A new era in the management of spinal metastasis.

Despite the recent advances in cancer treatment, the incidence of patients with spinal metastases continues to grow along with the total number of cancer patients. Spinal metastases can significantly impair activities of daily living (ADL) and quality of life (QOL), compared with other types of bone metastases, as they are characterized with severe pain and paralysis caused by skeletal-related events. Reduced ADL can also lead to treatment limitations as certain anticancer agents and radiation therapy are not compatible treatments; thus, leading to a shorter life expectancy. Consequently, maintaining ADLs in patients with spinal metastases is paramount, and spine surgeons have an integral role to play in this regard. However, neurosurgeon, orthopedic and spinal surgeons in Japan do not have a proactive treatment approach to spinal metastases, which may prevent them from providing appropriate treatment when needed (clinical inertia). To overcome such endemic inertia, it is essential for 1) spine surgeons to understand and be more actively involved with patients with musculoskeletal disorders (cancer locomo) and cancer patients; 2) the adoption of a multidisciplinary approach (coordination and meetings not only with the attending oncologist but also with spine surgeons, radiologists, rehabilitation specialists, and other professionals) to preemptive treatment such as medication, radiotherapy, and surgical treatment; and 3) the integration of the latest findings associated with minimally invasive spinal treatments that have expanded the indications for treatment of spinal metastases and improved treatment outcomes. This heralds a new era in the management of spinal metastases.

Analyzing lumbar vertebral shape and alignment in female patients with degenerative spondylolisthesis: Comparisons with spinal stenosis and risk factor exploration.

PURPOSE: This study aimed to examine the vertebral body shape characteristics and spondylopelvic alignment in L4 degenerative spondylolisthesis (DS) as well as the risk factors for the development of DS. METHODS: This cross-sectional study compared vertebral morphology and sagittal spinopelvic alignment in female patients with lumbar DS and lumbar spinal stenosis (LSS). The degree of lumbar lordosis (LL), pelvic incidence (PI), cross-sectional area (CSA), and vertebral body height ratio (ha/hp) of the lumbar spine were compared using full-length spine radiographs and computed tomography in 60 females with DS and in 60 women with LSS. RESULTS: No significant differences in age or body mass index were observed between the two groups; however, the DS and LSS groups significantly differed in PI (mean, 58.9±10.8 vs. 47.2±11.6, P < 0.001), L4 CSA (mean, 1,166.2 m2 vs. 1,242.0 m2, P = 0.002) and ha/hp (mean, 1.134 vs. 1.007, P < 0.001). The L4 ha/hp was significantly higher in the DS group than in the LSS group. Additionally, LL values were negatively correlated with vertebral L5 CSA in the DS group (r = -0.28, P < 0.05). The LSS and DS groups demonstrated positive correlations between LL and L2, L3, and L4 ha/hp (r = 0.331, 0.267, and 0.317; P < 0.01, < 0.05, and < 0.05, respectively) and between LL and L4 and L5 ha/hp (r = 0.333, 0.331; P < 0.01, respectively). Multivariate regression analyses revealed that PI and ha/hp ratio may be independent predictors of DS development. CONCLUSION: The DS group had significantly larger LL, PI, and L4 ha/hp and smaller L4 CSA than the LSS group. The lumbar vertebral body shape and sagittal spinopelvic alignment in females might be independent predictors of DS development.

Perioperative Cerebrovascular Accidents in Spine Surgery: A Retrospective Descriptive Study and A Systematic Review with Meta-Analysis.

