Search

NMR metabolomics has inherent capabilities for studying biofluids, such as reproducibility, minimal sample preparation, non-destructiveness, and molecular structure elucidation; however, reliable quantitation of metabolites is still a challenge because of the complex matrix of the samples. The serum is one of the most common samples in clinical studies but possibly the most difficult for NMR analysis because of the high content of proteins, which hampers the detection and quantification of metabolites. Different processes for protein removal, such as ultrafiltration and precipitation, have been proposed, but require sample manipulation, increase time and cost, and possibly lead to loss of information in the metabolic profile. Alternative methods that rely on filtering protein signals by NMR pulse sequencing are commonly used, but standardisation of acquisition parameters and spectra calibration is far from being reached. The present technical note is a critical assessment of the sparsely suggested calibrants, pulse sequences and acquisition parameters toward an optimised combination of the three for accurate and reproducible quantification of metabolites in intact serum., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to evaluate the results of different treatments for pelvic Osteoblastoma (OB)., Methods: We retrospectively evaluated 34 patients affected by primary pelvic OB from 3 oncologic referral centers. Patients with a minimum follow-up of 24 months were included. Local recurrence (LR) rate and complications were recorded., Results: The primary treatment was radio-frequency ablation (RFA) in 4 patients (11.8%), curettage (ILC) in 21 (61.7%) and resection (EBR) in 9 (26.5%). Mean follow-up was 8.9 years (SD ± 6.6). Local recurrence free survival (LRFS) rate after primary surgery was 79.4% at 3 and 5 years. In details, LRFS rate at 3 and 5 years was 50.0% in RFA, 81.0% in ILC and 88.9% in EBR. Post-operative complications occurred in 6/34 patients (17.7%), in particular after EBR., Conclusions: RFA is the least invasive technique to treat OB but with high LR rate. Thus, it should be reserved to very small lesions. ILC is a suitable treatment for stage II OB. For stage III OB, EBR is the treatment of choice, despite an increased risk of complications. For selected stage III OB (relatively small, periacetabular area) ILC might be considered., Competing Interests: Declaration of competing interest All the Authors have no conflict of interests to declare., (Copyright © 2021 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Clinical responses to anticancer therapies in advanced soft tissue sarcoma (STS) are unfortunately limited to a small subset of patients. Much of the inter-individual variability in treatment efficacy and risk of toxicities is as result of polymorphisms in genes encoding proteins involved in drug pharmacokinetics and pharmacodynamics. Therefore, the detection of pharmacogenomics (PGx) biomarkers that might predict drug response and toxicity can be useful to explain the genetic basis for the differences in treatment efficacy and toxicity among STS patients. PGx markers are frequently located in transporters, drug-metabolizing enzyme genes, drug targets, or HLA alleles. Along this line, genetic variability harbouring in the germline genome of the patients can influence systemic pharmacokinetics and pharmacodynamics of the treatments, acting as predictive biomarkers for drug-induced toxicity and treatment efficacy. By linking drug activity to the functional complexity of cancer genomes, also systematic pharmacogenomic profiling in cancer cell lines and primary STS samples represents area of active investigation that could eventually lead to enhanced efficacy and offer a powerful biomarker discovery platform to optimize current treatments and improve the knowledge about the individual's drug response in STS patients into the clinical practice., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The femur is the most frequent involved site by post-attinic fractures. The appropriate treatment of pathological fractures after radiotherapy is still controversial as they are associated with a high risk of delayed consolidation and non-union. Authors review a single Center series of pathological fractures after radiation therapy in patients affected by soft tissue sarcomas analyzing incidence, risk factors, failure rate and proposing a flow chart of treatment of postattinic fractures of the femur., Methods: Authors selected 570 patients treated by limb salvage surgery associated to radiation therapy from 1992 to 2018. A pathological fracture during follow up was observed in 28 cases (5%). The mean time between the onset of the fracture after the prior surgery + radiotherapy was 70 months (range 3-182). The mean follow-up from the fracture was 86 months (range 9-222)., Results: The fracture treatment was performed with an intramedullary nail in 15 cases. Eight femoral fractures healed uneventfully (57%) and 6 required further surgical procedures. A total of eight patients underwent prosthetic replacement, 3 as a primary treatment and 5 as a salvage procedure after failure of internal fixation. Five patients developed a deep infection (62.5%).We observed 10 non-union (53%) in 19 patients treated with osteosynthesis. Overall amputation rate of the entire series was 18%. Authors propose a flowchart of treatment for femoral fractures., Conclusion: Intramedullary nailing is the treatment of choice in postradiation diaphyseal fractures of long bones, prosthetic replacement in meta-epiphyseal fracture site. Free vascularized grafts remain a valid salvage solution after failure of internal fixation., (Copyright © 2020. Published by Elsevier Ltd.)

