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| 1.
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Shinmura, Kazuya ; Murakami, Hideki ; Demura, Satoru ; Kato, Satoshi ; Yoshioka, Katsuhito ; Hayashi, Hiroyuki ; Inoue, Kei ; Ota, Takashi ; Yokogawa, Noriaki ; Ishii, Takayoshi ; Igarashi, Takashi ; Tsuchiya, Hiroyuki ; 新村, 和也 ; 村上, 英樹 ; 出村, 諭 ; 加藤, 仁志 ; 土屋, 弘行
概要:
金沢大学医薬保健研究域医学系<br />Our aim was to compare the process of bone formation after reconstruction of the vertebral body usin
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g a titanium cage with either a liquid nitrogen-treated (frozen) bone autograft or non-treated fresh bone autograft. Twelve canine beagles underwent anterior reconstruction of the 5th lumbar vertebrae using a titanium cage and bone autograft. Bone formation was compared across four experimental groups: fresh bone autograft groups, with animals sacrificed at either 8 or 16 weeks post-reconstruction, and liquid nitrogen-treated (frozen) bone autograft groups, with animals again sacrificed at either 8 or 16 weeks post-reconstruction. Bone formation was evaluated histologically by calculating the proportion of 'reaction' and 'mature bone' regions at the ends of the cage, its center, and ventral/dorsal sides. The reaction region contained osteocytes with a nucleus and osteoblasts accumulated on the surface of an osteoid, while a laminar structure was visible for mature bone regions. For fresh bone autografts, the reaction and mature bone regions significantly increased from 8 to 16 weeks post-reconstruction. By comparison, for frozen autografts, the reaction bone region did not significantly increase from 8 to 16 weeks post-reconstruction, while the mature bone region did increase over this time period. The proportion of reaction bone was higher at the ends and dorsal side of the cage at 8 weeks, for both graft types, with greater bone formation at the center of the cage at 16 weeks only for the fresh bone autograft. Therefore, bone formation in the anterior spinal reconstruction site tended to be delayed when using a frozen bone autograft compared to a fresh bone autograft. The bone formation process, however, was similar for both groups, beginning at the ends and dorsal side of the cage adjacent to the surrounding vertebral bone. © 2018 Shinmura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 2.
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Higuchi, Takashi ; Takeuchi, Akihiko ; Munesue, Seiichi ; Yamamoto, Norio ; Hayashi, Katsuhiro ; Kimura, Hiroaki ; Miwa, Shinji ; Inaki, Hiroyuki ; Shimozaki, Shingo ; Kato, Takashi ; Aoki, Yu ; Abe, Kensaku ; Taniguchi, Yuta ; Aiba, Hisaki ; Murakami, Hideki ; Harashima, Ai ; Yamamoto, Yasuhiko ; Tsuchiya, Hiroyuki ; 武内 , 章彦 ; 棟居, 聖一 ; 山本, 憲男 ; 林 , 克洋 ; 三輪, 真嗣 ; 谷口, 裕太 ; 原島, 愛 ; 山本, 靖彦 ; 土屋, 弘行
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金沢大学医薬保健研究域医学系<br />Surgical resection is the only treatment for chondrosarcomas, because of their resistance to chemoth
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erapy and radiotherapy; therefore, additional strategies are crucial to treat chondrosarcomas. Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor, which has been reported as a possible therapeutic target in certain malignancies including chondrosarcomas. In this study, we demonstrated that a nonsteroidal anti-inflammatory drug, zaltoprofen, could induce PPARγ activation and elicit anti-tumor effects in chondrosarcoma cells. Zaltoprofen was found to induce expressions of PPARγ mRNA and protein in human chondrosarcoma SW1353 and OUMS27 cells, and induce PPARγ-responsible promoter reporter activities. Inhibitory effects of zaltoprofen were observed on cell viability, proliferation, migration, and invasion, and the activity of matrix metalloproteinase-2 (MMP2); these effects were dependent on PPARγ activation and evidenced by silencing PPARγ. Moreover, we showed a case of a patient with cervical chondrosarcoma (grade 2), who was treated with zaltoprofen and has been free from disease progression for more than 2 years. Histopathological findings revealed enhanced expression of PPARγ and reduced expression of MMP2 after administration of zaltoprofen. These findings demonstrate that zaltoprofen could be a promising drug against the malignant phenotypes in chondrosarcomas via activation of PPARγ and inhibition of MMP2 activity. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.<br />29573200
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| 3.