Introduction: Perioperative cerebrovascular accidents (CVAs) related to spine surgery, although rare, can lead to significant disabilities. More studies on spine surgeries are required to identify those at risk of perioperative CVAs. The characteristics and outcomes of patients that experienced CVAs during spine surgery were assessed through a retrospective descriptive study and meta-analysis. Methods: Patients aged ≥18 years who underwent spine surgery under general anesthesia at a hospital between April 2011 and March 2023 were examined. Of the 2,391 initially identified patients, 2,346 were included after excluding 45 who underwent debridement for surgical site infections. Subsequently, a meta-analysis including the present retrospective descriptive study was conducted. Databases such as PubMed and Google Scholar were searched for original peer-reviewed articles written in English. Results: Of the 2,346 patients, 4 (0.17%) (three men, one woman) exhibited perioperative CVAs associated with spine surgery. The CVAs were diverse in nature: one case of cerebral hemorrhage resulting from dural injury during posterior occipitocervical fusion, two cases of cerebral infarctions after lumbar laminectomy and anterior thoracic fusion due to anticoagulant discontinuation, and one case of posterior reversible encephalopathy syndrome following microscopic lumbar discectomy due to gestational hypertension. The subsequent meta-analysis included three studies (n=186,860). It showed several risk factors for perioperative CVAs, including cervical level (pooled odds ratio [OR]=1.33), hypertension (pooled OR=2.27), atrial fibrillation (pooled OR=8.78), history of heart disease (pooled OR=2.47), and diabetes (pooled OR=2.13). Conclusions: It was speculated that the potential risk factors for the four perioperative CVA cases of spine surgery in this retrospective descriptive study were intraoperative dural injury, preoperative anticoagulant discontinuation, and gestational hypertension history. The meta-analysis revealed that cervical spine surgery, hypertension, atrial fibrillation, heart disease, and diabetes increased the CVA risk. This highlights the need for risk assessment, preoperative optimization, and postoperative care to reduce spine surgery-associated perioperative CVAs.

Establishment and characterization of two novel patient-derived cell lines from giant cell tumor of bone: NCC-GCTB8-C1 and NCC-GCTB9-C1.

Giant cell tumor of bone (GCTB) is a rare osteolytic bone tumor consisting of mononuclear stromal cells, macrophages, and osteoclast-like giant cells. Although GCTB predominantly exhibits benign behavior, the tumor carries a significant risk of high local recurrence. Furthermore, GCTB can occasionally undergo malignant transformation and distal metastasis, making it potentially fatal. The standard treatment is complete surgical resection; nonetheless, an optimal treatment strategy for advanced GCTB remains unestablished, necessitating expanded preclinical research to identify appropriate therapeutic options. However, only one GCTB cell line is publicly available from a cell bank for research use worldwide. The present study reports the establishment of two novel cell lines, NCC-GCTB8-C1 and NCC-GCTB9-C1, derived from the primary tumor tissues of two patients with GCTB. Both cell lines maintained the hallmark mutation in the H3-3A gene, which is associated with tumor formation and development in GCTB. Characterization of these cell lines revealed their steady growth, spheroid-formation capability, and invasive traits. Potential therapeutic agents were identified via extensive drug screening of the two cell lines and seven previously established GCTB cell lines. Among the 214 antitumor agents tested, romidepsin, a histone deacetylase inhibitor, and mitoxantrone, a topoisomerase inhibitor, were identified as potential therapeutic agents against GCTB. Conclusively, the establishment of NCC-GCTB8-C1 and NCC-GCTB9-C1 provides novel and crucial resources that are expected to advance GCTB research and potentially revolutionize treatment strategies.

Establishment and characterization of NCC-ASPS2-C1: a novel patient-derived cell line of alveolar soft part sarcoma.

Alveolar soft part sarcoma (ASPS) is a rare mesenchymal tumor characterized by rearrangement of the ASPSCR1 and TFE3 genes and a histologically distinctive pseudoalveolar pattern. ASPS progresses slowly, but is prone to late metastasis. As ASPS is refractory to conventional chemotherapy, the only curative treatment is complete surgical resection. The prognosis of advanced and metastatic cases is poor, highlighting the need for preclinical research to develop appropriate treatment options. However, ASPS is extremely rare, accounting for < 1% of all soft tissue sarcomas, and only one patient-derived ASPS cell line is available from public cell banks worldwide for research. This study reports the establishment of a novel ASPS cell line derived from the primary tumor tissue of an ASPS patient, named NCC-ASPS2-C1. This cell line retains the ASPSCR1-TFE3 fusion gene, which is characteristic of ASPS. The characterization of this cell line revealed stable growth, spheroid formation, and invasive properties. By screening a drug library using NCC-ASPS2-C1, we identified several drugs that inhibited the proliferation of ASPS cells. In conclusion, the establishment of NCC-ASPS2-C1 provides a valuable resource for advancing ASPS research and developing novel treatments for this challenging disease.

