A retrospective study on the mechanism underlying quick transfer from response to resistance in a repeated recurrent chordoma patient with molecular alterations treated with Palbociclib.

PURPOSE: There is no approved targeted therapy for chordoma at present. Although several preclinical studies have implied the potential applicability of CDK4/6 inhibitor for this rare tumor, no clinical evidence has been documented so far. The purpose of this study was to elucidate the therapeutic efficacy of CDK4/6 inhibitor for chordoma. METHODS: The next generation sequencing (as for whole-exome sequencing, WES assay) and immunohistochemical (IHC) staining of the chordoma tissue from a patient with an advanced lesion were performed before treatment. Then, the patient was treated with Palbociclib for 4 months until progression occurred in the 5th month. Surgical resection was implemented and the tumor tissue was obtained postoperatively for assessment of molecular alterations. RESULTS: Molecular features of the tumor before medical treatment suggested applicability of CDK4/6 inhibitor and the patient showed partial response (PR) according to Choi Criteria after 4 months treating with Palbociclib until progression occurred. Then, a drastic molecular alteration of the tumor as represented by emergence of dramatic E2F amplification, which is known to induce CDK4/6 independent cell-cycle entry and progression after treatment, was detected. The findings in this patient demonstrated tumor evolution under drug pressure. CONCLUSION: The findings of the present study suggest the feasibility of Palbociclib for the clinical treatment of chordoma, and imply the necessity of combination therapies rather single drug administration due to the quick resistance of the tumor to Palbociclib treatment.

A Novel and Reproducible Classification of Cervical Dumbbell Tumors to Inform Surgical Approach and Reconstruction Techniques.

STUDY DESIGN: A retrospective case series. OBJECTIVE: This study developed a novel classification system based on imaging and anatomy to select optimal surgical approaches and reconstruction strategies to achieve total resection of cervical dumbbell tumors and restore spinal stability. SUMMARY OF BACKGROUND DATA: Total resection is necessary to decrease the recurrence rate of cervical dumbbell tumors. Previous cervical dumbbell tumor classifications are insufficient for determining surgical strategies; therefore, a practical classification is needed. MATERIALS AND METHODS: This study included 295 consecutive patients with cervical dumbbell tumors who underwent total surgical resection. A novel classification of cervical dumbbell tumors was developed based on magnetic resonance imaging and computed tomography. Continuous variables were expressed as mean±SD and were compared using an unpaired two-tailed Student t test. The χ 2 test or the Fisher exact test was used for categorical variables. Kendall's W test assessed three independent raters' inter-rater and intrarater reliabilities on 140 cervical dumbbell tumors. RESULTS: The inter-rater and intrarater consistency coefficient was 0.969 (χ 2 =404.3, P <0.001) and 0.984 (χ 2 =273.7, P <0.001). All patients with type I and II tumors underwent single-posterior surgeries to achieve total resection. Of the patients in this study, 86.1%, 25.9%, 75.9%, and 76.9% underwent posterior surgeries for types IIIa, IIIb, IVa, and V tumors, respectively. All patients with type IVb tumors underwent a combined anterior and posterior approach. Posterior internal fixation was used for all patients in posterior surgery. Anterior reconstruction was applied for patients with type IVb tumors (20/20, 100%) and some with type V tumors (3/13, 23.1%). The mean follow-up duration was 93.6±2.6 months. A recurrence was observed in 19 (6.4%) patients. CONCLUSION: The authors describe a novel classification system that is of practical use for planning the complete resection of cervical dumbbell tumors.

3D-printed Titanium Prosthetic Reconstruction of Unilateral Bone Deficiency After Surgical Resection of Tumor Lesions in the Upper Cervical Spine: Clinical Outcomes of Three Consecutive Cases and Narrative Review.

