研究者詳細 - 渡邉　航太

論文 - 渡邉　航太

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An international meta-analysis confirms the association of BNC2 with adolescent idiopathic scoliosis

Ogura Y., Takeda K., Kou I., Khanshour A., Grauers A., Zhou H., Liu G., Fan Y., Zhou T., Wu Z., Takahashi Y., Matsumoto M., Kawakami N., Tsuji T., Uno K., Suzuki T., Ito M., Minami S., Kotani T., Sakuma T., Yanagida H., Taneichi H., Yonezawa I., Sudo H., Chiba K., Hosogane N., Nishida K., Kakutani K., Akazawa T., Kaito T., Watanabe K., Harimaya K., Taniguchi Y., Shigematsu H., Demura S., Iida T., Kono K., Okada E., Fujita N., Yagi M., Nakamura M., Karol L., Rathjen K., Sucato D., Birch J., Johnston C., Richards B., Ramo B., McIntosh A., Herring J., Milbrandt T., Talwakar V., Iwinski H., Muchow R., Tassone J., Liu X., Shindell R., Schrader W., Eberson C., Lapinsky A., Loder R., Davey J., Einarsdottir E., Kere J., Huang D., Qiu G., Xu L., Qiu Y., Wise C., Song Y., Wu N., Su P., Gerdhem P., Watanabe K., Ikegawa S.

Scientific Reports （Scientific Reports） 8 （ 1 ） 2018年12月

© 2018 The Author(s). Adolescent idiopathic scoliosis (AIS) is a common spinal deformity with the prevalence of approximately 3%. We previously conducted a genome-wide association study (GWAS) using a Japanese cohort and identified a novel locus on chromosome 9p22.2. However, a replication study using multi-population cohorts has not been conducted. To confirm the association of 9p22.2 locus with AIS in multi-ethnic populations, we conducted international meta-Analysis using eight cohorts. In total, we analyzed 8,756 cases and 27,822 controls. The analysis showed a convincing evidence of association between rs3904778 and AIS. Seven out of eight cohorts had significant P value, and remaining one cohort also had the same trend as the seven. The combined P was 3.28 × 10 -18 (odds ratio = 1.19, 95% confidence interval = 1.14-1.24). In silico analyses suggested that BNC2 is the AIS susceptibility gene in this locus.

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Twenty-year Longitudinal Follow-up MRI Study of Asymptomatic Volunteers the Impact of Cervical Alignment on Disk Degeneration

Okada E., Daimon K., Fujiwara H., Nishiwaki Y., Nojiri K., Watanabe M., Katoh H., Shimizu K., Ishihama H., Fujita N., Tsuji T., Nakamura M., Matsumoto M., Watanabe K.

Clinical Spine Surgery （Clinical Spine Surgery） 31 （ 10 ） 446 - 451 2018年12月

ISSN 23800186

© 2018 Wolters Kluwer Health, Inc. All rights reserved. Study Design: A 20-year longitudinal study. Objective: To evaluate the long-term effect of sagittal alignment of the cervical spine on intervertebral disk degeneration in healthy asymptomatic subjects. Summary of Background Data: This study continues a previous 10-year longitudinal study to determine whether sagittal alignment affects disk degeneration during normal aging. Materials and Methods: We assessed 90 healthy subjects (30 men and 60 women) from among 497 volunteers who underwent magnetic resonance imaging (MRI) and plain radiographs of the cervical spine between 1994 and 1996 (follow-up rate 18.1%). The mean age at the initial study was 35.5 13.4 years (11-65 y). We compared initial MRIs and follow-up MRIs, conducted at an average of 21.6 years after the initial study, for (1) decreased signal intensity of the intervertebral disks, (2) posterior disk protrusion, and (3) disk-space narrowing from C2-3 to C7-T1. Subjects were grouped by age at follow-up (under 40 vs. 40 y and older) and by a lordotic or nonlordotic cervical sagittal alignment at baseline. We assessed neck pain, stiff shoulders, and upper-arm numbness at follow-up, and examined associations between clinical symptoms and MRI parameters. Results: Progressive changes during the 20-year period included a decrease in disk signal intensity (84.4% of subjects), posterior disk protrusion (86.7%), and disk-space narrowing (17.8%). No significant association was observed between sagittal alignment and decreased disk signal intensity, posterior disk protrusion, or disk-space narrowing. Among subjects over the age of 40, progressive degenerative changes at C7-T1 were significantly more frequent in nonlordotic subjects (90.9%) compared with those with cervical lordosis (54.2%, P= 0.032). The prevalence of clinical symptoms was similar in lordotic and nonlordotic subjects at follow-up. Conclusions: Nonlordotic cervical alignment was related to the progression of disk degeneration at C7-T1 but not other levels. Cervical alignment did not affect the development of clinical symptoms in healthy subjects.

