Faculty Profiles - KUNISADA Toshiyuki

Accurate diagnosis of musculoskeletal lesions by core needle biopsy Reviewed

G Mitsuyoshi, N Naito, A Kawai, T Kunisada, A Yoshida, H Yanai, S Dendo, T Yoshino, S Kanazawa, T Ozaki

JOURNAL OF SURGICAL ONCOLOGY 94 ( 1 ) 21 - 27 2006.7

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-LISS

Background: Percutaneous needle biopsy has many advantages over open biopsy in the treatment of neoplasms. However, the accuracy of needle biopsy in the diagnosis of musculoskeletal lesions has not yet been established. Here, we evaluate the accuracy and limitations of the procedure for musculloskeletal lesions.
Methods: The diagnoses of 163 needle biopsies (bone, 91; soft tissue, 72) performed on 157 consecutive patients using a Jamshidi needle or an Ostycut needle for bone lesions, or a Tru-cut needle for soft tissue lesions were compared with the final diagnoses made by open biopsy and/or a definitive operation.
Results: One hundred forty-three specimens (88%) were determined to be adequate for histological examination. Obtaining undamaged cores from very hard bony lesions or sclerotic cyst walls proved difficult. A pathologist with experience in musculoskeletal lesions was able to differentiate malignant tumors from benign lesions in 97% of the cases (bone, 100%; soft tissue, 94%) and arrive at a specific diagnosis in 88% (bone, 96%; soft tissue, 78%) when adequate cores were obtained. Differentiating a well-differentiated liposarcoma from a benign lipoma and inflammatory lesions from benign tumorous conditions, was difficult. The overall accuracy was 77% (bone, 85%; soft tissue, 68%). There was no morbidity related to the procedure.
Conclusion: The results indicate that needle biopsy is safe and accurate for diagnosing musculoskeletal lesions.

DOI： 10.1002/jso.20504

Chromosomal and genetic imbalances in synovial sarcoma detected by conventional and microarray comparative genomic hybridization Reviewed

Y Nakagawa, K Numoto, A Yoshida, T Kunisada, H Ohata, K Takeda, D Wai, C Poremba, T Ozaki

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 132 ( 7 ) 444 - 450 2006.7

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

Purpose: To analyze the relationship between chromosomal instabilities and clinicopathological factors in synovial sarcoma (SS). Methods: Twenty-two fresh-frozen SS were analyzed by metaphase comparative genomic hybridization (CGH). Additional microarray CGH was performed in 13 cases. Results: Fourteen patients with SYT-SSX1 rearrangements and nine patients with biphasic tumor subtypes had better prognosis than the eight patients with SYT-SSX2 rearrangements and 13 patients with monophasic subtypes, respectively. Gains (average 3.0) were more frequent than losses (average 1.0). Frequent gains were identified on chromosomal regions 2, 6q, 7, 8q, 12, 17q, 18q, and 21q, whereas frequent losses were over-lapped on chromosomes 1p31-p35, 3p, 6q, 16, and 17p. High-level gains were observed on chromosomes 1q21-q31, 7, 8, 12, 17q, 18q, and 21q. Thirteen monophasic and nine biphasic tumors had an average of 5.1 and 2.8 aberrations, respectively. Patients with tumors harboring numerous aberrations (>= 3) had a worse clinical course. Microarray CGH more specifically detected genetic imbalances including gains in MDM2, MSH2, KCNK12, DCC, CDK2, ERBB3, SAS, and CDK4 and losses in HRAS, RASSF1, and CCND1. Gain of SAS was an important prognostic factor of SS. Conclusion: We have identified several factors influencing the prognosis of SS patients by metaphase and microarray CGH.

DOI： 10.1007/s00432-006-0089-5

Magnetic resonance angiography without contrast enhancement medium in bone and soft tissue tumors Reviewed

H Doi, A Ono, A Kawai, Y Morimoto, T Kunisada, E Nakata, T Ozaki

ONCOLOGY REPORTS 15 ( 3 ) 681 - 685 2006.3

Language：English Publishing type：Research paper (scientific journal) Publisher：PROFESSOR D A SPANDIDOS

The aim of this study was to assess the ability of a new magnetic resonance (MR) angiography technique that does not use contrast enhancement medium to depict the vascularity of musculoskeletal neoplasms, and evaluate its clinical utility. We performed 3D fresh blood imaging (FBI) MR angiography in 57 patients with bone or soft tissue tumors, and the detection of vessels in and around the tumor was evaluated. Moreover, differences in vascularity between benign and malignant tumors were analyzed. In the lower leg, large arteries such as femoral or popliteal arteries were visible. In the trunk or arm, large vessels such as subclavian or iliac arteries were visible. Discrimination between benign and malignant tumors was impossible in bone tumors; however, the mean value of vascularity differed between benign and malignant tumors in the soft tissue tumors. This is the first trial of the FBI method for bone and soft tissue tumors. The still developing rnethod of MRA without contrast materials could clearly depict major arteries in the trunk and the extremities, this method may replace conventional MRA of bone and soft tissue tumors because it produces vivid images while being non-invasive.

