Personalizing Prophylactic Radiotherapy for Hip Heterotopic Ossification: An AMSTAR-2 Compliant Review of Meta-analyses.

BACKGROUND/AIM: Heterotopic ossification (HO) is a common complication following total hip arthroplasty. Various prophylactic treatments have been proposed, including radiotherapy (RT). This review summarizes the evidence from meta-analyses on the efficacy of RT in preventing hip HO. MATERIALS AND METHODS: A literature search was conducted on PubMed. The quality of the meta-analyses was assessed using the AMSTAR-2 tool. RESULTS: Seven meta-analyses were included. One meta-analysis reported a significant reduction in HO occurrence after RT compared to the control group. Comparing RT and non-steroidal anti-inflammatory drugs, one and two meta-analyses showed significantly greater efficacy of RT in preventing severe HO and better outcomes in patients receiving drugs, respectively. Regarding RT settings, the postoperative and preoperative RT were each supported by one meta-analysis. Furthermore, two meta-analyses showed an advantage of multi-fractionated RT over single fraction RT. The overall confidence rate of the meta-analyses was moderate, low, and critically low in one, three, and three meta-analyses, respectively. CONCLUSION: RT is a confirmed prophylactic intervention for HO. However, the precise optimization of timing, dosage, and fractionation requires elucidation. Future research should focus on the development of predictive models through large-scale data collection and advanced analytics to refine individualized treatment strategies and assess RT comparative effectiveness with drugs.

Management of periprosthetic joint infection of shoulder arthroplasty: Single-stage versus two-stage protocols. A systematic review and meta-analysis of the literature.

Background: The treatment of shoulder prosthetic joint infections (PJIs) requiring removal of the prosthesis is not well defined. This article aims to systematically review and compare the results of the literature in single-stage and two-stage protocols in the treatment of shoulder PJI. Methods: An in-depth search on PubMed/Scopus/Web of Science databases and cross-referencing search was carried out concerning the articles reporting detailed data on the topic. Results: A total of 486 shoulder PJIs were included: 137 treated with single-stage and 349 with two-stage procedure. A similar distribution between early and not-early infections (19.1% vs 80.9%) was found between the two groups. The overall rate of success in terms of PJI eradication was significantly higher in the single-stage group (95.6% vs 85.7%, p < 0.001). The non-infection-related complications rate was 13.8% in the single-stage group and 37.6% in the two-stage group (p < 0.001), the non-infection-related revision rate was 8% and 18.9%, respectively (p = 0.005). Discussion: The single-phase protocol showed a higher success rate in eradicating the infection and a lower complication rate. However, the low number of patients included, the low quality of the articles, the lack of data on clinical severity and bacteriological virulence suggest caution in conclusions.

Porous tantalum acetabular cups for reconstructions after peri-acetabular resections of primary bone tumours.

INTRODUCTION: Periacetabular reconstruction after resection of primary bone tumour is a very demanding procedure. They are frequently associated with scarce functional results and a high rate of complications. We report a series of patients with periacetabular resections for primary bone tumours and reconstruction with a porous tantalum (PT) acetabular cup (AC). MATERIALS AND METHODS: 27 patients (median age 30 years) were included, being affected by primary bone tumours of the pelvis and treated with peri-acetabular resection and reconstruction with a PT AC. The diagnoses were 13 osteosarcomas, 7 chondrosarcomas and 7 Ewing sarcomas. Function was assessed with the Harris Hip Score and complications were classified according to Zeifang. RESULTS: The median follow-up was 70 months. 1 patient required removal of the PT AC because of implant associated infection 55 months after surgery. There was 1 hip dislocation and no case of aseptic loosening. At final follow-up, the median HHS was 81 points (range 48-92). CONCLUSIONS: The used PT AC had good medium-term survival rates and good functional results. This technique is a viable reconstructive option after resections of periacetabular primary bone sarcomas.

Mechanical complications of hip spacers: a systematic review of the literature.