A view on the skin-bone axis: unraveling similarities and potential of crosstalk.

The phrase "skin as a mirror of internal medicine," which means that the skin reflects many of the diseases of the internal organs, is a well-known notion. Despite the phenotypic differences between the soft skin and hard bone, the skin and bone are highly associated. Skin and bone consist of fibroblasts and osteoblasts, respectively, which secrete collagen and are involved in synthesis, while Langerhans cells and osteoclasts control turnover. Moreover, the quality and quantity of collagen in the skin and bone may be modified by aging, inflammation, estrogen, diabetes, and glucocorticoids. Skin and bone collagen are pathologically modified by aging, drugs, and metabolic diseases, such as diabetes. The structural similarities between the skin and bone and the crosstalk controlling their mutual pathological effects have led to the advocacy of the skin-bone axis. Thus, the skin may mirror the health of the bones and conversely, the condition of the skin may be reflected in the bones. From the perspective of the skin-bone axis, the similarities between skin and bone anatomy, function, and pathology, as well as the crosstalk between the two, are discussed in this review. A thorough elucidation of the pathways governing the skin-bone axis crosstalk would enhance our understanding of disease pathophysiology, facilitating the development of new diagnostics and therapies for skin collagen-induced bone disease and of new osteoporosis diagnostics and therapies that enhance skin collagen to increase bone quality and density.

Establishment and characterization of NCC-DFSP5-C1: a novel patient-derived dermatofibrosarcoma protuberans cell line.

Dermatofibrosarcoma protuberans (DFSP) is the most prevalent dermal sarcoma, characterized by the presence of the fusion of the collagen type I alpha 1 (COL1A1) gene with the platelet-derived growth factor beta chain (PDGFB) gene. Although PDGF receptor inhibitor imatinib mesylate was approved for the treating patients with unresectable or metastatic DFSP, disease progression was shown in 9.2% of the patients. Therefore, developing novel therapeutic strategies is crucial for improving the prognosis of DFSP. Patient-derived cell lines play a vital role in preclinical studies; however, only a limited number of DFSP cell lines are currently available in public cell banks. Here, we successfully established a novel DFSP cell line (NCC-DFSP5-C1) using surgically resected tumor tissue from a patient with DFSP. NCC-DFSP5-C1 cells were confirmed to carry the COL1A1-PDGFB translocation and maintain the same mutation as the original tumor tissue. They exhibited consistent growth, formed spheroids, and were invasive. By screening a drug library using NCC-DFSP5-C1 and four previously established DFSP cell lines, we identified anti-cancer drugs that inhibit DFSP cell proliferation. Our observations suggest that the NCC-DFSP5-C1 cell line holds promise as a valuable tool for conducting fundamental and preclinical studies for DFSP.

Insights and preventive approaches of rod erosion in the occipital bone after complex posterior cervical spine surgery for destructive spondyloarthropathy: A case report.

RATIONALE: Complications of rod migration into the occipital bone after upper cervical fusion are very rare. No other cases have been reported, especially when associated with destructive spondyloarthropathy (DSA). The purpose of this case report is to remind clinicians of the risk of rod migration in cervical spine surgery in patients with DSA and to provide information on its causes, countermeasures, and treatment. PATIENT CONCERN: This case report presents the clinical course of a 61-year-old female patient with chronic kidney disease that required hemodialysis. DIAGNOSIS, INTERVENTION, OUTCOMES: The patient was diagnosed DSA involving the cervical spine. Initial treatment involved a halo vest, followed by anterior cervical corpectomy and fusion spanning from C5 to Th1. However, subsequent complications, including C5 fractures, kyphotic cervical alignment, and rod migration into the occipital bone, lead to multistage surgical interventions. This case highlights the challenges in managing DSA, the significance of optimal fixation strategies, and the importance of accounting for potential alignment changes. CONCLUSION: The effective management of occipital bone erosion after posterior cervical spine surgery for destructive spondyloarthropathy necessitates meticulous fixation planning, proactive rod length adjustment, preoperative assessment of the occipital position, and consideration of the compensatory upper cervical range of motion to prevent migration-related issues.

