A case of spinal metastasis with osteoblastic lesion: The risk of epidural extension and paralysis.

One patient with metastatic spinal tumors from colorectal cancer experienced malignant spinal cord compression (MSCC). Determining the extent of the lesion using magnetic resonance imaging is essential, even if the lesion is osteoblastic. Therefore, it is important to evaluate the risk of MSCC in patients with metastatic spinal tumors.

Statistics of Visceral Sarcoma in Japan: Report From the Population-Based National Cancer Registry (NCR) in Japan.

BACKGROUND AND OBJECTIVES: Sarcomas developing in the visceral organs are extremely rare, with no previous reports to describe their national epidemiology. We analyzed Japanese domestic statistics for visceral sarcoma, using the National Cancer Registry (NCR) in Japan, a population-based database launched in 2016. METHODS: We identified 3245 cases of visceral sarcomas in the NCR dated 2016-2019 to analyze demographic and disease information, initial diagnostic process, volume and type of the hospitals, treatment, and prognosis. RESULTS: Visceral sarcoma shows a higher prevalence in the older generation (60+ years), with a significant male predominance (p = 0.006). Leiomyosarcomas occurred frequently in the gastrointestinal tract (N = 240; 39.5%), and angiosarcomas in the liver, gall bladder, pancreas, and spleen (N = 244; 43.9%). Visceral sarcomas were often treated in facilities of lower volume without specific adjuvant treatments (p < 0.001). The cumulative 3-year overall survival was 44.8%, and several factors such as surgery or absence of chemotherapy positively affected survival. CONCLUSIONS: This is the first nationwide study in Japan to analyze the inclusive epidemiology of visceral sarcomas. Visceral sarcomas are characterized by senior and male predominance with relatively poor prognosis, often managed in nonspecialized facilities and rarely with adjuvant therapies. Several histologic subtypes had the propensity to develop in specific organs.

Traction Spurs in the Lumbar Spine: A Historical Overview and Future Perspectives.

Numerous studies have explored the connection between lumbar osteophytes, their pathophysiology, and instability since Macnab's 1971 report on traction spurs as an indicator of lumbar instability. This study provides a narrative historical overview of traction spurs, a classic finding that suggests lumbar instability. It summarizes the causes of anterior lumbar vertebral osteophytes, the relationship between traction spurs and lumbar spinal instability, and the clinical significance of traction spurs. Vertebral osteophytes are grouped into two categories, namely, traction spurs or claw spurs, which represent different stages of the same pathological process. Traction spurs are indicative of instability and occur in the early stage of disc degeneration, characterized by temporary dysfunction or instability. Traction spur formation following fusion surgery can predict union or nonunion, and it serves as an indicator of preoperative and postoperative segmental instability. The relationship between traction spurs and radiographic instability, as well as their association with imaging findings such as CT and MRI, has been clarified. Additionally, finite element analysis and mechanical testing have been used to investigate the significance of traction spurs. However, further research is needed to verify that traction spurs are an accurate indicator of pre- and postoperative lumbar instability.

Establishment and characterization of NCC-SS6-C1: a novel patient-derived cell line of synovial sarcoma.

Synovial sarcoma (SS) is identified as a sarcoma with monomorphic blue spindle cells that display variable epithelial differentiation and is characterized by the SS18::SSX fusion gene. SS accounts for approximately 5-10% of all soft tissue sarcomas, making it a relatively common type within this group of tumors. Since SS is generally sensitive to chemotherapy, the standard treatment for SS includes extensive surgical resection, complemented by neoadjuvant chemotherapy with several approved anticancer drugs. However, in advanced and metastatic cases, the efficacy of these drugs is limited, resulting in poor prognoses. This underscores the need for innovative therapeutic strategies. Patient-derived cancer cell lines are essential tools for basic and preclinical research, yet only four SS cell lines are publicly available. To facilitate the studies of SS, we have developed a novel SS cell line, named NCC-SS6-C1, derived from surgically excised tumor tissue of an SS patient. NCC-SS6-C1 cells preserve the SS18::SSX1 fusion gene, consistent with the genetic characteristics of the original tumor. The cells exhibit continuous proliferation, invasiveness, and the ability to form spheroids. Additionally, we confirmed that this cell line was useful for evaluating the efficacy of anticancer drugs. Our results suggest that NCC-SS6-C1 is a useful tool for basic and pre-clinical studies of SS.

Establishment and characterization of two novel patient-derived cell lines from myxofibrosarcoma: NCC-MFS7-C1 and NCC-MFS8-C1.

