Reoperation after surgery for bone metastasis of renal cell carcinoma.

BACKGROUND AND OBJECTIVE: The prognosis of metastatic renal cell carcinoma (RCC) has markedly improved with the advent of molecular targeted therapies and immune checkpoint inhibitors. However, the therapeutic response in patients with bone metastasis remains low; therefore, surgery still plays a significant role in treatment of bone metastasis. It is important to maintain quality of life for patients with bone metastasis from RCC and avoid reoperation after surgery for bone metastasis. Therefore, we investigated the risk factors for reoperation after surgery in patients with bone metastasis from RCC. METHODS: We retrospectively studied 103 bones of 97 patients who underwent surgery for bone metastasis of RCC from 2001 to 2023 at our institutions. RESULTS: Reoperation was performed in 10 (9.7%) of 103 bones. There was no correlation between reoperation-free survival and any of the following variables: preoperative and postoperative radiotherapy, site of bone metastasis, indication for surgery (solitary bone metastasis or impending or pathologic fractures), surgical method (intramedullary nailing fixation, curettage, or en bloc resection), preoperative embolization, or survival. CONCLUSION: The risk of reoperation for bone metastasis of RCC does not appear to be based on the surgical method.

Is perioperative chemotherapy effective in patients with localized myxoid liposarcoma?

BACKGROUND: This study aimed to compare the local recurrence, distant metastasis and disease-specific survival rates of patients with localized myxoid liposarcoma in the surgery and adjuvant chemotherapy group versus the surgery alone group. METHODS: A total of 456 patients in the Japanese National Bone and Soft Tissue Tumour Registry database who had localized myxoid liposarcoma and underwent surgery and adjuvant chemotherapy or surgery alone between 2001 and 2019 were included in this retrospective study. The study adjusted for background differences between patients who underwent surgery and adjuvant chemotherapy (n = 228) or surgery alone (n = 228) using propensity score matching. RESULTS: Univariate analysis showed no significant difference in local recurrence rate between the two groups (5-year local recurrence-free survival: 98.6% [95% confidence interval: 95.9-99.6] vs. 94.0% [95% confidence interval: 89.7-96.6], P = 0.052). Univariate analysis showed no difference in the incidence of distant metastases between the two groups (5-year distant metastasis-free survival: 80.5% [95% confidence interval: 73.9-85.8] vs. 75.1% [95% confidence interval: 67.7-81.2], P = 0.508). Univariate analysis showed no difference in disease-specific survival between the two groups (5-year disease-specific survival: 92.6% [95% confidence interval: 86.1-96.2] vs. 93.2% [95% confidence interval: 87.6-96.4], P = 0.804). In the high-risk group (n = 203) with high-grade tumours and tumour size ≥10 cm, there were no significant differences in the local recurrence, distant metastasis and disease-specific survival rates between the surgery and adjuvant chemotherapy group and the surgery alone group. CONCLUSION: The effect of adjuvant chemotherapy on localized myxoid liposarcoma appears to be limited.

What Is the Revision-free Survival of Resurfaced Allograft-prosthesis Composites for Proximal Humerus Reconstruction in Children With Bone Tumors?