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Yokogawa, Noriaki ; Murakami, Hideki ; Demura, Satoru ; Kato, Satoshi ; Yoshioka, Katsuhito ; Yamamoto, Miyuki ; Iseki, Shoichi ; Tsuchiya, Hiroyuki
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Purpose Spinal surgery in a previously irradiated field carries increased risk of perioperative complications, such as d
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elayed wound healing or wound infection. In addition, adhesion around the dura mater is often observed clinically. Therefore, similar to radiation-induced fibrosis- a major late-stage radiation injury in other tissue-epidural fibrosis is anticipated to occur after spinal radiation. In this study, we performed histopathologic assessment of postirradiation changes in the spinal dura mater and peridural tissue in mice. Materials and Methods The thoracolumbar transition of ddY mice was irradiated with a single dose of 10 or 20 Gy. After resection of the irradiated spine, occurrence of epidural fibrosis and expression of transforming growth factor beta 1 in the spinal dura mater were evaluated. In addition, microstructures in the spinal dura mater and peridural tissue were assessed using an electron microscope. Results In the 20-Gy irradiated mice, epidural fibrosis first occurred around 12 weeks postirradiation, and was observed in all cases from 16 weeks postirradiation. In contrast, epidural fibrosis was not observed in the nonirradiated mice. Compared with the nonirradiated mice, the 10- and 20-Gy irradiated mice had significantly more overexpression of transforming growth factor beta 1 at 1 week postirradiation and in the late stages after irradiation. In microstructural assessment, the arachnoid barrier cell layer was thinned at 12 and 24 weeks postirradiation compared with that in the nonirradiated mice. Conclusion In mice, spinal epidural fibrosis develops in the late stages after high-dose irradiation, and overexpression of transforming growth factor beta 1 occurs in a manner similar to that seen in radiation-induced fibrosis in other tissue. Additionally, thinning of the arachnoid barrier cell layer was observed in the late stages after irradiation. Thus, consideration should be given to the possibility that these phenomena can occur as radiation-induced injuries of the spine. Copyright © 2015 Yokogawa et al.
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Sasagawa, Takeshi ; Kawahara, Norio ; Murakami, Hideki ; Demura, Satoru ; Yoshioka, Katsuhito ; Yamaguchi, Takehiko ; Tsuchiya, Hiroyuki ; Tomita, Katsuro
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seikei@pop01.kanazawa-u.ac.jp<br />Background Each vertebra can be regarded as a compartment surrounded by several anato
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mically characterized barriers. However, in some cases tumorsextend beyond these barriers. The route of vertical extension to the adjacent vertebrae is unclear. The extent ofvertical extension of a metastatic spinal tumor is important in making the preoperative decision regarding the cranio-caudal surgical margin. The objective of this study was toinvestigate the route of vertical extension of metastatic vertebral tumors. Methods We examined 20 en bloc resected metastatic vertebral bodies in which the tumors had extendedoutside the vertebral body. Five to eight sagittal sections including the pedicle, and the lateral and central parts of the PLL were prepared from each resected specimen. The sections were stained with hematoxylin and eosin, and elastica van Gieson. Histological examination focused on the routes of the vertical extension of the tumor at each barrier tissue and the degree of tumor extension along each route. Results Vertical extension ofthe tumor was observed at the ALL in 6 cases, at the central part of the PLL in 14 cases, at the lateral part of the PLL in 20 cases, at the cartilaginous endplate in 3 cases, and at the periosteum on the lateral side of vertebral body in 7 cases. The tumor had extended the farthest at the lateral part of the PLL in 18 cases, at the lateral side of the vertebral body in 1 case, and through the disc in 1 case. Conclusions Metastatic vertebral tumors most commonly extend vertically at the lateral part of the PLL. The lateralpart of the PLL is raised by the tumor, which extends between the PLL and the posterior aspect of the disc. © The Japanese Orthopaedic Association 2011.
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| 5.
