Details of a Researcher - Matsumoto, Morio

Papers - Matsumoto, Morio

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TNFα promotes osteosarcoma progression by maintaining tumor cells in an undifferentiated state

Mori T., Sato Y., Miyamoto K., Kobayashi T., Shimizu T., Kanagawa H., Katsuyama E., Fujie A., Hao W., Tando T., Iwasaki R., Kawana H., Morioka H., Matsumoto M., Saya H., Toyama Y., Miyamoto T.

Oncogene 33 ( 33 ) 4236 - 4241 2014.08

ISSN 0950-9232

Chronic inflammation is frequently associated with tumorigenesis in elderly people. By contrast, young people without chronic inflammation often develop tumors considered independent of chronic inflammation but driven instead by mutations. Thus, whether inflammation has a significant role in tumor progression in tumors driven by mutations remains largely unknown. Here we show that TNFα is required for the tumorigenesis of osteosarcoma, the most common tumor in children and adolescents. We show that transplantation of AX osteosarcoma cells, which harbor mutations driving c-Myc overexpression and Ink4a-deficiency, in wild-type mice promotes lethal tumorigenesis accompanied by ectopic bone formation and multiple metastases, phenotypes seen in osteosarcoma patients. Such tumorigenesis was completely abrogated in TNFα-deficient mice. AX cells have the capacity to undergo osteoblastic differentiation; however, that activity was significantly inhibited by TNFα treatment, suggesting that TNFα maintains AX cells in an undifferentiated state. TNFα inhibition of AX cell osteoblastic differentiation occurred through ERK activation, and a pharmacological TNFα inhibitor effectively inhibited both AX cell tumorigenesis and increased osteoblastic gene expression and increased survival of tumor-bearing mice. Lethal tumorigenesis of AX cells was also abrogated in IL-1α/IL-1β doubly deficient mice. We found that both TNFα and IL-1 maintained AX cells in an undifferentiated state via ERK activation. Thus, inflammatory cytokines are required to promote tumorigenesis even in mutation-induced tumors, and TNFα/IL-1 and ERK may represent therapeutic targets for osteosarcoma. © 2014 Macmillan Publishers Limited.

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Risk factors for proximal junctional kyphosis associated with dual-rod growing-rod surgery for early-onset scoliosis

Watanabe Kota, Uno Koki, Suzuki Teppei, Kawakami Noriaki, Tsuji Taichi, Yanagida Haruhisa, Ito Manabu, Hirano Toru, Yamazaki Ken, Minami Shohei, Taneichi Hiroshi, Imagama Shiro, Takeshita Katsushi, Yamamoto Takuya, Matsumoto Morio

Journal of Spinal Disorders and Techniques 2014.07

ISSN 1536-0652

STUDY DESIGN: A retrospective, multicenter study. OBJECTIVE: To identify risk factors for proximal junctional kyphosis (PJK) when treating early-onset scoliosis (EOS) with dual-rod growing-rod (GR) procedure. SUMMARY OF BACKGROUND DATA: The risk factors for PJK associated with GR treatment for EOS have not been adequately studied. METHODS: We evaluated clinical and radiographic results from 88 patients with EOS who underwent dual-rod GR surgery in 12 spine centers in Japan. The mean age at the time of the initial surgery was 6.5±2.2 years (range, 1.5-9.8{medium shade}y), and the mean follow-up period was 3.9±2.6 years (range, 2.0-12.0{medium shade}y). Risk factors for PJK were analyzed by binomial multiple logistic regression analysis. The potential factors analyzed were gender, etiology, age, the number of rod-lengthening procedures, coronal and sagittal parameters on radiographs, the type of foundation (pedicle screws or hooks), the uppermost level of the proximal foundation, and the lowermost level of the distal foundation. RESULTS: PJK developed in 23 patients (26%); in 19 of these, the proximal foundation became dislodged following PJK. Binomial multiple logistic regression analysis identified the following significant independent risk factors for PJK: a lower instrumented vertebra (LIV) at or cranial to L3 (odds ratio; OR, 3.32), a proximal thoracic scoliosis of 40° or more (OR, 2.95), and a main thoracic kyphosis of 60° or more (OR, 5.08). CONCLUSIONS: The significant independent risk factors for PJK during dual-rod GR treatment for EOS were an LIV at or cranial to L3, a proximal thoracic scoliosis of 40° or more, and a main thoracic kyphosis of 60° or more.

