研究者詳細 - 相馬　智也

論文 - 相馬　智也

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WHO 頭頸部腫瘍分類の改訂(第5版)に伴う口腔潜在的悪性疾患と口腔上皮性異形成の臨床と病理

日本口腔腫瘍学会口腔表在癌ワーキンググループ, 柳下寿郎, 明石良彦, 莇生田整治, 石川文隆, 伊藤由美, 猪俣徹, 河内洋, 佐藤由紀子, 里見貴史, 関川翔一, 相馬智也, 舘原誠晃, 野村武史, 藤井誠志, 松坂賢一, 辺見卓男, 道泰之, 八木原一博, 山城正司

日本口腔腫瘍学会誌（一般社団法人日本口腔腫瘍学会） 37 （ 2 ） 41 - 51 2025年06月

査読有り, ISSN 0915-5988

World Health Organization（WHO）の腫瘍分類は，世界中で診断業務を標準化するための不可欠なツールであり，そのためのガイドブックであることは周知の事実である。本稿では，WHO頭頸部腫瘍分類改訂（第5版）における口腔領域の上皮性腫瘍の中で，表在性病変に関連する口腔潜在的悪性疾患と口腔上皮性異形成について改訂点を概説する。口腔潜在的悪性疾患については，2017年のWHO頭頸部腫瘍分類第4版において初めて記載され，従前の前癌状態と前癌病変を統合させる概念となった。今回の改訂では，3つの疾患が削除され，1つは新規に加えられた家族性癌症候群の中に組み込まれた。その他に，新たに3つの疾患，増殖性疣状白板症，口腔苔癬様病変，口腔移植片対宿主病が追加された。口腔上皮性異形成は主に口腔潜在的悪性疾患でみられ，扁平上皮癌への進展リスクを伴う病変であると定義されている。そして，口腔上皮性異形成のグレード分類が口腔潜在的悪性疾患の病理組織学的な評価ツールになっている。一方で，口腔上皮性異形成の取り扱いについては，矛盾が生じた内容と受け取られる改訂となっていることから，その問題点と口腔表在癌ワーキンググループの口腔上皮性異形成に対する考え方について概説する。

オスラー病を有する患者の上顎正中埋伏過剰歯の1例

木村大志, 相馬智也, 莇生田整治, 遠藤友樹, 中川種昭, 内田育宏

有病者歯科医療（(一社)日本有病者歯科医療学会） 32 （ 5 ） 291 - 303 2024年09月

査読有り, ISSN 0918-8150

オスラー病は皮膚や粘膜,全身臓器の血管異常をきたす常染色体優性遺伝疾患である.その診断にはCuracao criteriaと呼ばれる臨床診断が広く用いられている.今回われわれは,オスラー病を有する患者の上顎正中埋伏過剰歯の抜歯の1例を経験したためその概要を報告する.患者は8歳の男児,上顎正中埋伏過剰歯の精査・加療目的に当科を受診した.既往歴,家族歴から7歳時にオスラー病と診断されていた.上顎正中埋伏過剰歯は鼻腔底粘膜に接しており,反復性鼻出血の既往があることから入院・全身麻酔下に抜歯術を実施,術中・術後の異常出血は認められず経過は良好であった.本症例では術前からオスラー病と診断されていたが,既往歴や臨床所見,治療を契機として発見される可能性もあり,本疾患への理解を深める必要があると思われる.(著者抄録)

Factors affecting the quality of life of patients with medication-related osteonecrosis of the jaw during treatment: A quality-of-life survey and causal analysis

Kanako Munakata, Hidetaka Miyashita, Yuka Yamada, Tomoya Soma, Ryotaro Iwasaki, Taneaki Nakagawa, Seiji Asoda

Journal of Cranio-Maxillofacial Surgery （Journal of Cranio-Maxillofacial Surgery） 52 （ 6 ） 715 - 721 2024年03月

査読有り, ISSN 1010-5182

This prospective cohort study aimed to investigate the impact of medication-related osteonecrosis of the jaw (MRONJ) on health-related quality of life (HRQOL) and oral health-related QOL (OHRQOL) and the association between the downstaging of MRONJ and OHRQOL. The HRQOL and OHRQOL of 44 patients with MRONJ were assessed using the SF-36v2 and the General Oral Health Assessment Index (GOHAI), respectively. Treatment was performed in accordance with the AAOMS position paper (2014). The SF-36v2 and GOHAI scores at the beginning of the survey were used to evaluate the impact of MRONJ on QOL. Potential confounders affecting the association between downstaging and QOL improvement were selected using directed acyclic graphs. Multiple regression analysis was performed to evaluate causal inferences. HRQOL scale scores declined below the national average. The three-component summary score (3CS), comprising the physical component summary (PCS), mental component summary (MCS), and role/social component summary (RCS), revealed that performance status and primary disease significantly affected the PCS and RCS (P = 0.005 and P < 0.001, respectively) and PCS and MCS (P = 0.024 and P = 0.003, respectively). The MRONJ stage did not influence the 3CS; however, OHRQOL declined in a stage-dependent manner (P = 0.005). Downstaging of MRONJ was independently associated with the improvement rate of the total GOHAI scores after adjusting for variables (P = 0.045). The HRQOL of patients with MRONJ declined; however, this may depend on the underlying disease status rather than the MRONJ stage. Improvement of the disease status can potentially predict an improvement in OHRQOL, regardless of the treatment modality.

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Low energy availability reduces bone mass and gonadal function in male mice.

Ito E, Sato Y, Kobayashi T, Soma T, Matsumoto T, Kimura A, Miyamoto K, Matsumoto H, Matsumoto M, Nakamura M, Sato K, Miyamoto T

Journal of bone and mineral metabolism （Journal of Bone and Mineral Metabolism） 41 （ 2 ） 182 - 192 2023年03月

査読有り, ISSN 0914-8779

Introduction: In women, the female athlete triad, marked by low energy availability, functional hypothalamic amenorrhea and osteoporosis, is a recognized risk for stress fractures. Stress injuries also occur in men, but by contrast risks and mechanisms underlying them are less characterized. Materials and methods: 5 week-old wild-type male mice were fed ad libitum (ad) or subjected to 60% food restriction (FR) for five weeks. In both groups, some mice were allowed access to an exercise wheel in cages to allow voluntary wheel running (ex) and/or treated with active vitamin D analogues. Mice were sacrificed and analyzed at 10 weeks of age. Result: Male FR mice exhibited significantly reduced testicle weight, serum testosterone levels and bone mass. Such bone losses in FR male mice were enhanced by exercise. Histological analysis revealed that both bone-resorbing and -forming activities were significantly reduced in FR or FR plus exercise (FR + ex) mice, mimicking a state of low bone turnover. Significantly reduced bone mass in FR or FR + ex male mice was significantly rescued by treatment with active vitamin D analogues, with significant restoration of osteoblastic activities. Serum levels of insulin-like growth factor I (IGF-I), which is critical for bone remodeling, were significantly lower in FR versus control male mice. Conclusions: Low energy availability puts men at risk for stress injuries as well, and low energy availability is upstream of gonadal dysfunction and osteoporosis in males. Active vitamin D analogues could serve as therapeutic or preventive options for stress injuries in men.

