2008年10月, 日本癌学会, 奨励賞　　　　　　　　　　　　　　　
加藤達哉

先天性嚢胞性肺疾患に対するReduced port VATSの取り組み　　　　　　　　　　　　　　　
藤原 晶, 高桑 佑佳, 佐々木 明洋, 椎谷 洋彦, 大高 和人, 氏家 秀樹, 新垣 雅人, 本多 昌平, 川原 仁守, 加藤 達哉
日本気胸・嚢胞性肺疾患学会雑誌, 24, 2, 86, 86, 日本気胸・嚢胞性肺疾患学会, 2024年08月
日本語

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, 59, 1, 88, 88, (一社)日本移植学会, 2024年07月
日本語

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, 59, 1, 101, 101, (一社)日本移植学会, 2024年07月
日本語

Epithelioid pleural mesothelioma successfully treated with perioperative immunotherapy: a case report.
Gaku Yamazaki, Aki Fujiwara-Kuroda, Jun Muto, Hideki Ujiie, Masato Aragaki, Megumi Furuta, Sakurako Ohno, Kanako C Hatanaka, Yutaka Hatanaka, Yoshihiro Matsuno, Tatsuya Kato
General Thoracic and Cardiovascular Surgery Cases, 3, 1, 31, 31, 2024年06月11日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Pleural mesothelioma, characterized by a dismal prognosis even with multimodal therapy, has seen emerging interest in immune checkpoint inhibitors (ICIs) due to their demonstrated efficacy. Here, we present a case of epithelioid-type pleural mesothelioma with chest wall invasion treated with definitive ICI therapy, resulting in a remarkable pretreatment effect. CASE PRESENTATION: A 46-year-old man was diagnosed with an abnormal chest shadow on a medical check, and a computed tomography scan showed pleural thickening at the dorsal right upper chest wall. One of the nodules was suspected to have invaded the chest wall. A needle biopsy revealed epithelioid-type pleural mesothelioma. After five cycles of nivolumab plus ipilimumab, he underwent right pleurectomy/decortication (P/D). Pathological examination revealed a significant treatment effect, showing numerous lymphocytes infiltrating the tumor nodule and viable tumor cells localized at approximately 6 mm. CONCLUSION: Although further accumulation of cases is required to evaluate the effectiveness and case selection, P/D after immunotherapy is a useful curative treatment option for advanced pleural mesothelioma.

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, 98, 6, S1566, S1566, (公社)日本整形外科学会, 2024年06月
日本語

Impact of pulmonary vein-first ligation during lobectomy on the postoperative survival and recurrence rates in patients with non-small cell lung cancer: a multicenter propensity score-matched study.
Haruhiko Shiiya, Hideki Ujiie, Ryohei Chiba, Shunsuke Nomura, Kazuto Ohtaka, Aki Fujiwara-Kuroda, Masato Aragaki, Keita Takahashi, Kazufumi Okada, Tatsuya Kato
Surgery today, 2024年05月30日, ［国内誌］
英語, 研究論文（学術雑誌）, 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.

Dose Optimization of Intravenous Indocyanine Green for Malignant Lung Tumor Localization
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, MDPI AG, 2024年05月10日
研究論文（学術雑誌）, 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.

低侵襲手術の未来像 Reduced port Robot-assisted thoracic surgery(RATS)の未来
氏家 秀樹, 大塚 将平, 佐々木 明洋, 山崎 洋, 椎谷 洋彦, 大高 和人, 藤原 晶, 新垣 雅人, 江花 弘基, 加藤 達哉
気管支学, 46, Suppl., S171, S171, (一社)日本呼吸器内視鏡学会, 2024年05月
日本語

A simple and safe surgical technique for nonpalpable lung tumors: One-stop Solution for a nonpalpable lung tumor, Marking, Resection, and Confirmation of the surgical margin in a Hybrid operating room (OS-MRCH).
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年03月29日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 113, 1, 362, 362, (一社)日本病理学会, 2024年02月
日本語

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, 42, Suppl., 4, 4, (公社)日本医学放射線学会, 2024年02月
日本語

肺孤立性毛細血管腫の2症例
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, 64, 1, 58, 58, (NPO)日本肺癌学会, 2024年02月
日本語

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, 113, 1, 362, 362, (一社)日本病理学会, 2024年02月
日本語

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, 42, Suppl., 4, 4, (公社)日本医学放射線学会, 2024年02月
日本語

Developing a Virtual Reality Simulation System for Preoperative Planning of Robotic-Assisted Thoracic Surgery
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年01月21日
研究論文（学術雑誌）

薄壁空洞性病変を呈した原発性肺扁平上皮内癌の1例
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, 45, 6, 443, 443, (一社)日本呼吸器内視鏡学会, 2023年11月
日本語

Tumor-to-thoracic height ratio as an easy method to predict the feasibility of reduced-port video-assisted thoracic surgery for mediastinal lesions in children: a single-center experience.
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年09月28日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, BioMed Central, 2023年08月
英語

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, 23, 2, 90, 90, 日本気胸・嚢胞性肺疾患学会, 2023年08月
日本語

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, 23, 2, 90, 90, 日本気胸・嚢胞性肺疾患学会, 2023年08月
日本語

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, 37, 3, O39, 6, (一社)日本呼吸器外科学会, 2023年06月
日本語

