Prognostic role of PD-L1 and immune-related gene expression profiles in giant cell tumors of bone.

Giant cell tumor of bone (GCTB) is a locally aggressive and rarely metastatic tumor, with a relatively unpredictable clinical course. A retrospective series of 46 GCTB and a control group of 24 aneurysmal bone cysts (ABC) were selected with the aim of investigating the PD-L1 expression levels and immune-related gene expression profile, in correlation with clinicopathological features. PD-L1 and Ki67 were immunohistochemically tested in each case. Furthermore, comprehensive molecular analyses were carried out using NanoString technology and nCounter PanCancer Immune Profiling Panel, and the gene expression results were correlated with clinicopathological characteristics. PD-L1 expression was observed in 13/46 (28.3%) GCTB (and in 1/24, 4.2%, control ABC, only) and associated with a shorter disease free interval according to univariate analysis. Moreover, in PD-L1-positive lesions, three genes (CD27, CD6 and IL10) were significantly upregulated (p < 0.01), while two were downregulated (LCK and TLR8, showing borderline significance, p = 0.06). Interestingly, these genes can be related to maturation and immune tolerance of bone tissue microenvironment, suggesting a more immature/anergic phenotype of giant cell tumors. Our findings suggest that PD-L1 immunoreactivity may help to select GCTB patients with a higher risk of recurrence who could potentially benefit from immune checkpoint blockade.

Validation process of Toronto Exremity Salvage Score in Italian: A quality of life measure for patients with extremity bone and soft tissue tumors.

BACKGROUND AND OBJECTIVES: Limb salvage surgery remains the standard treatment in bone and soft tissue tumors. Toronto Extremity Salvage Score (TESS) is the most used quality of life measure. Our objective was to perform cross-cultural adaptation and validation in Italian, testing test-retest reliability, construct validity, and responsiveness. METHODS: We interviewed patients already treated for content validity. A total of 124 patients completed TESS and other questionnaires presurgery, at 3 months, 3 months + 2 weeks, and 6 months follow-up. We calculated intraclass correlation coefficients (ICCs) for reliability, associations with Pearson's r, and change over time with paired T tests. RESULTS: A new item regarding touch-screen devices was added to the upper extremity (UE) questionnaire. ICC resulted of 0.99 for lower extremity (LE) and 0.98 for UE patients, Pearson's r between TESS and Musculoskeletal Tumor Society was .66 and .64, EuroQol-5D-5L r was .62 and .61, and r between TESS and short form-36 physical function subscale was .76 and .71 for LE and UE groups, respectively. Paired T test results were statistically significant to detect change over time (0.03, 0.04, and 0.04 for LE groups and 0.03, 0.01, and 0.04 for UE groups). CONCLUSION: The Italian version of TESS can be used for the bone and soft tissue sarcoma population in clinical trials in Italy and with Italian speaking patients abroad to ensure patients' perspectives for efficacy and efficiency of treatments.

Outcomes of Long Bones Treated With Carbon-Fiber Nails for Oncologic Indications: International Multi-institutional Study.

BACKGROUND: Intramedullary nail fixation is commonly used for prophylactic stabilization of impending and fixation of complete pathological fractures of the long bones. However, metallic artifacts complicate imaging evaluation for bone healing or tumor progression and postoperative radiation planning. Carbon-fiber implants have gained popularity as an alternative, given their radiolucency and superior axial bending. This study evaluates incidences of mechanical and nonmechanical complications. METHODS: Adult patients (age 18 years and older) treated with carbon-fiber nails for impending/complete pathological long bone fractures secondary to metastases from 2013 to 2020 were analyzed for incidences and risk factors of mechanical and nonmechanical complications. Mechanical complications included aseptic screw loosening and structural failures of host bone and carbon-fiber implants. Deep infection and tumor progression were considered nonmechanical. Other complications/adverse events were also reported. RESULTS: A total of 239 patients were included; 47% were male, and 53% were female, with a median age of 68 (IQR, 59 to 75) years. Most common secondary metastases were related to breast cancer (19%), lung cancer (19%), multiple myeloma (18%), and sarcoma (13%). In total, 17 of 30 patients with metastatic sarcoma received palliative intramedullary nail fixation for impending/complete pathological fractures, and 13 of 30 received prophylactic nail stabilization of bone radiated preoperatively to manage juxta-osseous soft-tissue sarcomas, where partial resection of the periosteum or bone was necessary for negative margin resection. 33 (14%) patients had complications. Mechanical failures included 4 (1.7%) structural host bone failures, 7 (2.9%) implant structural failures, and 1 (0.4%) aseptic loosening of distal locking screws. Nonmechanical failures included 8 (3.3%) peri-implant infections and 15 (6.3%) tumor progressions with implant contamination. The 90-day and 1-year mortalities were 28% (61/239) and 53% (53/102), respectively. The literature reported comparable failure and mortality rates with conventional titanium treatment. CONCLUSIONS: Carbon-fiber implants might be an alternative for treating impending and sustained pathological fractures secondary to metastatic bone disease. The seemingly comparable complication profile warrants further cohort studies comparing carbon-fiber and titanium nail complications.

