Introduction. Major trauma during military conflicts involve heavily contaminated open fractures. Staphylococcus aureus (S. aureus) commonly causes infection within a protective biofilm. Lactoferrin (Lf), a natural milk glycoprotein, chelates iron and releases bacteria from biofilms, complimenting antibiotics. This research developed a periprosthetic biofilm infection model in rodents to test an Lf based lavage/sustained local release formulation embedded in Stimulin beads. Method. Surgery was performed on adult rats and received systemic Flucloxacillin (Flu). The craniomedial tibia was exposed, drilled, then inoculated with S. aureus biofilm. A metal pin was placed within the medullary cavity and treatments conducted. Lf in lavage solutions: The defect was subject to 2× 50 mL lavage with 4 treatment groups (saline only, Lf only, Bactisure with Lf, Bactisure with saline). Lf embedded in Stimulin beads: 4 bead types were introduced (Stimulin only, Lf only, Flu only, Lf with Flu). At day 7, rats are processed for bioluminescent and X-ray imaging, and tibial explants/pins collected for bacterial enumeration (CFU). Results. Rats without treatments established a mean infection of 2×106 CFU/tibia. 4 treatment groups with a day 0, one-off lavage demonstrated >95% reduction in bacterial load 7 days post-op, with a reduction in CFU from 1×106/tibia down to 1×104/tibia. There was no statistically significant difference between each group (p = 0.55 with one way ANOVA). The stimulin bead experiments are ongoing and complete results will be obtained in the end of July. Conclusions. This research demonstrated a clinically relevant animal model of implanted metalware that establishes infection. No additional benefit was observed with a one-off, adjuvant Lf lavage during the initial decontamination of the surgical wound, compared with saline alone, and in combination with the antiseptic Bactisure. This animal model provides the foundation for future antibiofilm therapies

We performed this systematic overview on the overlapping meta-analyses that analyzed autologous platelet-rich plasma (PRP) as an adjuvant in the repair of rotator cuff tears and identify the studies which provide the current best evidence on this subject and generate recommendations for the same. We conducted independent and duplicate electronic database searches in PubMed, Web of Science, Scopus, Embase, Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects on September 8, 2021, to identify meta-analyses that analyzed the efficacy of PRP as an adjuvant in the repair of rotator cuff tears. Methodological quality assessment was made using Oxford Levels of Evidence, AMSTAR scoring, and AMSTAR 2 grades and used the Jadad decision algorithm to generate recommendations. 20 meta-analyses fulfilling the eligibility criteria were included. The AMSTAR scores of the included studies varied from 6–10 (mean:7.9). All the included studies had critically low reliability in their summary of results due to their methodological flaws according to AMSTAR 2 grades. The initial size of the tear and type of repair performed do not seem to affect the benefit of PRPs. Among the different preparations used, leucocyte poor (LP)-PRP possibly offers the greatest benefit as a biological augment in these situations. Based on this systematic overview, we give a Level II recommendation that intra-operative use of PRPs at the bone-tendon interface can augment the healing rate, reduce re-tears, enhance the functional outcomes and mitigate pain in patients undergoing arthroscopic rotator cuff repair

Various chemicals are commonly used as adjuvant treatment to surgery for giant-cell tumour (GCT) of bone. The comparative effect of these solutions on the cells of GCT is not known. In this study we evaluated the cytotoxic effect of sterile water, 95% ethanol, 5% phenol, 3% hydrogen peroxide (H. 2. O. 2. ) and 50% zinc chloride (ZnCI. 2. ) on GCT monolayer tumour cultures which were established from six patients. The DNA content, the metabolic activity and the viability of the cultured samples of tumour cells were assessed at various times up to 120 hours after their exposure to these solutions. Equal cytotoxicity to the GCT monolayer culture was observed for 95% ethanol, 5% phenol, 3% H. 2. O. 2. and 50% ZnCI. 2. The treated samples showed significant reductions in DNA content and metabolic activity 24 hours after treatment and this was sustained for up to 120 hours. The samples treated with sterile water showed an initial decline in DNA content and viability 24 hours after treatment, but the surviving cells were viable and had proliferated. No multinucleated cell formation was seen in these cultures. These results suggest that the use of chemical adjuvants other than water could help improve local control in the treatment of GCT of bone

