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En bloc resection remains the cornerstone treatment for malignant bone tumors affecting the spine. The thoracic spine poses unique challenges because of the proximity of crucial structures. This study assesses outcomes of patients who underwent en bloc spondylectomy for malignant bone tumors at the thoracic level. We retrospectively reviewed 85 cases of primary and secondary bone tumors in the thoracic spine, undergoing en bloc spondylectomy from 1996 to 2016. Evaluation encompassed clinical presentation, tumor characteristics, surgical outcomes, complications, survival, and recurrence. Of 85 patients, 40 presented directly, whereas 45 had undergone previous intralesional surgery. Chondrosarcoma and chordoma comprised the most prevalent primary histologic types; thyroid and kidney carcinomas were the most frequent secondary tumors. Pain was reported in 75 patients at diagnosis. Margins were adequate in 54 cases and intralesional in 31. Immediate postoperative deaths amounted to 4. Major complications included substantial blood loss, neurologic deterioration, and paraplegia. The 5-year local recurrence-free survival was 58.7%, significantly influenced by the surgical margin: patients with wide margins experienced a 5-year local recurrence-free survival of 85.7%, whereas those with marginal and intralesional margins had rates of 56.7% and 45.6%, respectively; overall recurrence was 22.3%, with no notable disparities between previously treated and untreated patients. The 5-year overall survival was 63.2% and 56.2% for primary and secondary tumors, respectively. The overall survival was not significantly influenced by surgical margins. Managing malignant thoracic bone tumors poses significant challenges. This study underscores the criticality of achieving adequate margins, particularly after previous intralesional approaches. [ABSTRACT FROM AUTHOR]

En bloc surgery is the mainstay treatment for primary malignant bone tumors, as well as in the cervical spine. Unfortunately, literature on the topic is limited to case reports and small series. We reviewed all patients affected by primary cervical spine bone tumors treated with en bloc surgeries from 1996 to 2016 and identified 30 eligible cases. We evaluated the clinical presentation and tumor characteristics and reported surgical results, complications, recurrence, and survival rates. Only 17 of 30 patients had not been previously treated at presentation. Osteosarcoma and chordoma were the most frequent tumors, and pain was reported in all cases. En bloc spondylectomy, hemispondylectomy, and posterior arch en bloc resection were performed in 16, 12, and 2 patients, respectively. The obtained margin was adequate (wide and marginal) in 60% of cases and intralesional in the remaining cases. Two deaths occurred in the immediate postoperative period. Neurological deterioration, dural tear, and dysphagia were the most frequent complications. The 5-year local recurrence-free survival was 70.4%. The recurrence rate was 38.5% and 11.7% in previously and non–previously treated patients, respectively (χ2: 2.94; P = 0.086). Overall survival at 5 years was 58% and 47% for all series and malignant tumors, respectively. Primary cervical spine bone tumors present a difficult approach. Findings suggest that patients treated with en bloc surgery show recurrence and survival rates comparable to the same tumors located in the thoracolumbar spine. [ABSTRACT FROM AUTHOR]

