Evaluation of Conditions for the Development of Cryogenic Spinal Cord Injury Using a Canine Model: An Experimental Study on the Safety of Cryoablation for Metastatic Spinal Tumors.

BACKGROUND AND PURPOSE: Although the application of cryoablation to metastatic spinal tumors has been attempted, spinal cryoablation has the unique complication of cryogenic spinal cord injury. This study aimed to elucidate the conditions for the development of cryogenic spinal cord injury. MATERIALS AND METHODS: Fifteen canines were used in this study. A metal probe was inserted into the 13th thoracic vertebral body. Cryoablation was performed for 10 minutes by freezing the probe in liquid nitrogen. The control canine underwent probe insertion only. Spinal cord monitoring, epidural temperature measurement, motor function assessment, and pathologic examination of the spinal cord were performed. RESULTS: During the 10 minutes of cryoablation, the epidural temperature decreased and reached the lowest epidural temperature (LET) at the end of cryoablation. The LETs (degrees celsius [°C]) of each canine were -37, -30, -27, -8, -3, -2, 0, 1, 4, 8, 16, 18, 20, and 25, respectively. As the epidural temperature decreased, waveform amplitudes also decreased. At the end of cryoablation (10 minutes after the start of cryoablation), abnormal waves were observed in 92.9% (13/14) of canines. With epidural rewarming, the amplitude of the waveforms tended to recover. After epidural rewarming (2 hours after the start of cryoablation), abnormal waves were observed in 28.6% (4/14) of canines. The LETs (°C) of the canines with abnormal waves after epidural rewarming were -37, -30, -27, and -8. None of the canines with normal waves after epidural rewarming had any motor impairment. In contrast, all canines with remaining abnormal waves after epidural rewarming had motor impairment. In the pathologic assessment, cryogenic changes were found in canines with LETs (°C) of -37 -30, -27, -8, 0, and 1. CONCLUSIONS: This study showed that 10-minute spinal cryoablation with LETs (°C) of -37, -30, -27, -8, 0, and 1 caused cryogenic spinal cord injury. There was no evidence of cryogenic spinal cord injury in canines with LET of ≥4°C. The epidural temperature threshold for cryogenic spinal cord injury is between 1 and 4°C, suggesting that the epidural temperature should be maintained above at least 4°C to prevent cryogenic spinal cord injury.

Characteristics of Scoliosis in Mice Induced by Chondrocyte-specific Inactivation of L-type Amino Acid Transporter 1.

STUDY DESIGN: A mouse study of the Slc7a5 gene using conditional knockout to assess the effects of its inactivation on spinal deformity. OBJECTIVES: This study aimed to investigate whether the mice with scoliosis [induced by chondrocyte-specific inactivation of L-type amino acid transporter 1 (LAT1)] show a developmental process similar to that of pediatric scoliosis and to examine the relationship between reduced bone mineral density (BMD) and scoliosis. Furthermore, we aimed to obtain insights into elucidating the etiology and pathophysiology of scoliosis. SUMMARY OF BACKGROUND DATA: The etiology and pathogenesis of scoliosis are not fully understood despite substantial investigative efforts. LAT1 is an amino acid transporter that mediates the cellular uptake of large neutral amino acids. A recent study revealed that chondrocyte-specific inactivation of LAT1 in mice results in scoliosis (Col2a1-Cre;Slc7a5fl/fl mice: "Sko mice"). MATERIALS AND METHODS: Body length, body weight, Cobb angle, vertebral body rotation angle, and BMD at 1, 2, 4, 6, and 8 weeks of age were examined and statistically compared with those of normal control mice. Pathologic and morphologic evaluation was performed on specimens from 10-week-old euthanized mice. RESULTS: The Sko mice developed thoracic scoliosis in infancy without congenital malformations. This spinal deformity progressed rapidly during growth, with diverse curve patterns and hypoplastic vertebral bodies. Pathologic examination revealed thickening of the growth plates and decreased osteoblasts, suggesting that impaired endochondral ossification was the cause of the scoliosis. Sko mice were also observed to have decreased BMD and degraded bone microstructure. Reduced BMD and bone quality may not be the causes of the onset and progression of scoliosis in the Sko mice. CONCLUSIONS: In Sko mice, the characteristics of scoliosis and vertebral pathology showed many similarities with syndromic scoliosis in humans. Endochondral ossification defects may impair growth, leading to scoliosis and decreased BMD.

