Toshiyuki Takemori, Hitomi Hara, Teruya Kawamoto, Naomasa Fukase, Ryoko Sawada, Shuichi Fujiwara, Ikuo Fujita, Takuya Fujimoto, Masayuki Morishita, Shunsuke Yahiro, Tomohiro Miyamoto, Masanori Saito, Jun Sugaya, Katsuhiro Hayashi, Hiroyuki Kawashima, Tomoaki Torigoe, Tomoki Nakamura, Hiroya Kondo, Toru Wakamatsu, Munenori Watanuki, Munehisa Kito, Satoshi Tsukushi, Akihito Nagano, Hidetatsu Outani, Shun-ichi Toki, Shunji Nishimura, Hiroshi Kobayashi, Itsuo Watanabe, Yusuke Demizu, Ryohei Sasaki, Takumi Fukumoto, Tomoyuki Matsumoto, Ryosuke Kuroda and Toshihiro Akisue : Comparison of clinical outcome between surgical treatment and particle beam therapy for pelvic bone sarcomas: A retrospective multicenter study in Japan., Journal of Orthopaedic Science, 30, 3, 523-528, 2024.
(要約)
Few studies have compared the clinical outcomes of patients with pelvic bone sarcomas treated surgically and those treated with particle beam therapy. This is a multicenter retrospective cohort study which compared the clinical outcomes of patients with pelvic bone sarcoma who underwent surgical treatment and particle beam therapy in Japan.A total of 116 patients with pelvic bone sarcoma treated at 19 specialized sarcoma centers in Japan were included in this study. Fifty-seven patients underwent surgery (surgery group), and 59 patients underwent particle beam therapy (particle beam group; carbon-ion radiotherapy: 55 patients, proton: four patients).The median age at primary tumor diagnosis was 52 years in the surgery group and 66 years in the particle beam group (P < 0.001), and the median tumor size was 9 cm in the surgery group and 8 cm in the particle beam group (P = 0.091). Overall survival (OS), local control (LC), and metastasis-free survival (MFS) rates were evaluated using the Kaplan-Meier method and compared among 116 patients with bone sarcoma (surgery group, 57 patients; particle beam group, 59 patients). After propensity score matching, the 3-year OS, LC, and MFS rates were 82.9% (95% confidence interval [CI], 60.5-93.2%), 66.0% (95% CI, 43.3-81.3%), and 78.4% (95% CI, 55.5-90.5%), respectively, in the surgery group and 64.9% (95% CI, 41.7-80.8%), 86.4% (95% CI, 63.3-95.4%), and 62.6% (95% CI, 38.5-79.4%), respectively, in the particle beam group. In chordoma patients, only surgery was significantly correlated with worse LC in the univariate analysis.The groups had no significant differences in the OS, LC, and MFS rates. Among the patients with chordomas, the 3-year LC rate in the particle beam group was significantly higher than in the surgery group.
(キーワード)
Humans / Retrospective Studies / 女性 (female) / 男性 (male) / Middle Aged / Aged / Japan / Bone Neoplasms / 成人 (adult) / Pelvic Bones / Treatment Outcome / Osteosarcoma / Proton Therapy / Sarcoma / Young Adult / Heavy Ion Radiotherapy / Survival Rate
Yasuyuki Ohmichi, Shun-ichi Toki, Toshihiko Nishisho, Takeshi Harada, Nori Sato and Koichi Sairyo : Atypical femoral fracture in a multiple myeloma patient undergoing treatment with denosumab: A case report and literature review., International Journal of Surgery Case Reports, 108, 2023.
(要約)
A 71-year-old woman with multiple myeloma developed dull pain in her right thigh 8 months after restarting high-dose denosumab following its initial administration for 4 months and subsequent withdrawal for 2 years. Fourteen months later, complete atypical femoral fracture occurred. Osteosynthesis was achieved using an intramedullary nail and she was switched to oral bisphosphonate 7 months after cessation of denosumab. There was no exacerbation of the multiple myeloma. Bone union was achieved and she recovered to her pre-injury level of activities. The oncological outcome was alive with disease at 2 years after surgery.