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Perioperative Complications After Surgery for Thoracic Ossification of Posterior Longitudinal Ligament: A Nationwide Multicenter Prospective Study

Imagama S., Ando K., Takeuchi K., Kato S., Murakami H., Aizawa T., Ozawa H., Hasegawa T., Matsuyama Y., Koda M., Yamazaki M., Chikuda H., Shindo S., Nakagawa Y., Kimura A., Takeshita K., Wada K., Katoh H., Watanabe M., Yamada K., Furuya T., Tsuji T., Fujibayashi S., Mori K., Kawaguchi Y., Watanabe K., Matsumoto M., Yoshii T., Okawa A.

Spine （Spine） 43 （ 23 ） E1389 - E1397 2018年12月

ISSN 03622436

STUDY DESIGN: Prospective, multicenter, nationwide study. OBJECTIVE: To investigate perioperative complications and risk factors in surgery for thoracic ossification of the posterior longitudinal ligament (T-OPLL) using data from the registry of the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament. SUMMARY OF BACKGROUND DATA: There is no prospective multicenter study of surgical complications and risk factors for T-OPLL, and previous multicenter retrospective studies have lacked details. METHODS: Surgical methods, preoperative radiographic findings, pre- and postoperative thoracic myelopathy (Japanese Orthopaedic Association [JOA] score), prone and supine position test (PST), intraoperative ultrasonography, and intraoperative neurophysiological monitoring (IONM) were investigated prospectively in 115 cases (males: 55, females: 60, average age 53.1 y). Factors related to perioperative complications and risk factors for postoperative motor palsy were identified. RESULTS: Posterior decompression and fusion with instrumentation with or without dekyphosis was performed in 85 cases (74%). The JOA recovery rate at 1 year after surgery in all cases was 55%. Motor palsy occurred postoperatively in 37 cases (32.2%), with a mean recovery period of 2.7 months. A long recovery period for postoperative motor palsy was significantly associated with a high number of T-OPLL levels (P < 0.0001), lower preoperative JOA score (P < 0.05), and greater estimated blood loss (P < 0.05). Perioperative complications or postoperative motor palsy were significantly related to a higher number of T-OPLL levels, comorbid ossification of ligamentum flavum rate, lower preoperative JOA score, higher preoperative positive PST rate, more surgical invasiveness, a lower rate of intraoperative spinal cord floating in ultrasonography, and higher rate of deterioration of IONM. CONCLUSION: This study firstly demonstrated the perioperative complications with high postoperative motor palsy rate in a nationwide multicenter prospective study. Surgical outcomes for T-OPLL should be improved by identifying and preventing perioperative complications with significant risk factors.3.

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Imaging Comparison Between Chinese and Japanese Patients With Cervical Ossification of the Posterior Longitudinal Ligament

Xiao B., Nagoshi N., Takeuchi A., Mao J., Liu B., Tian W., Tsuji O., Okada E., Fujita N., Yagi M., Nakamura M., Matsumoto M., Ishii K., Watanabe K.

Spine （Spine） 43 （ 23 ） E1376 - E1383 2018年12月

ISSN 03622436

STUDY DESIGN: A retrospective study. OBJECTIVE: To identify the radiographic differences between Chinese and Japanese patients with cervical ossification of the posterior longitudinal ligament (OPLL) using computed tomography (CT) and magnetic resonance imaging (MRI), and to compare the characteristics of OPLL between the two nationalities. SUMMARY OF BACKGROUND DATA: OPLL has a high prevalence in East Asia. However, the differences between Chinese and Japanese OPLL patients are poorly known. METHODS: This was a retrospective study of Chinese (n = 300) and Japanese (n = 102) consecutive patients who received a diagnosis of cervical OPLL between January 2010 and December 2014. All patients underwent CT and MRI. The type and distribution of OPLL were determined. Spinal compression was assessed by MRI. OPLL type, distribution, comorbidity, and compression of the spinal cord were examined. The ossification index (OP-index) was used to evaluate the OPLL. Factors contributing to the OP-index were examined by multivariate analysis. RESULTS: The Chinese patients were younger than the Japanese patients (P < 0.0001), and there were more women among the Chinese patients (P = 0.0002). The OP-index was higher among the Japanese patients (median, 5 vs. 4, P = 0.003). Among men, OPLL lesions were more frequent in the under 55-year-old Japanese at C7 (P = 0.04), in the 55 to 64-year-old Japanese at C4, C5, and C6 (all P < 0.05), and in the over 64-year-old Japanese at C3/4 (P = 0.01), compared with their Chinese counterparts. Among women, OPLL lesions were more frequent in the 55 to 64-year-old Japanese at C6 (P = 0.04). The multivariate analysis showed that only age was independently associated with the OP-index (odds ratio [OR] = 1.023, 95% confidence interval [CI]: 1.002-1.045, P = 0.034). CONCLUSION: Japanese patients had a higher frequency of OPLL lesions at C5, C6, and C7. Age was independently associated with OPLL.3.

