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Master

Affiliation (Master)

  • Hokkaido University Hospital

Affiliation (Master)

  • Hokkaido University Hospital

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Profile and Settings

Profile and Settings

  • Name (Japanese)

    Kato
  • Name (Kana)

    Tatsuya
  • Name

    201701014100354391

Achievement

Awards

  • 2008/10 日本癌学会 奨励賞
     
    受賞者: 加藤達哉

Published Papers

  • ラット虚血再灌流傷害モデルを用いた新規抗炎症薬による肺傷害抑制効果の検討
    椎谷 洋彦, 千葉 龍平, 渡辺 正明, 大塚 将平, 佐々木 明洋, 大高 和人, 氏家 秀樹, 藤原 晶, 新垣 雅人, 加藤 達哉
    移植 (一社)日本移植学会 59 (1) 88 - 88 0578-7947 2024/07
  • 肺移植クラウドファンディングを経験して
    加藤 達哉, 大塚 将平, 佐々木 明洋, 椎谷 洋彦, 大高 和人, 藤原 晶, 氏家 秀樹, 新垣 雅人
    移植 (一社)日本移植学会 59 (1) 101 - 101 0578-7947 2024/07
  • 右大腿発生粘液型脂肪肉腫に肺転移を擬した肺クリプトコッカス病を併発した1例
    河村 茉莉子, 松岡 正剛, 氏家 秀樹, 有賀 伸, 中里 信一, 加藤 憲士郎, 橋本 孝之, 松野 吉宏, 加藤 達哉, 岩崎 倫政
    日本整形外科学会雑誌 (公社)日本整形外科学会 98 (6) S1566 - S1566 0021-5325 2024/06
  • Haruhiko Shiiya, Hideki Ujiie, Ryohei Chiba, Shunsuke Nomura, Kazuto Ohtaka, Aki Fujiwara-Kuroda, Masato Aragaki, Keita Takahashi, Kazufumi Okada, Tatsuya Kato
    Surgery today 2024/05/30 
    PURPOSE: Surgical manipulation of the lungs increases the number of circulating tumor cells and the subsequent risk of metastasis in patients with lung cancer. This study investigated whether or not ligating the tumor-draining pulmonary vein first during lobectomy could improve the prognosis of these patients. METHODS: We retrospectively evaluated patients who underwent curative lobectomy for solitary nonsmall-cell lung carcinoma between January 2012 and December 2016. We divided the patients into the vein-first group, in which all associated pulmonary veins were dissected and severed before cutting the pulmonary artery, bronchus, or pulmonary fissure, and the other procedure group. RESULTS: Overall, we included 177 and 413 patients in the vein-first and other procedure groups, respectively. Propensity score matching yielded 67 pairs of patients. The 5-year overall survival (85.6% [95% confidence interval, 77.3-94.8%] vs. 69.4% [58.7-81.9%], P = 0.03%) and recurrence-free survival (73.4% [63.3-85.1%] vs. 53.5% [42.5-67.3%], P = 0.02) were significantly better in the vein-first group than in the other procedure group. The cumulative recurrence rate at 5 years post-surgery was significantly lower in the vein-first group than in the other procedure group (21.7% vs. 38.3%, P = 0.04). CONCLUSION: Our study suggests that ligating the pulmonary vein first during lobectomy for lung cancer can improve the overall survival, recurrence-free survival, and cumulative recurrence rate.
  • Hideki Ujiie, Ryohei Chiba, Akihiro Sasaki, Shunsuke Nomura, Haruhiko Shiiya, Shohei Otsuka, Hiroshi Yamasaki, Aki Fujiwara-Kuroda, Kazuto Ohtaka, Masato Aragaki, Kazufumi Okada, Yuma Ebihara, Tatsuya Kato
    Journal of Clinical Medicine 13 (10) 2807 - 2807 2024/05/10 
    Background: Intravenously administered indocyanine green (ICG) accumulates in lung tumors, facilitating their detection via a fluorescence spectrum measurement. This method aids in identifying tumor locations that are invisible to the naked eye. We aim to determine the optimal ICG dose and administration method for accurate tumor identification during lung resection surgeries, utilizing a novel ICG fluorescence spectroscopy system for precise tumor localization. Materials and Methods: ICG should be dissolved in the provided solution or distilled water and administered intravenously approximately 24 h before surgery, beginning with an initial dose of 0.5 mg/kg. If the tumor detection rate is insufficient, the dose may be gradually increased to a maximum of 5.0 mg/kg to determine the optimal dosage for effective tumor detection. This fluorescence spectroscopy during surgery may reveal additional lesions that remain undetected in preoperative assessments. The primary endpoint includes the correct diagnostic rate of tumor localization. The secondary endpoints include the measurement of the intraoperative ICG fluorescence spectral intensity in lung tumors, the assessment of the operability and safety of intraperitoneal ICG administrations, the measurement of the ICG fluorescence spectral intensity in surgical specimens, the comparison of the spectral intensity in lung tissues during collapse and expansion, the correlation between ICG camera images and fluorescence spectral intensity, and the comparison of fluorescence analysis results with histopathological findings. The trial has been registered in the jRCT Clinical Trials Registry under the code jRCTs011230037. Results and Conclusions: This trial aims to establish an effective methodology for localizing and diagnosing malignant lung tumors, thereby potentially improving surgical outcomes and refining treatment protocols.
  • Aki Fujiwara-Kuroda, Masato Aragaki, Yasuhiro Hida, Hideki Ujiie, Kazuto Ohtaka, Haruhiko Shiiya, Kichizo Kaga, Tatsuya Kato
    Translational lung cancer research 13 (3) 603 - 611 2024/03/29 
    When performing thoracoscopic partial resections of nonpalpable lung tumors such as ground-glass opacities (GGOs) and small tumors, detecting the location of the lesion and assessing the resection margins can be challenging. We have developed a novel method to ease this difficulty, the One-stop Solution for a nonpalpable lung tumor, Marking, Resection, and Confirmation of the surgical margin in a Hybrid operating room (OS-MRCH), which uses a hybrid operating room wherein the operating table is seamlessly integrated with cone-beam computed tomography (CBCT). We performed the OS-MRCH method on 62 nodules including primary lung cancer presenting with GGO. Identification of the lesion and confirmation of the margin were performed in 58 of the cases, while nodules were detected in all. The frequency of computed tomography (CT) scans performed prior to resection was one time in 51 cases, two times in eight cases, and ≥3 times in three cases. Additional resection was performed in two cases. The median operative time was 85.0 minutes, and the median pathological margin was 11.0 mm. The key advantages of this method are that all surgical processes can be completed in a single session, specialized skill sets are not required, and it is feasible to perform in any facility equipped with a hybrid operating room. To overcome its disadvantages, such as longer operating time and limited patient positioning, we devised various methods for positioning patients and for CT imaging of the resected specimens. OS-MRCH is a simple, useful, and practical method for performing thoracoscopic partial resection of nonpalpable lung tumors.
  • 肺病立性毛細血管腫の2切除例と文献的考察
    大川 紘弥, 外丸 詩野, 若林 健人, 中里 信一, 岡崎 ななせ, 加藤 憲士郎, 宮石 陸, 氏家 秀樹, 加藤 達哉, 松野 吉宏
    日本病理学会会誌 (一社)日本病理学会 113 (1) 362 - 362 0300-9181 2024/02
  • 低血糖発作を合併した胸膜孤立性線維性腫瘍の1例
    村本 朋之, 中川 純一, 常田 慧徳, 高橋 文也, 木村 理奈, 西岡 典子, 坂本 圭太, 加藤 扶美, 氏家 秀樹, 加藤 達哉, 大藤 悠里, 亀田 啓, 中村 昭伸, 若林 健人, 松野 吉宏, 工藤 與亮
    Japanese Journal of Radiology (公社)日本医学放射線学会 42 (Suppl.) 4 - 4 1867-1071 2024/02
  • 大川 紘弥, 若林 健人, 中里 信一, 加藤 憲士郎, 宮石 陸, 松野 吉宏, 氏家 秀樹, 加藤 達哉
    肺癌 (NPO)日本肺癌学会 64 (1) 58 - 58 0386-9628 2024/02
  • 肺病立性毛細血管腫の2切除例と文献的考察
    大川 紘弥, 外丸 詩野, 若林 健人, 中里 信一, 岡崎 ななせ, 加藤 憲士郎, 宮石 陸, 氏家 秀樹, 加藤 達哉, 松野 吉宏
    日本病理学会会誌 (一社)日本病理学会 113 (1) 362 - 362 0300-9181 2024/02
  • 低血糖発作を合併した胸膜孤立性線維性腫瘍の1例
    村本 朋之, 中川 純一, 常田 慧徳, 高橋 文也, 木村 理奈, 西岡 典子, 坂本 圭太, 加藤 扶美, 氏家 秀樹, 加藤 達哉, 大藤 悠里, 亀田 啓, 中村 昭伸, 若林 健人, 松野 吉宏, 工藤 與亮
    Japanese Journal of Radiology (公社)日本医学放射線学会 42 (Suppl.) 4 - 4 1867-1071 2024/02
  • Hideki Ujiie, MD, PhD, Ryohei Chiba, Aogu Yamaguchi, Shunsuke Nomura, Haruhiko Shiiya, Aki Fujiwara-Kuroda, Kichizo Kaga, Chad Eitel, Tod Clapp, Tatsuya Kato
    Journal of Clinical Medicine 2024/01/21
  • 佐々木 明洋, 新垣 雅人, 竹野 巨樹, 山崎 洋, 野村 俊介, 大高 和人, 藤原 晶, 氏家 秀樹, 榊原 純, 大川 紘弥, 松野 吉宏, 加藤 達哉
    気管支学 (一社)日本呼吸器内視鏡学会 45 (6) 443 - 443 0287-2137 2023/11
  • Haruhiko Shiiya, Kichizo Kaga, Hideki Ujiie, Aki Fujiwara-Kuroda, Jun Muto, Shunsuke Nomura, Shohei Honda, Tatsuya Kato
    Journal of thoracic disease 15 (9) 5020 - 5028 2023/09/28 
    In the last few decades, reduced-port video-assisted thoracic surgery (RP-VATS) has been developed to minimize surgical invasiveness. Nevertheless, VATS in children can occasionally be difficult because the lesion occupies a small thoracic cavity, limiting the working space. This study aimed to assess the feasibility of RP-VATS for the resection of mediastinal lesions in children in association with the tumor-to-thoracic height ratio (TTH ratio). We reviewed all patients aged ≤10 years who underwent resection for mediastinal lesions in our institute between January 2008 and August 2022. Patients who underwent diagnostic procedures were excluded from this study. The TTH ratio was calculated as tumor height divided by thoracic height. Seven patients in the RP-VATS group and six in the conventional procedures (multi-portal VATS or open surgery) group were included in this study. The TTH ratio was significantly lower in the RP-VATS group than in the conventional procedures group (median, 26.3% vs. 50.8%; P=0.007). The operating time (P=0.01) and duration of drainage (P=0.003) were significantly shorter and the blood loss (P=0.001) was significantly lower in the RP-VATS group than in the conventional procedures group. After adjusting for age, a lower TTH ratio was significantly associated with the completion of RP-VATS (odds ratio: 0.776; 95% confidence interval: 0.529-0.926; P=0.048). In conclusion, RP-VATS can be performed appropriately in carefully selected cases of pediatric mediastinal lesions. A low TTH ratio may predict the feasibility of RP-VATS. Further studies are warranted to determine the criteria for the indications of RP-VATS in children, so that more children can benefit from RP-VATS.
  • Identification of micro-recurrent lesions using methylene blue for mediastinal ectopic parathyroid adenoma: a case report(タイトル和訳中)
    Nomura Shunsuke, Ujiie Hideki, Fujiwara-Kuroda Aki, Kaga Kichizo, Aragaki Masato, Muto Jun, Chiba Ryohei, Yamazaki Gaku, Wakabayashi Kento, Matsuno Yoshihiro, Kato Tatsuya
    General Thoracic and Cardiovascular Surgery Cases 2 1 of 4 - 4 of 4 2023/08
  • 肺胞出血を合併したLymphangioleiomyomatosisの1例
    大高 和人, 竹野 巨樹, 山崎 洋, 佐々木 明洋, 野村 俊介, 藤原 晶, 氏家 秀樹, 新垣 雅人, 加藤 達哉, 武井 望, 小熊 昂, 今野 哲, 大川 紘弥, 松野 吉宏
    日本気胸・嚢胞性肺疾患学会雑誌 日本気胸・嚢胞性肺疾患学会 23 (2) 90 - 90 1883-0412 2023/08
  • 肺胞出血を合併したLymphangioleiomyomatosisの1例
    大高 和人, 竹野 巨樹, 山崎 洋, 佐々木 明洋, 野村 俊介, 藤原 晶, 氏家 秀樹, 新垣 雅人, 加藤 達哉, 武井 望, 小熊 昂, 今野 哲, 大川 紘弥, 松野 吉宏
    日本気胸・嚢胞性肺疾患学会雑誌 日本気胸・嚢胞性肺疾患学会 23 (2) 90 - 90 1883-0412 2023/08
  • 気管支3Dモデルを用いた手術シミュレーション
    藤原 晶, 山崎 雅久, 千葉 龍平, 野村 俊介, 武藤 潤, 氏家 秀樹, 新垣 雅人, 加賀 基知三, 道田 共博, 若林 侑輝, 佐伯 和紀, 山口 仰, 加藤 達哉
    日本呼吸器外科学会雑誌 (一社)日本呼吸器外科学会 37 (3) O39 - 6 0919-0945 2023/06
  • 術後経時的ctDNA測定と腫瘍マーカーを併用した肺癌術後フォローアップ法は再発検出率を向上させる
    加藤 達哉, Ming Chin Yoon, Low Siew-Kee, 清谷 一馬, 氏家 秀樹, 藤原 晶, 新垣 雅人, 中村 祐輔
    日本呼吸器外科学会雑誌 (一社)日本呼吸器外科学会 37 (3) O52 - 3 0919-0945 2023/06
  • 術前、術後免疫チェックポイント阻害薬および肺剥皮術による集学的治療を行ったびまん性胸膜中皮腫の1例
    山崎 雅久, 藤原 晶, 千葉 龍平, 野村 俊介, 武藤 潤, 氏家 秀樹, 新垣 雅人, 加賀 基知三, 古田 恵, 大野 桜子, 松野 吉宏, 加藤 達哉
    日本呼吸器外科学会雑誌 (一社)日本呼吸器外科学会 37 (3) O59 - 2 0919-0945 2023/06
  • 左上葉切除後の脳梗塞発症予防として肺静脈心嚢内処理を施行した症例の検討
    武藤 潤, 山崎 雅久, 千葉 龍平, 野村 俊介, 藤原 晶, 氏家 秀樹, 新垣 雅人, 加賀 基知三, 加藤 達哉
    日本呼吸器外科学会雑誌 (一社)日本呼吸器外科学会 37 (3) O73 - 5 0919-0945 2023/06
  • 巨大ダンベル型脊髄腫瘍に対する、後方アプローチおよびロボット支援下手術(RATS)
    氏家 秀樹, 中谷 匠, 山崎 雅久, 野村 俊介, 千葉 龍平, 武藤 潤, 藤原 晶, 新垣 雅人, 加賀 基知三, 高畑 雅彦, 松野 吉宏, 加藤 達哉
    日本呼吸器外科学会雑誌 (一社)日本呼吸器外科学会 37 (3) P42 - 1 0919-0945 2023/06
  • 多発胸腺腫疑いに対し手術を施行し、胸腺癌と胸腺腫の同時多発が判明した1例
    中谷 匠, 野村 俊介, 藤原 晶, 氏家 秀樹, 新垣 雅人, 加賀 基知三, 加藤 憲士郎, 松野 吉宏, 加藤 達哉
    日本呼吸器外科学会雑誌 (一社)日本呼吸器外科学会 37 (3) P68 - 7 0919-0945 2023/06
  • Yuting Yin, Rie Sakakibara, Takayuki Honda, Susumu Kirimura, Pissacha Daroonpan, Masashi Kobayashi, Kohei Ando, Hideki Ujiie, Tatsuya Kato, Kichizo Kaga, Takahiro Mitsumura, Ryoji Nakano, Hiroyuki Sakashita, Shinichi Matsuge, Hironori Ishibashi, Takumi Akashi, Yasuhiro Hida, Takao Morohoshi, Miyuki Azuma, Kenichi Okubo, Yasunari Miyazaki
    Thoracic cancer 14 (20) 1991 - 2000 2023/05/30 
    BACKGROUND: The efficacy of immune checkpoint inhibitors (ICIs) in pleural mesothelioma has recently been established. The response to ICIs can be predicted by quantitative analysis of cells and their spatial distribution in the tumor microenvironment (TME). However, the detailed composition of the TME in pleural mesothelioma has not been reported. We evaluated the association between the TME and response to ICIs in this cancer. METHODS: A retrospective analysis of 22 pleural mesothelioma patients treated with nivolumab in different centers was performed using surgical specimens. Four patients had a partial response to nivolumab (response group) and 18 patients had stable or progressive disease (nonresponse group). The number of CD4, CD8, FoxP3, CK, and PD-L1 positive cells, cell density, and cell-to-cell distance were analyzed by multiplex immunofluorescence. RESULTS: PD-L1 expression did not differ significantly between the response and nonresponse groups. The density of total T cells and of CD8+ T cells was significantly higher in the response than in the nonresponse group. CD8+ T cells were more clustered and located closer to tumor cells, whereas regulatory T cells were located further from tumor cells in the response than in the nonresponse group. CONCLUSIONS: High density and spatial proximity of CD8+ T cells to tumor cells were associated with better response to nivolumab, whereas the proximity of regulatory T cells to tumor cells was associated with worse response, suggesting that the distinct landscape of the TME could be a potential predictor of ICI efficacy in pleural mesothelioma.
  • 新垣 雅人, 稲毛 輝長, 川島 光明, 谷口 大輔, 石綿 司, 加藤 達哉, 安福 和弘, Keshavjee Shaf, Cypel Marcelo
    移植 (一社)日本移植学会 57 (4) 396 - 396 0578-7947 2023/04
  • Aki Fujiwara-Kuroda, Yasuhiro Hida, Hideki Ujiie, Kichizo Kaga, Tatsuya Kato
    Interdisciplinary cardiovascular and thoracic surgery 36 (3) 2023/03/02 
    Total pleural covering is implemented to reinforce the visceral pleura with surgical sheets. It has been adopted for diffuse cystic lung diseases such as lymphangioleiomyomatosis to prevent pneumothorax and has achieved good results. The procedure is technically demanding, because it is difficult to cover the entire visceral pleura without disarrangement and jamming of surgical sheets, especially during thoracoscopic surgery, where grasping of a wrong site might happen when unfolding the sheets. Herein, we report a technique to cover the entire pleura with dotted line folded sheets to ease the thoracoscopic procedure. We found that the use of this marking method made the procedure easier, with just a little ingenuity, because marking the edges of sheets with dashed lines clarifies the site that should be grasped, thus preventing the incidence of grasping the wrong part of the sheet. Pleural covering with dotted line folded surgical sheets is a useful method for reduced port thoracoscopic surgery.
  • 医学生、研修医を対象とした医学教育とメディカルイラストの利用
    加賀 基知三, 藤原 晶, 山崎 雅久, 千葉 龍平, 野村 俊介, 武藤 潤, 氏家 秀樹, 新垣 雅人, 加藤 達哉
    日本メディカルイラストレーション学会学術集会・総会 日本メディカルイラストレーション学会 7回 O - 3 2023/03
  • 胸膜孤立性線維性腫瘍に合併したDoege-potter症候群の一例
    村本 朋之, 中川 純一, 常田 慧徳, 高橋 文也, 木村 理奈, 西岡 典子, 坂本 圭太, 加藤 扶美, 氏家 秀樹, 加藤 達哉, 大藤 悠理, 亀田 啓, 中村 昭伸, 若林 健人, 松野 吉宏, 工藤 與亮
    北海道放射線医学雑誌 (NPO)メディカルイメージラボ 3 28 - 32 2023/03 
    症例は60歳代女性。X-1年の検診で右胸部に異常影を指摘された。X年に胸部異常影増大と空腹時血糖38mg/dLの著明低値を認めたため前医を受診し、CTで右胸腔下部を占拠する巨大腫瘤を認めた。針生検で孤立性線維性腫瘍(solitary fibrous tumor:SFT)が疑われたため、手術目的に当院呼吸器外科に紹介受診となった。入院後低血糖時の採血でinsulinとC-peptideの低下を認めた。腫瘍はMRIではT2強調像で低信号を主体として高信号が混在し、内部にflow voidを認めた。造影後T1強調像では強く増強され、内部に血管が発達していた。腫瘍摘出術が施行され、SFTの確定診断となった。術前に頻発していた低血糖は術直後から消失し、SFTに伴う非膵島細胞腫瘍性低血糖症と考えられた。本病態はDoege-Potter症候群として知られ、SFTの5%以下の症例で生じるとされる。低血糖を合併した軟部腫瘍ではSFTが鑑別のひとつに挙げられる。(著者抄録)
  • Jenny Lou, Masato Aragaki, Nicholas Bernards, Tess Chee, Alexander Gregor, Yoshihisa Hiraishi, Tsukasa Ishiwata, Chelsea Leung, Lili Ding, Shinsuke Kitazawa, Takamasa Koga, Yuki Sata, Hiroyuki Ogawa, Juan Chen, Tatsuya Kato, Kazuhiro Yasufuku, Gang Zheng
    Biomaterials 292 121918 - 121918 2023/01 
    In combination with immune checkpoint inhibitors, photodynamic therapy can induce robust immune responses capable of preventing local tumor recurrence and delaying the growth of distant, untreated disease (ie. the abscopal effect). Previously, we found that repeated photodynamic therapy (R-PDT) using porphyrin lipoprotein (PLP) as a photosensitizer, without the addition of an immune checkpoint inhibitor, can induce the abscopal effect. To understand why PLP mediated R-PDT alone can induce the abscopal effect, and how the addition of an immune checkpoint inhibitor can further strengthen the abscopal effect, we investigated the broader immune mechanisms facilitated by R-PDT and combination R-PDT + anti-PD-1 monoclonal antibody (αPD-1) in a highly aggressive, subcutaneous AE17-OVA mesothelioma dual tumor-bearing C57BL/6 mice. We found a 46.64-fold and 61.33-fold increase in interleukin-6 (IL-6) after R-PDT and combination R-PDT + αPD-1 relative to PBS respectively, suggesting broad innate immune activation. There was a greater propensity for antigen presentation in the spleen and distal, non-irradiated tumor draining lymph nodes, as dendritic cells and macrophages had increased expression of MHC class II, CD80, and CD86, after R-PDT and combination R-PDT + αPD-1. Concurrently, there was a shift in the proportions of CD4+ T cell subsets in the spleen, and an increase in the frequency of CD8+ T cells in the distal, non-irradiated tumor draining lymph nodes. While R-PDT had an acceptable safety profile, combination R-PDT + αPD-1 induced 1.26-fold higher serum potassium and 1.33-fold phosphorus, suggestive of mild laboratory tumor lysis syndrome. Histology revealed an absence of gross inflammation in critical organs after R-PDT and combination R-PDT + αPD-1 relative to PBS-treated mice. Taken together, our findings shed light on how the abscopal effect can be induced by PDT and strengthened by combination R-PDT + αPD-1, and suggests minimal toxicities after R-PDT.
  • 腹臥位・人工気胸下での胸腔内剥離が有用であった巨大縦隔内甲状腺腫の1例
    武藤 潤, 加納 里志, 山崎 雅久, 千葉 龍平, 野村 俊介, 藤原 晶, 氏家 秀樹, 樋田 泰浩, 加賀 基知三, 本間 明宏, 加藤 達哉
    日本臨床外科学会雑誌 日本臨床外科学会 83 (12) 2119 - 2119 1345-2843 2022/12
  • 加賀 基知三, 藤原 晶, 長島 諒太, 野村 俊介, 千葉 龍平, 田畑 佑希子, 氏家 秀樹, 加藤 達哉, 樋田 泰浩
    日本メディカルイラストレーション学会雑誌 日本メディカルイラストレーション学会 4 (1) 12 - 12 2433-6181 2022/12
  • 胸部単純エックス線写真読影の教材としてのデジタルイラスト
    加賀 基知三, 藤原 晶, 長島 諒太, 野村 俊介, 千葉 龍平, 田畑 佑希子, 氏家 秀樹, 加藤 達哉, 樋田 泰浩
    日本メディカルイラストレーション学会雑誌 日本メディカルイラストレーション学会 4 (1) 12 - 12 2433-6181 2022/12
  • 武藤 潤, 山崎 雅久, 千葉 龍平, 野村 俊介, 高島 雄太, 藤原 晶, 氏家 秀樹, 村上 壮一, 倉島 庸, 海老原 裕磨, 七戸 俊明, 樋田 泰浩, 加賀 基知三, 平野 聡, 加藤 達哉
    気管支学 (NPO)日本呼吸器内視鏡学会 44 (6) 457 - 457 0287-2137 2022/11
  • 武藤 潤, 山崎 雅久, 千葉 龍平, 野村 俊介, 高島 雄太, 藤原 晶, 氏家 秀樹, 村上 壮一, 倉島 庸, 海老原 裕磨, 七戸 俊明, 樋田 泰浩, 加賀 基知三, 平野 聡, 加藤 達哉
    気管支学 (NPO)日本呼吸器内視鏡学会 44 (6) 457 - 457 0287-2137 2022/11
  • Masato Aragaki, Terunaga Inage, Tsukasa Ishiwata, Alexander Gregor, Nicholas Bernards, Tatsuya Kato, Kazuhiro Yasufuku
    The Journal of thoracic and cardiovascular surgery 165 (5) e210-e221  2022/09/14 
    OBJECTIVE: Severe pulmonary embolism is often managed with thrombolysis. We sought to determine whether endobronchial ultrasound (EBUS)-guided transbronchial thrombolysis remained effective at lower alteplase doses, with the goal of minimizing potential bleeding risk. METHODS: Yorkshire pigs were anesthetized and ventilated. Preformed autologous blood clots were administered into bilateral pulmonary arteries via EBUS-guided transbronchial injection. After documenting baseline clot sizes, alteplase was injected into the clots using a 25-gauge transbronchial needle and clot dissolution was monitored over 30 minutes. The study was performed in 2 phases. First, alteplase doses of 5 and 12.5 mg were evaluated. These results informed dose selection for the second phase. Results were compared with 25-mg dose data using EBUS from a previous study. RESULTS: In the first phase, 3 clots were evaluated. Distilled water, 5 mg, and 12.5 mg alteplase were administered. The dissolved clot volume (Vdis) and percentage clot volume loss (Rdis) were -10.9, 111.6, and 160.3 mm3, and -1.6%, 11.0%, and 59.3%, respectively. In the second phase, alteplase doses of 5, 10, and 15 mg were evaluated in 12 clots across 6 pigs. The Vdis were 247.5 mm3 (Rdis, 20.1%), 910.8 mm3 (Rdis, 80.9%), and 798.3 mm3 (Rdis, 76.0%) for 5, 10, and 15 mg alteplase, respectively. Remakably reduced performance was observed with 5 mg alteplase versus 10 mg (Vdis: P < .001, Rdis: P < .001), and 15 mg (Vdis: P = .004; Rdis: P < .001). No complications were observed. CONCLUSIONS: Alteplase doses ≥10 mg were optimal for EBUS-guided transbronchial thrombolysis. This technique might represent an effective alternative therapy for central pulmonary embolism.
  • Haruhiko Shiiya, Akihiko Tanaka, Motoki Sakuraba, Hideki Ujiie, Tatsuya Kato
    Journal of thoracic disease 14 (9) 3255 - 3264 2022/09 
    BACKGROUND: During surgery for spontaneous pneumothorax, parietal pleural small holes (PPSHs) are occasionally found around the apex of the intrapleural space; however, this has not been well recognized. Additionally, chest wall flatness is usually observed in patients with primary spontaneous pneumothorax (PSP) and PPSHs. This study aimed to investigate the prevalence of PPSH and evaluate the characteristics of patients with PPSH. We also investigated the degree of chest wall flatness in patients with PPSHs. METHODS: We retrospectively reviewed all patients who underwent thoracoscopic surgery for pneumothorax at our department between April 2014 and May 2021. A propensity-matched analysis was used to compare the characteristics of patients with and without PPSH. RESULTS: A total of 490 patients were enrolled in this study. PPSH was found in 45 of 297 (15.2%) patients with PSP and one of 193 (0.5%) patients with secondary pneumothorax. PSP was independently associated with the presence of PPSH after adjusting for age and sex [primary/secondary, odds ratio (OR) =34.3, 95% confidence interval (CI): 4.7-250.9; P<0.001]. Among patients with PSP, the flatness of the chest wall in patients with PPSH was not as severe as that in patients without PPSH {thoracic anteroposterior diameter (APDT) to transverse diameter (TDT) ratio; with PPSH: median =0.517 [interquartile range (IQR) =0.480-0.554] vs. without PPSH: median =0.487 (IQR =0.463-0.529; P=0.031)} after propensity score matching. CONCLUSIONS: PPSH is found in a non-negligible proportion of patients with PSP, and patients with PPSHs show a relatively mild flat chest among patients with PSP. Clinicians should be aware of PPSH, and further understanding of this condition may contribute to a better understanding of PSP.
  • Yuya Wada, Hideki Ujiie, Ryohei Chiba, Shunsuke Nomura, Aki Fujiwara-Kuroda, Kichizo Kaga, Satoru Wakasa, Tatsuya Kato
    VIDEO-ASSISTED THORACIC SURGERY 2519-0792 2022/08 
    Background: The use of complete video-assisted thoracoscopic surgery (c-VATS) for primary bronchial tumors has increased due to its less invasive nature and cosmetic advantages. However, no studies have reported about flap bronchoplasty using c-VATS due to its technicality. Case Description: A woman in her 20s presented with dyspnea and chest tightness. Computed tomography (CT) showed a 15x18-mm-sized mass located from the left second carina to the lower lobe bronchus root. Flap bronchoplasty using c-VATS was performed. The tumor developed from the second carina near the anterior wall of the left main bronchial cartilage. The upper lobe bronchial root was resected while ensuring surgical margin. The B6 bronchial wall was trimmed to create a flap, and bronchoplasty was performed to fill the defect. After bronchoplasty, the fifth intercostal muscle valve was wrapped around the flap. Postoperative course was uneventful, and bronchoscopy revealed no stenosis. There has been no adverse events and recurrence for 2 years after surgery. Conclusions: Flap bronchoplasty from the resected area allowed preservation of the basal area, and was a useful technique in terms of function preservation. Since the patient in this case was a young female, a full thoracoscopic surgery was completed successfully in consideration of invasion and appearance.
  • デジタルイラストで伝わる手術記録(オペレコ)を描こう
    加賀 基知三, 藤原 晶, 山崎 雅久, 千葉 龍平, 野村 俊介, 武藤 潤, 氏家 秀樹, 樋田 泰浩, 加藤 達哉
    日本気胸・嚢胞性肺疾患学会雑誌 日本気胸・嚢胞性肺疾患学会 22 (2) 94 - 94 1883-0412 2022/08
  • びまん性肺疾患を有する気胸に対しての治療戦略 骨髄移植後の移植片対宿主病(GVHD)肺病変を背景とした気胸手術症例の検討
    武藤 潤, 山崎 雅久, 千葉 龍平, 野村 俊介, 藤原 晶, 氏家 秀樹, 樋田 泰浩, 加賀 基知三, 加藤 達哉
    日本気胸・嚢胞性肺疾患学会雑誌 日本気胸・嚢胞性肺疾患学会 22 (2) 107 - 107 1883-0412 2022/08
  • Ryohei Chiba, Yuma Ebihara, Haruhiko Shiiya, Hideki Ujiie, Aki Fujiwara-Kuroda, Kichizo Kaga, Liming Li, Satoru Wakasa, Satoshi Hirano, Tatsuya Kato
    Journal of thoracic disease 14 (8) 2943 - 2952 2022/08 
    Background: Palpation of tumors during thoracoscopic surgery remains difficult, and identification of deep-seated tumors may be impossible. This preclinical study investigated the usefulness of a novel indocyanine green (ICG) fluorescence spectroscopy system for tumor localization. Methods: ICG was diluted to 5.0×10-2 mg/mL in fetal bovine serum (FBS) and mixed with silicone resin to prepare pseudo-tumors. Sponges of different densities and a porcine lung were placed on top of the pseudo-tumors, which were examined using a novel fluorescence spectroscopy system and a near-infrared (NIR) camera. Spectra were measured for different sponge and lung thicknesses, and the lung spectra were measured during both inflation and deflation. Results: The fluorescence spectroscopy system was able to identify tumors at depths ≥15 mm, while the NIR system was not. The spectroscopy system also detected tumors at greater depths when the density of the intervening material was lower. Depending on the density and thickness of the intervening material, the system could detect spectra as deep as 40 mm for sponges and 30 mm for lungs. Conclusions: This new fluorescence spectroscopy system can be used to identify lung tumors up to a depth of 30 mm in experiments using pseudo-tumors and a porcine lung, which may aid in tumor identification during thoracoscopic surgery.
  • 山崎 雅久, 氏家 秀樹, 野村 俊介, 千葉 龍平, 武藤 潤, 藤原 晶, 樋田 泰浩, 加賀 基知三, 三浦 瞬, 高島 雄太, 品川 尚文, 加藤 達哉
    小切開・鏡視外科学会雑誌 (NPO)小切開・鏡視外科学会 13 (1) 58 - 58 2185-2820 2022/06
  • 山崎 雅久, 氏家 秀樹, 野村 俊介, 千葉 龍平, 武藤 潤, 藤原 晶, 樋田 泰浩, 加賀 基知三, 三浦 瞬, 高島 雄太, 品川 尚文, 加藤 達哉
    小切開・鏡視外科学会雑誌 (NPO)小切開・鏡視外科学会 13 (1) 58 - 58 2185-2820 2022/06
  • Takuya Ikushima, Hideki Ujiie, Satonori Tsuneta, Ryohei Chiba, Yukiko Tabata, Aki Fujiwara-Kuroda, Yasuhiro Hida, Kichizo Kaga, Satoru Wakasa, Tatsuya Kato
    General thoracic and cardiovascular surgery 70 (7) 673 - 676 2022/04/06 
    Azygos vein aneurysm (AVA) is necessary to prevent pulmonary embolism due to the outflow of a thrombus or rupture of the aneurysm. However, there is no established modality to assess the properties of AVA. Time-resolved three-dimensional phase-contrast magnetic resonance imaging (4D-flow MRI) has been used to examine the hemodynamics in various fields. We report a case of AVA to evaluate the flow variability and adhesions of surrounding tissues using 4D-flow MRI. The findings of the study suggested aneurysm turbulence and the absence of thrombi. The cine image, which showed a sliding wall synchronized to the heartbeat, indicated no adhesion to the superior vena cava. Based on these results, the thoracoscopic approach was deemed possible preoperatively. Thoracoscopic AVA resection was performed, and the postoperative course was uneventful. This study documented the utility of 4D-flow MRI for a detailed evaluation of AVA.
  • 新規胸腔鏡用蛍光スペクトル測定システムは深部肺腫瘍の同定を可能にする
    千葉 龍平, 加藤 達哉, 海老原 裕磨, 氏家 秀樹, 田畑 佑希子, 藤原 晶, 樋田 泰浩, 加賀 基知三
    日本外科学会定期学術集会抄録集 (一社)日本外科学会 122回 SF - 5 2022/04
  • 新規胸腔鏡用蛍光スペクトル測定システムは深部肺腫瘍の同定を可能にする
    千葉 龍平, 加藤 達哉, 海老原 裕磨, 氏家 秀樹, 田畑 佑希子, 藤原 晶, 樋田 泰浩, 加賀 基知三
    日本外科学会定期学術集会抄録集 (一社)日本外科学会 122回 SF - 5 2022/04
  • 3D-バーチャル・リアリティー(VR)システムを用いた、呼吸器外科ロボット手術トレーニング法の開発
    氏家 秀樹, 幾島 拓也, 大塚 慎也, 千葉 龍平, 野村 俊介, 椎谷 洋彦, 田畑 佑希子, 藤原 晶, 加藤 達哉, 樋田 泰浩, 加賀 基知三, 若狭 哲
    日本外科学会定期学術集会抄録集 (一社)日本外科学会 122回 SF - 3 2022/04
  • Haruhiko Shiiya, Hideki Ujiie, Tatsuya Kato, Shohei Honda, Satoru Wakasa, Kichizo Kaga
    INDIAN JOURNAL OF SURGERY 0972-2068 2022/04 
    To the best of our knowledge, no previous reports have described the indication criteria and details of uniportal video-assisted thoracoscopic lobectomy in younger children. We report the utility of uniportal video-assisted thoracoscopic right lower lobectomy via a 2-cm incision in a 2-year-old child with a prenatal diagnosis of congenital cystic lung disease. A male infant with a prenatal diagnosis of congenital cystic lung disease was delivered vaginally at 36 weeks of gestation. Computed tomography after birth showed that the disease was limited to the right lower lobe. The patient was asymptomatic and was initially treated conservatively. At the age of 2 years and 10 months, when compensatory lung growth can still be expected, the patient had become large enough to safely undergo one-lung ventilation and thoracoscopic surgery. Therefore, we decided to perform a curative lobectomy. A single 2-cm incision was made at the anterior axillary line on the 6th intercostal space. The vessels and bronchus were approached from the anterior side. We used a 3-mm thoracoscope and instruments with a small diameter. The patient was discharged without any complications or need for analgesic drugs. The crossing technique was utilized to minimize the interference between multiple instruments in a small incision with a narrow intercostal space.
  • Shinya Otsuka, Kei Hiraoka, Masato Suzuoki, Hideki Ujiie, Tatsuya Kato, Isao Yokota, Kazuya Yonezawa, Keiji Oguma, Nozomu Iwashiro, Mototsugu Kato, Masanori Ohara
    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 28 (4) 539 - 542 2022/04 
    INTRODUCTION: The effectiveness of several vaccines against coronavirus disease (COVID-19) has been reported in the real-world setting. However, it is still unknown how long antibodies persist following vaccination and whether or not the persistence of antibodies has a protective effect against COVID-19. METHODS: Healthcare workers who had received two doses of the BNT162b2 mRNA COVID-19 vaccine were enrolled, and a single-center study was conducted at the National Hospital Organization Hakodate National Hospital. Serum samples from all participants were collected 13-21 weeks (median: 20 weeks) after the second dose of vaccination. The antibody titers were measured using an electrochemiluminescence immunoassay (Elecsys® Anti-SARS-CoV-2 S). Data on characteristics of the participants were gathered from patient records and interview sheets. RESULTS: A total of 401 participants, among whom 70.1% were women and the median age was 42 years, were evaluated in this study. None of the participants had a definite COVID-19 history, and all participants who received complete vaccination showed positive antibody titers. The antibody titer was observed to be higher in participants with younger age (p < 0.001) and those who were females (p = 0.028). Despite the higher risk of infection than that of the general public, no vaccinated staff developed breakthrough infections. CONCLUSIONS: This study demonstrates the significant contribution of the BNT162b2 vaccine in the acquisition of anti-SARS-CoV-2S antibodies; therefore, the general population should benefit from these two vaccine doses, which are expected to be protective for at least five months.
  • 胸部単純エックス線写真読影の教材としてのデジタルイラスト
    加賀 基知三, 藤原 晶, 長島 諒太, 野村 俊介, 千葉 龍平, 田畑 佑希子, 氏家 秀樹, 加藤 達哉, 樋田 泰浩
    日本メディカルイラストレーション学会学術集会・総会 日本メディカルイラストレーション学会 6回 np20 - np21 2022/03
  • Cadaverを用いた高難度呼吸器外科手術手技トレーニングの取り組み
    藤原 晶, 加藤 達哉, 幾島 拓也, 千葉 龍平, 田畑 佑希子, 氏家 秀樹, 樋田 泰浩, 加賀 基知三
    日本臨床外科学会雑誌 日本臨床外科学会 83 (3) 598 - 598 1345-2843 2022/03
  • 胸部単純エックス線写真読影の教材としてのデジタルイラスト
    加賀 基知三, 藤原 晶, 長島 諒太, 野村 俊介, 千葉 龍平, 田畑 佑希子, 氏家 秀樹, 加藤 達哉, 樋田 泰浩
    日本メディカルイラストレーション学会学術集会・総会 日本メディカルイラストレーション学会 6回 np20 - np21 2022/03
  • Cadaverを用いた高難度呼吸器外科手術手技トレーニングの取り組み
    藤原 晶, 加藤 達哉, 幾島 拓也, 千葉 龍平, 田畑 佑希子, 氏家 秀樹, 樋田 泰浩, 加賀 基知三
    日本臨床外科学会雑誌 日本臨床外科学会 83 (3) 598 - 598 1345-2843 2022/03
  • 切除を先行した巨大(>10cm)肺腫瘤の2症例
    千葉 龍平, 加賀 基知三, 幾島 拓也, 田畑 佑希子, 藤原 晶, 氏家 秀樹, 加藤 達哉, 樋田 泰浩, 若狭 哲, 岡崎 ななせ, 若林 健人, 松野 吉宏
    肺癌 (NPO)日本肺癌学会 62 (1) 72 - 73 0386-9628 2022/02
  • 切除を先行した巨大(>10cm)肺腫瘤の2症例
    千葉 龍平, 加賀 基知三, 幾島 拓也, 田畑 佑希子, 藤原 晶, 氏家 秀樹, 加藤 達哉, 樋田 泰浩, 若狭 哲, 岡崎 ななせ, 若林 健人, 松野 吉宏
    肺癌 (NPO)日本肺癌学会 62 (1) 72 - 73 0386-9628 2022/02
  • 難治性肺瘻をどう取り扱うか 肺切除後難治性肺瘻の治療戦略
    加賀 基知三, 樋田 泰浩, 加藤 達哉, 藤原 晶, 氏家 秀樹, 田畑 佑希子, 野村 俊介, 千葉 龍平, 幾島 拓也, 若狭 哲
    日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 26 (7) WS32 - 3 1344-6703 2021/12
  • 難治性肺瘻をどう取り扱うか 肺切除後難治性肺瘻の治療戦略
    加賀 基知三, 樋田 泰浩, 加藤 達哉, 藤原 晶, 氏家 秀樹, 田畑 佑希子, 野村 俊介, 千葉 龍平, 幾島 拓也, 若狭 哲
    日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 26 (7) WS32 - 3 1344-6703 2021/12
  • 田畑 佑希子, 加藤 達哉, 大塚 慎也, 幾島 拓也, 千葉 龍平, 藤原 晶, 氏家 秀樹, 樋田 泰浩, 品川 尚文, 有里 仁希, 高島 雄太, 加賀 基知三, 若狭 哲
    気管支学 (NPO)日本呼吸器内視鏡学会 43 (6) 689 - 689 0287-2137 2021/11
  • 未来のための今 胸部外科医育成のための新たなる挑戦 3D-バーチャル・リアリティー(VR)システムを用いた、呼吸器外科手術トレーニング法の開発
    氏家 秀樹, 幾島 拓也, 大塚 慎也, 千葉 龍平, 野村 俊介, 椎谷 洋彦, 田畑 佑希子, 藤原 晶, 加藤 達哉, 樋田 泰浩, 加賀 基知三, 若狭 哲
    日本胸部外科学会定期学術集会 (一社)日本胸部外科学会 74回 SP5 - 3 2021/10
  • 奇静脈瘤の伸展評価における4D-Flow MRIの有用性
    幾島 拓也, 氏家 秀樹, 加藤 達哉, 大塚 慎也, 千葉 龍平, 野村 俊介, 椎谷 洋彦, 田畑 佑希子, 藤原 晶, 樋田 泰浩, 加賀 基知三, 若狭 哲
    日本胸部外科学会定期学術集会 (一社)日本胸部外科学会 74回 LOD19 - 5 2021/10
  • 氏家 秀樹, 幾島 拓也, 千葉 龍平, 野村 俊介, 田畑 佑希子, 藤原 晶, 加藤 達哉, 樋田 泰浩, 加賀 基知三, 若狭 哲
    肺癌 (NPO)日本肺癌学会 61 (6) 613 - 613 0386-9628 2021/10
  • バーチャル・リアリティー(VR)システムを用いた,ロボット外科手術シミュレーション法の開発
    氏家 秀樹, 幾島 拓也, 千葉 龍平, 野村 俊介, 田畑 佑希子, 藤原 晶, 加藤 達哉, 樋田 泰浩, 加賀 基知三, 若狭 哲
    肺癌 (NPO)日本肺癌学会 61 (6) 613 - 613 0386-9628 2021/10
  • Shinya Otsuka, Tatsuya Kato, Hideki Ujiie, Aki Fujiwara-Kuroda, Yasuhiro Hida, Kichizo Kaga, Satoru Wakasa, Yuta Takashima, Naofumi Shinagawa
    General thoracic and cardiovascular surgery 69 (12) 1589 - 1592 2021/09/28 [Refereed]
     
