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PurposeReview a series of 22 patients below the age of 16 affected by primary bone tumors of the spine who underwent en bloc resection, and describe the clinical presentation, tumor characteristics, results and complications associated with the surgical treatment, underlining the specific issues related to a younger age. MethodsWe performed a review of all patients < 16 years old affected by primary bone tumors of the spine, surgically treated with en bloc resection from 1996 to 2016. Clinical and radiological characteristics, therapy, complications and survival are reported.ResultsOnly 12/22 cases had not been previously treated. 22.7% experienced at least one early complication; 18.2% and 4.1% experienced at least 2 and ≥ 3 early complications, respectively; 40.9% experienced at least one late complication, often related to hardware failure (27.3%); 18.2% and 4.5% at least 2 and ≥ 3 late complications. No early nor late complications were experienced in 12 out of 22 patients (54.54%). The overall survival and the local recurrence-free survival at 5 years were, respectively, 79.5% and 74.8%; considering only the patients with high-grade tumors, they were 70.9% and 65.5%, respectively. At 77.3 months of median follow-up, 17 patients are still alive, 16 of whom without any evidence of disease and 1 with evidence of local and systemic disease; four patients died with evidence of local disease and one with distant metastases but no local recurrence.ConclusionsYoung people with primary malignant or locally aggressive bone tumors of the spine should be treated in specialized centers, and wide surgery should be performed. The most frequent problems are related to reconstruction in a growing spine and subsequent hardware failure that make later surgeries necessary.Graphic abstractThese slides can be retrieved under Electronic Supplementary Material.

Bone metastases dramatically worsen breast cancer (BC) prognosis reducing overall survival. Natural killer (NK) cells recognize and eliminate malignant cells through the interaction with NKG2D receptor ligands (NKG2DLs) on cancer cells. Tumors often evade NK surveillance by downregulating the NKG2DLs expression and avoid recognition, but whether this occurs in bone metastases remains unclear. This study investigates mechanisms of NKG2DLs downregulation in primary BC and bone metastases (BoMet). Expression and localization of the NKG2D/NKG2DL axis components were investigated in BC tissues (with and without metastases), paired bone metastatic ductal carcinoma (bmDC), BoMet, and in BC cells lines of varying invasiveness. In bmDC and BoMet, major histocompatibility complex class I chain-related protein A and B (MICA/B) and UL16-binding protein 2 (ULBP2) localized in perinuclear area, contrasting with predominantly cytosolic distribution in non-metastatic BC. Similarly, invasive MDA-MB-231 and MDA-BoM-1833 showed NKG2DLs perinuclear localization and co-localization with the Golgi apparatus, while less invasive MCF7 showed a prominent cytosolic distribution. Accumulation of NKG2DLs in membrane and cytoskeletal fractions further supports this pattern. Additionally, when N-glycosilation is impaired, NKG2DLs fail to reach the cell surface in metastatic cell lines, while are still transported through the Golgi apparatus and delivered to the plasma membrane, resulting in increased surface expression irrespective of correct glycosylation. Our findings suggest that invasive and bone-metastatic breast cancer cells are more dependent on correct glycosylation and intracellular trafficking for NKG2DL surface expression than non-metastatic breast cancer cells. This difference may have important implications for potential immune evasion mechanisms and for the development of therapeutic strategies targeting bone metastases in breast cancer.

