Introduction

In Europe, injectable collagenase clostridium histolyticum (CCH) is a novel, minimally invasive, non-surgical therapy with efficacy in correcting Dupuytren's contracture (DC). We evaluated the efficacy and tolerability of 5 CCH injections using a protocol designed to follow clinical practice.

Introduction

Angiosarcomas are rare aggressive sarcomas of vascular endothelial origin. These tumours have the potential to be multicentric and are associated with high rates of local recurrence, which makes treatment challenging. The gold-standard is that these patients are managed in specialist centres by a multidisciplinary team. We present our experience of managing patients with angiosarcoma in the North of England Bone and Soft Tissue Tumour Service and a review of the literature.

This study evaluated the biologic fixation of two different titanium porous coatings: a clinically successful sintered spherical bead coating [1] and a new sintered asymmetric particle coating (STIKTITE™, Smith & Nephew). The spherical bead coating has a porosity of about 50% and an average pore size of about 220 μm, whereas the STIKTITE coating has greater porosity (about 62%) and slightly smaller average pore size (about 200 μm). Biologic fixation was assessed using a load-bearing ovine model in which coated semi-circular disc implants were inserted into a defect created in the cancellous bone parallel to and approximately 3 mm below the medial tibial plateau [2] similar to the method reported by Ignatius [3]. The implants were slightly thicker than the defect created, producing a 0.2-mm overall pressfit. Initial implant stability was assessed using mechanical push-out (n = 3) immediately after implantation into cadaveric ovine bone. Quantitative mechanical push-out testing and qualitative histology (n = 9 and n = 2, respectively, per group per time point) was performed after six and 26 weeks in vivo.

The time-zero average peak push-out load (±S.D.) of the STIKTITE group (95±3 N) was found to be significantly greater (p < 0.02) than that of the spherical bead group (36±5 N). By six weeks in vivo, the average peak push-out load for the STIKTITE group was up to 1001±362 N, and that for the spherical bead group was up to 985±425 N, both representing a significant increase compared to their time-zero results (p < 0.0005). From six to twenty-six weeks in vivo, there was again a significant increase in the peak push-out load irrespective of group (p < 0.0005), with the average peak push-out loads up to 1620±406 N and 1444±446 N for the STIK-TITE and spherical bead groups, respectively. Histology revealed bone ingrowth in both groups that confirmed the findings of the mechanical push-out testing. While the STIKTITE group showed a trend toward greater biologic fixation, overall there was insufficient evidence to support differences between the two groups (p = 0.47) irrespective of the amount of time in vivo.

The results of this study confirm the ability of the STIK-TITE coating to achieve superior initial stability. This improved initial stability reduces the reliance on adjunct fixation (such as screws) or large amounts of press-fit to prevent micromotion and create an environment suitable for long-term bone ingrowth. The results also suggest that the STIKTITE coating had a tendency to initiate and maintain bone ingrowth under load-bearing conditions to a level greater than that of a clinically successful sintered bead coating. Because loading of the implant can cause micromotion at the bone/implant interface, models like the one used in this study likely provide a more challenging and realistic representation of anticipated clinical conditions than models with minimal implant loading.

Purpose: Pinch strength has been shown to be a predictor of the ability to grip objects and perform functional hand-related tasks. As the sole flexor of the thumb IP joint, the flexor pollicus longus (FPL) muscle has previously been shown to play an essential role in directing thumb tip force as well as contribute to overall pinch strength. The relative contribution of FPL to pinch strength is unknown however. As the FPL may be affected in several acute and chronic conditions, determining the contribution of FPL to pinch strength may be useful in planning as well as evaluating treatment options. The purpose of this study was to estimate the contribution of FPL to pinch strength in-vivo using an EMG-guided, selective motor blockade, test-retest protocol.

Method: 11 healthy volunteers were recruited to participate in the study. All participants completed a brief questionnaire regarding prior hand injuries and subsequently underwent a physical examination to assess baseline hand function. Baseline pinch strength was recorded using three different pinch techniques: key pinch, 3-point chuck grasp, and tip pinch. Participants then underwent EMG-guided lidocaine blockade of the FPL muscle. Motor evoked potentials as well as skin potentials were used to confirm adequate FPL blockade. The physical exam was repeated as were pinch strength measurements. Post block splinting was necessary to stabilize the thumb IP joint. Grip strength, in addition to clinical examination, was utilized pre and post block to assess for inadvertent blockade of other muscle groups or nerves. A final clinical evaluation was conducted at study completion to note any complications or adverse effects.

