C. L. M. H. Gibbons

Pseudotumours associated with metal-on-metal hip resurfacings

We report 17 patients (20 hips) in whom metal-on-metal resurfacing had been performed and who presented with various symptoms and a soft-tissue mass which we termed a pseudotumour. Each patient underwent plain radiography and in some, CT, MRI and ultrasonography were also performed. In addition, histological examination of available samples was undertaken. All the patients were women and their presentation was variable. The most common symptom was discomfort in the region of the hip. Other symptoms included spontaneous dislocation, nerve palsy, a noticeable mass or a rash. The common histological features were extensive necrosis and lymphocytic infiltration. To date, 13 of the 20 hips have required revision to a conventional hip replacement. Two are awaiting revision. We estimate that approximately 1% of patients who have a metal-on-metal resurfacing develop a pseudotumour within five years. The cause is unknown and is probably multifactorial. There may be a toxic reaction to an excess of particulate metal wear debris or a hypersensitivity reaction to a normal amount of metal debris. We are concerned that with time the incidence of these pseudotumours may increase. Further investigation is required to define their cause.

The imaging spectrum of peri-articular inflammatory masses following metal-on-metal hip resurfacing

IntroductionResurfacing metal-on-metal hip arthroplasty is increasing in popularity, especially in younger patients. To date, studies indicate that the procedure is associated with a good outcome in the medium-term. Formation of a peri-articuar mass is a rarely reported complication. In this study we analyse the imaging findings in patients with resurfacing implants presenting to our institution with peri-articular masses identified on cross sectional imaging.Materials and methodsAll patients with documented peri-articular masses following resurfacing arthroplasty were included. The available imaging related to the masses was reviewed and the findings documented along with the patient’s demographics.ResultsThere were 10 patients (13 joints). All patients were female. Patients presented with periprosthetic anterior or posterolateral solid and cystic masses. The anterior masses involved psoas muscle and were predominately solid. The posterolateral masses were predominately cystic. In the three cases with bilateral arthroplasties, masses were detected in both hips. Histology in six cases showed features compatible with a type IV hypersensitivity reaction.ConclusionsThe preponderance of females, the bilateral nature of the masses and the histological features suggest that peri-articular masses following resurfacing arthroplasty is due to the metal hypersensitivity.

Classification of failure of limb salvage after reconstructive surgery for bone tumours: a modified system Including biological and expandable reconstructions

Previous classification systems of failure of limb salvage focused primarily on endoprosthetic failures and lacked sufficient depth for the effective study of the causes of failure. In order to address these inadequacies, the International Society of Limb Salvage (ISOLS) formed a committee to recommend revisions of the previous systems. The purpose of this study was to report on their recommendations. The modifications were prepared using an earlier, evidence-based model with subclassification based on the existing medical literature. Subclassification for all five primary types of failure of limb salvage following endoprosthetic reconstruction were formulated and a complementary system was derived for the failure of biological reconstruction. An additional classification of failure in paediatric patients was also described. Limb salvage surgery presents a complex array of potential mechanisms of failure, and a complete and precise classification of types of failure is required. Earlier classification systems lacked specificity, and the evidence-based system outlined here is designed to correct these weaknesses and to provide a means of reporting failures of limb salvage in order to allow the interpretation of outcome following reconstructive surgery.

The patho-anatomy of patellofemoral subluxation

Patella subluxation assessed on dynamic MRI has previously been shown to be associated with anterior knee pain. In this MRI study of 60 patients we investigated the relationship between subluxation and multiple bony, cartilaginous and soft-tissue factors that might predispose to subluxation using discriminant function analysis. Patella engagement (% of patella cartilage overlapping with trochlea cartilage) had the strongest relationship with subluxation. Patellae with > 30% engagement tended not to sublux; those with < 30% tended to sublux. Other factors that were associated with subluxation included the tibial tubercle-trochlea notch distance, vastus medialis obliquus distance from patella, patella alta, and the bony and cartilaginous sulcus angles in the superior part of the trochlea. No relationship was found between subluxation and sulcus angles for cartilage and bone in the middle and lower part of the trochlea, cartilage thicknesses and Wiberg classification of the patella. This study indicates that patella engagement is a key factor associated with patellar subluxation. This suggests that in patients with anterior knee pain with subluxation, resistant to conservative management, surgery directed towards improving patella engagement should be considered. A clinical trial is necessary to test this hypothesis.

Cellular and humoral mechanisms of osteoclast formation in Ewing's sarcoma.

