The spine is a common site of metastasis. Complications include pathologic fracture, spinal cord compression, and neurological deficits. Vertebroplasty (VP) and Balloon Kyphoplasty (KP) are minimally invasive stabilization procedures used as a palliative treatment to improve mechanical stability, quality of life, and reduce pain. Photodynamic therapy (PDT) is a tumour-ablative modality that may complement mechanical stability afforded by VP/KP. This first-in-human study evaluates PDT safety when applied in conjunction with VP/KP.

This dose escalation trial involved one light only control group and four light-drug doses (50,100,150,200J;n=6) delivered at 150mW from a 690nm diode laser by 800-micron optical fibers prior to KP/VP. Patients eligible for VP/KP in treating pathologic fracture or at-risk lesions at a single level were recruited. Exclusion criteria included spinal canal compromise or neurologic impairment. PDT is a two-step binary therapy of systemic drug followed by intravertebral light activation. Light was applied via bone trochar prior to cementation. This study used a benzoporphyrin derivative monoacid (BPD-MA), Verteporfin (VisudyneTm), as the photosensitizer drug in the therapy. Drug/light safety, neurologic safety, generic (SF-36), and disease-specific outcomes (VAS, EORTC-QLQ-BM22, EORTC-QLQ-C15-PAL) were recorded through six weeks. Phototoxicity and the side effects of the BPD-MA were also examined following PDT use.

Thirty (10 male, 20 female) patients were treated (13 KP, 17 VP). The average age was 61 and significantly different between genders (Male 70yrs vs. Female 57yrs: p 0.05), and tumour status (lytic vs. mixed blastic/lytic: p>0.05). In most cases, fluence rates were similar throughout PDT treatment time, indicating a relatively stable treatment. Twelve (40%) of patients experienced complications during the study, none of which were attributed to PDT therapy. This included two kyphoplasty failures due to progression of disease, one case of shingles, one ankle fracture, one prominent suture, one case of constipation due to a lung lesion, one case of fatigue, and five patients experienced pain that was surgically related or preceded therapy.

Vertebral PDT appears safe from pharmaceutical and neurologic perspectives. KP/VP failure rate is broadly in line with reported values and PDT did not compromise efficacy. The 50J group demonstrated an improved response. Ongoing study determining safe dose range and subsequent efficacy studies are necessary.

Object

Giant thoracic discs (occupying more than 40% of the spinal canal) are a difficult surgical pathology. They are increasingly being recognized as or particular subset of thoracic disc pathology. It has been recommended that an aggressive surgical approach of open 2 level verteberectomy and instruments should be utilized.21 However Retropleural thoracotomy provides the shortest direct route to the anterior thoracic spine and avoids pleural cavity entry making it an ideal if infrequently used approach to access ventral thoracic and thoracolumbar spine abnormalities. We present a detailed description of our experience utilising this approach, for the treatment of Giant Thoracic discs without the need for vertebrectomy or instrumentation

The “Wallis” implant is indicated to stabilize symptomatic degenerative lumbar spine segments, relieving low back pain related to instability and thus delaying the need for irreversible, more invasive surgical management. The purpose of this study was to provide the first objective clinical evaluation of the “Wallis” lumbar dynamic stabilisation system.

An independent prospective observational study was carried out utlising SF-36, Oswestry Disability Index (ODI) and visual analogue pain scores (VAS). Surgical pathologies in which this technique was used, the intra-operative and post-operative complications and length of post-op stay were recorded. 102 patients underwent Wallis insertion between June 2007- May 2009, Median age 51.5 (range 28-108). 94% of patients completed questionnaires and were followed up at 3, 6 and 12 month time points. ODI scores decreased from pre-op 39 to 27 at twelve months (p<.0016). VAS back pain scores decreased 59 to 36 (p<0.0001). Leg scores decreased 50 to 39 (p<0.0002). SF 36 scores improved significantly, physical functioning 46 to 59, physical health 30 to 54 and social functioning 47 to 68. 50% of patients believed their health to be better 12 months post-op. Pre-operatively 28% of patients were employed and working with 26% off work due to back problems. This rate increased steadily with 42% employed at 12 months. Two implants were removed, one due to non-benefit with subsequent arthrodesis and one due to infection. One superficial wound infection occurred.

The Wallis dynamic stabilization system provides a superficial and easily reversible surgical procedure with a lower complication rate than conventional athrodesis. Used in patients with painful degenerative lumbar conditions their quality of life objectively approached values of the age- and gender-matched general population.

BACKGROUND

In our institution we use the Winklestabile volar locking plate for operative fixation of distal radius fractures. This study aims to assess subjective and objective outcomes using this method of treatment.

Impaction allografting is a bone reconstruction technique currently used in lower limb revision arthroplasty. Demineralisation and addition of osteogenic protein-1 (OP-1) can improve the osteoinductivity of the allograft however recent reports indicate significant allograft resorption when it is combined with OP-1 during impaction. Our hypothesis was that hydroxyapatite (HA) and OP-1 could effectively replace demineralised allograft. The objective was to evaluate human mesenchymal stem cell (h-MSC) proliferation (tritiated thymidine incorporation, total DNA Hoechst 33258 and scanning electron microscopy) and osteogenic differentiation (alkaline phosphatase activity) in human demineralised bone matrix (h-DBM) and HA, with or without OP-1. Cell proliferation on HA+OP-1 was significantly higher compared to HA at all time points (p< 0.05) and to DBM alone (day 1, p=0.042; day 14, p< 0.001). Cell proliferation was higher in DBM+OP-1, at all time points compared to HA+OP-1 but only in absolute values. Cell differentiation was significantly higher in HA+OP-1 compared to HA (p< 0.05) but comparable to DBM alone. Differentiation was significantly higher on DBM+OP-1 at all time points compared to HA (p< 0.05) and to HA+OP-1 (p< 0.05). HA is a potential graft expander in impaction allografting. When combined with OP-1 is comparable to DBM alone and being non absorbable may support the impacted graft in the early stages after the administration of OP-1.