MAIN POINTS: Operational excision of tumor lesions in the upper cervical spine remains a tremendous challenge to surgeons due to the local complex anatomic relationships. Meanwhile, no commercially available device has been specially designed to address bone deficiency after surgical resection. Here, we described the reconstruction of unilateral bone deficiency after surgical resection of a giant cell tumor of the tendon sheath originating from the lateral atlantoaxial joint with the employment of a 3D printing technique and reviewed the relevant literature. In our study, 3 patients with giant cell tumor of the tendon sheath in the upper cervical spine achieved complete tumor removal, and received unilateral bone reconstruction with one-armed 3D-printed titanium prosthesis. During the follow-up, these patients remained neurologically intact and got back to a normal life without wearing the braces. Images demonstrated the satisfactory placement of 3D-printed prosthesis with no failure of fixation and no subsidence. In addition, 6 articles describing the employment of 3D-printed prostheses or models for tumor surgery in the upper cervical spine were reviewed, and satisfactory clinical outcomes were reported in these studies. Hence, 3D-printed titanium prosthetic reconstruction of bone deficiency in the upper cervical spine was a safe and effective technique. LEVEL OF EVIDENCE: Level IV.

An improved total en bloc spondylectomy for L5 vertebral giant cell tumor through a single-stage posterior approach.

PURPOSE: Although total en bloc spondylectomy (TES) is strongly recommended for spinal giant cell tumor (GCT), it is extremely difficult to excise a L5 neoplasm intactly through the single-stage posterior approach. Given the risk of neurological and vascular injury, intralesional curettage (IC) is usually recommended for the treatment of L5 GCT. In this study, we presented our experience with the use of an improved TES to treat L5 GCT through the single-stage posterior approach. METHODS: This study included 20 patients with L5 GCT who received surgical treatment in our department between September 2010 and April 2021. Of them, seven patients received improved TES without iliac osteotomy, and the other 13 patients received IC (n = 8), sagittal en bloc resection (n = 1), TES with iliac osteotomy (n = 3), and TES with radicotomy (n = 1) as control. RESULTS: The mean operative time was 331.43 ± 92.95 min for improved TES group and 365.77 ± 85.17 min for the control group (p = 0.415), with the mean blood loss of 1142.86 ± 340.87 ml vs. 1969.23 ± 563.30 ml (p = 0.002). Postoperative treatment included bisphosphonates in nine patients and denosumab in 12 patients including one patient who changed from bisphosphonates to denosumab. Three patients who received IC experienced local recurrence, and no relapse was observed in improved TES group. CONCLUSION: Single-stage posterior TES for L5 GCT was previously considered impossible. In this study, we presented our experience with the use of an improved surgical technique for L5 TES through the single-stage posterior approach, which has proved to be superior to the conventional procedures in terms of blood loss control and complication and recurrence rates. LEVEL OF EVIDENCE: IV.

The exploration of surgical outcomes in patients with giant cell tumor of the tendon sheath in spine: An epidemiological, radiological, and follow-up investigation.

PURPOSE: This study aimed to characterize giant cell tumor of the tendon sheath (GCTTS) in spine more fully and further validate the therapeutical effect of surgcial resection for treating this neoplasm. METHODS: Patients diagnosed with spinal GCTTS and received surgical resection in our hospital between January 2009 and September 2021 were identified retrospectively. The clinical data and radiological images were summarized and the clinical outcomes of patients with a follow-up period of more than 12 months were analyzed. RESULTS: Thirty patients with benign GCTTS and one with malignant GCTTS were included. Preoperative radiological images were available in 28 of 30 benign cases. Benign lesions were revealed as soft tissue masses centering on the facet joint with osteolytic bone destruction in 26 patients on CT, and as prevertebral or intramuscular masses without bone erosion in 2. MRI showed the signal of isointensity or hypointensity on T1 weighted images (T1WI) in 25 patients and slightly hyperintense in three. On T2 weighted images (T2WI), 17 lesions displayed homogeneous hypointense signal, and eight lesions possessed heterogeneous signals. The remaining three lesions featured slightly hyperintense signal on T2WI. Follow-up data were available in 23 of 30 benign cases treated with gross-total resection, and two patients experienced recurrence. CONCLUSIONS: Spinal GCTTS should be suspected in cases with features such as the mass mainly involving the posterior bone elements, the lack of intralesional calcification, T2-weighted dark signals, and free of any cancer. Gross-total resection is an effective means for treating spinal GCTTS.