BACKGROUND: Reconstruction of the proximal humerus in children who undergo bone tumor resection is challenging because of patients' small bone size and possible limb length discrepancy at the end of skeletal growth due to loss of the physis. There are several options for proximal humerus reconstruction in children, such as clavicula pro humero, free vascularized fibula grafting, massive bone osteoarticular allografting, endoprostheses, and allograft-prosthesis composites, but no consensus exists on the best method for reconstruction. Resurfaced allograft-prosthesis composites could be an alternative surgical option, but little is known about the results of this surgical technique. QUESTIONS/PURPOSES: (1) What are the complications and what is the survivorship free from reconstruction failure associated with resurfaced allograft-prosthesis composites in a small, single-center case series? (2) What Musculoskeletal Tumor Society scores do patients achieve after reconstructions with resurfaced allograft-prosthesis composites? METHODS: This study was a retrospective, single-arm case analysis in a single institution. We generally considered resurfaced allograft-prosthesis composites in children with malignant bone tumors involving the metaepiphysis of the proximal humerus in whom there was no evidence of joint contamination and in whom axillary nerve preservation was possible. Between 2003 and 2021, we treated 100 children (younger than 15 years) with bone tumors of the humerus. Thirty children (30%) with diaphyseal tumors (21 children) or distal tumors (9 children) were excluded. Among the potentially eligible children, 52 were not analyzed because they were treated with other procedures such as amputation, modular prostheses, cement spacers, free vascularized fibula grafting, and massive bone osteoarticular allografts. We included 18 children (26% of the potentially eligible children) who were treated with resurfaced allograft-prosthesis composites. There were 9 boys and 9 girls, with a median age of 10 years (range 4 to 15 years) at the time of diagnosis. A long stem (≥ 6 cm) in the resurfaced allograft-prosthesis composite was used in 9 children and a short stem (< 6 cm) was used in the remaining 9. One of the 18 children had a follow-up of less than 2 years. The median follow-up of the remaining 17 children was 4.7 years (range 2 to 19 years). The children' medical records were reviewed for clinical and functional outcomes. We performed a competing risk analysis to calculate the reconstruction failure-free survival of resurfaced allograft-prosthesis composites. Reconstruction failure was defined as removal of the implant or allograft because of implant loosening or breakage and allograft fracture or resorption. We analyzed the children's postoperative complications and functional outcomes at the end of the follow-up period using the Musculoskeletal Tumor Society functional scoring system. RESULTS: The competing risk analysis revealed that reconstruction failure was 25% (95% confidence interval 7% to 40%) at 3 years, reaching a plateau. Four of 18 children underwent surgical revision with a new reconstruction. The reasons for reconstruction revision were resorption of the allograft at the proximal part (2 children) and fracture of the allograft (2 children). Reconstruction revision was performed in 3 of 9 children who underwent reconstruction with a short stem and in 1 of 9 children who underwent reconstruction with a long stem. Several children had other complications that did not result in removal of the allograft. Allograft resorption was observed in 4 of 18 children, but no additional surgical treatment was performed. Shoulder instability or subluxation was observed in 4 of 18 children, but only 1 child underwent surgery with a reverse shoulder arthroplasty without removal of the resurfaced allograft-prosthesis composite. Limited elbow motion because of plate impingement was observed in 1 child who underwent surgical cutting of the protruding distal part of the plate. Incomplete radial nerve palsy after surgery occurred in 1 child, with spontaneous resolution after 2 months. Screw loosening occurred in 2 children who underwent surgery with removal of loose screws. Two children had a nonunion at the graft-host bone junction; 1 child underwent surgery with bone grafting and refixation of the graft-host bone junction, and the other child with both nonunion and plate breakage was treated with bone grafting and refixation of the graft-host bone junction with a new plate. Among 17 children who had a follow-up longer than 2 years, the median Musculoskeletal Tumor Society functional score at the last follow-up interval was 23 of 30 (range 20 to 26); 1 child was considered to have an excellent result (functional score ≥ 26), 15 children were considered to have a good result (functional score 21 to 25), and 1 child was considered to have a fair result (functional score ≤ 20). The Musculoskeletal Tumor Society functional score did not change after excluding 4 children who underwent replacement of resurfaced allograft-prosthesis composites (24 of 30 [range 20 to 26]). The median angle of flexion of the shoulder was 40° (range 20º to 90°), and the median angle of abduction was 30° (range 20º to 90°). CONCLUSION: Resurfaced allograft-prosthesis composites showed a high risk of complications, but not all complications resulted in removal of the reconstructed allograft. We used this technique mainly for very young children with small bones and for older children who underwent axillary nerve preservation. Although its success may be limited owing to a high risk of complications, a resurfaced allograft-prosthesis composite could be an alternative surgical option in order to preserve the bone stock and achieve good functional outcomes in very young children. We recommend using a long-stem resurfaced allograft-prosthesis composite, which may reduce the risk of complications. LEVEL OF EVIDENCE: Level IV, therapeutic study.

What Are the Complications, Reconstruction Survival, and Functional Outcomes of Modular Prosthesis and Allograft-prosthesis Composite for Proximal Femur Reconstruction in Children With Primary Bone Tumors?

