Health-related quality of life and associated risk factors in patients with Multiple Osteochondromas: a cross-sectional study.

PURPOSE: To evaluate the health-related quality of life and associated risk factors for Multiple Osteochondromas patients. METHODS: A cross-sectional, observational study was conducted from May to December 2022 during the routine visit to the referral center for rare skeletal disorders. All patients with Multiple Osteochondromas aged ≥ 3 years were included. EuroQol 5-dimension questionnaires, and demographic, clinical, and surgical history data were collected. Descriptive statistics, Fisher's exact test, One-sample t-test, Spearman's correlation, and multiple linear and logistic regression were performed to analyze the data. Results are reported following STROBE guidelines. RESULTS: A total of 128 patients were included in the study, with a mean age of 14 [SD, 10] years. The mean EQ-5D Index Value was 0.863 [SD, 0.200] and the EQ-VAS was 84 [SD, 19] with a positive correlation between two scores [r = 0.541, p < 0.001]. Patients frequently referred problems in pain/discomfort [78.8%], anxiety/depression [50%], and usual activities [38.8%] dimensions. Increasing age was the common risk factor for health-related quality of life [p < 0.000], as well as Index Value and VAS scores were significantly lower in surgical patients [p = 0.001 and p < 0.001, respectively]. CONCLUSION: Increasing age and surgical procedures were found highly associated with reduced health-related quality of life in Multiple Osteochondromas patients. Our findings provide relevant information to support the establishment of patient-centered healthcare pathways and pave the way for further research into medical and non-medical therapeutic strategies for these patients.

Tenosynovial Giant Cell Tumor Observational Platform Project (TOPP) Registry: A 2-Year Analysis of Patient-Reported Outcomes and Treatment Strategies.

BACKGROUND: The Tenosynovial giant cell tumor Observational Platform Project (TOPP) registry is an international prospective study that -previously described the impact of diffuse-type tenosynovial giant cell tumour (D-TGCT) on patient-reported outcomes (PROs) from a baseline snapshot. This analysis describes the impact of D-TGCT at 2-year follow-up based on treatment strategies. MATERIAL AND METHODS: TOPP was conducted at 12 sites (EU: 10; US: 2). Captured PRO measurements assessed at baseline, 1-year, and 2-year follow-ups were Brief Pain Inventory (BPI), Pain Interference, BPI Pain Severity, Worst Pain, EQ-5D-5L, Worst Stiffness, and -Patient-Reported Outcomes Measurement Information System. Treatment interventions were no current/planned treatment (Off-Treatment) and systemic treatment/surgery (On-Treatment). RESULTS: A total of 176 patients (mean age: 43.5 years) were included in the full analysis set. For patients without active treatment strategy -(Off-Treatment) at baseline (n = 79), BPI Pain Interference (1.00 vs. 2.86) and BPI Pain Severity scores (1.50 vs. 3.00) were numerically favorable in patients remaining Off-Treatment compared with those who switched to an active treatment strategy at year 1. From 1-year to 2-year -follow-ups, patients who remained Off-Treatment had better BPI Pain Interference (0.57 vs. 2.57) and Worst Pain (2.0 vs. 4.5) scores compared with patients who switched to an alternative treatment strategy. In addition, EQ-5D VAS scores (80.0 vs. 65.0) were higher in patients who remained -Off-Treatment between 1-year and 2-year follow-ups compared with patients who changed treatment strategy. For patients receiving systemic treatment at baseline, numerically favorable scores were seen in patients remaining on systemic therapy at 1-year follow-up: BPI Pain Interference (2.79 vs. 5.93), BPI Pain Severity (3.63 vs. 6.38), Worst Pain (4.5 vs. 7.5), and Worst Stiffness (4.0 vs. 7.5). From 1-year to 2-year follow-up, EQ-5D VAS scores (77.5 vs. 65.0) were higher in patients who changed from systemic treatment to a different treatment strategy. CONCLUSION: These findings highlight the impact D-TGCT has on patient quality of life, and how treatment strategies may be influenced by these outcome measures. (ClinicalTrials.gov number: NCT02948088).

Is the association of electrochemotherapy and bone fixation rational in patients with bone metastasis?

