In countries where Confucianism is popular, it is extremely difþcult to get allograft. Twenty seven cases of limb salvage with recycled autogenous bone were performed after wide resection of malignant tumors. Recycling was done in 9 cases with pasteurization and in 18 cases with irradiation. Pasteurization was done in 60¡-30minutes with thermostatic saline bath.
Summary Statement. Combination of sorafenib with irradiation achieved synergistic effect with dose reduction in both 143B and HOS cell lines. This demonstrated the potential application of sorafenib in the treatment of osteosarcoma metastasis and radiation resistance. Introduction. More than 20% of patients with osteosarcoma die of the disease within 5 years due to tumour relapse and metastasis. Identifying new treatment that works singly or in combination with conventional therapies is urgently required. We previously found that the Ras/Raf/MAPK pathway was associated with lung metastasis in a 143B inoculated osteosarcoma orthotopic mouse model. 1. Sorafenib, a multi-kinase inhibitor, has shown potent anticancer effect including in osteosarcoma. 2. through the inhibition of Raf-1 and other targets. 3. The aims of this study were to investigate effect of sorafenib on osteosarcoma cell lines with or without activated Ras/Raf/MAPK signalling and to decide whether sorafenib could enhance irradiation on these cells. Materials and Methods. Osteosarcoma cell lines 143B (HOS with Ras gene transfection), HOS and U2OS were used. Clonogenic assay was applied for assessing tumour growth and colony formation with or without treatment. Sorefenib was provided by Bayer gratis.
Background: The late effect of ionizing radiation on the development of sarcomas within the field of radiation is referred to as Post
Extracorporeal
Haemangioendothelioma of bone is a rare intermediate grade malignancy. Because of its rareness there is a lack of information in the literature about the well established treatment strategies depending on series with large numbers. The outcome of wide resection with postoperative external irradiation would be presented. 4 patients (2 females, 2 males) with a mean age of 40.5 (26–52) with solitary haemangioendothelioma of bone admitted with local pain on the affected bone and limited restriction of function. Anatomical sites were scapula, calcaneum, midshaft of radius and metaphysodiaphyseal region of femur. Plain X-ray, CT, MRI, Tc 99 tecnetium wholebody bone scan investigations were applied. All lesions were hot on bone scan and lytic irregular permeative lesions T1 hypo, T2 hyper with gadolinium enhancement were present. Open biopsy resulted with the diagnosis of intermediate haemangioendothelioma of bone. Wide resection of tubular bones and intercalary lyophilised allograft recostruction with IM rod and cerclage wire and total calcaneum resection and allograft replacement with talar arthrodesis, total scapulectomy subsequent autoclaved bone reimplantation were the surgical procedures applied. Mean follow-up was 96 months (40–132). Three patients except scapula case received 50 Gy external irradiation. No patient developed local recurrence in the follow up. Regarding complications calcaneum patient developed skin necrosis after the irradiation which led to removal of the allograft but eventually healed. Scapula patient had late infection treated by antibiotics. All patients had satisfactory function. Intercalary allografts united in 6 months time. Calcaneum patient developed multiple small lung metastasis 1 year after the operation and treated by adriamycin based chemotherapy and interpherone. The lung lesions showed slight regression but the patient is alive since 112 months with no further relapse. Wide excision with subsequent irradiation and wide excision of total scapula resulted with no local recurrence in our small group of patients with this rare malignancy.
It is not known if the radiation sterilisation dose (RSD) of 25 kGy affects mechanical properties and biocompability of allograft bone by alteration of collagen triple helix or cross-links. Our aim was to investigate the mechanical and biological performance, cross-links and degraded collagen content of irradiated bone allografts. Human femoral shafts were sectioned into cortical bone beams (40 × 4 × 2 mm) and irradiated at 0, 5, 10, 15, 20, and 25 kGy for three-point bending tests. Corresponding cortical bone slices were used for in vitro determination of macrophage activation, osteoblast proliferation and attachment, and osteoclast formation and fusion. Subsequently, irradiated cortical bone samples were hydrolised for determination of pyridinoline (PYD), deoxypyridinoline (DPD), and pentosidine (PEN) by high performance liquid chromatography (HPLC) and collagen degradation by the alpha chymotrypsin (ï. j. CT) method.
