clinicaltrials.gov Identifier: NCT00916409.
The objective of this study is to evaluate the effect of anterior cervical discectomy and fusion (ACDF) on the motion of the cervical spine and dynamic stress (tendency to kyphosis) on adjacent segments and on the overall spinal alignment which may predispose to symptomatic disc diseases at other levels. Twenty consecutive patients underwent ACDF with a mean follow-up of 28 months (range 13-38). Preoperative and postoperative clinical assessments were done by using the neck disability index (NDI) and the Japanese Orthopedic Association (JOA) score. In all cases, at the last follow-up control, a neuro-radiographic assessment [cervical spine static and dynamic X-ray and magnetic resonance imaging (MRI)] was done. The angle of the operated disc space, the disc space angle of contiguous segments, and their range of motion (ROM) and the kyphotic Cobb angle (C2-7) were measured by computer software. The study was done at Sant'Andrea Hospital, Rome, Italy in the period from November 2003 to November 2005. We observed that: the mean Cobb angle improved significantly (p < 0.001) from 3.4 degrees (kyphosis) to postoperative 14.5 degrees. This normalization of angle showed a direct effect on improvement of myelopathic patients, but it had a statistically nonsignificant effect on adjacent segments degeneration (ASD). The mean segmental ROM of adjacent segments did not show significant instability. The mean was 11.1 degrees at upper and 10.2 degrees at lower levels (close to normal). In six cases, the ROM was higher than normal: five of these patients demonstrated symptomatic adjacent segment pathology. Postoperative improvement of mean JOA and NDI scores was statistically significant (p < 0.001). Anyway, symptomatic ASD was observed in five patients (20%): in four of them, the higher disc spaces and in one, the lower disc spaces were involved. In four cases, the preoperative MRI showed slight and asymptomatic disc degeneration at the same levels involved subsequently. This ASD was significantly related to the increased ROM at the segments involved. Follow-up X-rays showed solid fusion with absence of movement in all but one case (at 13-month follow-up), who showed slight movement in the operated level in spite of clinical improvement. The follow-up MRI showed, in all cases, good decompression in the treated levels. Compensatory increase in ROM of the contiguous motion segments in patients subjected to ACDF may lead to ASD especially in those cases with asymptomatic adjacent subclinical degenerative disease. If these preliminary results will be confirmed by larger series, it could be reasonable in young selected patients with soft disc herniation to adopt total disc arthroplasty instead of fusion after cervical micro-discectomy.
The vacuolar H+ ATPase (V-ATPase) is a proton pump responsible for acidification of cellular microenvironments, an activity exploited by tumors to survive, proliferate and resist to therapy. Despite few observations, the role of V-ATPase in human tumorigenesis remains unclear.We investigated the expression of ATP6V0C, ATP6V0A2, encoding two subunits belonging to the V-ATPase V0 sector and ATP6V1C, ATP6V1G1, ATPT6V1G2, ATP6V1G3, which are part of the V1 sector, in series of adult gliomas and in cancer stem cell-enriched neurospheres isolated from glioblastoma (GBM) patients. ATP6V1G1 expression resulted significantly upregulated in tissues of patients with GBM and correlated with shorter patients' overall survival independent of clinical variables.ATP6V1G1 knockdown in GBM neurospheres hampered sphere-forming ability, induced cell death, and decreased matrix invasion, a phenotype not observed in GBM monolayer cultures. Treating GBM organotypic cultures or neurospheres with the selective V-ATPase inhibitor bafilomycin A1 reproduced the effects of ATP6V1G1 siRNA and strongly suppressed expression of the stem cell markers Nestin, CD133 and transcription factors SALL2 and POU3F2 in neurospheres.These data point to ATP6V1G1 as a novel marker of poor prognosis in GBM patients and identify V-ATPase inhibition as an innovative therapeutic strategy for GBM.
Background supratotal resection is advocated in lower-grade-gliomas (LGGs) based on theoretical advantages, but with limited verification of functional risk and data on oncological outcomes. We assessed the association of supratotal resection in molecular-defined LGGs with oncological outcomes. Methods 460 presumptive LGGs included; 404 resected; 347 were LGGs, 319 IDH-mutated, 28 wildtype. All patients had clinical, imaging, molecular data. Resection aimed at supratotal resection without any patient or tumor a-priori selection. The association of Extent-of-Resection (EOR), categorized on volumetric-FLAIR-images as residual-tumor-volume, along with post-surgical-management with Progression-free-survival (PFS), malignant-progression-free-survival (MPFS), and Overall-Survival (OS) assessed by univariate, multivariate, propensity-score-analysis. The study mainly focused on IDH-mutated-LGGs, the “typical LGGs”. Results Median follow-up:6.8 years(IQR:5-8). Out of 319 IDH-mutated-LGGs, 190 (59.6%) progressed, median PFS:4.7 years(95%CI:4–5.3). Total and supratotal resection obtained in 39% and 35% of patients of IDH1-mutated tumors. In IDH-mutated, most patients in partial/subtotal group progressed, 82.4% in total, only 6 (5.4%) in supratotal. Median PFS was 29 months(95%CI:25-36) in subtotal, 46 months(95%CI:38-48) in total, while at 92 months, PFS in supratotal was 94.0%. There was no association with molecular-subtypes and grade. At random-forest-analysis, PFS strongly associated with EOR,RT, previous treatment. In the propensity-score analysis, EOR associated with PFS (HR,0.03;95%CI,0.01-0.13). MPFS occurred in 32.1% of subtotal-total groups; 1 event in supratotal. EOR, grade-III, previous treatment correlated to MPFS. At random-forest analysis, OS associated with EOR as well. Conclusions Supratotal resection strongly associated with PFS, MPFS and OS in LGGs, regardless of molecular subtypes and grade, right from the beginning of clinical presentation.
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