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| 1.
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Matsubara, Hidenori ; Tsuchiya, Hiroyuki ; Watanabe, Koji ; Takeuchi, Akihiko ; Tomita, Katsuro
概要:
金沢大学医薬保健研究域医学系<br />Hepatocyte growth factor (HGF) was initially identified in cultured hepatocytes and subsequently rep
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orted to induce angiogenic, morphogenic, and antiapoptotic activity in various tissues. These properties suggest a potential influence of HGF on bone healing. We asked if gene transfer of human HGF (hHGF) into an osteotomy gap with a hemagglutinating virus of Japan-envelope (HVJ-E) vector promotes bone healing in rabbits. HVJ-E that contained either hHGF or control plasmid was percutaneously injected into the osteotomy gap of rabbit tibias on Day 14. The osteotomy gap was evaluated by radiography, pQCT, mechanical tests, and histology at Week 8. The expression of hHGF was evaluated by reverse transcriptase-polymerase chain reaction and immunohistochemistry at Week 3. Radiography, pQCT, and histology suggested the hHGF group had faster fracture healing. Mechanical tests demonstrated the hHGF group had greater mechanical strength. The injected tissues at 3 weeks expressed hHGF mRNA by reverse transcriptase-polymerase chain reaction. hHGF-positive immunohistochemical staining was observed in various cells at the osteotomy gap at Week 3. The data suggest delivery of hHGF plasmid into the osteotomy gap promotes fracture repair, and HGF could become a novel agent for fracture treatment.全文公開200912
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| 2.
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Tanzawa, Yoshikazu ; Tsuchiya, Hiroyuki ; Shirai, Toshiharu ; Hayashi, Katsuhiro ; Zen, Yoh ; Tomita, Katsuro
概要:
金沢大学医薬保健研究域医学系<br />Background: Several oncological sterilization methods involving autoclaving, irradiation, or pasteur
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ization have been developed for limb reconstruction of large bone defects following tumor excision. Studies involving histological examinations of these autografts have all found that osteogenesis occurs slowly. We have used frozen autografts treated by liquid nitrogen for limb reconstruction and have achieved excellent results for bone union. To determine if frozen autografts exhibit early bone remodeling, we investigated the repair processes of the frozen bones. Methods: We analyzed frozen autografts treated by liquid nitrogen, retrieved at a mean of 19.1 months (2-75 months) after implantation because of complications or local tumor recurrence. The specimens were obtained from six patients with a mean age of 36.2 years (8-68 years). The six grafts comprised three osteoarticular grafts, two intercalary grafts, and one joint graft. We histologically reviewed the autograft-containing sections for tumor cell necrosis, evidence of cortical repair, the cortical junction, and joint cartilage. Results: Tumor cells were completely eradicated from the frozen bone in all cases. In a specimen retrieved 5 months after implantation, a small area of the bone showed active osteocytes and osteoblasts. In three cases retrieved more than 1 year after implantation, osteocytes and osteoblasts were observed in broad portions of the frozen bones, indicating the onset of osteogenesis in the frozen bone at an early stage. The cortical host-graft junction showed incorporation along with continuity of bone trabeculae. In addition, we were able to fi nd normal chondrocytes on the articular surface. Conclusions: The frozen bone specimens in this study thus showed evidence of newly formed bone and earlier osteogenesis than has been previously reported. Our results suggest that frozen autografts may be considered one of the most useful recycled materials for biological reconstruction. © 2009 The Japanese Orthopaedic Association.
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| 3.
