Prospective Registration Study for Establishing Minimal Clinically Important Differences in Patients Undergoing Surgery for Spinal Metastases.

STUDY DESIGN: Multicenter, prospective registry study. OBJECTIVE: To clarify minimal clinically important differences (MCIDs) for surgical interventions for spinal metastases, thereby enhancing patient care by integrating quality of life (QoL) assessments with clinical outcomes. SUMMARY OF BACKGROUND DATA: Despite its proven usefulness in degenerative spinal diseases and deformities, the MCID remains unexplored regarding surgery for spinal metastases. METHODS: This study included 171 (out of 413) patients from the multicenter "Prospective Registration Study on Surgery for Metastatic Spinal Tumors" by the Japan Association of Spine Surgeons. These were evaluated preoperatively and at 6 months postoperatively using the Face scale, EuroQol-5 Dimensions-5 Levels (EQ-5D-5L), including the visual analog scale (VAS), and performance status. The MCIDs were calculated using an anchor-based method, classifying participants into the improved, unchanged, and deteriorated groups based on the Face scale scores. Focusing on the improved and unchanged groups, the change in the EQ-5D-5L values from before to after treatment was analyzed, and the cutoff value with the highest sensitivity and specificity was determined as the MCID through receiver operating characteristic curve analysis. The validity of the MCIDs was evaluated using a distribution-based calculation method for patient-reported outcomes. RESULTS: The improved, unchanged, and deteriorated groups comprised 121, 28, and 22 participants, respectively. The anchor-based MCIDs for the EQ-5D-5L index, EQ-VAS, and domains of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression were 0.21, 15.50, 1.50, 0.50, 0.50, 0.50, and 0.50, respectively; the corresponding distribution-based MCIDs were 0.17, 15,99, 0.77, 0.80, 0.78, 0.60, and 0.70, respectively. CONCLUSION: We identified MCIDs for surgical treatment of spinal metastases, providing benchmarks for future clinical research. By retrospectively examining whether the MCIDs are achieved, factors favoring their achievement and risks affecting them can be explored. This could aid in decisions on surgical candidacy and patient counseling.

Clinical Outcomes of Total En Bloc Spondylectomy for Previously Irradiated Spinal Metastases: A Retrospective Propensity Score-Matched Comparative Study.

This study aimed to investigate the clinical outcomes of total en bloc spondylectomy (TES) for spinal metastases previously treated with radiotherapy (RT). This study enrolled 142 patients who were divided into two groups: those with and those without an RT history. Forty-two patients were selected from each group through propensity score matching, and postoperative complications, local recurrence, and overall survival rates were compared. The incidence of postoperative complications was significantly higher in the group with an RT history than in the group without an RT history (57.1% vs. 35.7%, respectively). The group with an RT history had a higher local recurrence rate than the group without an RT history (1-year rate: 17.5% vs. 0%; 2-year rate: 20.8% vs. 2.9%; 5-year rate: 24.4% vs. 6.9%). The overall postoperative survival tended to be lower in the group with an RT history; however, there was no significant difference between the two groups (2-year survival: 64.3% vs. 66.7%; 5-year survival: 47.3% vs. 57.1%). When planning a TES for irradiated spinal metastases, the risk of postoperative complications and local recurrence should be fully considered.

The Impact of Frailty on Postoperative Complications in Total En Bloc Spondylectomy for Spinal Tumors.

Total en bloc spondylectomy (TES) is an effective treatment for spinal tumors. However, its complication rate is high, and the corresponding risk factors remain unclear. This study aimed to clarify the risk factors for postoperative complications after TES, including the patient's general condition, such as frailty and their levels of inflammatory biomarkers. We included 169 patients who underwent TES at our hospital from January 2011-December 2021. The complication group comprised patients who experienced postoperative complications that required additional intensive treatments. We analyzed the relationship between early complications and the following factors: age, sex, body mass index, type of tumor, location of tumor, American Society of Anesthesiologists score, physical status, frailty (categorized by the 5-factor Modified Frailty Index [mFI-5]), neutrophil-to-lymphocyte ratio, C-reactive protein/albumin ratio, preoperative chemotherapy, preoperative radiotherapy, surgical approach, and the number of resected vertebrae. Of the 169 patients, 86 (50.1%) were included in the complication group. Multivariate analysis showed that high mFI-5 scores (odds ratio [OR] = 2.99, p < 0.001) and an increased number of resected vertebrae (OR = 1.87, p = 0.018) were risk factors for postoperative complications. Frailty and the number of resected vertebrae were independent risk factors for postoperative complications after TES for spinal tumors.

Clinical outcomes following total en bloc spondylectomy for spinal metastases from lung cancer.