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FOXA1 suppresses oral cancer progression through inhibiting p38 activation induced by lipid-derived aldehydes

Okazaki Shogo, Yoshikawa Momoko, Soma Tomoya, Asoda Seiji, Imai Kenichi, Goitsuka Ryo, Saya Hideyuki, Nagano Osamu

CANCER SCIENCE 114 1787 - 1787 2023年02月

ISSN 1347-9032

頰部の小唾液腺に発生した多形腺腫由来癌の1例

宮下英高, 相馬智也, 竹内照美, 宗像花楠子, 山田有佳, 中川種昭, 莇生田整治

日本口腔腫瘍学会誌（一般社団法人日本口腔腫瘍学会） 35 （ 3 ） 115 - 121 2023年

査読有り, ISSN 0915-5988

多形腺腫由来癌は主に耳下腺などの大唾液腺に生じ，その癌腫成分は腺癌（NOS）や唾液腺導管癌が多い。今回われわれは，頰部の小唾液腺由来の筋上皮癌を主体とする多形腺腫由来癌の1例を経験したので報告する。症例は74歳，女性で，左側頰部の腫脹を主訴に受診した。MRIでは左側咬筋前縁を取り囲む分葉状の腫瘤性病変を認めた。生検では，多形腺腫と癌腫成分が混在した所見を認め，多形腺腫由来癌の診断を得た。全身麻酔下に腫瘍切除術，肩甲舌骨筋上頸部郭清術，血管柄付き前外側大腿皮弁移植による再建術を実施した。術後経過は良好であったが，術後約5か月経過時に他病死の転帰となった。多形腺腫由来癌は小唾液腺ではまれな疾患であり，多施設からの症例の蓄積による術前診断法および治療法の確立が望まれる。

An ionic silver coating prevents implant-associated infection by anaerobic bacteria in vitro and in vivo in mice.

Soma T, Iwasaki R, Sato Y, Kobayashi T, Ito E, Matsumoto T, Kimura A, Homma F, Saiki K, Takahashi Y, Miyamoto K, Matsumoto M, Nakamura M, Morita M, Ishii K, Asoda S, Kawana H, Xingyu Z, Aizawa M, Nakagawa T, Miyamoto T

Scientific reports （Scientific Reports） 12 （ 1 ） 18387 - 18387 2022年11月

筆頭著者, 査読有り, ISSN 2045-2322

Currently, implants are utilized clinically for bone transplant procedures. However, if infectious osteomyelitis occurs at implant sites, removal of bacteria can be challenging. Moreover, altered blood flow at peri-implant infectious sites can create an anaerobic environment, making it more difficult to treat infection with antibiotics. Thus, it would be beneficial if implants could be modified to exhibit antibacterial activity, even in anaerobic conditions. Here, we show antibacterial activity of silver ions coated on titanium rods, even against the anaerobic bacteria Porphyromonas gingivalis (P. gingivalis), both in vitro and in vivo. Specifically, we implanted silver-coated or control uncoated titanium rods along with P. gingivalis in mouse femoral bone BM cavities and observed significantly inhibited P. gingivalis infection with silver-coated compared with non-coated rods, based on in vivo bio-imaging. Osteonecrosis by infectious osteomyelitis and elevation of the inflammatory factors C-reactive protein and IL-6 promoted by P. gingivalis s were also significantly reduced in the presence of silver-coated rods. Overall, our study indicates that silver ion coating of an implant represents a therapeutic option to prevent associated infection, even in anaerobic conditions or against anaerobic bacteria.

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Evaluation of the surgical approach based on impacted position and direction of mesiodens

Kimura M., Yasui T., Asoda S., Nagamine H., Soma T., Karube T., Kodaka R., Muraoka W., Nakagawa T., Onizawa K.

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology （Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology） 35 （ 1 ） 23 - 29 2022年08月

査読有り, ISSN 2212-5558

Objective: This study aimed to reveal the relationship between the approach of extraction and the position of the mesiodens by systematic classification. Methods: This retrospective study included patients with impacted mesiodens that required computed tomography for extraction. The direction, sagittal and axial position, eruption from the nasal floor, surrounding bone thickness, surgical approach, and anesthesia type for the impacted mesiodens were analyzed. Mesiodens were classified into three groups (V: vertical position, H: horizontal position, and D: direction), and each group was classified into three subgroups (V1, 2, 3; H1, 2, 3; D1, 2, 3). Results: A total of 169 impacted mesiodens were included in this study. The palatal approach was the most common (151 teeth, 89.3%), followed by the labial approach (11 teeth, 6.5%) and nasal floor approach (6 teeth, 3.6%). The bone thickness from the mesiodens to the palatal surface were significantly shorter in palatal far region of nasopalatine duct (H3) than in palatal near region (H2) (P < 0.05). In vertical high position (V3), the percentage of the palatal approach in H3 (87.5%) was higher than that in H2 (71.4%). Additionally, 15 teeth erupting from the nasal floor wherein four were extracted by the nasal floor approach in H2 but only one tooth in H3. Conclusions: Even at higher positions, mesiodens located in the palatal far region tended to be extracted by the palatal approach because of the thin bone thickness.

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Transcription factor FOXA1 is a negative regulator for xCT-dependent tumor formation in oral cancer

Okazaki Shogo, Nakano Yuki, Yoshikawa Momoko, Soma Tomoya, Asoda Seiji, Goitsuka Ryo, Saya Hideyuki, Nagano Osamu

CANCER SCIENCE 113 1324 - 1324 2022年02月

ISSN 1347-9032

Hao1 Is Not a Pathogenic Factor for Ectopic Ossifications but Functions to Regulate the TCA Cycle In Vivo

Atsushi Kimura, Akiyoshi Hirayama, Tatsuaki Matsumoto, Yuiko Sato, Tami Kobayashi, Satsuki Ikeda, Midori Maruyama, Mari Kaneko, Mayo Shigeta, Eri Ito, Tomoya Soma, Kana Miyamoto, Tomoyoshi Soga, Masaru Tomita, Akihito Oya, Morio Matsumoto, Masaya Nakamura, Arihiko Kanaji, Takeshi Miyamoto

Metabolites （MDPI AG） 12 （ 1 ） 82 - 82 2022年01月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 2218-1989

Ossification of the posterior longitudinal ligament (OPLL), a disease characterized by the ectopic ossification of a spinal ligament, promotes neurological disorders associated with spinal canal stenosis. While blocking ectopic ossification is mandatory to prevent OPLL development and progression, the mechanisms underlying the condition remain unknown. Here we show that expression of hydroxyacid oxidase 1 (Hao1), a gene identified in a previous genome-wide association study (GWAS) as an OPLL-associated candidate gene, specifically and significantly decreased in fibroblasts during osteoblast differentiation. We then newly established Hao1-deficient mice by generating Hao1-flox mice and crossing them with CAG-Cre mice to yield global Hao1-knockout (CAG-Cre/Hao1flox/flox; Hao1 KO) animals. Hao1 KO mice were born normally and exhibited no obvious phenotypes, including growth retardation. Moreover, Hao1 KO mice did not exhibit ectopic ossification or calcification. However, urinary levels of some metabolites of the tricarboxylic acid (TCA) cycle were significantly lower in Hao1 KO compared to control mice based on comprehensive metabolomic analysis. Our data indicate that Hao1 loss does not promote ectopic ossification, but rather that Hao1 functions to regulate the TCA cycle in vivo.

