CD99 regulates neural differentiation of Ewing sarcoma cells through miR-34a-Notch-mediated control of NF-κB signaling.

Sarcomas are mesenchymal tumors characterized by blocked differentiation process. In Ewing sarcoma (EWS) both CD99 and EWS-FLI1 concur to oncogenesis and inhibition of differentiation. Here, we demonstrate that uncoupling CD99 from EWS-FLI1 by silencing the former, nuclear factor-κB (NF-κB) signaling is inhibited and the neural differentiation program is re-established. NF-κB inhibition passes through miR-34a-mediated repression of Notch pathway. CD99 counteracts EWS-FLI1 in controlling NF-κB signaling through the miR-34a, which is increased and secreted into exosomes released by CD99-silenced EWS cells. Delivery of exosomes from CD99-silenced cells was sufficient to induce neural differentiation in recipient EWS cells through miR-34a inhibition of Notch-NF-κB signaling. Notably, even the partial delivery of CD99 small interfering RNA may have a broad effect on the entire tumor cell population owing to the spread operated by their miR-34a-enriched exosomes, a feature opening to a new therapeutic option.

Lumbar spinal degenerative "microinstability": hype or hope? Proposal of a new classification to detect it and to assess surgical treatment.

PURPOSE: The stage of unstable dysfunction, also defined as "active discopathy" by Nguyen in 2015 and configuring the first phase of the degenerative cascade described by Kirkaldy-Willis, has specific pathoanatomical and clinical characteristics (low back pain) in the interested vertebral segment, without the presence of spondylolisthesis in flexion-extension radiography. This clinical condition has been defined as "microinstability" (MI). The term has currently not been recognized by the scientific community and is subject of debate for its diagnostic challenge. MI indicates a clinical condition in which the patient has a degeneration of the lumbar spine, causing low back pain, and radiological examinations do not show a spondylolisthesis. METHODS: We elaborated a clinical score test based on preoperative radiological examinations (static and dynamic X-Rays, CT and MRI) to detect and assess MI. Then, we enrolled 74 patients, all the levels from L1 to S1 were analysed, for a total amount of 370 retrospectively analysed levels. We excluded patients with degenerative scoliosis, as it is related to an advanced stage of degeneration. The test has been developed with the aim of furnishing quantitative data on the basis of the aforementioned radiological examinations and of elaborating a diagnosis and a treatment for the degenerative pathology in dysfunctional phase, responsible for low back pain. RESULTS: We performed a statistical analysis on the results obtained from the test in terms of significativity and predictive value with a 1-year follow-up, calculating the p value and the χ (2) value. CONCLUSIONS: In patients with low back pain and negative dynamic X-Rays, an accurate analysis of the radiological exams (CT, MRI, X-Rays) allows to formulate a diagnosis of suspect MI with a good predictive value. This situation opens many clinical and medicolegal scenarios. The preliminary results seem to validate the test with a good predictive value, especially towards ASD, but they need further studies. On the basis of the results obtained, the test seems to allow a good classification of the dysfunctional phase of the degenerative cascade, identifying and classifying MI as a pathologic entity, defining its pathoanatomical and clinical relevance and elaborating a treatment algorithm.

Post laminoplasty cervical kyphosis-Case report.

INTRODUCTION: Cervical kyphosis is a progressive cervical sagittal plane deformity that may cause a reduction in the ability to look horizontally, breathing and swallowing difficulties, sense of thoracic oppression and social isolation. Moreover, cervical kyphosis can cause myelopathy due to a direct compression by osteo-articular structures on the spinal cord or to a transitory ischaemic injury. The treatment of choice is surgery. The goals of surgery are: nervous structures decompression, cervical and global sagittal balance correction and vertebral stabilization and fusion. PRESENTATION OF CASE: In October 2008 a 35 years old woman underwent surgical removal of a cervical-bulbar ependymoma with C1-C5 laminectomy and a C2-C5 laminoplasty. Five months after surgery, the patient developed a kyphotic posture, with intense neck and scapular girdle pain. The patients had a flexible cervical kyphosis. Therefore, we decided to perform an anterior surgical approach. We performed a corpectomy C4-C5 in order to achieve the anterior decompression; we placed a titanium expansion mesh. DISCUSSION: Cervical kyphosis can be flexible or fixed. Some authors have reported the use of anterior surgery only for flexible cervical kyphosis as discectomy and corpectomy. This approach is useful for anterior column load sharing however it is not required for deformity correction. CONCLUSION: The anterior approach is a good surgical option in flexible cervical kyphosis. It is of primary importance the sagittal alignment of the cervical spine in order to decompress the nervous structures and to guarantee a long-term stability.