Bizarre parosteal osteochondromatous proliferation (BPOP) is a surface-based bone lesion belonging to the group of benign chondrogenic tumors. The aim of this review is to familiarize the readers with imaging features and differential diagnosis of BPOP, also addressing pathological presentation and treatment options. The peak of incidence of BPOP is in the third and fourth decades of life, although it can occur at any age. Hands are the most common location of BPOP (55%), followed by feet (15%) and long bones (25%). On imaging, BPOP appears as a well-marginated mass of heterotopic mineralization arising from the periosteal aspect of the bone. Typical features of BPOP are contiguity with the underlying bone and lack of cortico-medullary continuity, although cortical interruption and medullary involvement have been rarely reported. Histologically, BPOP is a benign bone surface lesion characterized by osteocartilaginous proliferation with disorganized admixture of cartilage with bizarre features, bone and spindle cells. Differential diagnosis includes both benign—such as florid reactive periostitis, osteochondroma, subungual exostosis, periosteal chondroma and myositis ossificans—and malignant lesions—such as periosteal chondrosarcoma and surface-based osteosarcoma. Treatment consists of surgical resection. Local recurrences are common and treated with re-excision.Critical relevance statement Bizarre parosteal osteochondromatous proliferation is a benign mineralized mass arising from the periosteal aspect of bone cortex. Multi-modality imaging characteristics, pathology features and differential diagnosis are here highlighted to familiarize the readers with this entity and offer optimal patient care.Key pointsBizarre parosteal osteochondromatous proliferation (BPOP) is a benign surface-based bone lesion.Hands are the most common location, followed by long bones and feet.BPOP is a mineralized mass arising from the periosteal aspect of bones.Histologically, it is composed of a mixture of cartilage, bone, fibrous tissue.Treatment consists of surgical resection, but local recurrences are common.

Study Design Narrative Review. Objective The management of spinal tumors requires a multi-disciplinary approach including surgery, radiation, and systemic therapy. Surgical approaches typically require posterior segmental instrumentation to maintain long-term spinal stability. Carbon fiber reinforced pedicle screws (CFRP) are increasingly used in the oncologic setting due to reductions in both imaging artifacts and radiotherapy perturbations compared to titanium implants. We performed a review of the literature and highlight advantages and future areas of study for CFRP. Methods We performed a systematic review of the literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and identified 10 articles including 573 patients. Across all studies we reviewed patient demographics, tumor types treated, hardware-related features, complication rates, recurrence, survival, and follow-up. Results Across 10 studies, a total of 1371 screws placed. Surgical and non-surgical complications were reported in 18.3% of patients. Disease progression at the surgical site was detected in 7.3% of patients. There was no significant difference in clinical or hardware complications between CFRP or titanium implants. The most frequent complication attributable to implanted CFRP hardware included screw breakage in 2.4% and loosening in 1.7% of patients, respectively. Conclusion CFRP provide a unique tool in the setting of spinal oncology. With a safety profile comparable to titanium, we review the documented advantages of CFRP posterior implants compared to titanium, while also addressing their current limitations. Additionally, we highlight several areas of future research to identify the optimal patients who will achieve the greatest benefit of CFRP.

Study Design Narrative Review. Objective Contextualized by a narrative review of recent literature, we propose a wound complication prevention and management algorithm for spinal oncology patients. We highlight available strategies and motivate future research to identify optimal and individualized wound management for this population. Methods We conducted a search of recent studies (2010-2022) using relevant keywords to identify primary literature in support of current strategies for wound complication prevention and management following spine tumor surgery. When primary literature specific to spine tumor cases was not available, data were extrapolated from studies of other spine surgery populations. Results were compiled into a proposed clinical algorithm to guide practice considering available evidence. Results Based on available literature, we recommend individualized stratification of patients according to identifiable risk factors for wound complication and propose several interventions which might be employed preventatively, including intrawound antibiotic administration, negative pressure wound therapy, and primary flap closure of the surgical wound. Of these, the available evidence, weighing possible risks vs benefits, most strongly favors primary flap closure of surgical wounds, particularly for patients with multiple risk factors. A secondary algorithm to guide management of wound complications is also proposed. Conclusions Wound complications such as SSI and dehiscence remain a significant source of morbidity following spine tumor surgery. Triaging patients on an individualized basis according to risk factors for complication may aid in selecting appropriate prophylactic strategies to prevent these complications. Future research in this area is still needed to strengthen recommendations.

