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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_8 | Pages 18 - 18
10 May 2024
Joseph R Callon K Lin J Matthews B Irwin S Williams D Ashton N Crawford H Wen J Swift S Cornish J
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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


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 64 - 64
22 Nov 2024
Mbuku RB Poilvache H Van Bambeke F Cornu O
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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


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_6 | Pages 10 - 10
1 May 2021
Aljawadi A Islam A Jahangir N Niazi N Ferguson Z Sephton B Elmajee M Reid A Wong J Pillai A
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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%


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXI | Pages 150 - 150
1 May 2012
H. S J. L R. R A. TR
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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


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_X | Pages 158 - 158
1 Apr 2012
Sharma H Reid R Reece A
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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


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_11 | Pages 5 - 5
1 Sep 2021
Raza M Sturt P Fragkakis A Ajayi B Lupu C Bishop T Bernard J Abdelhamid M Minhas P Lui D
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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


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 474 - 474
1 Jul 2010
van de Sande M Dijkstra P Bovee J Taminiau A
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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


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_I | Pages 45 - 45
1 Jan 2004
Lazerges C Daussin P Bacou F Chammas M
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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


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 387 - 387
1 Sep 2005
Kollender Y Bender B Nirkin A Shabat S Merimsky O Isaakov J Flusser G Meller I Bickels J
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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


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_19 | Pages 6 - 6
1 Nov 2016
Mohammad H Tabain T Pillai A
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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


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_II | Pages 167 - 167
1 Feb 2004
Bisbinas H Georgiannos D Koukakis A Chatzipapas C Vrangalas V Karanasos T
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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


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_I | Pages 67 - 67
1 Mar 2005
Morello E Martano M Peirone B Buracco P
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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


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 465 - 465
1 Jul 2010
Odri G Lamoureux F Picarda G Battaglia S Dumoucel S Trichet V Tirode F Laud K Burchill S Gouin F Heymann D Rédini F
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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


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 449 - 449
1 Jul 2010
Dijkstra P Vleggeert-Lankamp C Moojen W Krol A Taminiau A
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Sacrococcygeal chordoma is a slow growing, malignant tumour with a clinical poor outcome due to a high local recurrence (LR) rate. Several studies emphasize that margin-free tumour resection is the most important predictor of survival and LR in patients with sacrococcygeal chordoma. However, a high recurrence rate still remains. The purpose of this report is to define the role of postoperative radiotherapy (RT).

15 patients (7 females and 8 males) underwent surgical treatment for sacrococcygeal chordoma between 1981 and 2003. The mean age at surgery was 54 (range 31–70) years. The mean follow up was 8.5 (range 4 – 20) years. Most patients suffered from local swelling and pain; only one patient had a mild urinary continence being the only pre- and postoperative neurological deficit. Mean time of preoperative complaints was 4.5 (range 0.8 – 8) years. In 9 patients an en bloc resection was performed, in 6 patients a subtotal resection was achieved. Most patients with a subtotal resection received RT (5/6 patients) following surgery, patients with en bloc resection only received RT (> 50Gray) after LR (6/9 patients).

After en bloc resection (no initial RT) all patients had local recurrence of the tumour with a mean time to recurrence of 3 (range 0.8 – 13) yrs. Only two patients in the group with subtotal resection had LR after 11 yrs. Six of 9 patients with LR after en bloc surgery received RT after recurrence and had a survival of at least 9 (range 5 – 20) years. There were no major complications. The time to recurrence was significantly longer in the group that received immediate RT after surgery, even after resection with irradical margins. There was no difference in survival between both surgical groups.

Our results suggest that postoperative RT is more important in the prevention of local recurrence than margin-free tumour resection. This supports the strategy to add radiotherapy as a standard adjuvant therapy to tumour resection in patients with sacrococcygeal chordoma.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_III | Pages 481 - 481
1 Sep 2009
Gangone R Lakkireddi P Kotrba M Marsh G
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Background: A common problem achieving lumbar spinal fusion is developing a pseudarthrosis. The current gold standard in achieving fusion is the use of autograft from pelvis or posterior elements of the spine. However the potential limitations of insufficient quantity and donor site morbidity have led to the use of bone graft alternatives such as DBM which contains osteoinductive BMPs.

Aims & Methods: A prospective randomized control trial comparing the effectiveness of Demineralised Bone Matrix (DBM Putty)/autograft composite with autograft in lumbar postero-lateral or 270 degree spinal fusion.

35 patients were required for the study. They were randomized to have DBM and autograft on one side of the posterior approach and autograft alone on other side of the same approach. Patients were followed up with interval radiographs for total of 24mons. To date 32 patients have been recruited and with an average follow up a15.3 months. The mineralization of fusion mass lateral to the instrumentation on each side was graded as Absent, Mild (< 50%), Moderate (> 50%) or Complete fusion (100%). The assessment was made by independent orthopaedic consultant and a musculoskeletal radiologist who were blinded to graft assignment.