Purpose: The aim of this multi-institutional retrospective study was to compare osteoarticular graft reconstruction (OA) and wrist arthrodesis (WA) after distal radius resection for giant cell tumor., Material and Methods: Sixty-seven patients affected by giant cell tumor of the distal radius underwent resection and reconstruction with OA (47 patients) or WA (20 patients). The mean age was 40 years (range, 13-74 years). Grafts included fresh-frozen allograft or nonvascularized fibular autograft. Complications requiring surgical revision were recorded. Clinical outcome was assessed with the Musculoskeletal Tumour Society Score (MSTS) and Disabilities of the Arm, Shoulder, and Hand (DASH) score., Results: Fifteen patients developed a local recurrence after a median of 12 months (range, 6-137 months). Sixteen patients required revision surgery for complications. Of these, 10 were graft-related complications (7 in the OA group and 3 in the WA group). Among OA, 2 patients with painful instabilities and 4 with severe arthritis required conversion into WA after a mean of 26 months (range, 13-38 months) At a median follow-up of 105 months (range, 12-395 months), similar functional outcome (MSTS and DASH score) was observed between OA and WA., Conclusions: Our results did not show any advantage of OA or WA over the other technique. A patient-by-patient decision should be taken both regarding the type of reconstruction (OA or WA) and the type of graft (allograft or autograft). The reconstructive choice should also consider the patient's functional expectations., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2020 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Introduction: Displaced intra-articular calcaneal fractures (DIACF) represent a challenging and controversial issue in traumatology. Conservative treatment has been recommended to avoid surgical problems and complications. The final result, however, is often a painful malunioun of the calcaneus with peroneal impingement. Surgical treatment is gaining acceptance since it offers a chance to restore bone anatomy improving function as long as complications are avoided., Material and Method: We reviewed a series of 59 DIACF treated by a single surgeon during a 9 years period. A clinical and radiological follow-up was obtained in 44 cases (74,6%) (average of 5,5 years; range 2-9). There were 29 males and 15 females with an average age of 54 years (range 25-74). Patients were operated through an extended l-shaped lateral approach and fixation was achieved with lag screws and plate. Outcome measures method included the AOFAS score, the Maryland Foot Score, the Foot Function Index and the SF-36., Results: The average AOFAS score was 80,5 points. The result was excellent in 18 cases (40,9%), good in 14 cases (31,8%), fair in 10 cases (22,7%) and poor in 2 (4,6%). The mean score for pain was 33,5/40 points, for function 40/50 and for alignment 7/10. Pain was absent in 17 cases (38%), 19 patients (43%) had no functional limitations and 11 (25%) could walk on uneven ground without difficulties. The average FFI score was 25/100 points. The average MFS score was 89/100 points. Subtalar motion was reduced. Reconstruction of the calcaneus was anatomic in 20 cases (45,5%) with an improved clinical outcome. Eight patients (17%) had minor wound healing complications. Three patients (6,8%) required a subtalar arthrodesis after the procedure., Conclusions: Ostheosytesis through an extended lateral approach restored bone morphology with a reasonable complications rate. The clinical results were good but a normal function and complete subtalar motion were rarely achieved., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Tarsometatarsal joint complex (TMC) is the anatomical structure of midfoot composed by metatarsals, tarsometatarsal (TMT) joints, cuneiforms, cuboid and navicular. TMC lesion are rare but critical since they cause severe disability if misdiagnosed. The knowledge of anatomic pattern of the lesion and biomechanics of the midfoot is the key for a successful diagnosis and treatment. The aim of this study was to review a consecutive series of TMC injuries analyzing preoperative radiograph and CT scan to accurately define the pattern of ligament and bone injuries., Material and Methods: We reviewed a series of 24 complete TMC injuries with homolateral dorsolateral dislocation. The total TMT joints involved were 120. We observed if the lesions were pure ligamentous or fracture-dislocation detecting the extent and the location of fractures. Twenty-nine lesions (24%) were pure dislocations and they were mainly localized in the first and fifth ray. The fracture-dislocations were 91 (76%) and 25 were fractures of the proximal row (cuneiforms