BACKGROUND: Bone metastases are frequent in patients with cancer. Electrochemotherapy (ECT) is a minimally invasive treatment based on a high-voltage electric pulse combined with an anticancer drug. Preclinical and clinical studies supported the use of ECT in patients with metastatic bone disease, demonstrating that it does not damage the mineral structure of the bone and its regenerative capacity, and that is feasible and efficient for the treatment of bone metastases. Year 2014 saw the start of a registry of patients with bone metastases treated with ECT, whose data are recorded in a shared database. QUESTIONS/PURPOSES: (1) Among patients who underwent ECT and internal fixation for bone metastasis, how many experienced a reduction of pain? (2) How many cases showed a radiological response? (3) How many patients presented local or systemic complication after ECT and fixation? PATIENTS AND METHODS: Patients were treated in Bologna at Rizzoli Orthopaedic Institute between March 2014 and February 2022 and recorded in the REINBONE registry (a shared database protected by security passwords): clinical and radiological information, ECT session, adverse events, response, quality of life indicators, and duration of follow-up were registered. We consider only cases treated with ECT and intramedullary nail during the same surgical session. Patients included in the analysis were 32: 15 males and 17 females, mean age 65 ± 13 years (median 66, range 38-88 years), mean time since diagnosis of primary tumor 6.2 ± 7.0 years (median 2.9, range 0-22 years). Nail was indicated in 13 cases for a pathological fracture in, 19 for an impending fracture. Follow-up was available for 29 patients, as 2 patients were lost to follow-up and 1 was unable to return to controls. Mean follow-up time was 7.7 ± 6.5 months (median 5, range 1-24), and 16 patients (50%) had a follow-up longer than 6 months. RESULTS: A significant decrease in pain intensity was observed at the mean Visual Numeric Scale after treatment. Bone recovery was observed in 13 patients. The other 16 patients remained without changes, and one presented disease progression. One patient presented a fracture occurrence during the ECT procedure. Among all patients, bone recovery was observed in 13 patients: complete recovery in 1 patient (3%) and partial recovery in 12 patients (41%). The other 16 patients remained without changes, and one presented disease progression. One patient presented a fracture occurrence during the ECT procedure. However, healing was possible with normal fracture callus quality and healing time. No other local or systemic complications were observed. CONCLUSION: We found that pain levels decreased after treatment in 23 of the 29 cases for a pain relief rate of 79% at final follow-up. Pain is one of the most important indicators of quality of life in patients that undergo palliative treatments. Even if conventional external body radiotherapy is considered a noninvasive treatment, it presents a dose-dependent toxicity. ECT provides a chemical necrosis preserving osteogenic activity and structural integrity of bone trabeculae; this is a crucial difference with other local treatments and allows bone healing in case of pathological fracture. The risk of local progression in our patient population was small, and 44% experienced bone recovery while 53% of the cases remained unchanged. We observe intraoperative fracture in one case. This technique, in selected patients, improves outcome in bone metastatic patients combing both the efficacy of the ECT in the local control of the disease and the mechanical stability with the bone fixation to synergize their benefits. Moreover, the risk of complication is very low. Although encouraging data, comparative studies are required to quantify the real efficacy of the technique. Level of Evidence Level I, therapeutic study.

Aneurysmal bone cyst: Is selective arterial embolization effective as curettage and bone grafting?

INTRODUCTION: Aneurysmal bone cyst (ABC) is a lytic benign bone lesion representing about 1% of all primary bone tumors. Method to treat ABC's have developed over time. The standard of care cure for ABC has been curettage with or without bone grafting of the defect but is burdened by recurrence rates of approximately 25%-31%. Based on the assumption that ABCs usually supplied by one or more pathological feeding arteries, selective arterial embolization has been described as an adjuvant preoperative procedure to reduce intra-operative hemorrhage, and as primary treatment for lesions in difficult surgical access. In the current study, we therefore asked whether (1) a single or a repeat selective arterial embolization (SAE) for treating ABCs would produce comparable healing rates compared with curettage and bone grafting; (2) evaluated the relationship of recurrence in relation to the site of the cyst, the age, and gender of the patients; and (3) the two techniques differ in term of long-term complication. MATERIAL AND METHODS: We retrospectively reviewed 265 patients who underwent curettage and bone grafting or SAE performed at our institute from 1994 to 2018. The diagnosis of ABC was always established with percutaneous CT-guided biopsy or open biopsy. Patients were followed clinically with plain radiographs or CT scan at 3, 6, 9, and 12 months then annually in the absence of symptoms. Treatment success was determined evaluating pre- and postprocedural imaging according to Chang classification. RESULTS: Two hundred and nineteen were treated with curettage and bone grafting (curettage group), and 46 with SAE Group. Of the 219 patients treated with Curettage and bone grafting (curettage group), 165 out of 219 (75.3%) experienced bone healing, while local recurrence was observed in 54 cases (24.7%) after 12 months on average (range: 3-120 months) from surgery. After the first SAE, bone ossification was seen in 27 (58.7%), without needing any further treatment. Eleven recurred patients were treated with SAE (four patients need two while seven need three SAE to heal), and eight patients with curettage and bone grafting. Thirty-eight out of 46 (82%) patients experienced bone ossification regardless the number of SAE. The overall rate of local recurrence for all patients was 26.7%. SAE group presented a lower complication rate (6%) where two patients experienced skin necrosis, and one limb-length discrepancies (2% of all cohort). DISCUSSION: The use of SAE is an attractive option to treat ABC as it combines on one hand a lower complication rate than curettage and bone grafting, on the other it can be carried out in case of nonresectable ABCs, significantly reducing the size of viable ABC lesions, fostering bone remodeling and mineralization, and most importantly, significantly improving the patient's quality of life.