Results: All three types of pinch strength showed a significant difference between pre and post measurements (p< 0.01). The mean differences pre and post were 9.7N,6.4N, and 5.2N in key, 3-point chuck, and tip pinch respectively (p< 0.01). The relative contribution of FPL for each pinch type was 53.2%,39.5%, and 44.3%. EMG, motor evoked potentials, and skin potentials confirmed adequate paralysis of the FPL. Physical examination did reveal decreased sensation in median and radial nerve distributions in some individuals, however the effect on observed motor function was negligible. Grip strength decreased by only 4N post blockade confirming no clinically significant median nerve motor blockade. The protocol was well tolerated and no serious complications were noted.

Conclusion: Using an in-vivo model we were able to estimate the contribution of FPL to overall pinch strength. In our study, FPL’s contribution to pinch strength was estimated to be 9.7N,6.4N, and 5.2N in key, 3-point chuck, and tip pinch respectively (p< 0.01). The relative contribution of FPL for each pinch type was 53.2%, 39.5%, and 44.3%. Inherent limitations in study design may have tended to overestimate the contribution of FPL to pinch. This information may be useful in planning and evaluating treatments for acute and chronic conditions affecting FPL function.

Introduction: The Plastic Surgery challenge in groin sarcoma is often twofold involving restoration of integrity to the lower abdominal wall and provision of durable soft tissue cover for the groin and perineum.

Methods: This is a retrospective review of consecutive patients undergoing groin sarcoma excision with plastic surgery involvement over the last 7 years. The referral patterns of these patients, histological types, margins and details of reconstructions performed were analysed. Information was also gathered regarding adjuvant therapy, recurrences and survival.

Results: Thirteen patients were included in this review. In twelve out of the thirteen patients initial biopsies/explorations were performed by either General Surgeons or Urologists. Ten of these biopsies were incompletely excised. On average 4.4 months elapsed between initial biopsy and referral to the Regional Sarcoma Service.

The most frequently performed reconstruction was a rectus abdominis musculo-cutaneous flap. Six patients developed post operative complications.

Complete/adequate surgical margins were achieved in seven patients. A further five patients had margins designated as “narrow” or “marginal”.

Six patients received post operative radiotherapy based on the multidisciplinary clinic review. Three patients were referred for radiotherapy but did not receive treatment. Five patients developed recurrences and four of these patients died.

Discussion: Groin sarcomas represent a surgical and logistical challenge.

The anatomical topography makes complete surgical excision difficult without available reconstructive techniques and complication rates can be high.

Referral of these patients to the regional sarcoma service is often delayed whilst exploration or biopsy is performed. This delay can persist even after a diagnosis of sarcoma has been made. Communication with colleagues in other centres may be the key to improving this side of management.

Introduction: There is controversy regarding the effectiveness of PRC for bone healing. A possible explanation is the different bone graft substitutes (BGSs) used with PRC. Here we investigated the effect of combining different BGSs with PRC on hBMSCs differentiation and growth factor release from the BGS/PRC composites.

Method: hBMSCs, DBM and allograft were prepared from femoral heads donated by patients undergoing total hip replacement. Growth factor release (TGF-â, VEGF, PDGF-AB, BMP-2) was measured by ELISA. The effect of PRC on hBMSC differentiation was determined by ALP activity and mineralisation. PRC was produced using the CAPTION device (S& N) from 10 healthy volunteers.

Results: Combining PRC with BGSs increased hBMSC proliferation (p< 0.05) and decreased ALP activity (p< 0.05) compared to DBM or â-TCP (GenOS, S& N) alone, but had no effect on allograft following 3 and 5 days treatment. After 21 days PRC enhanced mineralisation compared to all BGSs alone (16%–56%). Compared to PRC alone addition of DBM and allograft increased proliferation (p< 0.05), decreased ALP activity (p< 0.005) and decreased mineralisation (p< 0.005). TGF-â, VEGF and BMP-2 release from PRC was unaffected when combined with DBM but PDGF-AB release was reduced by 50%.

Conclusions: Combining PRC with the majority of BGSs enhanced cell proliferation and decreased osteoblastic differentiation at early time points but increased total mineralisation compared to the BGSs alone. However, compared to PRC alone combining DBM or allograft with PRC reduced mineralisation. One potential explanation for the effects of combining PRC with DBM is altered growth factor release profiles compared to the components alone.

Autologous platelet rich plasma (PRP) has an established history of clinical use in dental and orthopaedic procedures. However, there is little scientific data demonstrating a mode of action and conflicting clinical data to support its use. The aim of this study was to determine the cellular and metabolic pathways by which PRP modulates the osteogenic response. PRP is a concentrate of platelets in a small volume of plasma derived from whole blood. Platelets contain pre-packaged growth factors in & #61537;-granules that are released during clotting at the trauma site and are an essential requirement for the hard (bone) and soft tissue healing process.