A Modified Spinal Reconstruction Method Reduces Instrumentation Failure in Total En Bloc Spondylectomy for Spinal Tumors.

Introduction: Long-term spinal stability after total en bloc spondylectomy (TES) is challenging. The aim of this study was to examine whether the new method could reduce the incidence of instrumentation failure (IF). Methods: We retrospectively compared 116 patients with spinal tumors who underwent TES between 2010 and 2019 and were followed up for >1 year. IF, cage subsidence, and complications were evaluated. Propensity score matching between conventional and new method groups was performed for age, sex, body mass index, preoperative radiotherapy, number of resected vertebrae, number of instrumented vertebrae, tumor level, and follow-up period. There were 25 cases each in the conventional and new method groups. The conventional method used a titanium mesh cage for anterior reconstruction and 5.5-mm-diameter titanium alloy rods for posterior fixation. The new method used a more robust cage for anterior reconstruction, bone grafting was performed around the cage, and 6.0-mm-diameter cobalt chromium rods were used for posterior fixation. We compared the incidence of IF and cage subsidence after TES between the conventional and new method groups. Results: While 5 out of 25 patients (20.0%) in the conventional method group experienced IF, none from the new method group experienced IF. Three-year implant survival rates were 87.3% in the conventional and 100% in the new method groups. The new method group had a significantly higher implant survival rate (p<0.01). Cage subsidence was observed in 11 of 25 (44/0%) patients in the conventional method and 1 of 25 (4.0%; significantly lower, p<0.05) in the new method group. Conclusions: The new reconstruction method significantly reduced IF incidence in patients with TES.

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.

Anatomical Characteristics and Variations of Thoracic Segmental Arteries With 3-Dimensional CT Analysis.

STUDY DESIGN: Observational study using retrospective contrast-enhanced computed tomography (CT) analysis. OBJECTIVE: This study aimed to investigate the anatomical characteristics and variations of the thoracic segmental arteries. SUMMARY OF BACKGROUND DATA: Few cadaver studies of segmental arteries to the thoracic spine have been reported; however, no previous studies have reported the use of contrast-enhanced CT in the upper to middle thoracic spine. Detailed anatomical information of the thoracic segmental arteries is essential to avoid vascular injuries in thoracic spine surgery, such as in the anterior and posterior approaches and minimally invasive surgery. MATERIALS AND METHODS: Patients who underwent CT angiography of the thoracic spine between 2012 and 2021 were retrospectively analyzed. The pathways of the thoracic segmental arteries were reviewed. Anatomical differences depending on the vertebral level and right/left segmental arteries were investigated. RESULTS: Thirty-one patients (15 men and 16 women; mean age 55.8 yr) with 591 segmental arteries were surveyed. The distribution of segmental arteries differed depending on the vertebral level, which ran more longitudinally in the upper thoracic region and transversely in the lower thoracic region. Common trunks were frequently observed in the segmental arteries of T3-5. Segmental arteries frequently crossed the disks in the right anterior and left middle areas of the thoracic spine, whereas in the T4/5 disks, segmental arteries crossed the disks over a wide area. The presence of multiple segmental arteries within a single vertebra was higher at the T5-7 vertebral level. CONCLUSION: The distribution of the segmental arteries was asymmetrical and varied depending on the vertebral level. In the upper to middle thoracic, segmental arteries ran at every position of the vertebral body due to their longitudinal nature and the presence of multiple segmental arteries within a single vertebra, especially in T5-7. The results of this study provide critical information for thoracic spine surgery.

Tumor-Specific Immunoenhancing Effects after Local Cryoablation for Metastatic Bone Tumor in a Mouse Model.