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Major complications and sequelae after total en bloc spondylectomy for malignant spinal tumors

Matsumoto Morio, Hikata Tomohiro, Iwanami Akio, Hosogane Naobumi, Watanabe Kota, Ishii Ken, Nakamura Masaya, Toyama Yoshiaki

Neurosurgery Quarterly 2014.07

ISSN 1050-6438

This retrospective study looked at 33 consecutive patients with malignant, aggressive tumors in the thoracic and lumbar spine who underwent TES (24 men and 9 women; mean age 49.9 years; mean follow-up 3.6 years; 14 primary tumors and 19 metastatic tumors). TES was performed by a posterior-only approach in 15 patients and by a combined anterior and posterior approach in 18 patients. We classified complications as intraoperative, early (within 1 month after surgery), or late (>1 month after surgery), and examined the relationships between major complications and potentially related factors. Ten died of disease at 22.3 months after TES. Local recurrence was observed in 8 patients (24%) at an average of 15.4 months. Thirty-one major complications occurred in 24 patients (72.7%). There were 3 intraoperative, 17 early, and 11 late complications. Intraoperative complications included injury to the segmental artery, to the aorta, and to the spinal cord in 1 patient each. Early complications included prolonged chest tube drainage, cerebrospinal fluid leakage, and monoplegia due to the severing of nerve roots in 3 patients each, and pulmonary embolism, recurrent nerve palsy, pneumonia, endplate fracture, implant dislodgement, gastric ulcer, and ileus in 1 patient each. Late complications included implant failures in 8 patients and infection in 3 patients. Major complications were significantly associated with major blood loss (P=0.047). TES was frequently associated with major intraoperative, early, and late postoperative complications; most complications were managed successfully.

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Sagittal spinopelvic malalignment in parkinson disease

Oh Jae Keun, Smith Justin S., Shaffrey Christopher I., Lafage Virginie, Schwab Frank, Ames Christopher P., Matsumoto Morio, Baik Jong Sam, Ha Yoon

Spine 39 ( 14 ) 2014.06

ISSN 0362-2436

STUDY DESIGN.: Prospective study. OBJECTIVE.: Our objectives were to evaluate the prevalence of sagittal spinopelvic malalignment in a consecutive series of patients with Parkinson disease (PD) and to identify factors associated with sagittal spinopelvic deformity in this population. SUMMARY OF BACKGROUND DATA.: PD is a degenerative neurological condition characterized by tremor, rigidity, bradykinesia, and loss of postural reflexes. The prevalence of spinal deformity in PD is higher than that of age-matched adults without PD. METHODS.: This study was a prospective assessment of consecutive patients with PD presenting to a neurology clinic during 12 months. Inclusion criteria included age more than 21 years and diagnosis of PD. Age- and sex-matched control group was selected from patients with cervical spondylosis. Clinical and demographic factors were collected including Unified Parkinson Disease Rating Scale score and Hoehn and Yahr stage. Full-length standing spine radiographs were assessed. Patients were grouped into either low C7 sagittal vertical axis (SVA) (<5 cm) or high C7 SVA (≥5 cm) and into matched (≤10°) or mismatched (>10°) pelvic incidence (PI)-lumbar lordosis. RESULTS.: Eighty-nine patients met criteria (41 males/48 females), including 52 with low C7 SVA and 37 with high C7 SVA. Significantly higher prevalence of high C7 SVA was found in PD (41.6 vs. 16.8%; P < 0.001). The high C7 SVA group was significantly older (72.4 vs. 65.1 yr; P < 0.001) and had a higher proportion of females (68% vs. 44%; P = 0.034), greater severity of PD based on Hoehn and Yahr stage (1.89 vs. 1.37; P < 0.001) and Unified Parkinson Disease Rating Scale (30.5 vs. 17.2; P = 0.002. Unified Parkinson Disease Rating Scale significantly correlated with C7 SVA (r = 0.474). Compared with the matched (≤10°) PI-lumbar lordosis group, the mismatch PI-lumbar lordosis group had higher C7 SVA, higher PI, higher pelvic tilt, lower lumbar lordosis, and lower thoracic kyphosis (P ≤ 0.003). CONCLUSION.: Patients with PD have a high prevalence of sagittal spinopelvic malalignment than control group patients. Greater severity of PD is associated with sagittal spinopelvic malalignment. © 2014 Lippincott Williams & Wilkins.

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Association of postoperative shoulder balance with adding-on in lenke type ii adolescent idiopathic scoliosis

Cao Kai, Watanabe Kota, Hosogane Naobumi, Toyama Yoshiaki, Yonezawa Ikuho, Machida Masafumi, Yagi Mitsuru, Kaneko Shinjiro, Kawakami Noriaki, Tsuji Taichi, Matsumoto Morio