SS18-SSX Antibody: A Useful Tool to Save Time and Reduce Costs in Synovial Sarcoma Diagnosis. Proposal of a Novel Diagnostic Algorithm.

Synovial sarcoma is a rare malignant mesenchymal neoplasm mostly affecting young adults, characterized by a specific translocation which results in the fusion of the SS18 gene on chromosome 18 with one of the three highly homologous SSX genes on chromosome X. Its morphological diagnosis, especially in monophasic or poorly differentiated variants, can be challenging because histological features often overlap with other malignant mesenchymal tumors. Until recently, the differential diagnosis mostly relied on the use of cytogenetic or molecular analyses to detect the specific t(X;18)(p11;q11) translocation, thus virtually restricting its correct identification to referral centers with a high histological and molecular pathology workflow. The recently commercialized highly sensitive and fusion-specific SS18-SSX antibody has significantly improved the approach to these tumors, representing a relatively cheap and easy to access tool for synovial sarcoma diagnosis. Through a retrospective analysis of 79 synovial sarcomas and histological mimickers, this study confirms the usefulness of the SS18-SSX antibody in the diagnosis of synovial sarcoma, particularly focusing on its application in the pathological response evaluation after neoadjuvant treatment as well as its time- and cost-saving advantages. Finally, we here propose a new diagnostic algorithm to apply into the routine practice.

Electrochemotherapy and Simultaneous Photodynamic Bone Stabilization of Upper Limbs in Metastatic Renal Cancer Disease: Case Report and Literature Review.

INTRODUCTION: Metastatic bone disease represents a systemic pathology that heavily affects the quality of life of oncologic patients causing pain and functional disability. Methodology. We present the case of a patient with a history of renal cell cancer presenting pathologic fractures of both humeri and proximal right radius. RESULTS: After a careful multidisciplinary approach, an adjuvant anticancer therapy and a photodynamic bone stabilization procedure were performed with a minimally invasive technique aiming to minimize pain and local disease progression, while restoring functional autonomy and improving the patient's quality of life. Electrochemotherapy was delivered on the lytic bone lesions with extraskeletal involvement of the proximal left humerus and the proximal right radius, and then polymeric bone stabilization was performed on both humeri. At two months of follow-up, the patient presented satisfactory functional scores (MSTS score: 12/30 bilaterally; DASH scores: 46.7/100 for the right side and 48.3/100 for the left one), and pain was well controlled with opioid analgesics. Radiographs showed good results in terms of ossification of lytic bone lesions and durability of polymeric stabilization. At four months of follow-up, the patient reported a stable clinical scenario. Six months after surgery, due to extremely poor prognosis after the progression of primary disease, the patient was referred to palliative care and died shortly thereafter. CONCLUSION: Over the last decade, the management of metastatic bone disease has changed. Low-toxicity and minimally invasive procedures such as electrochemotherapy and polymeric bone stabilization might be performed concomitantly in selected patients, as an alternative to radiation therapy and to more demanding surgical procedures such as plating and adjuvant cementing.

A Preliminary Study on the Mechanical Reliability and Regeneration Capability of Artificial Bone Grafts in Oncologic Cases, With and Without Osteosynthesis.