INTRODUCTION: Temporary spacers used in the staged revision of a hip prosthetic joint infection (PJI) have been associated with several mechanical complications with very variable reported general complications rates up to 73%. The aim of this systematic review was to assess the mechanical complications associated with hip antibiotic-loaded spacers when treating periprosthetic hip PJI. METHODS: Through an electronic systematic search of PubMed, articles reporting mechanical complications of spacers used in the treatment of hip PJI were reviewed. Dislocations, spacer fracture, femoral fractures, and acetabular lysis rates were evaluated. RESULTS: Forty studies were included. Standardized molded spacers had a significantly higher weighted mean of total mechanical complication rates (37.2%) when compared to standardized preformed spacers (13.8%, p = 0.039), while no significant difference was found between molded spacers and manually shaped spacers. Spacer dislocation was the most frequent complication. No significant difference in mechanical complication rate was found between spacers with and without any metallic component. CONCLUSIONS: Spacer placement in chronic PJI of the hip with bone and soft-tissue defects is challenging and bears a high risk of mechanical failures and progressive bone loss during the interim period. A careful patient selection for spacer implantation is mandatory.

Are Static Spacers Superior to Articulated Spacers in the Staged Treatment of Infected Primary Knee Arthroplasty? A Systematic Review and Meta-Analysis.

In the treatment of knee periprosthetic joint infection with a two-stage protocol, static spacers allow for the local delivery of high doses of antibiotics and help to preserve soft tissue tension. Articulated spacers were introduced to better preserve flexion after the reimplantation. The aim of this systematic review is to provide a comprehensive data collection of the results of these different spacers. An in-depth search on the main clinical databases was performed concerning the studies reporting data on the topic. A total of 87 studies and 4250 spacers were included. No significant differences were found both in pooling data analysis and meta-analysis of comparative studies about infection recurrences, complications, and clinical scores. Mean active knee flexion at last follow-up after total knee reimplantation was found to be significantly higher using articulated spacers (91.6° ± 7° for static spacers vs. 100.3° ± 9.9° for articulated spacers; p < 0.001). Meta-analysis also recognized this strong significant difference (p < 0.001). This review has confirmed that articulated spacers do not appear to be inferior to static spacers regarding all clinical outcomes, while they are superior in terms of active flexion. However, the low quality of the studies and the risk for selection bias with complex patients preferentially treated with static spacers need to be accounted for.

Combined Orthoplastic Approach in Fracture-Related Infections of the Distal Tibia.

This series reports on the treatment of distal tibia (DT) fracture-related infections (FRI) with a combined orthoplastic approach. Thirteen patients were included. In eight patients with extensive bone involvement and in those with a non-healed fracture, the DT was resected ("staged approach"). In five cases, the DT was preserved ("single-stage approach"). A wide debridement was performed, and the cavity was filled with antibiotic-loaded PerOssal beads. All patients had a soft-tissue defect covered by a free vascularized flap (anterolateral thigh perforator flap in eight cases, latissimus dorsi flap in five). At the final follow-up (mean 25 months, range, 13-37), no infection recurrence was observed. In one patient, the persistence of infection was observed, and the patient underwent a repeated debridement. In two cases, a voluminous hematoma was observed. However, none of these complications impacted the final outcome. The successful treatment of FRI depends on proper debridement and obliteration of dead spaces with a flap. Therefore, when dealing with DT FRI, debridement of infected bone and soft tissues must be as radical as required, with no fear of the need for massive reconstructions.

Synchronous Periprosthetic Joint Infections: A Scoping Review of the Literature.

Prosthetic joint infections (PJIs) occurring in multiple joints at the same time (synchronous PJI) are an extremely rare complication, frequently associated with bacteremia, and are associated with high mortality rates. The presence of three or more prosthetic joints, rheumatoid arthritis, neoplasia, bacteremia and immune-modulating therapy seem to be the recurring risk factors for synchronous PJI. In case of PJIs, all other replaced joints should be considered as potentially infected and investigated if PJI is suspected. Treatments of synchronous multiple PJIs vary and must be decided on a case-by-case basis. However, the advantages of one-stage exchange seem to outweigh the two-stage protocol, as it decreases the number of necessary surgical procedures. Nonetheless, too few studies have been conducted to allow firm conclusions about the best handling of synchronous PJI. Thus, additional studies are needed to understand this devastating complication and to design the most appropriate diagnostic and therapeutic path.