Quantified CIN Score From Cell-free DNA as a Novel Noninvasive Predictor of Survival in Patients With Spinal Metastasis.

Purpose: Most currently available scores for survival prediction of patients with bone metastasis lack accuracy. In this study, we present a novel quantified CIN (Chromosome Instability) score modeled from cfDNA copy number variation (CNV) for survival prediction. Experimental Design: Plasma samples collected from 67 patients with bone metastases from 11 different cancer types between November 2015 and May 2016 were sent through low-coverage whole genome sequencing followed by CIN computation to make a correlation analysis between the CIN score and survival prognosis. The results were validated in an independent cohort of 213 patients. Results: During the median follow-up period of 598 (95% CI 364-832) days until December 25, 2018, 124 (44.3%) of the total 280 patients died. Analysis of the discovery dataset showed that CIN score = 12 was the optimal CIN cutoff. Validation dataset showed that CIN was elevated (score ≥12) in 87 (40.8%) patients, including 5 (5.75%) with head and neck cancer, 11 (12.6%) with liver and gallbladder cancer, 11 (12.6%) with cancer from unidentified sites, 21 (24.1%) with lung cancer, 7 (8.05%) with breast cancer, 4 (4.60%) with thyroid cancer, 6 (6.90%) with colorectal cancer, 4 (4.60%) with kidney cancer, 2 (2.30%) with prostate cancer, and 16 (18.4%) with other types of cancer. Further analysis showed that patients with elevated CIN were associated with worse survival (p < 0.001). For patients with low Tokuhashi score (≤8) who had predictive survival of less than 6 months, the CIN score was able to distinguish patients with a median overall survival (OS) of 443 days (95% CI 301-585) from those with a median OS of 258 days (95% CI 184-332). Conclusion: CNV examination in bone metastatic cancer from cfDNA is superior to the traditional predictive model in that it provides a noninvasive and objective method of monitoring the survival of patients with spine metastasis.

REGγ regulates circadian clock by modulating BMAL1 protein stability.

Endogenous clocks generate rhythms in gene expression, which facilitates the organisms to cope through periodic environmental variations in accordance with 24-h light/dark time. A core question that needs to be elucidated is how such rhythms proliferate throughout the cells and regulate the dynamic physiology. In this study, we demonstrate the role of REGγ as a new regulator of circadian clock in mice, primary MEF, and SY5Y cells. Assessment of circadian conduct reveals a difference in circadian period, wheel mode, and the ability to acclimate the external light stimulus between WT and KO littermates. Compared to WT mice, REGγ KO mice attain the phase delay behavior upon light shock at early night. During the variation of 12/12 h light/dark (LD) exposure, levels of Per1, Per2, Cry1, Clock, Bmal1, and Rorα circadian genes in suprachiasmatic nucleus are significantly higher in REGγ KO than in WT mice, concomitant with remarkable changes in BMAL1 and PER2 proteins. In cultured cells depleted of REGγ, serum shock induces early response of the circadian genes Per1 and Per2 with the cyclic rhythm maintained. Mechanistic study indicates that REGγ directly degrades BMAL1 by the non-canonical proteasome pathway independent of ATP and ubiquitin. Silencing BMAL1 abrogates the changes in circadian genes in REGγ-deficient cells. However, inhibition of GSK-3ß, a known promoter for degradation of BMAL1, exacerbates the action of REGγ depletion. In conclusion, our findings define REGγ as a new factor, which functions as a rheostat of circadian rhythms to mitigate the levels of Per1 and Per2 via proteasome-dependent degradation of BMAL1.

