoscopic debridement: case report and therapeutic considerations.

BACKGROUND: Cerebral mucormycosis without rhino-orbital or systemic involvement is an extremely rare condition mostly associated with parenteral drug abuse. CASE DESCRIPTION: We report the case of a 42-year-old woman who presented with hemiparesis of the left side and altered mental status. Neuroradiologic workup demonstrated an inflammatory lesion involving the right basal ganglia. Proton magnetic resonance spectroscopy demonstrated features consistent with a pyogenic abscess. Computed tomography-guided stereotactic biopsy led to the diagnosis of cerebral mucormycosis. Parenteral AMB-L treatment was conducted, but the patient worsened clinically, presenting with a complete hemiplegia, and cerebral magnetic resonance imaging (MRI) scans demonstrated a voluminous abscess formation. Then, under stereotactic guidance, a surgical endoscopic debridement of the abscess cavity associated with the placement of an Ommaya reservoir was performed. Systemic and intralesional treatment with AmB associated with an adjunctive immune therapy was conducted. At 3-year follow-up, the patient had recovered partially from her left hemiplegia, allowing her to walk without help, and cerebral MRI scans showed complete resorption of the abscess. CONCLUSION: Our good results suggest that surgical endoscopic debridement associated with intravenous and intracavitary antifungal therapy might be valuable in treating voluminous deep-seated mucormycotic lesions.

Open kyphoplasty for management of metastatic and severe osteoporotic spinal fracture. Technical note.

OBJECT: Elderly patients in poor general health frequently suffer vertebral body (VB) fractures due to osteoporosis or vertebral metastatic lesions. Kyphoplasty and vertebroplasty have become the standard treatment for these types of fractures. In certain conditions that cause local kyphosis, such as spinal cord compression due to a metastatic epidural tumor or the shortening of the spinal canal secondary to vertebral compression, the surgical treatment should provide decompression and stabilization during a short intervention. In this study the authors evaluated a surgical technique that frequently combines a same-session surgical decompression, such as a laminectomy, and posterior instrumentation-assisted stabilization during the same open intervention in which the VB is stabilized by kyphoplasty. METHODS: During an 18-month period, the authors treated 18 patients with VB fractures according to this protocol: 14 patients with vertebral metastatic lesions and four with osteoporosis. The patients' mean age was 60 years. All suffered severe pain preoperatively (mean visual analog scale [VAS] score of 7). Fourteen of the 18 patients suffered a neurological deficit. Twenty-three vertebral levels were treated; in 15 patients it was necessary to place posterior instrumentation. The mean duration of the intervention was 90 minutes. Pain in all patients improved 3 days after the intervention, and the mean VAS score decreased to 2. Patients with a neurological dysfunction improved. The mean quantity of injected cement for the kyphoplasty procedure was 7 ml. The mean duration of hospitalization was 7 days. Neuroimaging revealed cement leaks in two cases: one into the disc interspace and one anteriorly into the fractured part of the vertebra. After the intervention, most patients with metastatic lesions underwent radiotherapy. No procedure-related complications occurred. CONCLUSIONS: This procedure allows decompression of the spinal cord, consolidation of the VB and thus a stabilization of the vertebral column, and may provide an alternative treatment to invasive VB excision in patients in poor general health.

Corpectomy and Vertebral Body Reconstruction with Expandable Cage Placement and Osteosynthesis via the single stage Posterior Approach: a Retrospective Series of 34 Patients with Thoracic and Lumbar Spine Vertebral Body Tumors.

BACKGROUND: Metastatic disease of the spine requires a multidisciplinary and comprehensive approach to patient care, especially, for patients in a lot of pain with neurological deficit or spinal instability requiring surgical stabilization. OBJECTIVES: The purpose of the study is to report our experience on 34 patients who underwent spinal metastasis resection. We used a single-stage posterior approach with vertebral body reconstruction by an expandable titanium cage and a posterior instrumentation. The parameters assessed were neurologic status, OMS score, angle of sagittal deformity, and morbidity. METHODS: Between January 2011 and June 2014 we performed a monocentric consecutive case review of 34 patients with vertebral body tumor. All of them underwent a single-stage vertebrectomy with circumferential reconstruction and an arthrodesis by posterior approach. RESULTS: 34 patients underwent a single stage surgery by posterior approach, including 30 thoracic lesions and 4 lumbar lesions. Pre operatively, sixteen patients presented a neurologic impairment. The mean follow-up was 13.7 months [1-32 m]. No neurologic impairment was observed in the 34 cases. At the last term of follow-up, neurologic status was improved in 23 cases. OMS score was improved in 23 cases (67.6 %), and worsened in one case. Before surgery, the average of visual analogic scale was 8.94/10 [7-10] and decreased to 2.62/10 [1-5] after surgery. Single posterior approach surgery significantly reduced the average sagittal deformity to 10.0° (0.01-19.96; P = 0.013, Mann-Whitney test). CONCLUSION: Our outcomes suggest that it will be more efficient to perform an aggressive approach in spinal metastatic treatment in order to improve quality of life.