Is Silver the New Gold? A Systematic Review of the Preclinical Evidence of Its Use in Bone Substitutes as Antiseptic.

Antibiotic-laden bone substitutes represent a viable option in the treatment of bone and joint infections with bone defects. In particular, the addition of silver ions or silver nanoparticles to bone substitutes to achieve local antiseptic activity could represent a further contribution, also helping to prevent bacterial resistance to antibiotics. An in-depth search of the main scientific databases was performed regarding the use of silver compounds for bone substitution. The available evidence is still limited to the preclinical level: 22 laboratory studies, 2 animal models, and 3 studies, with both in vitro and in vivo analysis, were found on the topic. Numerous biomaterials have been evaluated. In vitro studies confirmed that silver in bone substitutes retains the antibacterial activity already demonstrated in coatings materials. Cytotoxicity was generally found to be low and only related to silver concentrations higher than those sufficient to achieve antibacterial activity. Instead, there are only a few in vivo studies, which appear to confirm antibacterial efficacy, although there is insufficient evidence on the pharmacokinetics and safety profile of the compounds investigated. In conclusion, research on bone substitutes doped with silver is in its early stages, but the preliminary findings seem promising.

Prophylactic Radiotherapy of Hip Heterotopic Ossification: A Narrative Mini Review.

Evidence on prophylactic radiotherapy (RT) in hip heterotopic ossification (HO) is sparse and conflicting. The aim of this literature review was to collect and summarize the available data on RT efficacy in preventing hip HO. The results of this review show that RT is effective in the prevention of hip HO, albeit with large variability across series. Effective prophylactic RT requires optimal treatment fields and time intervals with surgery. On the contrary, there is no clear evidence on the optimal timing (post-operative versus pre-operative RT). Comparisons between prophylactic RT and use of non-steroidal anti-inflammatory drugs showed conflicting results, although most were in favor of RT. In conclusion, RT is an established prophylactic treatment for hip HO. However, optimal dose, technique and timing remain unclear, as does the usefulness of combining RT with drugs.

Anatomical and reverse megaprosthesis in proximal humerus reconstructions after oncologic resections: a systematic review and meta-analysis.

AIM: Anatomic (AN) Endoprosthesis (EPR) reconstructions of the shoulder after intra-articular proximal humerus (Malawer type 1) resections are characterized by early recovery and low complications rate. However, shoulder instability and limited mobility can occur. Reverse shoulder (RS) EPR has been introduced to improve functional outcome. The aim of this systematic review is to evaluate shoulder reconstructions with AN or RS EPR after Malawer type 1 resection, comparing complications and functional results. METHODS: Through an electronic systematic search of PubMed, articles concerning EPR after shoulder Malawer type 1 resections were reviewed. Complications rate, range of motion (ROM) and functional outcome (Musculoskeletal Society Tumor Society-MSTS score) of AN and RS EPR were evaluated. RESULTS: Sixteen studies were included. A similar complication rate was observed between AN and RS EPR rate (26.4% and 22.4%, respectively, p = 0.37). Soft tissue failure was the most frequent complication and cause of revision in both groups. Mean post-operative flexion and abduction ROM and MSTS scores were significantly higher in RS EPR, particularly among patients with preserved deltoid function (p = 0.013, p = 0.025 and p = 0.005, respectively). CONCLUSIONS: Anatomic and reverse shoulder EPR represent safe and effective implants for shoulder reconstruction, with similar implant stability and complication rates. RS EPR significantly improves post-operative ROM and functional outcomes, especially when at least a partial function of the abductor apparatus is preserved.

The Role of Imaging in Computer-Assisted Tumor Surgery of the Sacrum and Pelvis.