BACKGROUND: Proximal femur reconstruction after bone tumor resection in children is a demanding surgery for orthopaedic oncologists because of the small bone size and possible limb-length discrepancy at the end of skeletal growth owing to physis loss. The most commonly used reconstruction types used for the proximal femur are modular prostheses and allograft-prosthesis composites. To our knowledge, there are no previous studies comparing the outcomes after modular prosthesis and allograft-prosthesis composite reconstruction of the proximal femur in children with primary bone tumors. QUESTIONS/PURPOSES: (1) What was the cumulative incidence of reoperation for any reason after allograft-prosthesis composite and modular prosthesis reconstructions of the proximal femur in children with primary bone tumors? (2) What was the cumulative incidence of reconstruction removal or revision arthroplasty in those two treatment groups? (3) What complications occurred in those two treatment groups that were managed without further surgery or with surgery without reconstruction removal? METHODS: Between 2000 and 2021, 54 children with primary bone tumors underwent resection and reconstruction of the proximal femur at a single institution. During that time, allograft-prosthesis composite reconstruction was used in very young children, in whom we prioritize bone stock preservation for future surgeries, and children with good response to chemotherapy, while modular prosthesis reconstruction was used in older children and children with metastatic disease at presentation and poor response to chemotherapy. We excluded three children in whom limb salvage was not possible and 11 children who underwent either reconstruction with free vascularized fibular graft and massive bone allograft (n = 3), an expandable prosthesis (n = 3), a massive bone allograft reconstruction (n = 2), a rotationplasty (n = 1), standard (nonmodular) prosthesis (n = 1), or revision of preexisting reconstruction (n = 1). Further, we excluded two children who were not treated surgically, three children with no medical or imaging records, and three children with no follow-up. All the remaining 32 children with reconstruction of the proximal femur (12 children treated with modular prosthesis and 20 children treated with allograft-prosthesis composite reconstruction) were accounted for at a minimum follow-up time of 2 years. Children in the allograft-prosthesis group were younger at the time of diagnosis than those in the modular prosthesis group (median 8 years [range 1 to 16 years] versus 15 years [range 9 to 17 years]; p = 0.001]), and the follow-up in the allograft-prosthesis composite group was longer (median 5 years [range 1 to 23 years] versus 3 years [range 1 to 15 years]; p = 0.37). Reconstruction with hemiarthroplasty was performed in 19 of 20 children in the allograft-prosthesis composite group and in 9 of 12 children in the modular prosthesis group. A bipolar head was used in 16 of 19 children, and a femoral ceramic head without acetabular cup was used in 3 of 19 children in the allograft-prosthesis composite reconstruction group. All 9 children in the modular prosthesis group were reconstructed with a bipolar hemiarthroplasty. Reconstruction with total arthroplasty was performed in one child in the allograft-prosthesis composite group and in three children in the modular prosthesis group. For both groups, we calculated the cumulative incidence of reoperation for any reason and the cumulative incidence of reconstruction removal or revision arthroplasty; we also reported qualitative descriptions of serious complications treated nonoperatively in both groups. RESULTS: The cumulative incidence of any reoperation at 10 years did not differ between the groups with the numbers available (36% [95% confidence interval 15% to 58%] in the allograft-prosthesis composite group versus 28% [95% CI 5% to 58%] in the modular proximal femoral replacement group). The cumulative incidence of reconstruction removal or revision arthroplasty at 10 years likewise did not differ between the groups with the numbers available (10% [95% CI 2% to 28%] versus 12% [95% CI 0% to 45%], respectively). In the allograft-prosthesis composite group (20 children), hip instability (n = 3), nonunion (n = 2), fracture of the greater trochanter (n = 1), screw loosening (n = 1), limb-length discrepancy (n = 1), and coxalgia due to acetabular wear (n = 1) were treated surgically without reconstruction removal. Complications treated without surgery included resorption of the allograft at the trochanteric region (n = 4), fracture of the greater trochanter (n = 4), limb-length discrepancy (n = 6), and coxalgia due to acetabular wear (n = 2). In the modular prosthesis group (12 children), hip instability (n = 1), coxalgia due to acetabular wear (n = 1), and limb-length discrepancy (n = 1) were treated surgically without reconstruction removal. Complications treated without surgery included hip instability (n = 2), stress shielding (n = 6), infection (n = 1), sciatic nerve palsy (n = 1), and limb-length discrepancy (n = 3). CONCLUSION: Although the two groups of children were not directly comparable due to differences in age and clinical characteristics, both modular prosthesis and allograft-prosthesis composite reconstructions of the proximal femur after bone tumor resection appear to be reasonable options with similar revision-free survival and complications. Therefore, the type of reconstruction following proximal resection in children with bone sarcoma should be chosen taking into consideration factors such as patient age, bone size, implant availability, technical expertise, and the surgeon's preference. Although children treated with expandable prostheses were not included in this study, such prostheses may be useful in bridging the surgical defect while correcting residual limb-length discrepancies even though they face limitations such as small intramedullary diameter, short residual bone segments, as well as stress shielding, loosening, and breakage. LEVEL OF EVIDENCE: Level III, therapeutic study.

Histological and imaging features of myoepithelial carcinoma of the bone and soft tissue.

OBJECTIVE: To depict histological and imaging features of myoepithelial carcinoma of the bone and soft tissue. MATERIALS AND METHODS: We retrospectively examined histological features in 22 patients with myoepithelial carcinoma of the bone (4 patients) and soft tissue (18 patients) at a single institution. Imaging analysis of 15 patients (bone, 3 patients; soft tissue, 12 patients;) with preoperative images involved classifying lytic bone lesions via the modified Lodwick-Madewell classification; the growth patterns of soft tissue lesions were classified as well-defined, focally invasive, or diffusely invasive. RESULTS: Local recurrence occurred in eight out of 22 patients (36.3%). Four of 22 patients (18.2%) had metastasis at presentation, whereas 11 of 22 patients (50.0%) had distant metastasis during follow-up. Severe cytological pleomorphism was observed in 14 of 22 patients (63.6%), and 10 of 22 tumors (45.5%) showed ≥ 10 mitoses/10 high-power fields. Vascular invasion was observed in 10 of 22 patients (45.5%). Extracapsular/extraskeletal infiltration into the surrounding tissues was assessed in 20 patients, with 14 of them (70%) showing infiltration beyond the tumor border. Regarding imaging of bone lesions, two patients had Ludwick type IIIB, whereas one patient had type II. The growth pattern of soft tissue lesions was well-defined in two patients (16.7%), focally invasive in seven patients (58.3%), and diffusely invasive in three (25.0%) out of 12 patients. CONCLUSION: Myoepithelial carcinoma of the bone and soft tissue presents high risk of local recurrence and distant metastasis. Histological and imaging features might be important to understand the aggressive behavior of the tumor.

A reduction in tumor volume exceeding 65% predicts a good histological response to neoadjuvant chemotherapy in patients with Ewing sarcoma.