Makoto Takeuchi, Toshihiko Nishisho, Shun-ichi Toki, Shinji Kawaguchi, Shunsuke Tamaki, Takeshi Oya, Yoshihiro Uto, Toyomasa Katagiri and Koichi Sairyo : Blue light induces apoptosis and autophagy by promoting ROS-mediated mitochondrial dysfunction in synovial sarcoma., Cancer Medicine, 12, 8, 9668-9683, 2023.
(要約)
Taken together, our results revealed that BL induced apoptosis via the ROS-mitochondrial signaling pathway, and autophagy was activated in response to the production of ROS, which protected SS cells from apoptosis. Therefore, BL is a promising candidate for the development of an antitumor therapeutic strategy targeting SS.
Shun-ichi Toki, Toshihiko Nishisho, Ryo Miyagi, Yoshimi Bando, Mika Sakaki, Yusuke Demizu, Tomoaki Okimoto and Koichi Sairyo : Combination chemotherapy of doxorubicin and ifosfamide with proton beam therapy for myoepithelial carcinoma originating in the paraspinal region: A case report and literature review., Molecular and Clinical Oncology, 17, 6, 2022.
(要約)
Soft tissue myoepithelial carcinoma (MEC) is an extremely rare mesenchymal tumor that has a poor prognosis unless complete surgical resection is achieved. The present study reported a case of a 38-year-old woman with a tumor in the left paraspinal region at L2 to L3 with vertebral destruction. MEC was diagnosed based on molecular pathological examination of a biopsy specimen. Because curative surgery was expected to be difficult, a combination of chemotherapy with doxorubicin and ifosfamide and proton beam therapy as local therapy was performed, resulting in long-term survival for at least 7.8 years. To the best of our knowledge, this is the first case of soft tissue MEC for which classical cytotoxic chemotherapy and proton beam therapy were effective. Although surgical resection with negative margins is the mainstay of treatment for MEC, adequate doxorubicin-based systemic therapy and high-dose radiation therapy may be a feasible alternative in patients with unresectable or advanced MEC. Future studies on the relationship between molecular pathological features, including biomarkers, and the selection of therapeutic agents are warranted.
Satoshi Sumida, Shun-ichi Toki, Taisuke Mori, Kaishi Satomi, Shoichiro Takao, Sumihito Nobusawa, Takumi Kakimoto, Shinya Nakagawa, Eijitsu Ryo, Yuko Matsushita, Koichi Ichimura, Toshihiko Nishisho, Yoshimi Bando and Akihiko Yoshida : ZFTA::RELA fusion in a distinct liposarcoma morphologically overlapping with chondroid lipoma., Genes, Chromosomes & Cancer, 62, 2, 101-106, 2022.
(要約)
Chondroid lipoma is a rare benign adipose tumor characterized by a recurrent ZFTA::MRTFB fusion. Herein, we report an unusual liposarcoma that partly exhibited overlapping features with those of chondroid lipoma and harbored a ZFTA::RELA fusion. A 59-year-old man presented with a shoulder mass that had existed for approximately 8 years and with increasing pain due to a pelvic mass. The 5.8-cm resected shoulder tumor partly consisted of nests and strands of variably lipogenic epithelioid cells within a hyalinized or focally chondromyxoid stroma, indistinguishable from chondroid lipoma. The histological pattern gradually transitioned to highly cellular, stroma-poor, diffuse sheets of cells with greater nuclear atypia and mitotic activity. Vascular invasion and necrosis were present. The metastatic pelvic tumor revealed a similar histology. Despite multimodal treatment, the patient developed multiple bone metastases and succumbed to the disease 14 months after presentation. Targeted RNA sequencing identified an in-frame ZFTA (exon 3)::RELA (exon 2) fusion, which was confirmed by reverse transcription-polymerase chain reaction, Sanger sequencing, and break-apart fluorescent in situ hybridization assays. The tumor showed a different histology from that of ependymoma, no brain involvement, and no match with any sarcoma types or ZFTA::RELA-positive ependymomas according to DNA methylation analysis. p65 and L1CAM were diffusely expressed, and a CDKN2A/B deletion was present. This is the first report of an extra-central nervous system tumor with a ZFTA::RELA fusion. The tumor partly displayed an overlapping histology with that of chondroid lipoma, suggesting that it may represent a hitherto undescribed malignant chondroid lipoma with an alternative ZFTA fusion.