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Genome-wide meta-analysis and replication studies in multiple ethnicities identify novel adolescent idiopathic scoliosis susceptibility loci

Khanshour A., Kou I., Fan Y., Einarsdottir E., Makki N., Kidane Y., Kere J., Grauers A., Johnson T., Paria N., Patel C., Singhania R., Kamiya N., Takeda K., Otomo N., Watanabe K., Luk K., Cheung K., Herring J., Rios J., Ahituv N., Gerdhem P., Gurnett C., Song Y., Ikegawa S., Wise C.

Human Molecular Genetics （Human Molecular Genetics） 27 （ 22 ） 3986 - 3998 2018年11月

ISSN 09646906

© The Author(s) 2018. Published by Oxford University Press. All rights reserved. Adolescent idiopathic scoliosis (AIS) is the most common musculoskeletal disorder of childhood development. The genetic architecture of AIS is complex, and the great majority of risk factors are undiscovered. To identify new AIS susceptibility loci, we conducted the first genome-wide meta-analysis of AIS genome-wide association studies, including 7956 cases and 88 459 controls from 3 ancestral groups. Three novel loci that surpassed genome-wide significance were uncovered in intragenic regions of the CDH13 (P-value_rs4513093 = 1.7E-15), ABO (P-value_ rs687621 = 7.3E-10) and SOX6 (P-value_ rs1455114 = 2.98E-08) genes. Restricting the analysis to females improved the associations at multiple loci, most notably with variants within CDH13 despite the reduction in sample size. Genome-wide gene-functional enrichment analysis identified significant perturbation of pathways involving cartilage and connective tissue development. Expression of both SOX6 and CDH13 was detected in cartilage chondrocytes and chromatin immunoprecipitation sequencing experiments in that tissue revealed multiple HeK27ac-positive peaks overlapping associated loci. Our results further define the genetic architecture of AIS and highlight the importance of vertebral cartilage development in its pathogenesis.

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Prevalence and Distribution of Diffuse Idiopathic Skeletal Hyperostosis on Whole-spine Computed Tomography in Patients with Cervical Ossification of the Posterior Longitudinal Ligament

Nishimura S., Nagoshi N., Iwanami A., Takeuchi A., Hirai T., Yoshii T., Takeuchi K., Mori K., Yamada T., Seki S., Tsuji T., Fujiyoshi K., Furukawa M., Wada K., Koda M., Furuya T., Matsuyama Y., Hasegawa T., Takeshita K., Kimura A., Abematsu M., Haro H., Ohba T., Watanabe M., Katoh H., Watanabe K., Ozawa H., Kanno H., Imagama S., Ando K., Fujibayashi S., Yamazaki M., Watanabe K., Matsumoto M., Nakamura M., Okawa A., Kawaguchi Y.

Clinical Spine Surgery （Clinical Spine Surgery） 31 （ 9 ） E460 - E465 2018年11月

ISSN 23800186

© 2018 Wolters Kluwer Health, Inc. All rights reserved. Study Design: This was a retrospective multicenter study. Objective: To clarify the progression of diffuse idiopathic skeletal hyperostosis (DISH) using whole-spine computed tomography in patients with cervical ossification of the posterior longitudinal ligament (OPLL). Summary of Background Data: DISH and cervical OPLL frequently coexist, and can cause ankylosing spinal fractures due to biomechanical changes and fragility of the affected vertebrae. The epidemiology and pathophysiology of DISH occurring with cervical OPLL are unclear. Materials and Methods: We used whole-spine computed tomography to determine the prevalence of DISH in 234 patients with a diagnosis of cervical OPLL based on plain cervical radiographs. We established a novel system for grading the progression of DISH based on a cluster analysis of the DISH distribution along the spine. We calculated the correlation coefficient between this grading system and patient age. Results: The prevalence of DISH in patients with cervical OPLL was 48.7%. Patients with DISH were significantly older than those who did not have DISH (67.3 vs. 63.4 y; P=0.005). Cluster analysis classified the DISH distribution into 6 regions, based on the levels affected: C2-C5, C3-T1, C6-T5, T3-10, T8-L2, and T12-S1. DISH was observed most frequently at T3-T10. We defined a system for grading DISH progression based on the number of regions involved, from grade 0 to 6. DISH was distributed at T3-T10 in >60% of the grade 1 patients, whereas most patients with DISH at the cervical or lumbar spine were grade 4 or 5. There was a weak but significant correlation between the DISH grade and patient age. Conclusions: DISH was present in nearly half of the patients with cervical OPLL. DISH was more common in older patients. DISH developed at the thoracic level and progressed into the cervical and/or lumbar spine with age. Level of Evidence: Level III.