We investigated the abscopal effect after cryoablation (CA) on bone metastasis using a mouse model. Breast cancer cells were implanted in the bilateral tibiae of mice. The left tumor was treated locally with CA, and the right abscopal tumor (AT) was left untreated. The mice were divided into four groups based on the combination of CA and intraperitoneal administration of anti-PD-1 antibody (PD) as treatment interventions (Control, CA, PD, and CA + PD). The reduction ratio of the size of AT, the quantitative immune effects at enzyme-linked immunospot (ELISPOT) assay, and the intensity of infiltration of immune-related cells to AT were compared among the groups. CA alone showed a significant immunoenhancing effect on the volume change ratio of AT from day 0 to day 14 (Control-CA: p < 0.05), ELISPOT assay (Control-CA: p < 0.01), and CD4+ cell count in immunostaining (Control-CA: p < 0.05). CA alone showed no significant immunoenhancing effect on CD8+ and Foxp3+ cell counts in immunostaining, but the combination of CA and PD showed a significant immunoenhancing effect (Control-CA + PD: p < 0.01 [CD8, Foxp3]). The results suggested that the abscopal effect associated with the local cryotherapy of metastatic bone tumors was activated by CA and enhanced by its combination with PD.

Associations between Abdominal Trunk Muscle Weakness and Future Osteoporotic Vertebral Fracture in Middle-Aged and Older Adult Women: A Three-Year Prospective Longitudinal Cohort Study.

Potential risk factors associated with future osteoporotic vertebral fracture (OVF) were prospectively investigated in middle-aged and older adult women. We enrolled 197 female patients aged ≥50 years who were scheduled to undergo surgery for lower-extremity degenerative diseases. Patient anthropometric and muscle strength measurements, a bone mineral density measurement of the lumbar spine (L-BMD), and full-spine standing radiographs to examine the presence of old OVFs and spinopelvic sagittal parameters were obtained preoperatively. We evaluated 141 patients who underwent full-spine standing radiographs three years postoperatively to identify new OVFs. We excluded 54 patients who did not undergo a second radiographic examination and 2 with new traumatic OVFs. Univariate and multivariate analyses were performed to identify risk factors associated with new non-traumatic OVF occurrence. Ten (7.1%) patients developed new non-traumatic OVFs during the study period (fracture group). The fracture group had less abdominal trunk muscle strength, lower L-BMD, smaller sacral slopes, and larger pelvic tilt than the non-fracture group. The fracture group showed a higher prevalence of old OVFs preoperatively than the non-fracture group. Abdominal trunk muscle weakness, low L-BMD, and the presence of old OVFs were identified as significant risk factors for OVF occurrence. In middle-aged or older adult women, abdominal trunk muscle weakness, low L-BMD, and old OVFs were associated with future OVF.

Medium to Long-Term Clinical Outcomes of Spinal Metastasectomy.

The prolonged survival of metastatic cancer patients highlights the importance of the local control of spinal metastases, which reduce patient performance status. This retrospective study examined the medium to long-term outcomes of spinal metastasectomy by evaluating 124 patients who underwent metastasectomy for isolated spinal metastases (2006-2018) with a postoperative follow-up for a minimum of 3 years. The findings present information on patient demographics (i.e., performance status, location of non-spinal metastases, and history of systemic therapy) and postoperative outcomes, including perioperative complications, disease progression of non-operated metastases, and additional excisional surgeries. Additionally, postoperative survival, local tumor control in the operated spine, and maintenance of spinal reconstruction without instrumentation failure were determined using Kaplan-Meier analyses. The primary malignancy was kidney and thyroid cancer in 51 and 14 patients, respectively, low-grade sarcoma and lung cancer in 13 patients, breast cancer in 12 patients, and other malignancies in 21 patients. The 3-year and 5-year survival rates were 70% and 60%, respectively. We found that patients with thyroid cancer had the best survival results, with local tumor recurrence and instrumentation failure at 10% and 22%, respectively. These findings suggest that for certain patients with isolated and removable spine metastases, metastasectomy can improve function and survival.

Prevalence and Risk Factors for the Development of Venous Thromboembolism After Spinal Tumor Surgery.

OBJECTIVE: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE), is a deleterious complication that can be fatal. However, the prevalence and underlying risk factors for VTE after spinal tumor surgery remain poorly defined. METHODS: Ninety-six patients undergoing spinal tumor surgery with postoperative screening for DVT and PTE were reviewed. We evaluated the relationship between postoperative VTE and the following factors: age, sex, height, weight, body mass index, location of the tumor, type of tumor (primary or metastasis), type of operation (excisional surgery or palliative surgery), surgical approach (posterior or combined), operative time, intraoperative blood loss, perioperative transfusion, amount of transfusion, duration of postoperative bed rest (<7 days or >7 days), preoperative paralysis, postoperative paralysis, and postoperative neurological worsening. RESULTS: The overall prevalence of VTE was 25.0% (24/96). The rate of DVT and PTE was 20.8% (20/96) and 6.3% (6/96), respectively. PTE only was identified in 4 of 6 PTE-positive patients, and both PTE and DVT were identified in 2. In univariate analysis, the duration of postoperative bed rest of the VTE group was significantly longer than that of the non-VTE group (P = 0.03). In multivariate analysis, only prolonged duration of postoperative bed rest was a significant independent risk factor (P = 0.036). CONCLUSIONS: The prevalence of VTE after spinal tumor surgery was 25.0%. Prolonged duration of postoperative bed rest was a risk factor for postoperative VTE. No DVT was found in 4 of 6 PTE-positive patients, suggesting that screening for PTE itself is also needed in high-risk cases of VTE.