Early Major Complications After Radical Resection of Primary C2-Involved Upper Cervical Chordoma Through the Combined Anterior Retropharyngeal-Posterior Approach: Incidence and Risk Factors.

BACKGROUND: We investigated the frequency of postoperative major complications, length of stay (LOS), and associated risk factors for primary C2-involved upper cervical chordoma through the combined anterior retropharyngeal-posterior approach. METHODS: Clinical data were collected from 102 patients with primary C2-involved upper cervical chordoma treated at our institute from January 2016 to January 2021. Additionally, the Changzheng Hospital (CZH) surgical classification system was designed to describe the different anatomic types of C2 chordomas. A multivariate logistic regression analysis was performed and a multivariate Cox proportional hazards model was used to identify the risk factors associated with the occurrence of major complications and prolonged length of stay (LOS), respectively. RESULTS: The incidence of major complication was 29.41% (30 of 102) in our cohort. A long surgical duration (P = 0.001), increased age (P = 0.001), more preoperative comorbidities (P = 0.008) and CZH types indicating extensive tumor involvement (P < 0.001) were identified as significant predictors of the occurrence of a major complication postoperatively. The mean LOS for the entire study population was 21.50 ± 0.64 days. The patients who experienced complications required a significant longer LOS (25.50 ± 1.26 days) than those without complications (19.83 ± 0.65; P < 0.001). The independent factors affecting LOS included age (P = 0.001), Frankel grade (P = 0.001), CZH classification (P < 0.001), and surgical duration (P = 0.001). CONCLUSIONS: Patients who are older, experience longer operative duration, or have larger tumor extension have a greater risk of postoperative major complication. The LOS can be predicted by age, preoperative neurological deficit, CZH classification, surgical approach, and surgical duration. Accordingly, patients with these risk factors should be monitored and targeted with preventative measures.

Symptomatic spinal metastases from neuroendocrine neoplasms: surgical outcomes and prognostic analysis.

OBJECTIVES: In this article, we investigated the efficiency of surgery in treating symptomatic spinal metastases from neuroendocrine neoplasms and performed univariate analysis for identification of possible prognostic factors. METHODS: A retrospective study was performed, enrolling a total of 19 patients who received surgeries in our center for symptomatic spinal metastases from neuroendocrine neoplasms (NEN). The Kaplan-Meier method was adopted to estimate overall survival (OS) and recurrence free survival (RFS). Univariate analysis was performed for identification of possible prognostic factors. RESULTS: All patients recruited displayed stable recovery after surgical intervention, with a median OS of 27.3 months (95% Confidence Interval: 16.4-38.1 months) and a median RFS of 23.0 months (95% Confidence Interval: 12.1-33.8 months). Postoperatively, 15 patients exhibited improved neurological function based on the Frankel classification, while 16 patients experienced significant pain relief, with mean visual analog scale (VAS) score decreasing from 7.47 ± 2.32-2.47 ± 1.25 (p < 0.05). Univariate analysis revealed that the presence of visceral metastases (p = 0.034) and extraspinal bone metastases (p = 0.016) are both related with poor prognosis. Additionally, well histologic differentiation (p = 0.010) and administration of postoperative octreotide (p = 0.041) or bisphosphonate (p = 0.023) are all indicators for better outcome. CONCLUSIONS: Surgery is an efficient option for treating symptomatic spinal metastases from NEN due to its immediate and assured benefits in pain alleviation, restoration of function and stability reconstruction.

The first total vertebral involvement of benign fibrous histiocytoma: A case report and literature review.

