Barend J. van Royen

Repair, regenerative and supportive therapies of the annulus fibrosus: achievements and challenges

Lumbar discectomy is a very effective therapy for neurological decompression in patients suffering from sciatica due to hernia nuclei pulposus. However, high recurrence rates and persisting post-operative low back pain in these patients require serious attention. In the past decade, tissue engineering strategies have been developed mainly targeted to the regeneration of the nucleus pulposus (NP) of the intervertebral disc. Accompanying techniques that deal with the damaged annulus fibrous are now increasingly recognised as mandatory in order to prevent re-herniation to increase the potential of NP repair and to confine NP replacement therapies. In the current review, the requirements, achievements and challenges in this quickly emerging field of research are discussed.

Total disc replacement surgery for symptomatic degenerative lumbar disc disease: a systematic review of the literature.

The objective of this study is to evaluate the effectiveness and safety of total disc replacement surgery compared with spinal fusion in patients with symptomatic lumbar disc degeneration. Low back pain (LBP), a major health problem in Western countries, can be caused by a variety of pathologies, one of which is degenerative disc disease (DDD). When conservative treatment fails, surgery might be considered. For a long time, lumbar fusion has been the “gold standard” of surgical treatment for DDD. Total disc replacement (TDR) has increased in popularity as an alternative for lumbar fusion. A comprehensive systematic literature search was performed up to October 2008. Two reviewers independently checked all retrieved titles and abstracts, and relevant full text articles for inclusion. Two reviewers independently assessed the risk of bias of included studies and extracted relevant data and outcomes. Three randomized controlled trials and 16 prospective cohort studies were identified. In all three trials, the total disc replacement was compared with lumbar fusion techniques. The Charité trial (designed as a non-inferiority trail) was considered to have a low risk of bias for the 2-year follow up, but a high risk of bias for the 5-year follow up. The Charité artificial disc was non-inferior to the BAK® Interbody Fusion System on a composite outcome of “clinical success” (57.1 vs. 46.5%, for the 2-year follow up; 57.8 vs. 51.2% for the 5-year follow up). There were no statistically significant differences in mean pain and physical function scores. The Prodisc artificial disc (also designed as a non-inferiority trail) was found to be statistically significant more effective when compared with the lumbar circumferential fusion on the composite outcome of “clinical success” (53.4 vs. 40.8%), but the risk of bias of this study was high. Moreover, there were no statistically significant differences in mean pain and physical function scores. The Flexicore trial, with a high risk of bias, found no clinical relevant differences on pain and physical function when compared with circumferential spinal fusion at 2-year follow up. Because these are preliminary results, in addition to the high risk of bias, no conclusions can be drawn based on this study. In general, these results suggest that no clinical relevant differences between the total disc replacement and fusion techniques. The overall success rates in both treatment groups were small. Complications related to the surgical approach ranged from 2.1 to 18.7%, prosthesis related complications from 2.0 to 39.3%, treatment related complications from 1.9 to 62.0% and general complications from 1.0 to 14.0%. Reoperation at the index level was reported in 1.0 to 28.6% of the patients. In the three trials published, overall complication rates ranged from 7.3 to 29.1% in the TDR group and from 6.3 to 50.2% in the fusion group. The overall reoperation rate at index-level ranged from 3.7 to 11.4% in the TDR group and from 5.4 to 26.1% in the fusion group. In conclusion, there is low quality evidence that the Charité is non-inferior to the BAK cage at the 2-year follow up on the primary outcome measures. For the 5-year follow up, the same conclusion is supported only by very low quality evidence. For the ProDisc, there is very low quality evidence for contradictory results on the primary outcome measures when compared with anterior lumbar circumferential fusion. High quality randomized controlled trials with relevant control group and long-term follow-up is needed to evaluate the effectiveness and safety of TDR.

Transforaminal endoscopic surgery for symptomatic lumbar disc herniations: a systematic review of the literature

The study design includes a systematic literature review. The objective of the study was to evaluate the effectiveness of transforaminal endoscopic surgery and to compare this with open microdiscectomy in patients with symptomatic lumbar disc herniations. Transforaminal endoscopic techniques for patients with symptomatic lumbar disc herniations have become increasingly popular. The literature has not yet been systematically reviewed. A comprehensive systematic literature search of the MEDLINE and EMBASE databases was performed up to May 2008. Two reviewers independently checked all retrieved titles and abstracts and relevant full text articles for inclusion criteria. Included articles were assessed for quality and outcomes were extracted by the two reviewers independently. One randomized controlled trial, 7 non-randomized controlled trials and 31 observational studies were identified. Studies were heterogeneous regarding patient selection, indications, operation techniques, follow-up period and outcome measures and the methodological quality of these studies was poor. The eight trials did not find any statistically significant differences in leg pain reduction between the transforaminal endoscopic surgery group (89%) and the open microdiscectomy group (87%); overall improvement (84 vs. 78%), re-operation rate (6.8 vs. 4.7%) and complication rate (1.5 vs. 1%), respectively. In conclusion, current evidence on the effectiveness of transforaminal endoscopic surgery is poor and does not provide valid information to either support or refute using this type of surgery in patients with symptomatic lumbar disc herniations. High-quality randomized controlled trials with sufficiently large sample sizes are direly needed to evaluate if transforaminal endoscopic surgery is more effective than open microdiscectomy.