Toshiyuki Takemori, Teruya Kawamoto, Hitomi Hara, Naomasa Fukase, Shuichi Fujiwara, Ikuo Fujita, Takuya Fujimoto, Masayuki Morishita, Kazumichi Kitayama, Shunsuke Yahiro, Tomohiro Miyamoto, Masanori Saito, Jun Sugaya, Katsuhiro Hayashi, Hiroyuki Kawashima, Tomoaki Torigoe, Tomoki Nakamura, Hiroya Kondo, Toru Wakamatsu, Munenori Watanuki, Munehisa Kito, Satoshi Tsukushi, Akihito Nagano, Hidetatsu Outani, Shun-ichi Toki, Shunji Nishimura, Hiroshi Kobayashi, Itsuo Watanabe, Yusuke Demizu, Ryohei Sasaki, Takumi Fukumoto, Takahiro Niikura, Ryosuke Kuroda and Toshihiro Akisue : Clinical Outcome of Patients with Pelvic and Retroperitoneal Bone and Soft Tissue Sarcoma: A Retrospective Multicenter Study in Japan., Cancers, 14, 12, 3023, 2022.
(要約)
This study aimed to retrospectively analyze the clinical outcomes of patients with pelvic and retroperitoneal bone and soft tissue sarcoma (BSTS). Overall, 187 patients with BSTS in the pelvis and retroperitoneal region treated at 19 specialized sarcoma centers in Japan were included. The prognostic factors related to overall survival (OS), local control (LC), and progression-free survival (PFS) were evaluated. The 3-year OS and LC rates in the 187 patients were 71.7% and 79.1%, respectively. The 3-year PFS in 166 patients without any distant metastases at the time of primary tumor diagnosis was 48.6%. Osteosarcoma showed significantly worse OS and PFS than other sarcomas of the pelvis and retroperitoneum. In the univariate analyses, larger primary tumor size, soft tissue tumor, distant metastasis at the time of primary tumor diagnosis, P2 location, chemotherapy, and osteosarcoma were poor prognostic factors correlated with OS. Larger primary tumor size, higher age, soft tissue tumor, chemotherapy, and osteosarcoma were poor prognostic factors correlated with PFS in patients without any metastasis at the initial presentation. Larger primary tumor size was the only poor prognostic factor correlation with LC. This study has clarified the epidemiology and prognosis of patients with pelvic and retroperitoneal BSTS in Japan.
Yugen Fujii, Toshihiko Nishisho, Fumitake Tezuka, Akio Iwanami, Kazuta Yamashita, Shun-ichi Toki, Masatoshi Morimoto, Kosuke Sugiura, Toshinori Sakai, Toru Maeda and Koichi Sairyo : Hemangioblastoma of the Cauda Equina : A Case Report and Review of the Literature., The Journal of Medical Investigation : JMI, 69, 3.4, 312-315, 2022.
(要約)
Introduction : Hemangioblastoma in the spine mainly occurs at the cervical and thoracic levels and is often associated with von Hippel-Lindau (VHL) syndrome. Here, we reported a quite rare case of spinal sporadic hemangioblastoma arising from the cauda equina. Case presentation : A 66-year-old woman presented with a 5-year history of low back and leg pain. Imaging revealed a hypervascular intradural extramedullary tumor in the lumbar region. Preoperative angiography helped to identify the feeding arteries and draining vein, and so facilitated subsequent tumor resection. The pain was dramatically improved but weakness of the left tibialis anterior and left extensor hallucis longus muscles persisted. Discussion : We reported a rare case of spinal hemangioblastoma arising from the cauda equina. Preoperative angiography may be useful for diagnosis and understanding of the anatomy of feeding veins. J. Med. Invest. 69 : 312-315, August, 2022.
Shun-ichi Toki, Tetsuro Yoshimaru, Yosuke Matsushita, Hitoshi Aibara, Masaya Ono, Koichi Tsuneyama, Koichi Sairyo and Toyomasa Katagiri : The survival and proliferation of osteosarcoma cells are dependent on the mitochondrial BIG3-PHB2 complex formation., Cancer Science, 112, 10, 4208-4219, 2021.