BACKGROUND: The current guidelines for the treatment of non-small cell lung cancer encourage local curative treatment for selected patients with oligometastases. This study evaluated the surgical results of total en bloc spondylectomy (TES) for isolated spinal metastases originating from lung cancer in carefully selected patients. METHODS: We retrospectively reviewed 14 patients (7 men and 7 women) who underwent TES for spinal metastases originating from lung cancer between 2000 and 2017. The primary outcome measure was the postoperative overall survival time. The histological types included adenocarcinoma (n = 12), pleomorphic carcinoma (n = 1), and small cell lung carcinoma (SCLC) (n = 1 patient). We assessed postoperative survival using Kaplan-Meier analysis and the log-rank test. RESULTS: The median postoperative survival time was 83.0 months (6-162 months) in 13 patients with non-small cell lung carcinoma (NSCLC) and 6 months in 1 patient with SCLC. The 3-, 5-, and 10-year overall survival rates in patients with NSCLC were 61.5%, 53.8%, and 15.4%, respectively. Poor postoperative performance status (PS) and Frankel grade, and preoperative irradiation to the vertebrae to be resected were significantly associated with short-term survival after TES in patients with NSCLC (p < 0.05). CONCLUSIONS: The surgical results of TES for spinal metastases of lung cancer were relatively favorable among carefully selected patients. TES may be indicated for spinal metastases of lung cancer in patients with controlled primary lung cancer, NSCLC histology, prospect of good postoperative PS, and preferably no irradiation to the target vertebrae.

Metastasectomy of spinal lesions from thyroid carcinomas.

Patients with differentiated thyroid carcinomas (DTCs) have a favourable long-term survival. Spinal metastases (SMs) cause a decline in performance status (PS), directly affecting mortality and indirectly preventing the use of systemic therapies. Metastasectomy is indicated, if feasible, as it yields the best local tumour control. Our study aimed to examine the long-term clinical outcomes of metastasectomy for SMs of thyroid carcinomas. We collected data on 22 patients with DTC (16 follicular and six papillary carcinomas) and one patient with medullary carcinoma who underwent complete surgical resection of SMs at our institution between July 1992 and July 2017, with a minimum postoperative follow-up of five years. The cancer-specific survival (CSS) from the first spinal metastasectomy to death or the last follow-up was determined using Kaplan-Meier analysis. Potential factors associated with survival were evaluated using the log-rank test. We analyzed the clinical parameters and outcome data, including pre- and postoperative disability (Eastern Cooperative Oncology Group PS 3), lung and non-spinal bone metastases, and history of radioiodine and kinase inhibitor therapies. Lung and other bone metastases at the time of surgery were observed in ten and eight patients, respectively. Three patients experienced local tumour recurrences at the operated site. The five- and ten-year CSS rates in the 22 patients with DTC were 77% and 52%, respectively. Pre- and postoperative disability and operative site tumour recurrence were identified as risk factors for short postoperative survival. Metastasectomy for resectable SM from DTC yielded favourable results and has the potential to improve survival.

Biomechanical investigation of long spinal fusion models using three-dimensional finite element analysis.

BACKGROUND: This study represents the first finite element (FE) analysis of long-instrumented spinal fusion from the thoracic vertebrae to the pelvis in the context of adult spinal deformity (ASD) with osteoporosis. We aimed to evaluate the von Mises stress in long spinal instrumentation for models that differ in terms of spinal balance, fusion length, and implant type. METHODS: In this three-dimensional FE analysis, FE models were developed based on computed tomography images from a patient with osteoporosis. The von Mises stress was compared for three different sagittal vertical axes (SVAs) (0, 50, and 100 mm), two different fusion lengths (from the pelvis to the second [T2-S2AI] or 10th thoracic vertebra [T10-S2AI]), and two different types of implants (pedicle screw or transverse hook) in the upper instrumented vertebra (UIV). We created 12 models based on combinations of these conditions. RESULTS: The overall von Mises stress was 3.1 times higher on the vertebrae and 3.9 times higher on implants for the 50-mm SVA models than that for the 0-mm SVA models. Similarly, the values were 5.0 times higher on the vertebrae and 6.9 times higher on implants for the 100-mm SVA models than that for the 0-mm SVA models. Higher SVA was associated with greater stress below the fourth lumbar vertebrae and implants. In the T2-S2AI models, the peaks of vertebral stress were observed at the UIV, at the apex of kyphosis, and below the lower lumbar spine. In the T10-S2AI models, the peaks of stress were observed at the UIV and below the lower lumbar region. The von Mises stress in the UIV was also higher for the screw models than for the hook models. CONCLUSION: Higher SVA is associated with greater von Mises stress on the vertebrae and implants. The stress on the UIV is greater for the T10-S2AI models than for the T2-S2AI models. Using transverse hooks instead of screws at the UIV may reduce stress in patients with osteoporosis.