    Blunt tracheal injury is a rare but life-threatening condition. Several indications for treatment have been reported. Conservative treatment (i.e., stenting) can be performed when the patient is clinically stable or has medical contraindications to surgical treatment. Although some studies have reported the use of tracheal stents as treatment for iatrogenic injury and blunt trauma, the efficacy of these stents is unknown. Herein, we report a case of emergency tracheoplasty for the management of tracheal stent prolapse in a patient with blunt tracheobronchial trauma. This report highlights the necessity of being cautious about the migration and prolapse of tracheal stents, which can more frequently occur in blunt trauma than in malignant stenosis or iatrogenic injury. Due to the limitations of non-surgical treatments, early surgical intervention may be lifesaving.
  • Haruhiko Shiiya, Hideki Ujiie, Yasuhiro Hida, Tatsuya Kato, Kichizo Kaga, Satoru Wakasa, Eiki Kikuchi, Naofumi Shinagawa, Kazufumi Okada, Yoichi M Ito, Yoshihiro Matsuno
    Thoracic cancer 12 (21) 2933 - 2942 2021/09/27 [Refereed]
     
    BACKGROUND: No useful tumor markers have been identified for the diagnosis of thymic carcinomas. Serum cytokeratin 19 fragment, measured using the CYFRA 21-1 immunoassay, is used as a tumor marker for squamous cell carcinomas in various malignant tumors. Here, we evaluated the value of CYFRA 21-1 in diagnosing thymic carcinoma. METHODS: We retrospectively reviewed 94 patients with pathological diagnoses of thymic carcinoma or thymoma (32 and 62 patients, respectively) who were referred to our departments between January 2000 and March 2019. Primary outcomes included tumor marker levels and their diagnostic accuracy. RESULTS: Patients with thymic carcinoma were significantly more likely to be male (thymic carcinoma, 68.8%; thymoma, 40.3%; p = 0.02), have an advanced TNM stage (p < 0.01), and a significantly higher CYFRA 21-1 level than those with thymoma (thymic carcinoma: median = 4.2 ng/ml; interquartile range [IQR] = 2.1-6.1 ng/ml vs. thymoma: median = 1.2 ng/ml; IQR = 0.9-1.7 ng/ml; p < 0.01). Receiver operating characteristic curves demonstrated that the area under the curve for CYFRA 21-1 to distinguish thymic carcinoma from thymoma was 0.86 (95% confidence interval [CI]: 0.74-0.93; cutoff = 2.7 ng/ml; sensitivity = 68.8%; specificity = 95.2%). Multivariable analysis demonstrated that CYFRA 21-1 (odds ratio = 25.6; 95% CI: 4.6-141.6; p < 0.01) was an independent predictor for thymic carcinoma after adjusting for TNM stage. CONCLUSIONS: Serum CYFRA 21-1 level may help in diagnosing thymic carcinoma.
  • Yusuke Motohashi, Tatsuya Kato, Nobuyasu Kato, Masato Aragaki, Aki Fujiwara-Kuroda, Tsuyoshi Tachibana, Yasuhiro Hida, Kichizo Kaga, Satoru Wakasa
    General thoracic and cardiovascular surgery 69 (12) 1575 - 1579 2021/09/21 [Refereed]
     
    A 4-year-old boy with left intralobar pulmonary sequestration associated with left main coronary artery obstruction (LMCAO) and severe mitral regurgitation (MR) was admitted to our hospital. Since the patient presented with dyskinesia of the cardiac apex and increased left ventricular end-diastolic volume (LVEDV), left main coronary artery reconstruction and mitral annuloplasty were performed. The enlargement of the left ventricle was improved after sequential surgeries. There was a risk of deterioration of MR and regrowth of LVEDV due to shunt blood flow; therefore, left lower lobectomy and aberrant artery division were performed. This is a very rare case of a patient with pulmonary sequestration associated with LMCAO and severe MR.
  • Shinya Otsuka, Hideki Ujiie, Kosuke Ishikawa, Takahiro Miura, Satoru Wakasa, Tatsuya Kato
    The Annals of thoracic surgery 112 (6) e471  2021/09/04 [Refereed]
  • 胎児治療を施行したCongenital pulmonary airway malformation(CPAM)の患児に対し日齢9で完全胸腔鏡下右上葉切除術を施行した一例
    幾島 拓也, 氏家 秀樹, 加藤 達哉, 大塚 慎也, 千葉 龍平, 野村 俊介, 椎谷 洋彦, 田畑 佑希子, 藤原 晶, 樋田 泰浩, 加賀 基知三, 若狭 哲, 本多 昌平
    日本気胸・嚢胞性肺疾患学会雑誌 日本気胸・嚢胞性肺疾患学会 21 (2) 113 - 113 1883-0412 2021/09
  • 肝移植後にPleuroparenchymal fibroelastosis(PPFE)合併肺癌を発症した一例
    大塚 慎也, 加藤 達哉, 氏家 秀樹, 椎谷 洋彦, 加賀 基知三, 若狭 哲, 中村 順一, 中久保 祥, 木村 孔一, 渡辺 正明, 嶋村 剛, 岡崎 ななせ, 松野 吉宏, 田中 敏
    移植 (一社)日本移植学会 56 (総会臨時) P2 - 7 0578-7947 2021/09
  • Akihiro Sasaki, Tatsuya Kato, Hideki Ujiie, Satoru Wakasa, Setsuyuki Otake, Keisuke Kikuchi, Koichi Ohno
    Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia 28 (6) 448 - 452 2021/07/16 [Refereed]
     
    INTRODUCTION: Stiff-person syndrome (SPS) is a rare autoimmune neurological disorder. Paraneoplastic SPS associated with malignant tumors such as thymoma occurs in approximately 5% of all SPS cases. We present a rare case of thymoma accompanied by SPS successfully treated using surgery. PRESENTATION OF CASE: A 26-year-old woman presented with lower limbs convulsions and gait disturbance and complained of leg pain. Cerebrospinal fluid and blood test results showed a high level of anti-glutamic acid decarboxylase (GAD) antibodies. Computed tomography showed anterior mediastinal tumor suggestive of a thymoma. She underwent extended thymectomy, and her symptoms gradually improved after surgery. No evidence of recurrent thymoma and SPS has been observed over 44 months. CONCLUSION: Surgical treatment would be effective for patients with SPS and thymoma.
  • Yoshinobu Watabe, Hideki Ujiie, Yoshihiro Matsuno, Hideaki Fukui, Aki Fujiwara-Kuroda, Tatsuya Kato, Yasuhiro Hida, Kichizo Kaga, Satoru Wakasa
    Chest 160 (1) e63-e67  2021/07 [Refereed]
     
    CASE PRESENTATION: A 57-year-old woman was admitted to our hospital for an abnormal chest shadow found during routine chest radiography. She had no respiratory symptoms. Her medical history included dyslipidemia, and her surgical history included conization for cervical cancer at age 38 years. She was a social drinker and ex-smoker of approximately 10 cigarettes per day (from ages 20 to 30 years); she denied recreational drug use.
  • Hiroshi Yamasaki, Hideki Ujiie, Tatsuya Kato, Yasuhiro Hida, Kichizo Kaga, Satoru Wakasa, Yoshihiro Matsuno
    Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia 27 (6) 371 - 379 2021/05/14 [Refereed]
     
    PURPOSE: Pulmonary nodules suspected to be cancerous are rarely diagnosed as pulmonary infarction (PI). This study examined the clinical, radiological, and laboratory data in cases diagnosed with PI to determine their potential utility as preoperative diagnostic markers. We also assessed factors affecting the postoperative course. METHODS: A total of 603 cases of peripheral pulmonary nodules undiagnosed preoperatively were resected at Hokkaido University Hospital from 2012 to 2019. Of these, we reviewed cases with a postoperative diagnosis of PI. We investigated clinical symptoms, preoperative laboratory data, radiological characteristics, and postoperative complications. RESULTS: Four patients (0.7%) were diagnosed with PI. All patients had a smoking history. One patient received systemic steroid administration, and none had predisposing factors for thrombosis. One case showed chronologically increased nodule size. Three cases showed weak uptake of 18F-fluorodeoxyglucose. One patient with preoperative high D-dimer levels developed a massive pulmonary embolism (PE) in the postoperative chronic phase and was treated with anticoagulants. CONCLUSIONS: Preoperative diagnosis of PI is difficult, and we could not exclude lung cancer. However, if a patient diagnosed with PI has a high D-dimer level, we recommend postoperative physical examination for deep venous thrombosis. Prophylactic anticoagulation therapy should be considered to avoid fatal PE.
  • COVID-19に対する、北海道大学の取り組み
    氏家 秀樹, 大塚 慎也, 千葉 龍平, 椎谷 洋彦, 藤原 晶, 加藤 達哉, 樋田 泰浩, 加賀 基知三, 若狭 哲, 石黒 信久, 豊嶋 崇徳
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 35 (3) SP2 - 3 0919-0945 2021/05
  • 小児に対するReduced port VATS
    加賀 基知三, 大塚 慎也, 千葉 龍平, 椎谷 洋彦, 氏家 秀樹, 藤原 晶, 加藤 達哉, 樋田 泰浩, 若狭 哲
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 35 (3) SP4 - 6 0919-0945 2021/05
  • 呼吸器外科におけるトランスレーショナルリサーチの最前線 ctDNAを用いた肺癌術後のMinimal residual diseaseモニタリングの有用性
    加藤 達哉, Low Siew-Kee, 清谷 一馬, 林 理絵, 氏家 秀樹, 藤原 晶, 樋田 泰浩, 加賀 基知三, 若狭 哲, 中村 祐輔
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 35 (3) PD1 - 5 0919-0945 2021/05
  • 気管支充填術と分離陰圧閉鎖療法を併用した治療戦略
    大塚 慎也, 加藤 達哉, 千葉 龍平, 椎谷 洋彦, 氏家 秀樹, 藤原 晶, 樋田 泰浩, 加賀 基知三, 若狭 哲, 三浦 隆洋, 石川 耕資
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 35 (3) O14 - 3 0919-0945 2021/05
  • 大動脈弓部トンネリング法による効果的なドレーン留置法
    藤原 晶, 大塚 慎也, 千葉 龍平, 椎谷 洋彦, 氏家 秀樹, 加藤 達哉, 樋田 泰浩, 加賀 基知三
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 35 (3) MO16 - 5 0919-0945 2021/05
  • 当院でのUniportal VATS導入経験
    藤原 晶, 大塚 慎也, 千葉 龍平, 椎谷 洋彦, 氏家 秀樹, 加藤 達哉, 樋田 泰浩, 加賀 基知三
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 35 (3) MO54 - 4 0919-0945 2021/05
  • 大動脈弓部トンネリング法による効果的なドレーン留置法
    藤原 晶, 大塚 慎也, 千葉 龍平, 椎谷 洋彦, 氏家 秀樹, 加藤 達哉, 樋田 泰浩, 加賀 基知三
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 35 (3) MO16 - 5 0919-0945 2021/05
  • 当院でのUniportal VATS導入経験
    藤原 晶, 大塚 慎也, 千葉 龍平, 椎谷 洋彦, 氏家 秀樹, 加藤 達哉, 樋田 泰浩, 加賀 基知三
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 35 (3) MO54 - 4 0919-0945 2021/05
  • COVID-19に対する、北海道大学の取り組み
    氏家 秀樹, 大塚 慎也, 千葉 龍平, 椎谷 洋彦, 藤原 晶, 加藤 達哉, 樋田 泰浩, 加賀 基知三, 若狭 哲, 石黒 信久, 豊嶋 崇徳
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 35 (3) SP2 - 3 0919-0945 2021/05
  • 小児に対するReduced port VATS
    加賀 基知三, 大塚 慎也, 千葉 龍平, 椎谷 洋彦, 氏家 秀樹, 藤原 晶, 加藤 達哉, 樋田 泰浩, 若狭 哲
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 35 (3) SP4 - 6 0919-0945 2021/05
  • 呼吸器外科におけるトランスレーショナルリサーチの最前線 ctDNAを用いた肺癌術後のMinimal residual diseaseモニタリングの有用性
    加藤 達哉, Low Siew-Kee, 清谷 一馬, 林 理絵, 氏家 秀樹, 藤原 晶, 樋田 泰浩, 加賀 基知三, 若狭 哲, 中村 祐輔
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 35 (3) PD1 - 5 0919-0945 2021/05
  • 気管支充填術と分離陰圧閉鎖療法を併用した治療戦略
    大塚 慎也, 加藤 達哉, 千葉 龍平, 椎谷 洋彦, 氏家 秀樹, 藤原 晶, 樋田 泰浩, 加賀 基知三, 若狭 哲, 三浦 隆洋, 石川 耕資
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 35 (3) O14 - 3 0919-0945 2021/05
  • Masato Aragaki, Yasuhiro Hida, Tatsuya Kato, Aki Fujiwara-Kuroda, Kichizo Kaga, Satoru Wakasa
    Journal of cancer research and clinical oncology 147 (5) 1519 - 1527 2021/05 [Refereed]
     