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Shirai, Toshiharu ; Tsuchiya, Hiroyuki ; Shimizu, Tohru ; Ohtani, Kaori ; Zen, Yoh ; Tomita, Katsuro
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金沢大学医薬保健研究域医学系<br />The most frequent complication in external fixation is pin tract infection. To reduce the incidence
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of implant-associated infection, many published reports have looked at preventing bacterial adhesion by treating the pin surface. This study aimed to evaluate the antibacterial activity of a Titanium-Copper (Ti-Cu) alloy on implant infection, and to determine the potential use of the Ti-Cu alloy as a biomaterial. Two forms of Ti-Cu alloys were synthesized: one with 1% Cu and the other with 5% Cu. For analyzing infectious behavior, the implants were exposed to Staphylococcus aureus and Escherichia coli. The reaction of pathogens to the Ti-Cu alloys was compared with their reaction to stainless steel and pure titanium as controls. Both Ti-Cu alloys evidently inhibited colonization by both bacteria. Conversely, cytocompatibility studies were performed using fibroblasts and colony formation on the metals was assessed by counting the number of colonies. Ti-1% Cu alloy showed no difference in the number of colonies compared with the control. External fixator pins made of Ti-Cu alloys were evaluated in a rabbit model. The tissue-implant interactions were analyzed for the presence of infection, inflammatory changes and osteoid-formation. Ti-1% Cu alloy significantly inhibited inflammation and infection, and had excellent osteoid-formation. Copper blood levels were measured before surgery and at 14 days postoperatively. Preoperative and postoperative blood copper values were not statistically different. Overall, it was concluded that Ti-Cu alloys have antimicrobial activity and substantially reduce the incidence of pin tract infection. Ti-1% Cu alloy shows particular promise as a biomaterial. © 2009 Wiley Periodicals, Inc.
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| 4.
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Matsubara, Hidenori ; Tsuchiya, Hiroyuki ; Sakurakichi, Keisuke ; Watanabe, Koji ; Tomita, Katsuro
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金沢大学医学部附属病院整形外科<br />Deformities combined with shortening in 34 lower limb segments of 28 patients were treated with an
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Ilizarov external fixator or a Taylor spatial frame at the same level as the osteotomy. We compared an acute correction group (A) with a gradual correction group (G) in patients undergoing deformity correction followed by lengthening. We retrospectively examined the amount of deformity correction, length gained, distraction index, maturation index, and external fixation index in both groups. The mean age of subjects was 12.9 years for A, 17.9 years for G. The mean deformity correction was 17.8°for A, 25.1°for G. Mean lengthening was 5.5 cm for A, 5.0 cm for G. Mean distraction index was 16.4 days/cm for A, 10.6 days/cm for G (P<0.05). Mean maturation index was 40.5 days/cm for A, 29.5 days/cm for G (P=0.081). Mean external fixation index was 58.6 days/cm for A, 42.5 days/cm for G (P<0.05). The distraction index and external fixation index differences between the two groups were statistically significant. Gradual correction may represent a better approach than acute correction with the use of external fixators to treat deformity combined with shortening. © 2006 Springer-Verlag.
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Kawano, Masaya ; Taki, Junichi ; Tsuchiya, Hiroyuki ; Tomita, Katsuro ; Tonami, Norihisa
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金沢大学大学院医学系研究科<br />Distraction osteogenesis is an effective method for lengthening long bones and filling bone defects t
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hat result from bone resection. Insufficiency of bone consolidation in the distraction segment is problematic. In this study, we examined whether 3-phase bone scintigraphy can predict the outcome of distraction osteogenesis. We also investigated the effects of chemotherapy and surgical treatment on distraction osteogenesis. Methods: We performed 3-phase bone scintigraphy on 60 patients (9 high-grade malignant bone tumors as group A, 11 low-grade malignant or benign tumors as group B, 40 nontumoral conditions as group C) with distraction osteogenesis at the lengthening phase of the long bones. By setting the region of interest on the distraction segment and contralateral normal area, we calculated the perfusion index (PI), the uptake ratio of the blood-pool image (BPR), and the uptake ratio of the delayed image (DR). Patients were classified into poor and good consolidation groups from the radiographic findings of the distraction segment. Results: Good to fair correlations were obtained between the PI and BPR, the PI and DR, and the BPR and DR (r = 0.65, 0.45, and 0.57, respectively). The PI and BPR indicated no significant differences among group A-C (1.7 ± 0.6, 2.1 ± 0.7, and 1.8 ± 0.8 in PI, respectively; 1.8 ± 1.1, 1.9 ± 0.5, and 2.0 ± 0.7, in BPR, respectively). The DR of group A (2.4 ± 1.2) was significantly lower than that of group B (6.3 ± 1.8; P = 0.001) and group C (5.9 ± 2.8; P < 0.001). Eleven patients were classified in the poor consolidation group. The other 49 patients showed good consolidation. The poor consolidation group showed lower values in all indices obtained by 3-phase bone scintigraphy than the good consolidation group. The optimal cutoff levels, sensitivity, specificity, and accuracy of each index for detection of patients with poor consolidation were as follows: 1.1, 36%, 90%, and 80% in the PI, respectively; 1.2, 55%, 94%, and 87% in the BPR, respectively; and 2.2, 82%, 96%, and 93% in the DR, respectively. Conclusion: Three-phase bone scintigraphy is a promising method for the assessment of distraction osteogenesis. The delayed image of 3-phase bone scintigraphy, especially, is an excellent modality for predicting the outcome of distraction osteogenesis.