Results: The sex distribution was 17:15 male to females with a mean age of 55.2 (21–87years) and an average follow up of 15.3mons (3–24mons). 50% of patients had single level fusion and the remainder had more than one level fusion. At 12months, on the side of DBM 28% had complete fusion, 65% had moderate fusion, and 7% had no fusion mass. During the same period on the other side (non DBM side) approx 25% did not show any sign of fusion. There was no correlation with number of levels, age or sex.

Conclusions: Osteoinductive properties of DBM would appear to enhance the consolidation of the lumbar spinal fusion. DBM reduces the amount of harvested autograft graft and also minimises the morbidity of donor site complications.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_I | Pages 48 - 48
1 Mar 2008
Morin P Reindl R Steffen T Harvey E Guy P
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In our cadaver study plating the fibula in addition to nailing the tibia decreased the mean rotation across the tibial osteotomy site compared to nailing the tibia alone. Although this is statistically significant (p=0.0034) it may not be clinically relevant as the mean values for ROM were 19.10 and 17.96 degrees respectively. Plating the fibula resulted in no statistically significant difference in the mean vertical displacement, angulation or neutral zone.

Therefore, we may conclude that plating the fibula in a combined distal third tibia and fibula fracture does not enhance the stability of tibial IM nailing.

The purpose of this study was to determine if combined distal third tibia and fibula fractures are more stable when fibular fixation is added to the standard tibial IM rodding.

In combined distal third tibia and fibula fractures, plating the fibula does not enhance stability of intramedullary tibial nailing.

No additional incision or soft tissue stripping is required for plating of the fractured fibula.

The average range of motion in rotation was 19.1° for tibial and fibular fixation combined, and 18.0 ° for tibial fixation alone with a difference of 1.1°, which was clinically significant ( p=0.0034). The mean differences in vertical displacement, angulation, and neutral zone were not statistically significant.

Five matched pairs of embalmed cadaveric lower limbs were dissected and stripped of soft tissue. Each tibia received a 9mm solid titanium nail that was locked proximally and distally. Fibular fixation consisted of a seven- hole LCDCP. A 1.5 cm section of tibia and a 1.0 cm section of fibula were removed. Testing was accomplished with an MTS machine. Vertical displacement was tested with an axial load to 500 N, rotation was tested with an internal and external torque of 5 Nm, and angulation was calculated from the vertical displacement data. All displacement data was measured across the osteotomy site.

The mean range of motion in rotation was the only statistically significant finding. However, considering the average range of motion with and without fibular plating of 17.96° and 19.10° respectively, this finding is likely not clinically relevant.

Funding: Tibial nails, bolts, fibular plates and screws provided by Synthes (Paoli, PA, USA)


Bone & Joint Open
Vol. 3, Issue 7 | Pages 515 - 528
1 Jul 2022
van der Heijden L Bindt S Scorianz M Ng C Gibbons MCLH van de Sande MAJ Campanacci DA

Aims. Giant cell tumour of bone (GCTB) treatment changed since the introduction of denosumab from purely surgical towards a multidisciplinary approach, with recent concerns of higher recurrence rates after denosumab. We evaluated oncological, surgical, and functional outcomes for distal radius GCTB, with a critically appraised systematic literature review. Methods. We included 76 patients with distal radius GCTB in three sarcoma centres (1990 to 2019). Median follow-up was 8.8 years (2 to 23). Seven patients underwent curettage, 38 curettage with adjuvants, and 31 resection; 20 had denosumab. Results. Recurrence rate was 71% (5/7) after curettage, 32% (12/38) after curettage with adjuvants, and 6% (2/31) after resection. Median time to recurrence was 17 months (4 to 77). Recurrences were treated with curettage with adjuvants (11), resection (six), or curettage (two). Overall, 84% (38/45) was cured after one to thee intralesional procedures. Seven patients had 12 months neoadjuvant denosumab (5 to 15) and sixmonths adjuvant denosumab; two recurred (29%). Twelve patients had six months neoadjuvant denosumab (4 to 10); five recurred (42%). Two had pulmonary metastases (2.6%), both stable after denosumab. Complication rate was 18% (14/76, with 11 requiring surgery). At follow-up, median MusculoSkeletal Tumour Society score was 28 (18 to 30), median Short Form-36 Health Survey was 86 (41 to 95), and median Disability of Arm, Shoulder, and Hand was 7.8 (0 to 58). Conclusion. Distal radius GCTB treatment might deviate from general GCTB treatment because of complexity of wrist anatomy and function. Novel insights on surgical treatment are presented in this multicentre study and systematic review. Intralesional surgery resulted in high recurrence-rate for distal radius GCTB, also with additional denosumab. The large majority of patients however, were cured after repeated curettage. Cite this article: Bone Jt Open 2022;3(7):515–528


