TNFR1 and TNFR2 regulate the extrinsic apoptotic pathway in myeloma cells by multiple mechanisms

The huge majority of myeloma cell lines express TNFR2 while a substantial subset of them failed to show TNFR1 expression. Stimulation of TNFR1 in the TNFR1-expressing subset of MM cell lines had no or only a very mild effect on cellular viability. Surprisingly, however, TNF stimulation enhanced cell death induction by CD95L and attenuated the apoptotic effect of TRAIL. The contrasting regulation of TRAIL- and CD95L-induced cell death by TNF could be traced back to the concomitant NFκB-mediated upregulation of CD95 and the antiapoptotic FLIP protein. It appeared that CD95 induction, due to its strength, overcompensated a rather moderate upregulation of FLIP so that the net effect of TNF-induced NFκB activation in the context of CD95 signaling is pro-apoptotic. TRAIL-induced cell death, however, was antagonized in response to TNF because in this context only the induction of FLIP is relevant. Stimulation of TNFR2 in myeloma cells leads to TRAF2 depletion. In line with this, we observed cell death induction in TNFR1-TNFR2-costimulated JJN3 cells. Our studies revealed that the TNF-TNF receptor system adjusts the responsiveness of the extrinsic apoptotic pathway in myeloma cells by multiple mechanisms that generate a highly context-dependent net effect on myeloma cell survival

The ipsilateral lamina–pedicle angle: can it be used to guide pedicle screw placement in the sub-axial cervical spine?

Pedicle screws in the sub-axial spine are infrequently used because of concerns over their safety and difficulty in placement, despite their superior pullout strength. In the sub-axial cervical vertebrae, we have observed that the lamina appears to project at right angles to the ipsilateral pedicle axis. The aim of this investigation was to confirm the lamina orientation as a reliable landmark for pedicle screw placement. 80 digital cervical spine CT were analysed. The angle formed by the ipsilateral outer lamina cortex to the pedicle axis was recorded. A total of 398 vertebrae were analysed from patients with a mean age of 39.5 years (range 18–78). Average axial lamina–pedicle angle ranged from 96.6° at C3 to 87.2° at C7 in males, and from 95.6° to 87.5° in females. The angle formed by the posterior cortex of the lamina and the ipsilateral pedicle shows a high level of consistency for sub-axial cervical vertebrae ranging from 96° at C3 to 87° at C7. Although the angle is not exactly 90° at all levels as hypothesised, the orientation of the lamina, nevertheless, forms a useful reference plane for insertion of pedicle screws in the sub-axial cervical spine

Comparison of two novel fluoroscopy-based stereotactic methods for cervical pedicle screw placement and review of the literature

This experimental study was designed to compare two different fluoroscopy-based stereotactic surgical techniques for transcutaneous cervical pedicle screw (CPS) placement in the subaxial human cervical spine: (1) a custom-made aiming frame (AF) in combination with conventional fluoroscopy versus (2) a targeting device in combination with a computer-assisted image guidance system [i.e. virtual fluoroscopy (VF)]. Surgery was carried out on six preserved human total body specimens in a laboratory setting. Sixty pedicles (levels C3–C7) were measured in a multislice computed tomography (CT) image data set prior to surgery. Two groups consisting of three specimens and 30 pedicles each were defined according to the surgical technique. The AF consisted of radiolucent components with a fully adjustable arm for carrying the instruments necessary for placing the screws. The arm was angled according to the cervical pedicle axis, as determined by the preoperative CT scans and intraoperative lateral fluoroscopy. For VF, a targeting device was combined with a computer-assisted image-guided surgery unit. For both stereotactic techniques, 3.5 mm screws made of carbon fibre polyetheretherketone (ECF-PEEK) were inserted transcutaneously through stab incisions. Screw placement was assessed using a four-point grading system ranging from ideal (I) to unacceptable (III) where I = screw centred in pedicle, IIa = perforation of pedicle wall is less than one-fourth of the screw diameter, IIb = perforation of the pedicle wall is more than one-fourth of the screw diameter without contact to neurovascular structures, and III = CPS in contact with neurovascular structures. Fifty-eight pedicle screws could be evaluated without interfering metal artefacts according to the same CT protocol that was used preoperatively. The AF technique achieved a significantly smaller number of screws in contact with neurovascular structures compared with the VF technique (P = 0.021; Fisher’s exact test) (Grade I n = 15; 64.3% AF vs. n = 13; 43.3% VF and Grade III n = 2; 7.1% AF vs. n = 10; 33.3% VF). Although neither of the two techniques was capable of completely preventing CPS perforations, transcutaneous CPS placement with a conventional fluoroscopy-based stereotactic AF can be considered a less expensive alternative to VF. This AF technique is able to reduce the number and severity of lateral pedicle wall violations compared to screw placement via the wide standard posterior open midline approach to the subaxial cervical spine. The results of this study are discussed in context with those obtained from different published modifications, since the first technical description of this surgical technique in 1994 by Abumi and co-workers

Percutaneous instrumentation of the cervical and cervico-thoracic spine using pedicle screws: preliminary clinical results and analysis of accuracy

The pedicle screw instrumentation represents the most rigid construct of the cervical and cervicothoracic spine and in spite of the risks to neurovascular structures clinical relevant complications do not occur frequently. The steep angles of the cervical pedicles result in a wide surgical exposure with extensive muscular trauma. The objective of this study was the evaluation of the accuracy of cervical pedicle screw insertion through a minimally invasive technique to reduce access-related muscular trauma. Therefore, percutaneous transpedicular instrumentation of the cervical and cervicothoracic spine was performed in 15 patients using fluoroscopy. All instrumentations from C2 to Th4 were inserted bilaterally through 2 to 3-cm skin and fascia incisions even in multilevel procedures and the rods were placed by blunt insertion through the incision. Thin-cut CT scan was used postoperatively to analyze pedicle violations. 76.4% of 72 screws were placed accurately. Most pedicle perforations were seen laterally towards the vertebral artery. Critical breaches >2 mm or narrowing of the transversal foramen occurred in 12.5% of screws; however, no revision surgery for screw displacement was needed in the absence of clinical symptoms. No conversion from percutaneous to open surgery was necessary. It was concluded that percutaneous transpedicular instrumentation of the cervical spine is a surgically demanding technique and should be reserved for experienced spine surgeons. The indications are limited to instrumentation-only procedures or in combination with anterior treatment, but with the potential to minimize access-related morbidity