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Metabolite profiling of plasma in patients with ossification of the posterior longitudinal ligament

Tsuji T., Matsumoto M., Nakamura M., Miyamoto T., Yagi M., Fujita N., Okada E., Nagoshi N., Tsuji O., Watanabe K.

Journal of Orthopaedic Science （Journal of Orthopaedic Science） 23 （ 6 ） 878 - 883 2018年11月

ISSN 09492658

© 2018 The Japanese Orthopaedic Association Background: Metabolomics is one of the “omics” technologies, and is a comprehensive analysis of small molecule metabolites which include amino acid, nucleotides, carbohydrates and fatty acid. The purpose of the present study was to compare the differences of metabolite profiling between patients with ossification of the posterior longitudinal ligament (OPLL) and control subjects. Methods: We analyzed plasma metabolites in patients with cervical OPLL (n = 10) and in control subjects (n = 10). Ionic metabolites were analyzed using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) and lipophilic metabolites were analyzed using liquid chromatograph time-of-flight mass spectrometry (LC-TOFMS). Results: A total of 259 metabolites (144 metabolites in CE-TOFMS and 115 metabolites in LC-TOFMS) were detected. Among the 259 metabolites, six metabolites, namely acylcarnitine (AC) (14:0), palmitoylcarnitine, AC (18:2), fatty acid (FA) (24:2), thyroxine, thiaproline were significantly larger in OPLL group, even in analyzes excluding patients with diabetes mellitus and hyperlipidemia. Conclusions: We examined the metabolite profiling in patients with OPLL for the first time and detected six metabolites showing suggestive association with disease. These results of the present study could lead to new insights into clarifying the molecular pathomechanisms of OPLL.

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Screening of known disease genes in congenital scoliosis

Takeda K., Kou I., Mizumoto S., Yamada S., Kawakami N., Nakajima M., Otomo N., Ogura Y., Miyake N., Matsumoto N., Kotani T., Sudo H., Yonezawa I., Uno K., Taneichi H., Watanabe K., Shigematsu H., Sugawara R., Taniguchi Y., Minami S., Nakamura M., Matsumoto M., Watanabe K., Ikegawa S.

Molecular Genetics and Genomic Medicine （Molecular Genetics and Genomic Medicine） 6 （ 6 ） 966 - 974 2018年11月

© 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. Background: Congenital scoliosis (CS) is defined as a lateral curvature of the spine due to the vertebral malformations and has an incidence of 0.5–1/1,000 births. We previously examined TBX6 in Japanese CS patients and revealed that approximately 10% of CS was caused by TBX6 mutations. However, the genetic cause of remaining CS is unknown. Methods: We recruited 78 CS patients without TBX6 mutations and major comorbidities, and investigated the genes previously reported to be associated with CS and congenital vertebral malformations by whole-exome sequencing. Results: We identified the compound heterozygous missense variants in LFNG in one patient. No likely disease-causing variants were identified in other patients, however. LFNG encodes a GlcNAc-transferase. The LFNG variants showed loss of their enzyme function. Conclusions: A LFNG mutation is reported in a case of spondylocostal dysostosis (SCD), a skeletal dysplasia with severe malformations of vertebra and rib. The CS patient with LFNG mutations had multiple vertebral malformations including hemivertebrae, butterfly vertebrae, and block vertebrae, and rib malformations. LFNG mutations may cause a spectrum of phenotypes including CS and SCD. The current list of known disease genes could explain only a small fraction of genetic cause of CS.

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Modic changes and disc degeneration in adolescent idiopathic scoliosis patients who reach middle age without surgery: Can residual deformity cause lumbar spine degeneration?

Akazawa T., Watanabe K., Matsumoto M., Tsuji T., Kawakami N., Kotani T., Sakuma T., Yamamoto T., Demura S., Orita S., Fujimoto K., Shiga Y., Niki H.

Journal of Orthopaedic Science （Journal of Orthopaedic Science） 23 （ 6 ） 884 - 888 2018年11月