Characteristics and risk factors of instrumentation failure following total en bloc spondylectomy.

AIMS: The aim of this study was to investigate the incidence and characteristics of instrumentation failure (IF) after total en bloc spondylectomy (TES), and to analyze risk factors for IF. METHODS: The medical records from 136 patients (65 male, 71 female) with a mean age of 52.7 years (14 to 80) who underwent TES were retrospectively reviewed. The mean follow-up period was 101 months (36 to 232). Analyzed factors included incidence of IF, age, sex, BMI, history of chemotherapy or radiotherapy, tumour histology (primary or metastasis; benign or malignant), surgical approach (posterior or combined), tumour location (thoracic or lumbar; junctional or non-junctional), number of resected vertebrae (single or multilevel), anterior resection line (disc-to-disc or intravertebra), type of bone graft (autograft or frozen autograft), cage subsidence (CS), and local alignment (LA). A survival analysis of the instrumentation was performed, and relationships between IF and other factors were investigated using the Cox regression model. RESULTS: A total of 44 patients (32.4%) developed IF at a median of 31 months (interquartile range 23 to 74) following TES. Most IFs were rod fractures preceded by a mean CS of 6.1 mm (2 to 18) and LA kyphotic enhancement of 10.8° (-1 to 36). IF-free survival rates were 75.8% at five years and 56.9% at ten years. The interval from TES to IF peaked at two to three years postoperatively and continued to occur over a period of time thereafter; the early IF-developing group had greater CS at one month postoperatively (CS1M) and more lumbar TES. CS1M ≥ 3 mm and sole use of frozen autografts were identified as independent risk factors for IF. CONCLUSION: IF is a common complication following TES. We have demonstrated that robust spinal reconstruction preventing CS, and high-quality bone grafting are necessary for successful reconstruction.Cite this article: Bone Joint J 2023;105-B(2):172-179.

The influence of costal resection on pulmonary function after total en bloc spondylectomy for spine tumor.

BACKGROUND: Total en bloc spondylectomy (TES) is one of the surgical procedures which has been recognized as a complete resection for spine tumors. Although the surgery achieves favorable local control for solitary spinal lesion, performing the procedure in the thoracic spine requires circumferential dissection around the vertebral body and bilateral rib resections which might result in decline of pulmonary function postoperatively. This study aimed to clarify whether the number of rib resections negatively impacts pulmonary function after the procedure. METHODS: This study included 31 patients who underwent vertebrectomy (17 males and 14 females) with a mean age of 54.2 years. Pulmonary function testing (PFT) was performed before surgery and at 1 month, 6 months, and 1 year postoperative visits. Patients with restrictive disorders such as space occupying lesions in the lung, obstructive problems such as a history of asthma, and smoking history were excluded from this study. Associations between the number of rib resections and PFT data were analyzed based on the resected level of the thoracic spine. RESULTS: There was a significant decrease in forced vital capacity (FVC) at 1 month (72% of preoperative value), followed by gradual recovery at 6 months (89%) and 1 year (90%). The percentage of predicted forced expiratory volume in 1 s remained stable. Patients who underwent three pairs of rib resections showed a significant decrease in the FVC (83.5% of the preoperative value) and FEV1 (82.1% of the preoperative value) compared with one or two pairs of rib resections. CONCLUSION: FVC decreased 1 month after vertebrectomy and returned to 90% of preoperative value at 1 year postoperatively. Three pairs of rib resections showed a significant decrease in FVC, suggesting the influence of a greater numbers of rib resections on pulmonary function.

The L-type Amino Acid Transporter (LAT1) Expression in Patients with Scoliosis.

Introduction: Amino acid transporters are transmembrane proteins that are known to mediate the transfer of amino acids. As one of the amino acid transporters, LAT1, which is encoded by Slc7a5, mediates the cellular uptake of the essential amino acids. Recently, most studies have focused on examining the relationship between LAT1 and skeletal formation in terms of development. However, little is known regarding the clinical features of LAT1 in the cartilage, which might result in the development of skeletal deformities such as scoliosis. Thus, the aim of this study was to investigate the expression of L-type amino acid transporter 1 (LAT1) and its solute carrier transporter 7a5 (Slc7a5) in patients with pediatric scoliosis and to compare with the relationship between LAT1 and Slc7a5 expression and their clinical features. Methods: We have prospectively recruited 56 patients who underwent corrective spinal fusion for scoliosis. The patients comprised 40 girls and 16 boys, with a mean age of 13.1 years at the time of surgery. There were 34 idiopathic scoliosis (IS) patients, whereas 22 were congenital scoliosis (CS) patients. During the surgery, an epiphyseal part of the spinous process at apical vertebra was harvested; then, LAT1 and Slc7a5 expressions in the cartilage were evaluated. Results: As per our findings, LAT1 expression was observed in the cartilage in 60.7% (34 out of 56) of the patients. LAT1 expression in IS patients was 76%, which were statistically higher compared to 36% in CS patients. When compared with LAT1 expression, no statistical difference was noted in terms of age, gender, body mass index (BMI), Cobb angle, and Risser grade. Meanwhile, the mean Slc7a5 expression in IS patients was determined to be significantly higher than that in CS patients. No significant correlation was observed between Slc7a5 expression and age, BMI, and Cobb angle. Conclusions: LAT1 and Slc7a5 expression in IS and CS patients showed significant differences. These expressions were found to be not correlated with age, stature, and severity of the deformity.