Impaction allografting is a bone tissue engineering technique currently used in lower limb reconstruction orthopaedic surgery. Our hypothesis was that biological optimisation can be achieved by demineralisation and addition of osteogenic protein-1(OP-1) to the allograft. The objective of our in vitro study was to evaluate human mesenchymal stem cell (MSC) proliferation (Alamar Blue assay, titrated thymidine assay, total DNA Hoechst 33258 and scanning electron microscopy) and osteogenic differentiation (alkaline phosphatase assay) in two types of impacted carrier, namely demineralised bone matrix (DBM) and insoluble collagenous bone matrix (ICBM), with or without OP-1. The objective in vivo was to compare the osteogenic potential of impacted DBM with or without OP-1, with that of impacted fresh frozen allograft (FFA), again with or without OP-1. DBM+OP-1 optimized osteoinduction and significantly improved (p< 0.05) proliferation and differentiation in comparison to the majority of all other graft preparation in vitro. In addition DBM+OP-1 was significantly superior, with regard to osteogenesis, compared to the impacted FFA alone (p< 0.001), FFA+OP-1 (p=0.01) and DBM alone (p=0.02) in vivo. We propose that partial demineralisation and addition of OP-1 provides a good method for improving the osteoinductive properties of fresh allograft currently used in the impaction grafting technique.

Current bone grafts include allograft and autografts, both of which have limitations. Tissue engineering biotechnology has shown considerable promise in improving grafts. A competent graft material should ideally have osteoconductive and osteoinductive properties and comprise of bone forming cells and osteoinductive growth factors. In this study, we have evaluated the in vitro formation of bone and have used human demineralised bone matrix [DBM] and human insoluble collagenous matric [ICM] as scaffolds for mesenchymal stem cells [MSCs] and osteogenic protein [OP-1]. The objective was to determine whether combined addition of OP-1 and MSCs resulted in a superior bone graft substitute by improving the inherent osteoinductive property.

DBM and ICM were prepared and combined with rhOP [1.4 mg/0.25 mg of bone] and MSCs [1 x 105/ ml]. Statistically significant differences in MSC proliferation were seen between materials with and without OP-1 [P< 0.05}, n=8] in DBM on day 1, and both DBM and ICM on day 7 and 14. Enhanced osteogenic differentiation was observed in the presence of OP-1 when compared to DBM alone and on DBM and ICM with OP-1. In conclusion MSCs and OP-1 can be seeded together on DBM and ICM and Von Kossa staining and X-ray analysis confirmed in vitro de novo bone formation, with DBM + MSCs + OP-1 being more successful in this regard.

Conclusion: To date, no other study, to the author’s knowledge, has used MSCs and OP-1 together on a graft material; this funding, therefore, has very important clinical implications.

Aim: The biological activity of demineralised bone matrix (DBM) led to the discovery of bone morphogenetic proteins (BMP). OP-1 (BMP 7) is an osteoinductive protein and has been demonstrated to be capable of inducing new bone formation in rat subcutaneous tissue and in both orthotopic and heterotopic sites in primates. In this study we have investigated whether demineralisation and addition of osteogenic. protein 1 (OP-1) improves osteoinductive properties of allograft. Methods: A randomised controlled blind trial was performed in 16 rats. One group received two pellets of fresh frozen allograft; the other received two pellets of demineralised bone (DBM) intramuscularly. In each rat one pellet was treated with OP-1 (2mg/25mg of graft). The rats were sacriþced at 28 days and tissue þxed and processed for sectioning with haematoxylin and eosin for morphology and Alcian blue and Sirrus red for collagen types I, II. Qualitative observations were made and each specimen graded 0–5 on the degree of new bone formation and integration by two blind observers. Results & Conclusions: DBM with OP-1 yielded optimal results, being signiþcantly superior to allograft alone and allograft with OP-1. DBM alone was shown to be more effective compared to the allograft preparations. Hence we have shown that demineralization and OP-1 signiþcantly improve the osteoinductive properties of allograft

Aim:. The objective of this study was to improve the osseoinductive capacity of human demineralised bone matrix (DBM) and human insoluble collagenous matrix (ICM), following incorporation of recombinant human osteogenic protein 1 (rhOP-1) and human mesenchymal stem cells (MSCs). Ethical Committee approval has been obtained by our Institution. Methods: Recombinant human osteogenic protein Ð 1 (400ng/0.25g of bone) was seeded onto DBM and ICM together with human MSCs (1 x 105). Cellular proliferation was quantitatively evaluated in vitrousing Alamar Blue and 3H-TdR assays. Quantitative cellular differentiation was assessed using the alkaline phosphatase assay. Von Kossa staining, X-ray analysis, and PCR were used for qualitative evaluation of cellular differentiation. Qualitative analysis of proliferation and differentiation was assessed using scanning electron microscopy (SEM). Results: MSC proliferation and differentiation down the osteogenic lineage was observed on DBM and ICM in the presence of OP-1, and also on DBM alone. Alamar blue and 3H-TdR assays conþrmed that MSC proliferation occurred on both DBM and ICM, with the values being signiþcantly greater with addition of OP-1. The ALP activity showed that MSCs differentiated into osteo-blasts on DBM alone, and on DBM and ICM with OP-1. In all cases, OP-1 had a signiþcant effect on MSCs. Discussion: DBM and ICM when seeded with MSCs and OP-1 provide an improved osteoconductive and osteoinductive graft material resulting in de novo-bone formation.