Chromosomal imbalances in malignant peripheral nerve sheath tumor detected by metaphase and microarray comparative genomic hybridization Reviewed

Y Nakagawa, A Yoshida, K Numoto, T Kunisada, D Wai, N Ohata, K Takeda, A Kawai, T Ozaki

ONCOLOGY REPORTS 15 ( 2 ) 297 - 303 2006.2

Language：English Publishing type：Research paper (scientific journal) Publisher：PROFESSOR D A SPANDIDOS

Malignant peripheral nerve sheath tumors (MPNSTs) are highly malignant tumors affecting adolescents and adults. There have been a few reports on chromosomal aberrations of MPNSTs; however, the tumor-specific alteration remains unknown. We characterized the genomic alterations in 8 MPNSTs and 8 schwannomas by metaphase comparative genomic hybridization (CGH). In 5 of 8 MPNSTs, microarray CGH was added for more detailed analyses. Frequent gains were identified on 3q13-26, 5p13-14, and 12q11-23 and frequent losses were at 1p31, 10p, 11q24-qter, 16, and 17. Microarray CGH revealed frequent gains of EGFR, DAB2, MSH2, KCNK12, DDX15, CDK6, and LAMA3, and losses of CDH1, GLTSCR2, EGR1, CTSB, GATA3, and SULT2A1. These genes seem to be responsible for developing MPNSTs. The concordance rate between metaphase CGH and microarray CGH was 66%. Metaphase CGH was useful for identifying chromosomal alterations before applying rnicroarray CGH.

Novel transdermal photodynamic therapy using ATX-S10・Na(II) induces apoptosis of synovial fibroblasts and ameliorates collagen antibody-induced arthritis in mice

Miyazawa S, Nishida K, Komiyama T, Nakae Y, Takeda K, Yorimitsu M, Kitamura A, Kunisada T, Ohtsuka A, Inoue H

Rheumatol. Int 2006

Calpain inhibitors prevent neuronal cell death and ameliorate motor disturbances after compression-induced spinal cord injury in rats Reviewed

S Arataki, K Tomizawa, A Moriwaki, K Nishida, M Matsushita, T Ozaki, T Kunisada, A Yoshida, H Inoue, H Matsui

JOURNAL OF NEUROTRAUMA 22 ( 3 ) 398 - 406 2005.3

Language：English Publishing type：Research paper (scientific journal) Publisher：MARY ANN LIEBERT INC

Traumatic spinal cord injury (SCI) results in widespread neuronal cell death. Recent studies have suggested that activated calpain mediates neuronal cell death in the central nervous system. We conducted a study to determine whether calpain mediates neuronal cell death in the motor neurons of the spinal cord after SCI, and whether postinjury administration of the calpain inhibitors N-acetyl-Leu-Leu-Met-CHO (ALLM) and calpain inhibitor III (CI III) (MDL28170) reduces the motor disturbances in rats with a model of SCI. Adult male Wistar rats were subjected to SCI by application of a 20-g weight impactor probe to the spinal cord at T12 for 20 min. The rats were divided into three groups according to whether they were injected intravenously with 0.05-2.5 mg/kg ALLM, 10 mg/kg CI III, or 0.1% DMSO as a control every 24 h for I week after SCI. Calpain was activated in the spinal cord at 8 h, 24 h, and 5 days after SCI, and administration of ALLM inhibited its activation. ALLM, as compared to the DMSO vehicle alone, also significantly reduced the number of motor neurons in spinal-cord lesions that were positively labeled at 24 h after SCI with the terminal deoxynucleotidyl transferase-uridine nucleotide end-labeling (TUNEL) technique. Additionally, both the inclined plane test and footprint analysis showed markedly better motor activity after 4 weeks in rats injected with ALLM or CI III than in rats given vehicle only. These results suggest that activation of calpain plays a critical role in the neuronal cell death that follows SCI, and that calpain inhibitors may have benefit in treating the motor disturbances that follow SCI.