    PURPOSE: This study aimed to establish new criteria for limited resection of non-small cell lung cancer (NSCLC) based on computed tomography findings and maximum standardized uptake value (SUVmax). METHODS: Between December 2007 and December 2015, 611 patients underwent lung cancer surgery; of these, 70 with cT1aN0M0 who underwent limited resection were enrolled. Criteria for undergoing intentional limited resection (ILR) were (1) tumor ground-glass opacity (GGO) ratio of ≥ 0.75 and (2) tumor SUVmax ≤ 1.5. Patients who met criteria (1) and (2) underwent partial resection, and those who only met criteria (2) underwent segmentectomy as ILR. The control group was subjected to limited surgery without meeting the criteria. RESULTS: Overall, 45 and 25 patients who met the criteria were included in the ILR and control groups, respectively. In the ILR group, 13 patients underwent partial resection, and 32 underwent segmentectomy; in the control group, 18 patients underwent partial resection and 7 underwent segmentectomy. According to our criteria, no relapsed cases occurred in the ILR group, although six patients showed recurrence of lung cancer in the control group. The 5-year overall survival (OS) rates in the ILR and control groups were 100% and 67.7%, respectively, and the relapse-free survival (RFS) rates were 100% and 61.6%, respectively. The log-rank test showed that this difference was statistically significant (OS: P < 0.0001, RFS: P < 0.0001). CONCLUSIONS: SUVmax may serve as a predictive marker of recurrence to determine the treatment strategy for patients with NSCLC. Patients with low GGO ratio and low SUVmax may be cured by limited resection.
  • 通常採血管を用いたctDNA測定による肺癌術後モニタリングは術後早期再発検出に有用である
    加藤 達哉, Low Siew-Kee, 清谷 一馬, 氏家 秀樹, 藤原 晶, 樋田 泰浩, 加賀 基知三, 若狭 哲, 中村 祐輔
    日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 SF - 2 2021/04
  • 通常採血管を用いたctDNA測定による肺癌術後モニタリングは術後早期再発検出に有用である
    加藤 達哉, Low Siew-Kee, 清谷 一馬, 氏家 秀樹, 藤原 晶, 樋田 泰浩, 加賀 基知三, 若狭 哲, 中村 祐輔
    日本外科学会定期学術集会抄録集 (一社)日本外科学会 121回 SF - 2 2021/04
  • Shinya Otsuka, Hideki Ujiie, Tatsuya Kato, Haruhiko Shiiya, Aki Fujiwara-Kuroda, Yasuhiro Hida, Kichizo Kaga, Satoru Wakasa, Rei Inoue, Yasuaki Iimura
    Transplantation proceedings 53 (4) 1379 - 1381 2021/03/09 [Refereed]
     
    INTRODUCTION: Pneumatosis intestinalis (PI) is a rare but critical condition in which gas is found in the bowel wall. Although organ transplant recipients have an increased PI risk because of long-term immunosuppression, alpha-glucosidase inhibitors (α-GI), a standard diabetes therapy, often contribute to PI. However, little is known about the postorgan transplantation relationship between PI and α-GI. To the best of our knowledge, this is the first reported case of PI in a lung transplant recipient treated with α-GI. CASE REPORT: A 59-year-old man underwent hybrid (living-donor and cadaveric) lung transplantation (LTx). The patient was treated with prednisolone and tacrolimus as immunosuppressive therapy and α-GI for diabetes for 4 years. He developed asymptomatic PI 1031 days after transplantation without any acute abdominal finding. After excluding other possible causes of PI, his PI was attributed to α-GI. The suspected α-GI was immediately withdrawn. The patient was managed conservatively with bowel rest and oxygen therapy. After 11 days of α-GI discontinuation, PI improved, and the patient completely recovered. CONCLUSION: Physicians should keep this rare adverse drug reaction in mind when prescribing α-GI, particularly in patients with diabetes after organ transplantation and including LTx. The management strategy for asymptomatic PI caused by α-GI is the immediate discontinuation of α-GI therapy, followed by conservative management initiation.
  • 小児におけるニードルスコープを用いたReduced Port video assisted thoracoscopic surgery(RPVATS)(Reduced Port video assisted thoracoscopic surgery(RPVATS) using needle scope in children)
    Kaga Kichizo, Hida Yasuhiro, Kato Tatsuya, Kuroda Fujiwara Akira, Shiina Nobuyuki, Ujiie Hideki, Sasaki Akihiro, Yamasaki Hiroshi
    日本内視鏡外科学会雑誌 25 (7) OS82 - 7 1344-6703 2021/03
  • 樋田 泰浩, 加賀 基知三, 加藤 達哉, 藤原 晶, 椎名 伸行, 氏家 秀樹, 佐々木 明洋, 山崎 洋, 大岡 智学
    移植 (一社)日本移植学会 55 (4) 504 - 504 0578-7947 2021/03
  • Tatsuya Kato, Hideki Ujiie, Kanako C Hatanaka, Ayae Nange, Asami Okumura, Kaho Tsubame, Kentato Naruchi, Masaharu Sato, Kichizo Kaga, Yoshihiro Matsuno, Satoru Wakasa, Yutaka Hatanaka
    Oncology letters 21 (3) 202 - 202 2021/03 [Refereed]
     
    Mucin 1 (MUC1) expression is upregulated in multiple types of cancer, including lung cancer. However, the conventional anti-MUC1 antibody is not useful for the differentiation of malignant lung tumors and benign lesions due to its limited specificity. Our previous study screened a novel epitope-defined antibody against cancer-associated sugar chain structures that specifically recognizes the MUC1 Tn antigen (MUC1-Tn ED Ab). In the present study, its potential utility as a diagnostic marker and therapeutic tool for lung adenocarcinoma (ADC) was examined. Immunohistochemical analysis of a lung ADC tissue microarray was performed using the MUC1-Tn ED Ab (clone SN-102), and the results were compared with those of another clone and commercially available MUC1 antibodies. The association between positive immunoreactivity of SN-102 and clinicopathologic factors was analyzed. Furthermore, the association between MUC1-Tn expression and epithelial-mesenchymal transition markers and radiological characteristics was analyzed. Moderate or high MUC1-Tn expression (MUC1-Tn-H) was observed in 138 (78.9%) of the 175 lung ADC cases. MUC1-Tn-H was associated with male sex, cigarette smoking, tumor extension, pleural invasion, and higher preoperative serum carcinoembryonic antigen and cytokeratin 19 fragment levels. Tumors with MUC1-Tn-H had higher consolidation/tumor ratios according to computed tomography and greater uptakes of 18F-fluorodeoxyglucose. A total of 46 (26.9%) of the tumors had mesenchymal features, and MUC1-Tn positivity was higher in the mesenchymal group than in the epithelial and intermediate groups (P<0.01 and P<0.01, respectively). Patients with tumors exhibiting MUC1-Tn-H had significantly shorter 5-year overall and disease-free survival times (P=0.011 and P<0.001, respectively). Additionally, MUC1-Tn-H was identified as an independent prognostic factor in multivariate analysis (P=0.024). MUC1-Tn is specific for lung cancer cells and can improve diagnostic capabilities. Additionally, it may be a potential therapeutic target in lung ADC.
  • 大塚 慎也, 加藤 達哉, 佐々木 明洋, 山崎 洋, 氏家 秀樹, 藤原 晶, 樋田 泰浩, 加賀 基知三, 若狭 哲, 中村 順一, 篠崎 鮎香, 中久保 祥, 木村 孔一, 渡辺 正明, 岡崎 ななせ, 松野 吉宏
    肺癌 (NPO)日本肺癌学会 61 (1) 67 - 67 0386-9628 2021/02
  • 横山 誓也, 氏家 秀樹, 加藤 達哉, 大塚 慎也, 佐々木 明洋, 山崎 洋, 藤原 晶, 樋田 泰浩, 加賀 基知三, 若狭 哲, 松野 吉宏, 今井 陽子
    肺癌 (NPO)日本肺癌学会 61 (1) 67 - 68 0386-9628 2021/02
  • 大塚 慎也, 加藤 達哉, 佐々木 明洋, 山崎 洋, 氏家 秀樹, 藤原 晶, 樋田 泰浩, 加賀 基知三, 若狭 哲, 中村 順一, 篠崎 鮎香, 中久保 祥, 木村 孔一, 渡辺 正明, 岡崎 ななせ, 松野 吉宏
    肺癌 (NPO)日本肺癌学会 61 (1) 67 - 67 0386-9628 2021/02
  • 横山 誓也, 氏家 秀樹, 加藤 達哉, 大塚 慎也, 佐々木 明洋, 山崎 洋, 藤原 晶, 樋田 泰浩, 加賀 基知三, 若狭 哲, 松野 吉宏, 今井 陽子
    肺癌 (NPO)日本肺癌学会 61 (1) 67 - 68 0386-9628 2021/02
  • Yusuke Motohashi, Tatsuya Kato, Masato Aragaki, Aki Fujiwara-Kuroda, Yasuhiro Hida, Satoru Wakasa, Kichizo Kaga
    General thoracic and cardiovascular surgery 69 (2) 383 - 387 2021/02 [Refereed]
     
    A 33-year-old man with left pulmonary sequestration was admitted to our hospital. We planned left basilar segmentectomy to preserve the lung function, using indocyanine green (ICG) and near-infrared thoracoscopy. The intravenous (IV) administration of ICG (0.1 mg/kg) showed the distribution of fluorescence from the aberrant arteries, blood flow blockage from the aberrant arteries after they were divided, and the superior-basal boundary after the pulmonary artery and vein were divided. In adult patients with intralobar pulmonary sequestration, ICG and near-infrared thoracoscopic techniques are useful to confirm abnormal hemodynamics and demonstrate a safe and successful basilar segmentectomy.
  • Hideki Ujiie, Aogu Yamaguchi, Alexander Gregor, Harley Chan, Tatsuya Kato, Yasuhiro Hida, Kichizo Kaga, Satoru Wakasa, Chad Eitel, Tod R Clapp, Kazuhiro Yasufuku
    Journal of thoracic disease 13 (2) 778 - 783 2021/02 [Refereed]
     
    Background: Video-assisted thoracoscopic surgery (VATS) has become a standard approach for the treatment of lung cancer. However, its minimally invasive nature limits the field of view and reduces tactile feedback. These limitations make it vital that surgeons thoroughly familiarize themselves with the patient's anatomy preoperatively. We have developed a virtual reality (VR) surgical navigation system using head-mounted displays (HMD). The aim of this study was to investigate the potential utility of this VR simulation system in both preoperative planning and intraoperative assistance, including support during thoracoscopic sublobar resection. Methods: Three-dimensional (3D) polygon data derived from preoperative computed tomography data was loaded into BananaVision software developed at Colorado State University and displayed on an HMD. An interactive 3D reconstruction image was created, in which all the pulmonary structures could be individually imaged. Preoperative resection simulations were performed with patient-individualized reconstructed 3D images. Results: The 3D anatomic structure of pulmonary vessels and a clear vision into the space between the lesion and adjacent tissues were successfully appreciated during preoperative simulation. Surgeons could easily evaluate the real patient's anatomy in preoperative simulations to improve the accuracy and safety of actual surgery. The VR software and HMD allowed surgeons to visualize and interact with real patient data in true 3D providing a unique perspective. Conclusions: This initial experience suggests that a VR simulation with HMD facilitated preoperative simulation. Routine imaging modalities combined with VR systems could substantially improve preoperative planning and contribute to the safety and accuracy of anatomic resection.
  • Akihiro Sasaki, Tatsuya Kato, Hideki Ujiie, Yasushi Cho, Masaaki Sato, Mitsuhito Kaji
    International journal of surgery case reports 79 431 - 435 2021/02 [Refereed]
     
    INTRODUCTION AND IMPORTANCE: Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer (NSCLC) that is classified as a subtype of unclassified carcinoma by the WHO. LELC is usually associated with Epstein-Barr virus (EBV) infection. LELC has often been observed in Southeast Asia; however, it is extremely rare in Japan. CASE PRESENTATION: A 60-year-old Japanese woman presented with an abnormal shadow in the left lung on chest radiography. Chest computed tomography showed a nodule located between the lingular and basal anteromedial segments. A blood test suggested an existing EBV infection, and LELC was suspected preoperatively in the transbronchial lung biopsy. She underwent a lingular and basal bi-segmentectomy. The EBV-encoded small ribonucleic acid in-situ hybridization (EBER-ISH) was positive, and she was diagnosed with LELC. Moreover, programmed death-ligand 1 (PD-L1) expression was moderately positive. No recurrence was observed for 30 months. CLINICAL DISCUSSION: Although LELC has been reported as a low-grade malignancy with a good prognosis, the frequency of PD-L1 expression in LELC seems to be higher than that in other NSCLCs. Moreover, it has been reported that LELC patients with high PD-L1 expression are likely to have early recurrence/metastasis and poor prognosis. CONCLUSION: An investigation of PD-L1 expression for LELC would be useful considering the benefit of PD-1/PD-L1 blockade in patients with pulmonary LELC with high PD-L1 expression. The present case is the first report of LELC with positive expression of EBER-ISH and PD-L1 in Japan.
  • Laura L Donahoe, Tatsuya Kato, Andrew Healey, Thomas K Waddell, Jodie Heffren, Caitlin Mills, Maureen Meade, Diana Hallett, Shaf Keshavjee, Marcelo Cypel
    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 40 (9) 1020 - 1021 2021/01/23 [Refereed]
  • 藤原 晶, 大塚 慎也, 山崎 洋, 佐々木 明洋, 氏家 秀樹, 加藤 達哉, 樋田 泰浩, 加賀 基知三
    日本外科感染症学会雑誌 (一社)日本外科感染症学会 17 (5) 482 - 482 1349-5755 2020/10
  • 氏家 秀樹, 加藤 達哉, 稲毛 輝長, 石綿 司, 新垣 雅人, 樋田 泰浩, 加賀 基知三, 若狭 哲, Keshavjee Shaf, Yasufuku Kazuhiro
    移植 (一社)日本移植学会 55 (総会臨時) 383 - 383 0578-7947 2020/10
  • 高橋 桂, 品川 尚文, 加藤 達哉, 高橋 宏典, 國崎 守, 樋田 泰浩, 加賀 基知三, 土井 和尚, 松野 吉宏, 今野 哲
    気管支学 (NPO)日本呼吸器内視鏡学会 42 (5) 441 - 447 0287-2137 2020/09 
    背景.粘表皮癌は比較的稀な肺腫瘍であり、中でも粘液栓を伴った粘表皮癌は報告例も少ない。症例.症例は27歳、女性。左胸痛、咳嗽、喀痰が出現し、近医を受診。肺炎の診断で抗菌薬を開始されるも改善なく、胸部CTでは左主気管支の完全閉塞を認め、当科入院となった。全身麻酔下で気管支鏡検査を施行するも左主気管支は粘液栓が連なって存在しており、診断に耐えうる検体採取が困難であった。2回目の気管支鏡検査では迅速病理診断を併用し、粘表皮癌cT2aN0M0 stage IBと診断された。腫瘍の存在部位より左肺全摘も考慮されたが、術前に低悪性度な粘表皮癌と診断がついていたことで左下葉切除術+気管支形成術が施行され、腫瘍は完全切除され左肺全摘が回避された。結論.粘液栓を伴った粘表皮癌においては迅速病理診断を併用した気管支鏡検査が有用であり、本症例のように術前に確定診断をつけることで肺機能を温存した治療も検討される。(著者抄録)
  • Masato Aragaki, Tatsuya Kato, Aki Fujiwara-Kuroda, Yasuhiro Hida, Kichizo Kaga, Satoru Wakasa
    Journal of cardiothoracic surgery 15 (1) 229 - 229 2020/08/28 [Refereed]
     
    BACKGROUND: Given the difficulty in preoperatively diagnosing lymph node metastasis, patients with Stage I-III non-small cell lung cancer (NSCLC) are likely to be included in the clinical N1 (cN1) group. However, better treatment options might be selected through further stratification. This study aimed to identify preoperative clinicopathological prognostic and stratification factors for patients with cN1 NSCLC. METHODS: This retrospective study evaluated 60 patients who were diagnosed with NSCLC during 2004-2014. Clinical nodal status had been evaluated using routine chest computed tomography (CT) and/or positron emission tomography (PET). To avoid biasing the fluorodeoxyglucose uptake values based on inter-institution or inter-model differences, we used only two PET systems (one PET system and one PET/CT system). Relapse-free survival (RFS) and overall survival (OS) were the primary study outcomes. The maximum standardized uptake value (SUVmax) was calculated for each tumor and categorized as low or high based on the median value. Patient sex, age, histology, tumor size, and tumor markers were also assessed. RESULTS: Poor OS was associated with older age (P = 0.0159) and high SUVmax values (P = 0.0142). Poor RFS was associated with positive carcinoembryonic antigen (CEA) expression (P = 0.0035) and high SUVmax values (P = 0.015). Multivariate analyses confirmed that poor OS was independently predicted by older age (hazard ratio [HR] = 2.751, confidence interval [CI]: 1.300-5.822; P = 0.0081) and high SUVmax values (HR = 5.121, 95% CI: 1.759-14.910; P = 0.0027). Furthermore, poor RFS was independently predicted by positive CEA expression (HR = 2.376, 95% CI: 1.056-5.348; P = 0.0366) and high SUVmax values (HR = 2.789, 95% CI: 1.042-7.458; P = 0.0410). The primary tumor's SUVmax value was also an independent prognostic factor for both OS and RFS. CONCLUSIONS: For patients with cN1 NSCLC, preoperative prognosis and stratification might be performed based on CEA expression, age, and the primary tumor's SUVmax value. To enhance the prognostic value of the primary tumor's SUVmax value, minimizing bias between facilities and models could lead to a more accurate prognostication.
  • 非触知肺病変に対するVATS ハイブリッド手術室での切除断端のマーキング、切除、確認法(MaRCH)(VATS for an unpalpable lung tumor, Marking, Resection and Confirmation of the surgical margin at the Hybrid operating room(MaRCH))
    Hida Yasuhiro, Kaga Kichizo, Kato Tatsuya, Fujiwara Aki, Shiina Nobuyuki, Ujiie Hideki, Sasaki Akihiro, Yamasaki Hiroshi
    日本呼吸器外科学会雑誌 34 (3) IS2 - 1 0919-0945 2020/08
  • イメージガイド下センチネルリンパ節マッピングのためのマルチモーダルなナノスケール薬(A multi-modal nanoscale agent for image-guided sentinel lymph node mapping)
    Ujiie Hideki, Chan Harley, Gregor Alexander, Motooka Yamato, Inage Terunaga, Aragaki Masato, Kato Tatsuya, Hida Yasuhiro, Kaga Kichizo, Waddell Thomas K, Keshavjee Shaf, Yasufuku Kazuhiro
    日本呼吸器外科学会雑誌 34 (3) IS2 - 2 0919-0945 2020/08
  • MUC1がん特異的糖鎖抗原は肺腺癌の有力な新規診断マーカーかつ予後因子となりうる
    加藤 達哉, 畑中 佳奈子, 燕 果歩, 成地 健太郎, 佐藤 正治, 樋田 泰浩, 松野 吉宏, 畑中 豊, 加賀 基知三
    日本外科学会定期学術集会抄録集 (一社)日本外科学会 120回 DP - 3 2020/08
  • 非触知肺病変に対するVATS ハイブリッド手術室での切除断端の作成、切除、確認法(MaRCH)(VATS for an unpalpable lung tumor, Marking, Resection and Confirmation of the surgical margin at the Hybrid operating room(MaRCH))
    Hida Yasuhiro, Kaga Kichizo, Kato Tatsuya, Fujiwara Aki, Shiina Nobuyuki, Ujiie Hideki, Sasaki Akihiro, Yamasaki Hiroshi
    日本呼吸器外科学会雑誌 34 (3) IS2 - 1 0919-0945 2020/08
  • イメージガイド下センチネルリンパ節マッピングのためのマルチモーダルなナノスケール薬(A multi-modal nanoscale agent for image-guided sentinel lymph node mapping)
    Ujiie Hideki, Chan Harley, Gregor Alexander, Motooka Yamato, Inage Terunaga, Aragaki Masato, Kato Tatsuya, Hida Yasuhiro, Kaga Kichizo, Waddell Thomas K, Keshavjee Shaf, Yasufuku Kazuhiro
    日本呼吸器外科学会雑誌 34 (3) IS2 - 2 0919-0945 2020/08
  • 両側横隔神経、左反回神経切除、左浅深頸部・腋窩リンパ節、中葉肺転移摘除を行ったIV期胸腺カルチノイドの1例
    樋田 泰浩, 加賀 基知三, 加藤 達哉, 藤原 晶, 椎名 伸行, 氏家 秀樹, 佐々木 明洋, 山崎 洋
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 34 (3) SP3 - 3 0919-0945 2020/08
  • ドライバー遺伝子陽性c-stage IV肺癌患者に対する外科手術の意義
    加藤 達哉, 椎名 伸行, 藤原 晶, 氏家 秀樹, 佐々木 明洋, 山崎 洋, 樋田 泰浩, 加賀 基知三
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 34 (3) RO10 - 7 0919-0945 2020/08
  • 二窓法および細径光学視管を用いた一窓法によるReduced port surgeryと将来の展望
    加賀 基知三, 樋田 泰浩, 加藤 達哉, 藤原 晶, 氏家 秀樹, 佐々木 明洋, 山崎 洋
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 34 (3) O36 - 5 0919-0945 2020/08
  • 単孔式胸腔鏡への移行を念頭に置いた胸腔鏡手術の分類とトレーニング法
    樋田 泰浩, 加賀 基知三, 加藤 達哉, 藤原 晶, 椎名 伸行, 氏家 秀樹, 佐々木 明洋, 山崎 洋
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 34 (3) MO2 - 1 0919-0945 2020/08
  • 4D-CTにより術前に右房浸潤の有無を予測できた胸腺腫瘍の一例
    山崎 洋, 樋田 泰浩, 佐々木 明洋, 椎名 伸行, 藤原 晶, 氏家 秀樹, 加藤 達哉, 加賀 基知三
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 34 (3) MO26 - 5 0919-0945 2020/08
  • 手術可能な肺がんに対する術後のモニタリングとしてのctDNA測定の有用性の検証
    加藤 達哉, Low Siew-Kee, 清谷 一馬, 中村 透, 藤原 晶, 氏家 秀樹, 椎名 伸行, 樋田 泰浩, 加賀 基知三, 中村 祐輔
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 34 (3) MO27 - 2 0919-0945 2020/08
  • 手術介入を要した胸部外傷の検討
    佐々木 明洋, 山崎 洋, 椎名 伸行, 氏家 秀樹, 藤原 晶, 加藤 達哉, 樋田 泰浩, 加賀 基知三
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 34 (3) MO60 - 9 0919-0945 2020/08
  • 出産を契機に生じた奇静脈瘤内血栓に対し緊急手術を施行した1例
    椎名 伸行, 加藤 達哉, 佐々木 明洋, 山崎 洋, 藤原 晶, 氏家 秀樹, 樋田 泰浩, 福井 秀章, 松野 吉宏, 加賀 基知三
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 34 (3) MO64 - 4 0919-0945 2020/08
  • 非典型的な先天性嚢胞性肺疾患
    加賀 基知三, 大塚 慎也, 佐々木 明洋, 山崎 洋, 氏家 秀樹, 藤原 晶[黒田], 加藤 達哉, 樋田 泰浩, 若狭 哲
    日本気胸・嚢胞性肺疾患学会雑誌 日本気胸・嚢胞性肺疾患学会 20 (1) 69 - 69 1883-0412 2020/08
  • Tatsuya Kato, Aki Fujiwara-Kuroda, Nobuyuki Shiina, Masato Aragaki, Hideki Ujiie, Yasuhiro Hida, Kichizo Kaga
    Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia 26 (5) 294 - 297 2020/08/01 [Refereed][Not invited]
     
    The Montgomery T-tube is widely used to stent airway stenotic diseases. Conventional insertion methods can sometimes fail in the case of long-distance subglottic stenosis due to the flexibility of a T-tube made of silicon, which kinks when forced against resistance. Therefore, an alternative approach can assist in the insertion of an extra-long T-tube, especially when using a long proximal limb. We report herein the case of a patient with a large mediastinal tumor caused by neurofibromatosis type 1 in which airway obstruction was avoided through the use of a novel extra-long T-tube placement technique.
  • 藤原 晶, 大塚 慎也, 山崎 洋, 佐々木 明洋, 氏家 秀樹, 加藤 達哉, 樋田 泰浩, 加賀 基知三, 若狭 哲
    小切開・鏡視外科学会雑誌 (NPO)小切開・鏡視外科学会 11 (1) 38 - 38 2185-2820 2020/06
  • 加賀 基知三, 大塚 慎也, 佐々木 明洋, 山崎 洋, 氏家 秀樹, 藤原 晶[黒田], 加藤 達哉, 樋田 泰浩, 若狭 哲
    小切開・鏡視外科学会雑誌 (NPO)小切開・鏡視外科学会 11 (1) 50 - 50 2185-2820 2020/06
  • 佐々木 明洋, 大塚 慎也, 山崎 洋, 氏家 秀樹, 藤原 晶, 加藤 達哉, 樋田 泰浩, 加賀 基知三
    小切開・鏡視外科学会雑誌 (NPO)小切開・鏡視外科学会 11 (1) 58 - 58 2185-2820 2020/06
  • 樋田 泰浩, 加賀 基知三, 加藤 達哉, 藤原 晶, 椎名 伸行, 氏家 秀樹, 佐々木 明洋, 山崎 洋
    気管支学 (NPO)日本呼吸器内視鏡学会 42 (Suppl.) S179 - S179 0287-2137 2020/06
  • 加賀 基知三, 樋田 泰浩, 加藤 達哉, 藤原 晶[黒田], 椎名 伸行, 氏家 秀樹, 佐々木 明洋, 山崎 洋, 若狭 哲
    北海道外科雑誌 北海道外科学会 65 (1) 2 - 7 0288-7509 2020/06 
    先天性嚢胞性肺疾患で最も頻度の高い先天性肺気道奇形は、出生時の呼吸障害やその後の肺炎の併発のために外科的治療の対象となる。無症候性の先天性肺気道奇形の手術適応や適切な手術時期は明確ではない。一方、小児に対する胸腔鏡手術は低侵襲であると報告されているものの、成人と比較すると難易度は高い。小児に対する胸腔鏡手術が広く行われるようになると、適切な手術時期の決定はさらに複雑になるだろう。本疾患はまれな疾患であり、臨床的に小児外科と呼吸器外科の間(はざま)に存在するため、両領域の協力が必要である。本稿では現時点での論点を概説する。(著者抄録)
  • Yamato Motooka, Kosuke Fujino, Alexander Gregor, Nicholas Bernards, Harley Chan, Terunaga Inage, Hideki Ujiie, Tatsuya Kato, Tomonari Kinoshita, Tsukasa Ishiwata, Makoto Suzuki, Kazuhiro Yasufuku
    Seminars in thoracic and cardiovascular surgery 2020/02/10 [Refereed][Not invited]
     