ISSN 09492658

© 2018 The Japanese Orthopaedic Association Background: We have yet to determine what types of lumbar degenerative changes can be observed on MRI in middle-aged adolescent idiopathic scoliosis (AIS) patients without undergoing surgery. The aims of this study were to investigate AIS patients who have reached middle age without undergoing surgery and to clarify if residual spinal deformities may have affected health-related quality of life (HRQOL) and lumbar spine degeneration. Methods: Subjects comprised AIS patients who reached middle age without surgery and who underwent whole-spine X-rays, lumbar MRI, and SRS-22 surveys. Of the 60 cases collected from five scoliosis centers, 25 patients who met the inclusion criteria were enrolled into the residual deformity (RD) group and analyzed. Controls (CTR) group comprised 25 individuals matched for age, sex, and BMI with the patient group. Results: MRI revealed no significant differences in the percentage of individuals with Pfirrmann grade 4 or 5 disc degeneration in 1 or more segments (RD group: 84%, CTR group: 60%, p = 0.059). Significantly more patients with Modic changes in 1 or more segments were observed in the RD group (RD group: 56%, CTR group: 8%, p < 0.001). All SRS-22 scores were significantly lower in the RD group. The lumbar curve cutoff point based on whether or not Modic change could be observed using ROC analysis was 39.5°. Conclusions: Compared to healthy individuals, AIS patients with residual deformity who have never had surgery showed similar prevalence of disc degeneration, but they had more Modic changes and poor HRQOL. The cutoff point for lumbar curves of patients with and without Modic changes in middle age was 39.5°.

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Impact of Frailty and Comorbidities on Surgical Outcomes and Complications in Adult Spinal Disorders

Yagi M., Fujita N., Okada E., Tsuji O., Nagoshi N., Tsuji T., Asazuma T., Nakamura M., Matsumoto M., Watanabe K.

Spine （Spine） 43 （ 18 ） 1259 - 1267 2018年09月

ISSN 03622436

STUDY DESIGN: Retrospective review of surgically treated 481 adult patients with spinal disorders. OBJECTIVE: The aim of this study was to elucidate the effect of frailty and comorbidities on postoperative health-related quality of life (HRQoL) and complication rates. SUMMARY OF BACKGROUND DATA: Elective surgeries for spinal disorders not only improve clinical outcomes but also have high complication rates. METHODS: We retrospectively reviewed the results of consecutive elective spine surgeries for 156 adult spinal deformities (ASDs: 65 ± 9 years), 152 degenerative spondylolisthesis (DS: 64 ± 10 years), or 173 lumbar spinal canal stenosis (LSCS: 71 ± 9 years) with follow-up of at least 2 years. Modified Frailty Index (mFI) and Charlson Comorbidity Index (CCI) were determined from baseline demographics. We compared the prevalence and the influence of mFI and CCI on postoperative outcomes and complication rates. RESULTS: The mFI and CCI were significantly worse in ASD than in others (mFI: ASD 0.09 ± 0.12, DS 0.06 ± 0.06, LSCS 0.04 ± 0.05, P < 0.01. CCI: ASD 2.1 ± 1.6, DS 1.4 ± 0.7, LSCS 1.6 ± 0.9, P < 0.01). Postoperative HRQoL deteriorated as mFI worsened in ASD (nofrail: Oswestry Disability Index [ODI] 26 ± 11, Scoliosis Research Society Questionnaire [SRS] 3.7 ± 0.7; prefrail: ODI 32 ± 12, SRS 3.6 ± 0.6; frail: ODI 42 ± 15, SRS 3.2 ± 0.7). In DS and LSCS, however, SF-36 physical component score and mental component score improved regardless of mFI and CCI. The 2-year major complications rate increased with frailty (36%, 58%, and 81%) in ASD, but not in others. CONCLUSION: ASDs were more frail and had more comorbidities than the other populations. In ASD, postsurgical outcomes and complication rates deteriorated as frailty and CCI increased, whereas surgery produced favorable outcomes and acceptable complication rates in DS and LSCS regardless of frailty and CCI. Careful patient selection and treatment of comorbidities before surgery may decrease complications and improve outcomes for the surgical treatment of ASD.4.

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Postoperative pain management in patients undergoing posterior spinal fusion for adolescent idiopathic scoliosis: A narrative review

Seki H., Ideno S., Ishihara T., Watanabe K., Matsumoto M., Morisaki H.

Scoliosis and Spinal Disorders （Scoliosis and Spinal Disorders） 13 （ 1 ） 2018年09月

© 2018 The Author(s). Posterior spinal fusion for adolescent idiopathic scoliosis is one of the most invasive surgical procedures performed in children and adolescents. Because of the extensive surgical incision and massive tissue trauma, posterior spinal fusion causes severe postoperative pain. Intravenous patient-controlled analgesia with opioids has been the mainstay of postoperative pain management in these patients. However, the use of systemic opioids is sometimes limited by opioid-related side effects, resulting in poor analgesia. To improve pain management while reducing opioid consumption and opioid-related complications, concurrent use of analgesics and analgesic modalities with different mechanisms of action seems to be rational. The efficacy of intrathecal opioids and nonsteroidal anti-inflammatory drugs as components of multimodal analgesia in scoliosis surgery has been well established. However, there is either controversy or insufficient evidence regarding the use of other analgesic methods, such as continuous ketamine infusion, perioperative oral gabapentin, acetaminophen, continuous wound infiltration of local anesthetics, a single dose of systemic dexamethasone, and lidocaine infusion in this patient population. Moreover, appropriate combinations of analgesics have not been established. The aim of this literature review is to provide detailed information of each analgesic technique so that clinicians can make appropriate choices regarding pain management in patients with adolescent idiopathic scoliosis undergoing posterior spinal fusion.