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Osteonecrosis development by tooth extraction in zoledronate treated mice is inhibited by active vitamin D analogues, anti-inflammatory agents or antibiotics

Tomoya Soma, Ryotaro Iwasaki, Yuiko Sato, Tami Kobayashi, Eri Ito, Tatsuaki Matsumoto, Atsushi Kimura, Kana Miyamoto, Morio Matsumoto, Masaya Nakamura, Mayu Morita, Seiji Asoda, Hiromasa Kawana, Taneaki Nakagawa, Takeshi Miyamoto

Scientific Reports （Springer Science and Business Media LLC） 12 （ 1 ） 19 - 19 2022年01月

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り, ISSN 2045-2322

<title>Abstract</title>Invasive dental treatment such as tooth extraction following treatment with strong anti-bone resorptive agents, including bisphosphonates and denosumab, reportedly promotes osteonecrosis of the jaw (ONJ) at the extraction site, but strategies to prevent ONJ remain unclear. Here we show that in mice, administration of either active vitamin D analogues, antibiotics or anti-inflammatory agents can prevent ONJ development induced by tooth extraction during treatment with the bisphosphonate zoledronate. Specifically, tooth extraction during treatment with zoledronate induced osteonecrosis in mice, but administration of either 1,25(OH)₂D₃ or ED71, both active vitamin D analogues, significantly antagonized osteonecrosis development, even under continuous zoledronate treatment. 1,25(OH)₂D₃ or ED71 administration also significantly inhibited osteocyte apoptosis induced by tooth extraction and bisphosphonate treatment. Administration of either active vitamin D analogue significantly inhibited elevation of serum inflammatory cytokine levels in mice in response to injection of lipopolysaccharide, an infection mimetic. Furthermore, administration of either anti-inflammatory or antibiotic reagents significantly blocked ONJ development following tooth extraction and zoledronate treatment. These findings suggest that administration of active vitamin D, anti-inflammatory agents or antibiotics could prevent ONJ development induced by tooth extraction in patients treated with zoledronate.

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Remarkable response of diffuse sclerosing osteomyelitis of the mandible to zoledronate by single infusion without prior treatment of other bisphosphonates

Yamada M., Iwata S., Nishi K., Ochiai S., Araki D., Soma T., Yamada Y., Miyashita H., Suga K., Asoda S.

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology （Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology） 34 （ 6 ） 777 - 783 2022年

査読有り, ISSN 22125558

Diffuse sclerosing osteomyelitis of the mandible (DSOM) is a nonsuppurative osteomyelitis mainly characterized by recurrent local mandibular swelling and pain. Because of the unknown pathophysiological mechanism underlying DSOM, treatment can be challenging. Reported treatment options include long-term analgesic medication, non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, corticosteroids, hyperbaric oxygen, and surgical treatment. However, these treatments cannot reliably lead to a long-lasting reduction of complaints. Recently, bisphosphonates has been reported effective in managing DSOM. We herein report a case of DSOM with a favorable response to a single infusion of zoledronate without prior treatment of other bisphosphonates. The patient was a 19-year-old woman who visited our hospital complaining of swelling and remarkable spontaneous pain in the right mandibular angle region. Under the diagnosis of osteomyelitis of the mandible, the clinical symptoms were improved by administering an antimicrobial agent and anti-inflammatory analgesic, but computed tomography (CT) showed exacerbation of bone resorption. A biopsy showed fibrosis between the bone tissue and trabeculae, a finding consistent with post-inflammatory changes. 99mTc scintigraphy showed an abnormal accumulation in the right mandibular ramus. Based on these results, she was diagnosed with DSOM. As a result of discussing with the physician in charge of internal medicine, it became the policy of the bisphosphonates and the intravenous administration of zoledronate 4 mg was enforced. Her bone sclerosis and bone resorption showed an improving trend on CT three months after the zoledronate administration, and there have been no symptoms or exacerbation of findings in three years since the administration.

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Transient alendronate administration to pregnant or lactating mothers prevents bone loss in mice without adverse effects on offspring

Eri Ito, Yuiko Sato, Tami Kobayashi, Tomoya Soma, Tatsuaki Matsumoto, Atsushi Kimura, Kana Miyamoto, Hideo Matsumoto, Morio Matsumoto, Masaya Nakamura, Kazuki Sato, Takeshi Miyamoto

Bone （Elsevier BV） 153 116133 - 116133 2021年12月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 8756-3282

Changes in bone metabolism occur in mothers during pregnancy or lactation that may decrease bone mass and result in fragility fractures after partum. However, use of drugs during pregnancy or lactation to counteract these effects is often prohibited or strongly discouraged. Therefore, approaches to protect mothers from fragility fractures have not been established. Here we show that bone mineral density was significantly lower in female mice after partum than in age-matched female mice without partum. We also show that temporary administration of the bisphosphonate alendronate, either just before or just after pregnancy, to female mice was protective against bone loss due to pregnancy or lactation and had no adverse effects on offspring, such as growth retardation. Furthermore, we show that alendronate administration to female mice during lactation was effective in increasing bone mass in mothers without promoting bone abnormalities or growth retardation in offspring. Calcium levels in milk from female mice administered alendronate during lactation were equivalent to those in milk from mothers not treated with alendronate. Overall, we propose that alendronate administration to mothers could prevent bone loss and fragility fractures during pregnancy and lactation.

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Clinical value of entire-circumferential intraoperative frozen section analysis for the complete resection of superficial squamous cell carcinoma of the tongue.

Asoda S, Miyashita H, Soma T, Munakata K, Yamada Y, Yasui Y, Kudo Y, Usuda S, Hasegawa T, Nakagawa T, Kawana H

Oral oncology （Elsevier BV） 123 105629 - 105629 2021年11月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1368-8375

Objectives: We aimed to evaluate the clinical value of an entire-circumferential intraoperative frozen section analysis (e-IFSA) for the complete resection of superficial squamous cell carcinoma (SCC) of the tongue. Materials and Methods: A total 276 specimens from 51 patients with pT1-2, N0, mucosal or submucosal invasion SCC were analyzed to evaluate the diagnostic accuracy of the e-IFSA and the added value of the e-IFSA to iodine staining. The e-IFSA results were compared with the final histologic results obtained using permanent sections. All specimens for the e-IFSA were taken over the entire circumference 5 mm outside from the iodine unstained areas. The outline of the main resected specimen after taking these outer mucosal specimens were defined as the surgical margins determined by iodine staining alone. Results: The e-IFSA results were in excellent agreement with final histological results (Cohen's kappa value: 0.85) and the e-IFSA showed high sensitivity (100%) and high negative predictive value (100%). The actual complete resection rate with an e-IFSA was 100% (51/51), and no patient required additional resection after surgery. In contrast, 10/51 patients (20%) patients showed residual atypical mucosal epithelium at or beyond the margin determined by iodine staining alone; this difference was statistically significant (P = 0.002). The 5-year local control rate and 5-year overall survival rate after this procedure were both 100%. Conclusion: An e-IFSA has additional value when performed in conjunction with iodine staining. An e-IFSA would be useful for achieving complete resection of superficial SCC of the tongue.

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Adipose-Derived Stem Cell Sheets Improve Early Biomechanical Graft Strength in Rabbits After Anterior Cruciate Ligament Reconstruction.

Matsumoto T, Sato Y, Kobayashi T, Suzuki K, Kimura A, Soma T, Ito E, Kikuchi T, Kobayashi S, Harato K, Niki Y, Matsumoto M, Nakamura M, Miyamoto T

The American journal of sports medicine （American Journal of Sports Medicine） 49 （ 13 ） 3635465211041582 - 3635465211041582 2021年10月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0363-5465