Aim. The management of PJIs is slowed down by the presence of bacteria forming biofilms where they may withstand antibiotic therapy. The use of adjuvant strategies, such as hydrolytic enzymes cocktail targeting biofilm matrices and facilitating their dispersion, is a promising option to limit impact of biofilms. Our aim was to evaluate the effect of enzymes cocktail combined with antibiotic dual therapy of rifampicin and vancomycin in a relevant in-vitro model. Method. Mature methicillin-resistant Staphylococcus aureus biofilms were grown on Ti-6Al-4V coupons by adding 1mL of a 8Log10 ATCC 33591 suspension in TGN (TSB + 1% glucose + 2% NaCl) to 24-wells plates containing the coupons and incubating the plates for 24h at 37°C with a continuous 50rpm agitation. The samples were rinsed and placed in 6 wells plates containing 1ml of the enzymatic cocktail (C.D.D.) solution (tris-buffered (pH 7.0) solution of 400 U/ml of aspecific DNA/RNA endonuclease, 50 U/ml of endo-1,4-b-D-glucanase, and 0.06 U/ml of β-N-acetylhexosaminidase). 9ml of TGN or TGN containing antibiotics RIF/VAN (rifampicin 5µg/mL + vancomycin 8µg/mL) at clinically relevant concentrations found locally in bone or joints, was then added and the samples were incubated in identical conditions for 24h. The samples were then recovered and rinsed. CFU counts were obtained by recovering the bacteria with sonication, serial dilutions, and TSA plating. Biomass was determined via crystal violet staining, followed by dye solubilization in acetic acid, and absorbance measurement using a spectrophotometer. Results. Significant reductions in bacterial counts were observed in biofilms exposed to either RIF/VAN or RIF/VAN+CDD, by respectively 2,6 and 3,7Log10 when compared to samples reincubated with TGN alone (p <0.05). Additionally, CFU counts in samples exposed to RIF/VAN+CDD were reduced by 1,1Log10 when compared to those exposed to RIF/VAN (p<0,05). Significant reduction in biomass (-29,8%, p<0.05) was observed for coupons exposed to RIF/VAN+CDD when compared to C.D.D alone (figure 1). Conclusions. The concurrent utilization of enzymes with rifampicin and vancomycin, holds promise as a feasible method to address periprosthetic joint infections (PJIs). For any tables or figures, please contact the authors directly

Introduction. Management of open fractures is challenging and requires a multidisciplinary team approach. Gustilo Anderson Type IIIB fractures reportedly have a higher infection rate (up to 52%) and up to 16% amputation rate. This study aims to evaluate outcomes of using Adjuvant Local Antibiotic Hydroxyapatite Bio-Composite in management of Open Gustilo-Anderson IIIB fractures. Materials and Methods. We reviewed a prospective data of 80 patients who presented with Gustilo Anderson Type IIIB Open Fracture to a single ortho-plastic centre. Only patients who were managed with single-stage “Fix and Flap” along with intra-operative Adjuvant Local Antibiotic Bio-Composite were included. Results. Mean follow-up time was 22 months. The mean time from injury until definitive surgery was 7.73 days (1–30 days). Primary union achieved in 88.3% within 32 weeks on average. The delayed union reported in 7.8% of patients, for the bone healing stimulated by injecting the fracture site with Autologous Bone Marrow Aspirate Concentrate. Subsequent follow-up showed signs of successful fracture healing at 60 weeks post-injury. Three patients (3.9%) had non-union. Limb salvage rate was 96.25%, and only 1.25% deep infection rate. Conclusions. Our results highlight that low infection rates, high limb salvage rates and high union rates can be achieved in these complex injuries with a combined OrthoPlastic approach, MDT input, meticulous technique and the use of adjuvant local antibiotic bio-composite. Delay in definitive surgery, gentamicin resistance and smoking were not associated with any increased deep infection or non-union in our series. At 22 months of follow-up, deep infection rate was 1.25%, limbs salvage rate was 96.25%, fracture union rate was 96.1%, and reoperation rate 18.75%