(要約)
Previous studies reported the critical role of the brefeldin A-inhibited guanine nucleotide exchange protein 3-prohibitin 2 (BIG3-PHB2) complex in modulating estrogen signaling activation in breast cancer cells, yet its pathophysiological roles in osteosarcoma (OS) cells remain elusive. Here, we report a novel function of BIG3-PHB2 in OS malignancy. BIG3-PHB2 complexes were localized mainly in mitochondria in OS cells, unlike in estrogen-dependent breast cancer cells. Depletion of endogenous BIG3 expression by small interfering RNA (siRNA) treatment led to significant inhibition of OS cell growth. Disruption of BIG3-PHB2 complex formation by treatment with specific peptide inhibitor also resulted in significant dose-dependent suppression of OS cell growth, migration, and invasion resulting from G2/M-phase arrest and in PARP cleavage, ultimately leading to PARP-1/apoptosis-inducing factor (AIF) pathway activation-dependent apoptosis in OS cells. Subsequent proteomic and bioinformatic pathway analyses revealed that disruption of the BIG3-PHB2 complex might lead to downregulation of inner mitochondrial membrane protein complex activity. Our findings indicate that the mitochondrial BIG3-PHB2 complex might regulate PARP-1/AIF pathway-dependent apoptosis during OS cell proliferation and progression and that disruption of this complex may be a promising therapeutic strategy for OS.
Image-guided percutaneous core needle biopsy (CNB) has been an important diagnostic procedure for musculoskeletal lesions. Here we surveyed the variety of diagnostic strategies available and assessed the clinical usefulness and limitations of image-guided CNB carried out by a multidisciplinary team comprising specialists in various fields. We conducted a retrospective study of 284 image-guided CNBs among 1899 consecutive biopsy procedures carried out at our institution for musculoskeletal tumorous conditions, focusing on their effectiveness including diagnostic accuracy and utility for classification of specimens according to malignant potential and histological subtype as well as their correlation with biopsy routes. Among the 284 studied biopsies, 252 (88.7%) were considered clinically "effective". The sensitivity for detection of malignancy was 94.0% (110/117) and the specificity was 95.3% (41/43). The diagnostic accuracy for detection of malignancy was 94.4% (151/160) and that for histological subtype was 92.3% (48/52). The clinical effectiveness of the procedure was correlated with the complexity of the biopsy route (P = 0.015); the trans-pedicular, trans-retroperitoneal and trans-sciatic foramen approaches tended to yield ineffective results. Repeat biopsy did not have a significant impact on the effectiveness of image-guided CNB (P = 0.536). The diagnostic accuracy rates of image-guided CNB performed at multidisciplinary sarcoma units were usable even for patients who have variety of diagnostic biopsy procedures. It is important to establish and implement diagnostic strategies based on an understanding that complicated routes, especially for spine and pelvic lesions, may be associated with ineffectiveness and/or complications.
Keizo Wada, 三上 浩, Shun-ichi Toki, 甘利 留衣, Michihiro Takai and Koichi Sairyo : Intra- and inter-rater reliability of a three-dimensional classification system for intertrochanteric fracture using computed tomography, Injury, 51, 11, 2682-2685, 2020.
(要約)
Intertrochanteric fractures are common fragility fractures in elderly patients. The importance of a reliable classification system for these fractures has been increasingly recognized. The aim of this study was to test the hypothesis that three-dimensional classification by CT has better intra- and inter-observer reliability than conventional two-dimensional classification. Two hundred and three consecutive patients (39 male, 164 female; mean age 84.5 years) with intertrochanteric fracture were included in the study. In each case, the fracture was classified using the two-dimensional Evans-Jensen and AO/OTA systems that rely on plain radiographs and using a three-dimensional fragment-based CT system. The second evaluation was performed 1 month after the first evaluation by the same examiner to determine intra-observer reliability. Another blinded examiner also classified each case to assess inter-observer reliability. The kappa coefficient was used for determination of intra- and inter-observer reliability. The kappa values for the two-dimensional Evans-Jensen and AO/OTA classification systems showed moderate intra-observer reliability (κ=0.65 and κ=0.61, respectively) and slight inter-observer reliability (κ=0.20 and κ=0.19). The intra-observer kappa value for the three-dimensional classification system was 0.88, indicating almost perfect reliability; the inter-observer kappa value was 0.70, indicating substantial reliability. The findings of this study confirm that the fragment-based classification system has high reliability. Surgeons should be aware that the three-dimensional fragment-based CT system for classification of intertrochanteric fractures has better intra-observer and inter-observer reliability than the conventional two-dimensional systems.