The first case of methotrexate-associated lymphoproliferative disorder in the sacrum: a case report.

Methotrexate (MTX) is a drug used for treating rheumatoid arthritis. Recently, the reported incidence of methotrexate-associated lymphoproliferative disease (MTX-LPD) has increased, especially in Japan. Extranodal involvement is observed in half of MTX-LPD cases. However, only a few spinal lesions have been reported, with none in the sacrum. Additionally, Epstein-Barr virus (EBV) infection has also been implicated in the pathogenesis of MTX-LPD. Herein, we describe the case of a 74-year-old woman with MTX-LPD in the sacral spine who complained of severe back pain and nocturnal pain. Radiographs revealed a tumour on the right wing of the sacrum and a positive EBV immunoglobulin G antibody titre. MTX-LPD was suspected based on imaging findings and a history of MTX administration. A pathological examination was performed on the CT-guided biopsy specimen. The histopathological diagnosis was MTX-LPD, and MTX was discontinued. Three months after MTX administration ended, the tumour tended to shrink, and 1 year later, significant tumour shrinkage was observed. This experience suggests that MTX-LPD can be treated by discontinuing MTX administration. Therefore, early and accurate diagnosis is required, as is avoiding unnecessary treatment such as surgery. MTX-LPD should be considered, especially in spinal origin tumours in EBV-infected patients on MTX.

Gender Diversity of the Japanese Society for Spine Surgery and Related Research Annual Meetings from 2013 to 2022.

Introduction: There are no reports that have examined the annual trends of the percentage of women who are members of the Japanese Society for Spine Surgery and Related Research (JSSR) or their roles at annual meetings. Furthermore, the status of gender diversity in the JSSR remains unclear. This study aims to identify gender diversity in the JSSR by quantifying the role of women at annual meetings over the past decade. Methods: We performed a retrospective review to explore gender role in the JSSR annual meeting by examining the meeting programs for 2013-2022. The gender ratios were surveyed each year for the following: (1) first authors of general application abstracts (oral and poster), (2) meeting guest speakers, (3) meeting moderators, and (4) program editors of the abstracts. We also investigated the availability of gender equality symposiums. Results: The percentage of women applying (1.1%-2.1%) and those who were invited as participants [guest speaker (0%-0.9%), moderator (0%-5.8%), and program editor (0%-0.6%)] at the annual JSSR meetings was low, with no significant increase over the past decade. In addition, there has never been a symposium promoting gender equality at the annual JSSR meeting. Conclusions: Our findings suggest that a strong and active role for institutional leaders and senior members to support the scholarly activities of women spine surgeons is important for adopting gender diversity in the JSSR academia. The absence of gender equality symposiums and the few invited women participants at the JSSR annual meeting may be due to a lack of gender diversity awareness among conference organizers or unconscious gender bias. Monitoring the role of women in the JSSR annual meetings may solve the gender diversity problem.

Sagittal-spinopelvic alignment improves in patients with bilateral highly dislocated hip (Crowe type IV) after subtrochanteric shortening total hip arthroplasty: A retrospective radiographic study.

In patients with bilateral highly dislocated hips (HDHs), total hip arthroplasty with subtrochanteric shortening osteotomy (S-THA) is a viable option for achieving adequate reconstruction with restoration of the anatomical hip center. This procedure has the potential to improve sagittal spinopelvic alignment (SSPA). However, reports are scarce owing to the rarity of this disease. The objective of this study is to investigate pre- and post-operative SSPA in patients with HDHs who had undergone S-THA. This retrospective radiographic study included 55 patients (54 females and 1 male; average age, 63.1 ±â€…6.9 years) who underwent S-THA. Lateral spine radiographs in the standing position were obtained pre- and post-operatively. The SSPA included lumbar lordosis (LL), sacral slope (SS), pelvic incidence (PI), and intervertebral disc (ID) angle of L1/2-L5/S. The SSPA pre- and post-S-THA was compared using a paired t test. Pearson correlation coefficient was used to assess the relationships between parameters. The mean pre- and post-operative LL and SS values were 62° and 49° (LL) and 50° and 39° (SS), respectively (P < .001). The ID angle was significantly reduced post-operatively at all levels (P < .001). The correlation coefficients between preoperative LL and SS and postoperative LL and PI were 0.81 and 0.38, respectively (P < .01). The preoperative SSPA of Crowe type IV HDHs revealed excessive pelvic anteversion and lumbar hyperlordosis, with a high correlation between LL and SS, suggesting that these alterations were compensatory changes to maintain body balance. Furthermore, in patients with HDHs and residual spinal flexibility, restoring the original pelvic morphology with S-THA may contribute to improved SSPA.