Validation and comparison of trunk muscle activities in male participants during exercise using an innovative device and abdominal bracing maneuvers.

BACKGROUND: Abdominal bracing is effective in strengthening the trunk muscles; however, assessing performance can be challenging. We created a device for performing abdominal trunk muscle exercises. The effectiveness of this device has not yet been evaluated or comparedOBJECTIVE: We aimed to quantify muscle activity levels during exercise using our innovative device and to compare them with muscle activation during abdominal bracing maneuvers. METHODS: This study included 10 men who performed abdominal bracing exercises and exercises using our device. We measured surface electromyogram (EMG) activities of the rectus abdominis (RA), external oblique, internal oblique (IO), and erector spinae (ES) muscles in each of the exercises. The EMG data were normalized to those recorded during maximal voluntary contraction (%EMGmax). RESULTS: During the bracing exercise, the %EMGmax of IO was significantly higher than that of RA and ES (p< 0.05), whereas during the exercises using the device, the %EMGmax of IO was significantly higher than that of ES (p< 0.05). No significant difference was observed in the %EMGmax of any muscle between bracing exercises and the exercises using the device (p= 0.13-0.95). CONCLUSIONS: The use of our innovative device results in comparable activation to that observed during abdominal bracing.

Effects of Radiation on the Bone Strength of Spinal Vertebrae in Rats.

STUDY DESIGN: A controlled laboratory study. OBJECTIVE: The aim of this study was to examine bone damage caused by irradiation to spinal vertebrae in rats. SUMMARY OF BACKGROUND DATA: Radiotherapy is widely used in the treatment of malignant spine tumors. However, a few studies have reported vertebral fractures following radiotherapy as an adverse reaction. There are no reports on irradiation- induced changes in bone fragility, mechanical and structural changes focusing on the spine, and the mechanism of irradiation-induced bone osteoporosis. METHODS: Eighty-four female Wistar rats were randomly allocated to the 20 Gy irradiated or the nonirradiated (control) group. The lumbar vertebrae were irradiated with an external focal radiation dose of 20 Gy. Biomechanical, structural, and histological analyses were performed at 0, 2, 4, 6, 8, 12, and 24 weeks after irradiation. Structural analysis and bone density measurement of vertebral trabecular bone were performed by µCT. Histopathological evaluation was performed by hematoxylin and eosin staining and immunostaining. RESULTS: The bone strength at 2 weeks after irradiation (311 ±â€Š23 N) was 22% lower than that before irradiation (398 ±â€Š34 N) (P  < 0.05). The trabecular spacing increased, and trabecular connectivity and width decreased significantly in the irradiated group compared with those in the non-irradiated group. The three-dimensional structure model became coarse, and the trabecular structure continued to thin and disrupt after irradiation. There was no significant change in the bone mineral density in both groups. CONCLUSION: A decrease in bone strength was observed 2 weeks after irradiation. Bone mineral density remained unaltered, whereas the microstructure of trabecular bone changed, suggesting bone damage by irradiation.Level of Evidence: N/A.

Evaluation of locomotive syndrome in patients receiving surgical treatment for degenerative musculoskeletal diseases: A multicentre prospective study using the new criteria.

OBJECTIVES: This study aimed to evaluate the condition of patients with locomotive syndrome (LS) and their improvement after undergoing surgery for degenerative musculoskeletal diseases using the new criteria, including stage 3. METHODS: In total, 435 patients aged ≥40 years (167 middle-aged and 268 older) were divided into four groups based on the disease location: the lumbar (n = 118), hip (n = 191), knee (n = 80), and foot and ankle (n = 46) groups. Patients were evaluated by pre- and 1 year postoperative LS risk tests, including the stand-up test, two-step test, and 25-Question Geriatric Locomotive Function Scale. RESULTS: The pre- and postoperative prevalence of LS stage 3 were 78% and 29%, respectively. The postoperative LS stage improved in 62% of patients (77% and 53% in the middle-aged and older groups, respectively). Overall, the knee group showed the worst results, and the foot and ankle groups showed the best pre- and postoperative results. The pre- and postoperative prevalence of LS stage 3 according to the 25-Question Geriatric Locomotive Function Scale were comparable to those based on the total assessment. CONCLUSIONS: The new LS stage criteria are appropriate, and the 25-Question Geriatric Locomotive Function Scale is a good option for evaluating patients requiring surgery.