Background The mainstay treatment of primary malignant bone tumors is wide surgery in the spine. Unfortunately, most cases undergo the first approach in a nonspecialized center; this often means adopting an inappropriate approach with contamination, which consistently decreases the effectiveness of a second surgery. The aim of the present paper is to evaluate recurrence and survival rates after en-bloc resection. Methods All patients underwent wide resection by the senior author from January 1997 to December 2013 after the first inappropriate approach was reviewed. Fifty-six patients were included in the present evaluation. Epidemiologic and clinical characteristics, surgeries, early and late complications, and survival rate were reported. Results The margin obtained was wide, marginal, and intralesional in 9, 28, and 19 cases, respectively. The complication rates were 55.4% and 44.6% for early and late complications, respectively. Most (73.2%) of the patients had complications. The survival rate is 82.1% at 1 year and then decreases 10% each year until 42.1% at 5 years from surgeries. No statistically significant correlation was found between margin and local recurrence and survival. Conclusion In our series, the first inappropriate approach had already compromised patient prognosis, so in case of suspicious primary spine tumor, the patient had to be referred to a specialized center. The margin obtained during salvage surgery does not appear to influence recurrence and survival, probably because it is already compromised by the first surgery. More prospective studies are necessary to confirm our data and verify the impact of the margin obtained during salvage surgery on patients' survival. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the involvement of Hippo-related pathways in bone metastasis from breast cancer, by evaluating E-cadherin expression downstream of WWdomain-containing oxidoreductase (Wwox) and transcriptional co-activator with PDZ-binding motif (TAZ). These nuclear effectors functioned in a context-specific fashion on transcriptome, depending on breast-cancer aggressiveness and methylation state. Wwox and E-cadherin were found in human specimens of bone metastasis but not in primary-ductal breast carcinoma, while TAZ showed a characteristic localisation in metastasis nuclei. Wwox and E-cadherin were higher in 1833-metastatic clone with bone avidity than in parental-MDA-MB231 cells, while only metastatic cells presented TAZ. In 1833 cells, a complex interplay of transcriptional signalling controlled E-cadherin transactivation. Wwox and TAZ activated Hypoxia inducible factor-1 (HIF-1) binding to E-cadherin promoter, while Peroxisome proliferator-activated receptor γ (PPARγ) intervened in E-cadherin transactivation favouring and preventing Wwox and TAZ functions, respectively. Methylation impinged on Hippo-related pathways through Wwox and TAZ, modifying metastatic phenotype. The protract exposure to 5-azacytidine (Aza), by affecting methylation state modified the shape of 1833 cells, becoming mesenchymal as that of MDA-MB231 cells and reduced spontaneous-Matrigel invasion. The underlying-molecular mechanisms were diminutions of E-cadherin, Wwox, matrix metalloproteases 2 and 9, HIF-1- and PPARγ-activities, inversely correlated to Snail and nuclear-TAZ accumulations. Exogenous WWOX restored 1833-Aza invasion. Thus, 1833-Aza cells permitted to study the role played by methylation in metastasis plasticity, being E-cadherin loss part of an entire-gene reprogramming. Of note, bone-metastasis formation in 1833-Aza xenograft was partially impaired, prolonging mice survival. In conclusion, the methylation-heritable changes seemed important for cancer progression to establish bone metastasis engraftment/growth, by affecting steps requiring homotipic and/or heterotypic-adhesive properties and matrix degradation. [Copyright &y& Elsevier]

Objectives Few studies have evaluated surgical options in the treatment of cervical metastatic disease. The aim of this study is to report the surgical outcomes of patients treated with the posterior-only approach for metastatic cervical disease. Methods In this retrospective analysis, all cases treated in our institution from 2009 to 2017 were reviewed. Six (20%) patients had intracompartimental lesions (Tomita 1–3), whereas 24 (80%) patients had extracompartimental lesions (Tomita 4–7), with extensive anterior column involvement. All patients were surgically treated with laminectomy and posterior stabilization. Pain and neurologic function were evaluated before and after surgery. Results Thirty patients were included (15 female, 15 male), with a mean age of 60.6 ± 11.56 years (range 35–82 years). Lesions were located in 7 patients (23.3%) in the upper cervical spine and in 14 patients (46.6%) and in 9 patients (30,1%) in the mid-cervical and in the cervicothoracic junction, respectively. At a mean follow up of 13.7 ± 14.8 months, 15 (50%) patients died from their disease. Pain decreased in all patients after surgery, (preoperative NRS 5.57 ± 1.81 postoperative Numeric Rating Scale of 2.1 ± 1.0, P < 0.00001). Two patients (6.7%) had significant neurologic worsening after surgery. Two (6.9%) patients had surgical-site infection that required reintervention. No mechanical failures were observed. Conclusions In our series, posterior-only fixation provided postoperative pain relief and achieve spinal stability, ultimately improving the quality of life. In conclusion, posterior-approach decompression and stabilization is a safe and feasible procedure in patients with neurologic or mechanical instability for cervical spine metastasis. [ABSTRACT FROM AUTHOR]