OBJECTIVE: No consensus exists for tumor volume response criteria in patients with Ewing sarcoma. This study aimed to identify an optimal cutoff for predicting a good histological response by analyzing tumor volume changes and tumor necrosis after neoadjuvant chemotherapy. MATERIALS AND METHODS: We performed a retrospective analysis of 184 Ewing sarcoma patients, analyzing tumor volume changes before and after neoadjuvant chemotherapy. Patients were divided into two groups based on histological response: good (tumor necrosis ≥ 95%) and poor (tumor necrosis < 95%) responders. The receiver operating characteristic (ROC) area under the curve (AUC) method was used to determine the optimal thresholds for predicting the histological response. Additionally, the prognostic value of this cutoff for relapse-free survival was assessed. RESULTS: Out of 184 patients, 83 (45%) had tumor necrosis ≥ 95%, while 101 (55%) had tumor necrosis < 95%. ROC analysis identified the optimal cutoff for a good histological response as over 65% tumor volume reduction (AUC = 0.69; p < 0.001). Patients with volume reduction of ≥ 65% had a higher likelihood of a good histological response than those with lesser reductions (p = 0.004; odds ratio = 2.61). Multivariable analysis indicated a correlation between poor histological response and reduced relapse-free survival (hazard ratio = 2.17; p = 0.01), while tumor volume reduction itself did not impact survival. CONCLUSION: We reported that a tumor volume reduction of ≥ 65% was able to predict a good histological response in Ewing sarcoma patients. We recommend preoperative tumor volume assessment to identify patients at greater risk for poor histological response who could benefit from more intensive chemotherapy protocols or additional radiotherapy.

Malawer type I/V proximal humerus reconstruction after tumor resection: a systematic review.

BACKGROUND: Several reconstruction methods exist for Malawer type I/V proximal humerus reconstruction after bone tumor resection; however, no consensus has been reached regarding the preferred methods. METHODS: We conducted a literature search on various types of proximal humerus oncologic reconstruction methods. We collected data on postoperative functional outcomes assessed based on Musculoskeletal Tumor Society (MSTS) scores, 5-year reconstruction survival rates, and complications. We calculated each reconstruction's weighted mean based on the sample size and standard errors. Complications were categorized based on the Henderson classification. Based on these integrated data, our primary objective is to propose an optimal strategy for proximal humerus reconstruction after bone tumor resection. RESULTS: We examined various reconstruction techniques, including modular prosthesis (752 patients in 21 articles), osteoarticular allograft (142 patients in 6 articles), allograft prosthesis composites (APCs) (236 patients in 12 articles), reverse shoulder total arthroplasty (141 patients in 10 articles), composite reverse shoulder total arthroplasty (33 patients in 4 articles), claviculo-pro-humero (CPH) technique (51 patients in 6 articles), and cement spacer (207 patients in 4 articles). Weighted mean MSTS scores were: modular prosthesis (73.8%), osteoarticular allograft (74.4%), APCs (79.2%), reverse shoulder total arthroplasty (77.0%), composite reverse shoulder total arthroplasty (76.1%), CPH technique (75.1%), and cement spacer (69.1%). Weighted 5-year reconstruction survival rates were modular prosthesis (85.4%), osteoarticular allograft (67.6%), APCs (85.2%), reverse shoulder total arthroplasty (84.1%), and cement spacer (88.0%). Reconstruction survival data was unavailable for composite reverse shoulder total arthroplasty and CPH technique. Major complications included shoulder joint instability: modular prosthesis (26.2%), osteoarticular allograft (41.5%), APCs (33.9%), reverse shoulder total arthroplasty (17%), composite reverse shoulder total arthroplasty (6.1%), CPH technique (2.0%), and cement spacer (8.7%). Aseptic loosening of the prosthesis occurred: modular prosthesis (3.9%) and reverse shoulder total arthroplasty (5.7%). Allograft fracture was observed in 54.9% of patients with osteoarticular allograft. CONCLUSION: The complication profiles differed among reconstruction methods. Weighted mean MSTS scores exceeded 70% in all methods except cement spacer, and the 5-year reconstruction survival rate surpassed 80% for all methods except osteoarticular allograft. Proximal humerus reconstruction after bone tumor resection should consider potential complications and patients' individual factors.

Response rate specific to bone metastasis of various cancers for immune checkpoint inhibitors: a systematic review.

PURPOSE: Immune checkpoint inhibitors (ICIs) have improved the prognosis of patients with cancer, such as melanoma, renal cell carcinoma, head and neck cancer, non-small cell lung cancer (NSCLC), and urothelial carcinoma. The extension of life expectancy has led to an increased incidence of bone metastases (BM) among patients with cancer. BM result in skeletal-related events, including severe pain, pathological fractures, and nerve palsy. Surgery is typically required for the treatment of BM in patients with an impending fracture; however, it may be avoided in those who respond to ICIs. We systematically reviewed studies analyzing BM responses to treatment with ICIs. METHODS: This study was conducted in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 statement and registered in the UMIN Clinical Trials Registry (ID: UMIN000053707). Studies reporting response rates based on the Response Evaluation Criteria in Solid Tumors (RECIST) or the MD Anderson Cancer Center (MDA) criteria specific for BM in patients treated with ICIs were included; reports of fewer than five cases and review articles were excluded. Studies involving humans, published in English and Japanese, were searched. The PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched. Ultimately, nine studies were analyzed. The Risk of Bias Assessment tool for Non-randomized Studies was used to assess the quality of studies. RESULTS: Based on the MDA criteria, complete response (CR) or partial response (PR) was observed in 44-78% and 62% patients treated with ICIs plus denosumab for NSCLC and melanoma, respectively. According to the RECIST, CR or PR was recorded in 5% and 7-28% of patients treated with ICIs for renal cell carcinoma and urothelial carcinoma, respectively. CONCLUSION: Although response rates to ICIs for BM are poor, patients treated with ICI plus denosumab for bone metastases with impending fractures from NSCLC and melanoma are likely to avoid surgery to prevent fractures.

