B.J. van Royen

Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature

Treating metastatic osteosarcoma (OS) remains a challenge in oncology. Current treatment strategies target the primary tumour rather than metastases and have a limited efficacy in the treatment of metastatic disease. Metastatic cells have specific features that render them less sensitive to therapy and targeting these features might enhance the efficacy of current treatment. A detailed study of the biological characteristics and behaviour of metastatic OS cells may provide a rational basis for innovative treatment strategies. The aim of this review is to give an overview of the biological changes in metastatic OS cells and the preclinical and clinical efforts targeting the different steps in OS metastases and how these contribute to designing a metastasis directed treatment for OS.

Effect of integrated care for sick listed patients with chronic low back pain: economic evaluation alongside a randomised controlled trial

Objective To evaluate the cost effectiveness, cost utility, and cost-benefit of an integrated care programme compared with usual care for sick listed patients with chronic low back pain. Design Economic evaluation alongside a randomised controlled trial with 12 months’ follow-up. Setting Primary care (10 physiotherapy practices, one occupational health service, one occupational therapy practice) and secondary care (five hospitals) in the Netherlands, 2005-9. Participants 134 adults aged 18-65 sick listed because of chronic low back pain: 66 were randomised to integrated care and 68 to usual care. Interventions Integrated care consisted of a workplace intervention based on participatory ergonomics, with involvement of a supervisor, and a graded activity programme based on cognitive behavioural principles. Usual care was provided by general practitioners and occupational physicians according to Dutch guidelines. Main outcome measures The primary outcome was duration until sustainable return to work. The secondary outcome was quality adjusted life years (QALYs), measured using EuroQol. Results Total costs in the integrated care group (£13u2009165, SD £13u2009600) were significantly lower than in the usual care group (£18u2009475, SD £13u2009616). Cost effectiveness planes and acceptability curves showed that integrated care was cost effective compared with usual care for return to work and QALYs gained. The cost-benefit analyses showed that every £1 invested in integrated care would return an estimated £26. The net societal benefit of integrated care compared with usual care was £5744. Conclusions Implementation of an integrated care programme for patients sick listed with chronic low back pain has a large potential to significantly reduce societal costs, increase effectiveness of care, improve quality of life, and improve function on a broad scale. Integrated care therefore has large gains for patients and society as well as for employers.

The use of free vascularised bone grafts in spinal reconstruction

The use of free vascularised bone grafts (FVBGs) is an infrequently performed surgical technique for the reconstruction of spinal defects. This field of surgery brings many challenges concerning choice of FVBG, planning of the operative procedure and selection of recipient vessels. This study aims to report our experience with FVBGs, with special emphasis on the planning and surgical technique. Over a period of 10 years (1994-2004), we used FVBG for anterior spinal reconstruction in 23 patients. In 21 patients, a free vascularised fibular graft was used, and in two cases a free vascularised iliac crest graft was used. The spinal segments reconstructed involved the cervical spine (4 cases), the thoracic spine (13 cases) and the thoraco-lumbar and lumbo-sacral spine (6 cases). Re-vascularisation of the FVBG proved to be technically feasible in 22 patients, but failed in one fibular graft due to difficulties with recipient vessels in the lumbar spine. When necessary, the fibula was osteotomized and folded in a double-, triple- or quadruple-barrel construction to increase the strength of the reconstruction. Technical challenges were met with respect to the choice of the recipient vessel at various anatomical sites. The use of FVBG is a valuable technique for the reconstruction of complex spinal disorders. Successful execution requires microvascular expertise with respect to graft harvesting and appropriate choice of recipient vessels. Adequate preoperative planning in a multidisciplinary setting and adherence to the basic principles for spinal reconstruction are required.

Resorbability of rigid beta-tricalcium phosphate wedges in open-wedge high tibial osteotomy: A retrospective radiological study