and cuboid), 39 of the distal row (metatarsals), 27 of both the distal and proximal row., Results: Proximal fracture had a homogeneous distribution and they were more frequently simple than comminuted. Comminuted fractures were more frequent in the cuboid. In the proximal row, majority of partial articular fractures were localized in the dorsal side. Fracture-dislocations of the distal row were more frequent in the second metatarsal base (100%) and the partial articular fractures were always placed in the plantar side. In TMC injuries fracture-dislocations are more frequent than pure dislocations. Pure dislocations occur more often in the marginal rays that are characterized by weaker ligaments and larger mobility. The second ray, where there is the more stable joint of TMC, was never dislocated with a pure ligamentous lesion., Conclusions: We suppose that plantar avulsion from the distal row and dorsal compression fracture of the proximal row is consistent with a direct force applied to the forefoot and direct dorsolaterally. The direction of the forces may explain why some fractures occur in the distal row, some in the proximal and some in both rows. The thickness of plantar ligaments may explain the frequency of plantar bone fragment avulsion., (Copyright © 2019. Published by Elsevier Ltd.)

Background and Objectives: Liposarcoma (LPS) is a malignant mesenchymal tumor and the most common soft tissue sarcoma. Four different subtypes are described: well differentiated (WD) LPS or atypical lipomatous tumor (ALT), dedifferentiated (DD) LPS, myxoid LPS, and pleomorphic LPS (PLS). The objective of the study was to investigate prognostic factors and clinical outcome of liposarcoma., Methods: We retrospectively examined the clinico-pathological features of a series of 307 patients affected by Liposarcoma at a mean follow-up of 69 months (range 6-257). ALT/WD LPS were analyzed separately. The influence of site, size, type of presentation, grading, histotype and local recurrence on local and systemic control and survival was assessed., Results: The statistical analysis indicated that only surgical margins represented a significant prognostic factor for local recurrence in ALT/WD LPS (P = 0.0007) and other subtypes of LPS (P = 0.0055). In myxoid, PLS and DD LPS, significant prognostic factors for metastasis free survival (MFS) were surgical margins (P = 0.0009), size of the tumor (P = 0.0358), histology (P = 0.0117) and local recurrence (P = 0.0015). In multivariate analysis, surgical margins (0.0180), size (0.0432) and local recurrence (0.0288) correlated independently with MFS. Margins (P = 0.0315), local recurrence (P = 0.0482) and metastases (P < 0.0001) were prognostic factors for overall survival (OS)., Conclusion: Marginal surgery can be an accepted treatment for ALT/WD LPS. In other liposarcoma subtypes (Myxoid, DD, PLS) wide or radical surgery is recommended as the margins significantly influence local recurrence-free survival (LRFS), metastasis-free survival (MFS) and overall survival (OS). Local recurrence and metastases were significant prognostic factors for OS., (Copyright © 2018 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Giant cell tumor of bone (GCTB) is an osteolytic, locally aggressive, rarely metastazing bone tumor. This is a retrospective study evaluating a large series of GCTB patients treated with denosumab in routine practice in 6 European reference centers., Methods: Patients with locally advanced, unresectable or metastatic GCTB, treated with denosumab outside clinical trials were eligible. Primary end-point was progression-free survival (PFS) for all patients; secondary end-points were: type of surgery, relapse rate and event-free survival for patients after preoperative denosumab + surgery., Results: We identified 138 patients treated in the period 2011-2016. In 40/43 cases the diagnosis was confirmed by H3F3A gene mutation. Median follow-up time was 23 months (range 6-48). Primary tumor was located in lower limb (38%) - mostly in femur and tibia, in upper limb (34%), and in pelvis/axial skeleton/ribs (28%). 110 (80%) patients had primary tumors, 28 (22%) recurrent tumors after previous surgical procedures (+/- radiotherapy). 89/138 patients had locally advanced GCTB and underwent neoadjuvant denosumab. The median denosumab treatment duration was 8 months (median number of cycles 11), 98% had clinical benefit from therapy. 