Current Management of Bone Metastases from Differentiated Thyroid Cancer.

After the lung, the skeleton is the second most common site of distant metastases in differentiated thyroid carcinoma (DTC). Patients with osteolytic bone metastases (BMs) from thyroid carcinoma often have significantly reduced performance status and quality of life. Recent advancements in cancer therapy have improved overall survival in multiple cancer subtypes, including thyroid cancer. Therefore, long-term local control of thyroid BMs is desired, especially in patients with a single metastasis or oligometastases. Here, we reviewed the current management options for DTC-BMs and especially focused on local treatments for long-term local tumor control from an orthopedic tumor surgeon's point of view. Metastasectomy and stereotactic radiosurgery can be performed either alone or in combination with radioiodine therapy and kinase inhibitors to cure skeletal lesions in selected patients. Percutaneous procedures have been developed in recent years, and they can also have a curative role in small BMs. Recent advancements in local therapies have the potential to provide not only long-term local tumor control but also a better prognosis.

Surgical Metastasectomy in the Spine: A Review Article.

BACKGROUND: The use of surgical metastasectomy (SM) has increased across cancer types in recent decades despite the increasing efficacy of modern systemic treatment modalities. Symptomatic spinal metastases severely compromise patients' performance status. However, as spinal SM is a complex surgery with potentially significant complications, it is not considered the treatment of choice. METHODS: We reviewed the articles on SM in several primary cancers with different types of metastatic lesions and extracted the data from relevant articles to provide a comprehensive review including the surgical techniques, indications, reported outcomes, and future prospects of SM in spinal metastases. RESULTS: Total en bloc spondylectomy (TES) is a method of spinal SM associated with a lower risk of tumor recurrence and complications. Intralesional transpedicular osteotomy using a fine threadwire saw allows prevention of spinal cord and nerve root injuries. Spinal SM is considered suitable for patients with controlled primary disease having no evidence of disseminated extraspinal metastases, a completely resectable solitary lesion in the spine, and adequate cardiopulmonary reserve to tolerate the surgery. Metastatic lesions from kidney and thyroid cancers have been reported as the best candidates for spinal SM. Although data about spinal SM are limited, the reported outcomes are favorable with acceptable local recurrence rates in long-term follow-up. CONCLUSION: In patients with isolated resectable spinal metastases, complete SM including TES is a useful option as it can improve function and survival. However, appropriate patient selection and surgical feasibility remain the most important aspects of management. IMPLICATIONS FOR PRACTICE: Surgical metastasectomy for spinal metastases may be a potentially curative treatment option with a low risk of local recurrence and lead to prolonged long-term survival if appropriate patients are selected and if the surgery is carried out by experienced surgeons in high-volume centers.

Perioperative complications of total en bloc spondylectomy for spinal tumours.

AIMS: To evaluate the perioperative complications associated with total en bloc spondylectomy (TES) in patients with spinal tumours, based on the extent and level of tumour resection. METHODS: In total, 307 patients who underwent TES in a single centre were reviewed retrospectively. There were 164 male and 143 female patients with a mean age at the time of surgery of 52.9 years (SD 13.3). A total of 225 patients were operated on for spinal metastases, 34 for a malignant primary tumour, 41 for an aggressive benign tumour, and seven with a primary of unknown origin. The main lesion was located in the thoracic spine in 213, and in the lumbar spine in 94 patients. There were 97 patients who underwent TES for more than two consecutive vertebrae. RESULTS: Major and minor perioperative complications were observed in 122 (39.7%) and 84 (27.4%) patients respectively. The breakdown of complications was as follows: bleeding more than 2,000 ml in 60 (19.5%) patients, hardware failure in 82 (26.7%), neurological in 46 (15.0%), surgical site infection in 23 (7.5%), wound dehiscence in 16 (5.2%), cerebrospinal fluid leakage in 45 (14.7%), respiratory in 52 (16.9%), cardiovascular in 11 (3.6%), digestive in 19 (6.2%)/ The mortality within two months of surgery was four (1.3%). The total number of complications per operation were 1.01 (SD 1.0) in the single vertebral resection group and 1.56 (SD 1.2) in the group with more than two vertebral resections. Cardiovascular and respiratory complications, along with hardware failure were statistically higher in the group who had more than two vertebrae resected. Also, in this group the amount of bleeding in patients with a lumbar lesion or respiratory complication in patients with a thoracic lesion, were statistically higher. Multivariate analysis showed that using a combined anterior and posterior approach, when more than two vertebral resections were significant independent factors. CONCLUSION: The characteristics of perioperative complications after TES were different depending on the extent and level of the tumour resection. In addition to preoperative clinical and pathological factors, it is therefore important to consider these factors in patients who undergo en bloc resection for spinal tumours. Cite this article: Bone Joint J 2021;103-B(5):976-983.