Study Design This study is part of the AO Spine Metastatic Tumor Research and Outcomes Network [MTRON], an international multicenter prospective observational registry including patients with spinal metastases. Objectives This study aims to elucidate the incidence of surgical complications, their risk factors and consequent effects on survival outcomes, hospital length of stay, and overall health-related quality of life (HRQOL) parameters in a large cohort of patients affected by spinal metastases who were surgically treated. Methods Available data from February 2017 to July 2023 were analyzed. The primary outcome of this study was the evaluation of the incidence of intraoperative and postoperative adverse events (AEs). The secondary outcomes included the assessment of risk factors for surgery-related AEs and the impact of AEs on survival, length of hospital stay and quality of life. Results Among the 1267 patients analyzed, 6.9% experienced intraoperative AEs and 19.3% experienced at least 1 postoperative AE. Several factors resulted to be associated to the occurrence of postoperative AEs: age, smoking habit, poor Eastern Cooperative Oncology Group (ECOG) Performance status, previous radiation therapy at the index target, duration of surgery, number of instrumented levels, simultaneous anterior and posterior approach, presence of metastases at other sites, multiple spinal metastases. Postoperative AEs were associated with reduced survival rates, increased hospital length of stay and poorer HRQOL outcomes, particularly in domains such as neurological function and mental health. In general, surgery substantially improves HRQOL across multiple domains, with these benefits persisting over time despite the occurrence of AEs. However, patients with preoperative risk factors, including comorbidities, smoking, neurological impairment, and prior radiation therapy, experienced less improvement. Conclusions The negative impact of AEs on overall survival and HRQOL could be associated with the presence of some preoperative parameters of frailty that are detected as risk factors for AEs occurrence. This finding emphasizes the need for personalized preoperative assessments and optimized perioperative care strategies.

Breast cancer patients are at a high risk of complications from bone metastasis. Molecular characterization of bone metastases is essential for the discovery of new therapeutic targets. Here, we investigated the expression and the intracellular distribution of KH RNA binding domain containing, signal transduction associated 1 (KHDRBS1), leptin, leptin receptor (LEPR), and adiponectin in bone metastasis from breast carcinoma and looked for correlations between the data. The expression of these proteins is known in breast carcinoma, but it has not been investigated in bone metastatic tissue to date. Immunohistochemical analysis was carried out on bone metastasis specimens, then semiquantitative evaluation of the results and the Pearson test were performed to determine eventual correlations. KHDRBS1 expression was significantly higher in the nuclei than in the cytosol of metastatic cells; LEPR was prevalently observed in the cytosol and the nuclei; leptin and adiponectin were found in metastatic cells and stromal cells; the strongest positive correlation was between nuclear KHDRBS1 and nuclear LEPR expression. Taken together, our findings support the importance of the leptin/LEPR/KHDRBS1 axis and of adiponectin in the progression of bone metastasis and suggest their potential application in pharmacological interventions.

Background Over the years, en bloc spondylectomy has proven its efficacy in controlling spinal tumors and improving survival rates. However, there are few reports of large series that critically evaluate the results of multilevel en bloc spondylectomies for spinal neoplasms. Questions/purposes Using data from a large spine tumor center, we answered the following questions: (1) Does multilevel total en bloc spondylectomy result in acceptable function, survival rates, and local control in spinal neoplasms? (2) Is reconstruction after this procedure feasible? (3) What complications are associated with this procedure? (4) is it possible to achieve adequate surgical margins with this procedure? Methods We retrospectively investigated 38 patients undergoing multilevel total en bloc spondylectomy by a single surgeon (AL) from 1994 to 2011. Indications for this procedure were primary spinal sarcomas, solitary metastases, and aggressive primary benign tumors involving multiple segments of the thoracic or lumbar spine. Patients had to be medically fit and have no visceral metastases. Analysis was by chart and radiographic review. Margin quality was classified into intralesional, marginal, and wide. Radiographs, MR images, and CT scans were studied for local recurrence. Graft healing and instrumentation failures at subsequent followup were assessed. Complications were divided into major or minor and further classified as intraoperative and early and late postoperative. We evaluated the oncologic status using cumulative disease-specific and metastases-free survival analysis. Minimum followup was 24 months (mean, 39 months; range, 24–124 months). Results Of the 38 patients, 34 (89%) were alive and walking without support at final followup. Thirty-one (81%) had no evidence of disease. Two patients died postoperatively and another two died of systemic disease (without local recurrence). Only three patients (8%) had a local recurrence. There were 14 major complications and 22 minor complications in 25 patients (65%). Only one patient required revision of implants secondary to mechanical failure. Two cases of cage subsidence were noted but had no clinical significance. Wide margins were achieved in nine patients (23%), marginal in 25 (66%), and intralesional in four (11%). Conclusions In patients with multisegmental spinal tumors, oncologic resections were achieved by multilevel en bloc spondylectomy and led to an acceptable survival rate with reasonable local control. Multilevel en bloc surgery was associated with a high complication rate; however, most patients recovered from their complications. Although the surgical procedure is challenging, our encouraging mid-term results clearly favor and validate this technique. Level of Evidence Level IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