Augmentation of (pedicle) screws with calcium apatite cement in patients with severe progressive osteoporotic spinal deformities: an innovative technique.

Abstract Screw augmentation with calcium apatite cement (CAC) was used in seven patients with a progressive osteoporotic spinal deformity. Thirty-nine spinal segments (64 screws) were augmented: 15 anteriorly (three patients) and 24 posteriorly (five patients). Dorsally, hemilaminectomy was performed at the level of all augmented screws to rule out CAC leakage. Autogenous bone graft was applied in all patients to induce fusion. Screw augmentation failure occurred in only one patient: 1 of the 16 ventral augmented screws (5.5%) was still loose after the augmentation procedure. In three other patients, 4 out of 48 augmented dorsal screws (5.5%) showed CAC leakage at the pedicle corpus vertebra level. Pedicle wall damage was present at two levels, while at two other levels no wall damage was found during visualization. No CAC-related complications were observed perioperatively. No implant migration was observed, and fusion was observed in all cases at follow-up examination performed at a mean of 32 months after surgery.

WEE1 inhibition sensitizes osteosarcoma to radiotherapy

BackgroundThe use of radiotherapy in osteosarcoma (OS) is controversial due to its radioresistance. OS patients currently treated with radiotherapy generally are inoperable, have painful skeletal metastases, refuse surgery or have undergone an intralesional resection of the primary tumor. After irradiation-induced DNA damage, OS cells sustain a prolonged G2 cell cycle checkpoint arrest allowing DNA repair and evasion of cell death. Inhibition of WEE1 kinase leads to abrogation of the G2 arrest and could sensitize OS cells to irradiation induced cell death.MethodsWEE1 expression in OS was investigated by gene-expression data analysis and immunohistochemistry of tumor samples. WEE1 expression in OS cell lines and human osteoblasts was investigated by Western blot. The effect of WEE1 inhibition on the radiosensitivity of OS cells was assessed by cell viability and caspase activation analyses after combination treatment. The presence of DNA damage was visualized using immunofluorescence microscopy. Cell cycle effects were investigated by flow cytometry and WEE1 kinase regulation was analyzed by Western blot.ResultsWEE1 expression is found in the majority of tested OS tissue samples. Small molecule drug PD0166285 inhibits WEE1 kinase activity. In the presence of WEE1-inhibitor, irradiated cells fail to repair their damaged DNA, and show higher levels of caspase activation. The inhibition of WEE1 effectively abrogates the irradiation-induced G2 arrest in OS cells, forcing the cells into premature, catastrophic mitosis, thus enhancing cell death after irradiation treatment.ConclusionWe show that PD0166285, a small molecule WEE1 kinase inhibitor, can abrogate the G2 checkpoint in OS cells, pushing them into mitotic catastrophe and thus sensitizing OS cells to irradiation-induced cell death. This suggests that WEE1 inhibition may be a promising strategy to enhance the radiotherapy effect in patients with OS.

Discovertebral (Andersson) lesions of the spine in ankylosing spondylitis revisited

A well-known complication in patients with ankylosing spondylitis (AS) is the development of localised vertebral or discovertebral lesions of the spine, which was first described by Andersson in 1937. Since then, many different terms are used in literature to refer to these localised lesions of the spine, including the eponym ‘Andersson lesion’ (AL). The use of different terms reflects an ongoing debate on the exact aetiology of the AL. In the current study, we performed an extensive review of the literature in order to align communication on aetiology, diagnosis and management between treating physicians. AL may result from inflammation or (stress-) fractures of the complete ankylosed spine. There is no evidence for an infectious origin. Regardless of the exact aetiology, a final common pathway exists, in which mechanical stresses prevent the lesion from fusion and provoke the development of pseudarthrosis. The diagnosis of AL is established on conventional radiography, but computed tomography and magnetic resonance imaging both provide additional information. There is no indication for a diagnostic biopsy. Surgical instrumentation and fusion is considered the principle management in symptomatic AL that fails to resolve from a conservative treatment. We advise to use the term Andersson lesion for these spinal lesions in patients with AS.