Shun-ichi Toki, Kousaku Higashino, Hiroaki Manabe, Masatoshi Morimoto, Kosuke Sugiura, Fumitake Tezuka, Kazuta Yamashita, Yoichiro Takata, Toru Maeda, Toshinori Sakai, Natsuo Yasui and Koichi Sairyo : Morphometric Analysis of Subaxial Cervical Spine with Myelopathy: A Comparison with the Normal Population., Spine Surgery and Related Research, 5, 1, 34-40, 2020.
(要約)
The morphometry of the sagittal diameter of the spinal canal, sagittal-transverse ratio, and canal-body ratio on axial reconstructive CT images appears useful for distinguishing cervical spinal canal stenosis involving myelopathy.
Shota Shigekiyo, Toshihiko Nishisho, Yoichiro Takata, Shun-ichi Toki, Kosuke Sugiura, Yoshihiro Ishihama, Hiroaki Manabe, Fumitake Tezuka, Kazuta Yamashita, Toshinori Sakai, Toru Maeda and Koichi Sairyo : Intracanalicular Osteochondroma in the Lumbar Spine., NMC Case Report Journal, 7, 1, 11-15, 2020.
(要約)
resection of the osteochondroma with the ligamentum flavum relieved the symptoms. Spinal osteochondroma occurs relatively frequently in elderly individuals compared with peripheral lesions and mimics a degenerative spinal disorder. Careful physical examination and imaging evaluation can reveal this tumor and surgery is effective for relieving the symptoms.
Kaori Momota, Toshihiko Nishisho, Ryo Miyagi, Shun-ichi Toki, Kazuta Yamashita, Fumitake Tezuka, Yoichiro Takata, Toshinori Sakai, Akihiro Nagamachi, Toru Maeda and Koichi Sairyo : A Rare Case of Acute-Onset Spastic Quadriparesis Caused by a Chondroma of the Cervical Spine., Case Reports in Orthopedics, 2019, 2019.
(要約)
Chondromas are benign cartilaginous tumors that occur very rarely in the spine. Moreover, chondromas of the extraskeletal origin are also very rare. In this case report, we describe an extremely rare case of chondroma arising from the ligamentum flavum in the cervical spine. A 67-year-old man presented to our clinic with acute-onset spastic quadriparesis. We performed emergent magnetic resonance imaging and found an epidural mass in the right ligamentum flavum at C4-C5. The acute-onset presentation was suspicious for intraligamentous hematoma in the ligamentum flavum at this level. We performed emergency decompression surgery and en bloc removal of the epidural mass with the right C4 and C5 lamina. The lesion had the appearance of cartilaginous tissue rather than hematoma. Based on the histological investigation, the final diagnosis was intraligamentous chondroma of the cervical spine. The quadriparesis improved postoperatively, as did the results of manual muscle testing in the affected area, and he was able to resume walking independently with a cane. At the one-year follow-up, the manual muscle testing results were almost normal. Surgeons should keep in mind the possibility of benign tumors including chondroma of the cervical spine when a patient presents with acute-onset quadriparesis.
Keizo Wada, Hiroshi Mikami, Rui Amari, Shun-ichi Toki, Michihiro Takai and Koichi Sairyo : A novel three-dimensional classification system for intertrochanteric fractures based on computed tomography findings., The Journal of Medical Investigation : JMI, 66, 3.4, 362-366, 2019.