Local antibiotics released through a carrier is a commonly used technique to prevent infection in orthopaedic procedures. An interesting carrier in aseptic bone reconstructive surgery are bone chips impregnated with AB solution. Systemically administered Cefazolin (CFZ) is used for surgical site infection prophylaxis however in vitro study showed that fresh frozen and processed bone chips impregnated with CFZ solution completely release the CFZ within a few hours. On the other hand irradiated freeze-dried bone chips, treated with supercritical CO2 (scCO2) have been shown to be an efficient carrier for the antibiotics vancomycine or tobramycine. With this pilot study we wanted to investigate if CFZ solution impregnation of bone chips treated with scCO2 shows a more favorable release pattern of CFZ. The bone chips were prepared using the standard scCO2 protocol and were impregnated with 100 mg/ml cefazolin at different timepoints during the process: before freeze drying (BC type A), after freeze drying (BC type B) and after gamma-irradiation. 0.5g of the impregnated bone grafts were incubated with 5ml of fetal calf serum (FCS) at 37°C. At 2, 4, 6, 8 and 24h of incubation 200µl of eluate was taken for analysis. After 24h the remaining FCS was removed, bone grafts were washed and new FCS (5ml) was added. Consecutive eluate samples were taken at 48, 72 and 96h of incubation. The concentration of CFZ in the eluates was measured with the validated UPLC-DAD method. Analysis was performed in triplicate.Aim
Method
To investigate the effect of polyethylene manufacturing characteristics and irradiation dose on the survival of cemented and reverse hybrid total hip arthroplasties (THAs). In this registry study, data from the National Joint Registry of England, Wales, Northern Ireland and the Isle of Man (NJR) were linked with manufacturing data supplied by manufacturers. The primary endpoint was revision of any component. Cox proportional hazard regression was a primary analytic approach adjusting for competing risk of death, patient characteristics, head composition, and stem fixation.Aims
Methods
Aseptic loosening is a major cause of revision of total joint arthroplasty (TJA). Although crosslinked Ultra-high molecular weight polyethylene (UHMWPE) have improved wear resistance, residual radicals remaining in the material have a possibility to increase bio-reactivity of particles [2]. In this study, we attempt to evaluate the effects of irradiation and residual radicals on bio-reactivity of the material with a new method called the inverse culture method [1]. UHMWPE particles (10µm diameter in average, Mitsui chemicals Co., LTD) along with irradiated particles (RAD, 300kGy electron irradiation) and particles annealed after the irradiation (RAD+ANN, 100°C 72 hours) are co-incubated with mouse macrophage cell line RAW264 using the inverse culture method. The amount of TNF-α was measured with ELISA.Introduction
Material and methods
Extracorporeal irradiation and re-implantation of a bone segment is a technique employed in bone sarcoma surgery for limb salvage in the setting of reasonable bone stock. There is neither consensus nor rationale given for the dosage of irradiation used in previous studies, with values of up to 300Gy applied. We investigated the influence of extracorporeal irradiation on the elastic and viscoelastic properties of bone. Bone specimens were extracted from mature cattle and subdivided into thirteen groups; twelve groups exposed to increasing levels of irradiation and a control group. The specimens, once irradiated, underwent mechanical testing in saline at 37°C. Mechanical properties were calculated by experimental means which included Young's Modulus, Poisson's Ratio, Dissipation Factor, Storage Modulus, Loss Modulus and Dynamic Modulus. These were all obtained for comparison of the irradiated specimens to the control group. We found there to be a statistically significant increase in Poisson's ratio after increasing irradiation doses up to 300Gy were applied. However, there was negligible change in all other mechanical properties of bone that were assessed. Therefore, we conclude that the overall mechanical effect of high levels of extracorporeal irradiation (300Gy) is minute, and can be administered to reduce the risk of malignancy recurrence.