Several bone grafts are available for clinical use, each with their own peculiar biological and mechanical properties. A new bone graft was obtained by combining mineral structures from natural bovine bones with bioresorbable polymers and cellular nutrients. The study aims to evaluate the clinical, biological and structural properties of this bone graft and its reliability in orthopedic oncology. 23 adult patients (age range 18-85 years) were treated between October 2016 and December 2018; the oncologicdiagnoses were heterogeneous. After surgical curettage and bone grafting, a clinical-radiological follow up was conducted. Radiographs were used to evaluate graft integration according to the usual bone healing and oncologic follow up. Local complications (infection, local recurrence, wound dehiscence, fracture or early reabsorption) were evaluated. The mean followup was of 18.34 ± 4.83 months. No fracture or infection occurred. One case of patellar Giant Cell Tumor (GCT) and one of proximal tibia low-grade chondrosarcoma recurred after about one year. Two wound dehiscences occurred (one required a local flap). Follow-up X-rays showed good to excellent graft integration in most patients (20 out of 21). The investigated graft has a mechanical and structural function that can allow early weight-bearing and avoid a preventive bone fixation (only needed in four patients in this series). The graft blocks are different for shapes and dimensions, but they can be customized by the producer or sawcut by the surgeon in the operating theatre to fit the residual bone cavity. The complication rate was low, and a rapid integration was observed with no inflammatory reaction in the surrounding tissues. Further studies are mandatory to confirm these promising results.

Femoropatellar Osteoarthritis and Trochlear Femoral Bone Defect due to Giant Cell Tumor of the Knee: A Selected Patellofemoral Joint Arthroplasty and Reconstructive Technique: A Case Report.

CASE: A 35-year-old man with a giant cell tumor involving the lateral condyle and trochlea of the right distal femur underwent curettage of the lesion and cement grafting, which resulted in symptomatic patellofemoral osteoarthritis after more than 4 years. A standard follow-up excluded recurrence, whereas infection was ruled out while investigating the symptoms. Finally, a patellofemoral resurfacing prosthesis was implanted while filling the bone defects with tantalum cones. CONCLUSION: A "tailored" surgical technique with a selected patellofemoral joint arthroplasty could be used in oncologic setting to save further bone stock for possible revisions while permitting full and quick clinical recovery.

The intraoperative use of aortic balloon occlusion technique for sacral and pelvic tumor resections: A case-control study.

INTRODUCTION: Pelvic and sacral tumor surgery is traditionally characterized by several major complications. Bleeding is probably the most feared and dreadful complication. The aim of the study was to evaluate whether the intraoperative use of the intra-aortic balloon occlusion technique could decrease the perioperative blood loss. A secondary aim was to assess aortic balloon-related complications. MATERIALS AND METHODS: From January 2014 to December 2017 15 patients (Group 1) treated with intra-aortic balloon inflation were prospectively enrolled and compared to a historical control group (Group 2) of 11 patients with similar surgeries. Number of blood units transfused, perioperative hemoglobin values, hours spent in intensive care unit (ICU), length of inpatient stay, and perioperative complications were evaluated. RESULTS: Intraoperatively, a mean of 6.1 blood units per patient (BUPP) was used in Group 1 and 16.2 BUPP in Group 2. Postoperatively the averages were 2,8 and 5,4 BUPP in Group 1 and 2, respectively. Patients in Group 1 had a faster recovery in hemoglobin values, as well as a shorter length of overall inpatient stay (28,9 vs 59 days) and of ICU stay (33.9 vs 74.6 h). The most relevant complications observed in Group 1 were two thrombosis at the incannulation site that required a surgical arterial thrombectomy. CONCLUSION: The intra-aortic balloon occlusion is an effective technique to control bleeding during the resections of huge pelvic and sacral tumors. A proper training of a multidisciplinary team and an accurate patient selection are required to prevent major complications.

Gait analysis: Comparative evaluation of conventional total knee replacement and modular distal femoral megaprosthesis.