Similar complications, implant survival, and function following modular prosthesis and allograft-prosthesis composite reconstructions of the proximal femur for primary bone tumors: a systematic review and meta-analysis.

PURPOSE: There is a lack of consensus regarding the best type of reconstruction of the proximal femur following bone tumor resection. The objective of this study was to analyze the complication risks, implant survival, and functional outcomes following modular prosthesis (MP) and allograft-prosthesis composite (APC) reconstruction of the proximal femur after primary bone tumor resections. METHODS: We performed a search in the PubMed and Scopus libraries, obtaining 1 843 studies. We included studies reporting functional outcomes, complications, and implant survival of proximal femur reconstruction with MP or APC following primary bone tumor resection with a 2-year minimum follow-up. We excluded studies analyzing metastatic patients or studies with pooled data in which it was impossible to separate the data of patients with primary bone tumors from those with bone metastases. RESULTS: We analyzed 18 studies (483 patients) reporting on 234 (48%) patients with MP reconstruction and 249 (52%) patients with APC reconstruction. The risk of complications was similar in patients with MP reconstruction (29%; 95% CI [0.11; 0.47]) and APC reconstruction (36%; 95% CI [0.24; 0.47]) (p = 0.48). Implant survival following MP reconstruction ranged from 81 to 86% at 5 years, 75 to 86% at 10 years, and 82% at 15 years. Implant survival following APC reconstruction ranged from 86 to 100% at 5 years and 86% at 10 years, and 86% at 15 years. Functional outcomes following MP reconstruction and APC reconstruction ranged from 24.0 to 28.3 and from 21.9 to 27.8, respectively. CONCLUSION: Patients with primary bone tumor of the proximal femur who underwent MP or APC reconstruction seem to have similar complication risks, implant survival, and functional outcomes.

Risk of complications and implant survival of surgical treatment of proximal femoral metastasis: a meta-analysis.

PURPOSE: The patients with femoral metastasis in the inter- or subtrochanteric area could be treated with intramedullary nailing or prosthetic reconstruction, however, it is controversial which surgical treatment could offer less complications and implant failure. Our purpose was to define the risk of complications and implant survival in patients treated with intramedullary nailing or prosthetic reconstruction. METHODS: We analyzed studies reporting the risk of complications, reoperations and removal of the implant in patients treated with intramedullary nailing, hemiarthroplasty, arthroplasty or megaprosthesis. RESULTS: We analyzed 27 studies (1346 patients) reporting patients treated with intramedullary nail (51%), hemiarthroplasty (15%), arthroplasty (2%), megaprosthesis with (25%) or without (7%) acetabular component. No difference was found in the overall risk of complications between patients treated with intramedullary nailing 6%, hemiarthroplasty or total hip arthroplasty 7% and megaprosthesis 11% (p = 0.23). However, patients treated with megaprosthesis had increased risk of reoperation due to infection (70%), compared to the patients treated with intramedullary nail (13%), and patients treated with hemiarthroplasty or total hip arthroplasty (23%) (p = 0.02). Revision due to disease progression was required in 61% of the patients treated with intramedullary nail, but not in patients treated with hemiarthroplasty, total arthroplasty, and megaprosthesis (p = 0.03). CONCLUSION: Patients treated with megaprosthesis had higher risk of reoperation due to infection, while patients treated with intramedullary nailing had higher risk of revision due to disease progression. Regarding patients treated with megaprosthesis, the risk of reoperation due to dislocation was higher in those treated with acetabular component.

Fusion transcriptome profiling defines the monoclonal origin of multifocal epithelioid haemangioma of bone.

AIMS: Epithelioid haemangioma (EH) of bone remains a highly controversial entity. Indeed, the WHO classifies EHs of soft tissues as benign tumours, whereas bone EHs are considered intermediate-locally aggressive tumours due to common multifocal presentation and local destructive growth. To gain insights into the clinical behaviour and biology of EH of bone we retrospectively analysed 42 patients treated in a single institution from 1978 to 2021. METHODS AND RESULTS: Multifocal presentation was detected in 17 of 42 patients (40%) primarily as synchronous lesions. Patients were treated with curettage (57%), resection (29%) or biopsy, followed by radiotherapy or embolisation (14%). Follow-up (minimum 24 months) was available for 38 patients, with only five local recurrences (13%) and no death of disease. To clarify whether the synchronous bone lesions in multifocal EH represent multicentric disease or clonal dissemination, four cases were profiled by RNA-sequencing. Separate lesions from the same patient, which showed a similar transcriptional profile, expressed the same fusion transcript (involving FOS or FOSB) with identical gene breakpoints. CONCLUSIONS: These results indicate that, in EH of bone, multifocal lesions are clonally related and therefore represent the spread of a same neoplastic clone rather than simultaneous independent tumours. This finding is in apparent contradiction with the benign clinical course of the disease, and suggests that tumour dissemination in bone EH probably reflects a phenomenon of passive spreading, with tumour cells colonising distal sites while maintaining their benign biological nature.

Preoperative Arterial Embolization for Heterotopic Ossification of the Hip.

