Aneurysmal bone cyst-like changes developed in melorheostosis with epiphyseal osteopoikilosis.

Aneurysmal bone cyst (ABC) is a rare and usually painful condition, representing about 1% of all bone tumors. A geographical lytic, expansile, and septated radiological pattern, with fluid-fluid levels on MRI, is classically displayed. ABC can be a primary bone lesion (70% of patients) or can arise in an underlying condition and is subsequently named "ABC-like changes" (30%). ABC-like changes are more frequently encountered in skeletal segments affected by chondroblastoma, fibrous dysplasia, giant cell tumor, osteoblastoma, non-ossifying fibroma, and osteosarcoma. In this article, we describe the first case of ABC-like changes developed in association with an ultra-rare sclerosing bone disease: melorheostosis. Melorheostosis is characterized by recognizable patterns on radiological studies with a pathological increased bone density and a cortical thickening within the periosteal or endosteal space, usually with a "dripping candle wax" appearance. More rarely, other different radiological patterns can be observed, such as "osteopatia striata-like," "osteoma-like," "myositis ossificans-like," and mixed patterns. Pain and limb hypotrophy are the most common clinical manifestations. We report the case of a Caucasian male with a clinic-radiological diagnosis of melorheostosis (with epiphyseal osteopoikilosis) since the age of twelve. At the age of nineteen, he suffered from increased pain in the proximal right thigh, and the radiological control revealed an expansive septated lesion at the right proximal femoral bone. The diagnosis of ABC-like changes developed in melorheostosis was obtained after CT-guided bone biopsy and confirmed by open-incisional biopsy.

Imaging Features of Alveolar Soft Part Sarcoma: Single Institution Experience and Literature Review.

Alveolar soft part sarcoma (ASPS) is an extremely rare and aggressive soft-tissue sarcoma (STS) subtype with poor prognosis and limited response to radiation therapy and chemotherapy. Prompt recognition and referral to sarcoma centers for appropriate management are crucial for patients' survival. The purpose of this study was to report ASPS pre-treatment imaging features and to examine the existing literature on this topic. Twelve patients (7 women, 5 men-mean age 27.1 ± 10.7 years) were included from our single-center experience. Ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) available were reviewed according to an analysis grid incorporating features from the latest research on STS. Clinical, histological, and outcome data were collected. MRI was available in 10 patients (83.3%), US in 7 patients (58.3%), and CT in 3 patients (25%). Mean longest tumor diameter was 7.6 ± 2.9 cm, and all tumors were deeply seated. Large peritumoral feeding vessels were systematically found and identified on ultrasonography (7/7), MRI (10/10), and CT (3/3). US revealed a well-defined heterogeneous hypoechoic pattern, with abundant flow signals in all patients (7/7). In all patients, MRI showed mildly high signal intensity (SI) on T1-WI and high SI on T2-WI and peritumoral edema. Moreover, flow-voids (due to arteriosus high-flow) into the peritumoral/intratumoral feeding vessels were detected in the MRI fluid-sensitive sequences of all patients. At baseline, whole-body contrast-enhanced CT revealed metastases in 8/12 (66.7%) patients. A pre-treatment longest diameter > 5 cm was significantly associated with distant metastases at diagnosis (p = 0.01). A maximum diameter > 5 cm represents a risk of metastatic disease at diagnosis (odds ratio = 45.0000 (95% CI: 1.4908-1358.3585), p = 0.0285). In the comprehensive literature review, we found 14 articles (case series or original research) focusing on ASPS imaging, with a total of 151 patients included. Merging our experience with the data from the existing literature, we conclude that the hallmark of ASPS imaging at presentation are the following characteristics: deep location, a slight hyperintense MRI SI on T1-WI and a hyperintense SI on T2-WI, numerous MRI flow voids, high internal vascularization, and large peritumoral feeding vessels.

Percutaneous CT-Guided Bone Biopsies: Indications, Feasibility and Diagnostic Yield in the Different Skeletal Sites-From the Skull to the Toe.

CT-guided bone biopsies are currently the diagnostic tool of choice for histopathological (and microbiological) diagnoses of skeletal lesions. Several research works have well-demonstrated their safety and feasibility in almost all skeletal regions. This comprehensive review article aims at summarizing the general concepts in regard to bone biopsy procedures, current clinical indications, the feasibility and the diagnostic yield in different skeletal sites, particularly in the most delicate and difficult-to-reach ones. The choice of the correct imaging guidance and factors affecting the diagnostic rate, as well as possible complications, will also be discussed. Since the diagnostic yield, technical difficulties, and complications risk of a CT-guided bone biopsy significantly vary depending on the different skeletal sites, subdivided analyses of different anatomical sites are provided. The information included in the current review article may be useful for clinicians assisting patients with possible bone neoplasms, as well as radiologists involved in the imaging diagnoses of skeletal lesions and/or in performing bone biopsies.