Background Context: Spinal osteoid osteomas are benign primary tumors arising predominantly from the posterior column of the spine. These "osteoblastic" lesions have traditionally been treated with intralesional excision.Purpose: The purpose of the present study was to review the treatment and local recurrence rates for symptomatic spinal osteoid osteomas.Study Design/setting: Multicenter ambispective cross-sectional observational cohort study.Patient Sample: During the study period, a total of 84 patients (65 males, 19 females) were diagnosed with a spinal osteoid osteoma and received surgical treatment. The mean age at surgery was 21.8 ± 9.0 years (range: 6.7-52.4 years) and the mean follow-up was 2.7 years (13 days-14.5 years).Outcome Measures: Local recurrence, perioperative morbidity, and cross-sectional survival.Methods: Using the AOSpine Knowledge Forum Tumor multicenter ambispective database, surgically treated osteoid osteoma cases were identified. Patient demographic, clinical and diagnostic, treatment, local recurrence, perioperative morbidity, and cross-sectional survival data were collected and retrieved. Descriptive statistics were summarized using mean/standard deviation or frequency/percentage.Results: In our study, most of the tumors were localized in the mobile spine (81 of 84 [96%]); all patients reported pain as a symptom. According to the postoperative assessment, 10 (12%) patients received an en bloc resection with marginal or wide margins, whereas two (2%) patients received en bloc resections with intralesional margins, 69 (82%) patients were treated by piecemeal "intralesional" resection, and three (4%) patients were not assessed. A total of six patients (7%) experienced a local recurrence, all of which occurred in patients who had received an intralesional resection.Conclusions: Benign bone-forming tumors of the spine are uncommon. Most patients in our series underwent a piecemeal resection with intralesional margins. This remains safe with a low local recurrence rate. En bloc excision may provide more chance of complete excision of the nidus but is not mandatory. The importance of complete excision of the nidus cannot be overemphasized. [ABSTRACT FROM AUTHOR]

Abstract: The present study was undertaken to clarify the function(s) of Endothelin-1 and its receptors ETAR and ETBR in osteolytic-bone metastasis from breast cancer, and their regulation by hepatocyte and transforming growth factors (HGF, TGF-β) and hypoxia. The aim was to evaluate the adaptability of bone metastasis to microenvironmental stimuli through Endothelin-1-mediated epithelial-mesenchymal transition (EMT), or the reverse process MET, and through osteomimicry possible key features for bone colonization. We compared low (MCF-7) and high (MDA-MB231) invasive-breast carcinoma cells, and 1833-bone metastatic clone, with human pair-matched primary breast-carcinomas and bone metastases. Parental MDA-MB231 and the derived 1833-clone responded oppositely to the stimuli. In 1833 cells, TGF-β and hypoxia increased Endothelin-1 release, altogether reducing invasiveness important for engraftment, while Endothelin-1 enhanced MDA-MB231 cell invasiveness. The Endothelin-1-autocrine loop contributed to the cooperation of intracellular-signaling pathways and extracellular stimuli triggering MET in 1833 cells, and EMT in MDA-MB231 cells. Only in 1833 cells, HGF negatively influenced transactivation and release of Endothelin-1, suggesting a temporal sequence of these stimuli with an initial role of HGF-triggered Wnt/β-catenin pathway in metastatization. Then, Endothelin-1/ETAR conferred MET and osteomimetic phenotypes, with Runt-related transcription factor 2 activation and metalloproteinase 9 expression, contributing to colonization and osteolysis. Findings with human pair-matched primary ductal carcinomas and bone metastases gave a translational significance to the molecular study. Endothelin-1, ETAR and ETBR correlated with the acquisition of malignant potential, because of high expression already in the in situ carcinoma. These molecular markers might be used as predictive index of aggressive behavior and invasive/metastatic phenotype. [Copyright &y& Elsevier]