BACKGROUND: Benign fibrous histiocytoma (BFH) is a rare bone tumor, extremely seldom in the spine. METHODS: We present a 52-year-old patient diagnosed with a BFH in the thoracic spine treated with total en bloc spondylectomy. A review of the published literature was also conducted. RESULTS: Non-ossifying fibroma (NOF) and BFH are named as one tumor called NOF/BFH. A total of 20 spinal BFHs have been previously reported, mainly involving the posterior elements. We present a BFH with total vertebral involvement. Curettage and excision are the main treatment options with limited recurrence. CONCLUSIONS: This is the first total vertebral BFH up to now. Spinal BFH occupies rather low aggressiveness. With rather limited recurrence and malignant degeneration, surgical interventions seem enough for its management.

Customized anterior craniocervical reconstruction via a modified high-cervical retropharyngeal approach following resection of a spinal tumor involving C1-2/C1-3.

OBJECTIVE: The surgical treatment of an upper cervical spinal tumor (UCST) at C1-2/C1-3 is challenging due to anterior exposure and reconstruction. Limited information has been published concerning the effective approach and reconstruction for an anterior procedure after C1-2/C1-3 UCST resection. The authors attempted to introduce a novel, customized, anterior craniocervical reconstruction between the occipital condyles and inferior vertebrae through a modified high-cervical retropharyngeal approach (mHCRA) in addressing C1-2/C1-3 spinal tumors. METHODS: Seven consecutive patients underwent 2-stage UCST resection with circumferential reconstruction. Posterior decompression and occiput-cervical instrumentation was conducted at the stage 1 operation, and anterior craniocervical reconstruction using a 3D-printed implant was performed between the occipital condyles and inferior vertebrae via an mHCRA. The clinical characteristics, perioperative complications, and radiological outcomes were reviewed, and the rationale for anterior craniocervical reconstruction was also clarified. RESULTS: The mean age of the 7 patients in the study was 47.6 ± 19.0 years (range 12-72 years) when referred to the authors' center. Six patients (85.7%) had recurrent tumor status, and the interval from primary to recurrence status was 53.0 ± 33.7 months (range 24-105 months). Four patients (57.1%) were diagnosed with a spinal tumor involving C1-3, and 3 patients (42.9%) with a C1-2 tumor. For the anterior procedure, the mean surgical duration and average blood loss were 4.1 ± 0.9 hours (range 3.0-6.0 hours) and 558.3 ± 400.5 ml (range 100-1300 ml), respectively. No severe perioperative complications occurred, except 1 patient with transient dysphagia. The mean pre- and postoperative visual analog scale scores were 8.0 ± 0.8 (range 7-9) and 2.4 ± 0.5 (range 2.0-3.0; p < 0.001), respectively, and the mean improvement rate of cervical spinal cord function was 54.7% ± 13.8% (range 42.9%-83.3%) based on the modified Japanese Orthopaedic Association scale score (p < 0.001). Circumferential instrumentation was in good position and no evidence of disease was found at the mean follow-up of 14.8 months (range 7.3-24.2 months). CONCLUSIONS: The mHCRA provides optimal access to the surgical field at the C0-3 level. Customized anterior craniocervical fixation between the occipital condyles and inferior vertebrae can be feasible and effective in managing anterior reconstruction after UCST resection.

Surgical outcomes and prognostic factors for patients with gastric cancer spinal metastasis.