The use of a navigation system allows precise resection of a tumor and accurate reconstruction of the resultant defect thereby sparing important anatomical structures and preserving function. It is an "image-based" system where the imaging (computed tomography and magnetic resonance imaging) is required to supply the software with data. The fusion of the preoperative imaging provides pre-operative information about local anatomy and the extent of the tumor so that it allows accurate preoperative planning. Accurate pre-operative imaging is mandatory in order to minimize CATS errors, thus performing accurate tumor resections.

Primary Tumors of the Sacrum: Imaging Findings.

The diagnosis of sacral neoplasms is often delayed because they tend to remain clinically silent for a long time. Imaging is useful at all stages of the management of sacral bone tumors, i.e., from the detection of the neoplasm to the long-term follow-up. Radiographs are recommended as the modality of choice to begin the imaging workup of a patient with known or suspected sacral pathology. More sensitive examinations, such as Computerized Tomography (CT), magnetic resonance (MRI), or scintigraphy, are often necessary. The morphological features of the lesions on CT and MRI help orientate the diagnosis. Although some imaging characteristics are helpful to limit the differential diagnosis, an imaging-guided biopsy is often ultimately required to establish a specific diagnosis. Imaging is of paramount importance even in the long-term follow-up, in order to assess any residual tumor when surgical resection remains incomplete, to assess the efficacy of adjuvant chemotherapy and radiotherapy, and to detect recurrence.

Intercalary reconstruction of the distal femur with or without physeal preservation: results and impact on limb growth.

PURPOSE: Allograft reconstruction with or without vascularized fibula can be a valuable solution to treat childhood intercalary tumours of the distal femur. We aimed to assess the oncological status, complication rate and survival of distal femur intercalary reconstruction after trans-metaphyseal (TMR) and trans-epiphyseal resection (TER). We also evaluated the impact of distal temporary graft fixation on skeletal growth after TMR. METHODS: We retrospectively reviewed 23 skeletally immature patients affected by distal femur osteosarcoma (18) and Ewing sarcoma (5). Mean patients age was 10.3 years. In 11 cases, TMR was performed with physis preservation and temporary distal graft fixation. In 9 patients, TER was performed with growth plate sacrifice. The last 3 cases were treated with TMR and sliding plate fixation. RESULTS: Mean follow-up was 8.4 years. No deaths occurred, but 3 patients presented lung metastasis and 2 cases presented local recurrence in soft tissues. 10 implant-related complications occurred, all surgically treated. At skeletal maturity, mean femoral dysmetria was 2.3 cm after TMR and temporary epiphysiodesis, and 3.1 cm after TER. In TMR group, a strong trend towards physeal recovery was observed after epiphyseal screws removal (p = 0.061), but valgus deformity in distal femur was more frequent (p = 0.049). MSTS score was good or excellent in all patients, with no statistically significant difference between TMR and TER. CONCLUSIONS: Intercalary graft reconstruction after TMR and TER allows good local disease control and excellent functional results with long-term follow-up. Temporary distal fixation might reduce the final limb discrepancy after TMR, but valgus deformity could develop. LEVEL OF EVIDENCE: Level IV.

Surgical treatment scenario for osteoblastoma of the pelvis: Long-term follow-up results.

BACKGROUND: The aim of this study was to evaluate the results of different treatments for pelvic Osteoblastoma (OB). METHODS: We retrospectively evaluated 34 patients affected by primary pelvic OB from 3 oncologic referral centers. Patients with a minimum follow-up of 24 months were included. Local recurrence (LR) rate and complications were recorded. RESULTS: The primary treatment was radio-frequency ablation (RFA) in 4 patients (11.8%), curettage (ILC) in 21 (61.7%) and resection (EBR) in 9 (26.5%). Mean follow-up was 8.9 years (SD ± 6.6). Local recurrence free survival (LRFS) rate after primary surgery was 79.4% at 3 and 5 years. In details, LRFS rate at 3 and 5 years was 50.0% in RFA, 81.0% in ILC and 88.9% in EBR. Post-operative complications occurred in 6/34 patients (17.7%), in particular after EBR. CONCLUSIONS: RFA is the least invasive technique to treat OB but with high LR rate. Thus, it should be reserved to very small lesions. ILC is a suitable treatment for stage II OB. For stage III OB, EBR is the treatment of choice, despite an increased risk of complications. For selected stage III OB (relatively small, periacetabular area) ILC might be considered.