S& N’s Caption ™ device, a standalone disposable device that prepares autologous PRP in 15minutes, was used to prepare human PRP. We determined a platelet concentration factor of 3.4& #61617;1.2 fold and significant increases in the concentration of platelet derived growth factor–AB (PDGF-AB), transforming growth factor-& #61538; (TGF-& #61538;) and vascular endothelial growth factor (VEGF). A 5.9 fold increase in VEGF, 4 fold increase in TGF-& #61538; and 1.5 fold increase in PDGF-AB indicate that PRP has the potential to enhance bone repair as each of these growth factors individually and synergistically affect multiple cell responses essential for tissue repair.

An in vitro study was then undertaken to investigate the effect of human PRP compared to human serum on the proliferation and differentiation of human primary osteoblasts (hOBs) and human mesenchymal stem cells (hMSCs). A significant proliferative effect of PRP compared to serum was observed in both cell types. In hMSCs, PRP treatment significantly increased proliferation after 24 hours as determined by Pico green analysis. However, in osteoblasts a proliferative effect of PRP over and above that of serum was not observed until 72 hours. These data indicate that PRP may have specific differing stimulatory effects on each cell type. Quantitative RT-PCR analysis also determined that PRP significantly increased the expression of BMP 2 over and above that of serum in human osteoblasts at both 6 and 12 hour time points. Furthermore, in hMSCs, PRP increased both BMP-2 and alkaline phosphatase gene expression at early time points suggesting the commitment of these cells to the osteoblastic lineage. This hypothesis was consistent with alkaline phosphatase protein expression which was significantly increased at 72hrs in hMSCs and was further confirmed by increased alizarin red staining, indicative of calcium deposition, in long term cultures of hMCSs treated with PRP.

In summary, these data demonstrate that PRP initiates proliferation in hMSCs and osteoblasts, enhances BMP-2 mRNA expression and induces osteoblast differentiation and maturation in human MSC cultures. Together these data demonstrate a positive effect of PRP on osteogenesis and highlight the potential for Caption™ derived PRP to enhance bone repair.

Aims: Bone and soft tissue tumours not infrequently arise from the chest wall. Resection may require removal of ribs and reconstruction using mesh, biological materials such as lyophylised pig skin and muscle flaps. The purpose of this study was to review the experience of our multidisciplinary team in the management of chest wall resections for bone and soft tissue tumours. Patients and methods: This was a retrospective review of patient records. Between 2001 and 2005, 20 patients of mean age 50.3 years (13 to 92) underwent resections involving the chest wall. Ten were male.

Results: The diagnosis was chondrosarcoma in 8, osteosarcoma in 3, PNET/Ewings in 2, MPNST in 2, sarcoma NOS in 2, and one each of leiomyosarcoma, pleomorphic MFH, and metastatic renal carcinoma. 15 patients underwent rib resection, four sternal resections and one tumour of the clavicle was removed with the underlying rib. In 3 cases a latissimus dorsi flap was used as part of the chest wall reconstruction. The surgical margins were intralesional in 5, marginal in 11 and wide in 4 cases. Two patients died following a complication of treatment. Four patients died at a mean of 6 months (4 to 8 months) from metastatic disease. Two patients had local recurrence. At a mean follow up of 26 months (4 to 58) twelve patients were alive without evidence of disease, and two were alive with metastatic disease.

Conclusion: Chest wall resection for malignant bone or soft tissue tumours is feasible and can be achieved safely. However, there is a significant mortality rate associated with this procedure. This procedure demonstrates par excellence the value of multidisciplinary team working. Local anatomical constraints may mean that achieving a wide surgical margin is not always possible.

Introduction: A major complication associated with external fixation is pin tract infection¹. This can occur in as many as 17–57%² of cases and in severe cases leads to premature removal of the fixator. An antimicrobial coated (AMC) sleeve has been designed to be placed over external fixation pin and wires that delivers an antibiotic, gentamicin, directly into the pin tract. The function of the sleeve is to inhibit bacterial colonisation of the pins and wires, the first step in the development of a clinical infection. This study reports the in vitro testing carried out to establish the effectiveness of the AMC sleeve.