Spine 39 ( 12 ) 2014.05

ISSN 0362-2436

STUDY DESIGN.: A retrospective, multicenter study. OBJECTIVE.: To investigate the relationship between postoperative shoulder balance and adding-on in Lenke type 2 adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND DATA.: Postoperative shoulder imbalance (PSI) and adding-on are the main postoperative complications occurring at the proximal to upper instrumented vertebra and the distal to the lower instrumental vertebra (LIV), respectively. Inadequate selection of LIV in the selective thoracic fusion surgery may result in postoperative distal adding-on. It remains unclear whether postoperative shoulder balance is associated with postoperative adding-on. METHODS.: Preoperative, postoperative, and 2-year follow-up radiographs of 142 consecutive patients with Lenke type 2 curves who underwent posterior-fusion surgery were analyzed. The patients were grouped into PSI positive and negative at follow-up. Radiographical and categorical factors between patients with and without PSI were compared. The relationship between the radiographical shoulder height and the parameters of adding-on were analyzed. RESULTS.: PSI occurred in 23 patients (16.2%) and distal adding-on was recognized in 20 patients (14.1%) at final follow-up. The occurrence of adding-on was significantly lower in the shoulder imbalance group at follow-up (P < 0.01). There was no shoulder imbalance occurring in the patients with distal adding-on at final follow-up (P < 0.01). Correlation analysis showed that the radiographical shoulder height was positively correlated with the change in the angulation of the first disc below LIV (r = 0.228, P ≤ 0.01) and negatively correlated with the deviation change of the LIV+1 at follow-up (r =-0.254, P ≤ 0.01). CONCLUSION.: The postoperative shoulder balance and postoperative distal adding-on were weakly but significantly associated with each other, and both shoulder imbalance and adding-on need to be prevented in Lenke type 2 curves. Copyright © 2014 Lippincott Williams &Wilkins.

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Factors affecting the postoperative progression of thoracic kyphosis in surgically treated adult patients with lumbar degenerative scoliosis

Yagi Mitsuru, Hosogane Naobumi, Okada Eijiro, Watanabe Kota, Machida Masafumi, Tezuka Masaki, Matsumoto Morio, Asazuma Takashi

Spine 39 ( 8 ) E521 - E528 2014.04

ISSN 0362-2436

STUDY DESIGN: A retrospective case series of patients treated surgically for degenerative lumbar scoliosis (DLS).OBJECTIVE: To determine incidence and risk factors of progressive global thoracic kyphosis (pGTK) after surgery for DLS.SUMMARY OF BACKGROUND DATA: Sagittal balance affects the surgical treatment of spinal deformity in adults. Little is known about the loss of sagittal balance due to pGTK, or about the risk factors for pGTK, after surgery for DLS.METHODS: We reviewed records from a multicenter database of adults with DLS, treated with posterior spinal fusion. Inclusion required an age of 50 years or more at the time of surgery, an upper instrumented vertebra at T9 and below, more than 5 fused segments, and at least 2 years of follow-up. We included 73 patients with a mean age of 68.3 years (range, 51-77 yr) and a mean follow-up period of 3.6 years (range, 2-11 yr). Independent risk factors for pGTK were identified by logistic regression analysis.RESULTS: Significant pGTK, defined as an increase in thoracic kyphosis of more than 10° from before surgery to the time of final follow-up, was observed in 41% of the patients. Loss of the sagittal vertical axis was larger in patients with pGTK than without (4.7 vs. 1.5 cm; P = 0.02). Risk analysis showed larger lumbar lordosis correction in patients with pGTK. Multivariate logistic regression analysis identified an age greater than 75 (odds ratio, 5.53; P = 0.02, 95% confidence interval [1.4-22.4]) and sacropelvic fusion (odds ratio = 2.66, P = 0.02, 95% confidence interval [1.5-11.1]) as independent risk factors for pGTK.CONCLUSION: The pGTK incidence after surgery for DLS was 41%. Age, sacropelvic fusion, and a larger sagittal correction were identified as pGTK risk factors. Long-term follow-up will provide more data on the clinical impact of pGTK in elderly patients.3.

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Surgeons' exposure to radiation in single- and multi- level minimally invasive transforaminal lumbar interbody fusion; a prospective study

Funao Haruki, Ishii Ken, Momoshima Suketaka, Iwanami Akio, Hosogane Naobumi, Watanabe Kota, Nakamura Masaya, Toyama Yoshiaki, Matsumoto Morio