PURPOSE: To investigate the efficacy and safety of preoperative arterial embolization for neurogenic heterotopic ossification (NHO) of the hip. MATERIALS AND METHODS: This single-center retrospective study reviewed outcomes in 16 consecutive patients who had surgical resection of NHO of the hip: 8 of whom underwent preoperative arterial embolization and 8 of whom did not. Both patient cohorts had similar baseline characteristics. A mean of 2.62 ± 1.9 arteries per patient, including the gluteal, lateral circumflex femoral, and deep circumflex iliac branches, were embolized using an n-butyl cyanoacrylate (NBCA)-ethiodized oil mixture. Data from both cohorts regarding intraoperative blood loss, volume of blood transfused, complications, and duration of hospitalization were compared. RESULTS: A mean of 2.6 ± 1.9 arteries were embolized with NBCA-ethiodized oil, mainly the gluteal arteries, lateral circumflex femoral artery, and deep circumflex iliac artery. In the embolization group, mean intraoperative blood loss was 875 mL ± 320, mean number of units of blood used was 0.5 ± 0.7, and mean number of days of hospitalization was 6.4 days ± 1.6. In the control group, mean intraoperative blood loss was 1,350 mL ± 120, mean number of units of blood used was 2 ± 1.1, and average number of days of hospitalization was 11.5 days ± 1.4. The embolization group had a mean reduction in blood loss of 40.7% (P = 0.035), reduction in units of blood administered of 75% (P = 0.021), and reduction in days of hospitalization of 44.7% (P = 0.014). No procedural complications were recorded. CONCLUSIONS: Preoperative arterial embolization is effective and safe in reducing intraoperative blood loss, number of hospitalization days, and need for blood transfusions in surgical resection of NHO of the hip.

Giant cell tumor of bone with secondary aneurysmal bone cyst does not have a higher risk of local recurrence.

BACKGROUND: Fluid-fluid levels (FFLs) is found in 10%-16% of giant cell tumor of bone (GCTB), and the presence of FFLs raises the suspicion of GCTB with secondary aneurysmal bone cyst (ABC), which can lead to increased intraoperative bleeding and, blurring the operative field, be associated with a risk of local recurrence. The first objective of this study is to determine whether secondary ABC is associated with a higher risk of local recurrence after curettage in patients with GCTB of the extremities. The second objective of this study is to investigate the sensitivity, specificity, positive predictive value, and negative predictive value of the presence of FFLs detected on magnetic resonance imaging (MRI) to diagnose secondary ABC associated with GCTB. METHODS: Two hundred and eighty patients with GCTB of the extremities who underwent curettage at the authors' institutions between 1980 and 2021 were included in this study. RESULTS: Secondary ABC was found in 36 of 280 patients (12.9%) and local recurrence occurred in 66 of 280 patients (23.6%). Multivariate analysis showed no significant correlation between secondary ABC and local recurrence (hazard ratio [HR]: 1.87 (95% confidence interval [CI]: 1.00-3.53]; p = 0.051). Preoperative MRI revealed FFLs in 13 of 82 patients (15.9%). Sensitivity, specificity, positive predictive value, and negative predictive value of FFLs detected on preoperative MRI to diagnose secondary ABC were 36.8%, 90.5%, 53.8%, and 82.6%, respectively. CONCLUSION: The results of this study showed that secondary ABC does not increase the risk of local recurrence after curettage in patients with GCTB of the extremities. Although rare, FFLs were present in patients with GCTB and half of those with FFLs detected on preoperative MRI had secondary ABC.

Comparison of pre-operative and post-operative radiotherapy in patients with localized myxoid liposarcoma.

BACKGROUND: Myxoid liposarcoma is more radiosensitive than other soft tissue sarcomas, and radiotherapy has been reported to reduce tumour size. This study was performed to compare the rates of local recurrence, survival and wound complications between pre- and post-operative radiotherapy for localized myxoid liposarcoma. METHODS: From the Japanese Nationwide Bone and Soft Tissue Tumor Registry database, 200 patients with localized myxoid liposarcoma who received pre- (range, 30-56 Gy) or post-operative (range, 45-70 Gy) radiotherapy and surgery were included in this retrospective study. Propensity score matching was used to adjust for background differences between patients who received pre- and post-operative radiotherapy. RESULTS: Local recurrence occurred in five (5.0%) and nine (9.0%) patients in the pre- and post-operative radiotherapy groups, respectively (both n = 100). The median follow-up time from diagnosis was 40.5 months (IQR, 26.3-74). Univariate analysis showed a similar risk of local recurrence between the pre- and post-operative radiotherapy groups (5-year local recurrence-free survival 94.9% [95% CI 87.0-98.1] vs. 89.0% [95% CI 79.6-94.3]; P = 0.167). Disease-specific survival was similar between the pre- and post-operative radiotherapy groups (5-year disease-specific survival 88.1% [95% CI 75.5-94.6] vs. 88.4% [95% CI 77.3-94.5]; P = 0.900). The incidence of wound complications was similar between the pre- and post-operative radiotherapy groups (7.0% vs. 12.0%; P = 0.228). CONCLUSIONS: There was no difference in local recurrence, survival or incidence of wound complications between pre- and post-operative radiotherapy for localized myxoid liposarcoma. Therefore, pre-operative radiotherapy for myxoid liposarcoma provides clinical results equivalent to post-operative radiotherapy.