Gait in Pregnancy-related Pelvic girdle Pain: amplitudes, timing, and coordination of horizontal trunk rotations

Walking is impaired in Pregnancy-related Pelvic girdle Pain (PPP). Walking velocity is reduced, and in postpartum PPP relative phase between horizontal pelvis and thorax rotations was found to be lower at higher velocities, and rotational amplitudes tended to be larger. While attempting to confirm these findings for PPP during pregnancy, we wanted to identify underlying mechanisms. We compared gait kinematics of 12 healthy pregnant women and 12 pregnant women with PPP, focusing on the amplitudes of transverse segmental rotations, the timing and relative phase of these rotations, and the amplitude of spinal rotations. In PPP during pregnancy walking velocity was lower than in controls, and negatively correlated with fear of movement. While patients’ rotational amplitudes were larger, with large inter-individual differences, spinal rotations did not differ between groups. In the patients, peak thorax rotation occurred earlier in the stride cycle at higher velocities, and relative phase was lower. The earlier results on postpartum PPP were confirmed for PPP during pregnancy. Spinal rotations remained unaffected, while at higher velocities the peak of thorax rotations occurred earlier in the stride cycle. The latter change may serve to avoid excessive spine rotations caused by the larger segmental rotations.

Titanium-Nitride Coating of Orthopaedic Implants: A Review of the Literature

Surfaces of medical implants can be enhanced with the favorable properties of titanium-nitride (TiN). In a review of English medical literature, the effects of TiN-coating on orthopaedic implant material in preclinical studies were identified and the influence of these effects on the clinical outcome of TiN-coated orthopaedic implants was explored. The TiN-coating has a positive effect on the biocompatibility and tribological properties of implant surfaces; however, there are several reports of third body wear due to delamination, increased ultrahigh molecular weight polyethylene wear, and cohesive failure of the TiN-coating. This might be due to the coating process. The TiN-coating process should be optimized and standardized for titanium alloy articulating surfaces. The clinical benefit of TiN-coating of CoCrMo knee implant surfaces should be further investigated.

Osteoid osteoma of the spine: a novel technique using combined computer-assisted and gamma probe-guided high-speed intralesional drill excision.

Study Design. A report of five cases of thoracolumbar osteoid osteoma treated with combined computer-assisted and &ggr; probe-guided high-speed drill excision. Objectives. To document the surgical technique consisting of a combination of both computer-assisted and &ggr; probe-guided high-speed drill excision for osteoid osteoma of the spine. Summary of Background Data. Curative treatment of spinal osteoid osteoma is performed by surgical intralesional excision of the nidus, but intraoperative localization of the nidus is often difficult. Although intraoperative &ggr;-probe guidance facilitates accurate localization of the nidus, wide surgical resection of the bony structure is still mandatory to ensure removal of the nidus. Computer-assisted surgery has been proven to facilitate surgical intervention in spinal surgery. However, there is no clinical report regarding the application and usefulness of computer-assisted intralesional excision of the osteoid nidus. Excision of the nidus with a computer-assisted high-speed drill and intraoperative &ggr; probe control may result in complete intralesional excision without sacrificing more bone than necessary. Methods. One day before surgery, patients were injected with radioactive 99mTc-oxidronate. With a computed tomography-based electro-optical navigation system, real-time virtual images of the osteoid osteoma were generated by matching the intraoperative surface with preoperative computed tomography images. The osteoid osteoma was excised with the use of an image-guided high-speed drill, and complete excision was controlled with a &ggr; detection probe. Results. Excision of the nidus was confirmed by relief of symptoms, postexcision computed tomography scans, and histologic evaluation on clinical and radiographic follow-up observation. All five patients reported immediate complete relief of characteristic pain and no evidence of recurrence after 6 to 33 months of follow-up observation. There were no complications. Conclusions. The combination of both computer-assisted surgery and &ggr; probe-guided high-speed drill excision for osteoid osteoma of the spine helps to localize and excise the nidus of the osteoid osteoma with minimal bone resection of the posterior spinal structures.

Dynamic and Static Overloading Induce Early Degenerative Processes in Caprine Lumbar Intervertebral Discs

Mechanical overloading of the spine is associated with low back pain and intervertebral disc (IVD) degeneration. How excessive loading elicits degenerative changes in the IVD is poorly understood. Comprehensive knowledge of the interaction between mechanical loading, cell responses and changes in the extracellular matrix of the disc is needed in order to successfully intervene in this process. The purpose of the current study was to investigate whether dynamic and static overloading affect caprine lumbar discs differently and what mechanisms lead to mechanically induced IVD degeneration. Lumbar caprine IVDs (n = 175) were cultured 7, 14 and 21 days under simulated-physiological loading (control), high dynamic or high static loading. Axial deformation and stiffness were continuously measured. Cell viability, cell density, and gene expression were assessed in the nucleus, inner- and outer annulus. The extracellular matrix (ECM) was analyzed for water, glycosaminoglycan and collagen content. IVD height loss and changes in axial deformation were gradual with dynamic and acute with static overloading. Dynamic overloading caused cell death in all IVD regions, whereas static overloading mostly affected the outer annulus. IVDs expression of catabolic and inflammation-related genes was up-regulated directly, whereas loss of water and glycosaminoglycan were significant only after 21 days. Static and dynamic overloading both induced pathological changes to caprine lumbar IVDs within 21 days. The mechanism by which they inflict biomechanical, cellular, and extracellular changes to the nucleus and annulus differed. The described cascades provide leads for the development of new pharmacological and rehabilitative therapies to halt the progression of DDD.