    Radiofrequency ablation (RFA) can be a therapeutic option in medically inoperable lung cancer patients. In this study, we evaluated a prototype bipolar RFA device applicator that can be deployed from a standard endobronchial ultrasound (EBUS) bronchoscope to determine feasibility and histopathological analysis in animal models. Rabbit lung cancers were created by transbronchial injection of VX2 rabbit cancer cells. Once the tumors were developed, they were ablated transpleurally, under EBUS guidance using the prototype RFA device. The animals were then sacrificed for specimen resection. Pig inflammatory lung pseudo-tumors and lymphadenopathy were created by transbronchial injection of a talc paste and ablated transbronchially under EBUS guidance. Pigs were evaluated at five days, two weeks, and four weeks following ablation by bronchoscopy and cone-beam computed tomography before necropsy. Nicotinamide adenine dinucleotide hydrogen diaphorase staining was employed to measure the ablation area. Twenty-four VX2 rabbit tumors were ablated. The total ablated area ranged from 0.6 to 3.0 cm2 (mean: 1.8 cm2), corresponding to a total energy range of 1 to 6 kJ. Six pig lung pseudo-tumors and five mediastinal lymph nodes (LNs) were ablated. Adjacent airway ulceration was observed in three ablations of LNs. These airway complications resolved within four weeks of RFA without any treatment. There was no hemoptysis, air embolism, respiratory distress, or other serious complication noted. In these two animal models, we provide evidence that EBUS-guided bipolar RFA is feasible and histopathology shows that can ablate lung tumors and mediastinal lymph nodes under real-time ultrasound guidance.
  • Nobuhiro Tanaka, Ryoko Ito Katoh, Masataka Yamamoto, Koji Hoshino, Yuji Morimoto, Yoichi M Ito, Tatsuya Kato
    Journal of clinical anesthesia 59 99 - 100 0952-8180 2020/02 [Refereed][Not invited]
  • Masato Aragaki, Kichizo Kaga, Yasuhiro Hida, Tatsuya Kato, Yoshiro Matsui
    Journal of minimal access surgery 2020/01/28 [Refereed][Not invited]
     
    Background: Video-assisted thoracoscopic (VATS) lobectomy has recently become the standard for treating lung cancer. However, the complete removal of large tumours from the chest cavity is often difficult. Therefore, we developed a novel approach to extract large tumours from the wound without rib resection or fracture (the eXtraction of resected specimens through the Lower INterCostal route [XLINC] method). Subjects and Methods: In XLINC, a skin incision is made on the tenth intercostal space, and the resected lung tissue is extracted. This retrospective study included patients who underwent VATS lobectomy using XLINC in our institution from 2016 to 2018. As a control group, six patients who had undergone thoracotomy during VATS surgery due to a large tumour diameter were included in the conversion group. Results: Four men and six women (median age = 66 years, maximum median tumour diameter = 59 mm) were included in the study. The median length of the wound incision for XLINC was 4.5 (range: 4-8) cm. The median operative time was 183 min, and the estimated blood loss was 50 ml. Rib resection was not required, and no fractures were noted. The median length of hospital stay was 8 days. No patients developed major complications caused by XLINC. There were no significant differences, except in operation time and amount of blood loss, between the two groups. However, the XLINC group used fewer post-operative analgesics. Conclusion: Our report suggests that XLINC might be a simpler, less invasive procedure that could be used in patients with large tumours.
  • 氏家 秀樹, 加藤 達哉, 稲毛 輝長, 石綿 司, 新垣 雅人, 樋田 泰浩, 加賀 基知三, 若狭 哲
    移植 一般社団法人 日本移植学会 55 (Supplement) 383_2 - 383_2 0578-7947 2020 
    目的 気管支腔内超音波検査法(EBUS)は低侵襲かつ高い診断能を有する検査手技である。本研究では、肺移植待機患者および移植後患者の経過中に、悪性腫瘍が疑われた肺・リンパ節病変に対するEBUSの有用性を検討した。方法 2008年~2018年までの間にEBUSガイド下経気道的肺生検 (EBUS-GS-TBB, EBUS-TBNA)が施行された肺移植後患者及び待機患者に対し後方視的検討を行った。結果 全28例に対してEBUS-TBNA:20例、EBUS-GS-TBB:8例 が施行された。肺移植術後患者19例の内訳は、移植後に肺腫瘤を認め悪性腫瘍が疑われた11例、肺門及び縦隔リンパ節腫大を認め移植後リンパ増殖性疾患(PTLD)が疑われた8例であった。全症例において確定診断が可能であり、重篤な合併症を認めなかった。診断の内訳は、原発性肺癌6例、PTLD 4例、感染性疾患3例、良性疾患6例であった。PTLDが疑われた8例中、4例(50%)がPTLDと診断され、肺悪性腫瘍が疑われた11例中、6例(55%)で肺悪性腫瘍の確定診断が可能であった。また、肺移植待機9例のうち、5例(56%)にて肺悪性腫瘍の確定診断に至り、治療方針が変更された。結論 移植待機中の末期慢性肺疾患症例及び肺移植術前後症例におけるEBUSは、肺病変及び縦隔肺門リンパ節に対する安全かつ高精度な質的診断が可能な検査法と考えられた。
  • 呼吸器外科におけるReduced port surgery 細径内視鏡を用いたreduced port thoracic surgery一窓法の適応と限界
    樋田 泰浩, 加賀 基知三, 加藤 達哉, 藤原 晶, 椎名 伸行, 佐々木 明洋, 山崎 洋
    日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 24 (7) SY16 - 1 1344-6703 2019/12 [Not refereed][Not invited]
  • 胸腔鏡困難症例に対するknack & pitfall 気管支断端被覆や大きな腫瘍の摘出を要する症例に対する胸腔鏡下肺葉切除
    樋田 泰浩, 加賀 基知三, 加藤 達哉, 藤原 晶, 椎名 伸行, 佐々木 明洋, 山崎 洋
    日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 24 (7) WS25 - 3 1344-6703 2019/12 [Not refereed][Not invited]
  • 樋田 泰浩, 加藤 達哉, 藤原 晶, 椎名 伸行, 佐々木 明洋, 山崎 洋, 大岡 智学, 加賀 基知三
    移植 (一社)日本移植学会 54 (総会臨時) 211 - 211 0578-7947 2019/09 [Not refereed][Not invited]
  • Masato Aragaki, Kichizo Kaga, Yasuhiro Hida, Tatsuya Kato, Yoshiro Matsui
    Annals of medicine and surgery (2012) 45 70 - 74 2019/09 [Refereed][Not invited]
     
    Background: This study aimed to determine the usefulness and limitations of videoassisted thoracoscopic (VATS) lobectomy using one-window and puncture method (1WPM). Methods: This study involved 14 patients who underwent lobectomy using the 1WPM at our institute from 2008 to 2017. Results: The study patients comprised of 3 men and 11 women with a median age of 10.5 years (range, 0-72 years). There were eight cases in children younger than 18 years old and the youngest patient was 9 days old. The diagnoses were congenital pulmonary cystic disease (n = 7), primary lung cancer (n = 4), metastatic lung tumor (n = 1), and others (n = 2). The 1WPM was successful in 9 of 14 patients (64.3%) and, in 5 cases (35.7%), needed conversion to either two-window method (TWM) using additional port (n = 3) or open thoracotomy (n = 2). The causes for conversion were need for additional bronchoplasty or lymph node dissection (n = 3), failure of one-lung ventilation (n = 1), and presence of a small thoracic cavity that made the procedure extremely difficult (n = 1). In the group that was successfully treated with 1WPM, the median values were as follows: operation time, 193 min (range, 112-480 min); blood loss, 0 ml (range, 0-90 ml); drainage duration, 1 day (range, 1-4 days); and postoperative hospital stay, 7 days (range, 4-13 days). Conclusions: Lobectomy by 1WPM can be safely performed and has good postoperative course and this procedure can be applicable and effective in small infants.
  • Hirohashi K, Anayama T, Wada H, Nakajima T, Kato T, Keshavjee S, Orihashi K, Yasufuku K
    Interactive cardiovascular and thoracic surgery 1569-9293 2019/07 [Refereed][Not invited]
  • Kazuomi Ichinokawa, Yoshitsugu Nakanishi, Yasuhiro Hida, Takahiro Tsuchikawa, Tatsuya Kato, Tomoo Itoh, Mitsuhito Kaji, Kichizo Kaga, Satoshi Hirano
    Oncology letters 18 (1) 117 - 126 1792-1074 2019/07 [Refereed][Not invited]
     
    The aim of this study was to clarify the association between expression of human leukocyte antigen (HLA) class I in non-small-cell lung cancer (NSCLC) cells and patient survival. To address this, immunohistochemical staining for HLA class I was performed on specimens from 111 patients with NSCLC, and overall survival curves were compared using the log-rank test. In addition, multivariate analyses were performed using Cox's proportional hazard model. The cases were divided into 5 classes based on the expression of HLA class I heavy chain and β2-microglobulin. The overall survival rate for patients with tumors lacking HLA class I heavy chain (30 cases; 27.0%) was significantly decreased. The multivariate analysis demonstrated that the absence of HLA class I heavy chain was an independent predictor of poor prognosis. There was a trend towards an unfavorable prognosis for patients whose tumors did not express β2-microglobulin (57 cases; 51.4%). Downregulation of HLA class I heavy chain expression was significantly associated with the downregulation of β2-microglobulin. Cases lacking HLA class I heavy chain as well as β2-microglobulin expression (23 cases; 20.7%) had a statistically significant unfavorable prognosis compared with other cases. The present findings demonstrate that the lack of HLA class I heavy chain expression in tumor cells is an independent prognostic factor for poor NSCLC survival, and is likely to exert an important influence on immune surveillance in patients.
  • 加賀 基知三, 本橋 雄介, 藤原 晶, 新垣 雅人, 加藤 達哉, 樋田 泰浩, 本多 昌平, 松居 喜郎
    小切開・鏡視外科学会雑誌 (NPO)小切開・鏡視外科学会 10 (1) 54 - 54 2185-2820 2019/06
  • 加藤 達哉, 新垣 雅人, 長 靖, 道免 寛充, 樋田 泰浩, 七戸 俊明, 加賀 基知三, 平野 聡, 松居 喜郎
    北海道外科雑誌 北海道外科学会 64 (1) 43 - 50 0288-7509 2019/06 [Refereed][Not invited]
     
    肺移植未認定施設において移植手術手技の修練は課題の一つである。大動物を使った修練は実践的であるものの、倫理的な問題や解剖がヒトと異なるという欠点は否めない。我々はシール法固定献体を用いたカダバートレーニングを併用することによる肺移植シミュレーションとしての有用性を検討した。いずれもドナーより両肺を摘出し、レシピエントに片肺移植を行った。各々の講習前後でトレーニング効果を受講者のアンケートにて分析した。ブタ生体では心拍下の肺動脈カニュレーションや血管吻合が可能となる。シール法固定献体では組織の状態は生体に近く、手技は実際の手術に近い感覚で行える。この2つを組み合わせることで、参加者の肺移植の各行程に対する理解と手術スキルが向上した。献体とブタ生体を組み合わせた肺移植手術トレーニングは肺移植未認定施設におけるトレーニングプログラムとして有用と考えられた。(著者抄録)
  • 加賀 基知三, 本橋 雄介, 藤原 晶, 新垣 雅人, 加藤 達哉, 樋田 泰浩, 本多 昌平, 松居 喜郎
    小切開・鏡視外科学会雑誌 (NPO)小切開・鏡視外科学会 10 (1) 54 - 54 2185-2820 2019/06 [Not refereed][Not invited]
  • 左冠動脈閉鎖・僧帽弁閉鎖不全を合併した肺葉内肺分画症の1例
    本橋 雄介, 藤原 晶, 新垣 雅人, 加藤 達哉, 樋田 泰浩, 加賀 基知三, 新井 洋輔, 加藤 伸康, 橘 剛, 松居 喜郎
    日本臨床外科学会雑誌 日本臨床外科学会 80 (5) 1029 - 1029 1345-2843 2019/05 [Not refereed][Not invited]
  • 小児外科領域における真の低侵襲手術とは? 小児嚢胞性肺疾患に対する胸腔鏡下肺葉切除と手術時期の検討
    加賀 基知三, 本橋 雄介, 藤原 晶, 新垣 雅人, 加藤 達哉, 樋田 泰浩, 本多 昌平, 松居 喜郎
    日本外科学会定期学術集会抄録集 119回 WS - 4 2019/04 [Not refereed][Not invited]
  • ハイブリッド手術室における胸腔鏡下触知困難肺腫瘍部分切除のナビゲーションと切除肺のマージン確認(OS MaRCH法)
    樋田 泰浩, 加賀 基知三, 加藤 達哉, 新垣 雅人, 藤原 晶, 本橋 雄介, 松居 喜郎
    日本外科学会定期学術集会抄録集 119回 SF - 5 2019/04 [Not refereed][Not invited]
  • 肺癌に対する薬物療法の進歩と外科治療の役割 免疫チェックポイント阻害剤時代の根治的化学放射線療法後の肺切除の役割
    樋田 泰浩, 加賀 基知三, 加藤 達哉, 新垣 雅人, 藤原 晶, 本橋 雄介, 松居 喜郎
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 33 (3) S - 2 0919-0945 2019/04 [Not refereed][Not invited]
  • 異常血管の灌流領域の確認と区域間同定に赤外光胸腔鏡を用いた肺葉内肺分画症の一例
    本橋 雄介, 加藤 達哉, 新垣 雅人, 藤原 晶, 樋田 泰浩, 加賀 基知三, 松居 喜郎
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 33 (3) V8 - 1 0919-0945 2019/04 [Not refereed][Not invited]
  • ハイブリッド手術室における肺腫瘍のナビゲーションと切除肺のマージン確認(OS MaRCH法)
    樋田 泰浩, 加賀 基知三, 加藤 達哉, 新垣 雅人, 藤原 晶, 本橋 雄介, 松居 喜郎
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 33 (3) O10 - 4 0919-0945 2019/04 [Not refereed][Not invited]
  • 不全分葉間に発生した肺癌に対する胸腔鏡下複合区域切除における赤外光胸腔鏡の有用性
    加藤 達哉, 新垣 雅人, 藤原 晶, 本橋 雄介, 樋田 泰浩, 福井 秀章, 松野 吉宏, 加賀 基知三, 松居 喜郎
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 33 (3) P57 - 2 0919-0945 2019/04 [Not refereed][Not invited]
  • Hideki Ujiie, Lili Ding, Rong Fan, Tatsuya Kato, Daiyoon Lee, Kosuke Fujino, Tomonari Kinoshita, Chang Young Lee, Thomas K Waddell, Shaf Keshavjee, Brian C Wilson, Gang Zheng, Juan Chen, Kazuhiro Yasufuku
    The Annals of thoracic surgery 107 (2) 369 - 377 0003-4975 2019/02 [Refereed][Not invited]
     
    BACKGROUND: We have developed ultrasmall porphyrin-high-density lipoprotein (HDL) nanoparticles (<20 nm), called "porphyrinHDL," that have a high density of porphyrin molecules and dissociate rapidly upon tumor cell accumulation to become fluorescent and photoactive. This is introduced as a novel activatable photosensitizer for image-guided photodynamic therapy (PDT). Here, we report the studies of these nanoparticles targeted to scavenger receptor class B type I (SR-BI) expressed on lung cancer cells as a first step toward development of a minimally invasive treatment for peripheral lung cancer and metastatic lymph nodes of advanced lung cancer. METHODS: The in vitro uptake of porphyrinHDL and the corresponding PDT efficacy were evaluated in both SR-BI-positive and SR-BI-negative lung cancer cell lines. A clinically relevant orthotopic lung cancer model in mice was used to examine fluorescence activation and quantification of uptake in tumor. In addition, we investigated the effect of porphyrinHDL-mediated PDT. RESULTS: PorphyrinHDL promoted proper intracellular uptake in the H460 human lung cancer cell line. When irradiated with a 671-nm PDT laser, porphyrinHDL produced significant therapeutic effectiveness in vitro. After systemic administration in mice with orthotopic lung cancer xenografts, porphyrinHDL demonstrated selective accumulation and photoactivation in tumor with significantly enhanced disease-to-normal tissue contrast. Moreover, porphyrinHDL-PDT significantly induced cell apoptosis in lung tumors (73.2%) without toxicity in normal tissues or damage to adjacent critical structures. CONCLUSIONS: SR-BI-targeted porphyrinHDL-mediated PDT of lung cancer is selective and effective in vitro and in vivo. These initial proof-of-principle studies suggest the potential of a "smart" PDT approach for highly selective tumor ablation.
  • Hironobu Wada, Jinzi Zheng, Alexander Gregor, Kentaro Hirohashi, Hsin-Pei Hu, Priya Patel, Hideki Ujiie, Tatsuya Kato, Takashi Anayama, David A Jaffray, Kazuhiro Yasufuku
    The Annals of thoracic surgery 107 (1) 248 - 256 0003-4975 2019/01 [Refereed][Not invited]
     
    BACKGROUND: A novel liposomal nanoparticle, CF800, that co-encapsulates indocyanine green for near-infrared (NIR) imaging and iohexol for computed tomography (CT) imaging has shown preferential tumor accumulation after intravenous injection by the enhanced permeability and retention effect. We hypothesized that CF800-enhanced NIR imaging would facilitate intraoperative localization of small lung nodules. METHODS: A rabbit VX2 lung tumor model was implemented. CF800 was injected intravenously, followed by sequential CT acquisitions to track the biodistribution of CF800. Eleven rabbits were used for NIR fluorescence evaluation after thoracotomy at time points until 7 days after injection by using a NIR fluorescence thoracoscope in vivo. Organs of interests were removed for ex vivo analysis by using NIR imaging. Tumor-to-background (inflated lung) ratio was calculated and compared among the time points. RESULTS: Both CT and NIR imaging indicated enhanced accumulation of CF800 within the VX2 tumor. NIR image analysis revealed the highest tumor-to-background ratio on days 4 and 5. High background at day 2 and low tumor signal at day 7 prevented distinct demarcation. Metastatic pulmonary small nodules (less than 2 mm in diameter) were successfully visualized by NIR imaging on day 4. However, NIR signal penetration was limited, resulting in localization failure for the few tumors deep (>0 mm) to the lung surface. CONCLUSIONS: NIR image-guided localization of small lung nodules appears to be feasible under certain conditions. However, further refinement will be required to increase tumor signal intensity and to reduce background signal from normal lung parenchyma, which is at least in part a consequence of persistent CF800 in the vasculature.
  • 小児胸腔鏡手術-小児外科医と呼吸器外科医の立場から- 小児呼吸器疾患に対する胸腔鏡手術の現状と課題
    新垣 雅人, 加賀 基知三, 樋田 泰浩, 加藤 達哉, 藤原 晶, 本橋 雄介, 本多 昌平, 松居 喜郎
    日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 23 (7) PD15 - 4 1344-6703 2018/12 [Not refereed][Not invited]
  • Reduced Port VATSの短期および長期成績 二窓法および細径光学視管を用いた一窓法によるReduced port surgeryの実際と成績
    加賀 基知三, 樋田 泰浩, 加藤 達哉, 新垣 雅人, 藤原 晶, 本橋 雄介, 松居 喜郎
    日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 23 (7) WS19 - 3 1344-6703 2018/12 [Not refereed][Not invited]
  • 大学病院における胸腔鏡手術の教育体制
    樋田 泰浩, 加賀 基知三, 加藤 達哉, 新垣 雅人, 藤原 晶
    日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 23 (7) OS104 - 1 1344-6703 2018/12 [Not refereed][Not invited]
  • Tatsuya Kato, Cheng S Jin, Daiyoon Lee, Hideki Ujiie, Kosuke Fujino, Hsin-Pei Hu, Hironobu Wada, Licun Wu, Juan Chen, Rober A Weersink, Hiromi Kanno, Yutaka Hatanaka, Kanako C Hatanaka, Kichizo Kaga, Yoshiro Matsui, Yoshihiro Matsuno, Marc De Perrot, Brian C Wilson, Gang Zheng, Kazuhiro Yasufuku
    International journal of oncology 53 (5) 2034 - 2046 1019-6439 2018/11 [Refereed][Not invited]
     
    Photodynamic therapy (PDT) following lung-sparing extended pleurectomy for malignant pleural mesothelioma (MPM) has been investigated as a potential means to kill residual microscopic cells. High expression levels of folate receptor 1 (FOLR1) have been reported in MPM; therefore, targeting FOLR1 has been considered a novel potential strategy. The present study developed FOLR1‑targeting porphyrin-lipid nanoparticles (folate-porphysomes, FP) for the treatment of PDT. Furthermore, inhibition of activated epidermal growth factor (EGFR)-associated survival pathways enhance PDT efficacy. In the present study, these approaches were combined; FP-based PDT was used together with an EGFR-tyrosine kinase inhibitor (EGFR-TKI). The frequency of FOLR1 and EGFR expression in MPM was analyzed using tissue microarrays. Confocal microscopy and a cell viability assay were performed to confirm the specificity of FOLR1‑targeting cellular uptake and photocytotoxicity in vitro. In vivo fluorescence activation and therapeutic efficacy were subsequently examined. The effects of EGFR-TKI were also assessed in vitro. The in vivo combined antitumor effect of EGFR-TKI and FP-PDT was then evaluated. The results revealed that FOLR1 and EGFR were expressed in 79 and 89% of MPM samples, respectively. In addition, intracellular uptake of FP corresponded well with FOLR1 expression. When MPM cells were incubated with FP and then irradiated at 671 nm, there was significant in vitro cell death, which was inhibited in the presence of free folic acid, thus suggesting the specificity of FPs. FOLR1 targeting resulted in disassembly of the porphysomes and subsequent fluorescence activation in intrathoracic disseminated MPM tumors, as demonstrated by ex vivo tissue imaging. FP-PDT resulted in significant cellular damage and apoptosis in vivo. Furthermore, the combination of pretreatment with EGFR-TKI and FP-PDT induced a marked improvement of treatment responses. In conclusion, FP-based PDT induced selective destruction of MPM cells based on FOLR1 targeting, and pretreatment with EGFR-TKI further enhanced the therapeutic response.
  • 加藤 達哉, 新垣 雅人, 樋田 泰浩, 千葉 龍平, 本橋 雄介, 道免 寛充, 長 靖, 加賀 基知三, 松居 喜郎
    移植 (一社)日本移植学会 53 (総会臨時) 472 - 472 0578-7947 2018/09 [Not refereed][Not invited]
  • Aki Fujiwara-Kuroda, Tatsuya Kato, Takehiro Abiko, Takahiro Tsuchikawa, Noriaki Kyogoku, Masaomi Ichinokawa, Kimitaka Tanaka, Takehiro Noji, Yasuhiro Hida, Kichizo Kaga, Yoshiro Matsui, Hiroaki Ikeda, Shinichi Kageyama, Hiroshi Shiku, Satoshi Hirano
    International journal of oncology 53 (2) 713 - 724 1019-6439 2018/08 [Refereed][Not invited]
     
    Melanoma antigen family A4 (MAGEA4), a cancer/testis antigen, is overexpressed and is thus an immunotherapy target in various malignant tumors, including non-small cell lung cancer. However, whether MAGEA4 induces or inhibits the apoptosis of lung cancer cells remains controversial, as is its prognostic significance, particularly since there is no reliable method with which to detect MAGEA4 specifically. In this study, we optimized assay conditions to detect MAGEA4 based on cells transiently transfected with MAGEA genes, and found that MAGEA4 was expressed in four of eight non-small cell lung cancer cell lines, and in 25.4% of clinical lung cancer specimens. We also found that MAGEA4 overexpression decreased apoptosis, as measured by the levels of cleaved caspase-3 in stably transfected 293F cells. Notably, patients with nuclear MAGEA4, but not p53 expression exhibited a significantly poorer survival than those expressing both nuclear MAGEA4 and p53. Indeed, multivariate analysis identified nuclear MAGEA4 as an independent prognostic factor (P=0.0042), albeit only in the absence of p53. In this study, to the best of our knowledge, we are the first to demonstrate that the function and prognostic value of MAGEA4 depends on its subcellular localization and on the p53 status.
  • 加藤 達哉, 新垣 雅人, 八木 優樹, 千葉 龍平, 樋田 泰浩, 加賀 基知三, 松井 喜郎
    小切開・鏡視外科学会雑誌 (NPO)小切開・鏡視外科学会 9 (1) 22 - 22 2185-2820 2018/06 [Not refereed][Not invited]
  • 小児・新生児に対するReduced Port VATSによる肺葉切除
    加賀 基知三, 千葉 龍平, 八木 優樹, 久保田 玲子, 新垣 雅人, 加藤 達哉, 樋田 泰浩, 松居 喜郎
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 32 (3) O13 - 1 0919-0945 2018/04 [Not refereed][Not invited]
  • 触知困難肺腫瘍のone-stop solution、術中病変マーキングと切除肺のマージン確認(OS MaRCH法)
    樋田 泰浩, 加賀 基知三, 加藤 達哉, 新垣 雅人, 八木 優樹, 千葉 龍平, 松居 喜郎
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 32 (3) O26 - 2 0919-0945 2018/04 [Not refereed][Not invited]
  • 巨大縦隔神経線維腫症に対して可及的切除とTチューブ挿入により気道狭窄を回避できた1例
    加藤 達哉, 新垣 雅人, 八木 優樹, 千葉 龍平, 樋田 泰浩, 加賀 基知三, 松居 喜郎
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 32 (3) O32 - 1 0919-0945 2018/04 [Not refereed][Not invited]
  • 食道癌手術既往のある肺癌手術症例の検討
    新垣 雅人, 加賀 基知三, 樋田 泰浩, 加藤 達哉, 八木 優樹, 千葉 龍平, 松居 喜郎
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 32 (3) P10 - 6 0919-0945 2018/04 [Not refereed][Not invited]
  • 胸腔鏡下手術における下位肋間経路による新しい切除臓器の創外摘出法(eXtraction method of resected specimen through the Lower INterCostal route-XLINC-)
    新垣 雅人, 加賀 基知三, 樋田 泰浩, 加藤 達哉, 八木 優樹, 千葉 龍平, 松居 喜郎
    日本外科学会定期学術集会抄録集 (一社)日本外科学会 118回 1796 - 1796 2018/04 [Not refereed][Not invited]
  • 胸腔鏡手術における切除肺の創外摘出法の工夫
    千葉 龍平, 加賀 基知三, 樋田 泰浩, 加藤 達哉, 新垣 雅人, 久保田 玲子, 八木 優樹, 松居 喜郎
    日本臨床外科学会雑誌 日本臨床外科学会 79 (3) 619 - 620 1345-2843 2018/03 [Not refereed][Not invited]
  • Tatsuya Kato, Daiyoon Lee, Huang Huang, William Cruz, Hideki Ujiie, Kosuke Fujino, Hironobu Wada, Priya Patel, Hsin-Pei Hu, Kentaro Hirohashi, Takahiro Nakajima, Masaaki Sato, Mitsuhito Kaji, Kichizo Kaga, Yoshiro Matsui, Juan Chen, Gang Zheng, Kazuhiro Yasufuku
    Molecular cancer research : MCR 16 (1) 47 - 57 1541-7786 2018/01 [Refereed][Not invited]
     