Ultrasound-Guided Percutaneous Bone Biopsy: Feasibility, Diagnostic Yield and Technical Notes.

While nowadays, CT-guided bone biopsy represents the gold standard tool for histopathological and microbiological diagnosis of skeletal lesions, the role of US-guided bone biopsy has not yet been fully explored. US-guided biopsy offers several advantages, such as the absence of ionizing radiation, fast acquisition time, as well as good intra-lesional echo, and structural and vascular characterization. Despite that, a consensus in regard to its applications in bone neoplasms has not been established. Indeed CT-guided technique (or fluoroscopic ones) still represents the standard choice in clinical practice. This review article aims to review the literature data about US-guided bone biopsy, underlying clinical-radiological indications, advantages of the procedure and future perspectives. Bone lesions taking the best advantages of the US-guided biopsy are osteolytic, determining the erosion of the overlying bone cortex and/or with an extraosseous soft-tissue component. Indeed, osteolytic lesions with extra-skeletal soft-tissue involvement represent a clear indication for US-guided biopsy. Moreover, even lytic bone lesions with cortical thinning and/or cortical disruption, especially located in the extremities or pelvis, can be safely sampled with US guidance with very good diagnostic yield. US-guided bone biopsy is proven to be fast, effective and safe. Additionally, it offers real-time needle evaluation, an advantage when compared to CT-guided bone biopsy. In the current clinical settings, it seems relevant to select the exact eligibility criteria for this imaging guidance since the effectiveness can vary depending on the type of lesion and body site involved.

CT-Guided Radiofrequency Thermal Ablation for the Treatment of Atypical, Early-Onset Osteoid Osteoma in Children Younger than 4 Years Old: Single-Institution Experience and Literature Review.

The aim of our study is to report our experience on CT-guided radiofrequency ablation (RFA) for osteoid osteoma (OO) in children under 4 years of age and to review the literature regarding this atypical, early onset of the disease. We retrospectively reviewed the clinical and radiological records of the patients treated with CT-guided RFA for OO at our institution (2006−2021), including those under 4 years of age. Data regarding technical success, clinical success, and biopsy diagnostic yield were collected. Moreover, we performed a literature review including previous articles on early-onset OO. We found only 12 patients that were under 4 years of age (12/842−1.4%) at the time of RFA treatment: 4 F and 8 M, mean age at the time of the treatment 35.3 months (range 22−46 months). The mean follow-up was 22.8 months (range 6−96 months). Technical success was achieved in all cases (12/12). In all patients (12/12), a complete remission of the pain symptoms was achieved at clinical follow-up controls. No recurrence of pain or complications were documented. The histopathological diagnosis was confirmed in 4 patients (4/12−33.3%). Moreover, we found another 9 articles in the literature with a main focus on early-onset OO (<4 years old), with a total of 12 patients included; 6 of those patients (6/12−50%) were treated with CT-guided RFA, with success reported 5 cases (5/6−83.3%). Our series of cases treated at a single institution, together with the existing data from the literature, confirms that CT-guided RFA is effective and safe for the treatment of osteoid osteoma, even in atypical, early onset in children under 4 years of age.

The role of conventional radiography to assess the outcome of oncologic skeletal reconstructions of lower limbs aided by vascularized fibular autograft.