Mechanisms of tissue degeneration mediated by periostin in spinal degenerative diseases and their implications for pathology and diagnosis: a review.

Periostin (POSTN) serves a dual role as both a matricellular protein and an extracellular matrix (ECM) protein and is widely expressed in various tissues and cells. As an ECM protein, POSTN binds to integrin receptors, transduces signals to cells, enabling cell activation. POSTN has been linked with various diseases, including atopic dermatitis, asthma, and the progression of multiple cancers. Recently, its association with orthopedic diseases, such as osteoporosis, osteoarthritis resulting from cartilage destruction, degenerative diseases of the intervertebral disks, and ligament degenerative diseases, has also become apparent. Furthermore, POSTN has been shown to be a valuable biomarker for understanding the pathophysiology of orthopedic diseases. In addition to serum POSTN, synovial fluid POSTN in joints has been reported to be useful as a biomarker. Risk factors for spinal degenerative diseases include aging, mechanical stress, trauma, genetic predisposition, obesity, and metabolic syndrome, but the cause of spinal degenerative diseases (SDDs) remains unclear. Studies on the pathophysiological effects of POSTN may significantly contribute toward the diagnosis and treatment of spinal degenerative diseases. Therefore, in this review, we aim to examine the mechanisms of tissue degeneration caused by mechanical and inflammatory stresses in the bones, cartilage, intervertebral disks, and ligaments, which are crucial components of the spine, with a focus on POSTN.

Pediatric chance fracture with seatbelt syndrome: A case report.

Key Clinical Message: Prompt recognition and accurate diagnosis of seatbelt-related injuries such as Chance fractures are crucial for pediatric patients. Clinicians should be aware of the unique characteristics of children, including the presence of growth plates, and use advanced imaging techniques such as magnetic resonance imaging to guide appropriate treatment and minimize complications. Abstract: Seatbelt-related injuries, known as the "seatbelt syndrome," encompass various injuries resulting from automobile accidents, including vertebral fractures, abdominal injuries, and great vessel traumas. Seatbelt signs include bruising or peeling of the anterior chest or abdominal wall, indicating abdominal pressure against the seatbelt. Chance fractures are a type of vertebral fracture characterized by fracture lines through multiple vertebral structures and are often associated with seatbelt injuries in adults. However, the unique features of Chance fractures in pediatric patients, such as the presence of growth plates, require a comprehensive diagnostic approach using advanced imaging techniques, including magnetic resonance imaging (MRI). This case report highlights the complexity of seatbelt-related injuries in children and emphasizes the importance of accurate diagnosis and multidisciplinary management. Understanding these factors can improve clinical knowledge and outcomes in children with seatbelt-related injuries.

Establishment and characterization of NCC-DFSP4-C1: a novel cell line from a patient with dermatofibrosarcoma protuberans having the fibrosarcomatous transformation.

