Chemotherapy Regimens for Non-Metastatic Conventional Appendicular Osteosarcoma: A Literature Review Based on the Outcomes.

Osteosarcoma is a rare condition with a complex treatment. Most protocols include neoadjuvant chemotherapy, surgery, and consolidation chemotherapy as the standard of treatment. However, the use of neoadjuvant chemotherapy lacks scientific evidence proving superiority in opposition to the use of isolated chemotherapy in an adjuvant regimen after surgery. We conducted a review for studies published in English between 1980 and 2020, using the MEDLINE/PubMed and Scopus electronic databases, to evaluate the outcomes when using neoadjuvant chemotherapy or adjuvant chemotherapy strategies in the treatment of non-metastatic appendicular osteosarcoma, as well as the toxicity associated with different chemotherapeutic regimens. Patients were divided into a neoadjuvant chemotherapy group (NAC) and adjuvant chemotherapy group (ACT), depending on the chemotherapy regimen used in association with surgery. A total of 1254 articles in English were screened by title and abstract, and 146 were pre-selected for full reading and analysis. A total of 24 assays matching the inclusion criteria were selected: 10 prospective and 14 retrospective studies. This review points to an absence of significative differences in outcomes, namely overall survival, disease-free survival/event-free survival rates, or toxicity, regarding neoadjuvant or single adjuvant chemotherapy strategies used in the treatment of appendicular non-metastatic osteosarcomas. However, there is a significative difference in population dimensions between the NAC and the ACT groups. Additionally, clinical presentation, tumor localization, tumor volume, or histological type were not considered, with these variables presenting the potential to influence these results. Despite these limitations, our findings should allow a re-thinking of our current practice and promote new opportunities to optimize treatment, always looking towards better survival and lower complications rates.

Delayed Post-Operative Neurological Deficit After Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis: Possible Association With Post-Operative Anemia.

Background: To present a patient with adolescent idiopathic scoliosis who developed a significant neurological deficit after posterior spinal fusion, in association with anemia on postoperative day two. Case Report: A 14-year-old otherwise healthy female underwent a T3-L3 instrumented posterior spinal fusion for idiopathic scoliosis which was uneventful. Immediate post-operative clinical examination was unremarkable but at postoperative day three the patient developed generalized lower extremity weakness with inability to stand and an urinary retention needing continuous intermittent catheterization program. Her hemoglobin (Hg) dropped from 10 g/dL on postoperative day one to 6.2 g/dL at day two, despite no significant bleeding was noticed. Compressive etiology was ruled out by postoperative myelogram-CT. The patient started to improve significantly after transfusion support. At three months follow-up the patient was neurologically normal. Conclusion: Close clinical neurological evaluation over 48 to 72 hours is needed in order to detect unexpected delayed paralysis following scoliosis surgery. Level of Evidence: IV.

Benefits of Best Practice Guidelines in Spine Fusion: Comparable Correction in AIS with Higher Density and Fewer Complications.