INTRODUCTION: Vascularized fibular autografts (VFA) are used in the oncologic skeletal reconstructions of long bones, alone or combined with massive bone allografts (MBA). Data regarding the role of imaging in assessing these complex skeletal reconstructions are lacking, and have mainly focused on Computed Tomography (CT). Our aim was to evaluate if early conventional radiography (CR) findings are correlated with the outcome of these skeletal reconstructions. MATERIALS AND METHODS: All consecutive patients who underwent oncologic resection of lower limbs long bones followed by VFA reconstruction were included in this single-center retrospective study. We compared the CR obtained immediately after surgery with the CR at the 6-month control, as well as the CR at 6 months with the CT at 6 months when available. The following scores were assigned to the VFA: 0 (unchanged), 1 (osteopenia-cortical bone thinning), 2 (increase in bone density-cortical thickening). We then investigated whether this score correlated with the implant outcome within 12 months (optimal integration, suboptimal integration, integration requiring further surgery or lack of integration) using Kaplan-Meier and Cox regression analyses, considering the occurrence of integration and the duration time before the surgical removal of the whole bone reconstruction. RESULTS: Forty-five patients were included (32 men [71.1%], mean age 14.6 years), 26 affected by osteosarcoma, 14 by Ewing sarcoma, 3 by adamantinoma and 2 operated for the failure of previous reconstructions for bone sarcoma. VFA changes on 6-month CR were significantly associated with optimal integration of the implants (log-rank P = 0.0137, multivariate Hazard ratio = 7.62, 95% confidence interval = 1.13-51.25). None of the other clinical and surgical features were associated with the implant outcome. The findings on 6-month CR and CT follow-up were not significantly different. CT at 6 months was available in 36 patients (80.0%). CONCLUSION: The assessment of VFA morphological changes on CR performed at 6 months can predict the outcome of the skeletal implant. This data should be considered for clinical decision-making, selecting patients requiring additional images (CT), and possible subsequent revision surgical procedures.

Soft Tissue Sarcomas: The Role of Quantitative MRI in Treatment Response Evaluation.

BACKGROUND: Although curative surgery remains the cornerstone of the therapeutic strategy in patients with soft tissue sarcomas (STS), neoadjuvant radiotherapy and chemotherapy (NART and NACT, respectively) are increasingly used to improve operability, surgical margins and patient outcome. The best imaging modality for locoregional assessment of STS is MRI but these tumors are mostly evaluated in a qualitative manner. OBJECTIVE: After an overview of the current standard of care regarding treatment for patients with locally advanced STS, this review aims to summarize the principles and limitations of (i) the current methods used to evaluate response to neoadjuvant treatment in clinical practice and clinical trials in STS (RECIST 1.1 and modified Choi criteria), (ii) quantitative MRI sequences (i.e., diffusion weighted imaging and dynamic contrast enhanced MRI), and (iii) texture analyses and (delta-) radiomics.

Does the Addition of a Vascularized Fibula Improve the Results of a Massive Bone Allograft Alone for Intercalary Femur Reconstruction of Malignant Bone Tumors in Children?