PURPOSE: To investigate the outcome and prognostic factors of surgery in treating gastric cancer spinal metastasis (GCSM). PATIENTS AND METHODS: A total of 17 patients with GCSM who have undertaken spinal surgeries have been identified. Kaplan-Meier method and univariate analysis are adopted to investigate the prognostic factors affecting overall survival (OS) and progression-free survival (PFS). RESULTS: The median PFS and OS are 11.3 months (95% CI: 7.8-14.9 months) and 11.9 months (95% CI: 8.4-15.4 months), respectively. Postoperatively, all patients had substantial pain relief, with mean visual analog scale score descending from 6.6±1.6 to 3.4±1.2. Meanwhile, patients also showed improved neurological functions, with 8 of them having improvements of at least one level in Frankel classification. Univariate analysis presented that patients with carcinoembryonic antigen (CEA)<6 µg/L (p=0.020), lactate dehydrogenase (LDH)<300 U/L (p=0.012), alkaline phosphatase (ALP)<200 U/L (p=0.007), and Tokuhashi score>6 (p=0.027) show longer OS. Moreover, application of bone cement, low level of ALP (<200 U/L), and LDH (<300 U/L) are associated with longer PFS (p<0.05). CONCLUSIONS: Surgery is an efficient option in treating GCSM, due to its efficacy in pain alleviation, function restoration, and stability reconstruction. Low levels of CEA, LDH, ALP, and high Tokuhashi score (>6) are all favorable factors for better OS, whereas low levels of LDH, ALP, and application of bone cement are related with longer PFS.

Clinical significance of traditional clinical parameters and inflammatory biomarkers for the prognosis of patients with spinal chondrosarcoma: a retrospective study of 150 patients in a single center.

BACKGROUND: To investigate the clinical significance of five inflammatory biomarkers and conventional clinical parameters in prognostic prediction of spinal chondrosarcoma. METHODS: Univariate and multivariate analyses were performed to investigate independent prognostic factors for recurrence and death of patients with spinal chondrosarcoma. Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier curve, and differences were analyzed by log-rank test. The optimal cutoff values for NLR, PLR, LMR, and CAR were determined by X-tile program. RESULTS: The optimal cutoff value for NLR, PLR, LMR, AGR, and CAR was 2.7, 200, 3.0, 1.5, and 0.2, respectively. Of the 150 patients included, recurrence was detected in 105 patients, and death occurred in 78 patients. Multivariate analysis indicated that Tomita I-III, total resection, and CAR < 0.2 were significantly associated with longer DFS. Meanwhile, preoperative Frankel score D-E, total resection, and CAR < 0.2 were favorable prognostic factors for OS. Subtype analysis showed that only total resection was an independent prognostic factor for DFS of recurrent spinal chondrosarcoma. CONCLUSION: Total resection could significantly reduce the recurrence rate of spinal chondrosarcoma and improve OS of chondrosarcoma patients. Tomita classification I-III was a favorable factor for DFS, and preoperative Frankel score A-C was an adverse prognostic factor for OS. CAR was the most robust prognostic indicator with a discriminatory ability as compared with other inflammatory indicators. These slides can be retrieved under Electronic Supplementary Material.

A Novel Technique for Total En bloc Spondylectomy of the Fifth Lumbar Tumor Through Posterior-Only Approach.

STUDY DESIGN: A retrospective study. OBJECTIVE: To describe a new surgical technique for total en bloc spondylectomy (TES) of the fifth lumbar (L5) tumor and evaluate the efficacy and safety of this new technique. SUMMARY OF BACKGROUND DATA: TES has been considered an optimal treatment for tumor, including certain spinal tumors, but it requires a combined posterior-anterior approach, which is often complicated by a long operation time, considerable blood loss and severe trauma. METHODS: Seven patients with primary or solitary metastatic tumors of L5 were treated with this new technique in our center between March 2014 and November 2017. The critical points were fabrication of the iliac graft, dissection, resection, and reconstruction. Other parameters including surgical time, blood loss, complications, pre- and postoperative neurological function, tumor control, and overall survival (OS) were presented and analyzed. RESULTS: All the included patients received one stage TES. The mean surgical time was 365.7 minutes with an average blood loss of 2514.3 mL. No serious perioperative complication was observed or reported during the mean follow-up period of 27.4 months. Wound disruption occurred in one patient and numbness of the left lower limb in another, but both recovered rapidly after appropriate management. Adventitial avulsion of the abdominal aorta occurred during dissection in one patient. Two patients died during the follow-up period due to advanced malignancy. One patient was alive but developed a newly diagnosed thoracolumbar tumor in 40 months. The other four patients recovered well without evidence of disease. All patients were able to walk independently 3 to 4 weeks after operation, with satisfied fusion of the iliac grafts in a mean period of 6.7 months after operation. No evidence of internal fixation failure occurred. CONCLUSION: This new technique offers satisfactory surgical exposure, total en bloc spondylectomy, reliable reconstruction, and good tumor control for certain L5 tumors through the posterior-only approach. LEVEL OF EVIDENCE: 4.