BACKGROUND: There is significant variability in surgeons' instrumentation patterns for adolescent idiopathic scoliosis surgery. Implant density and costs are difficult to correlate with deformity correction, safety, and quality of life measures. MATERIALS AND METHODS: Two groups of postoperative adolescents were compared based on exposure to a best practice guidelines program (BPGP) introduced to decrease complications. Hybrid and stainless steel constructs were dropped, and posterior-based osteotomies, screws, and implant density were increased to 66.8 ± 12.03 vs. 57.5 ± 16.7% (p < 0.001). The evaluated outcomes were: initial and final correction, rate of correction loss, complications, OR returns, and SRS-22 scores (minimum two-year follow-up). RESULTS: 34 patients were operated on before BPGP and 48 after. The samples were comparable, with the exceptions of a higher density and longer operative times after BPGP. Initial and final corrections before BPGP were 67.9° ± 22.9 and 64.6° ± 23.7; after BPGP, the corrections were 70.6° ± 17.4 and 66.5° ± 14.9 (sd). A regression analysis did not show a relation between the number of implants and postoperative correction (beta = -0.116, p = 0.307), final correction (beta = -0.065, p = 0.578), or loss of correction (beta= -0.137, p = 0.246). Considering screw constructs only (n = 63), a regression model controlled for flexibility continued to show a slight negative effect of density on initial correction (b = -0.274; p = 0.019). Only with major curve concavity was density relevant in initial correction (b = 0.293; p = 0.038), with significance at 95% not being achieved for final correction despite a similar beta (b = 0.263; p = 0.069). Complications and OR returns dropped from 25.6% to 4.2%. Despite this, no difference was found in SRS-22 (4.30 ± 0.432 vs. 4.42 ± 0.39; sd) or subdomain scores pre- and post-program. FINDINGS: Although it appears counterintuitive that higher density, osteotomies, and operative time may lead to fewer complications, the study shows the value of best practice guidelines in spinal fusions. It also shows that a 66% implant density leads to better safety and efficacy, avoiding higher costs.

Complications associated with surgical treatment for pediatric spine deformities: A single center 10-years experience.

INTRODUCTION: The surgical treatment for pediatric spine deformity is complex and often associated with complications, which generates important clinical and economic impact. Herein the authors analyze the prevalence of complications in surgery for pediatric spine deformity, the correlation between complications and several risk factors, and present a preventive algorithm for these events. MATERIAL AND METHODS: We collected for analysis the data regarding pediatric patients with spine deformities surgically treated in our institution through a 10 years period with 100% revision rate and a 24-month minimum follow-up were included. The statistical analysis was performed using SPSS Statistics 23. RESULTS: 70 complications (33,4%) were identified in 56 patients (26,7%), of which 38 (54,2%) were acute and 32 (45,7%) late complications. Pulmonary complications (7.1%), surgical site infection (6.6%) and junctional kyphosis (4.3%) were the most frequent events. Scoliosis etiology was especially correlated with general complications (p < 0.05) and early complications (p < 0.01). A logistic regression model identified preoperative hemoglobin (Exp =1.476; P=0.044), fused levels (Exp =-0.677; P=0.023) and titanium implants (Exp =0.257, P < 0.000) as relevant factors for complications. Area under the curve was 0.744, and, when using the best cutting point, the model was capable of predicting absence of complications in 84% of cases, and its occurrence in 56%. DISCUSSION: Pulmonary complications, surgical site infection and junctional events were identified as the most frequent complications after pediatric scoliosis surgery. By developing high risk protocols to decrease these events, patient safety will be significantly enhanced. Risk assessment makes part of this process and our predictive model by identifying two modifiable factors and including another that relates to procedure invasiveness may help avoiding complications and improve outcomes. ctors for complications. Area under the curve was 0.744, and, when using the best cutting point, the model was capable of predicting absence of complications in 84% of cases, and its occurrence in 56%.

Closed-incision negative-pressure wound therapy (ciNPWT) to minimize wound-related complications in lower limb reconstruction after bone tumor resection: preliminary proof-of-concept study.

AIMS: The purpose of this study was to compare the impact of postoperative closed-incision negative-pressure wound therapy (ciNPWT) and conventional dressings in wound-related complications after bone tumor resection and reconstruction. PATIENTS AND METHODS: A total of 50 patients with bone tumors and clinical indication for wide resection and reconstruction were included and divided into two groups (A and B). Bone defect reconstructions were achieved with modular endoprosthesis or biologic techniques, mainly involving allografts with free vascularized fibula. Group A received ciNPWT, and Group B conventional dressings. Wound-related complications, including wound dehiscence, persistent wound leakage, surgical site infections (SSIs), and causes for surgical revision, were assessed. RESULTS: Nineteen patients were included in Group A and 31 in Group B. No significant differences were found between groups regarding epidemiologic and clinical presentation features, contrarily to reconstructive options, which were significantly different between both (Fisher = 10,100; p = 0.005). Additionally, Group A presented lower wound dehiscence rate (0 vs. 19.4%; χ2(1) = 4.179; p = 0.041), SSI rate (0 vs. 19.4%; χ2(1) = 4.179; p = 0.041), and surgical revision rate (5.3% vs. 32.3%; χ2(1) = 5.003; p = 0.025) compared to Group B. CONCLUSIONS: This is the first study reporting the impact of ciNPWT after bone tumor resection and reconstruction, and its results support a potential role for this technique in diminishing postoperative wound complications and SSIs. A multicentric randomized controlled trial may help clarify the role and impact of ciNPWT after bone tumor resection and reconstruction.