BACKGROUND: Although various reconstruction techniques are available for anterior cruciate ligament (ACL) injuries, a long recovery time is required before patients return to sports activities, as the reconstructed ACL requires time to regain strength. To date, several studies have reported use of mesenchymal stem cells in orthopaedic surgery; however, no studies have used adipose-derived stem cell (ADSC) sheets in ACL reconstruction (ACLR). HYPOTHESIS: ADSC sheet transplantation can improve biomechanical strength of the autograft used in ACLR. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 68 healthy Japanese white rabbits underwent unilateral ACLR with a semitendinosus tendon autograft after random enrollment into a control group (no sheet; n = 34) and a sheet group (ADSC sheet; n = 34). At 2, 4, 8, 16, and 24 weeks after surgery, rabbits in each group were sacrificed to evaluate tendon-bone healing using histological staining, micro-computed tomography, and biomechanical testing. At 24 weeks, scanning transmission electron microscopy of the graft midsubstance was performed. RESULTS: The ultimate failure load for the control and sheet groups, respectively, was as follows: 17.2 ± 5.5 versus 37.3 ± 10.3 (P = .01) at 2 weeks, 28.6 ± 1.9 versus 47.4 ± 10.4 (P = .003) at 4 weeks, 53.0 ± 14.3 versus 48.1 ± 9.3 (P = .59) at 8 weeks, 66.2 ± 9.3 versus 95.2 ± 43.1 (P = .24) at 16 weeks, and 66.7 ± 27.3 versus 85.3 ± 29.5 (P = .39) at 24 weeks. The histological score was also significantly higher in the sheet group compared with the control group at early stages up to 8 weeks. On micro-computed tomography, relative to the control group, the bone tunnel area was significantly narrower in the sheet group at 4 weeks, and the bone volume/tissue volume of the tendon-bone interface was significantly greater at 24 weeks. Scanning transmission electron microscopy at 24 weeks indicated that the mean collagen fiber diameter in the midsubstance was significantly greater, as was the occupation ratio of collagen fibers per field of view, in the sheet group. CONCLUSION: ADSC sheets improved biomechanical strength, prevented bone tunnel enlargement, and promoted tendon-bone interface healing and graft midsubstance healing in an in vivo rabbit model. CLINICAL RELEVANCE: ADSC sheets may be useful for early tendon-bone healing and graft maturation in ACLR.

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口腔扁平上皮癌においてFOXA1発現はxCT依存的腫瘍成長を抑制する

岡崎章悟, 中野友暉, 吉川桃子, 相馬智也, 莇生田整治, 後飯塚僚, 佐谷秀行, 永野修

日本癌学会総会記事（(一社)日本癌学会） 80回 [E11 - 3] 2021年09月

ISSN 0546-0476

Undifferentiated carcinoma of the mandible detected simultaneously with the liver: A case report

Seiji Asoda, Mayu Morita, Tomoya Soma, Hitoshi Sato, Toshihiro Hasegawa, Taneaki Nakagawa, Akinori Hashiguchi, Hiromasa Kawana

Oral and Maxillofacial Surgery Cases （Elsevier BV） 7 （ 3 ） 100228 - 100228 2021年08月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 2214-5419

We herein report a rare case of undifferentiated carcinoma that originated in the mandible with the same pathological findings as seen in the liver. A 64-year-old man underwent surgery for a hepatic tumor in October 2006, and the pathological diagnosis was undifferentiated carcinoma. The patient was referred to our department in January 2007, when whole-body positron emission tomography/computed tomography showed the uptake of fluorodeoxyglucose in the right mandibular ramus. The patient underwent right hemimandibulectomy in April 2007. The resected tumor was also undifferentiated carcinoma. In May 2014, seven years after the lower mandibular operation, the tumor recurred at the site corresponding to the right mandibular ramus after resection, and tumor resection and right neck dissection were performed. As a result of the histopathological examination, the undifferentiated carcinoma findings were the same as before. There have been no signs of local recurrence or metastases for over six years since the second mandibular surgery.

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Synoviolin is not a pathogenic factor for auto-inflammatory diseases.

Matsumoto T, Sato Y, Kobayashi T, Ito E, Soma T, Kimura A, Miyamoto K, Kobayashi S, Harato K, Matsumoto M, Nakamura M, Niki Y, Miyamoto T

Biochemical and biophysical research communications （Elsevier BV） 558 183 - 188 2021年04月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0006-291X

Auto-inflammatory syndromes are rare diseases characterized by arthritis and joint destruction, symptoms similar to but distinct from rheumatoid arthritis (RA). Therapeutic targets have not been well characterized for auto-inflammatory syndromes, although the E3 ligase Synoviolin was previously shown to be a novel therapeutic target for RA. Here, we show that Synoviolin loss has little impact on a model of auto-inflammatory diseases. We previously established such a model, the hIL-1 cTg mouse, in which IL-1 signaling was constitutively activated, and animals exhibit symptoms recapitulating auto-inflammatory syndromes such as major joint dominant arthritis. Here, we crossed hIL-1 cTg with Synoviolin flox'd mice to yield hIL-1 cTg/Synoviolin cKO mice. Synoviolin gene expression was ablated in adult hIL-1 cTg/Synoviolin cKO mice by injection of pIpC to activate Mx1 promoter-driven Cre recombinase. However, symptoms seen in hIL-1 cTg mice such as arthritis and joint destruction were not alleviated by targeting Synoviolin, ruling out Synoviolin as a therapeutic target for auto-inflammatory disease. Our results indicate that although similar, RA and auto-inflammatory diseases are different diseases, and treatment strategies should differ accordingly.

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Treatment with an active vitamin D analogue blocks hypothalamic dysfunction-induced bone loss in mice.

Eri Ito, Yuiko Sato, Tami Kobayashi, Satoshi Nakamura, Yosuke Kaneko, Tomoya Soma, Tatsuaki Matsumoto, Atushi Kimura, Kana Miyamoto, Hideo Matsumoto, Morio Matsumoto, Masaya Nakamura, Kazuki Sato, Takeshi Miyamoto

Biochemical and biophysical research communications （Elsevier BV） 542 48 - 53 2021年01月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0006-291X

Estrogen deficiency can be caused by ovarian dysfunction in females. Mechanisms underlying osteoporosis in this condition have been characterized in animal models, such as ovariectomized mice and rats, although it remains unclear how hypothalamic dysfunction promotes osteoporosis. Here, we show that administration of a gonadotropin-releasing hormone antagonist (GnRHa) significantly decreases uterine weight, a manifestation of hypothalamic dysfunction, and promotes both cortical and trabecular bone loss in female mice in vivo. We also report that osteoclast number significantly increased in mice administered GnRHa, and that the transcription factor hypoxia inducible factor 1 alpha (HIF1α) accumulated in those osteoclasts. We previously reported that treatment of mice with the active vitamin D analogue ED71, also known as eldecalcitol, inhibited HIF1α accumulation in osteoclasts. We show here that in mice, co-administration of ED71 with GnRHa significantly rescued the reduced cortical and trabecular bone mass promoted by GnRHa administration alone. GnRHa-dependent HIF1α accumulation in osteoclasts was also blocked by co-administration of ED71. We conclude that hypothalamic dysfunction promotes HIF1α accumulation in osteoclasts and likely results in reduced bone mass. We conclude that treatment with ED71 could serve as a therapeutic option to counter osteoporotic conditions in humans.

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Food restriction reduces cortical bone mass and serum insulin-like growth factor-1 levels and promotes uterine atrophy in mice.

Biochemical and biophysical research communications （Elsevier BV） 534 165 - 171 2021年01月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0006-291X

Low energy availability in female athletes often causes hypothalamic amenorrhea and osteoporosis, in turn promoting stress fractures. Mechanisms underlying these conditions remain unclear. Here we show that model mice subjected to food restriction (FR) or FR-plus-voluntary running exercise exhibit significantly reduced bone mineral density, cortical bone parameters and uterine weight than do control mice, and that these parameters worsen in the FR-plus-exercise group. Relative to controls, FR and FR-plus-exercise groups showed significantly lower mineral apposition rate and osteoclast number and significantly reduced serum insulin-like growth factor-1 (IGF1) levels. Outcomes were rescued by ED71 or 1.25(OH)2D3 treatment. Thus, we conclude that administration of active vitamin D analogues represents a possible treatment to prevent these conditions.