Radiofrequency ablation is as safe and effective as surgical excision for spinal osteoid osteoma: a systematic review and meta-analysis.

BACKGROUND: Osteoid osteoma (OO) is a primary benign tumor that affects mainly young patients. Ten percent of all OO are located in the vertebral column. Treatment of spinal OO is challenging and there is no consensus in the literature on the best operative approach. PURPOSE: The aim of this systematic review and meta-analysis was to determine safety and efficacy of radiofrequency ablation (RFA) versus surgical excision for the treatment of spinal OO. METHODS: A literature search was performed on PubMed, Web of Science, and Embase from inception up to 22 March 2022. Studies addressing surgical excision or RFA for the treatment of spinal OO were included. The main outcomes evaluated were pain before and after intervention, the treatments success rate, defined as complete pain relief with no recurrence until the last follow-up, and the number and type of complications. RESULTS: Thirty-one studies (749 patients) were included. For patients who underwent surgical excision, 19 studies reported a mean treatment success rate of 85.6%, while in the RFA treatment group, 18 studies reported a mean success rate of 88.6%. At last follow-up, the pooled mean difference in pain scores from baseline on a 0-10 scale was 5.8 points in the surgical excision group and 6.7 points in the RFA group. Recurrences were observed in 5.6% of the patients who underwent surgical excision and in 6.7% of the patients treated with RFA. The complication rate was 7.8% in the surgical excision group and 4.4% in the RFA group. CONCLUSIONS: This meta-analysis found high global success rates for both surgical and RFA treatments. Both treatments were efficient in pain relief and presented a low rate of recurrences. The complication rate was low for both treatments. Compared to surgical excision, RFA is a less invasive procedure which proved to be a safe and as effective option for the treatment of spinal OO.

Outcome of re-operation for local recurrence following pre-operative denosumab administration and curettage for giant cell tumour of bone with difficult joint preservation.

PURPOSE: Denosumab enables joint-sparing surgery (curettage) and surgical downstaging in patients with giant cell tumour of bone (GCTB), where joint preservation is not possible. However, denosumab treatment causes osteosclerosis of the lesion, making it difficult to curet the lesion, leaving the tumour behind, and increasing the local recurrence rate. We performed a three-centre retrospective study to investigate the postoperative local re-recurrence rate, joint preservation status, and functional outcomes of locally recurrent lesions after preoperative denosumab treatment and curettage in patients with difficult joint preservation. METHODS: We included 38 of 142 patients with primary GCTB of the extremities who underwent preoperative denosumab and curettage between 2009 and 2021 with local recurrence. Preoperative denosumab was indicated in patients with minimal residual periarticular and subchondral bones, large extraosseous lesions (Campanacci stage 3), and pathological fractures that made joint preservation difficult. RESULTS: Local re-recurrence occurred in 6 (15.8%) of the 38 patients. In 29 patients who underwent re-curettage, local re-recurrence occurred in six patients (20.7%); however, in nine patients who underwent en bloc resection, no local re-recurrence was observed. The joint preservation rate was 63.2% (24 of 38 patients), with a median Musculoskeletal Tumor Society score of 28 (interquartile range: 26.8-29.0). The median follow-up period after surgery for local recurrence was 63.5 months (interquartile range: 42.5-82.4). CONCLUSION: Since the local re-recurrence rate after re-curettage for local recurrence was low, and the joint preservation rate and affected limb function were good, preoperative denosumab administration may be considered in patients who require downstaging to maintain good limb function (joint preservation).

Vascularized fibular grafts for the treatment of long bone defects: pros and cons. A systematic review and meta-analysis.

PURPOSE: To quantify union rate, complication rate, reintervention rate, as well as functional outcome after vascularized fibular bone grafts (VFGs) for the treatment of long-bone defects. METHODS: A comprehensive search was performed in the PubMed, Web of Science, and Cochrane databases up to August 18, 2020. Randomized controlled trials, comparative studies, and case series describing the various techniques available involving VFGs for the reconstruction of segmental long-bone defects were included. A meta-analysis was performed on union results, complications, and reinterventions. Assessment of risk of bias and quality of evidence was performed with the Downs and Black's "Checklist for Measuring Quality". RESULTS: After full-text assessment, 110 articles on 2226 patients were included. Among the retrieved studies, 4 were classified as poor, 83 as fair, and 23 as good. Overall, good functional results were documented and a union rate of 80.1% (CI 74.1-86.2%) was found, with a 39.4% (CI 34.4-44.4%) complication rate, the most common being fractures, non-unions and delayed unions, infections, and thrombosis. Donor site morbidity represented 10.7% of the total complications. A 24.6% reintervention rate was documented (CI 21.0-28.1%), and 2.8% of the patients underwent amputation. CONCLUSIONS: This systematic review and meta-analysis documented good long-term outcomes both in the upper and lower limb. However, VFG is a complex and demanding technique; this complexity means an average high number of complications, especially fractures, non-unions, and vascular problems. Both potential and limitations of VFG should be considered when choosing the most suitable approach for the treatment of long-bone defects.

Effect of adjuvant chemotherapy on periosteal osteosarcoma: a systematic review.