On the Relevance of Soft Tissue Sarcomas Metabolic Landscape Mapping.

Soft tissue sarcomas (STS) prognosis is disappointing, with current treatment strategies being based on a "fit for all" principle and not taking distinct sarcoma subtypes specificities and genetic/metabolic differences into consideration. The paucity of precision therapies in STS reflects the shortage of studies that seek to decipher the sarcomagenesis mechanisms. There is an urge to improve STS diagnosis precision, refine STS classification criteria, and increase the capability of identifying STS prognostic biomarkers. Single-omics and multi-omics studies may play a key role on decodifying sarcomagenesis. Metabolomics provides a singular insight, either as a single-omics approach or as part of a multi-omics strategy, into the metabolic adaptations that support sarcomagenesis. Although STS metabolome is scarcely characterized, untargeted and targeted metabolomics approaches employing different data acquisition methods such as mass spectrometry (MS), MS imaging, and nuclear magnetic resonance (NMR) spectroscopy provided important information, warranting further studies. New chromatographic, MS, NMR-based, and flow cytometry-based methods will offer opportunities to therapeutically target metabolic pathways and to monitorize the response to such metabolic targeting therapies. Here we provide a comprehensive review of STS omics applications, comprising a detailed analysis of studies focused on the metabolic landscape of these tumors.

Therapeutic targeting of PD-1/PD-L1 blockade by novel small-molecule inhibitors recruits cytotoxic T cells into solid tumor microenvironment.

BACKGROUND: Inhibiting programmed cell death protein 1 (PD-1) or PD-ligand 1 (PD-L1) has shown exciting clinical outcomes in diverse human cancers. So far, only monoclonal antibodies are approved as PD-1/PD-L1 inhibitors. While significant clinical outcomes are observed on patients who respond to these therapeutics, a large proportion of the patients do not benefit from the currently available immune checkpoint inhibitors, which strongly emphasize the importance of developing new immunotherapeutic agents. METHODS: In this study, we followed a transdisciplinary approach to discover novel small molecules that can modulate PD-1/PD-L1 interaction. To that end, we employed in silico analyses combined with in vitro, ex vivo, and in vivo experimental studies to assess the ability of novel compounds to modulate PD-1/PD-L1 interaction and enhance T-cell function. RESULTS: Accordingly, in this study we report the identification of novel small molecules, which like anti-PD-L1/PD-1 antibodies, can stimulate human adaptive immune responses. Unlike these biological compounds, our newly-identified small molecules enabled an extensive infiltration of T lymphocytes into three-dimensional solid tumor models, and the recruitment of cytotoxic T lymphocytes to the tumor microenvironment in vivo, unveiling a unique potential to transform cancer immunotherapy. CONCLUSIONS: We identified a new promising family of small-molecule candidates that regulate the PD-L1/PD-1 signaling pathway, promoting an extensive infiltration of effector CD8 T cells to the tumor microenvironment.

Management of Unresectable Localized Pelvic Bone Sarcomas: Current Practice and Future Perspectives.