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.

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.

Efficacy of abdominal trunk muscles-strengthening exercise using an innovative device in treating chronic low back pain: a controlled clinical trial.

Exercise is the most common conservative intervention for chronic low back pain (CLBP). We have developed an innovative exercise device for the abdominal trunk muscles that also measures muscle strength in a sitting position. The device, which is easy for patients with CLBP to use, allows for lumbar stabilization exercise under pressure. This study aimed to examine the efficacy of abdominal trunk muscle strengthening using the device in improving CLBP. We conducted a two-group non-randomized controlled clinical trial. CLBP patients were allocated into two groups. The strengthening group underwent a 12-week exercise program that included abdominal trunk muscle strengthening using our device and stretching exercises, while the control group received a 12-week stretching exercise program. The outcome measures included the improvement of the abdominal trunk muscle strength measured by the device, pain intensity of CLBP, physical function, and quality of life (QOL). A total of 40 participants (20 in each group) were analyzed. The strengthening group showed better improvement in the abdominal trunk muscle strength, CLBP, physical function, and QOL than in the control group. In conclusion, the strengthening exercise using the device with easy stretching was effective in improving the strength of the abdominal trunk muscles, pain intensity of CLBP, physical function, and QOL.

Revision surgery for instrumentation failure after total en bloc spondylectomy: a retrospective case series.

BACKGROUND: There have been several reports of instrumentation failure after three-column resections such as total en bloc spondylectomy (TES) for spinal tumors; however, clinical outcomes of revision surgery for instrumentation failure after TES are seldom reported. Therefore, this study assessed the clinical outcomes of revision surgery for instrumentation failure after TES. METHODS: This study employed a retrospective case series in a single center and included 61 patients with spinal tumors who underwent TES between 2010 and 2015 and were followed up for > 2 years. Instrumentation failure rate, back pain, neurological deterioration, ambulatory status, operation time, blood loss, complications, bone fusion after revision surgery, and re-instrumentation failure were assessed. Data were collected on back pain, neurological deterioration, ambulatory status, and management for patients with instrumentation failure, and we documented radiological bone fusion and re-instrumentation failure in cases followed up for > 2 years after revision surgery. RESULTS: Of the 61 patients, 26 (42.6%) experienced instrumentation failure at an average of 32 (range, 11-92) months after TES. Of these, 23 underwent revision surgery. The average operation time and intraoperative blood loss were 204 min and 97 ml, respectively. Including the six patients who were unable to walk after instrumentation failure, all patients were able to walk after revision surgery. Perioperative complications of reoperation were surgical site infection (n = 2) and delayed wound healing (n = 1). At the final follow-up, bone fusion was observed in all patients. No re-instrumentation failure was recorded. CONCLUSION: Bone fusion was achieved by revision surgery using the posterior approach alone.

Long-Term Outcomes of Excision Surgery for Aggressive Vertebral Hemangiomas.