Phase 2 study for nonmetastatic extremity high-grade osteosarcoma in pediatric and adolescent and young adult patients with a risk-adapted strategy based on ABCB1/P-glycoprotein expression: An Italian Sarcoma Group trial (ISG/OS-2).

BACKGROUND: According to retrospective osteosarcoma series, ABCB1/P-glycoprotein (Pgp) overexpression predicts for poor outcomes. A prospective trial to assess a risk-adapted treatment strategy using mifamurtide in Pgp+ patients was performed. METHODS: This was a phase 2, multicenter, uncontrolled trial including patients 40 years old or younger with nonmetastatic extremity high-grade osteosarcoma stratified according to Pgp expression. All patients received high-dose methotrexate, doxorubicin, and cisplatin (MAP) preoperatively. In Pgp+ patients, mifamurtide was added postoperatively and combined with MAP for a good histologic response (necrosis ≥ 90%; good responders [GRs]) or with high-dose ifosfamide (HDIFO) at 3 g/m2 /d on days 1 to 5 for a histologic response < 90% (poor responders [PRs]). Pgp- patients received MAP postoperatively. After an amendment, the cumulative dose of methotrexate was increased from 60 to 120 g/m2 (from 5 to 10 courses). The primary end point was event-free survival (EFS). A postamendment analysis was performed. RESULTS: In all, 279 patients were recruited, and 194 were included in the postamendment analysis: 70 (36%) were Pgp-, and 124 (64%) were Pgp+. The median follow-up was 51 months. For Pgp+ patients, 5-year EFS after definitive surgery (null hypothesis, 40%) was 69.8% (90% confidence interval [CI], 62.2%-76.2%): 59.8% in PRs and 83.7% in GRs. For Pgp- patients, the 5-year EFS rate was 66.4% (90% CI, 55.6%-75.1%). CONCLUSIONS: This study showed that adjuvant mifamurtide, combined with HDIFO for a poor response to induction chemotherapy, could improve EFS in Pgp+ patients. Overall, the outcomes compared favorably with previous series. Mifamurtide and HDIFO as salvage chemotherapy are worth further study.

Treatment updates on tenosynovial giant cell tumor.

PURPOSE OF REVIEW: Diffuse-type tenosynovial giant cell tumor (dt-TGCT) is a benign clonal neoplastic proliferation arising from the synovium. Patients are often symptomatic, require multiple surgical procedures during their lifetime, and have reduced quality of life (QoL). Surgery is the main treatment with relapse rates ranging from 14 to 55%. The treatment strategy for patients with dt-TGCT is evolving. The purpose of this review is to describe current treatment options, and to highlight recent developments in the knowledge of the molecular pathogenesis of dt-TGCT as well as related therapeutic implications. RECENT FINDINGS: TGCT cells overexpress colony-stimulating factor 1 (CSF1), resulting in recruitment of CSF1 receptor (CSF1R)-bearing macrophages that are polyclonal and make up the bulk of the tumor, has led to clinical trials with CSF1R inhibitors. These inhibitors include small molecules such as pexidatinib, imatinib, nilotinib, DCC-3014 (vimseltinib), and the monoclonal antibody RG7155 (emactuzumab). SUMMARY: In conclusion, D-TGCT impairs patients' QoL. The evidence that the pathogenetic loop of D-TGCT can be inhibited has changed the therapeutic armamentarium for this condition. Clinical trials of agents that target CSF1R are currently ongoing. All this new evidence should be taken into consideration within multidisciplinary management.

Primary synovial sarcoma of bone: a retrospective analysis of 25 patients.