BACKGROUND: Massive bone allograft with or without a vascularized fibula is a potentially useful approach for femoral intercalary reconstruction after resection of bone sarcomas in children. However, inadequate data exist regarding whether it is preferable to use a massive bone allograft alone or a massive bone allograft combined with a vascularized free fibula for intercalary reconstructions of the femur after intercalary femur resections in children. Because the addition of a vascularized fibula adds to the time and complexity of the procedure, understanding more about whether it reduces complications and improves the function of patients who undergo these resections and reconstructions would be valuable for patients and treating physicians. QUESTIONS/PURPOSES: In an analysis of children with bone sarcomas of the femur who underwent an intercalary resection and reconstruction with massive bone allograft with or without a vascularized free fibula, we asked: (1) What was the difference in the surgical time of these two different surgical techniques? (2) What are the complications and number of reoperations associated with each procedure? (3) What were the Musculoskeletal Tumor Society scores after these reconstructions? (4) What was the survival rate of these two different reconstructions? METHODS: Between 1994 and 2016, we treated 285 patients younger than 16 years with a diagnosis of osteosarcoma or Ewing sarcoma of the femur. In all, 179 underwent resection and reconstruction of the distal femur and 36 patients underwent resection and reconstruction of the proximal femur. Additionally, in 70 patients with diaphyseal tumors, we performed total femur reconstruction in four patients, amputation in five, and a rotationplasty in one. The remaining 60 patients with diaphyseal tumors underwent intercalary resection and reconstruction with massive bone allograft with or without vascularized free fibula. The decision to use a massive bone allograft with or without a vascularized free fibula was probably influenced by tumor size, with the indication to use the vascularized free fibula in longer reconstructions. Twenty-seven patients underwent a femur reconstruction with massive bone allograft and vascularized free fibula, and 33 patients received massive bone allograft alone. In the group with massive bone allograft and vascularized fibula, two patients were excluded because they did not have the minimum data for the analysis. In the group with massive bone allograft alone, 12 patients were excluded: one patient was lost to follow-up before 2 years, five patients died before 2 years of follow-up, and six patients did not have the minimum data for the analysis. We analyzed the remaining 46 children with sarcoma of the femur treated with intercalary resection and biological reconstruction. Twenty-five patients underwent femur reconstruction with a massive bone allograft and vascularized free fibula, and 21 patients had reconstruction with a massive bone allograft alone. In the group of children treated with massive bone allograft and vascularized free fibula, there were 17 boys and eight girls, with a mean ± SD age of 11 ± 3 years. The diagnosis was osteosarcoma in 14 patients and Ewing sarcoma in 11. The mean length of resection was 18 ± 5 cm. The mean follow-up was 117 ± 61 months. In the group of children treated with massive bone allograft alone, there were 13 boys and eight girls, with a mean ± SD age of 12 ± 2 years. The diagnosis was osteosarcoma in 17 patients and Ewing sarcoma in four. The mean length of resection was 15 ± 4 cm. The mean follow-up was 130 ± 56 months. Some patients finished clinical and radiological checks as the follow-up exceeded 10 years. In the group with massive bone allograft and vascularized free fibula, four patients had a follow-up of 10, 12, 13, and 18 years, respectively, while in the group with massive bone allograft alone, five patients had a follow-up of 10 years, one patient had a follow-up of 11 years, and another had 13 years of follow-up. In general, there were no important differences between the groups in terms of age (mean difference 0.88 [95% CI -0.6 to 2.3]; p = 0.26), gender (p = 0.66), diagnosis (p = 0.11), and follow up (mean difference 12.9 [95% CI-22.7 to 48.62]; p = 0.46). There was a difference between groups regarding the length of the resection, which was greater in patients treated with a massive bone allograft and vascularized free fibula (18 ± 5 cm) than in those treated with a massive bone allograft alone (15 ± 4 cm) (mean difference -3.09 [95% CI -5.7 to -0.4]; p = 0.02). Complications related to the procedure like infection, neurovascular compromise, and graft-related complication, such as fracture and nonunion of massive bone allograft or vascularized free fibula and implant breakage, were analyzed by chart review of these patients by an orthopaedic surgeon with experience in musculoskeletal oncology. Survival of the reconstructions that had no graft or implant replacement was the endpoint. The Kaplan-Meier test was performed for a survival analysis of the reconstruction. A p value less than 0.05 was considered significant. RESULTS: The surgery was longer in patients treated with a massive bone allograft and vascularized free fibula than in patients treated with a massive bone allograft alone (10 ± 0.09 and 4 ± 0.77 hours, respectively; mean difference -6.8 [95% CI -7.1 to -6.4]; p = 0.001). Twelve of 25 patients treated with massive bone allograft and vascularized free fibula had one or more complication: allograft fracture (seven), nonunion (four), and infection (four). Twelve of 21 patients treated with massive bone allograft alone had the following complications: allograft fracture (five), nonunion (six), and infection (one). The mean functional results were 26 ± 4 in patients with a massive bone allograft and vascularized free fibula and 27 ± 2 in patients with a massive bone allograft alone (mean difference 0.75 [95% CI -10.6 to 2.57]; p = 0.39). With the numbers we had, we could not detect a difference in survival of the reconstruction between patients with a massive bone allograft and free vascularized fibula and those with a massive bone allograft alone (84% [95% CI 75% to 93%] and 87% [95% CI 80% to 94%], respectively; p = 0.89). CONCLUSION: We found no difference in the survival of reconstructions between patients treated with a massive bone allograft and vascularized free fibula and patients who underwent reconstruction with a massive bone allograft alone. Based on this experience, our belief is that we should reconstruct these femoral intercalary defects with an allograft alone and use a vascularized fibula to salvage the allograft only if a fracture or nonunion occurs. This approach would have resulted in about half of the patients we treated not undergoing the more invasive, difficult, and risky vascularized procedure.Level of Evidence Level III, therapeutic study.

Image-guided Cryotherapy for Musculoskeletal Tumors.