The open-wedge high tibial osteotomy (OWHTO) is a well accepted treatment modality for patients with osteoarthritis of the medial compartment associated with genu varum. To fill in the osteotomy gap 30% macroporosity rigid beta-tricalcium phosphate (beta-TCP) is frequently used as a stable resorbable bone substitute. However, the resorbability of these beta-TCP wedges is not known. The aim of this study was to investigate this. Twenty-one OWHTO procedures in seventeen patients were performed with the use of 30% macroporosity rigid beta-TCP wedges. The osteotomies were fixed using an angle-stable locking plate. Conventional AP and lateral radiographs were examined in order to assess the resorbability of the 30% macroporosity rigid beta-TCP wedges as a function of time. A radiological classification system consisting of five phases was used to monitor the resorption of the 30% macroporosity rigid beta-TCP wedges. The mean duration of follow-up was 62 months (+/-23 range of 28-99). In all 21 cases, remnants of the 30% macroporosity rigid beta-TCP wedges were still present at maximum follow-up. Although the boundaries between 30% macroporosity rigid beta-TCP wedges and bone remained slightly visible, all osteotomies were completely consolidated and full osseointegration took place. In 16 out of 21 knees the fixation system was removed after a mean duration of 32 months (+/-19 range of 6-62). In six out of 21 knees a conversion to a knee arthroplasty was performed after a mean duration of 56 months (+/-18 range of 37-82). The OWHTO did not interfere with the placement of knee prostheses. Complete resorption of 30% macroporosity rigid beta-TCP wedges did not take place up to 8 years after operation.

Transpedicular wedge resection osteotomy for the treatment of a kyphotic Andersson lesion-complicating ankylosing spondylitis

Two cases with a long-standing thoracolumbar kyphosis due to ankylosing spondylitis are presented with a symptomatic localized destructive kyphotic lesion of the spine. Clinical and radiographic findings demonstrated a progressive vertebral and discovertebral kyphotic pseudarthrosis, known as an Andersson lesion, at the L1 and L1-2 level, respectively. Surgical correction and stabilization was performed by an extending transpedicular wedge resection osteotomy to restore spinal stability, to facilitate fracture healing as well as to restore the sagittal balance of the ankylosed spine. To predict the effect of a surgical correction of the Andersson lesion on the sagittal balance, deformity planning was performed preoperatively. The indication for surgery, the surgical technique and the 2xa0years’ clinical results are described. In addition, the difficulties experienced with preoperative deformity planning are evaluated.

Prolonged treatment with the Pavlik harness in infants with developmental dysplasia of the hip

We prospectively studied the benefits and risks of prolonged treatment with the Pavlik harness in infants with idiopathic developmental dysplasia of the hip. Bracing was continued as long as abduction improved. It was started at a mean age of four months (1 to 6.9). Outcome measures were the number of successful reductions, the time to reduction, the acetabular index and evidence of avascular necrosis at follow-up at one year. In 50 infants with 62 subluxated and dislocated hips (42 Graf type III and 20 type IV), 37 were reduced successfully with a mean time to reduction of 13.4 weeks (sd 6.8). Bracing was successful in 31 type-III (73.8%) and in only six type-IV hips (20%, p = 0.002). Avascular necrosis was seen in ten hips. Prolonged treatment with the Pavlik harness for developmental dysplasia of the hip over the age of one month can be beneficial in type-III hips, but it is unclear as to whether this is the optimal treatment, since it may postpone the need for closed or open reduction to a more unfavourable age. The use of the Pavlik harness in type-IV hips in this age group is questionable, but if used, prolonged bracing is not advised.

Slipped capital femoral epiphysis and its association with endocrine, metabolic and chronic diseases: a systematic review of the literature

PurposePuberty, obesity, endocrine and chronic systemic diseases are known to be associated with slipped capital femoral epiphysis (SCFE). The mechanical insufficiency of the physis in SCFE is thought to be the result of an abnormal weakening of the physis. However, the mechanism at the cellular level has not been unravelled up to now.MethodsTo understand the pathophysiology of endocrine and metabolic factors acting on the physis, we performed a systematic review focussing on published studies reporting on hormonal, morphological and cellular abnormalities of the physis in children with SCFE. In addition, we looked for studies of the effects of endocrinopathies on the human physis which can lead to cause SCFE and focussed in detail on hormonal signalling, hormone receptor expression and extracellular matrix (ECM) composition of the physis. We searched in the PubMed, EMBASE.com and The Cochrane Library (via Wiley) databases from inception to 11th September 2012. The search generated a total of 689 references: 382 in PubMed, 232 in EMBASE.com and 75 in The Cochrane Library. After removing duplicate papers, 525 papers remained. Of these, 119 were selected based on titles and abstracts. After excluding 63 papers not related to the human physis, 56 papers were included in this review.ResultsActivation of the gonadal axis and the subsequent augmentation of the activity of the growth hormone–insulin-like growth factor 1 (GH-IGF-1) axis are important for the pubertal growth spurt, as well as for cessation of the physis at the end of puberty. The effects of leptin, thyroid hormone and corticosteroids on linear growth and on the physis are also discussed. Children with chronic diseases suffer from inflammation, acidosis and malnutrition. These consequences of chronic diseases affect the GH-IGF-1 axis, thereby, increasing the risk of the development of SCFE. The risk of SCFE and avascular necrosis in children with chronic renal insufficiency, growth hormone treatment and renal osteodystrophy remains equivocal.ConclusionsSCFE is most likely the result of a multi-factorial event during adolescence when height and weight increase dramatically and the delicate balance between the various hormonal equilibria can be disturbed. Up to now, there are no screening or diagnostic tests available to predict patients at risk.