Bone sarcomas (BS) are rare mesenchymal tumors usually located in the extremities and pelvis. While surgical resection is the cornerstone of curative treatment, some locally advanced tumors are deemed unresectable and hence not suitable for curative intent. This is often true for pelvic sarcoma due to anatomic complexity and proximity to vital structures, making treatment options for these tumors generally limited and not unanimous, with decisions being made on an individual basis after multidisciplinary discussion. Several studies have been published in recent years focusing on innovative treatment options for patients with locally advanced sarcoma not amenable to local surgery. The present article reviews the evidence regarding the treatment of patients with locally advanced and unresectable pelvic BS, with the goal of providing an overview of treatment options for the main BS histologic subtypes involving this anatomic area and exploring future therapeutic perspectives. The management of unresectable localized pelvic BS represents a major challenge and is hampered by the lack of comprehensive and standardized guidelines. As such, the optimal treatment needs to be individually tailored, weighing a panoply of patient- and tumor-related factors. Despite the bright prospects raised by novel therapeutic approaches, the role of each treatment option in the therapeutic armamentarium of these patients requires solid clinical evidence before becoming fully established.

A Tailored Approach for Appendicular Impending and Pathologic Fractures in Solid Cancer Metastases.

Advances in medical and surgical treatment have played a major role in increasing the survival rates of cancer patients with metastatic bone disease. The clinical course of patients with bone metastases is often impaired by bone complications, such as bone fractures, which have a substantial negative impact on clinical outcomes. To optimize clinical results and prevent a detrimental impact on patients' health, a tailored approach should be defined for any given patient. The optimal management of impending or pathologic fractures is unknown and relies on a multidisciplinary approach to tailor clinical decisions to each individual patient. The ability to control systemic disease, the extent, location and nature of bone metastases, and the biology of the underlying tumor, are the main factors that will define the strategy to follow. The present review covers the most recent data regarding impending and pathologic fractures in patients with bone metastases, and discusses the medical and surgical management of patients presenting with metastatic bone disease in different clinical settings.

Bone marrow edema syndrome: an unusual cause for spontaneous unrelentless bilateral knee pain.

Bone marrow edema syndrome is a rare disease with an unknown etiology, self-limited and usually associated with an indolent course, which can also generate severe pain with tremendous functional impairment. The authors present a case of a 19-year-old female patient with a progressive, non-traumatic and unrelentless pain involving both knees, requiring persistently walking aids and analgesic drugs. The imaging studies showed a bilateral distal femur and proximal tibia bone marrow edema in the magnetic resonance imaging. Finally, and after an extensive investigation without any abnormal findings, a bone marrow edema syndrome diagnosis was established, with a spontaneous regression of the clinical and imaging presentation. One year after the initial complaints the patient is fully recovered, without pain or medication, presenting an MRI showing complete regression of the initial findings. Despite the rarity of this entity, being aware of its existance and clinical manifestations is crutial to allow a proper diagnosis. The case herein presented is, to our understanding, pragmatic regarding bone marrow edema syndrome presentation and clinical course.

Giant cell tumour of bone around the knee: a systematic review of the functional and oncological outcomes.

Giant cell tumour of bone (GCT) is a relatively rare, locally aggressive benign neoplasm observed in the long bone epiphyseal-metaphyseal regions of young adults.The optimal treatment strategy for these tumours remains controversial, and a huge amount of contradictory data regarding the functional and oncological outcomes can be found. Therefore, we performed a systematic review intended to investigate the functional and oncological outcomes after surgical treatment of GCTs arising around the knee, namely in the distal femur and proximal tibia.A trend towards better oncological control was found using wide resections, nonetheless, curettage-based techniques achieve a highly acceptable recurrence rate with overall better knee function. A slight advantage favouring proximal tibia GCTs regarding the Musculoskeletal Tumor Society (MSTS) score was also observed.Prospective studies comparing groups of more homogeneous patients, tumours, and treatment options should be developed to obtain more conclusive and definitive results regarding the optimal strategy for treating GCTs. Cite this article: EFORT Open Rev 2021;6:641-650. DOI: 10.1302/2058-5241.6.200154.

Telangiectatic osteosarcoma arising in osteogenesis imperfecta.