BACKGROUND: This article represents a review of the use of image-guided cryotherapy in the treatment of musculoskeletal tumor lesions. Cryotherapy is able to induce a lethal effect on cancer cells through direct and indirect mechanisms. In this manuscript, we combined our experience with that of other authors who have published on this topic in order to provide indications on when to use cryotherapy in musculoskeletal oncology. DISCUSSION: Image-Guided percutaneous cryotherapy is a therapeutic method now widely accepted in the treatment of patients with musculoskeletal tumors. It can be used both for palliative treatments of metastatic bone lesions and for the curative treatment of benign bone tumors, such as osteoid osteoma or osteoblastoma. In the treatment of bone metastases, cryotherapy plays a major role in alleviating or resolving disease-related pain, but it has also been demonstrated that it can have a role in local disease control. In recent years, the use of cryotherapy has also expanded for the treatment of both benign and malignant soft tissue tumors. CONCLUSION: Percutaneous cryotherapy can be considered a safe and effective technique in the treatment of benign and malignant musculoskeletal tumors. Cryotherapy can be considered the first option in benign tumor lesions, such as osteoid osteoma, and a valid alternative to radiofrequency ablation. In the treatment of painful bone metastases, it must be considered secondarily to other standard treatments (radiotherapy, bisphosphonate therapy, and chemotherapy) when they are no longer effective in controlling the disease or when they cannot be repeated (for example, radiotherapy).

Difficult diagnosis of Angiomatoid Fibrous Histiocytoma of the leg mimicking a benign condition.

Angiomatoid fibrous histiocytoma is a rarely metastasizing soft-tissue tumor of low-grade malignancy. Here we report a case of angiomatoid fibrous histiocytoma located in the leg of a 15-year-old female. This case is of particular interest due to its radiological features that led to raise two questions concerning the nature of the disease (is it reactive or tumoral?) and its site of origin (within soft tissues or the tibial periosteum?). Here we describe ultrasound, magnetic resonance imaging, computed tomography scan and positron emission tomography findings that helped answer these questions, understand the real nature of the disease and its appropriate treatment. This case shows that a single type of imaging technique may not be sufficient to understand the real nature of a musculoskeletal lesion and that it is necessary to combine all information derived from various imaging techniques in order to correctly diagnose and treat the disease.

Neurofibromatosis type-1-associated diffuse lung disease in children.

OBJECTIVE: The purpose of the study was to investigate the occurrence of diffuse lung disease associated with neurofibromatosis type-1 in the pediatric population. We also aimed at evaluating computed tomography (CT) findings of the disease. INTRODUCTION: Diffuse lung disease associated with neurofibromatosis type-1 has been described mainly in the adult population; causes and connections between lung disease and the genetic disorder are still not completely understood. The occurrence of the disease in non-smokers, the presence of blebs, bullae or cysts distinct from smoking-related emphysema on CT and the histopathological pattern characterized by lymphoplasmocytic inflammation and fibrosis, are all factors that support the association of diffuse lung disease as a distinct manifestation of neurofibromatosis. METHODS: We retrospectively reviewed, with "lung window," all the spinal CTs performed in two institutions from 2004 to 2018 for scoliosis assessment in pediatric patients affected by neurofibromatosis type-1 (group 1). Moreover, we retrospectively analyzed a control group of pediatric patients, affected by severe scoliosis without neurofibromatosis (group 2). Differences between the two groups were analyzed to ascertain whether the disease can be related to neurofibromatosis type-1 rather than to scoliosis. RESULTS: Six out of thirty one subjects from group 1 (19.4%) showed a condition of diffuse lung disease while none (0 of 31) in group 2. The differences between the two groups were statistically significant (P = .01). All six patients showed subpleural blebs, bullae, or cysts without basilar fibrosis. CONCLUSION: Our research consolidates the hypothesis that diffuse lung disease is a direct manifestation of neurofibromatosis type-1 and that early onset is possible, even in pediatric patients.

Bone marrow biopsy in the initial staging of Ewing sarcoma: Experience from a single institution.

BACKGROUND: Ewing sarcoma (ES) is the second most common bone tumor in adolescents and children. Staging workup for ES includes imaging and bone marrow biopsy (BMB). The effective role of BMB is now under discussion. PROCEDURE: A monoinstitutional retrospective analysis reviewed clinical charts, imaging, and histology of patients with diagnosis of ES treated at the Rizzoli Institute between 1998 and 2017. RESULTS: The cohort included 504 cases of ES of bone; 137 (27%) had metastases at diagnosis, while the remaining 367 had localized disease. Twelve patients had a positive BMB (2.4%). Eleven had distant metastases detected at initial workup staging with imaging assessment: six patients presented with bone metastases, five with both bone and lung metastases. Only one patient with ES of the foot (second metatarsus) was found to have bone marrow involvement with negative imaging evaluation (0.3%). CONCLUSIONS: On the basis of our data, we suggest reconsidering the effective role of BMB in initial staging workup for patients with ES with no signs of metastases by modern imaging techniques. In metastatic disease, the assessment of the bone marrow status may remain useful to identify a group of patients at very high risk who could benefit from different treatment strategies.