Changing trends in the epidemiology of vertebral osteomyelitis in Marseille, France.

The incidence and significant morbidity of vertebral osteomyelitis are increasing despite the progress of diagnosis competences. Among the 50 cases of vertebral osteomyelitis managed in our centers over the past 5 years, 84% of the cases were in men. The mean age was 55 years. Sixty-two percent of patients had comorbidities and risk factors: diabetes mellitus (24%), malignancy (16%), intravenous drug use (10%) and alcoholism (4%). A source of infection was identified in 66% of cases, including postvertebral surgery infection (18%) and hematogenous infection (48%). The mean time to diagnosis was 36 days. Back pain were occurred in 90% of cases, fever (70%), neurologic deficits (40%), epidural abscesses (32%), completed vertebral bone destruction (26%) and psoas abscess (12%). A single organism was isolated in 92% of cases. Gram-positive bacteria were identified in 76% of cases, while Gram-negative bacilli (GNB) were found in 18% of cases. The presence of GNB was significantly associated with malignancy (p 0.041). The mean duration of antibiotic therapy was 123 days. Surgical treatment was performed in 41 cases: spinal stabilization (26%), drainage of abscesses (32%) and relief of compression (40%). Residual pain was found in 24% of cases, and neurologic sequelae in 22%. Cervical or thoracic localization was a risk factor for neurologic compromise (p 0.042). The epidemiology of vertebral osteomyelitis has changed; an increase in malignancy that was significantly associated with vertebral osteomyelitis due to GNB has been observed. Our study shows that the rate of neurologic complications remains high despite improved diagnostic capabilities and optimal treatment.

Reassessment of scoring systems and prognostic factors for metastatic spinal cord compression.

BACKGROUND CONTEXT: The incidence of metastatic spinal cord compression (MSCC) is increasing, paralleling increasing life expectancy of patients. However, management of MSCC and relevance of scoring systems remain controversial. PURPOSE: The aims of our study were to analyze the feasibility and outcomes of spinal surgery, to identify prognostic factors for survival, and to assess the accuracy of scoring systems in patients with malignancies associated with MSCC. STUDY DESIGN: Retrospective analysis of all patients with MSCC operated in our institution. METHODS: Outcomes of surgery, prognostic factors for survival, and relevance of Tomita and Tokuhashi scores were investigated. RESULTS: One hundred forty-eight patients were included: 66% were hyperalgic (pain score >6) and Frankel score (FS) was decreased in 49%. Seventy-three percent of patients had laminectomy with spinal fixation. After surgery, pain decreased in 75% of cases, FS was improved in 31%, and 92% of patients were ambulatory. Postoperative complication rate was 16%. Median overall survival (OS) was 8.9 months (95% confidence interval, 4.4-13). Only Tokuhashi score was relevant, but predictive accuracy of survival was just 51%. In univariate analyses, hyperalgia (p=.001), primary tumor site, extrabone metastases (p<.001), Karnofsky performance status (KPS) less than 70 (p<.001), poor American Society of Anesthesiologist (ASA) score (p<.001) or FS (p=.01), and absence of postoperative chemotherapy (p<.001) were associated with shorter OS. In multivariate analysis, only extrabone metastases (p=.004), KPS (p=.001), and ASA score (p=.007) remained significantly associated with OS. CONCLUSIONS: Surgery for MSCC is associated with limited morbidity, improved autonomy, and pain relief. Usual scores do not seem relevant, whereas ASA score, KPS, and extrabone metastases are significantly associated with OS.

Percutaneous cement-augmented screws fixation in the fractures of the aging spine: is it the solution?