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Comparisons of direct costs, outcomes, and cost-utility of decompression surgery with fusion versus decompression alone for degenerative lumbar spondylolisthesis

Yagi M., Fujita N., Okada E., Tsuji O., Nagoshi N., Tsuji T., Nakamura M., Matsumoto M., Watanabe K.

Journal of Orthopaedic Science （Journal of Orthopaedic Science） 23 （ 4 ） 653 - 657 2018年07月

ISSN 09492658

© 2018 Background: Cost-utility analysis of surgery for degenerative lumber spondylolisthesis (DS) is essential for healthcare providers and patients to select appropriate treatment. The purpose of this study was to review the cost-utility of decompression alone versus decompression with fusion for DS. Methods: A retrospective review of 99 consecutive patients who were treated for Meyerding grade 1 DS at two representative spine centers was performed. Patients with significant spinal instability were treated by decompression with fusion (F group, 40 patients); all others were treated by decompression surgery alone (D group, 59 patients). All patients were followed for three years. Demographic and radiographic data, health-related quality of life (HRQoL), and the direct cost for surgery were analyzed, and the incremental cost-effectiveness ratio (ICER) was determined using cost/quality-adjusted life years (QALY). Results: There were no differences between the groups in baseline demographics (D vs. F: age 68 ± 9 vs. 66 ± 7 years; 37% vs. 40% female) or HRQoL (ODI: D, 41 ± 16 vs. F, 46 ± 13%). The F group had a higher initial-surgery cost ($18,992 ± 2932) but lower reoperation frequency (7%) than the D group ($7660 ± 2182 and 12%, respectively). The three-year total direct cost was higher for F than for D ($19,222 ± 3332 vs. $9668 ± 6,168, p =.01). ICER was higher for F at one year ($136,408 ± 187,911 vs. $237,844 ± 212,049, p <.01), but was comparable for F and D at three years (D, $41,923 ± 44,503 vs. F, $51,313 ± 32,849, p =.17). Conclusion: At the three-year follow-up, the two methods had comparable cost-utility. Both methods were cost-effective (defined as an ICER within three times the per-capita gross domestic product).

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A screening method to distinguish syndromic from sporadic spinal extradural arachnoid cyst

Ogura Y., Yabuki S., Fujibayashi S., Okada E., Iwanami A., Watanabe K., Nakamura M., Matsumoto M., Ishii K., Ikegawa S.

Journal of Orthopaedic Science （Journal of Orthopaedic Science） 23 （ 3 ） 455 - 458 2018年05月

ISSN 09492658

© 2018 The Japanese Orthopaedic Association Background: Spinal extradural arachnoid cyst (SEDAC) is a cystic lesion that protrudes into the epidural space from a small dural defect. Early diagnosis of SEDAC is important because its expansion causes neurological damage. Two types of SEDAC, syndromic and sporadic, are present. Syndromic SEDAC is inherited as a part of lymphedema-distichiasis syndrome caused by mutations in the FOXC2 gene; however, it is often mistaken as sporadic because of low penetrance. It is not reasonable to conduct a genetic testing for all SEDAC patients and their family members. The aim of this study is to establish an effective screening method to distinguish syndromic SEDAC from sporadic SEDAC. Methods: We performed a retrospective review of medical records and imaging studies of 29 subjects who were diagnosed with SEDAC. Clinical features, family history and magnetic resonance imaging (MRI) were analyzed. Mutations in FOXC2 were examined by Sanger-sequencing of the entire coding region of the genes. SEDAC having a mutation in FOXC2 gene was defined with syndromic SEDAC. Results: Eleven subjects had a heterozygous mutation in FOXC2. They were all familial and hence syndromic SEDAC. Only one proband had known family history of SEDAC at diagnosis. MRI findings and physical examinations, especially eye and leg examinations, were quite useful to screen syndromic SEDAC. Physical examination often showed accompanying lymphedema and distichiasis in syndromic SEDAC. Syndromic SEDAC tended to have multiple cysts out of the thoracolumbar area. Conclusions: We established an effective screening method based on physical examinations and MRI findings.

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Low Bone-Mineral Density Is a Significant Risk for Proximal Junctional Failure after Surgical Correction of Adult Spinal Deformity

Yagi M., Fujita N., Tsuji O., Nagoshi N., Asazuma T., Ishii K., Nakamura M., Matsumoto M., Watanabe K.