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| 6.
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Sakayama, Kenshi ; Kidani, Teruki ; Tsuchiya, Hiroyuki ; Tanji, Nozomu ; Watanabe, Yuji ; Yamamoto, Haruyasu ; Sugawara, Yoshifumi
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金沢大学大学院医学系研究科機能再生学<br />The clinical significance of hyaluronan (HA) levels in the cerebrospinal fluid (CSF) of patients
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with spinal tumor (ST) was evaluated in order to clarify whether HA concentrations in the CSF of patients with ST differ according to such factors as the tumor site and histopathological diagnosis. CSF samples were obtained from 40 patients with ST who had undergone myelography and CSF examinations retrospectively. The HA levels were determined using a sandwich-binding protein assay. The total protein (TP) levels were also determined. The HA and TP concentrations in CSF were significantly higher in patients with extramedullary tumor than in patients with intramedullary tumor. There was a significant correlation between HA and TP concentrations in CSF patients with ST. A HA assay for CSF is therefore considered to be potentially useful for estimating the localization of ST. © 2006 World Scientific Publishing Company.
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| 7.
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Taki, Junichi ; Sumiya, Hisashi ; Higuchi, Takahiro ; Tsuchiya, Hiroyuki ; Takazawa, Kotaro ; Tomita, Katsuro ; Tonami, Norihisa
概要:
金沢大学大学院医学系研究科<br />In malignant bone and soft-tissue tumors, intra-arterial chemotherapy and limb-saving surgery have be
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come popular. Myocutaneous inflammatory change and necrosis are the major local side effects of intra-arterial chemotherapy. 99mTc-macroaggregated albumin (MAA) imaging with intra-arterial tracer administration was performed to evaluate drug distribution, and the ability of 99mTc-MAA imaging to predict local side effects was assessed. Methods: In 24 patients, 42 99mTc-MAA images were obtained with tracer injection through an intra-arterial catheter that was inserted into the proximal portion of the tumor-feeding artery. Abnormal uptake other than by tumor was assessed visually and quantitatively. Results: In visual analysis, abnormal 99mTc-MAA accumulation was observed in 21 of 42 images. In the first consecutive 13 of these 21 images, intra-arterial chemotherapy with cisplatin, doxorubicin, and caffeine was administered, and myocutaneous inflammation or necrosis in the area corresponding to the abnormal 99mTc-MAA uptake was observed in 11. In contrast, none of the 21 images without abnormal 99mTc-MAA uptake demonstrated any local adverse effect from intra-arterial chemotherapy. In the last consecutive 8 images with abnormal 99mTc-MAA uptake, intra-arterial chemotherapy was initiated with only cisplatin, and doxorubicin and caffeine administration was changed to the intravenous route. In all 8 of these images, no local adverse effects from chemotherapy were observed. Overall, the sensitivity, specificity, and accuracy of 99mTc-MAA imaging for the detection of myocutaneous damage were 100% (11/11), 91% (21/23), and 94% (32/34), respectively, and positive and negative predictive values were 85% (11/13) and 100% (21/21), respectively. In quantitative analysis, when the diagnostic threshold of the uptake ratio was set at 2.5, sensitivity, specificity, and accuracy for the detection of myocutaneous complications were 91% (10/11), 96% (22/ 23), and 94% (32/34), respectively, and positive and negative predictive values were 91% (10/11) and 96% (22/23), respectively. Conclusion: 99mTc-MAA imaging with intra-arterial infusion before intra-arterial chemotherapy for bone and soft-tissue tumors can facilitate prediction of local myocutaneous adverse effects due to chemotherapy.
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| 8.