Abstract: The hypoxic microenvironment of bone marrow favours the bone metastasis process. Hypoxia inducible factor (HIF)-1α is hallmark for hypoxia, correlating with poor prognosis and radio/chemotherapy resistance of primary-breast carcinoma. For bone metastasis, the molecular mechanisms involved in HIF-1α expression and HIF-1 (α/β heterodimer)-transcription factor activity are scarcely known. We studied the role played by HIF-1 in the cross-talk between neoplastic and supportive-microenvironmental cells. Also, WWdomain-containing oxidoreductase (Wwox) and transcriptional co-activator with PDZ-binding motif (TAZ) were taken into consideration evaluating whether these Hippo-pathway effectors affect bone-metastatic phenotype through HIF-1 activity. Considering bone-metastasis specimens, nuclear HIF-1α–TAZ co-localisation occurred in neoplastic and supportive cells, such as fibroblasts and endotheliocytes. Based on these data, the functional importance was verified using 1833-bone metastatic clone under hypoxia: nuclear HIF-1α and TAZ expression increased and co-immunoprecipitated, activating HIF-1-DNA binding and transactivation. In contrast, Wwox localised at perinuclear level in neoplastic cells of bone metastasis, being almost absent in supportive cells, and Wwox-protein expression diminished in hypoxic-1833 cells. Thus, TAZ regulation of HIF-1 activity might be important for bone-secondary growth, participating in metastasis-stroma cross-talk. Further, TAZ and HIF-1α-protein levels seemed correlated. In fact, blocking cyclooxygenase-2 with NS398 in hypoxic-1833 cells, not only HIF-1α decreased but also molecular-mechanism(s) upstream of the Hippo pathway were triggered: LATS-dependent TAZ phosphorylation seemed responsible for TAZ nucleus/cytoplasm translocation and degradation. In the 1833-xenograft model, NS398 largely prevented the outgrowth of bone-metastatic cells, probably related to remarkable-extracellular matrix assembly. We gained clinical insight into HIF-1α and TAZ as candidate biomarkers for bone avidity, relevant for early-therapeutic intervention against bone metastasis. [Copyright &y& Elsevier]

Purpose: Spinal lesion differential diagnosis remains challenging even in MRI. Radiomics and machine learning (ML) have proven useful even in absence of a standardized data mining pipeline. We aimed to assess ML diagnostic performance in spinal lesion differential diagnosis, employing radiomic data extracted by different software.Methods: Patients undergoing MRI for a vertebral lesion were retrospectively analyzed (n = 146, 67 males, 79 females; mean age 63 ± 16 years, range 8-89 years) and constituted the train (n = 100) and internal test cohorts (n = 46). Part of the latter had additional prior exams which constituted a multi-scanner, external test cohort (n = 35). Lesions were labeled as benign or malignant (2-label classification), and benign, primary malignant or metastases (3-label classification) for classification analyses. Features extracted via 3D Slicer heterogeneityCAD module (hCAD) and PyRadiomics were independently used to compare different combinations of feature selection methods and ML classifiers (n = 19).Results: In total, 90 and 1548 features were extracted by hCAD and PyRadiomics, respectively. The best feature selection method-ML algorithm combination was selected by 10 iterations of 10-fold cross-validation in the training data. For the 2-label classification ML obtained 94% accuracy in the internal test cohort, using hCAD data, and 86% in the external one. For the 3-label classification, PyRadiomics data allowed for 80% and 69% accuracy in the internal and external test sets, respectively.Conclusions: MRI radiomics combined with ML may be useful in spinal lesion assessment. More robust pre-processing led to better consistency despite scanner and protocol heterogeneity. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the diagnostic performance of machine learning for discrimination between low-grade and high-grade cartilaginous bone tumors based on radiomic parameters extracted from unenhanced magnetic resonance imaging (MRI).Methods: We retrospectively enrolled 58 patients with histologically-proven low-grade/atypical cartilaginous tumor of the appendicular skeleton (n = 26) or higher-grade chondrosarcoma (n = 32, including 16 appendicular and 16 axial lesions). They were randomly divided into training (n = 42) and test (n = 16) groups for model tuning and testing, respectively. All tumors were manually segmented on T1-weighted and T2-weighted images by drawing bidimensional regions of interest, which were used for first order and texture feature extraction. A Random Forest wrapper was employed for feature selection. The resulting dataset was used to train a locally weighted ensemble classifier (AdaboostM1). Its performance was assessed via 10-fold cross-validation on the training data and then on the previously unseen test set. Thereafter, an experienced musculoskeletal radiologist blinded to histological and radiomic data qualitatively evaluated the cartilaginous tumors in the test group.Results: After feature selection, the dataset was reduced to 4 features extracted from T1-weighted images. AdaboostM1 correctly classified 85.7 % and 75 % of the lesions in the training and test groups, respectively. The corresponding areas under the receiver operating characteristic curve were 0.85 and 0.78. The radiologist correctly graded 81.3 % of the lesions. There was no significant difference in performance between the radiologist and machine learning classifier (P = 0.453).Conclusions: Our machine learning approach showed good diagnostic performance for classification of low-to-high grade cartilaginous bone tumors and could prove a valuable aid in preoperative tumor characterization. [ABSTRACT FROM AUTHOR]