Extracorporeal irradiation and re-implantation of a bone segment is a technique employed in bone sarcoma surgery for limb salvage in the setting of reasonable bone stock. There is neither consensus nor rationale given for the dosage of irradiation used in previous studies, with values of up to 300Gy applied. We investigated the influence of extracorporeal irradiation on the elastic and viscoelastic properties of bone. Bone specimens were extracted from mature cattle and subdivided into thirteen groups; twelve groups exposed to increasing levels of irradiation and a control group. The specimens, once irradiated, underwent mechanical testing in saline at 37°C. Mechanical properties were calculated by experimental means which included Young's Modulus, Storage Modulus and Loss Modulus. These were all obtained for comparison of the irradiated specimens to the control group. There were non-significant negligible changes in all of the mechanical properties of bone that were assessed with increasing dosage of irradiation. Therefore, we conclude that the overall mechanical effect of high levels of extracorporeal irradiation (300Gy) is minute, and can be administered to reduce the risk of malignancy recurrence.
The intensity of scattered radiation in both a forward and a backward direction from a portable fluoroscope during pinning of the neck of the femur was measured by experiments on a cadaver. The intensity decreased rapidly with increasing distance from the flare of the greater trochanter. Hazard to the surgeon's hands from scattered radiation can be greatly reduced by positioning the C-arm of the fluoroscope so that the x-ray beam is directed laterally.
The effects of gamma irradiation on the growth plate have been studied in nineteen rabbits with a 1,000 rads/skin dose. The rabbits were killed after one to ninety days. The growth plates were studied by microscopic examination, thymidine-H3 autoradiography, and fluorescence with radiographic measurement. Changes were already detected after twenty-four hours at the cell mitosis level, which showed the sensitiveness of the chondrocyte itself. The lesions were clearly seen with the optical microscope after seven days, and they were most advanced between the fourteenth and twenty-first day after irradiation. Regeneration of the cartilage began in the fourth week and the histological appearance became normal after seventy days. Fluorescence with tetracycline showed a temporary retardation of growth, with consequent shortening of the affected limb.
The foregoing suggestions may be summarised in the following recommendations for the treatment of osteogenic sarcoma. 1. Deep x-ray therapy in high dosage, followed by local resection, should be given serious trial especially: 1) in the upper limb; 2) in the group with atypical clinical or radiographic signs, or histology resembling that of inflammatory lesions; 3) with Grade I histology; and 4) in the young. 2. Deep x-ray therapy followed at once by amputation should be used for osteogenic sarcoma if : 1) local resection would leave a lower limb more unstable than an artificial leg ; or 2) if response to x-rays is poor. 3. Deep x-ray therapy alone should be used: 1) if the patient is unsuitable for, or refuses, any operation ; and 2) palliatively, if metastases are present or the tumour is too advanced, or the patient is not fit for radical treatment. 4. Amputation alone should be used palliatively, for pain or fungation, when x-ray therapy has failed to relieve, or is not readily obtainable. 5. Biopsy and histological grading must be performed in every case. A histological diagnosis is most important. Coley (1949) and MacDonald and Budd (1943) support this view. 6. The records of every possible case should be sent to and discussed by a group with special experience of these tumours.
Neglected liposarcoma with late admission and huge tumour causes difficulties regarding surgical removal, obtaining tumour free margin and increased risk of local recurrence. Preoperative irradiation enables the surgeon to remove such tumours with ease of manipulation during surgery by maturation of the pseudocapsule with a decrease in local recurrence. Twenty-one patients with liposarcoma , 8 females, 13 males with a mean age of 49 (16–74) were treated by preoperative 5000 cGy irradiation and wide excision by the same surgeon between 1991–2004. Localization were 14 proximal thigh, 3 popliteal space, 3 gluteal region, 1 upper arm. Mean tumour volume was 550cc. Mean follow up was 37 months (6–144 mo.s). All patients were operated after 30 days of irradiation, 3 patients had arterial by pass and 1 patient had free latissimus dorsi flap reconstruction.