Abscopal Effect of Frozen Autograft Reconstruction Combined with an Immune Checkpoint Inhibitor Analyzed Using a Metastatic Bone Tumor Model.

We evaluated the abscopal effect of re-implantation of liquid nitrogen-treated tumor-bearing bone grafts and the synergistic effect of anti-PD-1 (programmed death-1) therapy using a bone metastasis model, created by injecting MMT-060562 cells into the bilateral tibiae of 6-8-week-old female C3H mice. After 2 weeks, the lateral tumors were treated by excision, cryotreatment using liquid nitrogen, excision with anti-PD-1 treatment, and cryotreatment with anti-PD-1 treatment. Anti-mouse PD-1 4H2 was injected on days 1, 6, 12, and 18 post-treatment. The mice were euthanized after 3 weeks; the abscopal effect was evaluated by focusing on growth inhibition of the abscopal tumor. The re-implantation of frozen autografts significantly inhibited the growth of the remaining abscopal tumors. However, a more potent abscopal effect was observed in the anti-PD-1 antibody group. The number of CD8+ T cells infiltrating the abscopal tumor and tumor-specific interferon-γ (IFN-γ)-producing spleen cells increased in the liquid nitrogen-treated group compared with those in the excision group, with no significant difference. The number was significantly higher in the anti-PD-1 antibody-treated group than in the non-treated group. Overall, re-implantation of tumor-bearing frozen autograft has an abscopal effect on abscopal tumor growth, although re-implantation of liquid nitrogen-treated bone grafts did not induce a strong T-cell response or tumor-suppressive effect.

Clinical outcomes and prognostic factors following the surgical resection of renal cell carcinoma spinal metastases.

The efficacy of surgical resection in metastatic renal cell carcinoma is an active and important research field in the postcytokine era. Bone metastases, especially in the spine, compromise patient performance status. Metastasectomy is indicated, if feasible, because it helps to achieve the best clinical outcomes possible compared with other treatments. This study examined the postoperative survival and prognostic factors in patients who underwent metastasectomy of spinal lesions. The retrospective study included 65 consecutive patients with metastatic renal cell carcinomas who were operated on by spinal metastasectomy between 1995 and 2017 at our institution. The cancer-specific survival times from the first spinal metastasectomy to death or the last follow-up (≥3 years) were determined using Kaplan-Meier analysis. Potential factors influencing survival were analyzed using Cox proportional hazard models. Planned surgical resection of all the spine tumors was achieved in all patients. Of these, 38 had complete metastasectomy of all visible metastases, including extraspinal lesions. In all patients, the estimated median cancer-specific survival time was 100 months. The 3-, 5-, and 10-year cancer-specific survival rates were 77%, 62%, and 48%, respectively. The survival times after spinal metastasectomy were similar in both cytokine and postcytokine groups. In multivariate analyses, postoperative disability, the coexistence of liver metastases, multiple spinal metastases, and incomplete metastasectomy were significant risk factors associated with short-term survival. Complete metastasectomy, including extraspinal metastases, was associated with improved cancer-specific survival. Proper patient selection and complete metastasectomy provide a better prognosis in metastatic renal cell carcinoma patients.

The efficacy of surgical treatment on locomotive syndrome and physical function in patients with lumbar spinal canal stenosis.