Aims. Intra-articular . 90. Yttrium (. 90. Y) is an adjunct to surgical treatment by synovectomy for patients with diffuse-type tenosynovial giant-cell tumour (dtTGCT) of the knee, with variable success rates. Clinical information is, however, sparse and its value remains unclear. We investigated the long-term outcome of patients who underwent synovectomy with and without adjuvant treatment with . 90. Yttrium. Patients and Methods. All patients with dtTGCT of the knee who underwent synovectomy between 1991 and 2014 were included in the study. Group A patients underwent synovectomy and an intra-articular injection of . 90. Yttrium between six and eight weeks after surgery. Group B patients underwent surgery alone. Results. There were 34 patients in group A and 22 in group B. Recurrence of dtTGCT was identified by MRI, which was undertaken in patients with further symptoms. At a mean follow-up of 7.3 years (2.5 to 25.4), there was residual disease in 15 patients in group A and 11 in group B (p < 0.363). The mean Musculoskeletal Tumor Society (MSTS) score at final follow-up was 85% and 83%, respectively (p < 0.91). Conclusion. There were no significant differences in outcome between patients treated surgically for dtTGCT of the knee with or without an adjuvant intra-articular injection of . 90. Yttrium. We were unable to provide conclusive evidence of any benefits derived from the adjuvant treatment. Cite this article: Bone Joint J 2018;100-B:984–8

Introduction. Sacro-coccygeal chordomas pose a difficult diagnostic and therapeutic problem due to late presentation, large size, soft-tisue extension, difficulties in obtaining adequate resection margins, higher local recurrence rate and uncertain effectiveness of adjuvant treatment. We present a series of 21 patients of sacral chordomas obtained from Scottish Bone Tumour Registry to analyse predictors of local control and survival. Patients and methods. The clinical and morphologic features, type of treatment and follow-up of 21 consecutive patients with sacral chordoma were retrospectively reviewed and analysed. Results. The average age at time of the biopsy was 59 years (range, 12 to 82 years): twelve patients were male and nine were female. Pain was the presenting symptom in all patients. Two had intralesional (both recurred), 9 marginal (4 recurred) and 3 wide resections (1 recurred). Fifteen of the twenty-one patients were treated with adjuvant radiation therapy. In seven patients, the chordoma was inoperable and all but one were treated with adjuvant radiotherapy. Local recurrence and metastases occurred in 7 (50%) and 5 (23.8%) patients. The 5-year and 10-year survival were 38% and 14.2%, respectively. Conclusion. Excision of the lesion combined with adjuvant radiation therapy provided satisfactory results. Local recurrence presents a major problem in the management of sacral chordomas (50%). Intralesional resection should be avoided as it is associated with 100% local recurrence in our series

Sacro-coccygeal chordomas pose a difficult diagnostic and therapeutic problem due to late presentation, large size, soft-tisue extension, difficulties in obtaining adequate resection margins, higher local recurrence rate and uncertain effectiveness of adjuvant treatment. We present a series of 21 patients of sacral chordomas obtained from Scottish Bone Tumour Registry to analyse predictors of local control and survival. The clinical and morphologic features, type of treatment and follow-up of 21 consecutive patients with sacral chordoma were retrospectively reviewed and analysed. The data were obtained from Scottish Bone Tumour Registry. The average age at time of the biopsy was 59 years (range, 12 to 82 years): twelve patients were male and nine were female. Pain was the presenting symptom in all patients. Two had intralesional (both recurred), 9 marginal (4 recurred) and 3 wide resections (1 recurred). Fifteen of the twenty-one patients were treated with adjuvant radiation therapy. In seven patients, the chordoma was inoperable and all but one were treated with adjuvant radiotherapy. Local recurrence and metastases occurred in 7 (50%) and 5 (23.8%) patients. The 5-year and 10-year survival were 38% and 14.2%, respectively. Excision of the lesion combined with adjuvant radiation therapy provided satisfactory results. Local recurrence presents a major problem in the management of sacral chordomas (50%). Intralesional resection should be avoided as it is associated with 100% local recurrence in our series