Giant cell tumors of the sacrum—a nationwide study on midterm results in 26 patients after intralesional excision

PurposeEvaluation of recurrences, complications and function at mid-term follow-up after curettage for sacral giant cell tumor (GCT).MethodsWe retrospectively studied all 26 patients treated for sacral GCT in the Netherlands (from 1990 to 2010). Median follow-up was 98 (6–229) months. All patients underwent intralesional excision, 21 with local adjuvants, 5 radiotherapy, 3 IFN-α, 1 bisphosphonates. Functional outcome was assessed using Musculoskeletal Tumor Society (MSTS) score. Statistics were performed with Kaplan–Meier, Cox regression, log rank and Mann–Whitney U.ResultsRecurrence rate was 14/26 after median 13 (3–139) months and was highest after isolated curettage (4/5). Soft tissue masses >10xa0cm increased recurrence risk (HRxa0=xa03.3, 95xa0% CIxa0=xa00.81–13, pxa0=xa00.09). Complications were reported in 12/26 patients. MSTS was superior in patients without complications (27 vs. 21; pxa0=xa00.024).ConclusionRecurrence rate for sacral GCT was highest after isolated curettage, indicating that (local) adjuvant treatment is desired to obtain immediate local control. Complications were common and impaired function.

Relation between radiological assessment and biomechanical stability of lumbar interbody fusion in a large animal model

PurposeTo relate the progress of vertebral segmental stability after interbody fusion surgery with radiological assessment of spinal fusion.MethodsTwenty goats received double-level interbody fusion and were followed for a period of 3, 6 and 12xa0months. After killing, interbody fusion was assessed radiographically by two independent observers. Subsequently, the lumbar spines were subjected to four-point bending and rotational deformation, assessed with an optoelectronic 3D movement registration system. In addition, four caprine lumbar spines were analysed in both the native situation and after the insertion of a cage device, as to mimic the direct post-surgical situation. The range of motion (ROM) in flexion/extension, lateral bending and axial rotation was analysed ex vivo using a multi-segment testing system.ResultsSignificant reduction in ROM in the operated segments was already achieved with moderate bone ingrowth in flexion/extension (71xa0% reduction in ROM) and with only limited bone ingrowth in lateral bending (71xa0% reduction in ROM) compared to the post-surgical situation. The presence of a sentinel sign always resulted in a stable vertebral segment in both flexion/extension and lateral bending. For axial rotation, the ROM was already limited in both native and cage inserted situations, resulting in non-significant differences for all radiographic scores.DiscussionIn vivo vertebral segment stability, defined as a significant reduction in ROM, is achieved in an early stage of spinal fusion, well before a radiological bony fusion between the vertebrae can be observed. Therefore, plain radiography underestimates vertebral segment stability.

Basilar impression in osteogenesis imperfecta: can it be treated with halo traction and posterior fusion?

SummaryBasilar impression (BI) and hydrocephalus complicating osteogenesis imperfecta (OI) is usually treated by anterior transoral decompression and posterior fixation. Nevertheless, it may be questioned if posterior fusion following axial halo traction is adequate in patients with symptomatic BI complicating OI. We report on a case with progressive symptomatic hydrocephalus and BI complicating OI that was successfully treated by halo traction followed by posterior occipitocervical fusion. However, after a symptom free interval of 2 years the patient suffered from recurrence of symptomatic hydrocephalus needing additional ventriculoperitoneal (VP) shunt placement. In conclusion, posterior fusion without additional VP shunt placement may not be effective in the long term for ameliorating symptoms and signs and halting progressive hydrocephalus in BI complicating OI.