We present the case of a 32-year-old man with a diagnosis of type-III osteogenesis imperfecta who developed a telangiectatic osteosarcoma in the proximal right tibia. An above-knee amputation was performed and after one-year follow-up, pulmonary metastatic lesions were detected on the thoracic CT scan. Palliative chemotherapy was proposed and to date the patient is still living and is under medical treatment. The association between osteogenesis imperfecta and osteosarcoma is rare. There are only ten confirmed reports of this unusual situation, but to our knowledge this is the first case reported with a telangiectatic osteosarcoma arising in this particular setting.

Sarcoma Metabolomics: Current Horizons and Future Perspectives.

The vast array of metabolic adaptations that cancer cells are capable of assuming, not only support their biosynthetic activity, but also fulfill their bioenergetic demands and keep their intracellular reduction-oxidation (redox) balance. Spotlight has recently been placed on the energy metabolism reprogramming strategies employed by cancer cells to proliferate. Knowledge regarding soft tissue and bone sarcomas metabolome is relatively sparse. Further characterization of sarcoma metabolic landscape may pave the way for diagnostic refinement and new therapeutic target identification, with benefit to sarcoma patients. This review covers the state-of-the-art knowledge on cancer metabolomics and explores in detail the most recent evidence on soft tissue and bone sarcoma metabolomics.

Open versus arthroscopic surgery for diffuse tenosynovial giant-cell tumours of the knee: a systematic review.

Diffuse-type tenosynovial giant-cell tumours of the knee (D-TGCT) have a very high complication rate.The recurrence rate for D-TGCT is mainly dependent on an initially successful resection of the lesion.The standard of care for this disease involves early surgery with synovectomy. Available surgical techniques may include an arthroscopic or open surgery; however, there is a lack of consensus on which technique should be used, and when.Arthroscopic excision is effective in minimizing morbidity and surgery-related complications, while an open surgical technique provides a more successful resection with a lower incidence of local recurrence.We could not conclude with confidence which of the surgical techniques is better at stopping a progression towards osteoarthritis and the need for a total knee arthroplasty. Cite this article: EFORT Open Rev 2020;5:339-346. DOI: 10.1302/2058-5241.5.200005.

Blood Management and Risk Assessment for Transfusion in Pediatric Spinal Deformity Surgery.

OBJECTIVES: Evaluate the impact of a Quality and Safety Program (QSP) on the reduction of blood loss and transfusion needs in pediatric spinal deformity surgery, while defining risk factors for transfusion. BACKGROUND: Multimodal plan aiming to minimize transfusion needs has been shown to reduce transfusions and index rates in spinal deformity surgery. Anticipating blood loss and transfusion may help direct resources to patient needs or encourage reconsideration of the surgical plan. METHODS: This is a single-center retrospective study of prospectively collected data. Impact of this multimodal plan was studied on idiopathic deformities (Group A, 109 patients) and scoliosis associated with syndromic, neuromuscular, and muscular dystrophies (Group B, 100 patients), both before and after QSP. RESULTS: A decrease in total estimated blood loss was observed. In Group A, transfused patients decreased from 83.7% to 28% (p < 0.001, odds: 0.077), and, in Group B, from 98.7% to 66% (p < 0.01, odds: 0.038). Pearson's correlation identified patient body weight (r = 0.245, p=0.001) and Cobb angle (r = 0.175, p=0.017) as factors related to blood loss. A linear regression model to estimate hematic losses revealed that only body weight and transfusion showed predictive power, resulting in a low predictive model (R 2 = 0.156; F(3,167) = 15.483, p < 0.001). A mediated model to explain blood loss was built based on a set of variables influencing transfusion which is, in turn, related to blood loss. CONCLUSION: Transfusion needs in scoliosis surgery can be substantially reduced following a multimodal approach. The success of a program is strongly dependent on team effort, and the introduction of a risk assessment tool for transfusion needs indirectly assesses surgical risk, thus allowing relocation of resources to decrease blood loss.