Bone and Joint Infections: The Role of Imaging in Tailoring Diagnosis to Improve Patients' Care.

Imaging is needed for the diagnosis of bone and joint infections, determining the severity and extent of disease, planning biopsy, and monitoring the response to treatment. Some radiological features are pathognomonic of bone and joint infections for each modality used. However, imaging diagnosis of these infections is challenging because of several overlaps with non-infectious etiologies. Interventional radiology is generally needed to verify the diagnosis and to identify the microorganism involved in the infectious process through imaging-guided biopsy. This narrative review aims to summarize the radiological features of the commonest orthopedic infections, the indications and the limits of different modalities in the diagnostic strategy as well as to outline recent findings that may facilitate diagnosis.

The Biology of Synovial Sarcoma: State-of-the-Art and Future Perspectives.

OPINION STATEMENT: New molecular insights are being achieved in synovial sarcoma (SS) that can provide new potential diagnostic and prognostic markers as well as therapeutic targets. In particular, the advancement of research on epigenomics and gene regulation is promising. The concrete hypothesis that the pathogenesis of SS might mainly depend on the disruption of the balance of the complex interaction between epigenomic regulatory complexes and the consequences on gene expression opens interesting new perspectives. The standard of care for primary SS is wide surgical resection combined with radiation in selected cases. The role of chemotherapy is still under refinement and can be considered in patients at high risk of metastasis or in those with advanced disease. Cytotoxic chemotherapy (anthracyclines, ifosfamide, trabectedin, and pazopanib) is the treatment of choice, despite several possible side effects. Many possible drug-able targets have been identified. However, the impact of these strategies in improving SS outcome is still limited, thus making current and future research strongly needed to improve the survival of patients with SS.

Distal Fibula Reconstruction in Primary Malignant Tumours.

(1) Background: Restoration of ankle biomechanics after distal fibula (DF) resection in bone sarcomas can be performed with different techniques. We report the functional and oncological outcomes of a case series; (2) Methods: Ten patients (5 females and 5 males) with a mean age of 27 years (range 10-71) were retrospectively evaluated. Following the resection, different techniques were used to reconstruct the ankle: tibiotalar arthrodesis, residual lateral malleolus fixed to the tibia, non-vascularized or rotational vascularized fibula transposition and intercalary allograft. All complications were recorded, and the functional outcomes were evaluated; (3) Results: The mean follow-up time was 54 months (range, 13-116). Six patients were free of disease while four patients died of disease. All patients had a stable ankle and bone union, which was achieved after a mean of 9.4 months (range 3-20). The mean MSTS Score was 26.7 (range 21-30). Chronic ankle pain and peroneal external nerve palsy were observed. Patients underwent additional surgeries for deep infection and for equinus ankle deformity. No local recurrence was observed. Metastasis occurred in four patients after a mean of 14.7 months (range 2-34); (4) Conclusions: After DF resection, the restoration of ankle biomechanics gives acceptable functional results, but a larger series of patients with long-time follow-up are required to confirm the durability of the reconstruction.

Megaprosthesis Reconstruction of the Proximal Femur following Bone Tumour Resection: When Do We Need the Cup?