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 44 - 44
24 Nov 2023
Bruyninckx S Vles G
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Aim. The objective of this systematic review is to evaluate the current evidence for or against this up-and-coming treatment modality. Method. A comprehensive literature search in accordance with the Preferred Reporting Items for Systematic review and Meta-analysis (PRISMA) guidelines was conducted using PubMed, Embase, MEDLINE and Cochrane databases. Exclusion criteria included patients < 18 years of age, follow-up <11 months, and a score < 6 on the National Institute of Health quality assessment tool. Results. 15 articles, encompassing 631 PJIs in 626 patients, were included in the final analysis, all level IV case series. The quality of many studies was impeded by a retrospective design (14/15), a relative small study population (10 out of 15 studies had less than 50 patients), selection bias, and remarkable heterogeneity in terms of catheter type, antibiotic type, dose and duration of IA antibiotics and techniques of surgical revision. 347 were chronic infections, 66 acute infections and 218 unknown. The majority was treated with single-stage revision with adjuvant IA antibiotic infusion (499/631, 79.1%). The remaining PJIs were treated with stand-alone IA antibiotic infusion (77/631, 12.2%), DAIR with adjuvant IA antibiotic infusion (36/631, 5.7%) or two-stage revision with adjuvant IA antibiotic infusion (19/631, 3.0%). Mean duration of IA antibiotic infusion was 19 days (range 3–50), although most patients received a combination of both IA and systemic (IV or PO) antibiotics. An overall failure rate (defined as failures of infection eradication/total PJIs) of approximately 11% was found. The use of IA antibiotic infusion as a stand-alone treatment was associated with a higher failure rate. In total 117 complications occurred in 631 cases (18.5%). Of these, 71 were non-catheter-related (60.7%) and 46 were catheter-related (39.3%). The most common catheter-related complications were premature loss of the catheter (18/46), developing a fistula (5/46), and elevated blood urea nitrogen (BUN) and creatinine levels (12/46). Conclusions. Due to the lack of comparative studies the (added) benefit of IA antibiotic infusion in the treatment of PJI remains uncertain. From a theoretical point of view it seems likely that is should not be used as a stand-alone treatment. A prospective randomized controlled trial using a well-described infusion protocol is needed to see if the potential benefits justify the increased costs, labour and catheter-related complications of this treatment modality


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_14 | Pages 36 - 36
1 Dec 2022
Falzetti L Fermi M Ghermandi R Girolami M Pipola V Presutti L Gasbarrini A
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Chordoma of the cervical spine is a rare but life-threatening disease with a relentless tendency towards local recurrence. Wide en bloc resection is recommended, but it is frequently not feasible in the cervical spine. Radiation therapy including high-energy particle therapy is commonly used as adjuvant therapy. The goal of this study was to examine treatment and outcome of patients with chordoma of the cervical spine. Patients affected by cervical spine chordoma who underwent surgery at the Rizzoli Institute and University Hospital of Modena, between 2007 and 2021 were identified. The clinical, pathologic, and radiographic data were reviewed in all cases. Patient outcomes including local recurrence and disease-specific survival (DSS) were analyzed using chi-square test and Kaplan-Meier survival analysis. Characteristics of the 29 patients (10 females; 19 males) included: median age at surgery 52.0 years (IQR 35.5 - 62.5 years), 10 (35%) involved upper cervical spine, 16 (55%) with tumors in the mid cervical spine, and 4 in the lower cervical spine (10%). Median tumor volume was 16 cm. 3. (IQR 8.7 - 20.8). Thirteen patients (45%) were previously treated surgically while 9 patients (31%) had previous radiation therapy. All patients underwent surgery: en bloc resection was passible in 4 patients (14 %), seventeen patients (59%) were treated with gross total resection while 8 patients (27%) underwent subtotal resection. Tumor volume was associated with a significantly higher risk of intraoperative complications (p < 0.01). Nineteen patients (65%) received adjuvant high-energy particle therapy. The median follow-up was 26 months (IQR 11 - 44). Twelve patients (41%) had local recurrence of disease. Patients treated with adjuvant high-energy particle therapy had a significant higher local control than patients who received photons or no adjuvant treatment (p = 0.01). Recurrence was the only factor significantly associated with worse DSS (p = 0.03 – OR 1.7), being the survival of the group of patients with recurrent disease 58.3% while the survival of the group of patients with no recurrent disease was 100%. Post-operative high-energy particle therapy improved local control in patients with cervical chordoma after surgical resection. Increased tumor volume was associated with increased risk of intraoperative complications. Recurrence of the disease was the only factor significantly associated with disease mortality