Surgical management and outcome of synovial sarcoma in the spine.

BACKGROUND: Synovial sarcoma (SS) is a soft tissue sarcoma that rarely occurs in the spine, and a minimal number of cases have been reported in the literature. Spinal SS is challenging in diagnosis and treatment and has a poor prognosis. The aim of this study was to summarize and analyse the clinical features and outcomes of patients with spinal SS. METHODS: A total of 16 cases of patients with spinal SS admitted to our institution were reviewed retrospectively. General information, radiological findings and treatment strategies were collected. These patients were followed up regarding their continuing treatment, local or distant recurrence and survival. RESULTS: Spinal SS patients in this series ranged in age from 12 to 68 years (median, 33). Four en bloc resections and 12 piecemeal resections were performed. Improved Frankel (P = 0.002), visual analogue scale (P = 0.002) and Karnofsky Performance Status (P = 0.002) scores were seen postoperatively. The mean follow-up period was 35.9 ± 23.5 (median 31.5, range 4-87) months, with four local recurrences and three distant metastases detected. Eight patients (50.0%) died of disease by the last follow-up. The 1-, 3- and 5-year overall survival rates were 87.5%, 61.4% and 40.9%, respectively. Preoperative chemotherapy was used in three patients to facilitate surgical resection, and adjuvant chemotherapy and radiotherapy were used in six patients. CONCLUSIONS: Spinal SS has a relatively high risk of local recurrence and distant metastasis. Surgical intervention can improve the neurological function and relieve pain in these patients. En bloc excision is an effective treatment strategy to improve survival and prevent local recurrence. Management of spinal SS should be under the instruction of a multidisciplinary team.

Outcomes and prognostic factors for surgically treated patients with breast cancer spine metastases.

PURPOSE: The aim of this study is to provide some useful insights into the treatments, outcomes, and prognostic factors of patients with breast cancer spine metastases (BCSM). METHODS: We report a retrospective case series analyzing 87 patients with BCSM who underwent surgical interventions. Independent prognostic factors for SMFS and OS were extracted using univariate and multivariate analyses, the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: The mean time between primary diagnoses and spinal metastases was 46.8 (median 41, range 0-147 months) months. The analysis showed that lymph node metastasis (p = 0.043, HR 10.498, 95%CI 1.074-102.588) and estrogen receptor (ER) status (p = 0.004, HR 0.368, 95%CI 0.189-0.721) can significantly affect SMFS. Furthermore, visceral metastasis (p = 0.042, HR 2.383, 95%CI 1.032-5.501), multiple metastases (p = 0.035, HR 2.538, 95%CI 1.066-6.048) and post-op chemotherapy (p = 0.003, HR 0.312, 95%CI 0.144-0.675) have significant effects on OS. Lastly, patients identified as Luminal A subtype have longer OS. CONCLUSIONS: Lymph node metastases and ER status are independent risk factors in predicting BCSM. Moreover, visceral metastasis, multiple metastases of the spine and post-op chemotherapy are independent prognostic factors. Luminal subtypes have higher rate, but late onset of spine metastases and prolonged survival.

The embryonic transcription factor Brachyury confers chordoma chemoresistance via upregulating CA9.