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Development of a microsurgery‐assisted robot for high‐precision thread traction and tension control, and confirmation of its applicability

Satoshi Hangai, Takahiro Nozaki, Tomoya Soma, Hidetaka Miyashita, Seiji Asoda, Masaki Yazawa, Kazuki Sato, Hiromasa Kawana, Kouhei Ohnishi, Eiji Kobayashi

The International Journal of Medical Robotics and Computer Assisted Surgery （Wiley） 17 （ 2 ） e2205 2020年11月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1478-5951

Background: Microsurgery requires high skills for suturing using fragile threads, often within narrow surgical fields. Precise tension is required for good healing and to avoid the risk of thread breakage. Methods: To meet the demands, we developed a novel assist robot utilizing high-precision sensorless haptic technology. The robot adopts a cable-driven mechanism to maintain a distance from the surgical area and enhances compatibility with surgical equipment such as microscopes. The robot performance was verified through in vitro and in vivo experiments using a rat model. Results: The realization of precise tension control was confirmed in both experiments. In particular, in the in vivo experiments, the developed robot succeeded to produce a knot with an accurate tension of 0.66% error. Conclusions: The developed robot can realize to control traction force precisely. This technology might open up the window for a full assist robot for microsurgery with haptic feeling.

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Tooth extraction in mice administered zoledronate increases inflammatory cytokine levels and promotes osteonecrosis of the jaw.

Tomoya Soma, Ryotaro Iwasaki, Yuiko Sato, Tami Kobayashi, Satoshi Nakamura, Yosuke Kaneko, Eri Ito, Hiroyuki Okada, Hisato Watanabe, Kana Miyamoto, Morio Matsumoto, Masaya Nakamura, Seiji Asoda, Hiromasa Kawana, Taneaki Nakagawa, Takeshi Miyamoto

Journal of bone and mineral metabolism （Journal of Bone and Mineral Metabolism） 39 （ 3 ） 372 - 384 2020年11月

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り, ISSN 09148779

INTRODUCTION: Osteonecrosis of the jaw (ONJ) occurring after invasive dental treatment often adversely affects patients' activities of daily living. Long-term administration of strong anti-bone resorptive agents such as bisphosphonates prior to invasive dental treatment is considered an ONJ risk factor; however, pathological mechanisms underlying ONJ development remain unclear. MATERIALS AND METHODS: We developed an ONJ mouse model in which a tooth is extracted during treatment with the bisphosphonate zoledronate. RESULTS: We observed induction of apoptosis in osteocytes, resulting in formation of empty lacunae in jaw bones at sites of tooth extraction but not in other bones of the same mice. We also observed elevated levels of inflammatory cytokines such as TNFα, IL-6 and IL-1 in jaw bone at the extraction site relative to other sites in zoledronate-treated mice. We also report that treatment in vitro with either zoledronate or an extract from Porphyromonas gingivalis, an oral bacteria, promotes expression of inflammatory cytokines in osteoclast progenitor cells. We demonstrate that gene-targeting of either TNFα, IL-6 or IL-1 or treatment with etanercept, a TNFα inhibitor, or a neutralizing antibody against IL-6 can antagonize ONJ development caused by combined tooth extraction and zoledronate treatment. CONCLUSIONS: Taken together, the cytokine storm induced by invasive dental treatment under bisphosphonate treatment promotes ONJ development due to elevated levels of inflammatory cytokine-producing cells. Our work identifies novel targets potentially useful to prevent ONJ.

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Clear cell carcinoma in the retromolar area: A case report

Yuta Yasui, Seiji Asoda, Tomoya Soma, Hidetaka Miyashita, Toshihiro Hasegawa, Takehito Ouchi, Takeshi Karube, Takazumi Yasui, Katsuhiro Onizawa, Taneaki Nakagawa, Hiromasa Kawana

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology （Elsevier BV） 32 （ 6 ） 507 - 513 2020年08月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 2212-5558

Clear cell carcinoma (CCC) is a malignant neoplasm of epithelial origin classified in the 2017 World Health Organization (WHO) classification as a low-grade salivary gland tumor consisting of glycogen-rich clear cytoplasm. We report a case of a 34-year-old woman presented in our department following the complaint of a mass in her right retromolar area. The tumor measured 10-mm in diameter and was elastic and hard mass. Spontaneous pain or tenderness and desensitization of the tongue were not observed. Marginal resection of the mandible was performed under general anesthesia. The lesion was located in the minor salivary gland that is mainly composed of mucus glands and had a relatively clearly defined circular shape. However, there was no film fabrication in the surrounding resions. Additionally, atypical cells comprising a clear cytoplasm and irregularly shaped pyknotic nuclei were growing in sheet form or island form, and markedly hyalinized fascicles were observed between the alveolar walls of the atypical cells. Immunohistochemical stains revealed these tumor cells to be positive for epithelial cell markers but negative for myoepithelial ones. Considering the above findings, the tumor was diagnosed as CCC. The patient is currently free from disease 37 months after surgery.

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Pimozide combined with paclitaxel demonstrates a significant antitumor effect in head and neck squamous cell carcinoma

Nakamura Shintaro, Ozawa Hiroyuki, Yamasaki Juntaro, Okazaki Shogo, Yoshikawa Momoko, Soma Tomoya, Asoda Seiji, Nagano Osamu, Sekimizu Mariko, Saito Shin, Yoshihama Keisuke, Mikoshiba Takuya, Ogawa Kaoru, Saya Hideyuki

CANCER RESEARCH 80 （ 16 ） 2020年08月

ISSN 0008-5472

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Vitamin D protects against immobilization-induced muscle atrophy via neural crest-derived cells in mice.

Satoshi Nakamura, Yuiko Sato, Tami Kobayashi, Yosuke Kaneko, Eri Ito, Tomoya Soma, Hiroyuki Okada, Kana Miyamoto, Akihito Oya, Morio Matsumoto, Masaya Nakamura, Arihiko Kanaji, Takeshi Miyamoto

Scientific reports （Scientific Reports） 10 （ 1 ） 12242 - 12242 2020年07月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 2045-2322

Vitamin D deficiency is a recognized risk factor for sarcopenia development, but mechanisms underlying this outcome are unclear. Here, we show that low vitamin D status worsens immobilization-induced muscle atrophy in mice. Mice globally lacking vitamin D receptor (VDR) exhibited more severe muscle atrophy following limb immobilization than controls. Moreover, immobilization-induced muscle atrophy was worse in neural crest-specific than in skeletal muscle-specific VDR-deficient mice. Tnfα expression was significantly higher in immobilized muscle of VDR-deficient relative to control mice, and was significantly elevated in neural crest-specific but not muscle-specific VDR-deficient mice. Furthermore, muscle atrophy induced by limb immobilization in low vitamin D mice was significantly inhibited in Tnfα-deficient mice. We conclude that vitamin D antagonizes immobilization-induced muscle atrophy via VDR expressed in neural crest-derived cells.

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A case of spindle cell/pleomorphic lipoma on inferior border of the mandible

Kanako Munakata, Seiji Asoda, Shin Usuda, Hidetaka Miyashita, Tomoya Soma, Toshihiro Hasegawa, Chiharu Ogawa, Sadao Ohyama, Tomohiro Yamauchi, Miho Kawaida, Kaori Kameyama, Taneaki Nakagawa, Hiromasa Kawana

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology （Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology） 32 （ 1 ） 49 - 52 2020年01月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 2212-5558

© 2019 Asian AOMS(+) ASOMP(+) JSOP(+) JSOMS(+) JSOM(+) and JAMI Spindle cell lipomas and pleomorphic lipomas are uncommon and distinct variants of benign lipomas. Although spindle cell lipomas and pleomorphic lipomas were originally considered different entities, the recent WHO classification defines them as spindle cell/pleomorphic lipoma (SCL/PL). This is because of their similar clinical features and the existence of intermediate histopathological features between them. A 77-year-old male presented to our clinic with a painless swelling on the left inferior border of the mandible. Computed tomography revealed a clearly defined mass in the subcutaneous lesion. With a histopathological diagnosis of myxolipoma, demonstrated by biopsy, excisional surgery was performed under general anesthesia. The histopathology revealed SCL/PL with the presence of spindle cells and mature adipocytes. No tumor recurrence had been noted at two year after surgery.