(要約)
A novel three-dimensional fragment-based classification system based on computed tomography findings was established to characterize femoral intertrochanteric fractures. The intertrochanteric bone fragments were defined as follows : neck, posterior portion of the greater trochanter, anterior portion of the greater trochanter, lesser trochanter, and shaft. Each type of fracture was classified as 2-, 3-, 4-, or 5-fragment according to the number of floating bone fragments. Following the description of the fracture type, each floating bone fragment was appended, with the exception of a fragment involving the shaft. Ninety-five intertrochanteric fractures were classified by the same surgeon. The fractures occurred in 14 men and 81 women with a mean age of 84.7 years. The frequency of each type of fracture was investigated. Thirty-one fractures (32.6%) were 2-fragment and 64 (67.4%) were ≥ 3-fragment. A fragment of the anterior portion of the greater trochanter, which cannot be classified using conventional systems, was included in 29 cases (30.5%). A 5-fragment fracture was detected in two cases (2.1%). Using this fragment-based classification system, intertrochanteric fractures can be evaluated in more detail than is possible using conventional classification systems. J. Med. Invest. 66 : 362-366, August, 2019.
Masashi Kano, Toshihiko Nishisho, Ryo Miyagi, Fumio Chikugo, Eiji Kudo, Shoichiro Takao, Seiji Iwamoto, Shun-ichi Toki and Koichi Sairyo : Intimal sarcoma arising from the common iliac artery presenting with artery occlusion : a case report and literature review., The Journal of Medical Investigation : JMI, 66, 1.2, 205-208, 2019.
(要約)
We present a rare case of intimal sarcoma arising from the common iliac artery in an 82-year-old man who presented with intermittent claudication. He had undergone endovascular therapy with self-expanding stents to both iliac arteries that had occluded soon after placement. After salvage bypass grafting, a diagnosis of intimal sarcoma with angiosarcoma phenotype from the iliac artery was made. Further bypass graft surgery relieved symptoms temporarily. However, the tumor progressed and the left limb became ischemic. The chemotherapy of eribulin did not prevent tumor progression. The patient died of the disease 20 months after the first surgery. J. Med. Invest. 66 : 205-208, February, 2019.
Toshihiko Nishisho, Shun-ichi Toki, Ryo Miyagi and Koichi Sairyo : ASSESSMENT OF SURGICAL MARGIN CLASSIFICATION FOR SOFT TISSUE SARCOMA: DEFINITIONS OF ADEQUATE MARGINS SYSTEM FOR PLANNING AND EVALUATION, The Connective Tissue Oncology Society 2022 annual meeting, Vancouver, Nov. 2022.
2.
Shun-ichi Toki, Toshihiko Nishisho and Numoto Kunihiko : Core needle biopsy versus open biopsy of malignant bone tumor in diagnostic accuracy, complications, and cost-effectiveness: A systematic review and meta-analysis, 21st General Meeting of the International Society of Limb Salvage (ISOLS), Los Angeles, Jun. 2022.
3.
Toshihiko Nishisho, Shun-ichi Toki, Ryo Miyagi and Koichi Sairyo : ACIDIC MICROENVIRONMENTS IN SOFT TISSUE SARCOMA PROMOTES FOXM1 EXPRESSION AND TUMORIGENESIS., The Connective Tissue Oncology Society Annual Meeting, Nov. 2020.
4.
Toshihiko Nishisho, Shun-ichi Toki, Ryo Miyagi and Koichi Sairyo : SOFT-TISSUE SARCOMA IN ELDERLY PATIENTS: PATTERNS OF CARE AND SURVIVAL, The Connective Tissue Oncology Society Annual Meeting, November 18-21, 2020., Nov. 2020.
5.
Shun-ichi Toki, Kobayashi Eisuke, Yoshida Akihiko and Kawai Akira : A Clinical Outcome of Dedifferentiated Low-grade Osteosarcoma Based on Molecular Pathological Confirmation, ESMO Asia 2018(November 23-25,2018), Singapore, Nov. 2018.
6.
Shun-ichi Toki, Eisuke Kobayashi, Akihiko Yoshida, Shintaro Iwata and Akira Kawai : The clinical outcome of dedifferentiated low-grade osteosarcoma based on molecular pathological confirmation: A retrospective cohort study in single institution, EMSOS 2018, Amsterdam, May 2018.