Cost-effectiveness of posterior versus anterior surgery for cervical radiculopathy: results from a multicentre randomised non-inferiority trial (FACET).

PURPOSE: For cervical nerve root compression, anterior cervical discectomy with fusion (anterior surgery) or posterior foraminotomy (posterior surgery) are safe and effective options. Posterior surgery might have a more beneficial economic profile compared to anterior surgery. The purpose of this study was to analyse if posterior surgery is cost-effective compared to anterior surgery. METHODS: An economic evaluation was performed as part of a multicentre, noninferiority randomised clinical trial (Foraminotomy ACDF Cost-effectiveness Trial) with a follow-up of 2 years. Primary outcomes were cost-effectiveness based on arm pain (Visual Analogue Scale (VAS; 0-100)) and cost-utility (quality adjusted life years (QALYs)). Missing values were estimated with multiple imputations and bootstrap simulations were used to obtain confidence intervals (CIs). RESULTS: In total, 265 patients were randomised and 243 included in the analyses. The pooled mean decrease in VAS arm at 2-year follow-up was 44.2 in the posterior and 40.0 in the anterior group (mean difference, 4.2; 95% CI, - 4.7 to 12.9). Pooled mean QALYs were 1.58 (posterior) and 1.56 (anterior) (mean difference, 0.02; 95% CI, - 0.05 to 0.08). Societal costs were €28,046 for posterior and €30,086 for the anterior group, with lower health care costs for posterior (€12,248) versus anterior (€16,055). Bootstrapped results demonstrated similar effectiveness between groups with in general lower costs associated with posterior surgery. CONCLUSION: In patients with cervical radiculopathy, arm pain and QALYs were similar between posterior and anterior surgery. Posterior surgery was associated with lower costs and is therefore likely to be cost-effective compared with anterior surgery.

Cervical Stabilization in Patients with Instability Resulting from Osteoradionecrosis with Subsequent Spondylodiscitis After Radiotherapeutic Treatment for Head- and Neck Carcinoma.

High dose of radiation to bone may cause necrosis. Osteoradionecrosis of the cervical vertebrae is a rare adverse event of radiotherapy in patients treated for head and neck cancer. The risk on osteoradionecrosis will increase with doses exceeding 60 Gy. Minimal trauma of the overlying mucosa of the heavily irradiated cervical spine causes subsequent infections or instability may cause neck pain and severe neurological disability. In four patients the cervical spine received up to 100 Gy due to reirradiation. Clinically the patients presented with neck pain. All patients had defects in the pharyngeal posterior wall and cervical instability due to osteoradionecrosis of several cervical vertebrae. Despite optimal conservative treatment the patients developed sensory and motor function loss of the upper extremities. Laminectomies were performed and the cervical spine was stabilized. The pharyngeal posterior wall defects could not be reconstructed. All patients received lifelong antibiotic treatment. Pain and neurological deficits declined after surgery and initiating antibiotics. Eventually all patients could take up their daily activities. Three patients died between 6 months and 2 years after surgery. The cause of death was not related to the osteoradionecrosis. In case of cervical osteoradionecrosis, with secondary infections, stability of the spine should be restored even when the integrity of the pharyngeal posterior wall cannot be restored. Our cases demonstrate that even when an anterior approach is impossible, due to irradiation changed tissue structures of the pharyngeal posterior wall, a combination of lifelong antibiotic treatment and posterior stabilization is a good alternative. The vertebrae affected by osteoradionecrosis and secondary infection can be left in situ. This intervention leads to improvement in quality of life.

Study protocol for a randomised controlled multicentre study: the Foraminotomy ACDF Cost-Effectiveness Trial (FACET) in patients with cervical radiculopathy.

INTRODUCTION: Cervical radiculopathy due to discogenic or spondylotic stenosis of the neuroforamen can be surgically treated by an anterior discectomy with fusion (ACDF) or a posterior foraminotomy (FOR). Most surgeons prefer ACDF, although there are indications that FOR is as effective as ACDF, has a lower complication rate and is less expensive. A head-to-head comparison of the 2 surgical techniques in a randomised controlled trial has not yet been performed. The study objectives of the Foraminotomy ACDF Cost-Effectiveness Trial (FACET) study are to compare clinical outcomes, complication rates and cost-effectiveness of FOR to ACDF. METHODS AND ANALYSIS: The FACET study is a prospective randomised controlled trial conducted in 7 medical centres in the Netherlands. The follow-up period is 2 years. The main inclusion criterion is a radiculopathy of the C4, C5, C6 or C7 nerve root, due to a single-level isolated cervical foraminal stenosis caused by a soft disc and/or osteophytic component, requiring operative decompression. A sample size of 308 patients is required to test the hypothesis of clinical non-inferiority of FOR versus ACDF. Primary outcomes are: 'operative success', the measured decrease in radiculopathy assessed by the visual analogue scale and 'patient success', assessed by the modified Odom's criteria. Secondary outcomes are: Work Ability Index (single-item WAI), quality of life (EuroQol 5 Dimensions 5 level Survey, EQ-5D-5L), Neck Disability Index (NDI) and complications. An economic evaluation will assess cost-effectiveness. In addition, a budget impact analysis will be performed. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Institutional Ethics Committee of the University Medical Center Groningen. Results of this study will be disseminated through national and international papers. The participants and relevant patient support groups will be informed about the results of the study. TRIAL REGISTRATION NUMBER: NTR5536, pre-results.