Rehabilitation needs in oncological patients: the On-rehab project results on patients operated for musculoskeletal tumors.

BACKGROUND: Rehabilitation plays an important role in improving functional outcome in patients operated on musculoskeletal tumors. Literature in the field is scarce and the specific needs for rehabilitation of these patients are still unknown. AIM: To analyze the rehabilitation needs of patients with primary malignant musculoskeletal tumors. DESIGN: Observational, longitudinal study on both inpatient and outpatient operated on musculoskeletal tumors. METHODS: Rehabilitation needs of oncological patients were explored by means of questionnaires administered by a physician. Demographic, oncological, psychological domains were also assessed. RESULTS: Twenty-nine patients were evaluated in the immediate post-operative period, 25 patients had a follow up at 6 months, and 11 patients at 12 months. Rehabilitation needs concerned essentially the neuromotor function and the improvement of independence at home/outside home. At first admission, support for occupational rehabilitation was also relevant, while its importance was reduced over the follow-up. Pain control need was greater at first admission (VAS over the follow-up 3.3, 0.52, and 1.09, respectively) and required treatment with painkillers. Quality of life (EORTC) increased over the three assessments (respectively 48.80; 71.42; 82.14). The Psychological Distress Inventory (PDI) scores were 26.23, 21.75, 23.6, and the Caregiver Needs Assessment (CNA) scores were 32.69, 27.95, and 31.7 respectively at the three follow up. CONCLUSIONS: The relevant domains in which rehabilitation needs emerged in up to 1 year follow up were the neuromotor area in order to gain independence at home and outside the home, pain control, particularly after surgery, nursing, psychological support of patients and caregivers, and occupational activities (personal, work, school, social). CLINICAL REHABILITATION IMPACT: The findings of the present study suggest that: short and midterm clinical rehabilitation programs should be made available for patients operated on musculoskeletal tumors. Physical function recovery is only one aspect of rehabilitation, and psychosocial functioning must be taken into account and coordinated by a comprehensive team of specialists. Appropriate assessment tools should be used, and a continuum of care from the hospital to the patient's home should be promoted.

Is There Benefit to Free Over Pedicled Vascularized Grafts in Augmenting Tibial Intercalary Allograft Constructs?

BACKGROUND: Intercalary reconstruction of tibial sarcomas with vascularized fibula autografts and massive bone allografts is reliable with predictable long-term results. However, inadequate data exist comparing free and pedicled vascularized fibula autografts in combination with a massive bone allograft in patients undergoing intercalary tibia reconstructions. QUESTIONS/PURPOSES: Among patients undergoing large-segment intercalary allografting, we sought to compare supplemental free vascularized fibular autografts with supplemental pedicled vascularized fibular autografts, in terms of (1) oncologic results, (2) complications associated with surgery, (3) Musculoskeletal Tumor Society (MSTS) scores, and (4) surgical time. METHODS: Between 1994 and 2013, we treated 320 patients, younger than 40 years, with tibial sarcomas. Thirty-five patients (11%) underwent amputations. One hundred ninety-five patients (61%) were treated with intraarticular resection of the tibia, which constituted 104 tumor endoprostheses, 63 proximal tibia allograft prosthetic composites, 21 osteoarticular allografts, and seven arthrodeses with allografts. Ninety patients (28%) underwent joint-sparing intercalary reconstruction. Forty-one (13%) of these 90 patients were treated with allografts alone, two (1%) with vascularized fibula grafts, and 47 (15%) with intercalary allografts supplemented by autografts (free fibular autografts, 22 patients, 7%; pedicled fibular autografts, 25 patients, 8%). During the study period, we used free vascularized fibular autografts in association with massive bone allograft for a resection longer than 12 cm with a very small periarticular residual segment. The choice for using a pedicled fibula harvested in the ipsilateral leg initially was for patients having only diaphyseal resections and the indication was later extended to intraepiphyseal osteotomies with a small periarticular residual segment. The goals of this study are to present the long-term results in this group of patients and compare their results based on the type of vascularized fibula harvest. There were 33 male and 14 female patients with mean age of 14 ± 6 years. The median followup was 84 months (range, 7-231 months). No patients were lost to followup before 1 year. Four patients died and were not available for followup after 18 months. The mean tibia resection length was 15 ± 4 cm and mean length of the harvested vascularized fibula was 18 ± 4 cm. RESULTS: Overall 5- and 10-year oncologic survival rates in this study were 87% ± 5% and 83% ± 6% respectively. With the numbers available, we observed no difference in survivorship free from death from disease between the study groups (85% ± 8% [95% CI, 174-232 months] of the free vascularized group versus 82% ± 8% [95% CI, 148-206 months] of the pedicled fibula graft group; p = 0.741). At last followup, 40 patients had no evidence of disease and seven had died of disease. Local recurrence was observed in two patients in the supplemental free vascularized fibula group and three patients in the supplemental pedicled vascularized fibula group, whereas metastases was observed in eight patients. With the numbers available, we observed no difference in the proportion of patients experiencing surgical complications between those treated with free vascularized fibula grafts and those treated with pedicled grafts (eight of 22 [36%] versus nine of 25 [36%] respectively; p = 0.605). With the numbers available, we observed no difference in mean MSTS scores between patients treated with free vascularized fibula grafts and those treated with pedicled grafts (24 ± 9 versus 25 ± 8; mean difference, 0.48; 95% CI, 0.54-4.6; p = 0.858). Mean surgical time was longer in the free vascularized fibula and massive bone allograft group at 9.4 ± 1.7 hours compared with that of the pedicled vascularized fibula and massive bone allograft group at 5.7 ± 1.3 hours (mean difference, 3.73 hours; 95% CI, 2.8-4.6 hours; p ≤ 0.001). CONCLUSIONS: Intercalary reconstruction of tibia sarcomas with massive bone allografts supplemented with vascularized fibula grafts provide predictable results. Complications occur as expected in a biologic reconstruction, but are salvageable, preserving the original construct. The pedicled fibula can be an alternative to a free contralateral fibula for intraepiphyseal resections. Comparative technical ease, shorter surgical time, avoidance of additional microvascular anastomosis, and avoidance of surgery on the contralateral leg are notable advantages of pedicled vascularized fibula over free fibula grafts to supplement allografts when indicated in intercalary tibia resections. LEVEL OF EVIDENCE: Level III, therapeutic study.