Cellular mechanisms that account for tumour osteolysis associated with Ewings sarcoma are uncertain. Osteoclasts are marrow-derived multinucleated cells (MNCs) that effect tumour osteolysis. Osteoclasts are known to form from macrophages by both receptor activator for nuclear factor-κB (RANK) ligand (RANKL)-dependent and -independent mechanisms. In this study, our aim has been to determine whether tumour-associated macrophages (TAMs) isolated from Ewings sarcoma are capable of differentiating into osteoclasts and to characterise the cellular and humoral mechanisms whereby this occurs. Tumour-associated macrophages were isolated from two Ewings sarcomas and cultured on both coverslips and dentine slices for up to 21 days with soluble RANKL and macrophage colony stimulating factor (M-CSF). Osteoclast formation from TAMs (CD14+) was evidenced by the formation of tartrate-resistant acid phosphatase (TRAP) and vitronectin receptor (VNR)-positive MNCs, which were capable of carrying out lacunar resorption. This osteoclast formation was inhibited by the addition of bisphosphonates. Both Ewings sarcoma-derived fibroblasts and some bone stromal cells expressed RANKL and supported osteoclast formation by a contact-dependent mechanism. We also found that osteoclast differentiation occurred when Ewings TAMs were cultured with tumour necrosis factor (TNF)-α in the presence of M-CSF and that TC71 Ewings sarcoma cells stimulated osteoclast formation through the release of a soluble factor, the action of which was abolished by an antibody to TNF-α. These results indicate that TAMs in Ewings sarcoma are capable of osteoclast differentiation by both RANKL-dependent and TNF-α-dependent mechanisms and that Ewings sarcoma cells produce osteoclastogenic factor(s). Our findings suggest that anti-resorptive and anti-osteoclastogenic therapies may be useful in inhibiting the osteolysis of Ewings sarcoma.

No difference in survivorship after unicompartmental knee arthroplasty with or without an intact anterior cruciate ligament.

PurposeAnterior cruciate ligament deficiency (ACLD) has been considered a contraindication for Oxford unicompartmental knee arthroplasty (UKA) because of the reported higher incidence of failure when implanted in ACLD knees. However, given the potential advantages of UKA over total knee arthroplasty (TKA), we have performed UKA in a limited number of patients with ACL deficiency and end-stage medial compartment osteoarthritis (OA) over the past 11xa0years. The primary aim of this study was to establish the clinical outcome of this cohort; the secondary aim was to compare both clinical and radiographic data with a matched cohort of ACL-intact (ACLI) patients who have undergone UKA for anteromedial OA.MethodsThis retrospective observational study describes the clinical and radiological outcome in 46 medial Oxford UKAs implanted in 42 consecutive patients with ACL deficiency and concomitant symptomatic medial compartment OA at mean follow-up of 5xa0years. It also compares the outcomes with a matched cohort of UKA patients with an intact ACL (ACLI group).ResultsAt the time of last follow-up, there was no significant difference in clinical results or survivorship between the two groups in this study.ConclusionThe successful short-term results of the ACLD group suggest ACL deficiency may not always be a contraindication to Oxford UKA as previously thought. Until long-term data is available, however, we maintain our recommendation that ACLD be considered a contraindication.Level of evidenceIII.

Early revisions of the Femoro-Patella Vialla joint replacement

The aim of this study was to review the early outcome of the Femoro-Patella Vialla (FPV) joint replacement. A total of 48 consecutive FPVs were implanted between December 2007 and June 2011. Case-note analysis was performed to evaluate the indications, operative histology, operative findings, post-operative complications and reasons for revision. The mean age of the patients was 63.3 years (48.2 to 81.0) and the mean follow-up was 25.0 months (6.1 to 48.9). Revision was performed in seven (14.6%) at a mean of 21.7 months, and there was one re-revision. Persistent pain was observed in three further patients who remain unrevised. The reasons for revision were pain due to progressive tibiofemoral disease in five, inflammatory arthritis in one, and patellar fracture following trauma in one. No failures were related to the implant or the technique. Trochlear dysplasia was associated with a significantly lower rate of revision (5.9% vs 35.7%, p = 0.017) and a lower incidence of revision or persistent pain (11.8% vs 42.9%, p = 0.045). Focal patellofemoral osteoarthritis secondary to trochlear dysplasia should be considered the best indication for patellofemoral replacement. Standardised radiological imaging, with MRI to exclude overt tibiofemoral disease should be part of the pre-operative assessment, especially for the non-dysplastic knee.