Spine （Spine） 43 （ 7 ） 485 - 491 2018年04月

ISSN 03622436

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. Study Design. A propensity-matched comparison of risk factors for proximal junctional failure (PJF), which is a symptomatic proximal junctional kyphosis developing after corrective surgery for adult spinal deformity (ASD). Objective. To elucidate the role of bone strength for developing PJF. Summary of Background Data. PJF, a devastating complication of corrective surgery for ASD, often recurs even after revision surgery. Most studies of risk factors for PJF are retrospective and have a selection bias in surgical strategy, making it difficult to identify modifiable PJF risk factors. Methods. We conducted propensity-matched comparisons of 113 surgically treated ASD patients who were followed for at least 2 years, to elucidate whether low bone-mineral density (BMD) was a true risk factor for PJF in a uniform population from a multicenter database. Patients were grouped as having mildly low to normal BMD (M group; T-score≧-1.5) or significantly low BMD (S group; T-score<-1.5), and were propensity-matched for age, upper and lower instrumented vertebrae, history of spine surgery, and Schwab-Scoliosis Research Society (SRS) ASD classification. PJF was defined as a ≥20° increase from the baseline proximal junction angle with a concomitant deterioration of at least one SRS-Schwab sagittal modifier grade, or any type of proximal junctional kyphosis requiring revision. Results. PJF developed in 22 of 113 patients (19%). There were 48 propensity-matched patients in the M and S groups (24 in each) with similar parameters for age, body mass index, number of vertebrae involved, C7SVA, pelvic incidence -LL, and SRS-Schwab type. In this propensity-matched population, the incidence of PJF was significantly higher in the S group (33% vs. 8%, P<0.01, odds ratio 6.4, 95% CI: 1.2-32.3). Conclusion. Low BMD was a significant risk factor for PJF in this propensity-matched cohort (odds ratio 6.4). Surgeons should consider prophylactic treatments when correcting ASD in patients with low BMD. Level of Evidence: 3

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A cost-effectiveness comparisons of adult spinal deformity surgery in the United States and Japan

Yagi M., Ames C., Keefe M., Hosogane N., Smith J., Shaffrey C., Schwab F., Lafage V., Shay Bess R., Matsumoto M., Watanabe K.

European Spine Journal （European Spine Journal） 27 （ 3 ） 678 - 684 2018年03月

ISSN 09406719

© 2017, Springer-Verlag GmbH Germany. Purpose: Information about the cost-effectiveness of surgical procedures for adult spinal deformity (ASD) is critical for providing appropriate treatments for these patients. The purposes of this study were to compare the direct cost and cost-effectiveness of surgery for ASD in the United States (US) and Japan (JP). Methods: Retrospective analysis of 76 US and 76 JP patients receiving surgery for ASD with ≥2-year follow-up was identified. Data analysis included preoperative and postoperative demographic, radiographic, health-related quality of life (HRQOL), and direct cost for surgery. An incremental cost-effectiveness ratio (ICER) was determined using cost/quality-adjusted life years (QALY). The cost/QALY was calculated from the 2-year cost and HRQOL data. Results: JP exhibited worse baseline spinopelvic alignment than the US (pelvic incidence and lumbar lordosis: 35.4° vs 22.7°, p OpenSPiltSPi 0.01). The US had more three-column osteotomies (50 vs 16%), and shorter hospital stay (7.9 vs 22.7 days) (p OpenSPiltSPi 0.05). The US demonstrated worse postoperative ODI (41.3 vs. 33.9%) and greater revision surgery rate (40 vs 10%) (p OpenSPiltSPi 0.05). Due to the high initial cost and revision frequency, the US had greater total cost ($92,133 vs. $49,647) and cost/QALY ($511,840 vs. $225,668) at 2-year follow-up (p OpenSPiltSPi 0.05). Conclusion: Retrospective analysis comparing the direct costs and cost-effectiveness of ASD surgery in the US vs JP demonstrated that the total direct costs and cost/QALY were substantially higher in the US than JP. Variations in patient cohort, healthcare costs, revision frequencies, and HRQOL improvement influenced the cost/QALY differential between these countries.

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Acute regrowth and dissemination of a mature spinal cord teratoma after partial resection

Kawai M., Nagoshi N., Iwanami A., Mikami S., Tsuji O., Fujita N., Yagi M., Watanabe K., Ishii K., Nakamura M., Matsumoto M.