Dermatofibrosarcoma protuberans (DFSP) is a superficial low-grade sarcoma, genetically characterized by a fusion gene in collagen type I α (COL1A1) gene and platelet-derived growth factor subunit ß (PDGFB). DFSP is locally aggressive and does not typically metastasize. However, DFSP with fibrosarcomatous transformation, which occurs in 7-16% of DFSP cases, demonstrates a poor prognosis than classic DFSP with a higher local recurrence rate and metastatic potential. Although imatinib, a PDGF receptor inhibitor, is a potent therapeutic agent for classic DFSP, it is less effective for DFSP with fibrosarcomatous transformation. The development of definitive chemotherapies for DFSP with fibrosarcomatous transformation is required. Patient-derived tumor cell lines are indispensable tools for preclinical research to discover novel therapeutic agents. However, only seven cell lines were derived from DFSP, out of which only two were established from DFSP with fibrosarcomatous transformation. Hence, in the present study, we established a novel DFSP cell line, NCC-DFSP4-C1, from a surgically resected DFSP tumor specimen with fibrosarcomatous transformation. NCC-DFSP4-C1 harbored an identical COL1A1-PDGFB fusion gene as its donor tumor. NCC-DFSP4-C1 cells retained the morphology of their donor tumor and demonstrated constant proliferation, spheroid formation, and invasion capability in vitro. By screening a drug library, we found that bortezomib and romidepsin demonstrated the strongest suppressive effects on the proliferation of NCC-DFSP4-C1 cells. In conclusion, we report a novel cell line of DFSP with fibrosarcomatous transformation, and demonstrate its utility in the development of novel therapeutic agents for DFSP.

A vessel sealing system can help reduce the risk of postoperative complications after tumour resection in the medial thigh.

Aims: The risk of postoperative complications after resection of soft-tissue sarcoma in the medial thigh is higher than in other locations. This study investigated whether a vessel sealing system (VSS) could help reduce the risk of postoperative complications after wide resection of soft-tissue sarcoma in the medial thigh. Methods: Of 285 patients who underwent wide resection for soft-tissue sarcoma between 2014 and 2021 at our institution, 78 patients with tumours in the medial thigh were extracted from our database. Information on clinicopathological characteristics, preoperative treatment, surgical treatment (use of VSS, blood loss volume, operating time), and postoperative course (complications, postoperative haemoglobin changes, total drainage volume, and drainage and hospitalization durations) were obtained from medical records. We statistically compared clinical outcomes between patients whose surgery did or did not use VSS (VSS and non-VSS groups, respectively). Results: There were 24 patients in the VSS group and 54 in the non-VSS group. There were no significant differences between the two groups in terms of clinicopathological background. The total drainage volume in the VSS group was significantly less than that in the non-VSS group (1,176 ml vs 3,114 ml; p = 0.018). Moreover, the drainage and hospitalization durations were significantly shorter in the VSS group compared to the non-VSS group (p = 0.017 and p = 0.024, respectively). Conclusion: Our results suggest that use of VSS can help reduce the risk of postoperative complications after wide resection of soft-tissue sarcoma in the medial thigh.

Establishment and characterization of two novel patient-derived cell lines from giant cell tumor of bone.

Giant cell tumor of bone (GCTB) is a rare bone tumor with osteolytic features, composed of stromal cells with a monotonous appearance, macrophages, and osteoclast-like giant cells. GCTB is commonly associated with a pathogenic mutation in the H3-3A gene. While complete surgical resection is the standard cure for GCTB, it often results in local recurrence and, rarely, metastasis. Thus, an effective multidisciplinary treatment approach is necessary. Although patient-derived cell lines is an essential tool for investigating novel treatment strategies, there are only four GCTB cell lines available in public cell banks. Therefore, this study aimed to establish novel GCTB cell lines and successfully created NCC-GCTB6-C1 and NCC-GCTB7-C1 cell lines from two patients' surgically removed tumor tissues. These cell lines exhibited H3-3A gene mutations, consistent proliferation, and invasive properties. After characterizing their behaviors, we performed high-throughput screening of 214 anti-cancer drugs for NCC-GCTB6-C1 and NCC-GCTB7-C1 and integrated their screening data with those of NCC-GCTB1-C1, NCC-GCTB2-C1, NCC-GCTB3-C1, NCC-GCTB4-C1, and NCC-GCTB5-C1 that we previously established. We identified histone deacetylase inhibitor romidepsin as a possible treatment for GCTB. These findings suggest that NCC-GCTB6-C1 and NCC-GCTB7-C1 could be valuable tools for preclinical and basic research on GCTB.