BACKGROUND: Locomotive syndrome is a condition of reduced mobility due to problems with locomotive organs. Although lumbar spinal canal stenosis is one of the major diseases constituting locomotive syndrome, only few studies have focused on the association between the two pathologies. We aimed to investigate the effect of surgery on lumbar spinal canal stenosis with respect to locomotive syndrome using various physical function tests, including locomotive syndrome risk tests, before and after surgery. METHODS: Clinical data of 101 consecutive patients (male = 46; female = 55; mean age, 69.3 years) who underwent surgery for lumbar spinal canal stenosis at our institute were prospectively collected. Results of physical function tests, including stand-up test, two-step test, and 25-Question Geriatric Locomotive Function Scale, and the sagittal vertical axis were evaluated before and 1 year after surgery. The association between several parameters and improvement of risk level in locomotive syndrome was evaluated. RESULTS: In the total assessment, 93.1% of cases were in stage 2 and 6.9% in stage 1 preoperatively, while 72.4% were in stage 2, 22.4% in stage 1, and 5.2% in stage 0 at 1 year postoperatively. Postoperative improvement in the total assessment was observed in 28.7% of cases. Several physical function tests and sagittal vertical axis showed significant improvement after surgery. On multiple logistic regression analysis, age >75 years (odds ratio = 10.9, confidence interval = 1.09-109) and postoperative sagittal vertical axis >40 mm (odds ratio = 17.8, confidence interval = 1.78-177) were significant risk factors associated with non-improvement in risk level of locomotive syndrome. CONCLUSIONS: Surgical treatment for lumbar spinal canal stenosis improved physical function, including locomotive syndrome. Risk factors associated with non-improvement of locomotive syndrome were later-stage elderly and postoperative sagittal balance impairment.

Radiation Disrupts the Protective Function of the Spinal Meninges in a Mouse Model of Tumor-induced Spinal Cord Compression.