DOI： 10.1089/neu.2005.22.398

Treatment result of distal lower leg malignant soft tissue tumors

NAKATA Eiji

The Central Japan Journal of Orthopaedic Surgery & Traumatology 48 ( 1 ) 109 - 110 2005

Treatment result of synovial osteochondromatosis

NAKATA Eiji

The Central Japan Journal of Orthopaedic Surgery & Traumatology 48 ( 6 ) 989 - 990 2005

Treatment result of giant cell tumor of tendon sheath

ITANI Satoru

The Central Japan Journal of Orthopaedic Surgery & Traumatology 48 ( 6 ) 981 - 982 2005

X-ray dark-field Imaging and potential of its clinical application Reviewed

Daisuke Shimao, Hiroshi Sugiyama, Toshiyuki Kunisada, Anton Maksimenko, Fukai Toyofuku, Ei Ueno, Katsuhito Yamasaki, Chiho Obayashi, Kazuyuki Hyodo, Gang Li, Lin Pan, Xiaoming Jiang, Masami Ando

Progress in Biomedical Optics and Imaging - Proceedings of SPIE 5745 ( I ) 32 - 39 2005

Language：English Publishing type：Research paper (international conference proceedings)

X-ray dark-field imaging (DFI) due to refraction is under development with intension of its clinical application. In this system we have adopted an asymmetric-cut monochro-collimator (M) and an angular analyzer (A) of Si 440 diffraction at around 35 keV of X-rays. By choosing an appropriate thickness T of A that satisfies the condition T = λN where λ is the extinction distance and N integer the transmissivity in the region of |W| (angular parameter) &lt
1 should be theoretically almost zero and |W| &gt
1 should be approximately 70-80%. This has been experimentally proven. Under this condition the X-rays whose propagation direction may not change such as those receiving only absorption will not go into the forward diffraction direction after A but go into the diffraction direction, while the X-rays refracted by object may go into the forward diffraction direction after A. We have settled two targets of clinical views: soft tissues at joints and early check of breast cancer. A first clear image of articular cartilage of small joint was successfully obtained using a proximal interphalangeal joint that was amputated from a cadaver. Since larger view field is needed for clinical use the size of approximately 90 mm in square has been successfully achieved. Using this beam articular cartilage of knee and shoulder joints from the same cadaver have been successfully visualized. Further visibility test by the DFI is under way for a phantom of breast cancer, paraffin fixed sliced breast samples containing micro-calcification, tumor and excised breast tissue.

DOI： 10.1117/12.595021

Scopus

Clinical step onward with X-ray dark-field imaging and perspective view of medical applications of synchrotron radiation in Japan

Ando, M, Hashimoto, E, Hashizume, H, Hyodo, K, Inoue, H, Kunisada, T, Maksimenko, A, Mori, K, Rubenstein, E, Roberson, J, Shimao, D, Sugiyama, H, Takeda, K, Toyofuku, F, Ueno, E, Umetani, K, Wada, H, Pattanasiriwisawa, W

Nucl. Instrum. Methods. Phys. Res. A 548 ( 1-2 ) 1 - 16 2005

The role of thallium-201 and pentavalent dimercaptosuccinic acid for staging cartilaginous tumours. Reviewed

Choong PF, Kunisada T, Slavin J, Schlicht S, Hicks R

International seminars in surgical oncology : ISSO 1 ( 1 ) 10 2004.11

Construction of X-ray dark-field imaging with a view size of 80mm square and first visualization of human articular cartilage of femoral head under a nearly clinical condition Reviewed

Masami Ando, Hiroshi Sugiyama, Toshiyuki Kunisada, Daisuke Shimao, Ken Takeda, Hiroyuki Hashizume, Hajime Inoue

Japanese Journal of Applied Physics, Part 2: Letters 43 ( 9 ) L1175 - L1177 2004.9

Language：English Publishing type：Research paper (scientific journal)

Field size of 80mm × 80mm for X-ray dark-field (DFI) imaging at 35keV using a 2.16-mm-thick 440 Laue diffraction analyzer has been achieved. Under this condition, only refracted X-rays from sample can transmit through this filter to form DFI while the beam that has not changed its direction is repelled to the diffraction direction. Its spatial resolution is 10 microns or better. An excised human femoral head in a water-filled vinyl bag simulating a clinical condition shows a high-contrast and high-spatial-resolution articular cartilage that has not been visualized by X-ray technique.