Introduction. Tomita En-bloc spondylectomy (TES) of L5 is one of the most challenging spinal surgical techniques. A 42-year-old female was referred with low back pain and L5 radiculopathy with background of right shoulder excision of liposarcoma. CT-PET confirmed a solitary L5 oligometastasis. MRI showed thecal sac indentation and therefore was not suitable for stereotactic ablative radiotherapy (SABR) alone. Planning Methodology. First Stage: Carbon fibre pedicle screws were planned from L2 to S2AI-Pelvis, aligned to her patient-specific rods. Custom 3D-printed navigation guides were used to overcome challenging limitations of carbon instruments. Radiofrequency ablation (RFA) of L5 pedicles prior to osteotomy was performed to prevent sarcoma cell seeding. Microscope-assisted thecal sac-tumour separation and L5 nerve root dissection was performed. Novel surgical navigation of the ultrasonic bone cutter assisted inferior L4 and superior S1 endplate osteotomies. Second stage: We performed a vascular-assisted retroperitoneal approach to L4-S1 with protection of the great vessels. Completion of osteotomies at L4 and S1 to en-bloc L5: (L4 inferior endplate, L4/5 disc, L5 body, L5/S1 disc and S1 superior endplate). Anterior reconstruction used an expandable PEEK cage obviating the need for a third posterior stage. Reinforced with a patient-specific carbon plate L4-S1 promontory. Sacrifice of left L5 nerve root undertaken. Results. Patient rehabilitated well and was discharged after 42 days. Patient underwent SABR two months post-operatively. Despite left foot drop, she was walking independently 9 months post-operatively. Conclusion. These challenging cases require a truly multi-disciplinary team approach. We share this technique for a dual stage TES and metal-free construct with post adjuvant SABR for maximum local control

Synovial sarcoma (SS) is rare but increasingly diagnosed and associated with poor prognosis. Primary surgical resection with wide margins and adjuvant radiation-therapy is considered gold standard in treatment of primary SS. Although (Neo)adjuvant chemo- and radiationtherapy are used in the primary treatment of SS, they are not advocated outside a clinical trial setting. In patients with primary SS and pulmonary metastases, (neo)adjuvant chemotherapy is often added to the treatment protocol but it’s effect on overall survival seems limited. Between 1985 and 2004 33 patients with primary SS were treated in our clinic. Seventeen patients were diagnosed with pulmonary metastases at presentation (9) or during postoperative follow-up (8). Wide resection or focally marginal resection followed by radiotherapy was used as primary treatment for all patients. All primary metastasized patients were treated with adjuvant multi-agent chemotherapy including Isofosfamide. Average survival in this group was 32 months (5 year OS 50%), compared to 60 months in the late metastasized patient-group (2 and 5 year OS 50 and 11%). Wide resection was not related to improved overall survival when compared to marginal margins and additional radiation therapy. In the early metastasized group combined chemo-radiaton therapy provided no significant improvement in overall survival over adjuvant chemotherapy or radiation therapy alone. However additional chemotherapy in the late metastasized group was slightly associated with increased overall survival (5 year OS 0% vs 66%). Treatment of early pulmonary metastasized SS remains highly dependent of the individual preference of patient and physician. In contrast to the reported prolonged disease free/overall survival of Enneking stage IIA and IIB SS patients, aggressive surgical and chemo-radiation therapy has not yet been associated with improvement of disease free/overall survival in stage III disease. Patients presenting with late pulmonary metastasis might benefit from adjuvant multi-agent chemotherapy treatment