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Clinical study of octacalcium phosphate and collagen composite in oral and maxillofacial surgery

Tadashi Kawai, Shinji Kamakura, Keiko Matsui, Masayuki Fukuda, Hiroshi Takano, Mitsuyoshi Iino, Shigeo Ishikawa, Hiromasa Kawana, Tomoya Soma, Eisaku Imamura, Hideki Kizu, Aya Michibata, Izumi Asahina, Keiichiro Miura, Norifumi Nakamura, Toshiro Kibe, Osamu Suzuki, Tetsu Takahashi

Journal of Tissue Engineering （SAGE Publications） 11 204173141989644 - 204173141989644 2020年01月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 2041-7314

Octacalcium phosphate and its collagen composite have been recognized as bone substitute materials possessing osteoconductivity and biodegradation properties. We evaluated the effectiveness of octacalcium phosphate and its collagen composite used for bone augmentation in major oral and maxillofacial surgeries in a clinical trial. Octacalcium phosphate and its collagen composite were used in cases of sinus floor elevation in 1- and 2-stage, socket preservation, cyst, and alveolar cleft procedures. A total of 60 patients were evaluated for effectiveness after the implantation of octacalcium phosphate and its collagen composite. Although sinus floor elevation in 1-stage, cyst, and alveolar cleft cases met the criteria for the judgment of success, sinus floor elevation in 2-stage and socket preservation groups did not meet the criteria in the initial evaluation. However, an additional evaluation for reconfirmation revealed the effectiveness of octacalcium phosphate and its collagen composite in those groups, and all evaluation results ultimately indicated the success of this clinical trial. Therefore, this clinical trial suggested that application of octacalcium phosphate and its collagen composite for oral and maxillofacial surgery was safe and effective and that octacalcium phosphate and its collagen composite could be a bone substitute candidate instead of autologous bone.

Oral administration of N-acetyl cysteine prevents osteoarthritis development and progression in a rat model.

Yosuke Kaneko, Nobuharu Tanigawa, Yuiko Sato, Tami Kobayashi, Satoshi Nakamura, Eri Ito, Tomoya Soma, Kana Miyamoto, Shu Kobayashi, Kengo Harato, Morio Matsumoto, Masaya Nakamura, Yasuo Niki, Takeshi Miyamoto

Scientific reports （Scientific Reports） 9 （ 1 ） 18741 - 18741 2019年12月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 2045-2322

The number of osteoarthritis patients is increasing with the rise in the number of elderly people in developed countries. Osteoarthritis, which causes joint pain and deformity leading to loss of activities of daily living, is often treated surgically. Here we show that mechanical stress promotes accumulation of reactive oxygen species (ROS) in chondrocytes in vivo, resulting in chondrocyte apoptosis and leading to osteoarthritis development in a rat model. We demonstrate that mechanical stress induces ROS accumulation and inflammatory cytokine expression in cultured chondrocytes in vitro and that both are inhibited by treatment with the anti-oxidant N-acetyl cysteine (NAC). In vivo, osteoarthritis development in a rat osteoarthritis model was also significantly inhibited by oral administration of NAC. MMP13 expression and down-regulation of type II collagen in chondrocytes, both of which indicate osteoarthritis, as well as chondrocyte apoptosis in osteoarthritis rats were inhibited by NAC. Interestingly, osteoarthritis development in sham-operated control sides, likely due to disruption of normal weight-bearing activity on the control side, was also significantly inhibited by NAC. We conclude that osteoarthritis development in rats is significantly antagonized by oral NAC administration. Currently, no oral medication is available to prevent osteoarthritis development. Our work suggests that NAC may represent such a reagent and serve as osteoarthritis treatment.

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Acute odontogenic infection combined with crowned dens syndrome: a case report.

Tomoya Soma, Seiji Asoda, Moemi Kimura, Kanako Munakata, Hidetaka Miyashita, Taneaki Nakagawa, Hiromasa Kawana

Journal of medical case reports （Journal of Medical Case Reports） 13 （ 1 ） 143 - 143 2019年05月

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り

BACKGROUND: Calcium pyrophosphate dihydrate crystal deposition disease is a condition in which calcium pyrophosphate dihydrate crystal is deposited in joint cartilage and ligaments. Calcium pyrophosphate dihydrate crystal deposition disease that involves calcification around the odontoid process of the second cervical vertebra is called crowned dens syndrome. Crowned dens syndrome is accompanied by fever in addition to acute and intense neck, posterior head, and temporal pain; thus, distinguishing crowned dens syndrome may be difficult in the presence of odontogenic infection. To the best of our knowledge, this is the first report describing a patient with crowned dens syndrome with coexisting odontogenic infection. CASE PRESENTATION: A 75-year-old Japanese woman was examined in the Emergency Department of this hospital due to a chief complaint of worsened buccal swelling on the left side. An odontogenic infection was considered, and she underwent her first examination. She presented with a body temperature of 37.4 °C, marked swelling and tenderness of her left lower eyelid through to her left cheek, and pain on the left temporal area. Blood tests revealed a leukocyte count of 6700/μL and a C-reactive protein level of 7.15 mg/dL. There was swelling and pain around the gingiva and acute purulent apical periodontitis of left maxillary second premolar. Cellulitis of the left cheek was diagnosed. After performing drainage of the pus, antibiotic treatment was initiated. Although her clinical symptoms improved, blood tests on day 9 of hospitalization revealed a leukocyte count of 6500/μL and a C-reactive protein level of 25.62 mg/dL, which were indicative of worsening symptoms. Computed tomography was performed to evaluate remote infection and images revealed a calcification around the odontoid process of her second cervical vertebra. When she was referred to the Orthopedic Surgery Department, pseudogout of the cervical spine was diagnosed. Subsequently, oral acetaminophen was initiated, and both her leukocyte count and C-reactive protein improved markedly. CONCLUSIONS: In the presence of persistent fever and abnormally high leukocyte and C-reactive protein indicative of an inflammatory reaction, coexistence of pseudogout should be considered. In particular, when symptoms of temporal pain are present, the possibility of pseudogout of the cervical spine must be considered in the differential diagnosis.

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A case of platelet transfusion refractoriness occurring after platelet transfusion for tooth extraction in myelodysplastic syndromes patient

Tomoya Soma, Seiji Asoda, Ryotaro Iwasaki, Hidetaka Miyashita, Mariko Inoue, Yuka Yamada, Kimio Uchiyama, Taneaki Nakagawa, Hiromasa Kawana

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology （Elsevier BV） 30 （ 6 ） 496 - 499 2018年11月

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り, ISSN 2212-5558

Myelodysplastic syndrome is an acquired hematopoietic disorder showing symptoms of pre-leukemia and refractory anemia. In the tooth extraction process of such cases, bleeding tendency due to pancytopenia, infection etc., becomes a problem. As such, a cautious approach is required. We have confirmed platelet transfusion refractoriness prior to tooth extraction in a myelodysplastic syndrome patient, and hereby report a case of tooth extraction following human leukocyte antigen (HLA)-compatible concentrated platelet transfusion. The patient was a 55-year-old female who was examined at our department due to a request for the extraction of tooth No. 36. Following consultation at the Hematology Department, platelet transfusion was performed as a pretreatment upon hospitalization. Increased body temperature, chills, shivers, and feelings of discomfort in the pharynx were observed. A close examination was performed due to a lack of increase in platelet count, and revealed platelet transfusion refractoriness caused by anti-HLA antibodies. Therefore, the patient was re-hospitalized and transfused with a platelet concentrate-HLA preparation. One hour later, an increase in platelet count was confirmed and the tooth extraction was performed. There was no evidence of bleeding or infection following extraction, and the prognosis was good.