BACKGROUND: Gait alterations have been studied with computer-assisted gait analysis after megaprosthetic replacement for tumors around the knee. It has never been proven that megaprostheses affects gait more than total knee arthroplasty (TKA); this study aims to compare via gait analysis patients who underwent megaprosthesis with patients with TKA. METHODS: We analyzed 26 patients with a megaprosthetic replacement of the distal femur and 21 patients with a standard TKA. For each subject computerized gait analysis was performed. Range of motion (ROM) of the knee was recorded, Quality of Life and functional evaluation in the oncologic group were assessed with the Musculoskeletal Tumor Society (MSTS) questionnaire, while Short Form-36 (SF-36) scores were calculated for both groups. RESULTS: All patients walked slower than healthy people (P < 0.05). Gait analysis showed a lower cadence than in the healthy population but no significant difference between the two groups. A longer swing and a shorter stance phase were detected in the megaprosthetic sample. The osteoarthritis group showed greater flexion during the phase of loading response, even if this was lower than the contralateral limb or healthy population. There was a statically significant difference between the healthy limb and the operated one in both groups regarding ROM, but no significant difference was registered between the two implants. MSTS score and most of SF-36 parameters showed no significant differences compared with literature data. CONCLUSIONS: Gait analysis shows little discrepancy between the two groups; gait pattern abnormalities do not affect patients with a megaprosthetic replacement more significantly than patients undergoing TKA.

Cruciate retaining and cruciate substituting ultra-congruent insert.

The posterior cruciate ligament (PCL) conservation and the polyethylene insert constraint in total knee arthroplasty (TKA) are still debated. The PCL is one of the primary stabilizers of the joint, but cruciate retaining (CR) implants have the disadvantage of a difficult balancing of the PCL. Postero-stabilized (PS) implants were introduced to reduce this problem. However, also the PS implants have some disadvantages, due to the cam-mechanism, such as high risk of cam-mechanism polyethylene wear. To minimize the polyethylene wear of the cam-mechanism and the bone sacrifice due to the intercondylar box, different types of inserts were developed, trying to increase the implant conformity and to reduce stresses on the bone-implant interface. In this scenario ultra-congruent (UC) inserts were developed. Those inserts are characterized by a high anterior wall and a deep-dished plate. This conformation should guarantee a good stability without the posterior cam. Few studies on both kinematic and clinical outcomes of UC inserts are available. Clinical and radiological outcomes, as well as kinematic data are similar between UC mobile bearing (MB) and standard PS MB inserts at short to mid-term follow-up. In this manuscript biomechanics and clinical outcomes of UC inserts will be described, and they will be compared to standard PS or CR inserts.

Total knee arthroplasty and infection: how surgeons can reduce the risks.

Total joint arthroplasty (TJA) is one of the most common orthopaedic procedures. Nevertheless, several complications can lead to implant failure.Peri-prosthetic joint infections (PJI) certainly represent a significant challenge in TJA, constituting a major cause of prosthetic revision. The surgeon may have an important role in reducing the PJI rate by limiting the impact of significant risk factors associated to either the patient, the operative environment or the post-operative care.In the pre-operative period, several preventive measures may be adopted to manage reversible medical comorbidities. Other recognised pre-operative risk factors are urinary tract infections, intra-articular corticosteroid injections and nasal colonisation with Staphylococcus (S.) aureus, particularly the methicillin-resistant strain (MRSA).In the intra-operative setting, protective measures for PJI include antibiotic prophylaxis, surgical-site antisepsis and use of pre-admission chlorhexidine washing and pulsed lavage during surgery. In this setting, the use of plastic adhesive drapes and sterile stockinette, as well as using personal protection systems, do not clearly reduce the risk of infection. On the contrary, using sterile theatre light handles and splash basins as well as an increased traffic in the operating room are all associated with an increased risk for PJI.In the post-operative period, other infections causing transient bacteraemia, blood transfusion and poor wound care are considered as risk factors for PJI. Cite this article: Ratto N, Arrigoni C, Rosso F, Bruzzone M, Dettoni F, Bonasia DE, Rossi R. Total knee arthroplasty and infection: how surgeons can reduce the risks. EFORT Open Rev 2016;1: 339-344 DOI: 10.1302/2058-5241.1.000032.