OBJECTIVE: We describe the clinical outcomes in patients with aggressive vertebral hemangiomas (AVHs) after total tumor excision and discuss the treatment options for AVHs. METHODS: A retrospective data review of 15 patients (6 men, 9 women) with AVHs who underwent total excision between 1996 and 2018 was performed. RESULTS: In total, 13 thoracic and 2 lumbar lesions were involved with 8 type A-D tumors and 7 type B-D tumors based on the Weinstein-Boriani-Biagini classification. All tumors showed low or low-iso signal intensity by T1-weighted magnetic resonance imaging. All patients received a combination of preoperative transarterial embolization and total tumor excision including the tumor margins. Eleven patients underwent total tumor excision as the initial surgery (total en bloc spondylectomy = 10 patients, piecemeal total tumor excision = 1 patient), and 4 underwent it as either a revision procedure 2 weeks after ineffective laminectomy or in the long-term follow-up (4-14 years) as a piecemeal total tumor excision. Intraoperative blood loss ranged from 150 to 3400 mL (mean, 1314 mL). None of the cases had a recurrence during the mean follow-up period of 128.4 ± 88.6 months. CONCLUSIONS: Low signal intensity on T1-weighted magnetic resonance imaging was observed in all the patients with AVHs. The long-term clinical results of the preoperative transarterial embolization and total tumor excision were satisfactory. The effect of decompressive incomplete tumor excision is temporary for AVHs, and repeated tumor excision may be necessary because of tumor recurrence in the long term. Reliable total tumor excision during the initial surgery is desirable.

More Than 10-year Follow-up After Laminoplasty and Pedicle Screw Fixation for Cervical Myelopathy Associated With Athetoid Cerebral Palsy.

STUDY DESIGN: Retrospective case series. OBJECTIVE: The aim of this study was to investigate the clinical outcomes >10 years following laminoplasty and pedicle screw fixation for cervical myelopathy associated with athetoid cerebral palsy (CP). SUMMARY OF BACKGROUND DATA: Surgery for cervical myelopathy associated with CP remains a challenge because of perioperative instrumentation failure and adjacent segment problems due to patients' repetitive involuntary neck movements with deformity of the cervical spine. METHODS: A single-center series of 14 patients were reviewed. The patients comprised seven women and seven men with a mean age of 52 years at the time of surgery. The mean follow-up period was 12.5 years. The Barthel index (BI), which shows independence in activities of daily life, and Japanese Orthopaedic Association (JOA) score were assessed. Radiographic evaluation included changes of the C2-C7 angle in the sagittal plane, fusion rate, adjacent segment degeneration, and instrument failure. RESULTS: The 10-year BI and JOA score significantly improved at 36% and 31%, respectively. The preoperative Cobb angle of the sagittal plane from C2-C7 measured 11.9° of kyphosis, which improved to 0.8° of lordosis. In the radiographic analysis, 35% (proximal) and 21% (distal) of the adjacent segment showed progression in degeneration of more than one grade after 10 years. More than 90% of the patients who underwent magnetic resonance imaging showed progressive disc degeneration on either side after 10 years. Autofusion inside the disc or anterior vertebral bony bridging was observed in 86% of intervertebral levels without anterior procedures. CONCLUSION: The procedure showed favorable initial stability and maintained favorable clinical outcomes in patients with CP. More than 90% of the patients showed disc degeneration on either side. The rate of proximal adjacent segment degeneration was higher than that of distal segments with or without symptoms at the >10-year follow-up. LEVEL OF EVIDENCE: 4.

Perioperative Complications and Prognosis of Curative Surgical Resection for Spinal Metastases in Elderly Patients.

OBJECTIVE: The purpose of this study was to evaluate perioperative complications and prognosis associated with curative surgical resection, such as total en bloc spondylectomy, for spinal metastases in elderly patients. METHODS: We retrospectively reviewed 103 consecutive patients who underwent curative surgery between 2010 and 2017 and divided them into group 1 (n = 27, age <50 years), group 2 (n = 47, age ≥50 and <65 years), and group 3 (n = 29, age ≥65 years). Perioperative complication rate and overall survival (OS) after surgery was evaluated. RESULTS: A total of 129 perioperative complications were observed in 76 of 112 surgeries. Among the 3 groups, the total number of complications per person was the highest in group 3, although the difference was not statistically significant. The total number of serious complications per person was the highest in group 3, which was statistically significant. (0.23 vs. 0.51 vs. 0.90; P < 0.05). No significant difference in OS was observed between the groups. In group 3, a significant difference in OS was found between subgroups 1 (renal cell, thyroid, and breast cancer metastasis) and 2 (other primary tumors) (P < 0.01). In group 3, 24 patients (83%) either maintained or had regained their ambulatory capacity at the final follow-up. CONCLUSIONS: Elderly patients who underwent curative surgery had significantly more frequent serious postoperative complications than nonelderly patients. Even in patients with advanced age, curative surgical resection can provide favorable prognosis and local control, especially in those with spinal metastases of renal cell and thyroid cancer.