Purpose: Prolonged denervation resulting from deferred nerve repair or long distance between the muscle and the repaired nerve, leads to major alterations concerning muscle fibre degeneration and their replacement by fibrous or fatty tissue. These structural modifications of the muscle are unfavourable for reinnervation and consequently affect the final functional outcome after peripheral nerve repair with its corollary of reduced muscle force. The purpose of this work was to assess the potential for regeneration of denervated-reinnervated muscles and their improvement with adjuvant cell therapy using in situ transfer of cultured autologus satellite cells. Material and methods: This work was conducted with the tibialis anterior muscle in different groups of New Zealand rabbits. The experimental model was a sectioned common fibular nerve and immediate or deferred (two months) microsurgical nerve suture. In vivo functional measurements and histomorphological analyses were performed four months after nerve repair. Results: Reinervation led to loss of mucle weight and maximal force (Fmax) which were greater with longer deferral of repair. Transfer of satellite cells performed immediately after reinervation did not improve muscle properties. Conversely, transfer of satellite cells two months after nerve suture increased Fmax 25% (p < 0.01) and muscle weight 28% (p = 0.005) in comparison with control muscles undergoing reinervation without cell transfer. Furthermore, the morphology of the muscle was improved as demonstrated by anti-myosine labelling studies. Discussion: Adjuvant cell therapy allows, in certain conditions, an improvement in functional recovery after peripheral nerve injury. Its clinical application still raises a certain number of ethical issues but taking into consideration data currently available, it would be reasonable to propose this therapeutic approach in humans to reduce involution of the denervated muscle and improve its receptivity for regenerating axons after peripheral nerve repair. Better post-operative results could be expected

Introduction: Diffused pigmented villonodular synovitis (PVNS) is a locally aggressive lesion for which surgery provides only marginal resection. An adjuvant treatment modality is therefore required to prevent local tumor recurrence. The authors describe their experience with intra-articular injection of Yttrium. 90. (Y. 90. ), a radioisotope, as an adjuvant for tumor resection. Materials and Methods: Between 1989 and 2002, 20 patients with diffuse PVNS were treated with post-operative, intraarticular injection of Y. 90. There were 15 male and 5 female patients who ranged in age from 13 to 67 years (mean, 35 years). Anatomic locations of the affected joints included: knee – 15, ankle – 4, hip – 1. Tumor resection was initially done in all patients: 13 patients required open arthrotomy, the remaining 7 underwent arthroscopic tumor resection. Ten patients were referred for treatment after having operation for a local tumor recurrence: 6 patients had one, 2 had two, 1 had three, and the remaining one had five local recurrences. Six to eight weeks after surgery, intraarticular injection of 15–25 mCi of Y. 90. was done. These procedures were conducted in the operating room under local anesthesia and fluoroscopic guidance. All patients were followed for a minimum of two years (range, 25–168 months; mean, 65 months). Results: Following Y. 90. injection, all patients reported mild pain around the affected joint. This pain was well controlled with the use of NSAID’s and typically resolved within a few days or weeks. Three patients had superficial skin inflammation and associated blisters around the site of injection, probably the result of Y. 90. effect on the soft-tissues. All were treated conservatively with complete resolution of their symptoms. All patients gained their pre-injection range-of-motion within 4–6 weeks. At the most recent follow-up, five patients had transient post-radiation skin changes (discoloration of the skin and dry and scaly skin) and local recurrence occurred in only one patient (5%) with PVNS around the knee; additional Y. 90. injections were unsuccessful and he eventually underwent knee arthrodesis. Conclusion: Y. 90. injection is a reliable adjuvant for surgery in the management of diffused PVNS. Local tumor control and good function, associated with only mild morbidity are achieved in the majority of the patients

Aim. We describe a case series using adjuvant calcium sulphate bio composites with antibiotics in treating infected metalwork in the foot and ankle. Method. 11 patients aged 22–81 (9 males, 2 females) were treated with clinical evidence of infected limb metal work from previous orthopaedic surgery. Metal work removal with intra osseous application of either cerement in 8 cases (10–20ml including 175mg–350mg gentamycin) or stimulan in 3 cases (5–12ml including 1g vancomycin) into the site was performed. Supplemental systemic antibiotic therapy (oral/intravenous) was instituted based on intraoperative tissue culture and sensitivity. Results. 7 patients had infected ankle metalwork, 2 had infected foot metalwork and 2 had infected external fixators. Metal work was removed in all cases. Mean pre operative CRP was 25.4 mg/l (range 1–137mg/l). Mean postoperative CRP at 1 week was 15.4mg/l (range 2–36mg/l) and at 1 month was 16.1mg/l (range 2–63mg/l). Mean pre op WCC was 8.5×10. 9. (range 6.2–10.6×10. 9. ). Mean post op WCC at 1 week was 8.8×10. 9. (range 5.1–12.7×10. 9. ) and 1 month was 7.1×10. 9. (range 3.7–10.4×10. 9. ). Organisms cultured included enterobacter, staphylococcus species, stenotrophomonas, acinetobacter, group B streptococcus, enterococcus, escherichia coli, pseudomonas, morganella morganii and finegoldia magna. Infection eradication as a single stage procedure with primary would closure and healing was achieved in 10 out of 11 cases (90.9%). No additional procedures were required in these cases. Conclusions. Our results support the use of a calcium sulphate bio composite with antibiotic as an adjuvant for effective local infection control in cases with implant related bone sepsis. The technique is well tolerated with no systemic or local side effects. Our results show that a single stage implant removal, debridement and local antibiotic delivery can achieve over 90% success rates. We theorise that it could minimise the need for prolonged systemic antibiotic therapy in such cases

