Introduction

Tissue diagnosis is essential to direct the definitive management of a suspected soft tissue or bone sarcoma tissue. Knowledge of both the diagnostic yield and accuracy of core needle biopsies is therefore important to give the investigating team information on the likelihood of their initial investigations achieving a diagnosis.

Purpose

The aim of this study was to investigate whether growth factors essential for fracture healing are released in the immediate aftermath following fracture and whether reaming of IM cavity causes increased liberation of these autocoids.

Purpose

The timing of definitive fixation for major fractures in polytrauma patients is controversial. To clarify this aspect of trauma management, we randomised patients with blunt multiple injuries to either initial definitive stabilisation of the femur shaft with an intramedullary nail or an external fixator which was converted to an intramedullary nail at a secondary procedure and documented the post-operative clinical condition.

The purpose of this study was to assess the effect of human autologous serum on the proliferation and differentiation of MSCs and to analyze the serum growth factor content. Serum was obtained from 8 patients suffering from lower limb long bone fractures requiring surgical intervention.

Serum samples were obtained on admission and the 1st-3rd–5th and 7th postoperative day. During the surgical procedure cancellous bone pieces from the fracture were obtained and MSCs were isolated. Cells were cultured with autologous serum from each sample. The cellular potential for proliferation and osteogenic differentiation was assessed. Fetal calf serum (FCS) was used for comparison. The presence of growth factors in the serum was investigated using commercially available colorimetric assays read on Elisa plate reader. We studied the serum content on Platelet Derived Growth Factor (PDGF), Vascular Endothelial Growth Factor (VEGF) and Insulin-like Growth Factor I (IGF-1).

The maximal upregulation of cellular proliferation and osteogenic differentiation was noted in cells cultured from serum obtained between third and seventh days. Cellular proliferation in comparison to FCS was increased by 32% with the use of serum from admission, 23% with the use of serum of the 1st day and 37% and 42% with the serum from 3rd and 7th days respectively. Serum analysis revealed an increase of 80% of PDGF between the 1st and 3rd postoperative day and 135% from 3rd–7th postoperative day. IGF-1 was increased by 35% between day 1 and 7. VEGF was increased by 120% during the first two postoperative days and a further increase of 190% occurred between days 3 and 7.

Growth factors are released in peripheral circulation and are gradually increased after fracture. MSCs under their influence proliferate faster and up-modulate their osteogenic differentiation. These findings should be considered when using functional assays for tissue regeneration techniques.

Patients with a femoral shaft fracture requiring intra-medullary nailing were recruited to investigate if the femoral canal could be a potential source of inflammatory cytokines, previously implicated in the pathogenesis of life-threatening inflammatory complications.

Femoral and peripheral blood samples were obtained at the time of surgery from patients with a femoral shaft fracture requiring intramedullary nailing. The local femoral intramedullary and peripheral release of a group of ten Th1 and Th2 cytokines concentrations (IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, GM-CSF, TNF-a and IFN-g) after femoral shaft fracture and intramedullary reaming, if performed, was measured using a Human Cytokine Antibody 10-plex Bead Kit. A control group of patients(n=3) undergoing hip replacement was established to allow comparison with the normal femoral intramedullary cytokine environment.

21 patients with a femoral shaft fracture were recruited. Femoral shaft fracture caused a significant increase in the local femoral concentrations of IL-6 (median 3967pg/ml; range 128–25,689pg/ml) and IL-8 (median 238pg/ml; range 8–8,288pg/ml) compared to the femoral control group(p=0.0005 and p=0.001 respectively). No significant local femoral release of the other cytokines was demonstrated. In the patients who underwent intramedullary reaming of the femoral canal (n=6), a further significant local release of IL-6 (median post-ream 15,903pg/ml; range 1,854–44,922pg/ml) and IL-8 (median post-ream 1,443pg/ml; range 493–3,734pg/ml) was demonstrated (p=0.01 and p=0.03 respectively), thus showing that intramedullary reaming can cause a significant local inflammatory response.