The role of FDG PET/CT in patients treated with neoadjuvant chemotherapy for localized bone sarcomas.

PURPOSE: The histological response to neoadjuvant chemotherapy is an important prognostic factor in patients with osteosarcoma (OS) and Ewing sarcoma (EWS). The aim of this study was to assess baseline primary tumour FDG uptake on PET/CT, and serum values of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), to establish whether these factors are correlated with tumour necrosis and prognosis. METHODS: Patients treated between 2009 and 2014 for localized EWS and OS, who underwent FDG PET/CT as part of their staging work-up, were included. The relationships between primary tumour SUVmax at baseline (SUV1), SUVmax after induction chemotherapy (SUV2), metabolic response calculated as [(SUV1 - SUV2)/SUV1)] × 100, LDH and ALP and tumour response/survival were analysed. A good response (GR) was defined as tumour necrosis >90 % in patients with OS, and grade II-III Picci necrosis (persitence of microscopic foci only or no viable tumor) in patients with Ewing sarcoma. RESULTS: The study included 77 patients, 45 with EWS and 32 with OS. A good histological response was achieved in 53 % of EWS patients, and 41 % of OS patients. The 3-year event-free survival (EFS) was 57 % in EWS patients and 48 % OS patients. The median SUV1 was 5.6 (range 0 - 17) in EWS patients and 7.9 (range 0 - 24) in OS patients (p = 0.006). In EWS patients the GR rate was 30 % in those with a high SUV1 (≥6) and 72 % in those with a lower SUV1 (p = 0.0004), and in OS patients the GR rate was 29 % in those with SUV1 ≥6 and 64 % in those with a lower SUV1 (p = 0.05). In the univariate analysis the 3-year EFS was significantly better in patients with a low ALP level (59 %) than in those with a high ALP level (22 %, p = 0.02) and in patients with a low LDH level (62 %) than in those with a high LDH level (37 %, p = 0.004). In EWS patients the 3-year EFS was 37 % in those with a high SUV1 and 75 % in those with a low SUV1 (p = 0.004), and in OS patients the 3-year EFS was 32 % in those with a high SUV1 and 66 % in those with a low SUV1 (p = 0.1). Histology, age and gender were not associated with survival. In the multivariate analysis, SUV1 was the only independent pretreatment prognostic factor to retain statistical significance (p = 0.017). SUV2 was assessed in 25 EWS patients: the median SUV2 was 1.9 (range 1 - 8). The GR rate was 20 % in patients with a high SUV2, and 67 % in those with a low SUV2 (p = 0.02). A good metabolic response (SUV reduction of ≥55 %) was associated with a 3-year EFS of 80 % and a poor metabolic response with a 3-year EFS of 20 % (p = 0.05). In the OS patients the median SUV2 was 2.7 (range 0 - 4.5). Neither SUV2 nor the metabolic response was associated with outcome in OS patients. CONCLUSION: FDG PET/CT is a useful and noninvasive tool for identifying patients who are more likely to be resistant to chemotherapy. If this finding is confirmed in a larger series, SUV1, SUV2 and metabolic response could be proposed as factors for stratifying EWS patients to identify those with high-grade localized bone EWS who would benefit from risk-adapted induction chemotherapy.