39 (44%) had wide en-bloc resection - WE (+implantation of the prosthesis in 17 cases), the other 50 (56%) cases had intralesional curettage - C. Progression after surgical treatment was observed in 19 patients, 16 of them after C (32%); 13 patients underwent denosumab re-challenge, and all responded. Two-year progression-free survival (PFS; from denosumab start) rate was 81%; 2-year EventFS (from surgery) was significantly better in WE group (93%) vs 55% in C group (p = 0.006). Treatment was well tolerated with only 2 cases of grade 3 toxicity and one osteonecrosis of the jaw., Conclusion: Our retrospective study confirms that denosumab is extremely efficient in unresectable/metastatic disease as well as in a neoadjuvant setting. Our data confirm excellent efficacy and short-term tolerability of this drug. Our data suggest that neoadjuvant therapy with denosumab is the option for treatment of initially locally advanced tumors to facilitate complete surgical resection or avoid mutilating surgery. The risk of recurrences after curettage of GCTB following denosumab raises questions about the optimal management of such cases., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: Infection in megaprostheses remains an unsolved problem, with a rate of occurrence ranging from 5% to 12%. Silver coating of medical devices has recently been proposed to reduce infection rate because of the antibacterial effect of silver. This innovation could be particularly interesting for megaprostheses, but few data have been reported in the literature., Materials and Methods: From June 2010 to August 2014 a modified MegaC System megaprosthesis with an innovative peripheral silver-added layer of titanium alloy ('Porag') was implanted in 33 patients after previous infection (21 patients) or at high risk for infection because of local or general conditions (12 patients). Previous infection followed megaprosthesis or standard arthroplasty procedures in 14 patients and trauma surgery in seven patients. A proximal femur replacement was performed in 13 patients, distal femur replacement in 13, total femur in one, and knee arthrodesis in six. Clinical results and levels of silver in blood, urine and wound drains were examined., Results: Minimum follow-up of the patients was one year (average 25.9 months). There was no infection during the first two years after surgery in the 12 patients who received a silver-coated megaprosthesis and had no previous history of infection. An infection developed in one patient at 25 months after surgery following two further surgical procedures. Infection recurred at seven months and 24 months in two out of the 21 patients (9.5%) who had received the implant because of previous septic complications. There was no clinical evidence of argyria, and no local or systemic side effects related to silver were detected. Mean levels of silver ranging from 0.41 to 5.33μg/L in blood and from 0.28 to 0.86μg/L in urine were detected at 24h to 36 months after surgery., Conclusions: Silver-coated megaprostheses showed promising results in this series in terms of prevention of infection in a high-risk group of patients, many of whom had a history of infection. No side-effects were detected. The circulating silver levels confirm both the persistence of silver-coating activity after three years and the safety of silver-coated implants. Longer follow-up and larger series are needed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Vascularised fibular grafts (VFGs) are widely used for primary reconstruction of long bones after bone tumour resections. The biological properties of VFGs are such that they can be a useful option even in failed intercalary reconstructions. The purpose of the current study was to investigate the results and the morbidity of VFGs as a salvage procedure in failed previous reconstructions after intercalary bone tumour resection of the femur. Our series included 12 patients, treated from April 1989 to March 2005, with an average age of 23 years (range 10-43 years) at presentation. The initial diagnosis was osteosarcoma in 10 cases and Ewing's sarcoma in two cases. All patients received chemotherapy and none received radiation therapy. Seven patients received VFG as biologic augmentation in intercalary allograft non-union and in the other five patients, a combination of allograft and VFG was used to replace a cement spacer with hardware failure (four patients) and a failed intercalary prosthesis (one patient). Three patients died during follow-up, in all cases because of metastatic disease. At an average follow-up of 147 months (range 11-260 months), the remaining nine patients were continuously disease-free. Complete healing of the osteotomy of both allograft and VFG was observed in 10 patients at final follow-up. Two major complications were observed that required surgical revision, eventually healing in one case and leading to a poor functional outcome in one case. Significant hypertrophy of the VFG was detected in seven of nine evaluable patients. At final follow-up the mean Musculoskeletal