INTRODUCTION: Management of elderly patients with thoracolumbar fractures is still challenging due to frequent osteoporosis and risk of screws pull-out. The aim of this study was to evaluate results of a percutaneous-only procedure to treat these fragile patients using cement-augmented screws. METHODS: 12 patients diagnosed with a thoracolumbar fracture associated with an important loss of bone stock were included in this prospective study. Surgical procedure included systematically a percutaneous osteosynthesis using cemented fenestrated screws. When necessary, additional anterior support was performed using a kyphoplasty procedure. Clinical and radiographic evaluations were performed using CT scan. RESULTS: On the whole series, 15 fractures were diagnosed and 96 cemented screws were inserted. The difference between the pre- and postoperative vertebral kyphosis was statistically significant (12.9° versus 4.4°, P = 0.0006). No extrapedicular screw was reported and one patient was diagnosed with a cement-related pulmonary embolism. During follow-up period, no infectious complications, implant failures, or pull-out screws were noticed. DISCUSSION: Aging spine is becoming an increasing public health issue. Management of these patients requires specific attention due to the augmented risk of complications. Using percutaneous-only screws fixation with cemented screw provides satisfactory results. A rigorous technique is mandatory in order to achieve best outcomes.

Open kyphoplasty for management of severe osteoporotic spinal fractures.

OBJECTIVE: Osteoporotic compression fractures, which can lead to neurological complications in some cases, are an increasingly frequent occurrence. These lesions require decompression surgery with or without spinal stabilization procedures. In this article, we present the preliminary results obtained using open kyphoplasty, a new method of treating vertebral compression disorders. METHODS: Sixteen patients were included in this prospective study, and a total of 17 vertebrae were treated. All of the patients had vertebral compression fractures associated with neurological disorders. The surgical treatment consisted of open kyphoplasty after laminectomy and decompression. Short-segment vertebral osteosynthesis was also performed in patients with pronounced local kyphosis. Pain was rated at clinical assessments, and radiological assessments were performed to determine the restored vertebral height and the correction of any local vertebral kyphosis. RESULTS: Analysis of the results obtained using this method showed that vertebral height was significantly improved (P < 0.001) and local kyphosis was significantly reduced (P < 0.001). The mean operating time was 90 minutes. The neurological status of all patients improved; 14 patients recovered completely from their neurological symptoms. The last 2 patients had associated neurological disease but were able to walk. There were 2 superficial postoperative infections. CONCLUSION: This method for treating severe osteoporotic compression fractures associated with neurological disorders gives successful results and can be used to treat neurological compression fractures while consolidating the vertebral body. Therefore, this less invasive approach seems to be particularly useful for treating compression fractures in the thoracolumbar spine junction in elderly patients who often have comorbidities.

Brown-Sequard-type myelopathy due to cervical disc herniation associated with severe carotid stenosis prompting rapid combined corpectomy and carotid endarterectomy under deep anticoagulant therapy.

BACKGROUND CONTEXT: The risk of stroke because of carotid retraction during an anterior cervical spine surgery as well as the risk of bleeding complications after an anterior cervical corpectomy under deep anticoagulation and antiplatelet therapy is a surgical issue poorly addressed in the literature. PURPOSE: To describe the feasibility and safety of a simultaneous carotid endarterectomy and anterior corpectomy and fusion under deep anticoagulation in a patient with a cervical spinal cord compression and a severe carotid artery stenosis. STUDY DESIGN: Case report. METHODS: The authors describe the case of a 79-year-old man who had a 1-month history of progressive pain in the neck and left arm, associated with progressive weakness in the left arm and leg. He also presented a history of coronaropathy and bilateral severe carotid stenosis for which he was receiving a regimen of antiplatelet therapy. RESULTS: The cervical magnetic resonance imaging demonstrated a C4-C5 disc herniation migrating down to C5. His condition worsened rapidly during hospitalization prompting a rapid decompression. Given the necessity of a C5 corpectomy and the risk of stroke during anterior cervical spine surgery, it was therefore decided to undertake the surgical procedure under efficient anticoagulant and antiplatelet therapy. A combined endarterectomy and spinal decompression and fusion were then performed. The postoperative course was uneventful, and the patient recovered neurologically. CONCLUSIONS: This case suggests that such a combined carotid endarterectomy and cervical corpectomy with fusion under anticoagulant and antiplatelet therapy is feasible. However, even if the unique clinical presentation of our patient led us to undertake such a surgical strategy, therapeutic decision in patients presenting with both severe carotid stenosis and cervical spinal cord compression should rely on a case-by-case analysis.