Long-term treatment with thiamine as possible medical therapy for Friedreich ataxia.

Thiamine (vitamin B1) is a cofactor of fundamental enzymes of cell energetic metabolism; its deficiency causes disorders affecting both the peripheral and central nervous system. Previous studies reported low thiamine levels in cerebrospinal fluid and pyruvate dehydrogenase dysfunction in Friedreich ataxia (FRDA). We investigated the effect of long-term treatment with thiamine in FRDA, evaluating changes in neurological symptoms, echocardiographic parameters, and plasma FXN mRNA levels. Thirty-four consecutive FRDA patients have been continuously treated with intramuscular thiamine 100 mg twice a week and have been assessed with the Scale for the Assessment and Rating of Ataxia (SARA) at baseline, after 1 month, and then every 3 months during treatment. Thiamine administration ranged from 80 to 930 days and was effective in improving total SARA scores from 26.6 ± 7.7 to 21.5 ± 6.2 (p < 0.02). Moreover, deep tendon reflexes reappeared in 57 % of patients with areflexia at baseline, and swallowing improved in 63 % of dysphagic patients. Clinical improvement was stable in all patients, who did not show worsening even after 2 years of treatment. In a subgroup of 13 patients who performed echocardiogram before and during treatment, interventricular septum thickness reduced significantly (p < 0.02). Frataxin mRNA blood levels were modestly increased in one-half of treated patients. We suppose that a focal thiamine deficiency may contribute to a selective neuronal damage in the areas involved in FRDA. Further studies are mandatory to evaluate thiamine role on FXN regulation, to exclude placebo effect, to verify our clinical results, and to confirm restorative and neuroprotective action of thiamine in FRDA.

Resurfaced Allograft-Prosthetic Composite for Proximal Tibial Reconstruction in Children.

INTRODUCTION: Reconstruction of the proximal part of the tibia in children with use of an unconstrained tibial component cemented in an allograft-prosthetic composite after proximal tibial resection spares the distal femoral physis and articular cartilage, maintains the bone stock of the tibia, and allows the allograft to be adapted to the small tibial dimension in very young patients. STEP 1 MAKE THE INCISION: Make a longitudinal incision medially or laterally, depending on the side of the biopsy (usually medial), encompassing and encircling the biopsy site. STEP 2 PERFORM THE ARTHROTOMY: A parapatellar arthrotomy is performed, and the cruciate ligaments are cut close to the femoral attachment. STEP 3 ISOLATE THE VASCULAR BUNDLE: Retract the medial gastrocnemius muscle and then isolate and protect the popliteal and posterior tibial vessels. STEP 4 PERFORM AN OSTEOTOMY OF THE TIBIA: Perform an osteotomy of the tibiofibular joint and the tibial shaft at the appropriate level as determined on the basis of the preoperative imaging, and then complete the resection. STEP 5 PREPARE THE ALLOGRAFT ON A SEPARATE TABLE: Cut and prepare the allograft according to the specimen dimensions. STEP 6 PREPARE THE COMPOSITE DEVICE: Cement the tibial component of an unconstrained total knee prosthesis in the allograft and place the trial device. STEP 7 FIX THE COMPOSITE DEVICE AND SUTURE THE CAPSULE AND LIGAMENTS: Place the trial composite device and then fix the composite device to the host tibia and suture the capsule and ligaments. STEP 8 POSTOPERATIVE CARE: Immobilize the knee with an above-the-knee plaster cast, which is worn for six weeks, and then have the patient perform progressive functional rehabilitation. RESULTS: The rate of postoperative infection after proximal tibial reconstruction with a resurfaced allograft composite in children has been found to be no higher than that with other reconstructive techniques for the proximal part of the tibia; our series had a 5% rate of deep infection.IndicationsContraindicationsPitfalls & Challenges.