PLoS ONE 9 ( 4 ) 2014.04

Although minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) has widely been developed in patients with lumbar diseases, surgeons risk exposure to fluoroscopic radiation. However, to date, there is no studies quantifying the effective dose during MIS-TLIF procedure, and the radiation dose distribution is still unclear. In this study, the surgeons' radiation doses at 5 places on the bodies were measured and the effective doses were assessed during 31 consecutive 1- to 3-level MIS-TLIF surgeries. The operating surgeon, assisting surgeon, and radiological technologist wore thermoluminescent dosimeter on the unshielded thyroid, chest, genitals, right middle finger, and on the chest beneath a lead apron. The doses at the lens and the effective doses were also calculated. Mean fluoroscopy times were 38.7, 53.1, and 58.5 seconds for 1, 2, or 3 fusion levels, respectively. The operating surgeon's mean exposures at the lens, thyroid, chest, genitals, finger, and the chest beneath the shield, respectively, were 0.07, 0.07, 0.09, 0.14, 0.32, and 0.05 mSv in 1-level MIS-TLIF; 0.07, 0.08, 0.09, 0.18, 0.34, and 0.05 mSv in 2-level; 0.08, 0.09, 0.14, 0.15, 0.36, and 0.06 mSv in 3-level; and 0.07, 0.08, 0.10, 0.15, 0.33, and 0.05 mSv in all cases. Mean dose at the operating surgeon's right finger was significantly higher than other measurements parts (P,0.001). The operating surgeon's effective doses (0.06, 0.06, and 0.07 mSv for 1, 2, and 3 fusion levels) were low, and didn't differ significantly from those of the assisting surgeon or radiological technologist. Revision MIS-TLIF was not associated with higher surgeons' radiation doses compared to primary MIS-TLIF. There were significantly higher surgeons' radiation doses in over-weight than in normal-weight patients. The surgeons' radiation exposure during MIS-TLIF was within the safe level by the International Commission on Radiological Protection's guidelines. The accumulated radiation exposure, especially to surgeon's hands, should be carefully monitored. © 2014 Funao et al.

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Mycobacterium tuberculosis promotes arthritis development through toll-like receptor 2

Kanagawa Hiroya, Niki Yasuo, Kobayashi Tami, Sato Yuiko, Katsuyama Eri, Fujie Atsuhiro, Hao Wu, Miyamoto Kana, Tando Toshimi, Watanabe Ryuichi, Morita Mayu, Morioka Hideo, Matsumoto Morio, Toyama Yoshiaki, Miyamoto Takeshi

Journal of Bone and Mineral Metabolism 2014.03

ISSN 0914-8779

Rheumatoid arthritis (RA) is a multifactorial disease caused by genetic and environmental factors: however, precise molecular mechanisms underlying its pathogenesis remain largely unknown. Treatment of RA patients with disease-modifying biological agents occasionally promotes Mycobacterium tuberculosis infection or recurrence of M. tuberculosis, although how infection promotes arthritis has not been characterized. Here, we found that arthritis phenotypes in a collagen-induced mouse model were evident only when killed M. tuberculosis was co-administered. Treatment of cultured macrophages with killed M. tuberculosis promoted production of IL-6, a major inflammatory cytokine in RA patients, while similar treatment of TLR2-deficient macrophages failed to induce IL-6 expression. Arthritis scores, joint destruction, and serum IL-6 levels were all significantly ameliorated in TLR2-deficient compared with wild-type mice, even in animals treated with killed M. tuberculosis. These results suggest that M. tuberculosis infection enhances arthritis development and that TLR2 could serve as a therapeutic target for some forms of the disease. © 2014 The Japanese Society for Bone and Mineral Research and Springer Japan.

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Selection of lower instrumented vertebra in treating lenke type 2A adolescent idiopathic scoliosis

Cao Kai, Watanabe Kota, Kawakami Noriaki, Tsuji Taichi, Hosogane Naobumi, Yonezawa Ikuho, Machida Masafumi, Yagi Mitsuru, Kaneko Shinjiro, Toyama Yoshiaki, Matsumoto Morio

Spine 39 ( 4 ) 2014.02

ISSN 0362-2436

STUDY DESIGN.: A retrospective, observational, and multicenter study. OBJECTIVE.: To identify the ideal lower instrumented vertebra (LIV) to prevent distal adding-on after surgical correction of Lenke type 2A curve. SUMMARY OF BACKGROUND DATA.: LIV level may affect the risk of postsurgical adding-on. The choice of the last touching vertebra (LTV) - the most caudal vertebra of the main thoracic curve that touches the central sacral vertical line when standing - as an appropriate LIV has been validated for Lenke type 1A but not type 2A curve. METHODS.: Radiographs obtained before, immediately after, and 2 years after surgery were evaluated for 116 consecutive patients who underwent posterior thoracic fusion surgery for Lenke type 2A curve. The LIV was proximal to the LTV in 18 patients (PLTV), distal in 43 (DLTV), and at the LTV in 55 (ALTV). Significant independent factors associated with adding-on were analyzed first by univariate analysis, and then by stepwise logistic regression analysis. RESULTS.: Distal adding-on was present in 16 patients (13.8%) at follow-up: 9 PLTV (50.0%), 3 DLTV (7.0%), and 4 ALTV (7.3%). Adding-on was significantly more common in the PLTV group. One PLTV-group patient required revision surgery to treat adding-on. Univariate analysis identified the following significant factors associated with adding-on: the T2-T5 kyphosis angle and shoulder height before, immediately after, and 2 years after surgery; the lumbar Cobb angle at the 2-year follow-up; the 2-year postoperative lumbar curve correction rate; and the difference between the LIV and the end vertebra, neutral vertebra, and LTV levels. Significant independent risk factors identified by stepwise logistic regression analysis included the clavicle angle at follow-up, the correction rate of the lumbar curve immediately after surgery, and the difference between the LIV and LTV levels. CONCLUSION.: A LIV at or distal to the LTV may prevent postoperative adding-on in Lenke type 2A curve. © 2014 Lippincott Williams and Wilkins.