BMJ Case Reports （BMJ Case Reports） 2018 2018年

© BMJ Publishing Group Limited 2018. A 23-year-old man presented with difficulty walking and leg pain and numbness. MRI revealed a cystic mass at Th11-12 and a pineal-region tumour. The patient underwent surgery to resect the thoracic-level mass. The tumour adhered strongly to the neural tissue and could only be partially resected. On pathological examination, the resected tumour was diagnosed as a mature teratoma. The tumour regrew and disseminated within 3 months after resection. Both the spinal cord tumour and the tumour in the pineal region shrank significantly after chemotherapy and radiotherapy. Although the tumour was pathologically diagnosed as a mature teratoma, we suspect that the residual tumour contained an immature or malignant component. Thus, careful follow-up observation is mandatory after partial resection of a mature teratoma. In addition, because teratomas can disseminate in the central nervous system, the presence of teratoma should prompt an examination of both the spinal cord and brain.

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Total resection of cervical ventral intramedullary cavernous hemangiomas with an anterior corpectomy

Nagoshi N., Ishii K., Kameyama K., Tsuji O., Okada E., Fujita N., Yagi M., Matsumoto M., Nakamura M., Watanabe K.

Spine Surgery and Related Research （Spine Surgery and Related Research） 2 （ 4 ） 331 - 334 2018年

Introduction: Intramedullary lesions and tumors are generally accessed by a posterior approach. However, if the lesion is located on the ventral side of the spinal cord, a posterior resection with myelotomy poses technical difficulties. We report two cases of complete resection of a cervical ventral intramedullary cavernous hemangioma using an anterior approach. Case Report: Two cases of intramedullary cavernous hemangioma located on the ventral side of the spinal cord were successfully treated by total resection with anterior cervical corpectomy followed by anterior spinal fusion with an autologous bone strut from the iliac crest. In both cases, the postoperative course was uneventful, and there was no neurological deficit. Bony fusion was achieved, and there was no recurrence or complication during a follow-up period of at least two years. Conclusions: Here, we describe an anterior approach for total resection of cavernous hemangiomas on the ventral side of the cervical spinal cord. Outcomes were stable two years after the operations. Although the method should be assessed with more patients and a longer follow-up time, this anterior approach may be useful for the radical resection of a vascular malformation or tumor.

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A 20-year prospective longitudinal study of degeneration of the cervical spine in a volunteer cohort assessed using MRI follow-up of a cross-sectional study

Daimon K., Fujiwara H., Nishiwaki Y., Okada E., Nojiri K., Watanabe M., Katoh H., Shimizu K., Ishihama H., Fujita N., Tsuji T., Nakamura M., Matsumoto M., Watanabe K.

Journal of Bone and Joint Surgery - American Volume （Journal of Bone and Joint Surgery - American Volume） 100 （ 10 ） 843 - 849 2018年

ISSN 00219355

Background: Few studies have addressed in detail long-term degenerative changes in the cervical spine. In this study, we evaluated the progression of degenerative changes of the cervical spine that occurred over a 20-year period in an originally healthy cohort. We also sought to clarify the relationship between the progression of cervical degenerative changes and the development of clinical symptoms. Methods: For this prospective follow-up investigation, we recruited 193 subjects from an original cohort of 497 participants who had undergone magnetic resonance imaging (MRI) of the cervical spine between 1993 and 1996. The subjects were asked about the presence or absence of cervical spine-related symptoms. Degenerative changes of the cervical spine were assessed on MRI using an original numerical grading system. The relationship between the progression of degenerative changes and the onset of clinical symptoms was evaluated by logistic regression analysis. Results: Degeneration in the cervical spine was found to have progressed in 95% of the subjects during the 20-year period. The finding of a decrease in signal intensity of the intervertebral disc progressed in a relatively high proportion of the subjects in all age groups and occurred with similar frequency (around 60%) at all intervertebral disc levels. The rate of progression of other structural failures on MRI increased with age and was highest at C5-C6. The progression of foraminal stenosis was associated with the onset of upper-limb pain (odds ratio, 4.71 [95% confidence interval, 1.02 to 21.7]). Conclusions: A progression of degenerative changes in the cervical spine on MRI over the 20-year period was detected in nearly all subjects. There was no relationship between the progression of degeneration on MRI and the development of clinical symptoms, with the exception of an association found between foraminal stenosis and upper-limb pain. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

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Spinal arteriovenous fistula coexisting within a spinal lipoma: report of two cases

Horiuchi Y, Iwanami A, Akiyama T, Hikata T, Watanabe K, Yagi M, Fujita N, Okada E, Nagoshi N, Tsuji O, Ishii K, Yoshida K, Nakamura M, Matsumoto M

Spinal cord series and cases 3 17079 2017年

研究論文（学術雑誌）

Physical Activities and Lifestyle Factors Related to Adolescent Idiopathic Scoliosis.

Watanabe K, Michikawa T, Yonezawa I, Takaso M, Minami S, Soshi S, Tsuji T, Okada E, Abe K, Takahashi M, Asakura K, Nishiwaki Y, Matsumoto M

The Journal of bone and joint surgery 99 （ 4 ） 284 - 294 2017年

研究論文（学術雑誌）

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