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Sasagawa, Takeshi ; Kunogi, Junichi ; Masuyama, Shigeru ; Ogihara, Satoshi ; Takeuchi, Yosuke ; Takeshita, Yujiro ; Fukushima, Masayoshi ; Kamiya, Naokazu ; Murakami, Hideki ; Tsuchiya, Hiroyuki
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Background The interpretation of thoracic spine X-rays is difficult because these images cannot clearly visualize the th
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oracic spine because of the overlap with soft tissues, such as the heart and pulmonary blood vessels. Thus, to improve the clarity of thoracic spine radiographs using existing radiograph equipment, we have investigated a one-shot energy subtraction method to visualize thoracic spine radiographs. Our objective was to evaluate whether the thoracic spine radiographs generated using this method could visualize the spine more clearly than the corresponding original thoracic spine radiographs. Methods This study included 29 patients who underwent thoracic spine radiographs. We used a one-shot energy subtraction method to improve the clarity of thoracic spine radiographs. Image definition was evaluated using vertebrae sampled from each region of the thoracic spine. Specifically, these were: Th1, Th5, Th9, and Th12. Image definition was assessed using a three-point grading system. The conventional and processed computed radiographs (both frontal and lateral views) of all 29 study patients were evaluated by 5 spine surgeons. Results In all thoracic regions on both frontal and lateral views, the processed images showed statistically significantly better clarity than the corresponding conventional images, especially at all sampling sites on the frontal view and T5 and 9 on the lateral view. Conclusions Thoracic spine radiographs generated using this method visualized the spine more clearly than the corresponding original thoracic spine radiographs. The greatest advantages of this image processing technique were its ability to clearly depict the whole thoracic spine on frontal views and the middle thoracic spine on lateral views. © The Japanese Orthopaedic Association 2012.
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Tsuchiya, Hiroyuki ; Shirai, Toshiharu ; Nishida, Hideji ; Murakami, Hideki ; Kabata, Tamon ; Yamamoto, Norio ; Watanabe, Koji ; Nakase, Junsuke
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Background: Postoperative infection associated with implants remains a serious complication in orthopedic surgery. Several biomaterial surface treatments have been proposed as a means of reducing the incidence of implantassociated
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infections. In this study, a clinical trial was performed using an iodine-supported titanium that suppresses the microbial activities. Methods: A total of 222 patients with postoperative infection or compromised status were treated using iodinesupported titanium implants. The mean age of the patients was 49.4 years (range 5-85 years). One hundred twentyseven patients were male and 95 were female. In 158 patients, iodine-supported implants were used to prevent infection, such as compromised hosts and conditions, and in 64 patients to treat active infection. White blood cell (WBCs) and C-reactive protein (CRP) levels were measured pre- and postoperatively in all patients. To confirm whether iodine from the implant affected physiological functions, thyroid hormone levels in the blood were examined. Both examinations were conducted sequentially for a year. Radiological evaluations were performed regularly after the operation. The chronological changes of the iodine amount were evaluated using half pins removed after completion of external fixation. Results: The mean follow-up period was 18.4 months (range 3-44 months). Acute infection developed in three tumor cases among the 158 patients on preventive therapy. All three recovered without removal of the implants. Infection was cured in all 64 patients with infection. Median WBC levels were in the normal range, and median CRP levels returned to <0.5 within 4 weeks after surgery. Abnormalities of thyroid gland function were not detected. None of the patients experienced loosening of the implants. There were two patients with mechanical implant failure, which was treated by re-implantation. Excellent bone ingrowth and ongrowth were found around all hip and tumor prostheses. One year later, the amount of iodine on external fixation pins remained about 20-30 %. Conclusions: Iodine-supported titanium implants can be very effective for preventing and treating infections after orthopedic surgery. Cytotoxicity and adverse effects were not detected.
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| 7.
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Hayashi, Hiroyuki ; Murakami, Hideki ; Demura, Satoru ; Kato, Satoshi ; Yoshioka, Katsuhito ; Shinmura, Kazuya ; Yokogawa, Noriaki ; Ishii, Takayoshi ; Fang, Xiang ; Shirai, Toshiharu ; Tsuchiya, Hiroyuki
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Background context Surgical site infection (SSI) associated with instruments remains a serious and common complication in patients who undergo total en bloc spondylectomy (TES). It is very important that the risk factors for SSI are
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known to prevent it.Purpose The purpose of the study was to identify independent risk factors for SSI after TES and evaluate the positive effect of iodine-supported spinal instruments in the prevention of SSI after TES.Study design This is a retrospective clinical study.Patient sample One hundred twenty-five patients who underwent TES for vertebral tumor were evaluated.Outcome measures Incidence rate of SSI, risk factors for SSI after TES, and safety of iodine-supported spinal instruments were the outcome measures.Methods Risk factors for SSI were analyzed using logistic regression. In recent 69 patients with iodine-supported spinal instruments, the thyroid hormone levels in the blood were examined to confirm if iodine from the implant influenced thyroid function. Postoperative radiological evaluations were performed regularly.Results The rate of SSI was 6.4% (8/125 patients). By multivariate logistic regression, combined anterior and posterior approach and nonuse of iodine-supported spinal instruments were associated with an increased risk of SSI. The rate of SSI without iodine-supported spinal instruments was 12.5%, whereas the rate with iodine-supported spinal instruments was 1.4%. This difference was statistically significant. There were no detected abnormalities of thyroid gland function with the use of iodine-supported instruments. Among the 69 patients with iodine-supported spinal instruments, 2 patients required additional surgery because of instrument failure. However, there were no obvious involvements with the use of iodine-supported spinal instruments.Conclusions This study identified combined anterior and posterior approach and nonuse of iodine-supported spinal instruments to be independent risk factors for SSI after TES. Iodine-supported spinal instrument was extremely effective for prevention of SSI in patients with compromised status, and it had no detection of cytotoxic or adverse effects on the patients.