AIMS: To evaluate the diagnostic accuracy of SSX and SSX::SS18 antibodies in decalcified surgical specimens and outcome of synovial sarcomas (SS) of bone. METHODS AND RESULTS: Twenty-five cases were classified as bone SS (prevalence 0.32% among malignant primary bone sarcoma). Median age was 34 years (range = 9-79). Twenty-four of 25 patients presented with non-metastatic tumours, one with lung metastases. The majority of tumours involved the long bones of extremities with metaphyseal origin. Mean size of the tumour was 7.1 cm. Twenty cases (80%) were monophasic and five (20%) were biphasic. SS18::SSX fusion-specific antibody had 92% sensitivity and 99% specificity for primary bone SS, whereas SSX C-terminus antibody had 100% sensitivity and 94% specificity. Fluorescence in-situ hybridisation (FISH) analysis was feasible in nine (36%) cases and detected SS18 rearrangement in all nine cases. All patients underwent surgical removal of their primary tumour, with adequate margins in 18 (72%) patients. Chemotherapy with metothrexate, cisplatin, doxorubicin and ifosfamide was used in the seven patients. Two patients with inadequate surgical margins received radiotherapy. With a median follow-up of 80 months (range = 6-428), 5- and 10-year overall survival (OS) was 66.6% and 47.9%, respectively, and 5 and 10 years' disease-free survival (DFS) was 36.8% [95% confidence interval (CI) = 18.0-55.7%] and 32.2% (95% CI = 14.6-51.2%), respectively. A significant improvement in 10 years' DFS in patients undergoing chemotherapy compared with patients who did not was observed (P = 0.039). CONCLUSIONS: Our series highlights the utility of SS18::SSX fusion-specific and SSX C-terminus antibodies to support the diagnosis of SS. Adjustment chemotherapy was associated with improved prognosis in this series.

A prospective real-world study of the diffuse-type tenosynovial giant cell tumor patient journey: A 2-year observational analysis.

BACKGROUND AND OBJECTIVES: Diffuse-tenosynovial giant cell tumor (D-TGCT) is a rare, locally aggressive, typically benign neoplasm affecting mainly large joints, representing a wide clinical spectrum. We provide a picture of the treatment journey of D-TGCT patients as a 2-year observational follow-up. METHODS: The TGCT Observational Platform Project registry was a multinational, multicenter, prospective observational study at tertiary sarcoma centers spanning seven European countries and two US sites. Histologically confirmed D-TGCT patients were categorized as either those who remained on initial treatment strategy (determined at baseline visit) or those who changed treatment strategy with specific changes documented (e.g., systemic treatment to surgery) at the 1-year and/or 2-year follow-up visits. RESULTS: A total of 176 patients were assessed, mean diagnosis age was 38.4 (SD ± 14.6) years; most patients had a knee tumor (120/176, 68.2%). For the 2-year observation period, most patients (75.5%) remained on the baseline treatment strategy throughout, 54/79 patients (68.4%) remained no treatment, 30/45 patients (66.7%) remained systemic treatment, 39/39 patients (100%) remained surgery. Those who changed treatment strategy utilized multimodal treatment options. CONCLUSIONS: This is the first prospectively collected analysis to describe D-TGCT patient treatments over an extended follow-up and demonstrates the need for multidisciplinary teams to determine an optimal treatment strategy.

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.

Long-term outcomes of pexidartinib in tenosynovial giant cell tumors.

BACKGROUND: The objective of this study was to report on the long-term effects of pexidartinib on tenosynovial giant cell tumor (TGCT). METHODS: This was a pooled analysis encompassing 3 pexidartinib-treated TGCT cohorts: 1) a phase 1 extension study (NCT01004861; 1000 mg/d; n = 39), 2) ENLIVEN patients randomized to pexidartinib (1000 mg/d for 2 weeks and then 800 mg/d; n = 61), and 3) ENLIVEN crossover patients (NCT02371369; 800 mg/d; n = 30). Eligible patients were 18 years old or older and had a histologically confirmed TGCT that was unresectable and symptomatic. Efficacy endpoints included the best overall response (complete or partial response) and the duration of response (DOR) by the Response Evaluation Criteria in Solid Tumors (RECIST) and the tumor volume score (TVS). The safety assessment included the frequency of treatment-emergent adverse events (TEAEs) and hepatic laboratory abnormalities (aminotransferase elevations and mixed/cholestatic hepatotoxicity). The data cutoff was May 31, 2019. RESULTS: One hundred thirty patients with TGCT received pexidartinib (median treatment duration, 19 months; range, 1 to 76+ months); 54 (42%) remained on treatment at the end of the analysis (26 months after initial data cut of March 2017). The RECIST overall response rate (ORR) was 60%; the TVS ORR was 65%. The median times to response were 3.4 (RECIST) and 2.8 months (TVS), with 48 of the responding patients (62%) achieving a RECIST partial response by 6 months and with 72 (92%) doing so by 18 months. The median DOR was reached for TVS (46.8 months). Reported TEAEs were mostly low-grade, with hair color changes being most frequent (75%). Most liver abnormalities (92%) were aminotransferase elevations; 4 patients (3%) experienced mixed/cholestatic hepatotoxicity (all within the first 2 months of treatment), which was reversible in all cases (recovery spanned 1-7 months). CONCLUSIONS: This study demonstrates the prolonged efficacy and tolerability of long-term pexidartinib treatment for TGCT.