    Inhibiting specific gene expression with siRNA provides a new therapeutic strategy to tackle many diseases at the molecular level. Recent strategies called high-density lipoprotein (HDL)-mimicking peptide-phospholipid nanoscaffold (HPPS) nanoparticles have been used to induce siRNAs-targeted delivery to scavenger receptor class B type I receptor (SCARB1)-expressing cancer cells with high efficiency. Here, eight ideal therapeutic target genes were identified for advanced lung cancer throughout the screenings using endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA) and the establishment of a personalized siRNA-nanoparticle therapy. The relevance of these genes was evaluated by means of siRNA experiments in cancer cell growth. To establish a therapeutic model, kinesin family member-11 (KIF11) was selected as a target gene. A total of 356 lung cancers were analyzed immunohistochemically for its clinicopathologic significance. The antitumor effect of HPPS-conjugated siRNA was evaluated in vivo using xenograft tumor models. Inhibition of gene expression for these targets effectively suppressed lung cancer cell growth. SCARB1 was highly expressed in a subset of tumors from the lung large-cell carcinoma (LCC) and small-cell lung cancer (SCLC) patients. High-level KIF11 expression was identified as an independent prognostic factor in LCC and squamous cell carcinoma (SqCC) patients. Finally, a conjugate of siRNA against KIF11 and HPPS nanoparticles induced downregulation of KIF11 expression and mediated dramatic inhibition of tumor growth in vivoImplications: This approach showed delivering personalized cancer-specific siRNAs via the appropriate nanocarrier may be a novel therapeutic option for patients with advanced lung cancer. Mol Cancer Res; 16(1); 47-57. ©2017 AACR.
  • 根治的化学放射線療法後再発・再燃肺癌に対するサルベージ手術と周術期合併症の予防
    樋田 泰浩, 加賀 基知三, 加藤 達哉, 新垣 雅人, 久保田 玲子[中田], 八木 優樹, 千葉 龍平, 松居 喜郎
    肺癌 (NPO)日本肺癌学会 57 (7) 917 - 918 0386-9628 2017/12 [Not refereed][Not invited]
  • 外科的切除を行った縦隔脂肪肉腫の3症例
    千葉 龍平, 加賀 基知三, 樋田 泰浩, 八木 優樹, 久保田 玲子, 新垣 雅人, 加藤 達哉, 松居 喜郎
    肺癌 (NPO)日本肺癌学会 57 (7) 919 - 919 0386-9628 2017/12 [Not refereed][Not invited]
  • Reduced port surgery・Single port VATS lobectomy:標準化できるのか?標準化するのか? 二窓法および細径光学視管を用いた一窓法によるReduced port surgery肺葉切除の適応
    加賀 基知三, 樋田 泰浩, 加藤 達哉, 新垣 雅人, 千葉 龍平, 八木 優樹, 久保田 玲子, 松居 喜郎
    日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 22 (7) WS2 - 2 1344-6703 2017/12 [Not refereed][Not invited]
  • 切除肺創外摘出法の工夫
    新垣 雅人, 加賀 基知三, 樋田 泰浩, 加藤 達哉, 八木 優樹
    日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 22 (7) SF012 - 03 1344-6703 2017/12 [Not refereed][Not invited]
  • 新垣 雅人, 加賀 基知三, 樋田 泰浩, 加藤 達哉, 久保田 玲子[中田], 八木 優樹, 千葉 龍平, 松居 喜郎
    北海道外科雑誌 北海道外科学会 62 (2) 182 - 182 0288-7509 2017/12 [Not refereed][Not invited]
  • Tatsuya Kato, Cheng S Jin, Hideki Ujiie, Daiyoon Lee, Kosuke Fujino, Hironobu Wada, Hsin-Pei Hu, Robert A Weersink, Juan Chen, Mitsuhito Kaji, Kichizo Kaga, Yoshiro Matsui, Brian C Wilson, Gang Zheng, Kazuhiro Yasufuku
    Lung cancer (Amsterdam, Netherlands) 113 59 - 68 0169-5002 2017/11 [Refereed][Not invited]
     
    OBJECTIVE: Despite modest improvements, the prognosis of lung cancer patients has still remained poor and new treatment are urgently needed. Photodynamic therapy (PDT), the use of light-activated compounds (photosensitizers) is a treatment option but its use has been restricted to central airway lesions. Here, we report the use of novel porphyrin-lipid nanoparticles (porphysomes) targeted to folate receptor 1 (FOLR1) to enhance the efficacy and specificity of PDT that may translate into a minimally-invasive intervention for peripheral lung cancer and metastatic lymph nodes of advanced lung cancer. MATERIALS AND METHODS: The frequency of FOLR1 expression in primary lung cancer and metastatic lymph nodes was first analyzed by human tissue samples from surgery and endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA). Confocal fluorescence microscopy was then used to confirm the cellular uptake and fluorescence activation in lung cancer cells, and the photocytotoxicity was evaluated using a cell viability assay. In vivo fluorescence activation and quantification of uptake were investigated in mouse lung orthotopic tumor models, followed by the evaluation of in vivo PDT efficacy. RESULTS: FOLR1 was highly expressed in metastatic lymph node samples from patients with advanced lung cancer and was mainly expressed in lung adenocarcinomas in primary lung cancer. Expression of FOLR1 in lung cancer cell lines corresponded with the intracellular uptake of folate-porphysomes in vitro. When irradiated with a 671nm laser at a dose of 10J/cm2, folate-porphysomes showed marked therapeutic efficacy compared with untargeted porphysomes (28% vs. 83% and 24% vs. 99% cell viability in A549 and SBC5 lung cancer cells, respectively). Systemically-administered folate-porphysomes accumulated in lung tumors with significantly enhanced disease-to-normal tissue contrast. Folate-porphysomes mediated PDT successfully inhibited tumor cell proliferation and activated tumor cell apoptosis. CONCLUSION: Folate-porphysome based PDT shows promise in selectively ablating lung cancer based on FOLR1 expression in these preclinical models.
  • 加藤 達哉, Donahoe Laura, 大石 久, 中島 大輔, 橋本 浩平, Azad Sassan, Cypel Marcelo, de Perrot Marc, Pierre Andrew, Yasufuku Kazuhiro, Waddell Thomas, Granton John, Singer Lianne G., 加賀 基知三, 樋田 泰浩, 松居 喜郎, Jee Shaf Keshav
    移植 (一社)日本移植学会 52 (2-3) 275 - 275 0578-7947 2017/09 [Not refereed][Not invited]
  • 先天性嚢胞性肺疾患に対する胸腔鏡下肺葉切除の適応と限界
    加賀 基知三, 千葉 龍平, 八木 優樹, 久保田 玲子, 新垣 雅人, 加藤 達哉, 樋田 泰浩, 松居 喜郎
    日本気胸・嚢胞性肺疾患学会雑誌 日本気胸・嚢胞性肺疾患学会 17 (2) 96 - 96 1883-0412 2017/08 [Not refereed][Not invited]
  • Hideki Ujiie, Tatsuya Kato, Hsin-pei Hu, Priya Patel, Hironobu Wada, Kosuke Fujino, Robert Weersink, Elsie Nguyen, Marcelo Cypel, Andrew Pierre, Marc de Perrot, Gail Darling, Thomas K. Waddell, Shaf Keshavjee, Kazuhiro Yasufuku
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 154 (2) 702 - 711 0022-5223 2017/08 [Refereed][Not invited]
     
    Objectives: Localization and resection of nonvisible, nonpalpable pulmonary nodules during video-assisted thoracoscopic surgery are challenging. Our study was to determine the feasibility and safety of indocyanine green fluorescence localization and resection of small nodules using a near-infrared fluorescence thoracoscope.Methods: Twenty patients with undiagnosed peripheral nodules smaller than 3 cm scheduled for computed tomography-guided microcoil placement followed by video-assisted thoracoscopic surgery wedge resection were enrolled. After microcoil deployment, 100 to 150 mu L of diluted indocyanine green was injected percutaneously near the nodule. The nodule initially was localized solely by using a near-infrared thoracoscope to visualize indocyanine green fluorescence. Thoracoscopic instruments were used to determine the staple line. Wedge resection was performed after confirmation of the location of the microcoil using fluoroscopy.Results: Twenty patients underwent near-infrared, image-guided, video-assisted thoracoscopic surgery resection. The median computed tomography tumor size was 1.2 cm. The median depth from the pleural surface was 1.4 cm (range, 0.24.8 cm). The median computed tomography-guided intervention time was 35 minutes, and video-assisted thoracoscopic surgery procedural time was 54 minutes. Indocyanine green fluorescence was clearly identified in 18 of 20 patients (90%). The surgical margins were all negative on final pathology without the need for additional resection. The final diagnoses included 18 primary lung cancers, 1 metastatic lung cancer, and 1 benign lung tumor.Conclusions: Computed tomography-guided percutaneous indocyanine green injection and intraoperative near-infrared localization of small nodules are safe and feasible. These offer surgeons the ease of localization through direct indocyanine green fluorescence imaging without the use of fluoroscopy and may be a complementary technique to preoperative microcoil placement for nonvisible, nonpalpable intrapulmonary nodules.
  • Hideki Ujiie, Tatsuya Kato, Daiyoon Lee, Hsin-Pei Hu, Kosuke Fujino, Mitsuhito Kaji, Kichizo Kaga, Yoshiro Matsui, Kazuhiro Yasufuku
    INTERNATIONAL JOURNAL OF ONCOLOGY 50 (6) 2154 - 2170 1019-6439 2017/06 [Refereed][Not invited]
     
    Melanoma-associated antigens (MAGE) are expressed in different type of cancers including lung cancer and have been shown to be functionally related to p53 tumor suppressor gene. Little is known about the relationship between MAGE genes and p53 aberrant expression in lung cancer. The aims of this study were to observe the expression of MAGEA2, examine the role of MAGEA2 in lung cancer survival, investigate its correlation between MAGEA2 and p53, and explore its clinicopathologic significance as a prognostic marker. Quantitative reverse transcription-polymerase chain reaction was performed to detect the expression of MAGEA2 using 36 primary tumors and 31 metastatic lymph nodes from patients with lung cancer. The role of MAGEA2 in cancer cell growth and in the regulation of p53 downstream genes were examined using small interfering RNA. The expression of MAGEA2 and p53 were analyzed immunohistochemically using tissue microarray from 353 resected lung specimens. High-level expression of MAGEA2 (High-MAGEA2) was confirmed in lung tumors with high frequency. Inhibiting MAGEA2 expression effectively suppressed cancer cell growth and decreased the expression of p53 downstream target genes in vitro. In adenocarcinoma, High-MAGEA2 was strongly associated with aberrant p53 expression (P<0.001) and was associated with worse clinical outcomes (5-year OS, 87.1% in low vs. 74.1% in high, P=0.014). Aberrant p53 expression was also significant worse prognostic factor (P=0.029). Among the adenocarcinoma patients with wild-type p53, High-MAGEA2 had poorer prognosis than low-level MAGEA2 groups (5-year OS, 90.1% vs. 72.1%, P=0.037), whereas had no difference in p53 aberrant tumors. On multivariate analysis, MAGEA2 was independently associated with survival (hazard ratio; 2.12, P=0.030). In conclusion, suppression of MAGEA2 in lung cancer cells significantly reduced the growth/survival of cancer cells. High-MAGEA2 was identified as an independent prognostic factor in lung adenocarcinoma. Specific inhibition of MAGEA2 may be a promising therapeutic strategy for patients with lung cancer.
  • Hideki Ujiie, Tatsuya Kato, Hsin-Pei Hu, Patrycja Bauer, Priya Patel, Hironobu Wada, Daiyoon Lee, Kosuke Fujino, Colin Schieman, Andrew Pierre, Thomas K. Waddell, Shaf Keshavjee, Gail E. Darling, Kazuhiro Yasufuku
    JOURNAL OF THORACIC DISEASE 9 (6) 1517 - + 2072-1439 2017/06 [Refereed][Not invited]
     
    Background: Surgical trainees are required to develop competency in a variety of laparoscopic operations. Developing laparoscopic technical skills can be difficult as there has been a decrease in the number of procedures performed. This study aims to develop an inexpensive and anatomically relevant model for training in laparoscopic foregut procedures.Methods: An ex vivo, anatomic model of the human upper abdomen was developed using intact porcine esophagus, stomach, diaphragm and spleen. The Toronto lap-Nissen simulator was contained in a laparoscopic box-trainer and included an arch system to simulate the normal radial shape and tension of the diaphragm. We integrated the use of this training model as a part of our laparoscopic skills laboratory-training curriculum. Afterwards, we surveyed trainees to evaluate the observed benefit of the learning session.Results: Twenty-five trainees and five faculty members completed a survey regarding the use of this model. Among the trainees, only 4 (16%) had experience with laparoscopic Heller myotomy and Nissen fundoplication. They reported that practicing with the model was a valuable use of their limited time, repeating the exercise would be of additional benefit, and that the exercise improved their ability to perform or assist in an actual case in the operating room. Significant improvements were found in the following subjective measures comparing pre- vs. post-training: (I) knowledge level (5.6 vs. 8.0, P<0.001); (II) comfort level in assisting (6.3 vs. 7.6, P<0.001); and (III) comfort level in performing as the primary surgeon (4.9 vs. 7.1, P<0.001). The trainees and faculty members agreed that this model was of adequate fidelity and was a representative simulation of actual human anatomy.Conclusions: We developed an easily reproducible training model for laparoscopic procedures. This simulator reproduces human anatomy and increases the trainees' comfort level in performing and assisting with myotomy and fundoplication.
  • 肋骨弓下切開による摘出肺創外摘出法の工夫
    新垣 雅人, 加賀 基知三, 樋田 泰浩, 加藤 達哉, 久保田 玲子, 八木 優樹, 千葉 龍平, 松居 喜郎
    小切開・鏡視外科学会雑誌 (NPO)小切開・鏡視外科学会 8 (1) 43 - 43 2185-2820 2017/05 [Not refereed][Not invited]
  • Tronto general hospitalにおける小型肺結節に関する胸腔鏡を用いた新規位置特定法(A novel thoracoscopic localization technique of small pulmonary nodules at Toronto general hospital)
    Ujiie Hideki, Kato Tatsuya, Fujino Kosuke, Igai Hitoshi, Waddell Thomas K., Keshavjee Shaf
    日本外科学会定期学術集会抄録集 117回 SF - 1 2017/04
  • Priya Patel, Hironobu Wada, Hsin-Pei Hu, Kentaro Hirohashi, Tatsuya Kato, Hideki Ujiie, Jin Young Ahn, Daiyoon Lee, William Geddie, Kazuhiro Yasufuku
    ANNALS OF THORACIC SURGERY 103 (4) 1158 - 1164 0003-4975 2017/04 [Refereed][Not invited]
     
    Background. Endobronchial ultrasonography (EBUS)guided transbronchial needle aspiration allows for sampling of mediastinal lymph nodes. The external diameter, rigidity, and angulation of the convex probe EBUS renders limited accessibility. This study compares the accessibility and transbronchial needle aspiration capability of the prototype thin convex probe EBUS against the convex probe EBUS in human ex vivo lungs rejected for transplant.Methods. The prototype thin convex probe EBUS (BF-Y0055; Olympus, Tokyo, Japan) with a thinner tip (5.9 mm), greater upward angle (170 degrees), and decreased forward oblique direction of view (20 degrees) was compared with the current convex probe EBUS (6.9-mm tip, 120 degrees, and 35 degrees, respectively). Accessibility and transbronchial needle aspiration capability was assessed in ex vivo human lungs declined for lung transplant. The distance of maximum reach and sustainable endoscopic limit were measured. Transbronchial needle aspiration capability was assessed using the prototype 25G aspiration needle in segmental lymph nodes.Results. In all evaluated lungs (n = 5), the thin convex probe EBUS demonstrated greater reach and a higher success rate, averaging 22.1 mm greater maximum reach and 10.3 mm further endoscopic visibility range than convex probe EBUS, and could assess selectively almost all segmental bronchi (98% right, 91% left), demonstrating nearly twice the accessibility as the convex probe EBUS (48% right, 47% left). The prototype successfully enabled cytologic assessment of subsegmental lymph nodes with adequate quality using the dedicated 25G aspiration needle.Conclusions. Thin convex probe EBUS has greater accessibility to peripheral airways in human lungs and is capable of sampling segmental lymph nodes using the aspiration needle. That will allow for more precise assessment of N1 nodes and, possibly, intrapulmonary lesions normally inaccessible to the conventional convex probe EBUS. (C) 2017 by The Society of Thoracic Surgeons
  • Hideki Ujiie, Tatsuya Kato, Hsin-pei Hu, Suhaib Hasan, Priya Patel, Hironobu Wada, Daiyoon Lee, Kosuke Fujino, David M. Hwang, Marcelo Cypel, Marc de Perrot, Andrew Pierre, Gail Darling, Thomas K. Waddell, Shaf Keshavjee, Kazuhiro Yasufuku
    ANNALS OF THORACIC SURGERY 103 (3) 926 - 934 0003-4975 2017/03 [Refereed][Not invited]
     
    Background. Localization of small, nonvisible and nonpalpable nodules is challenging during video-assisted thoracoscopic surgery. We evaluated the feasibility of using a new ultrasound thoracoscope to localize nodules in resected ex vivo human lungs.Methods. The tumor was localized and measured in its greatest dimension with a prototype ultrasound thoracoscope (XLTF-UC180; Olympus Corporation, Tokyo, Japan) at different frequencies (5.0 to 12.0 MHz) and different lung specimen states (deflated, semiinflated). Measured tumor size and depth from lung surface were compared and correlated to the true diameter and depth from lung surface acquired from pathologic morphology.Results. Ex vivo evaluation was performed on 16 solid nodules and nine part solid ground-glass nodules. All tumors were successfully localized in the deflated lung specimens (average size, 13.7 +/- 5.2 mm). The tumor boundaries were best evaluated with an ultrasound frequency of 10 MHz. Solid nodules were more easily visualized than ground-glass nodules. Part solid ground-glass nodules were not easily detected in the semiinflated specimen owing to peritumoral air surrounding the tumor. Tumor boundaries were also difficult to identify in deeply situated tumors and in lungs with underlying disease. A strong positive correlation existed between the ultrasound measurement and true measurement of tumor size (R-2 = 0.89, p < 0.001).Conclusions. The ultrasound thoracoscope can be used to localize nodules in resected human lungs. The clarity of the tumor boundaries is influenced by the tumor type and depth and the underlying pulmonary disease. Complete lung deflation and the use of 10 MHz ultrasound frequency optimize the visualization of target tumors. (C) 2017 by The Society of Thoracic Surgeons
  • Hideki Ujiie, Daiyoon Lee, Tatsuya Kato, Kazuhiro Yasufuku
    Molecular Targeted Therapy of Lung Cancer 279 - 292 2017/01/01 [Refereed][Not invited]
     
    © Springer Science+Business Media Singapore 2017. In the past decade, there has been seen an increase in the number of cancer therapies that aim to circumscribe the spread and expansion of primary and metastatic tumors. A common characteristic among these therapies is their ability to target cancer progression via different pathways, which is fundamental to preventing successful tumor spreading and dissemination. Recent advancements in gene expression profiling have been fundamental in the identification of new cancer targets, and, consequently, improved targeted therapies have emerged as gene expression arrays, and DNA sequencing have enhanced our understanding of cancer genetics. Modern tumor pathology is now understood and studied at the molecular level ranging from immunohistochemistry (IHC) biomarkers to gene signature classifications and gene mutations, all of which provide significant knowledge about which patients will respond to targeted therapy regimens. We briefly discuss the common types of targeted therapies currently used clinically and provide a brief background on IHC, gene expression, and DNA sequencing technologies. We further provide a discussion on guided therapies and also focus on the appropriate targeted therapies and the pathways they inhibit. A number of prognostic gene expression signatures have been reported to predict survival in non-small cell lung cancer (NSCLC). We focus on the role of gene expression profiling in NSCLC as predictive and prognostic biomarker and its potential use for personalized therapy in the years to come.
  • Tatsuya Kato, Daiyoon Lee, Licun Wu, Priya Patel, Jin Young, Hironobu Wada, Hsin-Pei Hu, Hideki Ujiie, Mitsuhito Kaji, Satoshi Kano, Shinichi Matsuge, Hiromitsu Domen, Hiromi Kanno, Yutaka Hatanaka, Kanako C. Hatanaka, Kichizo Kaga, Yoshiro Matsui, Yoshihiro Matsuno, Marc De Perrot, Kazuhiro Yasufuku
    INTERNATIONAL JOURNAL OF ONCOLOGY 49 (6) 2411 - 2420 1019-6439 2016/12 [Refereed][Not invited]
     
    Malignant pleural mesothelioma (MPM) is an aggressive type of cancer of the thoracic cavity commonly associated with asbestos exposure and a high mortality rate. There is a need for new molecular targets for the development of more effective therapies for MPM. Using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and an RNA interference-based screening, we examined the SORORIN gene as potential therapeutic targets for MPM in addition to the PLKI gene, which is known for kinase of SORORIN. Following in vitro investigation of the effects of target silencing on MPM cells, cell cycle analyses were performed. SORORIN expression was analyzed immunohistochemically using a total of 53 MPM samples on tissue microarray. SORORIN was found to be overexpressed in the majority of clinical MPM samples and human MPM cell lines as determined by qRT-PCR. Gene suppression of each SORORIN and PLK1 led to growth inhibition in MPM cell lines. Knockdown of SORORIN showed an increased number of G2M-phase population and a larger nuclear size, suggesting mitotic arrest. High expression of SORORIN (SORORIN-H) was found in 50.9% of all the MPM cases, and there is a tendency towards poorer prognosis for the SORORIN-H group but the difference is not significant. Suppression of SORORIN with PLK1 inhibitor BI 6727 showed a combinational growth suppressive effect on MPM cell growth. Given high-dose PLK1 inhibitor induced drug-related adverse effects in several clinical trials, our results suggest inhibition SORORIN-PLK1 axis may hold promise for the treatment of MPMs.
  • Ujiie, Hideki, Nakajima, Takahiro, Hu, Hsin-pei, Fujino, Kosuke, Kato, Tatsuya, Yasufuku, Kazuhiro
    CHEST 150 (4) 1045A - 1045A 0012-3692 2016/10 [Not refereed][Not invited]
  • Cheng S. Jin, Hironobu Wada, Takashi Anayama, Patrick Z. McVeigh, Hsin Pei Hu, Kentaro Hirohashi, Takahiro Nakajima, Tatsuya Kato, Shaf Keshavjee, David Hwang, Brian C. Wilson, Gang Zheng, Kazuhiro Yasufuku
    CANCER RESEARCH 76 (19) 5870 - 5880 0008-5472 2016/10 [Refereed][Not invited]
     
    Early detection and efficient treatment modality of early-stage peripheral lung cancer is essential. Current nonsurgical treatments for peripheral lung cancer show critical limitations associated with various complications, requiring alternative minimally invasive therapeutics. Porphysome nanoparticle-enabled fluorescence-guided transbronchial photothermal therapy (PTT) of peripheral lung cancer was developed and demonstrated in preclinical animal models. Systemically administered porphysomes accumulated in lung tumors with significantly enhanced disease-to-normal tissue contrast, as confirmed in three subtypes of orthotopic human lung cancer xenografts (A549, H460, and H520) in mice and in an ortho-topic VX2 tumor in rabbits. An in-house prototype fluorescence bronchoscope demonstrated the capability of porphysomes for in vivo imaging of lung tumors in the mucosal/ submucosal layers, providing real-time fluorescence guidance for transbronchial PTT. Porphysomes also enhanced the efficacy of transbronchial PTT significantly and resulted in selective and efficient tumor tissue ablation in the rabbit model. A clinically used cylindrical diffuser fiber successfully achieved tumor-specific thermal ablation, showing promising evidence for the clinical translation of this novel platform to impact upon nonsurgical treatment of early-stage peripheral lung cancer. (C) 2016 AACR.
  • Priya Patel, Tatsuya Kato, Hideki Ujiie, Hironobu Wada, Daiyoon Lee, Hsin-pei Hu, Kentaro Hirohashi, Jin Young Ahn, Jinzi Zheng, Kazuhiro Yasufuku
    PLOS ONE 11 (9) e0161991  1932-6203 2016/09 [Refereed][Not invited]
     
    BackgroundInvestigation of CF800, a novel PEGylated nano-liposomal imaging agent containing indocyanine green (ICG) and iohexol, for real-time near infrared (NIR) fluorescence and computed tomography (CT) image-guided surgery in an orthotopic lung cancer model in nude mice.MethodsCF800 was intravenously administered into 13 mice bearing the H460 orthotopic human lung cancer. At 48 h post-injection (peak imaging agent accumulation time point), ex vivo NIR and CT imaging was performed. A clinical NIR imaging system (SPY (R), Novadaq) was used to measure fluorescence intensity of tumor and lung. Tumor-to-background-ratios (TBR) were calculated in inflated and deflated states. The mean Hounsfield unit (HU) of lung tumor was quantified using the CT data set and a semi-automated threshold-based method. Histological evaluation using H&E, the macrophage marker F4/80 and the endothelial cell marker CD31, was performed, and compared to the liposomal fluorescence signal obtained from adjacent tissue sectionsResultsThe fluorescence TBR measured when the lung is in the inflated state (2.0 +/- 0.58) was significantly greater than in the deflated state (1.42 +/- 0.380 (n = 7, p<0.003). Mean fluorescent signal in tumor was highly variable across samples, (49.0 +/- 18.8 AU). CT image analysis revealed greater contrast enhancement in lung tumors (a mean increase of 110 +/- 57 HU) when CF800 is administered compared to the no contrast enhanced tumors (p = 0.0002).ConclusionPreliminary data suggests that the high fluorescence TBR and CT tumor contrast enhancement provided by CF800 may have clinical utility in localization of lung cancer during CT and NIR image-guided surgery.
  • Tatsuya Kato, Daiyoon Lee, Licun Wu, Priya Patel, Ahn Mn Young, Hironobu Wada, Hsin-Pei Hu, Hideki Ujiie, Mitsuhito Kaji, Satoshi Kano, Shinichi Matsuge, Hiromitsu Domen, Kichizo Kaga, Yoshiro Matsui, Hiromi Kanno, Yutaka Hatanaka, Kanako C. Hatanaka, Yoshihiro Matsun, Marc de Perrot, Kazuhiro Yasufuku
    INTERNATIONAL JOURNAL OF ONCOLOGY 49 (2) 448 - 456 1019-6439 2016/08 [Refereed][Not invited]
     
    Malignant pleural mesothelioma (MPM) is a rare and aggressive form of cancer commonly associated with asbestos exposure that stems from the thoracic mesothelium with high mortality rate. Currently, treatment options for MPM are limited, and new molecular targets for treatments are urgently needed. Using quantitative reverse transcription-polymerase chain reaction (RT-PCR) and an RNA interference-based screening, we screened two kinesin family members as potential therapeutic targets for MPM. Following in vitro investigation of the target silencing effects on MPM cells, a total of 53 MPMs were analyzed immunohistochemically with tissue microarray. KIF11 and KIF23 transcripts were found to be overexpressed in the majority of clinical MPM samples as well as human MPM cell lines as determined by quantitative RT-PCR. Gene knockdown in MPM cell lines identified growth inhibition following knockdown of KIF11 and KIF23. High expression of KIF11 (KIF11-H) and KIF23 (KIF23-H) were found in 43.4 and 50.9% of all the MPM cases, respectively. Patients who received curative resection with tumors displaying KIF23-H showed shorter overall survival (P=0.0194). These results provide that inhibition of KIF11 and KIF23 may hold promise for treatment of MPMs, raising the possibility that kinesin-based drug targets may be developed in the future.
  • Hironobu Wada, Takashi Anayama, Kentaro Hirohashi, Takahiro Nakajima, Tatsuya Kato, Thomas K. Waddell, Shaf Keshavjee, Ichiro Yoshino, Kazuhiro Yasufuku
    EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 49 (2) 690 - 697 1010-7940 2016/02 [Refereed][Not invited]
     