BACKGROUND AND OBJECTIVE: The effects of adjuvant chemotherapy on periosteal osteosarcoma are controversial. Therefore, we conducted a systematic review of studies comparing mortality, local recurrence, distant metastasis and secondary malignancy incidence among patients who underwent surgery and (neo-) adjuvant chemotherapy or surgery alone for periosteal osteosarcoma without distant metastases at diagnosis. METHODS: Of the 210 studies identified in the search, 13 were included in this study, involving 291 patients with periosteal osteosarcoma in total. RESULTS: The mortality rates in the surgery and (neo-) adjuvant chemotherapy and surgery alone groups were 11.3% (8/71) and 16.3% (16/98), respectively. The overall pooled odds ratio was 0.89 (P = 0.800). The local recurrence rate in the surgery and (neo-) adjuvant chemotherapy group was 12.1% (8/66), while that in the surgery alone group was 17.6% (13/74). The overall pooled odds ratio was 1.31 (P = 0.601). The distant metastasis rate in the surgery and (neo-) adjuvant chemotherapy group was 15.2% (10/66) and that in the surgery alone group was 10.8% (8/74). The overall pooled odds ratio was 1.51 (P = 0.444). The incidence of secondary malignancy in the surgery and (neo-) adjuvant chemotherapy group was 7.6% (9/118) and that in the surgery alone group was 2.7% (2/74). The overall pooled odds ratio was 2.29 (P = 0.187). CONCLUSIONS: Adjuvant chemotherapy did not appear to improve the prognosis of patients with periosteal osteosarcoma. No association was found between the use of adjuvant chemotherapy and development of secondary malignancies.

Risk factors of fracture following curettage for bone giant cell tumors of the extremities.

BACKGROUND: Following curettage of giant cell tumor of bone (GCTB), it is common to fill the cavity with polymethylmethacrylate (PMMA) bone cement, bone allograft, or artificial bone to maintain bone strength; however, there is a 2-14% risk of postoperative fractures. We conducted this retrospective study to clarify the risk factors for fractures after curettage for GCTB of the extremities. METHODS: This study included 284 patients with GCTBs of the extremities who underwent curettage at our institutions between 1980 and 2018 after excluding patients whose cavities were not filled with anything or who had additional plate fixation. The tumor cavity was filled with PMMA bone cement alone (n = 124), PMMA bone cement and bone allograft (n = 81), bone allograft alone (n = 63), or hydroxyapatite graft alone (n = 16). RESULTS: Fractures after curettage occurred in 10 (3.5%) patients, and the median time from the curettage to fracture was 3.5 months (interquartile range [IQR], 1.8-8.3 months). The median postoperative follow-up period was 86.5 months (IQR, 50.3-118.8 months). On univariate analysis, patients who had GCTB of the proximal or distal femur (1-year fracture-free survival, 92.5%; 95% confidence interval [CI]: 85.8-96.2) presented a higher risk for postoperative fracture than those who had GCTB at another site (100%; p = 0.0005). Patients with a pathological fracture at presentation (1-year fracture-free survival, 88.2%; 95% CI: 63.2-97.0) presented a higher risk for postoperative fracture than those without a pathological fracture at presentation (97.8%; 95% CI: 95.1-99.0; p = 0.048). Patients who received bone grafting (1-year fracture-free survival, 99.4%; 95% CI: 95.7-99.9) had a lower risk of postoperative fracture than those who did not receive bone grafting (94.4%; 95% CI: 88.7-97.3; p = 0.003). CONCLUSIONS: For GCTBs of the femur, especially those with pathological fracture at presentation, bone grafting after curettage is recommended to reduce the risk of postoperative fracture. Additional plate fixation should be considered when curettage and cement filling without bone grafting are performed in patients with GCTB of the femur. This should be specially performed for those patients with a pathological fracture at presentation.

Soft-tissue reconstruction after soft-tissue sarcoma resection: the clinical outcomes of 24 patients.

PURPOSE: Pedicle or free-flap reconstruction is important in surgical sarcoma management. Free flaps are indicated only when pedicle flaps are considered inadequate; however, they are associated with a higher risk of flap failure, longer surgical times, and technical difficulty. To determine the skin defect size that can be covered by a pedicle flap, we investigated the clinical outcomes and complications of reconstruction using pedicle flaps vs. free flaps after sarcoma resection. METHODS: We retrospectively studied the medical records of 24 patients with soft-tissue sarcomas who underwent reconstruction using a pedicle (n = 20) or free flap (n = 4) following wide tumour resection. RESULTS: All skin defects of the knee, lower leg, and ankle were reconstructed using a pedicle flap. Skin defects of the knee, lower leg, and ankle were covered by up to 525 cm2, 325 cm2, and 234 cm2, respectively. The amount of blood loss was significantly greater in the free-flap group than in the pedicle flap group (p = 0.011). Surgical time was significantly shorter in the pedicle flap group than in the free-flap group (p = 0.006). Total necrosis was observed in one (25%) patient in the free-flap group; no case of total necrosis was observed in the pedicle flap group. CONCLUSION: Less blood loss, shorter surgical time, and lower risk of total flap necrosis are notable advantages of pedicle flaps over free flaps. Most skin defects, even large ones, of the lower extremities following sarcoma resection can be covered using a single pedicle flap or multiple pedicle flaps.