Purpose To review a series of ten cases with epithelioid hemangioendothelioma of the spine, that have undergone surgery to describe clinical presentation, results and complications associated with surgical treatment; a review of literature reporting the main characteristics of the cases already published has been reported. Methods A review of patients affected by epithelioid hemangioendothelioma surgically treated by the senior author from 1995 to 2012 was carried out. Ten cases were identified and clinical and radiological characteristics, therapy, complications and survival were valued. Results Wide margin was achieved in two out of ten cases, marginal margin in seven and intralesional margin in one case. Average intraoperative blood loss was about 2,800 ml. Reported complications were one case of cord injury, one of dural tear, two cases of massive blood loss, a case of reconstruction failure, a wound dehiscence with deep infection, a pneumonia episode and a deep vein thrombosis with pulmonary embolism. Average follow-up was 84.4 months. Two local recurrences, after 32 and 37 months and two deaths for metastasis, after 14 and 36 months, were reported. Although several chemotherapy protocols are available for the treatment of EH of soft tissue, they are not relevant for the bone. Conclusions Wide surgery is probably associated with a better prognosis. Indeed most deaths and local recurrences reported in literature happened after intralesional surgery or chemotherapy/RT alone. The presenting study suggests that the best approach to achieve long-term local control and a major survival could be wide surgery, nevertheless more cases series are necessary to verify survival rate.

Introduction Wide Surgery is the reference treatment for malignant and aggressive benign primary bone tumors in the spine. When located in the lumbar spine, En-Bloc Spondylectomy (EBS) remains a complex challenge. Moreover, surgery is complicated by the presence of the diaphragm in the thoracolumbar junction and the hinderance of the iliac wings at the lumbosacral levels. Therefore, EBS in the lumbar spine frequently requires combined approaches. The purpose of this study is to describe clinical presentation, tumor characteristics and results of a series of 47 consecutive patients affected by malignant primary bone tumors of the lumbar spine who underwent EBS. Materials and methods 47 patients were reviewed. Complications were distinguished in early and late whether they occurred before or after 30 days from surgery. Overall survival (OS), disease-free survival (DFS) and local recurrence-free survival (LRFS) were calculated by the Kaplan–Meier product-limit method from surgery until relapse or death. Results 27 patients presented to observation after a first intralesional approach in a non-specialized center. Chordoma was the most represented histotype. Vertebrectomies were: 23 one-level, 10 two-level, 12 three-level and 2 four-level. Reconstructions were always carried out with screws and rods. The main postoperative complication was blood loss, while hardware failure was the main long-term complication. The 5-year LRFS was 75.5%, the 5-year DFS was 54.3%, and 5-year OS was 63.6%. Conclusions The surgical margin obtained during the index surgery was statistically associated with Local Recurrence, DFS and OS, underlining the importance of treating patients in reference centers.