    Localization of small, non-visible and non-palpable subcentimetre nodules can be challenging during video-assisted thoracoscopic surgery (VATS). Intraoperative ultrasonography is an option for localization of such lesions, yet this technology has not been fully adapted to thoracic surgery. The objective of this study was to assess a newly developed thoracoscopic ultrasound for localization and biopsy of subcentimetre pulmonary nodules in animal models. A prototype convex probe ultrasound thoracoscope (XLTF-UC180, Olympus Medical Systems Corp.) was used in this study. Multiple 5% agar pseudo-tumours were created in porcine lungs (n = 10) and assessed for localization with different frequencies (5.0-12.0 MHz) in deflated lungs. The evaluated pseudo-tumours were divided into two groups based on the distinctness of the tumour margin on the ultrasound images and compared in terms of the size and depth of the tumours. The visualization of real tumours and the biopsy capability were assessed using rabbit VX2 lung tumour models (n = 7). The thoracoscopic ultrasound clearly visualized normal lung structures within a 1.5-cm depth including small vessels and bronchioles less than 5 mm in diameter in the completely deflated lung. Twenty-eight of 30 agar pseudo-tumours (93.3%) were successfully detected in deflated lungs (average size: 8.5 +/- 2.1 mm; average depth: 7.4 +/- 7.5 mm and depth range: 0-24.8 mm). Two tumours were not detected due to residual air surrounding the tumour. Higher frequency (12 MHz) tended to show more distinct margins of the targets. Indistinct tumours were located significantly deeper in the lung than the distinct tumours (14.11vs 2.42 mm), regardless of them being in a similar size range. VX2 tumours were identified as heterogeneous isoechoic lesions and adequate tissue sampling for diagnosis was achieved using a dedicated needle. The newly developed convex probe ultrasound thoracoscope was capable of localizing subcentimetre nodules in the porcine deflated lung as well as of obtaining sufficient sampling from lung tumours in the rabbit model, which may enable single-port VATS lung nodule biopsy in a human clinical setting. However, the depth of the tumours significantly influenced the quality of ultrasound images. Complete collapse of the lung and use of high frequency may facilitate achieving distinct visualization of the targets.
  • Tatsuya Kato, Hironobu Wada, Priya Patel, Hsin-pei Hu, Daiyoon Lee, Hideki Ujiie, Kentaro Hirohashi, Takahiro Nakajima, Masaaki Sato, Mitsuhito Kaji, Kichizo Kaga, Yoshiro Matsui, Ming-Sound Tsao, Kazuhiro Yasufuku
    LUNG CANCER 92 53 - 61 0169-5002 2016/02 [Refereed][Not invited]
     
    Objective: High-level expression of kinesin family member 23 (KIF23), a member of microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division, has been observed in a variety of human malignancies. The aims of the present study were to observe the expression of KIF23 in lung cancer, examine the role of KIF23 in lung cancer cell growth and/or survival by small interfering RNA experiments, and explore its clinicopathologic significance and evaluate KIF23 expression as a prognostic marker.Materials and methods: Quantitative reverse transcription-polymerase chain reaction analysis was performed to detect the expression of KIF23 mRNA using metastatic lymph nodes from patients with advanced lung cancer obtained by endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA) and primary lung tumors through surgical sample. The role of KIF23 in cancer cell growth was examined by small interfering RNA experiments. A total of 339 lung cancers were analyzed immunohistochemically on tissue microarrays to examine the expression of KIF23 protein and its clinicopathologic significance.Results: KIF23 transcript was found to be overexpressed in the great majority of metastatic lymph nodes from advanced lung cancers and primary lung tumors. Inhibiting KIF23 expression effectively suppressed lung cancer cell growth. High-level KIF23 expression was observed in 67.8% of the 339 cases. Lung adenocarcinoma patients with tumors displaying a high-level of KIF23 expression was also identified as an independent prognostic factor by multivariate analysis (P = 0.0064).Conclusion: KIF23 not only provides additional prognostic information for surgical treatment of lung cancer, but may also be a novel therapeutic target for these patients. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
  • Hironobu Wada, Kentaro Hirohashi, Takashi Anayama, Takahiro Nakajima, Tatsuya Kato, Harley H. L. Chan, Jimmy Qiu, Michael Daly, Robert Weersink, David A. Jaffray, Jonathan C. Irish, Thomas K. Waddell, Shaf Keshavjee, Ichiro Yoshino, Kazuhiro Yasufuku
    PLOS ONE 10 (5) e0126945  1932-6203 2015/05 [Refereed][Not invited]
     
    Background The use of near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) for sentinel lymph node (SN) mapping has been investigated in lung cancer; however, this has not been fully adapted for minimally invasive surgery (MIS). The aim of our study was to develop a minimally invasive SN mapping integrating pre-operative electro-magnetic navigational bronchoscopy (ENB)-guided transbronchial ICG injection and intraoperative NIR thoracoscopic imaging. Methods A NIR thoracoscope was used to visualize ICG fluorescence. ICG solutions in a 96-well plate and ex vivo porcine lungs were examined to optimize ICG concentrations and injection volumes. Transbronchial ICG injection (n=4) was assessed in comparison to a traditional transpleural approach (n=3), where after thoracotomy an ICG solution (100 mu L at 100 mu g/mL) was injected into the porcine right upper lobe for SN identification. For further translation into clinical use, transbronchial ICG injection prior to thoracotomy followed by NIR thoracoscopic imaging was validated (n=3). ENB was used for accurate targeting in two pigs with a pseudo-tumor. Results The ICG fluorescence at 10 mu g/mL was the brightest among various concentrations, unchanged by the distance between the thoracoscope and ICG solutions. Injected ICG of no more than 500 mu L showed a localized fluorescence area. All 7 pigs showed a bright paratracheal lymph node within 15 minutes post-injection, with persistent fluorescence for 60 minutes. The antecedent transbronchial ICG injection succeeded in SN identification in all 3 cases at the first thoracoscopic inspection within 20 minutes post-injection. The ENB system allowed accurate ICG injection surrounding the pseudo-tumors. Conclusions ENB-guided ICG injection followed by NIR thoracoscopy was technically feasible for SN mapping in the porcine lung. This promising platform may be translated into human clinical trials and is suited for MIS.
  • Kentaro Hirohashi, Takashi Anayama, Hironobu Wada, Takahiro Nakajima, Tatsuya Kato, Shaf Keshavjee, Kazumasa Orihashi, Kazuhiro Yasufuku
    Journal of Bronchology and Interventional Pulmonology 22 (2) 99 - 106 1948-8270 2015/04/24 [Refereed][Not invited]
     
    The present study was designed to evaluate the efficacy of photothermal ablation therapy for lung cancer by low-power near-infrared laser and topical injection of indocyanine green (ICG). In vitro study 1: an 808 nm laser with 250 mW was irradiated for 10 minutes using different dilutions of ICG and the temporal thermal effect was monitored. ICG (1 mL of 0.5 g/L) was heated to a temperature of > 30°C from the base temperature by laser irradiation. In vitro study 2: the cytotoxic effect of hyperthermia on human lung cancer cells was examined in different temperature and time settings. Cell viability was quantified by both an MTS assay and reculturing. Fatal conditions evaluated by reculturing were as follows: thermal treatment at 55°C for 5 minutes, 53°C for 10 minutes, and 51°C for 15 minutes. The MTS assay study suggested that thermal treatment at 59°C for 5 minutes and 57°C for 20 minutes showed a severe cytotoxic effect. In vivo study: nude mouse subcutaneous NCI-H460 human lung cancer xenograft models were used for the study. Saline or 0.5 g/L of ICG was injected topically into the tumor (n=3/group). Tumors were irradiated with a laser at 500 mW for 10 minutes. Although the tumor diameter reached 1 cm within 24 days after treatment in all 3 mice using saline/laser, tumor sizes were gradually reduced in all 3 mice using the ICG/laser. In 2 of the 3 mice using ICG/laser, tumors had disappeared macroscopically. The efficacy of the photothermal ablation therapy by low-power near-infrared laser and a topical injection of ICG was clarified using a mouse subcutaneous a lung cancer xenograft model.
  • Wada H, Anayama T, Hirohashi K, Nakajima T, Kato T, Waddell TK, Keshavjee S, Yoshino I, Yasufuku K
    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 49 (2) 690 - 7 1873-734X 2015/04 [Refereed][Not invited]
     
    Owner : NLM
    Status : Publisher
    PubModel : Print-Electronic
    Language : ENG
    Pagination :
  • Hironobu Wada, Kentaro Hirohashi, Takahiro Nakajima, Takashi Anayama, Tatsuya Kato, Alexandria Grindlay, Judy McConnell, Ichiro Yoshino, Kazuhiro Yasufuku
    Journal of Bronchology and Interventional Pulmonology 22 (1) 20 - 27 1948-8270 2015/03/16 [Refereed][Not invited]
     
    Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) allows for accurate minimally invasive mediastinal lymph node staging of lung cancer. The current convex probe EBUS (CP-EBUS) has limitations in the access to certain N1 lymph nodes (lobar and segmental) because of its size. The aim of this study was to assess the new thin CP-EBUS (TCP-EBUS) and an aspiration needle for sampling of N1 lymph nodes in a porcine model. Methods: The prototype TCP-EBUS (BF-Y0046, Olympus Medical Systems Corp.) with a thinner tip (5.9mm) and larger bending angle (170 degrees upward) was used. Accessibility, operability, and TBNA capability of the TCP-EBUS were assessed and compared with the current CP-EBUS using porcine lungs. The endoscopic visibility range and the maximum reach were evaluated at the left upper lobe bronchus, tracheobronchus, and right lower lobe bronchus. The prototype aspiration needle (Olympus Medical Systems Corp.) was used for EBUS-TBNA. Results: In all of the evaluated bronchi (n=9), the TCP-EBUS had a greater reach (14.7mm in the endoscopic visibility range, 16.0mm in the maximum reach) than the current CP-EBUS. The TCP-EBUS was able to visualize 1 to 3 distal bifurcations farther compared with the current CP-EBUS. Adequate lymph node sampling from lobar and segmental lymph nodes was possible using the aspiration needle. Conclusions: The TCP-EBUS has improved accessibility to peripheral bronchi with excellent operability and is capable of sampling lobar and segmental lymph nodes using the dedicated aspiration needle.
  • Keidai Ishikawa, Tatsuya Kato, Masato Aragaki, Toshiro Ohbuchi, Sachiko Kimura, Yoshiro Matsui, Mitsuhito Kaji
    ANNALS OF THORACIC AND CARDIOVASCULAR SURGERY 20 585 - 588 1341-1098 2014 [Refereed][Not invited]
     
    A rare case of Castleman's disease with myasthenia gravis is reported. A 55-year-old woman with bilateral ptosis, speech impairment, and severe dyspnea had been previously diagnosed with myasthenia gravis. Computed tomography showed a 5 cm x 3 cm paratracheal mass in the mediastinum, thought to be an ectopic thymoma. Two days after surgical resection, the patient suddenly developed dyspnea. Postoperative myasthenic crisis was diagnosed, and plasmapheresis was performed. Her general condition improved, and her subsequent course was uneventful. The final pathological diagnosis was mediastinal solitary Castleman's disease, hyaline vascular type. Castleman's disease with myasthenia gravis is especially rare. One of the serious complications is postoperative myasthenic crisis. For patients with myasthenia gravis, the rate of postoperative myasthenic crisis seems significantly higher in Castleman's disease patients than in patients with thymic epithelial tumors. Castleman's disease with myasthenia gravis is discussed along with a review of the literature.
  • Kichizo Kaga, Yasuhiro Hida, Reiko Nakada-Kubota, Kazuto Ohtaka, Jun Muto, Keidai Ishikawa, Tatsuya Kato, Yoshiro Matsui
    INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY 17 (2) 268 - 272 1569-9293 2013/08 [Refereed][Not invited]
     
    There are many recent and minimally invasive surgical innovations, yet there has been little evaluation of the limitations of such techniques, particularly those related to video-assisted thoracoscopic surgery. The aims of this study were to determine the usefulness and limitations of video-assisted thoracoscopic surgery using one-port access and needle scope and to evaluate the feasibility of this procedure based on our institutional experience. This retrospective study involved 127 patients who underwent video-assisted thoracoscopic surgery using the one-window and puncture method at our institute from 1997 to 2011. One hundred patients underwent surgical treatment and 27 underwent diagnostic procedures. If there was one lesion present with only mild adhesion that did not require lymph node dissection, we decided to opt for the one-direction approach that provisionally indicates the one-window and puncture method. We compared the conversion and success groups for factors like age, sex, laterality of surgery, objective of surgery, target organ and surgery location. Of 127 cases, 115 (91%) successfully underwent the one-window and puncture procedure. Twelve cases (9%) were converted to the two-window method or thoracotomy. Compared with those targeting the lung, patients with mediastinal lesions demonstrated a higher tendency for conversion (P < 0.05). However, age (P = 0.89), sex (P = 0.46), laterality of surgery (P = 0.34) and purpose of surgery (P = 0.68) did not show any significant differences between the groups. For lung and mediastinal diseases, video-assisted thoracoscopic surgery with the one-window and puncture method can be performed at any location (upper, middle and lower lobe of lung and anterior, middle and posterior of the mediastinum) under limited indications that include the possibility of one-way resection, mild adhesion and no requirement of lymph node dissection. Under provisional criteria, the procedure may be feasible.
  • Hideto Oshita, Ryohei Nishino, Atsushi Takano, Takashi Fujitomo, Masato Aragaki, Tatsuya Kato, Hirohiko Akiyama, Eiju Tsuchiya, Nobuoki Kohno, Yusuke Nakamura, Yataro Daigo
    MOLECULAR CANCER RESEARCH 11 (8) 937 - 951 1541-7786 2013/08 [Refereed][Not invited]
     
    Genome-wide gene expression profiling revealed that the Ras and EF-hand domain containing (RASEF) transcript was significantly transactivated in the majority of lung cancers. Using lung cancer cells, transient expression of RASEF promoted cell growth, whereas RASEF knockdown not only reduced its expression but resulted in growth suppression of the cancer cells. Immunohistochemical staining using tumor tissue microarrays consisting of 341 archived non-small cell lung cancers (NSCLC) revealed the association of strong RASEF positivity with poor prognosis (P = 0.0034 by multivariate analysis). Mechanistically, RASEF interacted with extracellular signal-regulated kinase (ERK) 1/2 and enhanced ERK1/2 signaling. Importantly, inhibiting the interaction between RASEF and ERK1/2 using a cell-permeable peptide that corresponded to the ERK1/2-interacting site of RASEF, suppressed growth of lung cancer cells. This study demonstrates that elevated RASEF promoted cell growth via enhanced ERK signaling and is associated with poor prognosis of NSCLC. Implications: RASEF may play an important role in lung carcinogenesis and could serve as a vaiable prognostic biomarker and target for the development of new molecular therapies. (C) 2013 AACR.
  • Ohtaka K, Hida Y, Kaga K, Kato T, Muto J, Nakada-Kubota R, Sasaki T, Matsui Y
    The Annals of thoracic surgery Elsevier 95 (6) 1924 - 1928 0003-4975 2013/06 [Refereed][Not invited]
     
    Background. Thrombus in the stump of the pulmonary vein (PV) is not a well-known complication after lung resection, and it has the potential to cause embolism to vital organs. To clarify the frequency, risk factors, and cause of this complication, a retrospective clinical study of patients who underwent lobectomy was performed. Methods. The study evaluated 193 patients with primary lung cancer who underwent lobectomy from 2005 to 2011 and contrast-enhanced chest computed tomography (CT) within 2 years after lobectomy. Contrast-enhanced CT was retrospectively interpreted to check for thrombus in the PV stump. Results. The operative procedures were 65 right upper lobectomies, 14 right middle lobectomies, 40 right lower lobectomies, 52 left upper lobectomies (LUL), and 22 left lower lobectomies. Thrombus developed in the PV stump in 7 of the 193 patients (3.6%) after lobectomy. All patients with thrombus had undergone LUL, and 13.5% of those who had undergone LUL developed thrombus. Univariate analyses revealed that LUL and operation time were significant risk factors and that adjuvant chemotherapy was marginally significant. It appears that thrombus may be attributable to the length of the PV stump. Measurement of the length of the PV stump using 3-dimensional CT images of the PV revealed that the stump of the left superior PV was longer than the others. Conclusions. Thrombus in the PV stump occurred in 13.5% of patients after LUL. These findings suggest that contrast-enhanced CT should be recommended for patients after LUL to help identify those with a high risk for thromboembolism. (C) 2013 by The Society of Thoracic Surgeons
  • Tatsuya Kato, Keidai Ishikawa, Masato Aragaki, Masaaki Sato, Kenzo Okamoto, Tetsuya Ishibashi, Koji Oba, Mitsuhito Kaji
    Journal of surgical oncology 107 (6) 619 - 24 0022-4790 2013/05 [Refereed][Not invited]
     
    BACKGROUND: The cutoff value of preoperative serum carcinoembryonic antigen (CEA) levels has not been investigated using appropriate subgroup analyses for non-small cell lung carcinoma (NSCLC). This study was undertaken to determine whether the most predictive preoperative CEA level for risk of recurrence differs according to histological type, and how smoking status influences predictive values in Stage I NSCLC. METHODS: Subjects comprised Stage I NSCLC patients [141 patients with adenocarcinoma (ADC) and 36 with squamous cell carcinoma (SCC)]. RESULTS: In patients with Stage I ADC, recurrence-free survival (RFS) differed most significantly at a preoperative CEA level of 2.5 ng/ml, regardless of smoking status. Cases with preoperative CEA >2.5 ng/ml correlated with male sex, high maximum standard uptake value on (18) F-fluorodeoxyglucose positron emission tomography, poorer histopathological grade, lymphatic invasion, and smoking status. Importantly, preoperative CEA >2.5 ng/ml was identified as an independent risk factor for recurrence (P = 0.0015). Conversely, in patients with SCC, a preoperative CEA level of 3.0 ng/ml was the most predictive threshold. CONCLUSIONS: Thresholds of preoperative CEA should be considered when predicting risk of relapse, even if these levels are within normal limits, as optimal cutoff levels may vary according to histological type.
  • 分葉不全に対する完全胸腔鏡下右上葉切除のコツ
    樋田 泰浩, 加賀 基知三, 加藤 達哉, 石川 慶大, 久保田 玲子[中田], 佐藤 大介, 松居 喜郎
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 27 (3) V01 - 07 0919-0945 2013/04 [Not refereed][Not invited]
  • Ohtaka K, Hida Y, Kaga K, Kato T, Muto J, Nakada-Kubota R, Hirano S, Matsui Y
    Journal of cardiothoracic surgery BioMed Central 8 111  1749-8090 2013/04 [Refereed][Not invited]
     
    Background: Lung tumors showing ground-glass opacities on high-resolution computed tomography indicate the presence of inflammation, atypical adenomatous hyperplasia, or localized bronchioloalveolar carcinoma. We adopted a two-staged video-assisted thoracoscopic lobectomy strategy involving completion lobectomy for localized bronchioloalveolar carcinoma with an invasive component according to postoperative pathological examination by permanent section after partial resection. Methods: Forty-one patients with undiagnosed small peripheral ground-glass opacity lesions underwent partial resection from 2001 to 2007 in Hokkaido University Hospital. Localized bronchioloalveolar carcinoma was classified according to the Noguchi classification for adenocarcinoma. Malignant lesions other than Noguchi types A and B were considered for completion lobectomy and systemic mediastinal lymphadenectomy. Perioperative data of completion video-assisted thoracoscopic lobectomies were compared with data of 67 upfront video-assisted thoracoscopic lobectomies for clinical stage IA adenocarcinoma performed during the same period. Results: Postoperative pathological examination revealed 35 malignant and 6 non-malignant diseases. Histologically, all of the malignant diseases were adenocarcinomas of Noguchi type A (n = 7), B (n = 9), C (n = 18), and F (n = 1). Eleven of 19 patients (58%) with Noguchi type C or F underwent two-staged video-assisted thoracoscopic lobectomy. Three patients refused a second surgery. There was no cancer recurrence. The two-staged lobectomy group had a significantly longer operative time and more blood loss than the upfront lobectomy group. There was no surgical mortality or cancer recurrence. Conclusions: Two-staged lobectomy for undiagnosed small peripheral ground-glass opacity lesions showed satisfactory oncological results. However, low compliance for and invasiveness of the second surgery are concerns associated with this strategy.
  • Keidai Ishikawa, Masaki Miyamoto, Tatsuya Yoshioka, Masatoshi Kadoya, Li Li, Roshan Mishra, Kazuomi Ichinokawa, Yasuhito Shoji, Yoshiyuki Matsumura, Yasuhiro Hida, Kichizo Kaga, Tatsuya Kato, Mitsuhito Kaji, Toshiro Ohbuchi, Tomoo Itoh, Hirotoshi Dosaka-Akita, Yoshiro Matsui, Satoshi Hirano
    ONCOLOGY REPORTS 29 (4) 1315 - 1321 1021-335X 2013/04 [Refereed][Not invited]
     
    This report proposes a concept for the standardization of immunohistochemical evaluation. Immunohistochemical staining has several problems associated with the sensitivity of the technical process and standardization of the assessment of potent staining. We provided data focusing on this concept through immunostaining for CD154 in non-small cell lung cancer (NSCLC). We used two types of anti-CD154 antibody as primary antibodies in immunohistochemical staining, as previously reported. Western blot analysis confirmed strong CD154 expression in the cultured cell line PC10, but not in LK2. We also assessed CD154 expression in SCID mouse xenografts of these cell lines. SCID xenograft data on western blot analysis were consistent with those of cultured cell lines. These xenografts could thus be used as positive or negative tissue controls for CD154 immunostaining. Primary antibodies should therefore be confirmed as recognizing target lesions, while control tissue specimens should be objectively confirmed as having target products using another experimental method. Our method would allow results to be unified at more than one laboratory and could act as an objective control assessment method in immunohistochemistry.
  • Keidai Ishikawa, Tatsuya Kato, Masato Aragaki, Ryunosuke Hase, Toyohiro Saikai, Yoshiro Matsui, Mitsuhito Kaji
    Annals of Thoracic and Cardiovascular Surgery 19 (6) 423 - 427 1341-1098 2013 [Refereed][Not invited]
     
    Bronchopleural fistulas associated with empyema can occur as life-threatening sequelae after pulmonary resection, occurring most frequently after pneumonectomy. Three bronchopleural fistulas, 5-6 mm in diameter, were successfully treated using a fibrin gluecoated collagen patch (FGCCP) and fibrin glue (FG) at the site of a bronchopleural fistula. Through the clinical experiences, we introduce the methodology to perform the endobronchial closure of bronchopleural fistulas. Data were collected by reviewing the clinical charts of patients diagnosed with post-lobectomy bronchopleural fistula at Sapporo Minami-Sanjo Hospital from June 2004 to December 2010. Bronchopleural fistula was diagnosed by means of endoscopic visualization. Three cases of post-lobectomy and one case of post-pneumonectomy bronchopleural fistula were collected. A FGCCP fragment was packed within the fistula, and the fragment grasped with the forceps was kept in this position for approximately a minute, a time during which a FGCCP becomes adhesive, and the patch fragment was released. After releasing the patch fragment, the FG was applied directly on the FGCCP using a two-channel catheter. There have been few reports of the bronchoscopic closure of bronchopleural fistulas using a FGCCP and FG. Closure of small bronchopleural fistulas with the application of a FGCCP and FG may offer a valuable therapeutic alternative. © 2013 The Editorial Committee of Annals of Thoracic and Cardiovascular Surgery. All rights reserved.
  • 区域切除 Hybrid or Complete VATS 完全胸腔鏡下肺区域切除と縦隔リンパ節郭清
    樋田 泰浩, 加賀 基知三, 加藤 達哉, 石川 慶大, 久保田 玲子[中田], 佐藤 彰記, 高野 博信, 松居 喜郎
    日本内視鏡外科学会雑誌 (一社)日本内視鏡外科学会 17 (7) 268 - 268 1344-6703 2012/12 [Not refereed][Not invited]
  • 樋田 泰浩, 武藤 潤, 加賀 基知三, 加藤 達哉, 石川 慶大, 久保田 玲子[中田], 大高 和人, 松居 喜郎
    胸部外科 (株)南江堂 65 (11) 934 - 938 0021-5252 2012/10 [Not refereed][Not invited]
  • Hida Y, Muto J, Kaga K, Kato T, Ishikawa K, Nakada-Kubota R, Ohtaka K, Matsui Y
    Kyobu geka. The Japanese journal of thoracic surgery 65 (11) 934 - 938 0021-5252 2012/10 [Not refereed][Not invited]
  • Tatsuya Kato, Keidai Ishikawa, Masatoshi Kadoya, Kenzo Okamoto, Mitsuhito Kaji
    SURGERY TODAY 42 (9) 903 - 908 0941-1291 2012/09 [Refereed][Not invited]
     
    We report herein the rare case of a patient with dendriform pulmonary ossification (DPO) who developed spontaneous pneumothorax. A 33-year-old male with a history of bronchial asthma presented with pneumothorax of the left lung. An intraoperative inspection revealed no findings of bullae in the entire left lung, but inflammatory pleural changes were identified on the interlobular surface of the left lower lobe. In addition, hard, twig-like configurations were clearly palpable in the subpleural parenchyma and were resected. A histological examination showed acicular bone formations containing myeloid tissue and marrow fat in the lung. DPO was thus diagnosed, and the bony spines were considered to have caused a rupture of the elastic fiber layer of the visceral pleura. DPO may thus have been directly responsible for the pneumothorax in this case.
  • Tatsuya Kato, Yataro Daigo, Masato Aragaki, Keidai Ishikawa, Masaaki Sato, Mitsuhito Kaji
    JOURNAL OF SURGICAL ONCOLOGY 106 (4) 423 - 430 0022-4790 2012/09 [Refereed][Not invited]
     
    Background This study examined the expression of CDC20 in human non-small cell lung cancer (NSCLC), explored its clinicopathological significance, and evaluated as a potential prognostic marker. Methods A total of 362 cases of NSCLCs were analyzed immunohistochemically on tissue microarrays (TMAs). Additionally, the immunoreactivity of mitotic arrest defective protein 2 (MAD2) was also studied. The clinicopathological implications of these molecules were analyzed statistically. Results High-level CDC20 protein expression (CDC20-H) was detected in 71 cases (19.6%). Additionally, CDC20-H was correlated with male sex, pT status, pleural invasion, and non-adenocarcinoma (non-ADC) histology. Significant correlation between CDC20 and MAD2 expression was found. NSCLC patients with tumor exhibiting CDC20-H showed significantly shorter 5-year overall survival (P?=?0.0007). According to subset analyses, CDC20-H was associated with shorter survival than CDC20-L only among ADC patients (P?=?0.0008), and not among squamous cell carcinoma (SCC) patients (P?=?0.5100). Importantly, CDC20-H was also identified as an independent prognostic factor in multivariate analysis (P?=?0.0065). Conclusions CDC20 was a negative prognostic marker with significance in patients with resected NSCLC, particularly those with ADC histology. These results provide additional information for determining postoperative adjuvant treatment. J. Surg. Oncol. 2012; 106:423430. (c) 2012 Wiley Periodicals, Inc.
  • Tatsuya Kato, Keidai Ishikawa, Masato Aragaki, Masaaki Sato, Kenzo Okamoto, Tetsuya Ishibashi, Mitsuhito Kaji
    LUNG CANCER 77 (2) 394 - 400 0169-5002 2012/08 [Refereed][Not invited]
     