BACKGROUND: Recent advances in multidisciplinary treatments for various cancers have extended the survival period of patients with spinal metastases. Radiotherapy has been widely used to treat spinal metastases; nevertheless, long-term survivors sometimes undergo more surgical intervention after radiotherapy because of local tumor relapse. Generally, intradural invasion of a spinal tumor seldom occurs because the dura mater serves as a tissue barrier against tumor infiltration. However, after radiation exposure, some spinal tumors invade the dura mater, resulting in leptomeningeal dissemination, intraoperative dural injury, or postoperative local recurrence. The mechanisms of how radiation might affect the dura have not been well-studied. QUESTIONS/PURPOSES: To investigate how radiation affects the spinal meninges, we asked: (1) What is the effect of irradiation on the meningeal barrier's ability to protect against carcinoma infiltration? (2) What is the effect of irradiation on the meningeal barrier's ability to protect against sarcoma infiltration? (3) What is the effect of irradiation on dural microstructure observed by scanning electron microscopy (SEM)? (4) What is the effect of irradiation on dural microstructure observed by transmission electron microscopy (TEM)? METHODS: Eighty-four 10-week-old female ddY mice were randomly divided into eight groups: mouse mammary tumor (MMT) implantation 6 weeks after 0-Gy irradiation (nonirradiation) (n = 11), MMT implantation 6 weeks after 20-Gy irradiation (n = 10), MMT implantation 12 weeks after nonirradiation (n = 10), MMT implantation 12 weeks after 20-Gy irradiation (n = 11), mouse osteosarcoma (LM8) implantation 6 weeks after nonirradiation (n = 11), LM8 implantation 6 weeks after 20-Gy irradiation (n = 11), LM8 implantation 12 weeks after nonirradiation (n = 10), and LM8 implantation 12 weeks after 20-Gy irradiation (n = 10); female mice were used for a mammary tumor metastasis model and ddY mice, a closed-colony mice with genetic diversity, were selected to represent interhuman diversity. Mice in each group underwent surgery to generate a tumor-induced spinal cord compression model at either 6 weeks or 12 weeks after irradiation to assess changes in the meningeal barrier's ability to protect against tumor infiltration. During surgery, the mice were implanted with MMT (representative of a carcinoma) or LM8 tumor. When the mice became paraplegic because of spinal cord compression by the growing implanted tumor, they were euthanized and evaluated histologically. Four mice died from anesthesia and 10 mice per group were euthanized (MMT-implanted groups: MMT implantation occurred 6 weeks after nonirradiation [n = 10], 6 weeks after irradiation [n = 10], 12 weeks after nonirradiation [n = 10], and 12 weeks after irradiation [n = 10]; LM8-implanted groups: LM8 implantation performed 6 weeks after nonirradiation [n = 10], 6 weeks after irradiation [n = 10], 12 weeks after nonirradiation [n = 10], and 12 weeks after irradiation [n = 10]); 80 mice were evaluated. The spines of the euthanized mice were harvested; hematoxylin and eosin staining and Masson's trichrome staining slides were prepared for histologic assessment of each specimen. In the histologic assessment, intradural invasion of the implanted tumor was graded in each group by three observers blinded to the type of tumor, presence of irradiation, and the timing of the surgery. Grade 0 was defined as no intradural invasion with intact dura mater, Grade 1 was defined as intradural invasion with linear dural continuity, and Grade 2 was defined as intradural invasion with disruption of the dural continuity. Additionally, we euthanized 12 mice for a microstructural analysis of dura mater changes by two observers blinded to the presence of irradiation. Six mice (three mice in the 12 weeks after nonirradiation group and three mice in the 12 weeks after 20-Gy irradiation group) were quantitatively analyzed for defects on the dural surface with SEM. The other six mice (three mice in the 12 weeks after nonirradiation group and three mice in the 12 weeks after 20-Gy irradiation group) were analyzed for layer structure of collagen fibers constituting dura mater by TEM. In the SEM assessment, the number and size of defects on the dural surface on images (200 µm × 300 µm) at low magnification (× 2680) were evaluated. A total of 12 images (two per mouse) were evaluated for this assessment. The days from surgery to paraplegia were compared between each of the tumor groups using the Kruskal-Wallis test. The scores of intradural tumor invasion grades and the number of defects on dural surface per SEM image were compared between irradiation group and nonirradiation group using the Mann-Whitney U test. Interobserver reliabilities of assessing intradural tumor invasion grades and the number of dural defects on the dural surface were analyzed using Fleiss'κ coefficient. P values < 0.05 were considered statistically significant. RESULTS: There was no difference in the median (range) time to paraplegia among the MMT implantation 6 weeks after nonirradiation group, the 6 weeks after irradiation group, the 12 weeks after nonirradiation group, and the 12 weeks after irradiation group (16 days [14 to 17] versus 14 days [12 to 18] versus 16 days [14 to 17] versus 14 days [12 to 15]; χ2 = 4.7; p = 0.19). There was also no difference in the intradural invasion score between the MMT implantation 6 weeks after irradiation group and the 6 weeks after nonirradiation group (8 of 10 Grade 0 and 2 of 10 Grade 1 versus 10 of 10 Grade 0; p = 0.17). On the other hand, there was a higher intradural invasion score in the MMT implantation 12 weeks after irradiation group than the 12 weeks after nonirradiation group (5 of 10 Grade 0, 3 of 10 Grade 1 and 2 of 10 Grade 2 versus 10 of 10 Grade 0; p = 0.02). Interobserver reliability of assessing intradural tumor invasion grades in the MMT-implanted group was 0.94. There was no difference in the median (range) time to paraplegia among in the LM8 implantation 6 weeks after nonirradiation group, the 6 weeks after irradiation group, the 12 weeks after nonirradiation group, and the 12 weeks after irradiation group (12 days [9 to 13] versus 10 days [8 to 13] versus 11 days [8 to 13] versus 9 days [6 to 12]; χ2 = 2.4; p = 0.50). There was also no difference in the intradural invasion score between the LM8 implantation 6 weeks after irradiation group and the 6 weeks after nonirradiation group (7 of 10 Grade 0, 1 of 10 Grade 1 and 2 of 10 Grade 2 versus 8 of 10 Grade 0 and 2 of 10 Grade 1; p = 0.51), whereas there was a higher intradural invasion score in the LM8 implantation 12 weeks after irradiation group than the 12 weeks after nonirradiation group (3 of 10 Grade 0, 3 of 10 Grade 1 and 4 of 10 Grade 2 versus 8 of 10 Grade 0 and 2 of 10 Grade 1; p = 0.04). Interobserver reliability of assessing intradural tumor invasion grades in the LM8-implanted group was 0.93. In the microstructural analysis of the dura mater using SEM, irradiated mice had small defects on the dural surface at low magnification and degeneration of collagen fibers at high magnification. The median (range) number of defects on the dural surface per image in the irradiated mice was larger than that of nonirradiated mice (2 [1 to 3] versus 0; difference of medians, 2/image; p = 0.002) and the median size of defects was 60 µm (30 to 80). Interobserver reliability of assessing number of defects on the dural surface was 1.00. TEM revealed that nonirradiated mice demonstrated well-organized, multilayer structures, while irradiated mice demonstrated irregularly layered structures at low magnification. At high magnification, well-ordered cross-sections of collagen fibers were observed in the nonirradiated mice. However, disordered alignment of collagen fibers was observed in irradiated mice. CONCLUSION: Intradural tumor invasion and disruptions of the dural microstructure were observed in the meninges of mice after irradiation, indicating radiation-induced disruption of the meningeal barrier. CLINICAL RELEVANCE: We conclude that in this form of delivery, radiation is associated with disruption of the dural meningeal barrier, indicating a need to consider methods to avoid or limit Postradiation tumor relapse and spinal cord compression when treating spinal metastases so that patients do not experience intradural tumor invasion. Surgeons should be aware of the potential for intradural tumor invasion when they perform post-irradiation spinal surgery to minimize the risks for intraoperative dural injury and spinal cord injury. Further research in patients with irradiated spinal metastases is necessary to confirm that the same findings are observed in humans and to seek irradiation methods that prevent or minimize the disruption of meningeal barrier function.