Review: on TRAIL for malignant glioma therapy?

Glioblastoma (GBM) is a devastating cancer with a median survival of around 15 months. Significant advances in treatment have not been achieved yet, even with a host of new therapeutics under investigation. Therefore, the quest for a cure for GBM remains as intense as ever. Of particular interest for GBM therapy is the selective induction of apoptosis using the pro-apoptotic tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL signals apoptosis via its two agonistic receptors TRAIL-R1 and TRAIL-R2. TRAIL is normally present as homotrimeric transmembrane protein, but can also be processed into a soluble trimeric form (sTRAIL). Recombinant sTRAIL has strong tumouricidal activity towards GBM cells, with no or minimal toxicity towards normal human cells. Unfortunately, GBM is a very heterogeneous tumour, with multiple genetically aberrant clones within one tumour. Consequently, any single agent therapy is likely to be not effective enough. However, the anti-GBM activity of TRAIL can be synergistically enhanced by a variety of conventional and novel targeted therapies, making TRAIL an ideal candidate for combinatorial strategies. Here we will, after briefly detailing the biology of TRAIL/TRAIL receptor signalling, focus on the promises and pitfalls of recombinant TRAIL as a therapeutic agent alone and in combinatorial therapeutic approaches for GBM.

Neurogenic claudication, a delayed complication of a retained bullet.

STUDY DESIGN: A case report is presented of a 31-year-old man who visited the authors' neurosurgical department in 1993, complaining of neurogenic claudication. History revealed a gunshot incident 11 years ago, with a bullet left in situ. OBJECTIVES: To determine whether to operate on patients who have a bullet in situ near the spinal cord without initial neurologic deficits. SUMMARY OF BACKGROUND DATA: In the literature, only four publications report an epidural chronic inflammatory mass as a reaction to a retained bullet, thereby causing delayed neurologic symptoms. Previous to this report, only one case is described of a patient with a bullet lodged in the paravertebral musculature. METHODS: Clinically, the patient had pain radiating from his lower back to both his thighs, provoked by walking, standing, and the Valsalva maneuver. Comparison of radiographs made in 1990 and in 1993 showed the lead bullet still completely intact in 1990, whereas in 1993, a partial disintegration and displacement of the bullet, causing a chronic inflammatory reaction (extraspinal and intraspinal), as well as cyst formation, was seen. Particularly notable was the radiographic feature of a sort of "fallen leaf sign" at the level of L5-S1. RESULTS: The preoperative complaints were still absent 1 year after surgery. CONCLUSIONS: It is argued that with regard to a retained bullet in the vicinity of the spinal canal, the presence or absence of neurologic symptoms should be the guide for further diagnostic procedures. Only if a neurologic deficit develops, which is possible after many years, should surgical intervention be considered, depending on the severity and type of the deficit, as presented in this case report.

Effectiveness of antiepileptic prophylaxis used with supratentorial craniotomies: a meta-analysis.

Thirty publications on the effectiveness of prophylactic antiepileptic drugs (AEDs) with supratentorial craniotomies were reviewed (1980-1995). After a first selection, six controlled studies remained (11 publications). These six were evaluated according to previously defined methodological criteria. The criteria were divided into three main categories: (1) internal validity, (2) proper and relevant outcome-measures and (3) analysis. In this way a maximum of 145 points could be obtained for each study. Three studies were considered to be of satisfactory methodological quality (> or = 55% or 145 points) and the odds ratios were calculated as a measure of association between treatment and occurrence of convulsions. The odds ratios of these three studies were statistically pooled using the Mantel-Haenszel Estimator. From this test it appeared that prophylactically used AEDs showed a tendency to prevent postoperative convulsions, but this effect was certainly not statistically significant (P = 0.1 one-tailed). Points of attention concerning possible future investigations are stressed.