    Angiolymphatic invasion (ALL), representing lymphatic invasion (Ly) and intratumoral vascular invasion (V), is considered to be a useful prognostic factor for pathological stage I non-small cell lung carcinoma (NSCLC). However, the types of tumor for which prognoses are most influenced by ALL positivity have not previously been discussed, nor has the question of whether these findings should influence postoperative therapeutic decision-making after complete resection. The present study investigated 195 cases of stage I NSCLC treated by potentially curative surgical resection of the primary tumor and systematic lymphadenectomy. ALI-positive (ALI(+)) results were found in 31.8% of tumors, and 5.1% exhibited both Ly(+) and V(+). Five-year recurrence-free survival was significantly lower in ALI(+) cases (50.6%) than in AL(-) cases (85.9%; p < 0.0001, log-rank test). In particular, 5-year recurrence-free survival rate was only 10.0% for Ly(+)V(+) cases. ALI(+) correlated with high age, male sex, tumor size (>2.0 cm), elevated preoperative serum carcinoembryonic antigen level (>= 5.0 ng/mL), high maximum standard uptake value (SUVmax) on F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) (>= 5.0), pleural invasion, and histological classification of non-adenocarcinoma (ADC). According to histopathological subset analyses. ALIN was associated with shorter recurrence-free survival than ALI() only among ADC patients (p<0.0001, log-rank test), and not among non-ADC patients (p = 0.7710). High preoperative serum CEA level, high SUVmax on FDG-PET, pleural invasion, Ly(+), and V(+) were significant risk factors for recurrence in univariate Cox survival analysis among stage I ADC patients. Importantly, Ly(+) and V(+) were identified as independent risk factors for recurrence by multivariate analysis. Histopathological detection of ALI as a risk factor for recurrence should be considered for inclusion in the staging criteria and as additional information for determining postoperative adjuvant treatment of stage I NSCLC, particularly among ADC patients, but not among non-ADC patients. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
  • 完全胸腔鏡下気管支断端肋間筋弁被覆
    樋田 泰浩, 加賀 基知三, 加藤 達哉, 井上 玲, 大高 和人, 武藤 潤, 武内 慎太郎, 松居 喜郎
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 26 (3) RS03 - 02 0919-0945 2012/04 [Not refereed][Not invited]
  • 完全胸腔鏡下肺区域切除の適応、手技およびその成績
    加賀 基知三, 樋田 泰浩, 加藤 達哉, 井上 玲, 大高 和人, 武藤 潤, 中田 玲子, 松居 喜郎
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 26 (3) RV10 - 05 0919-0945 2012/04 [Not refereed][Not invited]
  • 原発性肺腺癌における術前血清CYFRA値と予後との関連に関する検討
    武内 慎太郎, 加藤 達哉, 樋田 泰浩, 加賀 基知三, 中田 玲子, 大高 和人, 武藤 潤, 井上 玲, 平野 聡, 松居 喜郎
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 26 (3) O02 - 02 0919-0945 2012/04 [Not refereed][Not invited]
  • 肺癌術後脳血管障害の機序と対策 左上葉切除術は肺静脈断端内血栓の危険因子である
    大高 和人, 樋田 泰浩, 加賀 基知三, 加藤 達哉, 井上 玲, 武藤 潤, 中田 玲子, 松居 喜郎
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 26 (3) O12 - 01 0919-0945 2012/04 [Not refereed][Not invited]
  • 病理病期III悪性胸膜中皮腫切除症例の検討
    中田 玲子, 樋田 泰浩, 加賀 基知三, 加藤 達哉, 井上 玲, 大高 和人, 武藤 潤, 平野 聡, 松井 喜郎
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 26 (3) O13 - 05 0919-0945 2012/04 [Not refereed][Not invited]
  • 横隔膜交通症手術における交通部同定法としての気腹法の有用性
    井上 玲, 樋田 泰浩, 加賀 基知三, 武藤 潤, 大高 かずと, 加藤 達哉, 加藤 弘明, 成田 吉明, 樫村 暢一, 平野 聡, 松居 喜郎
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 26 (3) O29 - 03 0919-0945 2012/04 [Not refereed][Not invited]
  • 原発巣へのFDG集積による非浸潤性非小細胞肺癌の判定
    武藤 潤, 樋田 泰浩, 加賀 基知三, 加藤 達哉, 大高 和人, 井上 玲, 中田 玲子, 平野 聡, 松居 喜郎
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 26 (3) P16 - 02 0919-0945 2012/04 [Not refereed][Not invited]
  • 頸部切開と胸腔鏡操作で摘除し得た縦隔上部胸腺腫の一例
    阿部 早和子, 樋田 泰浩, 加賀 基知三, 加藤 達哉, 大高 和人, 武藤 潤, 井上 玲, 中田 玲子, 松居 喜郎
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 26 (3) P45 - 03 0919-0945 2012/04 [Not refereed][Not invited]
  • Tatsuya Kato, Yataro Daigo, Masato Aragaki, Keidai Ishikawa, Masaaki Sato, Mitsuhito Kaji
    LUNG CANCER 75 (1) 110 - 118 0169-5002 2012/01 [Refereed][Not invited]
     
    High expression of KIAA0101 (p15(PAF)/OEATC-1) which contains a proliferating cell nuclear antigen (PCNA)-binding motif, a key factor in DNA repair and/or apoptosis and cell cycle regulation, has been observed in a variety of human malignancies. The aim of this study was to observe the expression of KIAA0101 in human non-small-cell lung cancer (NSCLC), explore its clinicopathological significance and evaluate KIAA0101 expression as a potential prognostic marker. KIAA0101 transcript was found to be overexpressed in the great majority of lung cancers by semi-quantitative RT-PCR. A total of 357 NSCLCs were analyzed immunohistochemically on tissue microarrays. High-level KIAA0101 expression was observed in 33.9% (121 of 357 cases), and correlated with male gender (P < 0.0001), tumor progression (pT status) (P=0.0008), lymph node metastasis (pN status) (P=0.0003), non-adenocarcinoma histological classification (P < 0.0001), and smoking history (P < 0.0001), but not with patient age or pleural invasion. Patients with tumors displaying high-level KIAA0101 expression showed significantly shorter survival (P < 0.0001, log-rank test). Similarly, gender, pT status, pN status, pleural invasion, histological classification, and smoking history were significant prognostic markers in univariate Cox survival analysis. Importantly, high-level KIAA0101 expression was also identified as an independent prognostic factor by multivariate analysis (P=0.0320). These results provide additional information for determining postoperative adjuvant treatment of NSCLC. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
  • Tatsuya Kato, Yataro Daigo, Masato Aragaki, Keidai Ishikawa, Masaaki Sato, Satoshi Kondo, Mitsuhito Kaji
    LUNG CANCER 74 (1) 124 - 131 0169-5002 2011/10 [Refereed][Not invited]
     
    High-level expression of mitotic arrest defective protein 2 (MAD2), a central component of the spindle assembly checkpoint, has been observed in a variety of human malignancies. Aim of the present study was to observe the expression of MAD2 in human non-small-cell lung cancer (NSCLC) and explore its clinicopathologic significance and evaluate MAD2 expression as a prognostic marker. MAD2 transcript was found to be overexpressed in the great majority of lung cancers by semi-quantitative RT-PCR. A total of 358 NSCLCs were analyzed immunohistochemically on tissue microarrays. High-level MAD2 expression was observed in 26.3% (94 of 358 cases), and correlated with male sex (P = 0.0002), tumor progression (pT status) (P = 0.0009), visceral or parietal pleural invasion (P = 0.0151), non-adenocarcinoma, histological classification (P < 0.0001), and smoking history (P = 0.0022), but not with patient age or lymph node metastasis (pN status). Patients with tumors displaying high-level MAD2 expression showed significantly shorter survival (P < 0.0001, log-rank test). Similarly, gender, pT status, pN status, pleural invasion, histological classification, and smoking history were significant prognostic markers in univariate Cox survival analysis. Importantly, high-level MAD2 expression was also identified as an independent prognostic factor by multivariate analysis (P = 0.0076). These results provide additional prognostic information for surgical treatment of NSCLC. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
  • Tetsuya Ishibashi, Mitsuhito Kaji, Tatsuya Kato, Keidai Ishikawa, Masatoshi Kadoya, Nagara Tamaki
    ANNALS OF NUCLEAR MEDICINE 25 (8) 547 - 553 0914-7187 2011/10 [Refereed][Not invited]
     
    Objective This study investigated how fluorodeoxyglucose (FDG) uptake on PET in the primary tumor may predict intratumoral vessel invasion (IVI) in it. Methods A total of 512 patients with lung neoplasms determined by a surgical procedure and histopathological diagnosis had undergone FDG-PET scanning. Results Among the 440 cases confirmed to be malignant, the maximum standardized uptake value (SUV(max)) was significantly lower in IVI-negative cases than IVI-positive cases (P < 0.001). In the substudy on adenocarcinoma (AC), SUV(max) was significantly lower in IVI-negative cases too (P < 0.001), but SUV(max) in squamous cell carcinoma was without significant difference. In addition, IVI was associated with a significantly higher probability of lymph node metastasis (P < 0.001). Conclusions This study indicates that a malignant lung tumor with higher SUV(max) has a significantly higher probability of IVI and lymph node metastasis, particularly if the malignancy is an AC.
  • Tatsuya Kato, Keidai Ishikawa, Masaaki Satoh, Satoshi Kondo, Mitsuhito Kaji
    SURGERY TODAY 41 (6) 841 - 845 0941-1291 2011/06 [Refereed][Not invited]
     
    We herein report the case of a patient with Li-Fraumeni syndrome (LFS) who developed lung pleomorphic carcinoma. A 28-year-old female patient with a family history of early-onset malignancies was diagnosed with lung carcinoma and treated by surgical resection. Histological examination revealed a heterogeneous tumor with epithelial and mesenchymal components. The final pathological diagnosis was pulmonary pleomorphic carcinoma. In this patient, a constitutional mutation at codon 213 in exon 6 of the p53 gene was identified in the peripheral lymphocytes and the resected tumor, and LFS was suspected. This mutation causes a nonsense mutation (Arg-to-Stop codon) that has been shown to attenuate p53 function. This is the first report of pulmonary pleomorphic carcinoma developing in an LFS patient, and may suggest a relationship between germline p53 mutation and carcinogenesis in pulmonary pleomorphic carcinoma.
  • 非小細胞肺癌症例においてHLA Class IH鎖分子発現低下は予後不良因子である(Cases of NSCLC that have down-regulated expression of HLA class I heavy chain show poor prognoses)
    市之川 一臣, 宮本 正樹, 石川 慶大, 加藤 達哉, 吉岡 達也, ローシャン・ミシュラ, 東海林 安人, 樋田 泰浩, 加賀 基知三, 平野 聡, 加地 苗人, 近藤 哲
    日本癌学会総会記事 67回 217 - 217 0546-0476 2008/09 [Not refereed][Not invited]
  • Keidai Ishikawa, Masaki Miyamoto, Tatsuya Yoshioka, Tatsuya Kato, Mitsuhito Kaji, Toshiro Ohbuchi, Satoshi Hirano, Tomoo Itoh, Hirotoshi Dosaka-Akita, Satoshi Kondo
    CANCER 113 (3) 530 - 541 0008-543X 2008/08 [Refereed][Not invited]
     
    BACKGROUND. CD40 and its ligand, CD154 play a regulatory role in several signaling pathways among lymphocytes. Recently, it was reported that CD40 is expressed in several malignant tumors. However, the clinical impact of CD40 expression in nonsmall cell lung cancer has not been studied widely. METHODS. One hundred twenty-nine surgical specimens of nonsmall cell lung cancer were assessed inummohistochemically for CD40 and CD154 expression, and that expression was correlated with patients' clinicopathologic parameters and outcome. Subsequently, in vitro analysis of CD40-CD154 signaling was performed. RESULTS. Immunohistochemical staining of tumor cells confirmed that 67 patients (51.9%) were positive for CD40, and 76 patients (58.9%) were positive for CD154. The survival of patients who had tumors that were negative for CD40 was significantly better than the survival of patients who had tumors that were positive for CD40 (P = .0004). Multivariate analysis using a Cox regression model indicated that CD40 expression in cancer cells is an independent, unfavorable prognostic factor (risk ratio, 1.855; P = .0403). By using an in vitro juxtacrine growth factor assay, the growth of LK2 cells (CD40-positive/CD 154-negative) was accelerated by CD154-positive cancer cells, such as PC10 cells (CD40-negative/CD154-positive), by a juxtacrine mechanism. CONCLUSIONS. The current results suggested that CD40 expression in tumors is associated with a poor prognosis and that the juxtacrine interaction of CD40-CD154 among cancer cells facilitates the development of malignant potential in nonsmall cell lung cancer.
  • Tatsuya Kato, Nagato Sato, Atsushi Takano, Masaki Miyamoto, Hitoshi Nishimura, Eiju Tsuchiya, Satoshi Kondo, Yusuke Nakamura, Yataro Daigo
    CLINICAL CANCER RESEARCH 14 (8) 2363 - 2370 1078-0432 2008/04 [Refereed][Not invited]
     
    Purpose and Experimental Design: To identify novel biomarkers and therapeutic targets for lung cancers, we screened for genes that were highly transactivated in lung cancers using a cDNA microarray representing 27,648 genes. DLX5 gene, a member of the human distal-less homeobox transcriptional factor family that is expressed during early embryonic development, was found to be overexpressed in the great majority of lung cancers. Tissue microarray consisting of archival non -small cell lung cancer samples from 369 patients was applied to examine the clinicopathologic significance of DLX5 protein. A role of DLX5 in cancer cell growth and/or survival was investigated through small interfering RNA experiments, Results: Northern blot and immunohistochemical analyses detected expression of DLX5 only in placenta among 23 normal tissues examined. Immunohistochemical analysis showed that positive immunostaining of DLX5 was correlated with tumor size (pT classification; P = 0.0053) and poorer prognosis of non -small cell lung cancer patients (P = 0.0045). It was also shown to be an independent prognostic factor (P = 0.0415). Treatment of lung cancer cells with small interfering RNAs for DLX5 effectively knocked down its expression and suppressed cell growth. Conclusions: These data implied that DLX5 is useful as a target for the development of anticancer drugs and cancer vaccines as well as for a prognostic biomarker in clinic.
  • UEHARA Hirofumi, KAJI Mitsuhito, KATO Tatsuya
    The Journal of the Japanese Association for Chest Surgery 特定非営利活動法人日本呼吸器外科学会 22 (2) 169 - 174 0919-0945 2008/03/07 
    Recently, 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) has come to be considered a useful tool for the diagnosis of lung cancer. Especially, FDG-PET is very sensitive to the detection of lung cancer appearing as solid tumors on chest computed tomography (CT) scanning. However, false negative cases are still sometime reported. We report two cases of mucinous type of bronchioloalveolar carcinoma with negative FDG-PET scanning. Mucin of malignant cells can be a cause of false-negative FDG-PET scanning. Clinicians should note that FDG-PET-negative lung tumors might be a mucinous type of bronchioloalveolar carcinoma.
  • 加藤 達哉, 石川 慶大, 加地 苗人
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 22 (3) 532 - 532 2008
  • Tatsuya Kato, Nagato Sato, Satoshi Hayama, Takumi Yamabuki, Tomoo Ito, Masaki Miyamoto, Satoshi Kondo, Yusuke Nakamura, Yataro Daigo
    CANCER RESEARCH 67 (18) 8544 - 8553 0008-5472 2007/09 [Refereed][Not invited]
     
    We identified a novel gene HJURP (Holliday junction-recognizing protein) whose activation seemed to play a pivotal role in the immortality of cancer cells. HJURP was considered a possible downstream target for ataxia telangiectasia mutated signaling, and its expression was increased by DNA double-strand breaks (DSB). HJURP was involved in the homologous recombination pathway in the DSB repair process through interaction with hMSH5 and NBS1, which is a part of the MRN protein complex. HJURP formed nuclear foci in cells at S phase and those subjected to DNA damage. In vitro assays implied that HJURP bound directly to the Holliday junction and rDNA arrays. Treatment of cancer cells with small interfering RNA (siRNA) against HJURP caused abnormal chromosomal fusions and led to genomic instability and senescence. In addition, HJURP overexpression was observed in a majority of lung cancers and was associated with poor prognosis as well. We suggest that HJURP is an indispensable factor for chromosomal stability in immortalized cancer cells and is a potential novel therapeutic target for the development of anticancer drugs.
  • ヒト小細胞肺癌細胞におけるjuxtacrine活性によるCD40の上方制御は予後不良と関連する(Up-regulation of CD40 with juxtacrine activity in human non-small lung cancer cells correlates with poor prognosis)
    石川 慶大, 宮本 正樹, 吉岡 達也, 樋田 泰浩, 加藤 達哉, 加地 苗人, 秋田 弘俊, 近藤 哲
    日本癌学会総会記事 66回 375 - 375 0546-0476 2007/08 [Not refereed][Not invited]
  • Satoshi Hayama, Yataro Daigo, Takumi Yamabuki, Daizaburo Hirata, Tatsuya Kato, Masaki Miyamoto, Tomoo Ito, Eiju Tsuchiya, Satoshi Kondo, Yusuke Nakamura
    CANCER RESEARCH 67 (9) 4113 - 4122 0008-5472 2007/05 [Refereed][Not invited]
     
    Through genome-wide gene expression analysis of lung carcinomas, we detected in the great majority of lung cancer samples cotransactivation of cell division cycle associated 8 (CDCA8) and aurora kinase B (AURKB), which were considered to be components of the vertebrate chromosomal passenger complex. Immunohistochemical analysis of lung cancer tissue microarrays showed that overexpression of CDCA8 and AURKB was significantly associated with poor prognosis of lung cancer patients. AURKB directly phosphorylated CDCA8 at Ser(154), Ser(219), Ser(275), and Thr(278) and seemed to stabilize CDCA8 protein in cancer cells. Suppression of CDCA8 expression with small interfering RNA against CDCA8 significantly suppressed the growth of lung cancer cells. In addition, functional inhibition of interaction between CDCA8 and AURKB by a cell-permeable peptide corresponding to 20amino acid sequence of a part of CDCA8 (11R-CDCA8(261-280)), which included two phosphorylation sites by AURKB, significantly reduced phosphorylation of CDCA8 and resulted in growth suppression of lung cancer cells. Our data imply that selective suppression of the CDCA8-AURKB pathway could be a promising therapeutic strategy for treatment of lung cancer patients.
  • Takumi Yamabuki, Atsushi Takano, Satoshi Hayama, Nobuhisa Ishikawa, Tatsuya Kato, Masaki Miyamoto, Tomoo Ito, Hiroyuki Ito, Yohei Miyagi, Haruhiko Nakayama, Masahiro Fujita, Masao Hosokawa, Eiju Tsuchiya, Nobuoki Kohno, Satoshi Kondo, Yusuke Nakamura, Yataro Daigo
    CANCER RESEARCH 67 (6) 2517 - 2525 0008-5472 2007/03 [Refereed][Not invited]
     
    Gene expression profile analysis of lung and esophageal carcinomas revealed that Dikkopf-1 (DKK1) was highly transactivated in the great majority of lung cancers and esophageal squamous cell carcinomas (ESCC). Immunohistochemical staining using tumor tissue microarrays consisting of 279 archived non-small cell lung cancers (NSCLC) and 280 ESCC specimens showed that a high level of DKK1 expression was associated with poor prognosis of patients with NSCLC as well as ESCC, and multivariate analysis confirmed its independent prognostic value for NSCLC. In addition, we identified that exogenous expression of DKK1 increased the migratory activity of mammalian cells, suggesting that DKK1 may play a significant role in progression of human cancer. We established an ELISA system to measure serum levels of DKK1 and found that serum DKK1 levels were significantly higher in lung and esophageal cancer patients than in healthy controls. The proportion of the DKK1-positive cases was 126 of 180 (70.0%) NSCLC, 59 of 85 (69.4%) SCLC, and 51 of 81 (63.0%) ESCC patients, whereas only 10 of 207 (4.8%) healthy volunteers were falsely diagnosed as positive. A combined ELISA assays for both DKK1 and carcinoembryonic antigen increased sensitivity and classified 82.2% of the NSCLC patients as positive whereas only 7.7% of healthy volunteers were falsely diagnosed to be positive. The use of both DKK1 and ProGRP increased sensitivity to detect SCLCs up to 89.4%, whereas false-positive rate in healthy donors was only 6.3%. Our data imply that DKK1 should be useful as a novel diagnostic/prognostic biomarker in clinic and probably as a therapeutic target for lung and esophageal cancer.
  • Chie Suzuki, Koji Takahashi, Satoshi Hayama, Nobuhisa Ishikavva, Tatsuya Kato, Tomoo Ito, Eiju Tsuchiya, Yusuke Nakamura, Yataro Daigo
    MOLECULAR CANCER THERAPEUTICS 6 (2) 542 - 551 1535-7163 2007/02 [Refereed][Not invited]
     
    Through genome-wide expression profile analysis for non small cell lung cancers (NSCLC), we found overexpression of a Myc-associated protein with JmjC domain (MAPJD) gene in the great majority of NSCLC cases. Induction of exogenous expression of MAPJD into NIH3T3 cells conferred growth-promoting activity. Concordantly, in vitro suppression of MAPJD expression with small interfering RNA effectively suppressed growth of NSCLC cells, in which MAPJD was overexpressed. We found four candidate MAPJD target genes, SBNO1, TGFBRAP1, RIOK1, and RASGEF1A, which were the most significantly induced by exogenous MAPJD expression. Through interaction with MYC protein, MAPJD transactivates a set of genes, including kinases and cell signal transducers that are possibly related to proliferation of lung cancer cells. As our data imply that MAPJD is a novel member of the MYC transcriptional complex and its activation is a common feature of lung cancer, selective suppression of this pathway could be a promising therapeutic target for treatment of lung cancers.
  • 加藤 達哉, 上原 浩文, 加地 苗人
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 21 (3) 458 - 458 2007
  • 上原 浩文, 加地 苗人, 加藤 達哉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 21 (3) 362 - 362 2007
  • 加地 苗人, 加藤 達哉, 上原 浩文
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 21 (3) 322 - 322 2007
  • Tatsuya Kato, Satoshi Hayama, Takumi Yamabuki, Nobuhisa Ishikawa, Masaki Miyamoto, Tomoo Ito, Eiju Tsuchiya, Satoshi Kondo, Yusuke Nakamura, Yataro Daigo
    CLINICAL CANCER RESEARCH 13 (2) 434 - 442 1078-0432 2007/01 [Refereed][Not invited]
     
    Purpose: To identify novel biomarkers and therapeutic targets for lung cancers, we screened for genes that were highly transactivated in a large proportion of non-small cell lung cancers (NSCLC) using a cDNA microarray representing 27,648 genes. Experimental Design: A gene encoding insulin-like growth factor-II mRNA-binding protein 1 (IMP-1) was selected as a candidate (>= 3-folcl expression than in normal lung tissue in about 70% of NSCLCs). Tumor tissue microarray was applied to examine expression of IMP-1 protein in archival lung cancer samples from 267 patients and investigated its clinicopathologic significance. A role of IMP-1 in cancer cell growth and/or survival was examined by small interfering RNA experiments. Cellular invasive activity of IMP-1 on mammalian cells was examined using Matrigel assays. mRNAs associated with IMP-1 in cancer cells were also isolated by RNA immunoprecipitation followed by cDNA microarray analysis. Results: Positive immunostaining of IMP-1 was correlated with male (P = 0.0001), tumor size (P = 0.0003), non-adenocarcinoma histology (P < 0.0001), smoking history (P = 0.0005), non - well-differentiated tumor grade (P = 0.0001), and poor prognosis (P = 0.0053). Suppression of IMP-1 expression with small interfering RNA effectively suppressed growth of NSCLC cells. In addition, we identified that exogenous expression of IMP-1 increased the migratory activity of mammalian cells. IMP-1 was able to bind to mRNAs encoding a variety of proteins involved in signal transduction, cell cycle progression, cell adhesion and cytoskeleton, and various types of enzymatic activities. Conclusions: These results suggest that IMP-1 expression is likely to play important roles in lung cancer development and progression, and that IMP-1 is a prognostic biomarker and a promising therapeutic target for lung cancer.
  • Satoshi Hayama, Yataro Daigo, Tatsuya Kato, Nobuhisa Ishikawa, Takumi Yamabuki, Masaki Miyamoto, Tomoo Ito, Eiju Tsuchiya, Satoshi Kondo, Yusuke Nakamura
    CANCER RESEARCH 66 (21) 10339 - 10348 0008-5472 2006/11 [Refereed][Not invited]
     
    We found cotransactivation of cell division associated 1 (CDCA1) and kinetochore associated 2 (KNTC2), members of the evolutionarily conserved centromere protein complex, in non-small cell lung carcinomas (NSCLC). Immunobistochemical analysis using lung cancer tissue microarray confirmed high levels of CDCA1 and KNTC2 proteins in the great majority of lung cancers of various histologic types. Their elevated expressions were associated with poorer prognosis of NSCLC patients. Knockdown of either CDCA1 or KNTC2 expression with small interfering RNA significantly suppressed growth of NSCLC cells. Furthermore, inhibition of their binding by a cell-permeable peptide carrying the CDCA1-derived 19-amino-acid peptide (11R-CDCA1(398-416)) that correspond to the binding domain to KNTC2 effectively suppressed growth of NSCLC cells. As our data imply that human CDCA1 and KNTC2 seem to fall in the category of cancer-testis antigens, and that their simultaneous up-regulation is a frequent and important feature of cell growth/survival of lung cancer, selective suppression of CDCA1 or KNTC2 activity and/or inhibition of the CDCA1-KNTC2 complex formation could be a promising therapeutic target for treatment of lung cancers.
  • Koji Takahashi, Chiyuki Furukawa, Atsushi Takano, Nobuhisa Ishikawa, Tatsuya Kato, Satoshi Hayama, Chie Suzuki, Wataru Yasui, Kouki Inai, Saburo Sone, Tomoo Ito, Fetoshi Nishimura, Eiju Tsuchiya, Yusuke Nakamura, Yataro Daigo
    CANCER RESEARCH 66 (19) 9408 - 9419 0008-5472 2006/10 [Refereed][Not invited]
     
    Using a genome-wide cDNA microarray to search for genes that were specifically up-regulated in non-small cell lung cancers (NSCLC), we identified an abundant expression of neuromedin U (NMU) in the great majority of lung cancers. Immunohistochemical analysis showed a significant association of NMU expression with poorer prognosis of patients with NSCLC. Treatment of NSCLC cells with short interfering RNA against NMU suppressed its expression and inhibited the growth of the cells; on the other hand, the induction of exogenous expression of NMU conferred growth-promoting activity and enhanced cell mobility in vitro. We found that two G protein-coupled receptors, growth hormone secretagogue receptor 1b and neurotensin receptor 1, were also overexpressed in NSCLC cells, and that a heterodimer complex of these receptors functioned as an NMU receptor. The NMU-receptor interaction subsequently induced the generation of a second messenger, cyclic AMP, to activate its downstream genes including transcription factors and cell cycle regulators. Treatment of NSCLC cells with short interfering RNAs for growth hormone secretagogue receptor or neurotensin receptor I suppressed the expression of those genes and the growth of NSCLC cells. These data strongly implied that targeting the NMU signaling pathway would be a promising therapeutic strategy for the treatment of lung cancers.
  • N Ishikawa, Y Daigo, A Takano, M Taniwaki, T Kato, S Tanaka, W Yasui, Y Takeshima, K Inai, H Nishimura, E Tsuchiya, N Kohno, Y Nakamura
    CANCER SCIENCE 97 (8) 737 - 745 1347-9032 2006/08 [Refereed][Not invited]
     
    To identify molecules that might serve as biomarkers or targets for development of novel molecular therapies, we have been screening genes encoding transmembrane/secretory proteins that are up-regulated in lung cancers, using cDNA microarrays coupled with purification of tumor cells by laser microdissection. A gene encoding seizure-related 6 homolog (mouse)-like 2 (SEZ6L2) protein, was chosen as a candidate for such molecule. Semi-quantitative RT-PCR and western-blot analyses documented increased expression of SEZ6L2 in the majority of primary lung cancers and lung-cancer cell lines examined. SEZ6L2 protein was proven to be present on the surface of lung-cancer cells by flow cytometrical analysis using anti-SEZ6L2 antibody. Immunohistochemical staining for tumor tissue microarray consisting of 440 archived lung-cancer specimens detected positive SEZ6L2 staining in 327 (78%) of 420 non-small cell lung cancers (NSCLCs) and 13 (65%) of 20 small-cell lung cancers (SCLCs) examined. Moreover, NSCLC patients whose tumors revealed a higher level of SEZ6L2 expression suffered shorter tumor-specific survival compared to those with no SEZ6L2 expression. These results indicate that SEZ6L2 should be a useful prognostic marker of lung cancers.
  • T Yamabuki, Y Daigo, T Kato, S Hayama, T Tsunoda, M Miyamoto, T Ito, M Fujita, M Hosokawa, S Kondo, Y Nakamura
    INTERNATIONAL JOURNAL OF ONCOLOGY 28 (6) 1375 - 1384 1019-6439 2006/06 [Refereed][Not invited]
     
    To identify the molecules involved in esophageal carcinogenesis and those applicable as novel tumor markers and for the development of new molecular therapies, we performed gene expression profile analysis of 19 esophageal squamous cell carcinoma (ESCC) cells purified by laser microbeam microdissection (LMM). Using a cDNA microarray representing 32,256 genes, we identified 147 genes that were commonly up-regulated and 376 transcripts that were down-regulated in ESCC cells compared with non-cancerous esophageal epithelial cells. A comparison of clinicopathological data with the expression profiles of the 19 ESCCs identified 20 genes whose expression levels could most significantly separate cases with lymph node metastasis from those without. In addition, immunohistochemical analysis of candidate tumor markers on tissue microarrays demonstrated transactivation of a secretory protein, transforming growth factor alpha (TGFA) in the great majority of 228 ESCC cases and an association of their expression with the poor prognosis of patients. Our data provide valuable information for establishing novel diagnostic markers for early diagnosis and choice of therapy, and identifying therapeutic target molecules for the development of novel anti-cancer drugs and immunotherapy in esophageal cancer treatment.
  • C Suzuki, Y Daigo, N Ishikawa, T Kato, S Hayama, T Ito, E Tsuchiya, Y Nakamura
    CANCER RESEARCH 65 (24) 11314 - 11325 0008-5472 2005/12 [Refereed][Not invited]
     
