Giant cell tumors of bone (GCTs) are locally aggressive tumors with recurrence potential that represent up to 10% of primary tumors of the bone. GCTs pathogenesis is driven by neoplastic mononuclear stromal cells that overexpress receptor activator of nuclear factor kappa-B/ligand (RANKL). Treatment with specific anti-RANKL antibody (denosumab) was recently introduced, used either as a neo-adjuvant in resectable tumors or as a stand-alone treatment in unresectable tumors. While denosumab has been increasingly used, a percentage of patients do not improve after treatment. Here, we aim to determine molecular and histological patterns that would help predicting GCTs response to denosumab to improve personalized treatment.

Nine pre-treatment biopsies of patients with spinal GCT were collected at 2 centres. In 4 patients denosumab was used as a neo-adjuvant, 3 as a stand-alone and 2 received denosumab as adjuvant treatment. Clinical data was extracted retrospectively. Total mRNA was extracted by using a formalin-fixed paraffin-embedded extraction kit and we determined the transcript profile of 730 immune-oncology related genes by using the Pan Cancer Immune Profiling panel (Nanostring). The gene expression was compared between patients with good and poor response to Denosumab treatment by using the nSolver Analysis Software (Nanostring). Immunohistochemistry was performed in the tissue slides to characterize cell populations and immune response in CGTs.

Two out of 9 patients showed poor clinical response with tumor progression and metastasis. Our analysis using unsupervised hierarchical clustering determined differences in gene expression between poor responders and good responders before denosumab treatment. Poor responding lesions are characterized by increased expression of inflammatory cytokines as IL8, IL1, interferon a and g, among a myriad of cytokines and chemokines (CCL25, IL5, IL26, IL25, IL13, CCL20, IL24, IL22, etc.), while good responders are characterized by elevated expression of platelets (CD31 and PECAM), coagulation (CD74, F13A1), and complement classic pathway (C1QB, C1R, C1QBP, C1S, C2) markers, together with extracellular matrix proteins (COL3A1, FN1,. Interestingly the T-cell response is also different between groups. Poor responding lesions have increased Th1 and Th2 component, but good responders have an increased Th17 component. Interestingly, the checkpoint inhibitor of the immune response PD1 (PDCD1) is increased ~10 fold in poor responders.

This preliminary study using a novel experimental approach revealed differences in the immune response in GCTs associated with clinical response to denosumab. The increased activity of checkpoint inhibitor PD1 in poor responders to denosumab treatment may have implications for therapy, raising the potential to investigate immunotherapy as is currently used in other neoplasms. Further validation using a larger independent cohort will be required but these results could potentially identify the patients who would most benefit from denosumab therapy.

This study investigated the intra-observer errors in obtaining visually selected anatomic landmarks that were used in registration process in a non-image based computer assisted TKR system.

The landmarks studied were centre of distal femur, medial and lateral femoral epicondyle, centre of proximal tibia, medial malleolus and lateral malleolus. Repeated registration in the above sequence was done for one hundred times by one single surgeon.

The maximum combined errors in the mechanical axis of the lower limb were only 1.32 degrees (varus/valgus) in the coronal plane and 4.17 degrees (flexion/extension) in the sagittal plane. The maximum error in transepicondylar axis was 8.2 degrees.

The errors using the visual selection of anatomic landmarks for the registration technique of bony landmarks in non-image based navigated TKR did not introduce significant error in the mechanical axis of the lower limb in the coronal plane. However, the error in the transepicondylar axis was significant in the “worst case scenario”.

Two hundred and thirty six posterior stabilized total knee arthroplasties were performed consecutively. Twenty seven patellar clunk syndromes were identified in 25 patients. Insall-Salvati ratio, position of joint line, postoperative patellar height and anterior-posterior position of tibial tray were measured. We found that post-operative low-lying patella (p< 0.001) and anterior placement of tibial tray (p=0.011) was associated with patellar clunk syndrome. Thirteen patients had bilateral total knee replacements of the same prosthesis (5 bilateral AMK and 8 bilateral IB) but unilateral patellar clunk syndrome. The non-clunk sides were used as control for comparison with the clunk sides. The congruency and tilting of the patellar button in the skyline view were documented. We observed that the congruency of the patella button was less satisfactory in the clunk side (p=0.019).

Objective: To compare the outcomes of two cementless total hip arthroplasty systems in young patients.

Methods: Between 1987 and 1995, 68 cementless total hip replacements were performed in 50 patients younger than 40 years (range 22–40). Five patients were excluded, and 61 hips in 45 patients were available for evaluation after 7.6 years (range 3.1–11.4). There were 27 Anatomic Medullary Locking (AML, Depuy, Warsaw, Indiana) and 34 Porous Coated Anatomic (PCA, Howmedica, Rutherford, New Jersey) prostheses. The two groups were comparable in gender, age, pre-operative diagnoses, activity levels, sizes of components used and the follow-up periods.

Results: Seven PCA (20.6%) and one AML acetabular components (3.7%) were radiologically loose (p = 0.02). Osteolysis was seen in five AML (18.5%) and 24 PCA hips (70.6%) (p = 0.001). Harris hip scores, revision rates, cumulative survival rates, femoral loosening rates, extent of stress shielding and the average linear penetration rates did not show significant differences between AML and PCA hips.

Discussion and conclusion: the PCA acetabular components had a higher loosening rate; the latter was comparable to the reported rates with this design. Osteolysis was more frequently seen in the PCA hips. Since the two groups were otherwise comparable, it was possible that either the polyethylene particles generated at the articulation could be different, or there could be increased backside wear in PCA acetabular components.

Introduction: We compared the early results of mobile-bearing knee prosthesis with fixed-bearing knee prosthesis in 20 patients who had one-stage, sequential, bilateral replacements.

Patients and Methods: In each patient, a Low Contact Stress (LCS, Depuy) rotating-platform prosthesis was inserted in one side, and an Anatomic Modular Knee (AMK, Depuy) posterior-stabilised prosthesis was inserted in the other side. The same surgical routines were adopted for both sides in each patient. The LCS and AMK knees were comparable in Knee Society knee scores, knee flexion and flexion contracture before surgery.

Results: There were significant improvements in the Knee Society knee and functional scores after surgery (p < 0.001) for both LCS and AMK knees. Although the LCS knees had better Knee Society knee score, better knee flexion, and less residual flexion contracture at final follow-up, all these were not statistically significant when compared with the AMK knees.

Discussion and Conclusion: The results of mobile-bearing knee replacements were as good as those that followed fixed-bearing knee replacements.

From 1992 to 1999, 713 total joint arthroplasties were performed in The Department of Orthopaedic Surgery, The University of Hong Kong. Since January 1993, a uniform prophylactic antibiotic regime was employed: one dose of first generation cephalosporin (one gram cephazonlin) on induction and every 4-hourly. In case of sequential bilateral total knee arthroplasty, one gram of cephazolin will be given on induction for the first knee and one hour before the operation on the opposite knee. Antibiotic will be discontinued post-operatively. No significant difference was identified between the infection rate before (1.4%) and after (1.2%) the adoption of the prophylactic antibiotic guidelines (p > 0.4). The study had shown that one dose of first generation cephalosporin is as effective as multiple dose of prophylactic antibiotic, either first or second generation cephalosporin, in preventing infection in total joint arthroplasty.