The Rizzoli Multiple Osteochondromas Classification revised: describing the phenotype to improve clinical practice.

Multiple osteochondromas (MO) is a rare disorder, characterized by benign osteocartilaginous tumors (osteochondromas), arising from the perichondrium of bones. The osteochondromas increase during growth, frequently causing deformities and limitations. Our study aims to analyze the data captured by the Registry of Multiple Osteochondromas, to refine Istituto Ortopedico Rizzoli (IOR) Classification, providing a representative picture of the phenotypic manifestations throughout the lifespan. We conducted a single-institution cross-sectional study. Patients were categorized according to IOR Classification, which identifies three patients' classes on the presence/absence of deformities and/or limitations. The present dataset was compared with our previously published data, to refine the classification. Nine hundred sixty-eight patients were included: 243 children (<10 years), 136 adolescents (10-15 years), and 589 adults. Of the entire population, half patients presented at least one deformity, and one quarter reported at least one limitation. Compared with our previous study, the amount of children was more than doubled and the percentage of mild/moderate cases was notably increased, giving a better disease overview throughout the lifespan and suggesting a different cut-off for dividing Class II in subclasses. We confirmed that MO is characterized by phenotypic heterogeneity, suggesting that an early classification of the disease may offer a useful tool to follow disease pattern and evolution, to support clinical practice, and to propose timely interventions.

What Is the Survival of the Telescope Allograft Technique to Augment a Short Proximal Femur Segment in Children After Resection and Distal Femur Endoprosthesis Reconstruction for a Bone Sarcoma?

BACKGROUND: Large, malignant bone tumors and revision limb salvage procedures often result in the resection of extensive lengths of the involved bone segment, leaving a residual segment of bone that may be too short to support a standard intramedullary stem for endoprosthetic reconstruction. Telescope allografting, in which an allograft is used to augment the remaining bone segment by telescoping it into the residual bone segment, was described for situations in which residual bone stock is insufficient after tumor resection or prosthetic revision. Apart from one study that first described the procedure [15], there are no other studies reporting the outcome of this telescopic concept for restoring bone stock. QUESTIONS/PURPOSES: For patients younger than 18 years who underwent the telescopic allograft technique to augment a short segment of the proximal femur after resection of bone sarcomas who also underwent endoprosthesis reconstruction of the distal femur, we asked: (1) What is the survivorship free from removal of the telescopic allograft and the endoprosthetic stem at 7 years after surgery? (2) What proportion of these reconstructions will heal to the host bone without delayed union or nonunion? (3) What is the functional outcome based on the Musculoskeletal Tumor Society (MSTS) score? METHODS: We retrospectively studied our institutional database and identified 127 patients younger than 18 years who underwent surgery for a primary malignant bone tumor of the distal femur between December 2008 and October 2018. After excluding 16 patients undergoing amputation and rotationplasty and 57 patients undergoing recycled autograft/allograft reconstruction, 54 patients who underwent primary or revision distal femur endoprosthesis reconstruction were identified. Among these patients, we considered 15 patients who underwent telescopic allograft augmentation of the femur for analysis. One patient was lost to follow-up before 2 years but was not known to have died, leaving 14 for analysis at a median (range) 49 months (24 to 136 months) of follow-up. The indications for telescopic allograft augmentation of the femur in our institution were a proximal femur length of less than 120 mm after resection or resection of more than two-thirds of the total length of the femur. Ten of 14 patients underwent telescopic allograft augmentation as a revision procedure (distal femur resorption in five patients, endoprosthesis stem loosening in three patients, implant fracture in one patient, and infection in one patient), and the remaining four patients underwent telescopic allograft augmentation as a primary limb salvage procedure for large malignant bone tumors of the distal femur. The histologic diagnosis in all patients was osteosarcoma. At the time of telescopic allograft augmentation and reconstruction, the median age of the patients was 14 years (7 to 18 years). The size and the type of bone allograft to be used (femoral shaft or proximal femur) was planned before surgery, with consideration of the extent of resection, level of osteotomy, diameter of the host bone at the osteotomy site, and approximate diameter of the endoprosthesis stem to be used. The segment of the cylindrical allograft used for telescoping was thoroughly washed, prepared, and impacted onto the native femur to achieve telescoping and overlap. Serial digital radiographs were performed once a month for the first 6 months after the procedure, every 2 months until 1 year, and then every 6 months thereafter. Two surgeons in the department (at least one of which was involved in the surgery) retrieved and reviewed clinical notes and radiographs to determine the status of the telescopic allograft and endoprosthesis stem. We defined delayed union as radiological union at the osteotomy site more than 6 months after the procedure without additional surgery; we defined nonunion as no radiological evidence of callus formation at the osteotomy site 9 months after the procedure, necessitating additional surgery. The reviewers did not disagree about the definition of healing time. None of the patients missed radiographic follow-up. Kaplan-Meier survivorship free from removal of telescopic allograft and the endoprosthesis stem at 7 years after surgery was estimated. Patient function was assessed using the 1993 version of the MSTS [9], as determined by chart review of the institutional database performed by one of the surgeons from the department. RESULTS: The survivorship free from removal of the telescopic allograft and endoprosthesis stem at 7 years after surgery was 80% (95% confidence interval 22% to 96%). The allograft united with the host bone in 100% (14 of 14) of the patients. Though 21% (3 of 14) had delayed union, no nonunions were seen. The median (range) MSTS score at the final follow-up interval was 27 (22 to 30). CONCLUSION: Although this is a small group of patients, we believe that allograft segments help augment short bone stock of the proximal femur after long-segment resections, and the telescopic technique seems to be associated with a low proportion of nonunion or delayed union, which is one of the most common complications of allografts. Maintaining an adequate length of the proximal femur is important in preserving the hip, and this technique may be especially useful for young individuals who may undergo repeated revision procedures. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Early results with a bicruciate-retaining total knee arthroplasty: a match-paired study.