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Dedifferentiated parosteal osteosarcoma of the maxilla: a case report and review of the literature.

Hidetaka Miyashita, Kazunari Yoshida, Tomoya Soma, Kaori Kameyama, Aya Sasaki, Masanori Hisaoka, Masaki Yazawa, Hideo Morioka, Moe Takahashi, Taneaki Nakagawa, Hiromasa Kawana

Journal of medical case reports （Journal of Medical Case Reports） 12 （ 1 ） 235 - 235 2018年08月

研究論文（学術雑誌）, 共著, 査読有り

BACKGROUND: Parosteal osteosarcomas are usually low-grade tumors, however, sometimes they transform to high-grade tumors, which is named dedifferentiation. This phenomenon has been reported in long bones. Recently, we encountered a patient with dedifferentiated parosteal osteosarcoma occurring in the maxilla. Here, we report a first case of dedifferentiated parosteal osteosarcoma of the head and neck region. CASE PRESENTATION: A 45-year-old Japanese woman with a refractory bone lesion in the maxilla presented to our hospital. A biopsy showed atypical spindle cell proliferation involving dedifferentiated high-grade component, which was diagnosed as dedifferentiated parosteal osteosarcoma. Three cycles of neoadjuvant chemotherapy using ifosfamide and pirarubicin were performed followed by sub-total maxillectomy. Histopathological results showed that neoadjuvant chemotherapy was effective for high-grade component. The decision to perform adjuvant chemotherapy (cisplatin and pirarubicin) was made because distant metastasis has been reported, even in cases with dedifferentiated parosteal osteosarcoma in which complete necrosis of high-grade component was achieved due to neoadjuvant chemotherapy. There was no recurrence 15 months after surgery. CONCLUSIONS: Dedifferentiated parosteal osteosarcoma can occur in the head and neck region. Chemotherapy including anthracycline anticancer agent could be effective for high-grade component of dedifferentiated parosteal osteosarcoma.

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Recurrent Spindle Cell Carcinoma Shows Features of Mesenchymal Stem Cells

T. Ouchi, S. Morikawa, S. Shibata, M. Takahashi, M. Yoshikawa, T. Soma, H. Miyashita, W. Muraoka, K. Kameyama, H. Kawana, Y. Arima, H. Saya, H. Okano, T. Nakagawa, S. Asoda

Journal of Dental Research （SAGE Publications Inc.） 97 （ 7 ） 779 - 786 2018年07月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1544-0591

This study investigated a case of spindle cell carcinoma (SpCC) in tongue pathological lesions. The patient experienced a local recurrence and distant metastasis after surgical intervention. Although standard chemotherapy was administered, a granulomatous mass continued to develop. This aggressive growth led to survival of the tumor. Secondary debulking surgery was performed to improve the patient’s quality of life at the request of the patient. Using a tissue sample derived from the secondary debulking surgery, we performed an analysis of the tumor’s cell surface antigens, differentiation potential, metastatic ability, and inhibition potential by anticancer reagents. In vitro analysis revealed that the cell population grown under adherent culture conditions expressed the mesenchymal stem cell (MSC) markers CD73, CD90, and CD105. The cell line established from this SpCC contained colony-forming unit fibroblasts (CFU-Fs) and exhibited multipotent differentiation into several mesenchymal lineages, including bone, cartilage, and fat. The SpCC cells also displayed vigorous mobilization. These characteristics suggested that they had the differentiation potential of mesenchymal cells, especially MSCs, rather than that of epithelial cells. The surgical specimen analyzed in this study resisted the molecular target reagent cetuximab, which is an epidermal growth factor receptor inhibitor. This clinical insight revealed that chemotherapy-resistant SpCC cells have different characteristics compared to most other cancer cells, which are sensitive to cetuximab. Our cell death assay revealed that SpCC cell death was induced by the anticancer drug imatinib, which is known to inhibit protein tyrosine kinase activity of ABL, platelet-derived growth factor receptor α (PDGFRα), and KIT. Here, we report recurrent SpCC with characteristics of MSCs and potential for treatment with imatinib.

本態性血小板血症患者に発生した口底癌の1例

長谷川稔洋, 宗像花楠子, 小川千晴, 家崎憲博, 莇生田整治, 宮下英高, 相馬智也, 福田仁, 吉田俊一, 内田育宏, 寺尾保信, 大山定男

日本口腔腫瘍学会誌（(一社)日本口腔腫瘍学会） 30 （ 4 ） 59‐166(J‐STAGE) - 166 2018年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0915-5988

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The onset risk of carcinoma in patients continuing tacrolimus topical treatment for oral lichen planus: a case report

Mayu Morita, Seiji Asoda, Kazuyuki Tsunoda, Tomoya Soma, Taneaki Nakagawa, Masayori Shirakawa, Hirofumi Shoji, Hisao Yagishita, Takeji Nishikawa, Hiromasa Kawana

Odontology （Springer Tokyo） 105 （ 2 ） 262 - 266 2017年04月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1618-1247

Oral lichen planus is a chronic inflammatory mucocutaneous disease. Topical use of steroids and other immuno-modulating therapies have been tried for this intractable condition. Nowadays, tacrolimus ointment is used more commonly as a choice for treatment. However, a number of discussions have taken place after tacrolimus was reported to be carcinogenic. This report describes a patient who applied tacrolimus ointment to the lower lip after being diagnosed with oral lichen planus in 2008, and whose lesion developed squamous cell carcinoma in 2010. Since the relationship between tacrolimus and cancer development has been reported in only a few cases, including this case report, the clinician must be careful selecting tacrolimus as a second-line treatment for oral lichen planus.

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IGF-II産生非膵島細胞腫瘍性低血糖症を発症した上顎歯肉癌の1例

宮下英高, 莇生田整治, 森泰昌, 山田有佳, 相馬智也and 河奈裕正

日本口腔外科学会雑誌 62 （ 9 ） 448 - 453 2016年09月

共著, ISSN 0021-5163

72歳男。上顎左側歯肉の腫脹・疼痛を主訴に受診し、諸検査により歯肉癌(中分化型扁平上皮癌)と診断した。手術を勧めたが、同意が得られず、他院での治療を希望したため当科での治療はいったん終了としたが、他院を受診することなく、初診の4ヵ月後に当科を再受診した。腫瘍は増大しており、鼻腔や外側翼突筋に浸潤していた。手術は希望しなかったため化学放射線療法を行い、治療終了3週間後に突然見当識障害が出現した。血糖値の著明な低下を認めたため精査を行い、低血糖発作時にインスリンの過剰分泌を認めないことや、血中IGF-I分泌が抑制されていることに加え、大きな膵外腫瘍(歯肉癌)を認めていることからIGF-II産生非膵島細胞腫瘍性低血糖症と診断した。診断後に追加で歯肉癌生検標本のIGF-II免疫染色を行ったところ陽性であった。

Desmoid-type fibromatosis of the head and neck in children: A case report and review of the literature

Hidetaka Miyashita, Seiji Asoda, Tomoya Soma, Kanako Munakata, Masaki Yazawa, Taneaki Nakagawa, Hiromasa Kawana

Journal of Medical Case Reports （BioMed Central Ltd.） 10 （ 1 ） 173 2016年06月

共著, 査読有り, ISSN 1752-1947

Background: Desmoid-type fibromatosis is defined as an intermediate tumor that rarely occurs in the head and neck of children. There is no doubt as to the value of complete surgical excision for desmoid-type fibromatosis. However, in pediatric patients, surgeons may often be concerned about making a wide excision because of the potential for functional morbidity. Some studies have reported a lack of correlation between margin status and recurrence. Therefore, we discussed our findings with a focus on the state of surgical margins. Case presentation: We report an unusual case of a 9-month-old Japanese girl who prior to presenting at our hospital underwent debulking surgery twice with chemotherapy for desmoid-type fibromatosis of the tongue at another hospital. We performed a partial glossectomy and simultaneous reconstruction with local flap and achieved microscopic complete resection. We also reviewed available literature of pediatric desmoid-type fibromatosis in the head and neck. Conclusions: We described successful treatment for the refractory case of pediatric desmoid-type fibromatosis. The review results showed that some microscopic incomplete resections of tumors in pediatric patients with desmoid-type fibromatosis tended to be acceptable with surgical treatment.