Extracorporeal irradiation of resected bone segments has been used for pelvic reconstruction for 12 years in our unit. The technique allows for a perfect fit, preservation of muscle attachments, and thus, facilitating reconstruction, more rapid osteotomy of autograft bone, low cost, and a low infection rate. Of particular interest is its use in children; revascularisation appears more complete with irradiated autograft, as compared to allograft. There is sparing of adjacent growth plates if the irradiation is given outside the body, whereas external beam radiation would destroy the proximal femoral growth plate—leading to significant leg length discrepancy. Avoiding external beam irradiation also removes any risk of late radiation induced sarcoma and removes the late effects of soft tissue fibrosis due to external beam irradiation. Twenty-seven pelvic reconstructions have been done over a 12-year period, with three failures due to infection and seven due to further disease. Four of these have been for de-differentiated chondrosarcoma of the pelvis, where local recurrence led to failure. In the presence of de-differentiated pelvic chondrosarcoma, we do not recommend this form of reconstruction. Long term functional outcome scores for the first 50 cases completed between August 1996 and June 2003 gave a TESS score of 82% and MSTS score of 78%. This is more than comparable to published series using other forms of reconstruction.
In relation to the conduct of this study, one or more of the authors is in receipt of a research grant from a commercial source.
Acellular porcine super flexor tendon (pSFT) offers a promising solution to replacement of damaged anterior cruciate ligament [1]. It is desirable to package and terminally sterilise the acellular grafts to eliminate any possible harmful pathogens. However, irradiation techniques can damage the collagen ultra-structure and consequently reduce the mechanical properties [2]. The aims of this study were to investigate the effects of irradiation sterilisation of varying dosages on the biomechanical properties of the acellular pSFT. Tendons were decellularised using a previously established protocol [1] and subjected to irradiation sterilisation using either 30 kGy gamma, 55 kGy gamma, 34 kGy E-beam, 15 kGy gamma, 15 kGy E-beam and (15+15) kGy E-beam (fractionated dose). Specimens then underwent stress relaxation and strength testing at 0 and 12 months post sterilisation to determine whether any effect on these properties was progressive. For stress relaxation testing, specimens were analysed using a Maxwell-Wiechert model. For strength testing, the ultimate tensile strength, Young's modulus and failure strain were assessed. Significant differences were found which demonstrated that all irradiation treatments had an effect on the time-independent and time-dependent viscoelastic properties of irradiated tendons compared to per-acetic acid only treated controls. Interestingly, no significant differences were found between the irradiated groups. Similar trends were found for the strength testing properties. No significant differences were found between groups at 0 and 12 months. Tendons retained sufficient biomechanical properties following sterilisation, however it was notable that there were no significant differences between the irradiated groups, as it was believed higher dosages would lead to a greater reduction in the mechanical properties. The changes observed were not altered further after 12 months storage, indicating the acellular pSFT graft has a stable shelf-life.
We have used extracorporeal irradiation as part of the treatment of primary bone tumours since 1996. It is a technique that preserves bone stock, with no allograft cost, is tailor made for the individual and can protect the epiphyseal plates in the immature skeleton. All cases are biopsied, staged and if appropriate undergo pre-operative chemotherapy. The resected specimen is wrapped in sterile drapes, sealed and then irradiated in either the linear accelerator or a blood product irradiator. The mid-plane dose delivered to the specimens was 50 Gy. The specimen is then reimplanted using varied methods. Post-operative chemotherapy is given if indicated, and the patients have 6 weeks of antibiotics. Regular review is undertaken in the outpatients. We individually reviewed all the patients, examined them and scored their functional results according to the Mankin and Enneking Systems. The pelvic/proximal femur patients also had a Harris Hip Score recorded. There were 31 cases all over 6 months from surgery with an average follow up of 24 months. Mean age at diagnosis was 24.9 years (range 3 to 66), in 15 males and 16 females. Pathology included 10 osteosarcomas, 13 Ewing’s and 8 chondrosarcomas. Affected bones were 4 proximal humeri, 14 hemipelvises, 12 femurs and 1 tibia. Reconstruction varied from autograft alone, to autograft with a prosthesis, intramedullary nail or blade plate. 10 patients had supplementary vascularized fibula grafts and 2 pedicle flaps. There have been 4 deaths of disease, 2 alive with disease and 25 currently disease free. The Enneking scores averaged 70%, the Harris Hip Scores averaged 74 in the pelvic reconstructions and 92 in the proximal femurs.