BACKGROUND: The aim of this study is to compare 2 groups of total knee arthroplasties (TKAs): the bicruciate-retaining (BCR-group) and cruciate-retaining total knee arthroplasty (CR-group), evaluating the functional results in the short-term follow-up. METHODS: 24 BCR were included in the study and were compared with a group of 24 TKAs performed with the same implant, but with sacrifice of the ACL and retention of the posterior cruciate ligament. For preoperative and postoperative clinical evaluation, the visual analogue score (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used. Radiological evaluation included weight-bearing long-leg view, a Rosemberg view, lateral view of the knee and tangential view of the patella. Hip-knee-ankle angle (HKA) was recorded pre and postoperatively. Radiolucent lines (RLLs) were evaluated according the Knee Society Roentgenographic Evaluation System (KSRES). RESULTS: At last follow-up the mean VAS score was 1.81 for BCR group and 1.43 for CR group (p = 0.61). The mean WOMAC score was 8.68 for BCR group and 12.81 for CR group (p = 0.33). As for the radiological evaluation, preoperative HKA angle was 0.53° varus for BCR group and 3.14° varus for CR group (p = 0.24); postoperative HKA was 0.72° valgus for BCR group and 0.38° valgus for CR group (p = 0.75). The percentage of RLLs was similar between the two groups (12% versus 15%). CONCLUSIONS: BCR-TKA has showed to give similar functional and radiographic outcomes compared to conventional CR-TKA in a similar cohort of patients. An higher operative times and higher number of complications respect were found in BCR group. These results can be explained by the early learning curve experiences. Future randomized controlled trials should be performed to support new implant designs such as BCR. LEVEL OF EVIDENCE: Level of evidence Case-control study, level III.

Expandable distal femur megaprosthesis: A European Musculoskeletal Oncology Society study on 299 cases.

BACKGROUND AND OBJECTIVES: Expandable distal femur prostheses have become more popular over the last decades, but scientific data is limited. METHODS: A retrospective study was performed, including cases treated between 1986 and 2019 in 15 European referral centers for bone sarcomas. RESULTS: A total of 299 cases were included. Average follow-up was 80 months (range, 8-287 months). Mean patient age was 10 years. Most (80%) of the implants were noninvasive growers and a fixed hinge knee was used more often (64%) than a rotating hinge. Most prosthetic designs showed good (>80%) implant survival at 10 years, but repeat surgery was required for 63% of the patients. The most frequent reason for revision procedure was the completion of lengthening potential. Noninvasive expandable implants showed less risk of infection compared to invasive growers (11.8% vs 22.9% at 10 years). No difference in aseptic loosening was found between cemented and uncemented stems. CONCLUSIONS: This study shows the increasing popularity of expandable distal femur prostheses, with overall good results for function and implant survival. However, repeat surgery is frequently required, especially in patients under the age of 10 years old. Infection is less frequent in noninvasive growers compared to implants that require invasive lengthening procedures.

Role of (Neo)adjuvant Denosumab for Giant Cell Tumor of Bone.