Oncogenic hypophosphataemic osteomalacia : biomarker roles of fibroblast growth factor 23, 1,25 -dihydroxyvitamin D3 and lymphatic vessel endothelial hyaluronan receptor 1

Oncogenic osteomalacia (OOM) is characterised by tumour production of fibroblast growth factor 23 (FGF23) that results in hypophosphataemia and renal phosphate wasting, reduced 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) synthesis and osteomalacia. Here, we demonstrate the roles of serum FGF23 and 1,25(OH)2D3, together with the lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), as biomarkers for OOM. A previously well 52-year-old man presented with a 2-year history of generalised musculoskeletal pain and proximal myopathy. He had hypophosphataemia, elevated serum alkaline phosphatase activity, low serum 1,25(OH)2D3 and a reduced tubular maximum of phosphate/glomerular filtration rate. These findings indicated a diagnosis of OOM, but magnetic resonance imaging (MRI) and octreotide scintigraphy did not identify any tumours. Treatment with oral phosphate and calcitriol resolved the symptoms and biochemical abnormalities within 6 months. Four years later, he relapsed whilst on treatment with oral phosphate and calcitriol. Serum FGF23 concentration was elevated and MRI identified a 2 cm tumour within Hoffas fat pad of the left knee. Removal of the tumour resulted in a complete resolution of symptoms and normalisation of the serum biochemical abnormalities including serum FGF23. Histology demonstrated a phosphaturic mesenchymal tumour, mixed connective tissue variant (PMTMCT), which revealed immunostaining with anti-LYVE-1 antibody and hence the presence of lymphatic vessels. Serum FGF23 and 1,25(OH)2D3 were found to be reliable biomarkers for OOM. In addition, the demonstration of lymphatics in the PMTMCT helps to distinguish this tumour from most typical benign haemangiomas.

Functional and oncological outcome following marginal excision of well-differentiated forearm liposarcoma with nerve involvement.

PURPOSEnLiposarcoma is one of the most common soft tissue sarcomas in adults. It is often low-grade and can occasionally involve neurovascular structures. We present the functional and oncological outcome resulting from planned marginal excision of a series of forearm low-grade liposarcomas with nerve involvement.nnnMETHODSnThe Oxford tumor registry was used to identify cases of histologically proven, well-differentiated liposarcoma of the forearm, with nerve involvement, treated surgically between 1997 and 2006. Nerve involvement was identified clinically with symptoms or signs of nerve compression, or by images showing direct contact of the tumor with a nerve on magnetic resonance imaging. This was then further defined at the time of surgery as tumor abutting (capsular involvement) or encasing a peripheral nerve. Demographic and clinical data were collected and oncological outcome was assessed by noting local and distant recurrence during follow-up. Postoperative functional outcome was assessed using the Toronto Extremity Salvage Scores.nnnRESULTSnEight cases were identified, 6 with preoperative neurological symptoms. The total group comprised 6 men and 2 women with a mean age of 61 (range, 30-71) years. At surgery, all had their tumors successfully excised, with preservation of the involved nerves. In those with preoperative neurological symptoms, complete recovery occurred by 18 months after surgery. The average follow-up was 5 years (range, 3-9 y). There were no cases of either local or distant recurrence of disease, with a mean Toronto Extremity Salvage Score of 99%.nnnCONCLUSIONSnPlanned marginal excision of a well-differentiated liposarcoma, arising in the forearm and involving nerve, can result in excellent functional and oncological outcome.nnnTYPE OF STUDY/LEVEL OF EVIDENCEnTherapeutic IV.

Osteoclast-like cells in soft tissue leiomyosarcomas

Giant cell-rich leiomyosarcoma of soft tissues is an unusual variant of malignant smooth muscle tumor characterized by the presence of numerous multinucleated giant cells (MNGCs). The nature of MNGCs and the cellular mechanisms underlying their accumulation in this tumor are poorly understood. Analysis of the expression of osteoclast, macrophage, and smooth muscle markers in two cases of giant cell-rich leiomyosarcoma revealed that the MNGCs in giant cell-rich leiomyosarcoma were negative for smooth muscle markers and that these cells expressed an osteoclast-like phenotype, being positive for CD45, CD68, tartrate-resistant acid phosphatase, and CD51 but negative for CD14 and HLA-DR. Scattered tumor-associated macrophages (TAMs) also expressed this phenotype. Leiomyosarcoma tumor cells strongly reacted for CD51 but were negative for CD14, CD45, and CD68. An analysis of 25 conventional (nongiant cell-containing) leiomyosarcomas found isolated CD68+ MNGCs in three cases (12%), all of which were grade II/III leiomyosarcomas containing a prominent TAM infiltrate. Leiomyosarcoma-derived TAMs in the presence of receptor activator for nuclear factor kappa B ligand (RANKL) and macrophage colony-stimulating factor were capable of differentiating into osteoclast-like cells capable of resorbing bone. Reverse transcription polymerase chain reaction studies showed that RANKL, osteoprotegerin, and TNF-related apoptosis-inducing ligand were expressed by leiomyosarcoma cells. Our findings indicate that the giant cells found in leiomyosarcomas are osteoclast-like and that they are formed from TAMs by a RANKL-dependent mechanism.