Introduction: Enchondromas are benign cartilaginous tumors, which are most often localized, in the small bones of the hand. Treatment methods fall into a broad spectrum ranging from conservative, medical therapies, to a variety of surgical procedures, which may or may not employ the use of local adjuvant treatment or bone grafting. Material & Method: We present thirty four patients with hand enchondromas treated surgically in our department during the last eleven years. Their medical records and radiographs were reviewed retrospectively and the patients were contacted and interviewed by telephone. Results: The patients were treated operatively with an intralesional approach, with meticulous curettage of the bone lesion, use of phenol 5% and grafting using coralline hydroxyapatite. X-rays taken over the first postoperative year revealed adequate bone synthesis at the site of enchondroma excavation, and there was no evidence of recurrence, fracture, infection or other complication related to the procedure. Conclusion: We conclude that the combination of curettage of the lesion with the use of phenol as local adjuvant and grafting using coralline hydroxyapatite during the surgical treatment of enchondromas, is a safe technique to reduce or prevent recurrence and allow adequate and uncomplicated local new bone formation

We retrospectively compared the outcome after the treatment of giant cell tumours of bone either with curettage alone or with adjuvant cementation. Between 1975 and 2008, 330 patients with a giant cell tumour were treated primarily by intralesional curettage, with 84 (25%) receiving adjuvant bone cement in the cavity. The local recurrence rate for curettage alone was 29.7% (73 of 246) compared with 14.3% (12 of 84) for curettage and cementation (p = 0.001). On multivariate analysis both the stage of disease and use of cement were independent significant factors associated with local recurrence. The use of cement was associated with a higher risk of the subsequent need for joint replacement. In patients without local recurrence, 18.1% (13 of 72) of those with cement needed a subsequent joint replacement compared to 2.3% (4 of 173) of those without cement (p = 0.001). In patients who developed local recurrence, 75.0% (9 of 12) of those with previous cementation required a joint replacement, compared with 45.2% (33 of 73) of those without cement (p = 0.044)

Aims. To report the outcome observed in 34 dogs with non metastatic distal radial osteosarcoma (OSA) treated by a combination of adjuvant chemotherapy and limb-sparing surgery. Limb-sparing procedures were based on the use of a frozen bone cortical allograft (group A; 18 cases) and of a pasteurised tumoral autograft (group B; 16 cases), respectively. Methods. In group A, limb-sparing procedure was performed using a fresh-frozen cortical allograft from a bone bank. In the group B, the bone graft was realized from the excised tumoral segment after its pasteurisation at 65A1C for 40 minutes. Adjuvant chemotherapy (cisplatin or cisplatin and doxorubicin) was administered in all dogs. Results. In group A, mean and median survival times were 478-266 days, respectively (range 80–2611 days). Overall survival was 78% at 6 months, 35% at 12 months, 23% at 18 months and 19% at 24 months. Lung metastasis occurred in 10 cases (55%). Observed complications were local recurrence (28%), graft infection (39%) and implant failure (11%). In group B, mean and median survival times were 533-368 days, respectively (range 137–1944 days). Overall survival was 100% at 6 months, 57% at 12 months, 45% at 18 months and 20% at 24 months. Metastasis were observed in 7 dogs (44%). Complications were local recurrence (12%), graft infection (44%) and implant failure (19%). Limb function was good in 72% (group A), and 92% (group B) of the dogs, respectively. Conclusions. Limb-sparing techniques with bone grafts represent an alternative to amputation in the treatment of selected cases of distal radial osteosarcoma. Limb sparing techniques are not free of complication (infection, implant failure, recurrence) if compared to amputation. The latter represents the elective option in most cases of appendicular OSA and is usually free of complication. Comparing the two treatment groups, pasteurised bone autograft derived from the tumoral bone segment represents an effective alternative to cortical bone allograft coming from a bone bank, considering the difficulties encountered in finding donor dogs and national legal limitations on establishing a canine cortical bone graft bank. Alternative limb sparing procedures (metallic implant, Ilizarov) will be also discussed