OPINION STATEMENT: Denosumab is a RANK ligand inhibitor approved for the treatment of giant cell tumor of bone. While the role of denosumab in the setting of advanced and unresectable disease is well established, its role in surgically resectable disease is currently under discussion. Several prospective and retrospective series on neoadjuvant therapy in potentially resectable tumor with high morbidity surgery reported a relapse rate of 10-20% after resection and 30-40% after curettage. At the same time, less morbid surgery has obvious clinical advantages for the patient, and several studies have shown the efficacy of denosumab in downgrading of the surgical procedure. Currently, the role of neoadjuvant denosumab in operable GCTB is limited to selected cases in which a diffuse reactive bone formation and peripheral ossification can make an easier surgical procedure, for example, in tumors with a large soft tissue component. A planned resection may become less morbid when preoperative denosumab is administered. Whenever a segmental resection is thought to be indicated at diagnosis, denosumab may be considered in the neoadjuvant setting. A preoperative course of 6 months is considered safe and effective. Two case scenarios are presented and critically discussed. Because of the high recurrence rates after denosumab treatment followed by curettage, we discourage the use of denosumab when curettage is considered feasible. In this setting, a short course of preoperative denosumab (2-6 months) may be considered for highly selected cases, for example in pathological fractures. The role of adjuvant denosumab needs further investigation. Long-term disease control has been reported in case of non-surgical lesions, even after treatment interruption, but there is no consensus on ideal treatment duration and dosage for these scenarios. In all cases, multidisciplinary discussion with oncology, pathologist, radiologist, and surgeons is mandatory. Patient's comorbidities, dental conditions, and preferences, including family planning, should always be taken into account.

Incomplete resection increases the risk of local recurrence and negatively affects functional outcome in patients with tenosynovial giant cell tumor of the hindfoot.

BACKGROUND: Diffuse tenosynovial giant cell tumors (TGCT) are more likely to occur in the hindfoot and tend to recur after surgical excision. We performed a pooled analysis of hindfoot TGCT cases to identify factors associated with local recurrence and functional outcomes. METHODS: We retrospectively reviewed medical records of 33 patients diagnosed with TGCT (15, localized cases; 18 diffused cases) of the hindfoot between 1998 and 2017. Median follow-up was 32 months. Multivariable Cox proportional hazards regression analysis was conducted to estimate the hazard ratios for risk factors for local failure. Generalized linear regression models were used to assess whether resection status, tumor size, tumor type or bone involvement correlated with the Musculoskeletal Tumor Society (MSTS) score. RESULTS: Local failure was reported in 30% (10/33) patients. Multivariable analysis showed that macroscopically incomplete resection was the only independent prognostic factor for poor local failure-free survival (P=.001). Incomplete resection significantly decreased MSTS score and negatively affected functional outcome (P=.047). CONCLUSIONS: Incomplete resection increases the risk of local recurrence and negatively affects functional outcome in patients with TGCT of the hindfoot.

Surgical outcomes of patients with diffuse-type tenosynovial giant-cell tumours: an international, retrospective, cohort study.

BACKGROUND: Diffuse-type tenosynovial giant-cell tumour is a rare, locally aggressive, and difficult-to-treat soft tissue tumour. Clinical and surgical outcomes depend on multiple factors, including preoperative diagnostic assessment, the localisation and extent of disease, and possibly the choice of treatment modalities by orthopaedic surgeons. We did a retrospective cohort study to characterise global surgical treatment protocols, and assess surgical outcomes, complications, and functional results in patients with diffuse-type tenosynovial giant-cell tumours. METHODS: In this international, multicentre, retrospective cohort study, we included consecutive patients treated in 31 sarcoma reference centres between Jan 1, 1990, and Dec 31, 2017. Eligible patients were of any age and had histologically proven diffuse-type tenosynovial giant-cell tumour of large joints. Patient data were retrieved from the local databases of participating centres. Patients with localised-type tenosynovial giant-cell tumour were excluded. In the analysis, we only included patients with complete core criteria data regarding admission status, date of treatment, type of treatment at participating centre, and first local recurrence after treatment. We used a non-parametric method to estimate recurrence-free survival at 3, 5, and 10 years after initial surgical resection in a tertiary centre. We used a multivariate Cox regression model to estimate the effect of risk factors. We also present subgroup analyses of disease status at presentation (primary vs recurrent disease) and recurrence-free survival by surgery type (open surgery vs arthroscopic synovectomy), and prespecified risk factors were tested in a univariate and multivariable analyses, with an endpoint of first local recurrence after treatment in a tertiary centre. FINDINGS: Data collection for these analyses occurred between January, 2016, and May, 2018. We received the records of 1192 patients, of which 966 (81%) were surgically treated and had complete information on core criteria. 445 patients were admitted with therapy-naive disease of the knee and were primarily treated in a tertiary centre. Since patients with wait and see treatment do not have a starting date of treatment, these patients were excluded in the calculation of median follow-up time for all patients. For this calculation we used time of surgery as a starting date. 758 (64%) of 1192 patients had knee involvement and 628 (54%) of 1163 patients with complete data on type of surgery had one-staged open synovectomy. At a median follow-up of 54 months (IQR 27-97), recurrent disease developed in 425 (44%) of all 966 surgically treated cases, and recurrence-free survival was 62% (95% CI 59-65) at 3 years, 55% (51-58) at 5 years, and 40% (35-45) at 10 years. Surgical complications were reported in 105 (12%) of 906 patients who had complete data on surgical complications. Pain improved after surgical treatment in 255 (59%) of 434 patients and swelling improved in 328 (72%) of 453 patients who had complete data. INTERPRETATION: This study of patients with diffuse-type tenosynovial giant-cell tumour provides a comprehensive and up-to-date disease overview, assessing the clinical profile and management of the disease in multiple specialised referral centres. Surgical treatment of diffuse-type tenosynovial giant cell tumours is not a definitive treatment for every patient because it involves a high risk for local recurrent disease and a relatively high risk for postoperative complications. After surgical treatment in treatment-naive patients, risk factors for recurrent disease in individual patients were not identified in what we believe is the largest cohort to date. FUNDING: Daiichi Sankyo.