Proximal Femur Chondrosarcoma Misdiagnosed as Hip Arthritis: A Case Report.

CASE: A 60-year-old man presented with left hip pain, and a radiograph showed reduced joint space. During the surgical procedure for a total hip replacement, a proximal femur mass was identified and biopsy was subsequently interpreted as grade 2 chondrosarcoma. A wide resection was needed, but he developed local recurrence after 2 years and was treated with an external hemipelvectomy. CONCLUSIONS: Chondrosarcoma does not always present with a classical clinical picture or imaging, and it can be misdiagnosed. Practitioners should be highly suspicious of malignant disease as a cause for hip pain even if there is no direct indication of a neoplasm such as chondrosarcoma.

Sternoclavicular dislocation as a possible complication for surgical Scheuermann's deformity correction: a case report.

OBJECTIVE: We present a sternoclavicular dislocation as a non-reported complication after spinal kyphotic deformity surgical correction. BACKGROUND: The sternocostal complex seems to have an important role in the pathology of Scheuermann's kyphotic deformity. A role for the sternoclavicular complex has never been reported in association with Scheuermann's disease pathology but could explain anterior sternoclavicular dislocation after spinal kyphotic deformity correction. METHODS: A 19-year-old male patient underwent surgery for a 74° thoracic kyphosis associated with a 35° thoracic and a 50° lumbar scoliotic curve. In the early post-operative period, the patient developed pain over the left sternoclavicular joint articulation, with a very obvious lump. An X-ray disclosed an anterior sternoclavicular dislocation. After surgical treatment failed, the dislocation was repaired in a second surgical procedure with a flexion and lengthening osteotomy of the middle third of the clavicle followed by capsular repair reinforced with sternocleidomastoid fascia. RESULTS: At an 8-year follow-up after his spine procedure and 6 years after his clavicular surgery, the patient had full shoulder range of motion and no joint pain, despite the presence of a new sternoclavicular anterior dislocation. CONCLUSION: Sternoclavicular dislocation after spine kyphotic deformity correction is presented for the first time; however, it is not possible to establish a causative association. Additional studies are necessary to delineate the role of the sternoclavicular complex in Scheuermann's disease.

Management of Pipkin Fractures Using a Safe Surgical Hip Dislocation.

INTRODUCTION: Pipkin fractures are rare events and usually occur as a consequence for high-energy trauma. Surgery to obtain anatomical reduction and fixation is the mainstay treatment for the majority of these injuries; nonetheless, controversy exists regarding the best surgical approach. DESCRIPTION OF THE CASE: We present the case of a 41-year-old male, which sustained a type II Pipkin fracture following a motorcycle accident. In the emergency department, an emergent closed reduction was performed, followed by surgery five days later. Using a surgical hip dislocation, a successful anatomical reduction and fixation was performed. After three years of follow-up, the patient presented with a normal range of motion, absent signs for avascular necrosis or posttraumatic arthritis, but with a grade II heterotopic ossification. DISCUSSION: Safe surgical hip dislocation allows full access to the femoral head and acetabulum, without increasing the risk for a femoral head avascular necrosis or posttraumatic arthritis. Simultaneously, this surgical approach gives the opportunity to repair associated acetabular or labral lesions, which explains the growing popularity with this technique. CONCLUSION: Although technically demanding, safe surgical hip dislocation represents an excellent option in the reduction and fixation for Pipkin fractures.

Late implant migration with neurologic compromise as a complication of scoliosis surgery.

Late neurological deficit following scoliosis surgery is a rare event and any change in the patient's neurological status deserves immediate attention. We report on two clinical cases (at 2 and 6 years of follow-up) where two different types of proximal instrumentation resulted in lateral drift into the spinal canal causing cord compression with neurological deficit. Late neurological compromise in a posterior spinal-fusion setting deserves a prompt and complete spine investigative search for non-union, infection, or implant migration into the spinal canal.