Percutaneous short fixation vs conservative treatment: comparative analysis of clinical and radiological outcome for A.3 burst fractures of thoraco-lumbar junction and lumbar spine.

PURPOSE: The aim of the study is to use an algorithm previously published to decide whether to perform open surgery or percutaneous surgery with short fixation in patients with thoraco-lumbar junction and lumbar spine fractures, and to compare retrospectively surgical and conservative options of treatment. METHODS: Between 2005 and 2009, two groups of 25 patients were analyzed to compare retrospectively surgical and conservative option of treatment to assess perception of pain and to evaluate quality of life during treatment, to evaluate how quickly patients return to work and to their daily activities, to evaluate patients' satisfaction. X-ray controls were performed to evaluate the fusion rate at 3 and 6 months and CT scans at 6 months. RESULTS: The surgical group had a better functional recovery, a better quality of life and returned to work earlier in comparison to the conservative group. CONCLUSIONS: We can conclude that the percutaneous procedure seems to give better results in terms of satisfaction and return to normal activities, although both procedures guarantee excellent fusion rates.

Spinal schwannomatosis in the absence of neurofibromatosis: A very rare condition.

Schwannomatosis is defined as an extremely rare tumors syndrome characterized by the presence of multiple schwannomas in the absence of typical signs of NF1 and NF2 syndromes. The genetic and molecular analysis performed on these tumors makes it possible to name schwannomatosis as distinct clinical and genetic syndrome. The treatment in the case of symptomatic lesions is surgical removal; if the lesions are asymptomatic it is better to perform serial MRI studies. Given the high incidence of developing additional lesions in patients with schwannomatosis, it remains imperative to perform serial brain and spinal cord MRI studies during follow-up. The differential diagnosis is important including clinical and radiological criteria plus molecular genetic analysis of tumor cells and lymphocyte DNA. We report a rare case of spinal schwannomatosis in which genetic analysis performed on surgical samples showed two different mutations in the cells of the two lesions.

Management of calcified thoracic disc herniation using ultrasonic bone curette SONO-PET®: technical description.

This paper describes the surgical management of a post-traumatic calcified thoracic disc herniation treated using ultrasonic bone curette SONO-PET®. The case described concerns a young man with a symptomatic calcified thoracic disc herniation, who underwent posterolateral approach and transversoarthropediculectomy. Patient underwent posterolateral approach with excellent postoperative results. Neurophysiological monitoring somato-sensory evoked potential (SSEP) and muscle motor evoked potentials (MMEP), inclination of 30° toward the unaffected side of the operating table, the use of Ultrasonic Bone-Curette SONO-PET® and proper reconstruction of the three floors of the back muscles allows the removal of the disc herniation safer and risk's free, and less invasive for the patient.

Five-year outcome of stand-alone fusion using carbon cages in cervical disc arthrosis.

From January 1, 2001 to December 31, 2003, in the Neurosurgery Department of Rome University o "Sapienza," 167 patients underwent anterior surgery for cervical spondylodiscoarthrosis. The levels treated by the anterior stand-alone technique were: C3-C4 (11%), C4-C5 (19%), C5-C6 (40%), and C6-C7 (30%). All patients underwent left anterior presternocleidomastoid-precarotid approach, microdiscectomy, and interbody fusion using a carbon fiber cage filled with hydroxyapatite. All patients were discharged within 48 h after surgery with cervical orthosis. In one case, a hematoma of the surgical site occurred within 12 h of surgery; for this reason the patient underwent surgical revision and was discharged 4 days later. All patients have worn cervical orthosis for a mean period of 7 weeks and underwent radiological follow-up with cervical RX at 1 and 3 months after surgery. All patients underwent follow-up from 54 to 90 months after surgery, and all of them underwent cervical RX, cervical CT scans for the estimate of fusion, and evaluation of neurological status using VAS and NDI. Of 167 patients, 132 were cooperative for this study, 18 were non-cooperative, and 17 died. The estimation of fusion made by cervical CT scans with sagittal reconstruction showed complete osteointegration of the cage in 115 patients (87.1%), while it showed pseudoarthrosis in 17 patients (12.9%). In 24 patients, we observed adjacent segment degeneration, and 13 of these underwent new surgical procedures in this institute or in another hospital. Clinical evaluation with VAS and NDI showed a good outcome, with poorest benefit in patients over 60 years. The clinical analysis showed a good fusion rate in according with literature, 13% of non-fusion rate without clinical evidence and 20% of ASDegeneration but only 10% had required new surgery. We also observed that patients over 60 years of age had less satisfactory outcome, probably related with the evolution of pathophysiological degeneration of the cervical spine. In the opinion, pseudoarthrosis is caused by malpositioning of the carbon fiber cage.