Femoral shaft fracture produces a local inflammatory response releasing large amounts of the cytokines IL-6 and IL-8 into the local femoral environment but not of the other Th1 and Th2 cytokines studied. Reaming, produced significant elevation in local femoral IL-6 and IL-8 concentration, suggesting a local femoral response as a result of this procedure. Possibly, local femoral environment may act as a cell-priming or stimulating zone, for circulating inflammatory cells.

Purpose: The aim of this study was to investigate whether growth factors essential for fracture healing are released in the immediate aftermath following fracture and whether reaming of IM cavity causes increased liberation of these autocoids.

Methods: Consecutive adult patients with femoral shaft fractures forming two groups (a group who received unreamed nail (n=10) and a second group who received reamed nail (n=10) were recruited for this study. Peripheral blood samples and samples from the femoral canal before and after reaming and before and after the solid nail insertion were collected. Serum was extracted and using Elisa colorimetric assays the concentration of Platelet Derived Growth Factor (PDGF), Vascular Endothelial Growth Factor (VEGF), Insulin-like Growth Factor I (IGF-I) Transforming Growth Factor beta 1 (TGF-²1) and BMP-2 levels was measured.

Results: In total 20 patients were studied. The mean age was 38 years (range 20–63). Reaming substantially increased all studied growth factors locally in the femoral canal. VEGF and PDGF were increased after reaming by 111.2% and 115.6% respectively. IGF-1 was increased by 31.5% and TGF-b1 was increased by 54.2%. In the unreamed group the levels of PDGF-BB, VEGF and TGF-²1 were not changed while the levels of IGF-I were decreased by 10%. The levels of these factors in peripheral circulation were not altered despite the technique used. BMP-2 levels during all time points were below the detection limit of the immunoassay.

Conclusion and Significance: This study indicates that reaming of IM Canal is associated with increased liberation of growth factors. The osteogenic effect of reaming could be secondary not only to grafting debris but also to the increased liberation of these molecules.

Purpose: Growth factors are released and circulate in peripheral blood after fracture. The purpose of this study was to characterize the early systemic release of several growth factors following accidental fractures and surgery.

Methods: 14 patients (8 male and 6 female) suffering from lower limb long bone fractures were prospectively included in the study. The mean age was 34 years (range 18-61). In all patients the time from fracture occurrence till operation was less than 24 hours. Peripheral blood samples were collected on patients’ admission, induction, and postoperatively at 1, 3 and 5 days. Serum was extracted and using Elisa colorimetric assays the concentration of Platelet Derived Growth Factor (PDGF), Vascular Endothelial Growth Factor (VEGF), Insulin-like Growth Factor I (IGF-1) and Transforming Growth Factor beta 1 (TGF-b1) was measured.

Results: From fracture occurrence till induction for surgery a substantial decreased was observed (VEGF concentration was decreased by 189%, PDGF was decreased by 363%, TGF-b1 was decreased by 247 % and IGF-1 was decreased only by 25%. Surgery itself decreased VEGF peripheral levels by a further 50% and PDGF by 40 % while IGF and TGF-b1 levels remained unchanged. During the first post-operative day the levels of VEGF were increased by 82%, TGF-b1 and IGF-1 remained constant and PDGF was further decreased by 20%. Between the 1st and 3rd postoperative days VEGF was increased by 132%, PDGF by 220% and TGF-b1 by 230 %. During this period, IGF-1 was decreased by 20 %. Finally, during the 3rd to 5th postoperative day, the levels of all growth factors continue to increase.

Conclusion: This study illustrates the early pattern of release of 4 growth factors following fractures and surgery. A substantial decreased during the first 24 hours was noted but thereafter an upward trend was observed. This data provide insight into the levels and kinetics of growth factors before and after surgery of fractures.