Tumour Society (MSTS)'93 functional score of the nine evaluable patients was 90% (range 66-100%). These results indicate that VFG is a valid salvage procedure in failed intercalary reconstructions of the femur after bone resection., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Extrapelvic endometriosis is an uncommon condition but can involve nearly every organ, resulting in a wide range of clinical manifestations. Herein, we describe the case of a 45-year-old woman not a candidate for hormonal therapy who had cyclic pain in the left thigh associated with progressive impairment of walking ability. Clinical, instrumental, and laboratory data supported the diagnosis of endometriosis involving the adductor muscles compartment associated with ovarian endometriomas. Laparoscopic bilateral salpingo-oophorectomy and local wide excision in collaboration with an experienced orthopedic oncologist were performed, and definitive histologic analysis confirmed the diagnosis of endometriosis. The patient was pain-free at 6-month follow-up and demonstrated substantial improvement in ambulation and quality of life. Large-muscle endometriosis is a rare entity that can compromise musculoskeletal integrity and decrease quality of life. In this case, surgical excision in collaboration with an orthopedic oncologist was the cornerstone of treatment., (Copyright 2010 AAGL. Published by Elsevier Inc. All rights reserved.)

While combined treatment of high-grade soft tissue sarcoma with resection and radiotherapy has become an accepted standard, outlines of treatment algorithms remain a matter of debate. Our institutional practice foresees wide surgical resection with adjuvant brachytherapy and external beam radiation. It was the purpose of this study to determine long-term outcome, prognostic factors for local and systemic recurrence and morbidity in patients with high-grade soft tissue sarcomas of the extremities, who were subjected to this regimen. One hundred and twelve patients met the inclusion criteria (56 male, 56 female; median age, 50 years). Median follow-up was 75 months (min. 11 months). Overall survival rate was 77.5% and 71.1% at 5 and 7 years, respectively. Disease-free survival rate was 63.3% and 58.4% at 5 and 10 years, respectively. Local control was achieved in 91.5% and 87.0% at 5 and 10 years, respectively. Wide surgical margins were associated with a significantly better local control rate compared to marginal or intralesional margins. Tumor size did correlate with systemic but not local recurrence. Tumor site and histotype did not appear to have an impact on outcome. Chemotherapy did not show to have an impact on local or systemic control. Fourteen patients (12.5%) had local complications attributed to radiotherapy. Eleven patients developed wound-healing problems, which needed further surgery. Using our treatment algorithm for high-grade soft tissue sarcoma of the extremities, good local and systemic control can be achieved with a low complication rate.

Background: Limb salvage surgery of popliteal soft tissue sarcomas may be hampered due to the incomplete anatomical containment of this region and the vicinity of neurovascular structures. The scope of this study was to determine outcome and to define risk factors., Patients and Methods: 27 patients (53.3+/-15.8 y; 16/27 male) with popliteal soft tissue sarcomas were assessed. Mean follow-up was 40.9+/-33.8 months (48.5+/-36.7 months in surviving patients). 9/27 patients were included after prior treatment elsewhere (5 after intralesional resections and 4 local recurrences). The lesions were staged IB in 8/27 patients, IIB in 17/27 and III in 2/27. Immediate amputations were performed in 7/27 patients. 15/27 patients were subjected to radiation therapy (preoperative in 6/15 cases), 8/27 patients received chemotherapy (5/8 preoperatively)., Results: Overall survival and disease-free survival at 5 y was 63.0% and 59.5%. Local recurrence occurred in 2 patients. 8/27 patients developed metastatic disease after 28.9+/-9.8 months. Survival (p=0.397) and disease-free survival (p=0.113) did not differ in patients after amputations vs limb salvage. Application of radiation therapy was associated with a better survival (p=0.003). Complications related to the surgical intervention were recorded in 2/27 patients, complications related to radiation therapy occurred in 6/15 patients., Discussion: Despite being extra-compartmental, popliteal sarcomas can be treated with a high rate of limb salvage while equal safety compared to amputations is maintained. Irradiation improved survival in our patient population. In cases with involvement of neurovascular structures, preoperative down-staging with radio or chemo-therapy may prevent amputation.