Melorheostosis and Osteopoikilosis Clinical and Molecular Description of an Italian Case Series.

Melorheostosis (MEL) is an uncommon, sclerosing disease, characterised by hyperostosis of long bones, resembling the flowing of candle wax. The disease is sporadic and the pathogenesis is still poorly understood. Occasionally, the same family can include individuals with MEL and Osteopoikilosis (OPK), a disease characterised by multiple round foci of increased bone density. LEMD3 gene mutations are related to OPK and Buschke-Ollendorff Syndrome, a genetic condition in which an association between MEL, OPK and skin lesions is observed. In rare cases, LEMD3 mutations and recently mosaic MAP2K1 gene mutations have been correlated to MEL suggesting that somatic mosaicism could be causative of the disease. In this study, we described the clinical, radiological and molecular findings of 19 individuals with MEL and 8 with OPK and compared the results to the medical literature. The molecular analyses of this case series corroborate the available data in the medical literature, indicating that LEMD3 germline mutations are not a major cause of isolated MEL and reporting five further cases of OPK caused by LEMD3 germline mutations.

Stanmore noninvasive extendible endoprosthesis in the treatment of bone sarcoma in the preadolescent.

AIMS: The aim of this study is to assess outcomes of patients ≤12 years who undergo Stanmore noninvasive extendible endoprosthetic replacement of the distal femur (DF NIEPR). PATIENTS AND METHODS: A total of 101 children (mean age 9.6 years) were included. All complications which required further surgery were recorded. Clinical and functional outcomes were evaluated with Musculoskeletal Tumor Society (MSTS) scores at a mean follow-up of 64 months (range 6-174). RESULTS: Thirty-one (30.7%) patients died at a mean of 33 months. Forty had prosthesis removed after a mean of 43 months (range, 7-103). Attaining of the full lengthening potential before skeletal maturity was the most frequent reason for revision surgery, particularly in those with smaller lengthening potential (P = 0.039). Implant survival rate for other causes was 61.7% at 5 years and 45.0% at 10 years. At final follow-up mean MSTS score was 26 (range, 13-29). Twenty-two (21.5%) patients had a final limb-length discrepancy (LLD) > 2 cm. CONCLUSIONS: DF NIEPR produces a good functional outcome, with the prevention of major LLD at skeletal maturity in the majority of the cases. We suggest patient selection criteria to account for the stage of the disease due to the high cost of the NIEPR, and high percentage requiring revision, and a 60% mortality rate in those patients presenting with distant disease burden.

Treatment of chronic osteomyelitis with antibiotic-loaded bone void filler systems: an experience with hydroxyapatites calcium-sulfate biomaterials.

This is a retrospective study that aims to quantify the problem of chronic osteomyelitis in one of the largest Italian orthopedic centers. Furthermore this study is focused on evaluation of efficacy of bone void filler systems with particular attention to a subgroup of patients treated with PerOssal®. Ninety-seven patients were included in this study between 2008 and 2013 with a minimum follow up of 24 months. A subgroup of 52 patients was treated with curettage plus PerOssal®, another group was treated with curettage only or curettage with other bone void filler systems. Overall we obtained a cure rate of 80,4%, whereas 19,6% had recurrent infection. Looking at the subgroup treated with PerOssal® we found a healing rate of 86,5%, which was significantly higher compared to the other groups. Of the patients with recurrence of infection, those treated with PerOssal® recurred 106 days later than the other patients.