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Sasagawa, Takeshi ; Hashimoto, Fumio ; Nakamura, Takuya ; Maruhashi, Yoshinobu ; Matsumoto, Naoyuki ; Segawa, Takeshi ; Yamamoto, Daiki ; Goshima, Kenichi ; Murakami, Hideki ; Tsuchiya, Hiroyuki
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Yokogawa, Noriaki ; Murakami, Hideki ; Demura, Satoru ; Kato, Satoshi ; Yoshioka, Katsuhito ; Hayashi, Hiroyuki ; Ishii, Takayoshi ; Fujii, Moriyuki ; Igarashi, Takashi ; Tsuchiya, Hiroyuki
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Background: In total en bloc spondylectomy (TES) of upper thoracic spine including the second thoracic (T2) vertebra, T2 nerve roots are usually transected. In this study, we examined the association between transection of
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the T2 nerve roots and upper-extremity motor function in patients with upper thoracic TES. Copyright:Methods: We assessed 16 patients who underwent upper thoracic TES with bilateral transection of the T2 nerve roots. Patients were divided into three groups: 3 patients without any processing of T1 and upper nerve roots (T2 group), 7 with extensive dissection of T1 nerve roots (T1-2 group), and 6 with extensive dissection of T1 and upper nerve roots (C-T2 group). Postoperative upper-extremity motor function was compared between the groups.Results: Postoperative deterioration of upper-extremity motor function was observed in 9 of the 16 patients (56.3%). Three of the 7 patients in the T1-2 group and all 6 patients in the C-T2 group showed deterioration of upper-extremity motor function, but there was no deterioration in the T2 group. In the T1-2 group, 3 patients showed mild deterioration that did not affect their activities of daily living and they achieved complete recovery at the latest follow-up examination. In contrast, severe dysfunction occurred frequently in the C-T2 group, without recovery at the latest follow-up.Conclusions: The transection of the T2 nerve roots alone did not result in upper-extremity motor dysfunction; rather, the dysfunction is caused by the extensive dissection of the T1 and upper nerve roots. Therefore, transection of the T2 nerve roots in upper thoracic TES seems to be an acceptable procedure with satisfactory outcomes.
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Sugita, Shurei ; Murakami, Hideki ; Demura, Satoru ; Kato, Satoshi ; Yoshioka, Katsuhito ; Yokogawa, Noriaki ; Tanaka, Sakae ; Tsuchiya, Hiroyuki
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Purpose: Total en bloc spondylectomy (TES) is accompanied by preoperative embolization of segmental arteries, which is l
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imited to three consecutive levels to avoid the risk of spinal cord ischemia. We retrospectively examined the efficacy and safety of repeated TES with embolization of more than three levels of segmental arteries. Methods: Seven patients underwent TES twice for spinal metastases at different levels. Every patient underwent embolization of the bilateral segmental arteries before each surgery. We assessed the total number of segmental arteries embolized, the existence of Adamkiewicz arteries during the embolization procedure, intraoperative blood loss, and the motor function of the lower limbs, using the American Spinal Injury Association (ASIA) motor score. Results: No patient experienced any motor deficit after embolization. During the embolization procedure, an Adamkiewicz artery was depicted in five patients, which precluded embolization at that level. The median number of segmental arteries embolized in total was 9 (9–11). Intraoperative blood loss (median, IQR) was 480 (420–630) ml during the first surgery and 520 (280–600) ml during the second surgery. The ASIA motor scores (median, IQR) were as follows; 100 (98–100) (first admission), 100 (100–100) (first discharge), 100 (98–100) (second admission), and 97 (94–100) (second discharge). No patients had developed statistically significant neurological deterioration, and there had been no local recurrence after a median follow-up of 17.8 months (range 1–51 months). Conclusion: Repeated TES procedures can be performed safely even if more than three levels of segmental arteries are embolized. © 2015 Springer-Verlag Berlin Heidelberg<br />Embargo Period 12 months
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