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Quantification of the spatial strain distribution of scoliosis using a thin-plate spline method

Kiriyama Yoshimori, Watanabe Kota, Matsumoto Morio, Toyama Yoshiaki, Nagura Takeo

Journal of Biomechanics 47 ( 1 ) 302 - 307 2014.01

ISSN 0021-9290

The objective of this study was to quantify the three-dimensional spatial strain distribution of a scoliotic spine by nonhomogeneous transformation without using a statistically averaged reference spine. The shape of the scoliotic spine was determined from computed tomography images from a female patient with adolescent idiopathic scoliosis. The shape of the scoliotic spine was enclosed in a rectangular grid, and symmetrized using a thin-plate spline method according to the node positions of the grid. The node positions of the grid were determined by numerical optimization to satisfy symmetry. The obtained symmetric spinal shape was enclosed within a new rectangular grid and distorted back to the original scoliotic shape using a thin-plate spline method. The distorted grid was compared to the rectangular grid that surrounded the symmetrical spine. Cobb's angle was reduced from 35° in the scoliotic spine to 7° in the symmetrized spine, and the scoliotic shape was almost fully symmetrized. The scoliotic spine showed a complex Green-Lagrange strain distribution in three dimensions. The vertical and transverse compressive/tensile strains in the frontal plane were consistent with the major scoliotic deformation. The compressive, tensile and shear strains on the convex side of the apical vertebra were opposite to those on the concave side. These results indicate that the proposed method can be used to quantify the three-dimensional spatial strain distribution of a scoliotic spine, and may be useful in quantifying the deformity of scoliosis. © 2013 Elsevier Ltd.

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Pediatric myxopapillary ependymoma treated with subtotal resection and radiation therapy

Shirasawa H., Ishii K., Iwanami A., Mikami S., Toyama Y., Matsumoto M., Nakamura M.

Spinal Cord 52 ( SUPPL. 2 ) 2014

ISSN 1362-4393

Study design:Case report and review of the literature.Objectives: Myxopapillary ependymoma (MPE) is a relatively rare glioma that develops from the spinal part of the filum terminale, usually in adulthood. While it is generally benign, MPE can disseminate intraspinally, and this malignant behavior requires a multidisciplinary response with surgery and radiotherapy. We report here a case of MPE occurring in the lumbosacral spine area of an 8-year-old boy.Setting:Japan, Tokyo.Methods:We report here a case of MPE, treated with subtotal surgical resection followed by craniospinal irradiation (CSI), in an 8-year-old boy. The patient was referred to our hospital with a 6-month history of severe pain in the lower back and legs, paralysis of the legs and dysuria. Magnetic resonance imaging images showed a large tumor that filled the entire spinal canal below L1. After subtotal resection of the tumor, the pathological findings established a diagnosis of MPE. Since the tumor had perforated its capsule, increasing the risk of intraspinal dissemination, the patient underwent radiotherapy and CSI after surgery.Results:Magnetic resonance images obtained 3 years after the surgery did not show any recurrence of MPE.Conclusion:Although tumor resection followed by CSI can be considered an effective strategy for treating a child with MPE, long-term follow-up is necessary to ensure early detection of any local recurrence or dissemination of the tumor, or of post-radiotherapy scoliosis. © 2014 International Spinal Cord Society All rights reserved.

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Response

Matsumoto Morio

Journal of Neurosurgery: Spine 20 ( 5 ) 596 2014

ISSN 1547-5654

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An outcome measure for patients with cervical myelopathy

Tanaka Nobuhiro, Konno Shin Ichi, Takeshita Katsushi, Fukui Mitsuru, Takahashi Kazuhisa, Chiba Kazuhiro, Miyamoto Masabumi, Matsumoto Morio, Kasai Yuichi, Kanamori Masahiko, Matsunaga Shunji, Hosono Noboru, Kanchiku Tsukasa, Taneichi Hiroshi, Hashizume Hiroshi, Kanayama Masahiro, Shimizu Takachika, Kawakami Mamoru