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Hayashi, M. ; Tsuchiya, Hiroyuki ; Otoi, Takeshige ; Agung, Budiyanto ; Yamamoto, N. ; Tomita, Katsuro
概要:
Improving survival rates for sarcoma patients are necessitating more functional and durable methods of reconstruction af
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ter tumor resection. Frozen osteoarticular grafts are utilized for joint reconstruction, but the joint may develop osteoarthritic change. We used a frozen autologous whole-rabbit knee joint graft model to investigate the influence of freezing on joint components. Thirty rabbit knee joints that had been directly immersed into liquid nitrogen (L) or saline (C) without use of cryoprotectants were re-implanted. Histological observations were made after 4, 8, and 12 weeks. Both groups had bone healing. In group L, despite restoration of cellularity to the menisci and ligaments, no live chondrocytes were observed and cartilage deterioration progressed over time. It was concluded that cryoinjury of chondrocytes caused osteoarthritic change. Then we tested whether a vitrification method could protect cartilage from cryoinjury. Full-thickness articular cartilage of rabbit knee was immersed into liquid nitrogen with and without vitrification. Histology, ultrastructure, and chondrocyte viability were examined before and after 24 h of culture. Vitrified cartilage cell viability was >85% compared with that of fresh cartilage. Transmission electron microscopy revealed preservation of original chondrocyte structure. Our vitrification method was effective for protecting chondrocytes from cryoinjury. Since reconstructing joints with osteoarticular grafts containing living cartilage avert osteoarthritic changes, vitrification method may be useful for storage of living cartilage for allografts or, in Asian countries, for reconstruction with frozen autografts containing tumors. © 2009 Elsevier Inc. All rights reserved.
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| 9.
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Watanabe, Koji ; Tsuchiya, Hiroyuki ; Sakurakichi, Keisuke ; Matsubara, Hidenori ; Tomita, Katsuro
概要:
石川県立中央病院 整形外科<br />金沢大学医薬保健研究域医学系<br />Background: Correction of deformities about knee joint may prevent or delay the o
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nset of osteoarthritis or mitigate its effects. Accurate correction of such deformities without production of secondary deformities depends on precise localization and quantification of the deformities. Methods: We corrected deformities around the knee using acute correction with focal dome osteotomy in 21 segments (15 patients). Five segments underwent limb lengthening postoperatively. Results: The mean correction angle was 16.0°. We were able to correct all segments. In the five lengthening cases, the mean external fixation index (EFI) was 70.9 days/cm, which is much higher than the generally reported EFI. There were eight complications, all but one of which occurred in lengthening cases. Conclusions: We believe that acute correction with focal dome osteotomy is very useful for cases of alignment correction, but is not indicated for cases of alignment correction with lengthening, due to a high risk of complications related to poor callus formation. © Springer-Verlag 2008.
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| 10.
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Matsubara, Hidenori ; Tsuchiya, Hiroyuki ; Sakurakichi, Keisuke ; Yamashiro, Teruhisa ; Watanabe, Koji ; Tomita, Katsuro
概要:
金沢大学医学部附属病院整形外科<br />Background. Multiple cartilaginous exostoses cause various deformities of the epiphysis. In exostos
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es of the ulna, the ulna is shortened and the radius acquires varus deformity, which may lead to dislocation of the radial head. In this study, we present the results of exostoses resection, with correction and lengthening with external fixators for functional and cosmetic improvement, and prevention of radial head dislocation. Methods. We retrospectively reviewed seven forearms of seven patients who had deformities of the forearm associated with multiple cartilaginous exostoses. One patient had dislocation of the radial head. Operative technique was excision of osteochondromas from the distal ulna, correction of the radius, and ulnar lengthening with external fixation up to 5 mm plus variance. We evaluated radiographs and the range of pronation and supination. Furthermore, we conducted a follow-up of ulnar length after the operation. Results. Dislocation of the radial head of one patient was naturally reduced without any operative intervention. At the most recent follow-up, six of the seven patients showed full improvement in pronation-supination. Ulnar shortening recurred with skeletal growth of four skeletally immature patients; however, it did not recur in one skeletally mature patient. Overlength of 5 mm was negated by the recurrence of ulnar shortening about 1.5 years after the operation. Conclusions. We treated seven forearms of seven patients by excision of osteochondromas, correction of radii, and gradual lengthening of ulnas with external fixators. The results of the procedure were satisfactory, especially for function of the elbow and wrist. However, we must consider the possible recurrence of ulnar shortening within about 1.5 years during skeletal growth periods in immature patients. © 2006 The Japanese Orthopaedic Association.
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