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口腔癌患者に対するDocetaxel、Nedaplatin(5日間分割投与)、5-Fluorouracil併用化学療法時の悪心に対する効果的なAprepitant投与タイミングの検討

内山公男, 山田学, 小松俊一, 相馬智也, 岩渕博史, 鬼澤勝弘, 安居孝純 and 中山成一

癌と化学療法 42 （ 10 ） 1191 - 1195 2015年10月

共著, ISSN 0385-0684

口腔癌に対してdocetaxel、nedaplatin(5日間分割投与)、5-fluorouracilの3剤併用化学療法を実施した患者を対象に、aprepitantをコース初日から投与した場合とコース3日目から投与した場合の制吐効果を比較し、適切なaprepitantの投与タイミングを明らかにすることを目的とした。1.嘔吐は両群ともほとんどみられず、比較できなかった。2.最大悪心gradeは初日群が平均0.78±0.22であったのに対し、3日目群では平均2.33±0.71と有意(p=0.002、U-test)に高かった。3.経日的な悪心gradeの推移下面積(AUC)も初日群が平均3.11±3.59であったのに対し、3日目群では平均13.44±9.58と有意(p=0.019、U-test)に高かった。4.3日目群ではgrade 2以上の悪心が8/9例(88.9%)にみられたのに対し、初日群では1/9(11.1%)と有意(p<0.001、χ2test)に低かった。aprepitantは初日から投与することで悪心の発現をよく抑えることが確認された。(著者抄録)

Determination of the Appropriate Timing of Aprepitant Administration for Nausea in Patients with Head and Neck Cancer Receiving Combination Chemotherapy with Docetaxel, Nedaplatin（Divided Doses for 5 Days), and 5-fluorouracil.

Kimio Uchiyama, Manabu Yamada, Shunichi Komatsu, Tomoya Souma, Hiroshi Iwabuchi, Katsuhiro Onizawa, Takazumi Yasui, Seiichi Nakayama

Gan to kagaku ryoho. Cancer & chemotherapy 42 （ 10 ） 1191 - 5 2015年10月

研究論文（学術雑誌）, 共著, ISSN 0385-0684

The objective of this study was to determine the appropriate timing of aprepitant administration in patients with oral cancer by comparing the antiemetic effect of aprepitant administered on the first day (first-day group) and third day (third-day group) of combination chemotherapy with docetaxel, nedaplatin (divided doses for 5 days), and 5-fluorouracil. 1. In both groups, very few cases of vomiting were observed. Therefore, we could not compare the incidence of vomiting. 2. The mean highest grade of nausea in the third-day group was significantly higher than that in the first-day group (2.33±0.71 vs 0.78±0.22, p=0.002; U-test). 3. In addition, the mean area under the curve of the chronological changes in the grade of nausea in the third-day group was significantly higher than that in the first-day group (13.44±9.58 vs 3.11±3.59, p=0.019; U-test). 4. The incidence of nausea of grade 2 or higher in the first-day group was significantly lower than that in the third-day group (11.1% [1/9] vs 88.9% [8/9], p<0.001; c 2 test). These results indicate that initiation of aprepitant administration on the first day of combination chemotherapy with docetaxel, nedaplatin, and 5-fluorouracil successfully prevented the development of nausea in patients with oral cancer.

笠崎真悟, 三友啓介,相馬智也, 山田学, 岩渕絵美, 岩渕博史 and 内山公男

栃木県歯科医学会誌 65 53 - 58 2013年04月

共著

症例1は65歳男性で、原発不明癌・多発骨転移のためゾレドロン酸水和物の静脈注射を受けていたが、左側下顎臼歯部舌側の骨露出を指摘された。CTで腐骨を認め、ビスホスホネート関連顎骨壊死と診断した。ビスホスホネート(BP)製剤は休薬として抗菌薬による消炎、局所洗浄を行ったが腐骨露出範囲は大きくなり、外科的治療を施行した。健康な骨を一部含めて腐骨を除去し、減張切開を加え完全閉創した。症例2は85歳女性で、骨粗鬆症のためリセドロン酸ナトリウム水和物を内服していたが、以前抜歯後義歯装着した右側上顎第一・第二大臼歯部に疼痛、排膿、骨露出が出現した。CTで右側上顎骨に腐骨を認め、上顎洞粘膜に中等度の肥厚がみられた。症例1と同様の診断でBP製剤は休薬し、抗菌薬で消炎した後、腐骨除去術、瘻孔閉鎖術を行い、粘膜欠損部は頬脂肪体で完全閉創した。症例1は術後4ヵ月、症例2は6ヵ月経過し、術創は上皮で覆われ、新たな顎骨壊死は認めない。

化学療法後に敗血症性ショックを起こし救命しえた一例

相馬智也, 小松俊一, 杉山健太郎, 山田学, 岩渕絵美, 岩渕博史 and 内山公男

栃木県歯科医学会誌 64 81 - 86 2012年04月

共著, 筆頭著者

53歳女。右側舌側縁部腫瘤(潰瘍部)精査加療依頼で受診した。右側舌側縁部〜口底に周囲に硬結を伴う潰瘍性病変を認め、血液検査、画像検査所見より舌・口底扁平上皮癌(T3N1M0)、高分化型扁平上皮癌と診断された。術前化学療法(TPF療法)2クール後、腫瘍切除術(舌亜全摘)・頸部郭清術・再建術の方針としたが、化学療法開始後8日目に好中球数低下と38℃の発熱を認めた。また、化学療法開始後30日目より全身状態が悪化をしてショック・急性腎不全の状態となり、血液培養にてFusobacterium nucleatumが検出された。一連の経過より、同菌による敗血症性ショックとそれに伴う急性腎不全の合併と考えられたが、膿瘍は確認できず、敗血症の原因は不明であった。

12年間にわたった多発性口腔癌の1例

小松俊一,相馬智也, 杉山健太郎, 山田学, 岩渕絵美, 岩渕博史 and 内山公男

栃木県歯科医学会誌（(一社)栃木県歯科医師会） 64 161 - 167 2012年04月

共著

61歳男。右上顎第2大臼歯遠心部歯肉潰瘍精査依頼および疼痛と主訴とした。初診時には右上顎に潰瘍を伴う歯肉の腫脹を認め、右上顎歯肉癌(T2N0M0、扁平上皮癌)と診断された。化学療法と外科的切除を行い、病理組織診断は中分化型・浸潤様式2型の扁平上皮癌であった。1次癌の術後1年2ヵ月に左下顎第1大臼歯部頬側歯肉にびらん形成と周囲の白斑を認め、左下顎歯肉癌(T2N0M0、扁平上皮癌)と診断された。化学療法と外科的切除を行い、病理組織診断は中分化型扁平上皮癌であった。2次癌の術後8年10ヵ月に右下顎第2小臼歯・第1大臼歯舌側歯肉に外向性の腫瘤を認め、右下顎歯肉癌(T2N0M0、扁平上皮癌)と診断された。化学療法と外科的切除を行い、現在まで再発・転移を認めず経過良好である。自験例は12年間にわたって上下顎歯肉に異所性、異時性に発生した典型的な多発性癌であった。

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