Myxofibrosarcoma (MFS), an aggressive soft tissue sarcoma, presents a significant challenge because of its high recurrence rate, distal metastasis, and complex genetic background. Although surgical resection is the standard treatment for MFS, the outcomes are unsatisfactory and effective non-surgical treatment strategies, including drug therapy, are urgently warranted. MFS is a rare tumor that requires comprehensive preclinical research to develop promising drug therapies; however, only two MFS cell lines are publicly available worldwide. The present study reports two novel patient-derived MFS cell lines, NCC-MFS7-C1 and NCC-MFS8-C1. These cell lines have been extensively characterized for their genetic profile, proliferation, spheroid-forming capacity, and invasive behavior, confirming that they retain MFS hallmarks. Furthermore, we conducted comprehensive drug screening against these cell lines and six others previously established in our laboratory to identify potential therapeutic candidates for MFS. Among the screened agents, actinomycin D, bortezomib, and romidepsin demonstrated considerable antiproliferative effects that were superior to those of doxorubicin, a standard drug, highlighting their potential as novel drugs. In conclusion, NCC-MFS7-C1 and NCC-MFS8-C1 are valuable research resources that contribute to the understanding of the pathogenesis and development of novel therapies for MFS.

Clear cell sarcoma in Japan: an analysis of the population-based cancer registry in Japan.

BACKGROUND: Clear cell sarcoma is rare, so no reports have previously characterized its national profiles. We examined the nationwide epidemiology and clinical outcomes of patients with clear cell sarcoma based on the National Cancer Registry in Japan. METHODS: Overall, 23 522 patients with soft tissue sarcoma-entered in the National Cancer Registry in 2016-2019 using the International Classification of Diseases for Oncology, Third Edition cancer topography and morphology codes-were enrolled in either the clear cell or the non-clear cell sarcoma group. Data extracted included: demographics (sex and age), tumor details (reason for diagnosis, tumor location, histology and stage), hospital volume and facility type, treatment and prognosis for each patient. RESULTS: Of 23 522 soft tissue sarcoma patients, 122 were enrolled in the clear cell sarcoma group and 23 400 in the non-clear cell sarcoma group. The incidence of clear cell sarcoma was 0.52% of all soft tissue sarcoma, with an age-adjusted incidence of 0.024/100 000/year. The age at diagnosis was significantly younger, and more tumors were at the localized stage in the clear cell than the non-clear cell sarcoma group. In addition, the overall survival in the clear cell group was worse than in the non-clear cell group (P < 0.001). Of 122 patients with clear cell sarcoma, the localized stage, surgical treatment and treatment without chemotherapy were associated with better overall survival in the univariate analyses. CONCLUSIONS: The present study is the first to have clarified the epidemiology, clinical features, treatment, prognosis and significant factors affecting the prognosis of patients with clear cell sarcoma in Japan.

Soft-tissue sarcoma in Japan: National Cancer Registry-based analysis from 2016 to 2019.

BACKGROUND: No previous reports have characterized national profiles of soft-tissue sarcoma overall. We examined the nationwide statistics for soft-tissue sarcoma in Japan using data from the population-based National Cancer Registry. METHODS: We identified 23 522 soft-tissue-sarcoma patients who were entered in the National Cancer Registry during 2016-19 using International Classification of Diseases-Oncology, Third Edition codes for cancer topography and morphology. We extracted data on patient demographics, tumor details (reason for diagnosis, tumor location, histology, extent of disease), hospital volume/type, treatment, and prognosis for each patient. RESULTS: Soft-tissue sarcoma showed a slight male preponderance. Approximately 5500-6000 new cases were diagnosed as soft-tissue sarcoma per year, with the age-adjusted incidence of soft-tissue sarcoma being 3.22/100000/year. The age distribution showed a single peak in the 70-79 age range, and sex-stratified data showed it was higher in men. The most common histologic subtype was liposarcoma. The most frequent tumor locations were the soft tissue and skin, followed by the retroperitoneum. Extent of disease was categorized as: "localized" (31.3%), "regional" (38.9%), or "distant" (10.5%). We found significant associations between overall survival and sex, age, tumor location, facility type, hospital volume, reason for diagnosis, extent of disease, and surgical treatment. CONCLUSIONS: This is the first study to outline the epidemiology, clinical features, treatment, prognosis, and significant factors affecting prognosis of soft-tissue sarcoma in Japan using the National Cancer Registry. Documenting our data regarding elderly patients' outcomes is essential so other countries showing similar population-aging trends can learn from our experiences. LEVEL OF EVIDENCE: Prognostic studies, Level III.

The diagnostic and prognostic value of tartrate-resistant acid phosphatase isoform 5b for giant cell tumor of bone.