Methods: The prevalence of gentamicin susceptibility amongst bacteria typically associated with pin tract infections was determined by comparing minimum inhibitory concentrations (MIC) of clinical isolates from the SENTRY Antimicrobial Surveillance Programme (1997–2002) to the NCCLS susceptibility breakpoint of < 4 μg/ml. The amount of gentamicin released over time from AMC sleeves into phosphate buffered saline (PBS) was measured using a microbiological zone of inhibition assay against S. epidermidis (NCTC 8853). Three 5 cm long sleeves, fitted over 6 mm diameter pins, were agitated in 5 ml of PBS eluant at 37°C. The eluant was replaced and tested at 2, 24, 48, 72 hours, then weekly until 26 weeks. Concentrations of gentamicin in the pin tract were calculated from these values using an estimated pin-tract volume. The ability of the sleeves to kill bacteria was measured by inoculating single 5 cm long, 5 mm diameter sleeves on pins with 1.5 ml of bacterial suspensions containing approx. 1 x 10⁸ cfu/ml. Surviving numbers of bacteria were counted after contact with the sleeves for 0.5, 1, 2 & 4 hours at 37°C. Effectiveness against clinical isolates of E. coli, S. aureus, S. epidermidis & Ps. aeruginosa was measured.

Results: The SENTRY database showed that of the 1456 individual surgical wound isolates gathered and evaluated, 1210 (83.1%) were found to be susceptible to gentamicin. Estimated concentrations of gentamicin in the pin tract reached 43.3 μg/ml at the end of the first week and exceeded the susceptibility threshold of 4 μg/ml over the next 19 weeks. The sleeves were able to reduce inoculum cell numbers of all organisms tested by 5 logs (99.9999% reduction) in ≤4h.

Discussion and Conclusion: Surveillance data confirms that gentamicin provides high level efficacy against pathogens commonly associated with pin tract infections. The AMC sleeves release gentamicin directly into the pin tract at concentrations above the susceptibility threshold for most clinically-encountered bacteria. These sleeves are also able to reduce significantly bacterial cell numbers when directly in contact with them. Therefore, this study demonstrates that the sleeves will inhibit bacterial colonisation of external fixation pins and emphasises their contribution to reducing the effects of pin tract infection.

Metacarpophalangeal (MCP) arthroplasty usually involves the fitting of a silicone spacer, commonly Swanson prosthesis, but more recently the Sutter prosthesis has been introduced.

Four Sutter MCP prostheses, two each sized 30 and 40, were removed from the right hand of a female patient. The patient aged 61 years ate revision, had longstanding rheumatoid arthritis. Using a single station finger stimulator¹ two Sutter size 50 MCP prostheses were tested. This stimulator ran at a speed of 100 cycles per minute. During each of these cycles, which flexed the test prosthesis through a 90° arc of motion, the load across the test prosthesis varied between 10N and 15N after 3000 cycles, the stimulator applied a static ‘pinch’ load and the whole combined load cycle began again. Ringer solution heated at 37°C was used as a lubricant. Clinically, the prostheses had been implanted for 53 months. All four had fractured at the junction of the hinge and distal stem. In the simulator tests the Sutter size 50 prosthesis managed just over 10 million cycles of flexion-extension, including over 3300 ‘pinch’ loads before fracture occurred, at the junction of the distal stem and hinge. The second prosthesis fractured in the same manner after 5.3 million cycles of flexion-extension.

These are the first reported in vitro results of fracture of Sutter prosthesis as well as the first paper to state the site of ex vivo fractures of Sutter prostheses. A computer model described in a recent paper ² indicated that failure of the Sutter prosthesis should occur at the central hinge region. Clearly the in vitro results and the ex vivo experience disagree with the computer model. McArthur and Milner ³ have shown clinically that the Swanson joint appears to be superior to the Sutter implant, a result confirmed elsewhere4. The finger stimulator has previously caused fracture of Swanson pros-thesis in a time and a manner comparable with surgical experience¹. Therefore another correlation with ex vivo results, but testing the Sutter prostheses has further validated the finger simulator.

The release of gentamicin sulphate, sodium fusidate and diethanolamine fusidate from Palacos and CMW cements was studied using elution and serial plate transfer tests. Further tests were made to assay the drug remaining in the cement after antibacterial activity could no longer be detected by the above methods, to detect the sustained slow release of the residual drug, and to ascertain the mechanism of release. The results confirmed that the release of gentamicin sulphate could be detected for longer from Palacos cement than from CMW cement, but the opposite was true for sodium fusidate. Little difference was found in the case of diethanolamine fusidate. Comparison of elution and serial plate transfer tests, and of results of elution in buffers of different pH, demonstrated that the test method employed had a significant effect on the results, and the omission of details of methodology from some publications made comparison and evaluation of results difficult. Varying quantities of residual drug were found in cement from which antibacterial activity could no longer be demonstrated; further tests for sustained, slow release showed that the antibiotic did not remain fixed in the cement but was released at a rate too slow to be detected in the elution and serial plate transfer tests. It is concluded that antibiotics are released from the cement by a process of diffusion, but tests to determine the mechanism of diffusion were unhelpful. The theory of diffusion of drugs through solid matrices, and the clinical implications of the experimental findings, are discussed.