Journal of Orthopaedic Science 19 ( 1 ) 33 - 48 2014

ISSN 0949-2658

Background: An outcome measure to evaluate the neurological function of patients with cervical myelopathy was proposed by the Japanese Orthopaedic Association (JOA score) and has been widely used in Japan. However, the JOA score does not include patients' satisfaction, disability, handicaps, or general health, which can be affected by cervical myelopathy. In 2007, a new outcome measure, the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), which is a self-administered questionnaire, was developed. However, the influence of age and gender on the scores has not been fully examined. The purpose of this study was to establish the standard value of the JOACMEQ by age using healthy volunteers. Methods: This study was conducted in 23 university hospitals and their affiliated hospitals from September to December 2011. The questionnaire included 24 questions for evaluation of physical function of the cervical spine and spinal cord. A total of 1,629 healthy volunteers were recruited for the study. The ages ranged from 20 to 89 years old. Results: The volunteers comprised 798 men and 831 women. In the elderly healthy volunteers, the JOACMEQ scores decreased with age. In general, the scores for cervical spine function and upper/lower extremity function were retained up to the 60s, then decreased in the 70s and 80s. The scores for quality of life were retained up to the 70s; however, the score for bladder function was retained up to the 40s, then declined with age from the 50s to 80s. Conclusion: The standard values of the JOACMEQ by age were established. Differences in the scores were found among different generations. Patients with cervical myelopathy should be evaluated with this new self-administered questionnaire taking into account the standard values according to different ages. © The Japanese Orthopaedic Association 2013.

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A meta-analysis identifies adolescent idiopathic scoliosis association with LBX1 locus in multiple ethnic groups

Londono Douglas, Kou Ikuyo, Johnson Todd A., Sharma Swarkar, Ogura Yoji, Tsunoda Tatsuhiko, Takahashi Atsushi, Matsumoto Morio, Herring John A., Lam Tsz Ping, Wang Xingyan, Tam Elisa M S, Song You Qiang, Fan Yan Hui, Chan Danny, Cheah Kathryn S E, Qiu Xusheng, Jiang Hua, Huang Dongsheng, Su Peiqiang, Sham Pak, Cheung Kenneth M C, Luk Keith D K, Gordon Derek, Qiu Yong, Cheng Jack, Tang Nelson, Ikegawa Shiro, Wise Carol A.

Journal of Medical Genetics 51 ( 6 ) 401 - 406 2014

ISSN 0022-2593

Background: Adolescent idiopathic scoliosis (AIS) is a common rotational deformity of the spine that presents in children worldwide, yet its etiology is poorly understood. Recent genome-wide association studies (GWAS) have identified a few candidate risk loci. One locus near the chromosome 10q24.31 LBX1 gene (OMIM #604255) was originally identified by a GWAS of Japanese subjects and replicated in additional Asian populations. To extend this result, and to create larger AIS cohorts for the purpose of large-scale meta-analyses in multiple ethnicities, we formed a collaborative group called the International Consortium for Scoliosis Genetics (ICSG). Methods: Here, we report the first ICSG study, a metaanalysis of the LBX1 locus in six Asian and three non- Asian cohorts. Results: We find significant evidence for association of this locus with AIS susceptibility in all nine cohorts. Results for seven cohorts containing both genders yielded P=1.22-10-43 for rs11190870, and P=2.94-10-48 for females in all nine cohorts. Comparing the regional haplotype structures for three populations, we refined the boundaries of association to a ̃25 kb block encompassing the LBX1 gene. The LBX1 protein, a homeobox transcription factor that is orthologous to the Drosophila ladybird late gene, is involved in proper migration of muscle precursor cells, specification of cardiac neural crest cells, and neuronal determination in developing neural tubes. Conclusions: Our results firmly establish the LBX1 region as the first major susceptibility locus for AIS in Asian and non-Hispanic white groups, and provide a platform for larger studies in additional ancestral groups.

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Dumbbell mesenchymal chondrosarcoma

Iida Tsuyoshi, Nakamura Masaya, Tsuji Osahiko, Iwanami Akio, Mikami Shuji, Toyama Yoshiaki, Chiba Kazuhiro, Matsumoto Morio

Journal of Orthopaedic Science 19 ( 1 ) 190 - 193 2014

ISSN 0949-2658

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A novel mouse model of soft-tissue infection using bioluminescence imaging allows noninvasive, real-time monitoring of bacterial growth

Yoshioka Kenji, Ishii Ken, Kuramoto Tetsuya, Nagai Shigenori, Funao Haruki, Ishihama Hiroko, Shiono Yuta, Sasaki Aya, Aizawa Mamoru, Okada Yasunori, Koyasu Shigeo, Toyama Yoshiaki, Matsumoto Morio