BACKGROUND: Serum level of tartrate-resistant acid phosphatase 5b (TRACP5b) is an excellent serum marker of bone resorption. In patients with giant cell tumor of bone (GCTB), TRACP5b levels are reportedly elevated. This study investigated whether TRACP5b could be a diagnostic serum marker and be useful for detecting postoperative disease progression for GCTB. METHODS: Cohort 1: We abstracted data from 120 patients with TRACP5b measurements from our database: 49 patients with GCTB and 71 patients non-GCTB. We compared serum TRACP5b values between the GCTB and non-GCTB groups. Cohort 2 included 47 patients with GCTB who had more than 6 months of follow-up and multiple TRACP5b values. For patients with local recurrence, TRACP5b change rate was calculated by comparing the TRACP5b value just before progression (a) with the value at the time of progression (b): Change rate = [(b)-(a)]/(a). In the non-progression group, the change rate was calculated from the two consecutive TRACP5b values, (c) and (d): Change rate =[(c)-(d)]/(c). We compared TRACP5b change rates between the progression and non-progression groups. RESULTS: Cohort 1: The GCTB group had a significantly higher mean TRACP5b value (1756 ± 2021 mU/dL) than the non-GCTB group (415 ± 219 mU/dL) (p < 0.0001). Cohort 2: The mean TRACP5b change rate of the progression group was significantly higher than the non-progression group (8.53 ± 8.52 and 0.24 ± 0.27, respectively; p < 0.0001). CONCLUSION: TRACP5b is a useful diagnostic marker in GCTB. The rate of change in serum TRACP5b values is a highly sensitive marker for predicting local recurrence in GCTB.

Thick Skin on the Dorsal Spine in Osteoproliferative Disease: Ossification of the Posterior Longitudinal Ligament and Diffuse Idiopathic Skeletal Hyperostosis.

Background Although the correlation between reduced skin thickness and reduced bone density has been investigated, no study has evaluated skin thickness and osteoproliferative diseases, including ossification of the posterior longitudinal ligament (OPLL) and diffuse idiopathic skeletal hyperostosis (DISH). Methodology This retrospective cohort study consisted of 99 consecutive patients aged ≥60 years treated for spinal surgery at our hospital between January 2022 and March 2023. Skin thickness was measured at the dorsal side of the cervical, thoracic, and lumbar vertebrae on the sagittal cross-section image of whole-spine CT. Based on the median value, skin thickness was categorized into two groups based on a median thickness of 4 mm. Bone mineral density (BMD) was assessed. The sum of the vertebral body and intervertebral bridging osteophytes of the anterior longitudinal and posterior longitudinal ligament were defined as the OALL index and OPLL index. Serum levels of bone metabolism-related markers, such as tartrate-resistant acid phosphatase type 5b, procollagen I N-propeptide, 25-hydroxyvitamin D, and periostin, were measured. To assess the association between skin thickness and imaging findings, we calculated the adjusted odds ratios, adjusting for age, sex, and body mass index (BMI) and using univariate and multivariate logistic regression analyses. Results No significant differences were found in skin thickness in the three dorsal regions of the cervical, thoracic, and lumbar spine (median = 3.3 mm versus 3.5 mm versus 3.4 mm, p = 0.357) and bone metabolism-related markers. Adjusting for age, sex, and BMI, cervical, thoracic, and lumbar skin thicknesses were related to DISH, the OPLL index, and the OPLL and OPLL index, respectively. Conclusions Skin thickness did not correlate with BMD but with the amount of spinal ossification. A correlation was found between skin thickness and vertebral and intervertebral ossification; vertebral osteophytes, OPLL, and DISH may be more common in thicker skin.

Statistics of bone sarcoma in Japan: report from the population-based cancer registry in Japan.

BACKGROUND: No previous reports have characterized national bone sarcoma profiles overall. We examined the nationwide statistics for bone sarcoma in Japan using data from the National Cancer Registry (NCR), a population-based cancer registry. METHODS: We identified 3,755 patients with bone sarcomas entered in the NCR during 2016-2019 using International Classification of Diseases-Oncology, Third Edition codes for cancer topography and morphology. We extracted data on patient demographics, tumor details (reason for diagnosis, tumor location, histology, extent of disease), hospital volume/type, treatment, and prognosis for each patient. RESULTS: Bone sarcoma showed a slight male preponderance. The age distribution peaked at ages 10-20 and 60-80; approximately 44% of patients were aged over 60 years. Chordoma, chondrosarcoma, and malignant fibrous histiocytoma of bone peaked in the elderly, and Ewing's sarcoma peaked in children. Osteosarcoma had two peaks in Japan as well as in Western countries. The most frequent tumor locations were the limb (45%) and the pelvis (21%). Extent of disease was categorized as: "localized" (39%), "regional" (27%), and "distant" (11%). We found significant associations between overall survival and age, tumor location, facility type, hospital volume, histologic subtype, reason for diagnosis, and extent of disease. The latter had the poorest survival. CONCLUSIONS: This is the first study to outline the epidemiology, clinical features, treatment, prognosis, and significant factors affecting prognosis of bone sarcoma in Japan using the NCR. Documenting our data regarding elderly patients' outcomes is essential so other countries showing similar population-aging trends can learn from our experiences. LEVEL OF EVIDENCE: Prognostic studies, Level III.

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.

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.

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.

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.