PURPOSE: Reconstruction of the proximal femur after tumour resection can be performed with proximal femoral endopros-theses (PFE). Many studies have reported that bipolar hemiarthroplasty (BHA) reduce the risk of dislocation after oncological resections. However, progressive cotyloiditis which might require acetabular resurfacing (total hip arthroplasty [THA]) has been reported. The aim of this study is to compare the results of BHA and THA after proximal femur resection. MATERIALS AND METHODS: A total of 104 consecutive patients affected by primary (n=52) and metastatic (n=52) bone tumours were included. Ninety patients underwent BHA and 14 patients underwent THA. Complications were recorded and classified according to the Henderson classification. At final follow-up, patients with the implant in site were functionally evaluated with modified Harris hip score (HHS). RESULTS: The mean follow-up was 50 months (range, 2-171 months). Twenty-four (23.1%) patients developed major complications. Eleven (12.2%) BHA required acetabular resurfacing. Patients affected by primary bone tumours showed an increased risk of THA conversion (P=0.042). A reduced risk was observed in patients younger than 35 years (P=0.043) and in those older than 65 years (P=0.033). Dislocation occurred in four case (3.8%), in particular after THA (P=0.021). At final follow-up, 93 patients had the prosthesis in site (80 BHA and 13 THA). Mean postoperative HHS was 70 (range, 30-90). CONCLUSION: The risk of dislocation is lower for bipolar endoprosthesis compared to THA. However cotyloiditis and acetabular resurfacing might occurred.

Margin Assessment in Soft Tissue Sarcomas: Review of the Literature.

Adequacy of margins must take into consideration both the resection margin width (quantity) and anatomic barrier (quality). There are several classification schemes for reporting surgical resection margin status for soft tissue sarcomas (STS). Most of the studies regarding treatment outcomes in STS included all histologic grades and histological subtypes, which include infiltrative and non-infiltrative subtypes and are very heterogeneous in terms of both histologic characteristics and treatment modalities (adjuvant treatments or not). This lack of consistency makes it difficult to compare results from study to study. Therefore, there is a great need for evidence-based standardization concerning the width of resection margins. The aim of this narrative review is to provide a comprehensive assessment of the literature on margins, and to highlight the need for a uniform description of the margin status for patients with STS. Patient cases should be discussed at multidisciplinary tumor boards and treatments should be individualized to clinical and demographic characteristics, which must include also a deep knowledge of specific histotypes behaviors, particularly infiltrative ones.

Silver-coated megaprosthesis in prevention and treatment of peri-prosthetic infections: a systematic review and meta-analysis about efficacy and toxicity in primary and revision surgery.

AIM: Prosthetic joint infection (PJI) is a common complication following orthopedic megaprosthetic implantations (EPR), estimated up to 50%. Silver coatings were introduced in order to reduce the incidence of PJI, by using the antibacterial activity of silver. Three different silver coatings are available: MUTARS® (Implantcast), Agluna® (Accentus Medical), PorAg® (Waldemar Link). The aim of this review is to provide an overview on efficacy and safety of silver-coated EPR both in primary and revision surgery, comparing infection rate according to the type of implant. METHODS: Through an electronic systematic search, we reviewed the articles concerning silver-coated EPRs. Infection rate, silver-related complications, local and blood concentrations of the silver were evaluated. Meta-analyses were performed to compare results from each study included. RESULTS: Nineteen studies were included. The overall infection rate in patients with silver-coated implants was 17.6% (133/755). Overall infection rate in primary silver-coated EPR was been 9.2% (44/445), compared to 11.2% (57/507) of non-silver-coated implants. The overall infection rate after revisions was 13.7% (25/183) in patients with silver-coated EPR and 29.2% (47/161) when uncoated EPR were used, revealing a strength statistically significative utility of silver coatings in preventing infections in this group (p: 0.019). Generally, the use of MUTARS® EPR had produced an almost constant decrease in the incidence of primary PJI but there are few data on the effectiveness in revisions. The results from the use of Agluna® in both primary and revisions implants are inconstant. Conversely, PorAg® had proven to be effective both in PJI prevention but, especially, when used in PJI revision settings. Local argyria was reported in 8 out of 357 patients (2.2%), while no systemic complications were described. Local and blood concentrations of silver were always reported very far to the threshold of toxicity, with the lowest concentration found using PorAg®. CONCLUSIONS: Silver-coated EPRs are safe and effective in reduction in PJI and re-infection rate, in particular when used in higher risk patients and after two-stage revisions to fight PJI.