Being a rare malignant bone tumor on the axial skeleton, chordoma is locally invasive and has a high rate of recurrence. Despite extensive studies, the mechanisms of chordoma recurrence after surgical intervention, as well as resistance to radiation and chemotherapy, remain elusive. In this study, primary chordoma cell lines PCH1 and PCH2 were established and characterized by chordoma specific markers. We found that the embryonic transcription factor Brachyury inhibits Paclitaxel induced apoptosis in different cells, including PCH1 and U2OS cells. T gene regulated genes were identified in PCH1 and U2OS using microarray. After comparing gene regulated by Brachyury in different cells and the chromatin immunoprecipitation assay, we identified carbonic anhydrase IX (CA9) as a common target gene of Brachyury. Besides, immunohistochemical staining of CA9 and Brachyury in chordoma tissues revealed that their expression levels were positively correlated. We further showed that CA9 is responsible for Paclitaxel resistance in PCH1 cell. Our data suggest that CA9 plays a role in Brachyury mediated Paclitaxel resistance and serves as a potential target for chordoma treatment.

Single-stage multi-level construct design incorporating ribs and chest wall reconstruction after en bloc resection of spinal tumour.

PURPOSE: Multi-level reconstruction incorporating the chest wall and ribs is technically demanding after multi-segmental total en bloc spondylectomy (TES) of thoracic spinal tumours. Few surgical techniques are reported for effective reconstruction. A novel and straightforward technical reconstruction through posterior-lateral approach was presented to solve the extensive chest wall defect and prevent occurrences of severe respiratory dysfunctions after performing TES. The preliminary outcomes of surgery were reviewed. METHODS: Multi-level TES was performed for five patients with primary or recurrent thoracic spinal malignancies through posterior-lateral approach. The involved ribs and chest wall were removed to achieve tumour-free margin. Then titanium mesh with allograft bone and pedicle screw-rod system were adopted for the circumferential spinal reconstruction routinely. Titanium rods were modified accordingly to attach to the screw-rod system proximally, and the distal end of rods was dynamically inserted into the ribs. RESULTS: The mean surgery time was 6.7 hours (range 5-8), with the average blood loss of 3260 ml (range 2300-4500). No severe neurological complications were reported while three patients had complaints of slight numbness of chest skin (no. 1, 3, and 5). No severe respiratory complications occurred during peri-operative period. No implant failure and no local recurrence or distant metastases were observed with an average follow-up of 12.5 months. CONCLUSIONS: The single-stage reconstructions incorporating spine and chest wall are straightforward and easy to perform. The preliminary outcomes of co-reconstructions are promising and favourable. More studies and longer follow-up are required to validate this technique.

One-stage Posterior Approach in the Treatment of Consecutive Multi-segment Thoracic Tuberculosis with Kyphosis.

AIM: To evaluate the clinical efficacy of the one-stage posterior approach in treating consecutive multiple-segment thoracic tuberculosis with kyphosis. MATERIAL AND METHODS: A retrospective study was performed. The data of 22 patients with consecutive multi-level thoracic tuberculosis and kyphosis who underwent the one-stage posterior approach of debridement, bone grafting, drainage and pedicle screws fixation were collected. The kyphotic angle was 61.6°±3.1° pre-operatively. The neurologic status based on American Spinal Injury Association (ASIA) scoring was A in 5 cases, B in 4 cases, C in 9 cases, D in 3 cases and E in 1 case. RESULTS: The average follow-up period was 43.4±5.0 months. The kyphotic angle was 19.8°±0.7° after operation (p < 0.01), and 21.9°±1.2° at the last visit (p < 0.01). No neurological deterioration was observed in any patients after surgery. A significant difference in ASIA score was detected when the state before the operation and at the last visit was compared (p < 0.01). There was no recurrent paravertebral abscess of thoracic tuberculosis in any of these cases. CONCLUSION: The one-stage posterior approach of debridement and drainage is a feasible surgical option for consecutive multisegment thoracic tuberculosis with kyphosis. It can achieve debridement, decompression, and stabilization simultaneously.