    Gene expression profile analysis of non-small cell lung cancers (NSCLC) and subsequent functional analyses revealed that human ANLN, a homologue of anillin, an actin-binding protein in Drosophila, was transactivated in lung cancer cells and seemed to play a significant role in pulmonary carcinogenesis. Induction of small interfering RNAs against ANLN in NSCLC cells suppressed its expression and resulted in growth suppression; moreover, treatment with small interfering RNA yielded cells with larger morphology and multiple nuclei, which subsequently died. On the other hand, induction of exogenous expression of ANLN enhanced the migrating ability of mammalian cells by interacting with RHOA, a small guanosine triphosphatase, and inducing actin stress fibers. Interestingly, inhibition of phosphoinositide 3-kinase/AKT activity in NSCLC cells decreased the stability of ANLN and caused a reduction of the nuclear ANLN level. Immunohistochemical staining of nuclear ANLN on lung cancer tissue microarrays was associated with the poor survival of NSCLC patients, indicating that this molecule might serve as a prognostic indicator. Our data imply that up-regulation of ANLN is a common feature of the carcinogenetic process in lung tissue, and suggests that selective suppression of ANLN could be a promising approach for developing a new strategy to treat lung cancers.
  • N Ishikawa, Y Daigo, A Takano, M Taniwaki, T Kato, S Hayama, H Murakami, Y Takeshima, K Inai, H Nishimura, E Tsuchiya, N Kohno, Y Nakamura
    CANCER RESEARCH 65 (20) 9176 - 9184 0008-5472 2005/10 [Refereed][Not invited]
     
    Serum levels of amphiregulin and transforming growth factor-alpha (TGF-alpha), which were identified previously to be expressed at high levels in non-small cell lung cancer (NSCLC) with poor response to gefitinib, were examined by ELISA using blood samples taken from 50 patients with advanced NSCLCs. Of 14 cases that revealed above the cutoff line for amphiregulin in serum, 12 responded poorly to gefitinib, whereas 18 of the 36 cases showing below the cutoff revealed partial response (PR) or stable disease (SD; P = 0.026). Thirteen of 15 patients who were positive for TGF-alpha responded poorly to gefitinib, whereas IS of the 35 patients with negative TGF-alpha levels turned out to be relatively good responders (P = 0.014). Of 22 patients with positive values for either or both markers, 19 were poor responders. On the other hand, among 28 patients negative for both markers, 17 were classified into the PR or SD groups (P = 0.001). Gefitinib-treated NSCLC patients whose serum amphiregulin or TGF-alpha was positive showed a poorer tumor-specific survival (P = 0.037 and 0.002, respectively, by univariate analysis) compared with those whose serum amphiregulin or TGF-alpha concentrations were negative. Multivariate analysis showed an independent association between positivity for TGF-alpha and shorter survival times among NSCLC patients treated with gefitinib (P = 0.034). Amphiregulin or TGF-alpha positivity in NSCLC tissues was significantly higher in male, nonadenocarcinomas, and smokers. Our data suggest that the status of amphiregulin and TGF-alpha in serum can be an important predictor of the resistance to gefitinib among patients with advanced NSCLC.
  • C Furukawa, Y Daigo, N Ishikawa, T Kato, T Ito, E Tsuchiya, S Sone, Y Nakamura
    CANCER RESEARCH 65 (16) 7102 - 7110 0008-5472 2005/08 [Refereed][Not invited]
     
    We investigated gene expression profiles of non-small cell lung carcinomas (NSCLC) to screen candidate molecules that might be useful as diagnostic markers or for development of novel molecular-targeting therapies. Here we report evidence that a member of the armadillo protein family, plakophilin 3 (PKP3), is a potential molecular target for treatment of lung cancers and might also serve as a prognostic indicator. We documented elevated expression of PKP3 in the great majority of NSCLC samples examined. Treatment of NSCLC cells with small interfering RNAs of PKP3 suppressed growth of the cancer cells; on the other hand, induction of exogenous expression of PKP3 conferred growth-promoting activity on COS-7 cells and enhanced their mobility in vitro. To investigate its function, we searched for PKP3-interacting proteins and identified dynamin I-like, which was also activated in NSCLC. In addition, a high level of PKP3 expression was associated with poor survival as well as disease stage and node status for patients with lung adenocarcinoma, suggesting an important role of the protein in development and progression of this disease. As our data imply that up-regulation of PKP3 is a frequent and important feature of lung carcinogenesis, we suggest that targeting the PKP3 molecule might hold promise for development of a new therapeutic and diagnostic strategy for clinical management of lung cancers.
  • T Kato, Y Daigo, S Hayama, N Ishikawa, T Yamabuki, T Ito, M Myamoto, S Kondo, Y Nakamura
    CANCER RESEARCH 65 (13) 5638 - 5646 0008-5472 2005/07 [Refereed][Not invited]
     
    An increased level of dihydrouridine in tRNA(Phe) was found in human malignant tissues nearly three decades ago, but its biological significance in carcinogenesis has remained unclear. Through analysis of genome-wide gene-expression profiles among non-small cell lung carcinomas (NSCLC), we identified overexpression of a novel human gene, termed hDUS2, encoding a protein that shared structural features with tRNA-dihydrouridine synthases (DUS). The deduced 493-amino-acid sequence showed 39% homology to the dihydrouridine synthase 2 enzyme (Dus2) of Saccharomycescerevisiae and contained a conserved double-strand RNA-binding motif (DSRM). We found that hDUS2 protein had tRNA-DUS activity and that it physically interacted with EPRS, a glutamyl-prolyl tRNA synthetase, and was likely to enhance translational efficiencies. A small interfering RNA against hDUS2 transfected into NSCLC cells suppressed expression of the gene, reduced the amount of dihydrouridine in tRNA molecules, and suppressed growth. Immunohistochemical analysis showed significant association between higher levels of hDUS2 in tumors and poorer prognosis of lung cancer patients. Our data imply that upregulation of hDUS2 is a relatively common feature of pulmonary carcinogenesis and that selective suppression of hDUS2 enzyme activity and/or inhibition of formation of the hDUS2-tRNA synthetase complex could be a promising therapeutic strategy for treatment of many lung cancers.
  • T Kato, M Miyamoto, K Kato, Y Cho, T Itoh, T Morikawa, S Okushiba, S Kondo, T Ohbuchi, H Katoh
    CANCER LETTERS 214 (1) 121 - 128 0304-3835 2004/10 [Refereed][Not invited]
     
    Caveolin-1 has been implicated in cellular transformation and tumorigenesis. We assessed lung cancer specimens for caveolin-1 expression immunohistochemistry. A majority of the cell types in the lung and the bronchial epithelium normally exhibited positive staining for caveolin-1. In adenocarcinomas (ADs) of positive staining for caveolin-1, pT1 tumors exhibited significantly higher staining than pT2-pT4 tumors (P=0.0240). In squamous cell carcinomas (SCCs), pT1-pT2 tumors expressed significantly lower expression levels than pT3-pT4 tumors (P=0.0175). In AD, loss of caveolin-1 may be essential for tumor extension and dedifferentiation. In contrast, caveolin-1 overexpression. may be correlated with tumor extension in SCC. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
  • T Kato, T Kojima, T Shimizu, H Sasaki, M Abe, S Okushiba, S Kondo, H Kato, H Sato
    SURGERY TODAY 32 (1) 81 - 85 0941-1291 2002 [Refereed][Not invited]
     
    We describe herein a case of inflammatory malignant fibrous histiocytoma (IMFH) of the gallbladder that subsequently metastasized to the ascending colon and later to the stomach. A 70-year-old Japanese man with a palpable mass in the right upper quadrant of the abdomen was referred to our hospital for investigation and treatment. Laboratory data showed severe leukocytosis and elevated serum granulocyte colony-stimulating factor (G-CSF) concentrations. A laparotomy was performed, and the tumor was excised en bloc with the gallbladder and part of the liver bed. Histopathologically, the tumor was composed of ordinary malignant fibrous histiocytoma (MFH) components characterized by pleomorphic tumor cells, bizarre giant cells, and conventional spindle cells in a storiform growth pattern, as well as a xanthogranulomatous component, including inflammatory cells, foamy histiocytes, and plasma cells. Immunohistochemical study revealed that the pleomorphic tumor cells and bizarre giant cells were positive for antibodies against alpha(1)-antitrypsin and alpha(1)-antichymotrypsin. The final pathologic diagnosis was IMFH. The tumor cells were diffusely positive for anti-G-CSF monoclonal antibody, and the inflammatory reaction subsided immediately after tumor resection, strongly suggesting that the primary tumor cells produced G-CSF. This patient is still alive with no signs of recurrence more than 3 years after his primary operation, which to our knowledge is the longest survival period ever reported. Therefore, visceral IMFH is manageable in some cases by resecting the primary and isolated metastatic lesions.
  • T Kato, H Kato, S Kondo, S Okushiba, T Morikawa
    SURGERY TODAY 32 (8) 727 - 730 0941-1291 2002 [Refereed][Not invited]
     
    We describe the case of a patient with gastric cancer complicated by portal hypertension due to liver cirrhosis. Endoscopy showed esophageal varices in the lower third of the esophagus and a superficially depressed lesion in the middle third of the stomach, while a biopsy suggested signet-ring cell carcinoma. Laboratory data showed pancytopenia. the indocyanine green fraction after 15 min was 29%, and the symptoms corresponded to the Child B criteria. A preoperative arteriogram revealed a remarkably dilated left gastric vein and the development of collateral pathways. We performed a distal subtotal gastrectomy with a reconstruction by the Billroth I method combined with a distal splenorenal shunt (DSRS) and a splenopancreatic disconnection (SPD). The endoscopic findings of the esophageal varices 15 months after surgery showed only a few white veins and the red color sign had disappeared. Now 7 years have passed since surgery, the risk of variceal hemorrhage has disappeared. and the patient is ambulatory and well. These results seems to be attributable to the long-term maintenance of the shunt selectivity and good portal hemodynamics. In patients with gastric cancer complicated with esophageal and/or gastric varices, it is recommended that DSRS with SPD be performed after a reconstruction using the Billroth I method.
  • T Kato, T Motohara, Y Kaneko, H Shikishima, S Okushiba, S Kondo, H Kato
    HEPATO-GASTROENTEROLOGY 48 (42) 1656 - 1658 0172-6390 2001/11 [Refereed][Not invited]
     
    We performed venous shunt procedure in the reconstruction of the esophagus after esophagectomy using the gastric tube in two cases of esophageal cancer with portal hypertension due to liver cirrhosis. In both cases, the short-term postoperative course was uneventful, without congestion in the gastric tube. In Case 1 where the short gastric vein had been used as the shunt vein, the long-term postoperative course was also uneventful, without hepatic encephalopathy or hemorrhage from deterioration of the varices of the gastric tube. However, in Case 2 where the left gastroepiploic vein had been used, hepatic encephalopathy developed due to excessive shunt flow. These results suggested that appropriate shunt flow could be expected by using short gastric vein.
  • HIRAOKA Kei, MORITA Takayuki, KATOH Tatsuya, SENMARU Naoto, MIYASAKA Yuji, FUJITA Miyoshi, KATOH Hiroyuki
    The journal of the Japanese Practical Surgeon Society Japan Surgical Association 61 (1) 204 - 208 1345-2843 2000/01/25 
    (Case 1) A 70-year-old man was admitted to our hospital because of abdominal distension. An abdominal computed tomography scan showed a large cystic mass of the stomach. The patient was diagnosed as having a submucosal tumor of the stomach and was operated on. (Case 2) A 59-year-old man was admitted to our hospital because of melena. An abdominal computed tomography scan and ultrasonography showed a mass of the small bowel. Partial resection of the jejunum was performed with a diagnosis of small-bowel tumor. During laparotomy in both cases, a large number of small nodules of peritoneum were noted. Histologically, and immunohistochemically, both of the tumors were diagnosed as gastrointestinal stromal tumors (GIST), uncommitted type, with peritoneal dissemination. The prognosis of GIST with unresectable peritoneal dissemination is poor, therefore, surgical resection should be done as soon as possible.
  • HIRAOKA Kei, MORITA Takayuki, FUJITA Miyoshi, MIYASAKA Yuji, SENMARU Naoto, KATOH Tatsuya, KATOH Hiroyuki
    The journal of the Japanese Practical Surgeon Society Japan Surgical Association 61 (3) 689 - 692 1345-2843 2000 
    A 59-year-old man was admitted to the hospital because of melena and dizziness. Barium X-ray study of the small intestine revealed a filling defect in the ileum. Partial resection of the ileum was performed with a diagnosis of ileal tumor. The tumor was 1.8×1.5×1.8cm in size, and located on a site, 60cm oral to the Bauhin's valve.
    Histopathological diagnosis was leiomyoblastoma. Thereafter the patient had liver metastasis and peritoneal dissemination which were resected respectively, however, he died of metastases to the whole body 4 years and 2 months after the initial operation. Leiomyoblastoma of the small intestine is relatively rare and presents difficulty in diagnosis of the degree of malignancy of the tumor. Surgical resection of the tumor is said to carry a good prognosis. Nevertheless, some patients have a poor prognosis like this case and careful observation of clinical course would be mandatary.
  • Tatsuya Kato, Tetsufumi Kojima, Tetsuya Shimizu, Syuji Kitashiro, Kazuya Konishi, Takumi Yamabuki, Shunichi Okushiba, Hiroyuki Kato, Hidetoshi Sato
    Japanese Journal of Gastroenterological Surgery 33 (8) 1529 - 1533 0386-9768 2000 [Refereed][Not invited]
     
    A 23-year-old woman, complaining of right lower abdominal pain and fever, was diagnosed as having typical acute appendicitis, and treated by laparoscopic appendectomy. The pathological diagnosis was acute on chronic appendicitis. However, slight fever, right lower abdominal pain, and elevation of serum CRP persisted postoperatively, and Crohn's disease was diagnosed based on the results of further investigation. Subsequently, because strictures of the ascending and transverse colon had been aggravated and ileac symptom was appeared, right hemicolectomy was performed and histopathological study of the resected specimen showed typical Crohn's disease features. A retrospective review of the appendiceal specimen revealed localized acute inflammation associated with a fissuring ulcer at the base of the appendix, and a non-caseous epithelioid cell granuloma with Langhans' giant cells in its deeper layer. Therefore, the appendicits was ultimately attributed to Crohn's disease. In the differential diagnosis of the causes of acute appendicitis, Crohn's disease should be considered as in this case. Furthermore, investigation of suspected Crohn's disease is important in patients with persistent fever, abdominal pain, and inflammatory reactions after appendectomy.
  • T Kato, T Morita, M Fujita, Y Miyasaka, S Horita, Y Watanabe, H Kato
    SURGERY TODAY-THE JAPANESE JOURNAL OF SURGERY 30 (2) 163 - 167 0941-1291 2000 [Refereed][Not invited]
     
    We report herein the case of a 69-year-old man with basaloid-squamous carcinoma (BSC) of the esophagus. To the best of our knowledge, this is the 60th case of BSC of the esophagus to be reported in Japan, and a review of the other 59 cases is presented after this case report. In our patient, endoscopic findings revealed a circumferential erosion in the middle intrathoracic esophagus (Im), and a protruding tumor with friable ulceration in the center of the erosion, A biopsy suggested that it was moderately differentiated squamous cell carcinoma (SCC), and a thoracoscopic total thoracic esophagectomy was performed. Histologically, the protruding-type lesion with ulceration was composed of BSC, and the circumferential 0 - I + IIc type lesion was composed of moderately differentiated SCC. The immunohistochemical findings of these resected specimens led us to suspect that the basal-layer-type SCC had transformed into BSC by undergoing differentiation and expansive proliferation.
  • T Kato, T Motohara, Y Kaneko, H Shikishima, T Takahashi, S Okushiba, S Kondo, H Kato
    JOURNAL OF SURGICAL ONCOLOGY 72 (1) 32 - 36 0022-4790 1999/09 [Refereed][Not invited]
     
    In a case of retroperitoneal dedifferentiated mixed-type liposarcoma, a dedifferentiated component was observed in the so-called mixed-type liposarcoma consisting of well-differentiated and myxoid components. The proliferative activity was compared among the different components of the tumor by immunohistochemical study using the proliferating cell nuclear antigen (PCNA) and MIB-1 monoclonal antibodies. The dedifferentiated component showed higher positivity than the well-differentiated and myxoid components, and tumor progression was most advanced in the dedifferentiated component. In the chronological examination of each component, the labeling indices of PCNA and MIB-1 were significantly higher at the third recurrence than in the primary lesion in all types, indicating that the proliferative activity of the tumor cells increased gradually. Considering the surgical treatment of liposarcoma, an extended resection encompassing normal adjacent tissues is required in cases containing the dedifferentiated component in comparison to the cases containing only well-differentiated or myxoid components. (C) 1999 Wiley-Liss, Inc.
  • T Kato, T Morita, M Fujita, Y Miyasaka, N Senmaru, K Hiraoka, S Horita, S Kondo, H Kato
    INTERNATIONAL JOURNAL OF PANCREATOLOGY 24 (3) 237 - 242 0169-4197 1998/12 [Refereed][Not invited]
     
    A 37-yr-old man underwent an open drainage operation for severe acute pancreatitis and received respiratory ventilation support for 4 mo because of respiratory failure based on disseminated intravascular coagulation (DIC) and septic shock. Under intensive care, he sometimes had bloody diarrhea for about 6 wk. Colonoscopic findings suggested that the bleeding had derived from the small intestine. The patient then gradually recovered from acute pancreatitis and was discharged from the hospital. Thereafter, he suffered relapses of ileus and his symptoms progressively worsened. The patient underwent a second operation about 2 yr after the onset of acute pancreatitis. At celiotomy, multiple stenoses of the distal ileum measuring about 60 cm in length were found and the segment was resected. The resected specimen demonstrated six separate circumferential strictures and shallow ulcerations. Histologically, multiple ulcerations were restricted to the mucosa and were accompanied by marked submucosal edema and fibrosis. The mucosa between the ulcers revealed chronic regenerative changes: intimal thickening of small mesenteric arteries causing luminal narrowing and organized thrombosis in small mesenteric veins. Therefore, these were considered to be a series of segmental ischemic lesions. Note that delayed ischemic stricture of the small intestine may occur as a chronic complication of acute pancreatitis.
  • 平岡 圭, 加藤 達哉, 樋田 泰浩, 宮坂 祐司, 藤田 美芳, 森田 高行, 加藤 紘之
    北海道外科雑誌 北海道外科学会 42 (2) 281 - 281 0288-7509 1997/12 [Refereed][Not invited]

MISC

Association Memberships

  • THE JAPAN LUNG CANCER SOCIETY   JAPAN SURGICAL ASSOCIATION   THE JAPAN SOCIETY FOR TRANSPLANTATION   The Japanese Association for Chest Surgery   JAPAN SURGICAL SOCIETY   

Research Projects

  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research
    Date (from‐to) : 2024/04 -2029/03 
    Author : 田中 伸哉, 津田 真寿美, 黒川 孝幸, 丸山 玲緒, 加藤 達哉
  • 日本学術振興会:科学研究費助成事業
    Date (from‐to) : 2022/01 -2024/03 
    Author : 新垣 雅人, 加藤 達哉, 海老原 裕磨, 櫻井 遊, 樋田 泰浩, 加賀 基知三
     
    5-ALAの含め複数のポルフィリンを主体としたphotosensityzerを使用し、マウスxenograftモデルでの腫瘍集積性を検討した。使用細胞株はヒト肺腺癌細胞株であるA549と扁平上皮癌細胞株であるH2170、またマウス悪性胸膜中脾腫細胞株であるAE17OVAを使用した。投与濃度と投与から解析までの時間を比較検討し、蛍光強度を解析し、至適投与濃度、至適観察時間を確認した。5ALAも含め複数photosensityzerを投与後にマウスxenograftモデルに投与し、生体内のphotosensityzerの他臓器への集積を蛍光強度にて解析した。photosensityzer投与後のマウスxenograftを使用し、腫瘍摘出後に正常ブタ肺の胸膜直下に留置し、正常肺越しに蛍光を確認できるか確認したところ、maestroを使用し確認したところ,5ALAにおいてはblue light excitationによって励起される蛍光は非常に浅い位置に腫瘍を留置した場合でも観察されなかった。現在red light excitationを使用し、蛍光が観察される条件を検討している。比較対象として使用している他のphotosensityzerは671nmのexcitaion lightにて励起されるため、胸膜下の腫瘍からの蛍光が確認できた。 並行してrabbit悪性腫瘍株であるVX2を使用し、rabbit orthotopic modelを作成中である同モデルを使用し、5ALAと他のphotosensityzerの集積性、径胸膜的な蛍光の観察が可能かどうか検討予定である。
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research
    Date (from‐to) : 2021/04 -2024/03 
    Author : 加藤 達哉, 櫻井 遊, 畑中 佳奈子, 小川 美香子, 樋田 泰浩, 畑中 豊
     
    本研究はMUC1がん特異的糖鎖抗原のみを選択的に認識する新規モノクローナル抗体(MUC1-Tn抗体)と光感受性物質であるIR700との結合体を用いて、がん細胞のみを特異的に攻撃する新たな治療法を確立し、新規の肺がん治療法の開発を目指すものである。 今年度は、まず本研究の肝となるMUC1-Tn抗体の供給源である㈱医化学創薬と共同で研究をすすめ、MTAを締結し、本実験で想定される抗体量の確保に努め、動物実験まで含めた十分量の抗体を得ることに成功した。 さらに今年度は、研究実施計画に則り、まず今後in vitro実験およびin vivo実験に用いる予定のMUC1-Tn高発現の細胞株の選定を行った。乳癌細胞株であるT47DがMUC1-Tnが高発現していることが判明したが、その後21個の肺癌細胞株のセルブロックを作成し、抗MUC1-Tn抗体を用いて免疫染色を行った。うち2株(RERF-LC-KJ, H2228)に高発現が認められ、今後、in vitroおよびin vivo実験に使用可能と判断した。その他、陰性コントロールとしての細胞株も複数選定した。 また、実験遂行者はすでにIR700と抗MUC1-Tn抗体を合成する技術を習得しており、予備実験として、MUC1-Tn抗体とIR700の結合体を作成し、T47Dに導入後、FACSにて細胞膜表面に抗体が結合していることを確認した。また、タイムラプス顕微鏡でレーザー照射により導入細胞で細胞膜よりブレブが隆起し、細胞死に至ることを確認することができた。したがって今後肺癌細胞株を用いた本実験を開始できる状況にある。
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research
    Date (from‐to) : 2021/04 -2024/03 
    Author : 畑中 豊, 加藤 達哉, 小川 美香子, 畑中 佳奈子
     
    がん微小環境において,低酸素状態下ではATPからAMPを介しアデノシンを生成する CD39/CD73カスケード分子の発現が誘導され,さらにアデノシンはリンパ球上のA2受容体を介して免疫抑制状態を誘導することから,免疫チェックポイント阻害(ICI)療法に対し抵抗性を示す. 本研究は,先行研究として実施した非小細胞肺癌(NSCLC)の一部でCD73発現が亢進し,またPD-L1発現と相関する点に着目し,(a) NSCLC組織検体を用いたCD73およびPD-L1発現と腫瘍微小環境との関連性について検討し,次いで(b) ヒトおよびマウス肺癌細胞株を用いたCD73-IR700-Cのがん細胞への集積確認と治療効果のin vitro評価,および(c) ヒトおよびマウス肺癌細胞株の移植腫瘍モデルを用いたCD73抗体-IR700結合体(CD73-IR700-C)の腫瘍集積性の確認および近赤外線免疫療法(NIR-PIT)の抗腫瘍効果のin vivo評価を行う. 本年度は以下の課題に取り組んだ.肺扁平上皮癌症例を用いた組織マイクロアレイ(TMA)標本123例を用いた低酸素関連タンパクの臨床病理学的検討:CD73,PD-L1およびHIF-1a発現について検討したところ,先行研究同様,CD73とPD-L1発現間に有意な関連性(p=0.019)が認められ,またCD73とHIF-1a発現間にも関連傾向(p=0.0548)が観察された.これら3分子の生存解析においては,低発現群に比べ高発現群で,それぞれ有意な無再発生存期間(RFS)の短縮が認められ,さらにCD73高発現/HIF-1a高発現群ではさらに短縮した(p=0.0187).
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research
    Date (from‐to) : 2017/08 -2019/03 
    Author : Kato Tatsuya
     
    Photodynamic therapy (PDT) irradiates a photosensitizer that accumulates in cancer cells with laser light and causes degenerative necrosis of the tumor by the oxidative action of reactive oxygen species. The purpose of this study was to encapsulate the photosensitizer talaporfin (NPe6) in nanoparticles and to reach the deep part of the tumor with high concentration of NPe6. This novel nanoparticle was observed with an electron microscope to observe the structure of the nanoparticle and to confirm the particle size. Flow cytometry and fluorescence microscopic analyses using lung cancer and mesothelioma cell lines showed that nanoparticle with encapsulated NPe6 enhanced the uptake into cancer cells significantly. It was also confirmed that the uptake was enhanced by adding folic acid as a ligand.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research
    Date (from‐to) : 2012/04 -2016/03 
    Author : Hida Yasuhiro, KAGA KICHIZO, MATSUI YOSHIRO
     
    Tumor endothelial cells (TEC) from mouse xenografted tumor, especially that from highly metastatic tumor expresses high level of biglycan. Knock down of biglycan by siRNA suppressed tumor cell invasion thorough endothelial cell sheet. Co-implantation of low metastatic tumor cells with TEC developed lung metastases. This metastatic ability was abandoned by suppression of biglycan expression in TEC. Immunohistochemistry of human clinical tumors revealed specific expression of biglycan in TEC. ELISA of serum showed high biglycan level in cancer patients, especially those with metastasis.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research
    Date (from‐to) : 2012/04 -2014/03 
    Author : HIDA Yasuhiro, KAGA Kichizou, MATSUI Yoshirou, KATOH Tatsuya, HIDA Kyoko
     
    We hypothesized that tumor-associated endothelial cells (TEC) facilitate tumor metastasis. We established TEC from xenograft tumor of the low metastatic malignant melanoma cell , A375 and from that of high metastatic counter part, A375SM("super metasitatic"). Comparison of those 2 TEC revealed specific up regulation of some microRNA in A375SM TEC. Transfection of the microRNA change the phenotype of normal endothelial cells from normal skin to that of A375SM TEC.
  • 日本学術振興会:科学研究費助成事業
    Date (from‐to) : 2012 -2012 
    Author : 加藤 達哉, 樋田 泰浩, 樋田 京子, 加賀 基知三, 松居 喜郎
     
    我々は、癌幹細胞に特化した「分泌型miRNA」に着目し、「非小細胞肺癌幹細胞における分泌型miRNAの同定とその治療応用へ向けての解析」というテーマで平成24年4月より研究を開始した。まず非小細胞肺癌における癌幹細胞の最も良いsorting方法を検討するため種々の方法を試みたが、中でも我々はsphere形成能を持つ癌細胞がマウス皮下腫瘍形成能を高率に有することに着目した。まず肺癌細胞株を用いてsphere形成能を持つ肺癌幹細胞の培養条件検討を行い、足場非依存性のためにpolyHEMA coatedを使用し、またserum-free、EGF+bFGF+ITS premixの培養液を用いて限界希釈を行ったのち培養を継続することで、同細胞群は約1ヶ月に渡りsphere形成能を維持したまま生育することを見出した。次に培養上清中の癌幹細胞における特異的な分泌型miRNAの検索として、マイクロアレイによる解析を行う方針とした。先に述べたsphere形成能を有する細胞群の培養上清と通常の肺癌細胞培養上清におけるmiRNA発現プロファイルを比較検討するため、両群の培養上清よりキットを用いてmiRNAの抽出を行った。細胞株レベルで条件検討が終了し、実際の臨床検体において同様の研究を開始する予定で倫理申請まで行っていたが、筆頭研究者である加藤達哉が海外へ留学することとなり、今回やむなく研究中止の申請をするに至った。


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