DOI： 10.1143/JJAP.43.L1175

Scopus

Evaluation of X-ray dark-field imaging in visualization of nearly clinical articular cartilage Reviewed

D Shimao, H Sugiyama, K Hyodo, T Kunisada, M Ando

NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT 548 ( 1-2 ) 129 - 134 2004.8

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Angular dependence of visibility at articular cartilage of an intact human finger and knee by X-ray dark-field imaging (DFI) and bright-field imaging (BFI) was tested. These specimens were fixed by formalin. Good contrast of the articular cartilage has been obtained, as a preliminary result, not only by DFI but also by pseudo-DFI and BFI around the just Bragg angle of the angular analyzing crystal. This may indicate that it is useful for clinical purpose to use both DFI and BFI not only at just Bragg angle but also around it. (c) 2005 Elsevier B.V. All rights reserved.

Influence of telomerase activity on bone and soft tissue tumors Reviewed

N Umehara, T Ozaki, S Sugihara, T Kunisada, Y Morimoto, A Kawai, K Nishida, A Yoshida, T Murakami, H Inoue

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 130 ( 7 ) 411 - 416 2004.7

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

Purpose. Telomeres consisting of a repeating nucleotide sequence (TTAGGG)n are shortened in normal somatic cells. Telomerase is an enzyme that elongates the telomere sequence and is detected in most human cancers and usually not in normal somatic cells. Little is known about telomerase activity in bone and soft tissue tumors. The aim of this study was to investigate the relationship between telomerase activity and clinical factors in bone and soft tissue tumors. Methods. Telomerase activity was measured using the modified telomeric repeat amplification protocol (TRAP) assay in 115 bone and soft tissue tumors obtained through open biopsy or resection. Results. Telomerase activity was detected in 10% of benign tumors and 44% of malignant tumors (p<0.001). A higher incidence of telomerase activity was detected in high-grade tumors than in low-grade tumors (p=0.002). The cumulative metastasis-free and overall survival in telomerase-positive patients was significantly worse than in telomerase-negative patients (p=0.045 and p=0.048). Conclusion. Our study suggests that telomerase activity is associated with tumor aggressiveness and may be a useful parameter to predict the prognosis of patients with malignant bone and soft tissue tumors.

DOI： 10.1007/s00432-004-0553-z

Reconstruction with ipsilateral fibula transfer with pasteurized bone after excision of bone sarcoma of the tibia Reviewed

Toshifumi Ozaki, Kazuo Fujiwara, Toshiyuki Kunisada, Tatsuo Ito, Akira Kawai, Hajime Inoue

Sarcoma 8 ( 2-3 ) 97 - 102 2004.6

Language：English Publishing type：Research paper (scientific journal)

We report a technique of implantation of the ipsilateral vascularized fibula with pasteurized recycled bone after excision of tibia sarcoma in two cases. Plate and screws were used for osteosynthesis of die tibia or talus, vascularized fibula, and pasteurized bone. Microsurgery is not necessary for this reconstruction technique. Two patients who underwent this technique have obtained good functional results without tumor relapse 5 and 6 years after operation. The technique produced excellent results with regard to tibial reconstruction in these cases. We found it to be simple, speedy, safe, and a low cost technique by use of recycled bone.

DOI： 10.1080/13577140400017794

Scopus

Extended total sacrectomy and reconstruction for sacral tumor Reviewed

N Ohata, T Ozaki, T Kunisada, Y Morimoto, M Tanaka, H Inoue

SPINE 29 ( 6 ) E123 - E126 2004.3

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Study Design. This case report includes the results of long-term follow-up after extended total sacrectomy in a 13-year-old boy with a sarcoma originating in the sacrum with an extraskeletal extension and infiltration into the left ilium.
Objective. To report and discuss a case of sacral tumor treated by extended sacrectomy.
Summary of Background Data. Sacral tumors are often at an advanced stage with a large volume at diagnosis. Although total or extended sacrectomy is the only radical means to treat the massive sacral tumor, unavoidable complications in total sacrectomy are serious in the treatment selection.
Methods. Initial histologic findings indicated a synovial sarcoma. Additional genetic analysis redesignated the tumor as an unclassified sarcoma. Preoperative neoadjuvant chemotherapy and radiotherapy were completed. The response to the preoperative treatment appeared as a reduction in tumor size ( approximately 50%) on radiographs. After extended sacrectomy, the L5 vertebral body was fixed between the ilia, and the pelvic ring was compressed by the Zielke system. The ISOLA instrumentation system connected the lumbar spine and both ilia. All sacral nerve roots and the L5 root on the left side were cut.
Results. At the 5-year follow-up examination, the patient was disease- free, could walk with crutches, and could climb stairs using the handrail and one crutch.
Conclusions. The patient's excellent response to preoperative antitumor treatment was considered crucial to the long-term outcome. But the decision between a radical resection with reconstruction and a less extensive procedure with combined therapy remains controversial.