The results are presented of thirty-seven patients with Ewing's sarcoma; ten were treated by a combination of operation, radiotherapy and cyclic chemotherapy, the remainder by radiotherapy and chemotherapy but without operation. The drugs, vincristine, cyclophosphamide and adriamycin were used in combination and were continued for two years. The follow-up ranged from twelve to sixty-two months. The mortality rate and the incidence of metastases were both markedly lower than in a comparable previous series treated by radiotherapy alone, or by operation plus radiotherapy, but all without chemotherapy. The percentage of local recurrences and of metastases was much higher in the twenty-seven patients who had radiotherapy and adjuvant chemotherapy, than in the ten in whom operation was also performed. It is suggested that on the basis of these results (and on theoretical grounds) treatment should consist of radiotherapy combined with chemotherapy plus, whenever feasible, operative excision of the primary tumour

The development of multidisciplinary therapy for Ewing’s sarcoma (ES) has increased current long-term survival rates to greater than 50%, but only 20% for patients with clinically detectable metastases at diagnosis, or not responding to therapy or with disease relapse. Anti-bone resorption bisphosphonates (BP) may represent promising adjuvant molecules to limit the osteolytic component of bone tumor. The combination of zoledronic acid (ZOL) and ifosfamide (IFOS) or mafosfamide (MAFOS) was studied in ES models and in 8 human cell lines all expressing the EWS-FLI1 fusion gene. Cell proliferation, viability, apoptosis and cell cycle distribution were analysed. The ES models were developed in immuno-deficient mice by inoculating the human tumor cells either intra-muscular (soft tissue tumor development) or intra-osseous (bone tumor development). Mice were then treated with ZOL (100 μg/kg twice or 4 times/week) and/or ifosfamide (IFOS 30 mg/kg, one to 3 sequences of 3 injections). All the cell lines studied were more or less sensitive to ZOL and MAFOS in terms of cell proliferation. Both drugs induced cell cycle arrest respectively in S and G2M phase and final apoptosis associated to caspase 3 activation. In vivo, ZOL had no effect on soft tumor progression although it dramatically inhibits ES development in bone site. When combined with IFOS, ZOL exerts synergistic effects in the soft tissue model leading to a similar quantitative inhibitory effect when associated with 1 sequence IFOS as compared to 3 sequences of IFOS alone. In the bone model, ZOL prevents tumor recurrence observed with a lonely sequence of IFOS. Combination of ZOL with conventional chemotherapy showed promising results in both ES models and could allow the clinicians to diminish the doses of chemotherapy. Moreover, as ZOL and MAFOS induce cell death by different pathways, respective resistance may be circumvented

Between December 1995 and March 2003, 38 adult patients with intermediate or high-grade liposarcoma in a limb were treated by limb-sparing surgery and post-operative radiotherapy. The ten-year local recurrence-free survival was 83%, the ten-year metastasis-free survival 61%, the ten-year disease-free survival 51% and the ten-year overall survival 67%. Analysis of failure and success showed no association with the age of the patients, gender, the location of the primary tumour, the type of liposarcoma and the quality of resection.

Our results indicate that liposarcoma may recur even ten years after the end of definitive therapy and may spread to unexpected sites as for soft-tissue sarcoma.

Aims

The aims of this study were to evaluate the efficacy of preoperative denosumab in achieving prospectively decided intention of therapy in operable giant cell tumour of bone (GCTB) patients, and to document local recurrence-free survival (LRFS).