PLoS ONE 9 ( 9 ) 2014

Musculoskeletal infections, including surgical-site and implant-associated infections, often cause progressive inflammation and destroy areas of the soft tissue. Treating infections, especially those caused by multi-antibiotic resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) remains a challenge. Although there are a few animal models that enable the quantitative evaluation of infection in soft tissues, these models are not always reproducible or sustainable. Here, we successfully established a real-time, in vivo, quantitative mouse model of soft-tissue infection in the superficial gluteus muscle (SGM) using bioluminescence imaging. A bioluminescent strain of MRSA was inoculated into the SGM of BALB/c adult male mice, followed by sequential measurement of bacterial photon intensity and serological and histological analyses of the mice. The mean photon intensity in the mice peaked immediately after inoculation and remained stable until day 28. The serum levels of interleukin-6, interleukin-1 and C-reactive protein at 12 hours after inoculation were significantly higher than those prior to inoculation, and the C-reactive protein remained significantly elevated until day 21. Histological analyses showed marked neutrophil infiltration and abscesses containing necrotic and fibrous tissues in the SGM. With this SGM mouse model, we successfully visualized and quantified stable bacterial growth over an extended period of time with bioluminescence imaging, which allowed us to monitor the process of infection without euthanizing the experimental animals. This model is applicable to in vivo evaluations of the long-term efficacy of novel antibiotics or antibacterial implants.

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Postoperative behavior of thoracolumbar/lumbar curve and coronal balance after posterior thoracic fusion for Lenke 1C and 2C adolescent idiopathic scoliosis

Ishikawa Masayuki, Cao Kai, Pang Long, Watanabe Kota, Yagi Mitsuru, Hosogane Naobumi, Machida Masafumi, Shiono Yuta, Nishiyama Makoto, Fukui Yasuyuki, Matsumoto Morio

Journal of Orthopaedic Science 20 ( 1 ) 31 - 37 2014

ISSN 0949-2658

Methods: Twenty-four Lenke 1C and 2C AIS patients who underwent posterior thoracic fusion were included. The mean age of patients was 15.7 years old at time of surgery. Constructs used for surgery in all cases were pedicle screw constructs ending at L3 or above. Radiographic measurements were performed on Cobb angles of the main thoracic and TLL curves and coronal balance. Factors related to final Cobb angle of TLL curve and postoperative change of coronal balance were investigated.Results: Mean Cobb angles for main thoracic and TLL curves were 59.0° and 43.9° preoperatively, and were corrected to 21.5° and 22.0° at final follow-up, respectively. Mean coronal balance was −5.6 mm preoperatively and was corrected to −14.6 mm at final follow-up. Final Cobb angle of TLL curve was significantly correlated with immediate postoperative Cobb angle of main thoracic curve and tilt of lowest instrumented vertebra (LIV). Postoperative change of coronal balance was significantly correlated with selection of LIV relative to stable vertebra.Conclusion: Spontaneous correction of TLL curve occurred consistently by correcting the main thoracic curve and making the LIV more horizontal after posterior thoracic fusion for Lenke 1C and 2C AIS. The more distal fixation to stable vertebra resulted in coronal balance shifting more to the left postoperatively.Background: Controversy still exists around surgical strategies for Lenke type 1C and 2C curves with primary thoracic and compensatory lumbar curves in adolescent idiopathic scoliosis (AIS). The benefit of selective thoracic fusion (STF) for these curve types is spontaneous lumbar curve correction while saving more mobile lumbar segments. However, a risk of postoperative coronal decompensation after STF has also been reported. This multicenter retrospective study was conducted to evaluate postoperative behavior of thoracolumbar/lumbar (TLL) curve and coronal balance after posterior thoracic fusion for Lenke 1C and 2C AIS.

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Updates on surgical treatments for pediatric scoliosis

Matsumoto Morio, Watanabe Kota, Hosogane Naobumi, Toyama Yoshiaki

Journal of Orthopaedic Science 19 ( 1 ) 6 - 14 2014

ISSN 0949-2658

Scoliosis in children poses serious problems including respiratory problems, trunk imbalance, and depression, as well as detracting from the child's appearance. Scoliosis can also contribute to back pain later in life. Advanced surgical techniques allow for good correction and maintenance of progressive curves, and growth-sparing treatments are now available for patients with early-onset scoliosis (EOS). Posterior corrective surgeries using pedicle screw (PS) constructs, which allow curves to be corrected in three dimensions, has become the most popular surgical treatment for scoliosis. Several navigation systems and probes have been developed to aid in accurate PS placement. For thoracolumbar and lumbar curves, anterior surgery remains the method of choice. Growth-sparing techniques for treating EOS include growing rods, the Shilla method, anterior stapling, and vertical expandable prosthetic titanium rib, which was originally designed to treat thoracic insufficiency syndrome. However, these advanced surgical techniques do not always offer a perfect solution for pediatric scoliosis, and they are associated with complications such as infections and problems with instrumentation. Surgeons have developed several techniques in efforts to address these complications. We here review historic and recent advances in the surgical treatment of scoliosis in children, the problems associated with various techniques, and the challenges that remain to be overcome. Scoliosis can affect a child's appearance, hamper respiratory function and trunk balance, lead to depression, and cause back pain later in life. Moderate scoliotic curves are usually treated conservatively using a brace, but a curve that continues to progress despite treatment requires corrective surgery, either with or without fusion. Recent advances in surgical techniques have made it possible to obtain good correction and maintenance of progressive curves, and several growth-sparing techniques are now available for treating patients with early-onset scoliosis (EOS). However, these advanced surgical techniques do not provide a perfect solution for pediatric scoliosis, and some are associated with suboptimal clinical outcomes. In this article, we review recent technical advances and problems associated with the surgical treatment of scoliosis in children, both from a historic perspective and with a view to the future. © The Japanese Orthopaedic Association 2013.

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High preoperative hemoglobin A1c is a risk factor for surgical site infection after posterior thoracic and lumbar spinal instrumentation surgery

Hikata Tomohiro, Iwanami Akio, Hosogane Naobumi, Watanabe Kota, Ishii Ken, Nakamura Masaya, Kamata Michihiro, Toyama Yoshiaki, Matsumoto Morio

Journal of Orthopaedic Science 19 ( 2 ) 223 - 228 2014

ISSN 0949-2658

Background: Diabetes mellitus (DM) is reported to be a risk factor for surgical site infection (SSI), which is a serious complication after spinal surgery. The effect of DM on SSI after instrumented spinal surgery remains to be clarified. The aim was to elucidate perioperative risk factors for infection at the surgical site after posterior thoracic and lumbar spinal arthrodesis with instrumentation in patients with DM. Methods: Consecutive patients who underwent posterior instrumented thoracic and lumbar spinal arthrodesis during the years 2005-2011, who could be followed for at least 1 year after surgery, were included. These included 36 patients with DM (19 males and 17 females; mean age 64.3 years). The patients' medical records were retrospectively reviewed to determine the SSI rate. The characteristics of the DM patients were examined in detail, including the levels of serum glucose and HbA1c, which indicate the level of diabetes control. Results: Patients with DM had a higher rate of SSI (6 of 36 patients, 16.7 %) than patients without DM (10 of 309 patients, 3.2 %). Although the perioperative serum glucose level did not differ between DM patients that did or did not develop SSI, the preoperative HbA1c value was significantly higher in the patients who developed SSI (7.6 %) than in those who did not (6.9 %). SSI developed in 0.0 % of the patients with controlled diabetes (HbA1c <7.0 %) and in 35.3 % of the patients with uncontrolled diabetes (HbA1c ≥7.0 %). Conclusions: DM patients whose blood glucose levels were poorly controlled before surgery were at high risk for SSI. To prevent SSI in DM patients, we recommend lowering the HbA1c to <7.0 % before performing surgery. © 2013 The Japanese Orthopaedic Association.

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New classification system for ossification of the posterior longitudinal ligament using CT images

Kawaguchi Yoshiharu, Matsumoto Morio, Iwasaki Motoki, Izumi Tomohiro, Okawa Atsushi, Matsunaga Shunji, Chiba Kazuhiro, Tsuji Takashi, Yamazaki Masashi, Fujimori Takahito, Yoshii Toshitaka, Toyama Yoshiaki

Journal of Orthopaedic Science 19 ( 4 ) 530 - 536 2014

ISSN 0949-2658

Background: Ossification of the posterior longitudinal ligament (OPLL) is most frequently seen in the cervical spine. The types of cervical OPLL are classified into continuous, mixed, segmental, and other based on plain lateral X-ray. Computed tomography (CT) imaging is often used in clinical practice for evaluating ossified lesions as it can detect their precise location, size, and shape. However, to date, no CT classification of OPLL lesions has been proposed. Methods: One hundred and forty-four patients diagnosed with cervical OPLL by plain radiograph were included in this study. Sagittal and axial CT images of the cervical spine were obtained. We propose three classification systems: A, B, and axial. Classification A comprises two lesion types: bridge and nonbridge. Classification B requires examiners to describe all vertebral and intervertebral levels where OPLL exits in the cervical spine. Axial classification comprises central and lateral lesions identified on axial CT images. Seven observers evaluated CT images using this classification system, and intra- and interrater reliability were examined. Results: Averaged Fleiss' kappa coefficient of interrater agreement was 0.43 ± 0.26 among the seven observers, averaged intrarater reliability for the existence of OPLL was 72.4 ± 8.8 % [95 % confidence interval (CI) 67.5-76.8]. Fifty-four patients (37.5 %) had the bridge type and 90 the nonbridge type according to Classification A; 102 (70.8 %) had central and 42 (29.2 %) lateral OPLL in the axial classification. Four representative cases defined according to the three classification types are reported here. Conclusion: Subcommittee members of the Investigation Committee on the Ossification of the Spinal Ligaments of the Japanese Ministry of Public Health and Welfare propose three new classification systems of cervical OPLL based on CT imaging: A, B, and axial. © 2014 The Japanese Orthopaedic Association.

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