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, 37, 3, O52, 3, (一社)日本呼吸器外科学会, 2023年06月
日本語

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, 37, 3, O59, 2, (一社)日本呼吸器外科学会, 2023年06月
日本語

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, 37, 3, O73, 5, (一社)日本呼吸器外科学会, 2023年06月
日本語

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, 37, 3, P42, 1, (一社)日本呼吸器外科学会, 2023年06月
日本語

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, 37, 3, P68, 7, (一社)日本呼吸器外科学会, 2023年06月
日本語

High density and proximity of CD8+ T cells to tumor cells are correlated with better response to nivolumab treatment in metastatic pleural mesothelioma.
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年05月30日, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Invasive thymoma metastases to the pancreas: A case report.
Shinya Otsuka, Kei Hiraoka, Noriko Kimura, Satoshi Hirano, Tatsuya Kato, Masato Suzuoki
International journal of surgery case reports, 105, 108004, 108004, 2023年04月, ［国際誌］
英語, INTRODUCTION AND IMPORTANCE: Thymoma is the most common type of tumor that develops in the thymic epithelial cells. Although thymomas can invade surrounding organs in the chest cavity, extrathoracic metastasis is very rare, and little is known about the prognosis and effective treatments for such tumors. Herein, we report a case of an invasive thymoma metastasizing to the pancreas after incomplete resection. CASE PRESENTATION: A 47-year-old man presented to our hospital with an anterior mediastinal mass. Although a thymic tumor was suspected, complete resection was not achieved because the tumor had invaded the pulmonary artery trunk, superior pulmonary vein, and left brachiocephalic vein. The pathological diagnosis was a Type B3 thymoma. The patient underwent chemotherapy and radiotherapy after surgery. Three years after surgery, computed tomography indicated a pancreatic mass suggestive of pancreatic cancer. Distal pancreatectomy was performed after neoadjuvant chemotherapy and radiotherapy. The pancreatic mass was diagnosed as Type B3 thymoma metastasis. Thirteen months after surgery for the pancreatic lesion, the patient underwent resection of the bilateral lung metastases. CLINICAL DISCUSSION: To the best of our knowledge, only four cases of metastatic thymic tumors in the pancreas have been reported. All patients who underwent surgical resection for pancreatic metastasis survived for >6 months including our case. CONCLUSION: In cases of thymic tumors with metastasis to extra-thoracic organs, complete resection of the metastatic lesions can contribute to prolonged survival.

10℃保存により24時間の全肺虚血時間においても良好な経過をとった両側肺葉移植の一例
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, 57, 4, 396, 396, (一社)日本移植学会, 2023年04月
日本語

A novel edge-marking method in pleural covering with video-assisted thoracic surgery.
Aki Fujiwara-Kuroda, Yasuhiro Hida, Hideki Ujiie, Kichizo Kaga, Tatsuya Kato
Interdisciplinary cardiovascular and thoracic surgery, 36, 3, 2023年03月02日, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 7回, O, 3, 日本メディカルイラストレーション学会, 2023年03月
日本語

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, 3, 28, 32, (NPO)メディカルイメージラボ, 2023年03月
日本語, 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)

Repeated photodynamic therapy mediates the abscopal effect through multiple innate and adaptive immune responses with and without immune checkpoint therapy.
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年01月, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 83, 12, 2119, 2119, 日本臨床外科学会, 2022年12月
日本語

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, 4, 1, 12, 12, 日本メディカルイラストレーション学会, 2022年12月
日本語

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, 4, 1, 12, 12, 日本メディカルイラストレーション学会, 2022年12月
日本語

胸・腹腔鏡併用下に横隔膜縫縮術を施行した食道癌術後横隔膜弛緩症の1例
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, 44, 6, 457, 457, (NPO)日本呼吸器内視鏡学会, 2022年11月
日本語

胸・腹腔鏡併用下に横隔膜縫縮術を施行した食道癌術後横隔膜弛緩症の1例
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, 44, 6, 457, 457, (NPO)日本呼吸器内視鏡学会, 2022年11月
日本語

Optimization of thrombolytic dose for treatment of pulmonary emboli using endobronchial ultrasound-guided transbronchial needle injection.
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年09月14日, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Parietal pleural small holes found in patients with primary spontaneous pneumothorax associated with relatively mild chest wall flatness: a retrospective study.
Haruhiko Shiiya, Akihiko Tanaka, Motoki Sakuraba, Hideki Ujiie, Tatsuya Kato
Journal of thoracic disease, 14, 9, 3255, 3264, 2022年09月, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

A case report of video-assisted flap bronchoplasty for central type typical carcinoid
Yuya Wada, Hideki Ujiie, Ryohei Chiba, Shunsuke Nomura, Aki Fujiwara-Kuroda, Kichizo Kaga, Satoru Wakasa, Tatsuya Kato
VIDEO-ASSISTED THORACIC SURGERY, AME PUBLISHING COMPANY, 2022年08月
英語, 研究論文（学術雑誌）, 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, 22, 2, 94, 94, 日本気胸・嚢胞性肺疾患学会, 2022年08月
日本語

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, 22, 2, 107, 107, 日本気胸・嚢胞性肺疾患学会, 2022年08月
日本語

A novel system for analyzing indocyanine green (ICG) fluorescence spectra enables deeper lung tumor localization during thoracoscopic surgery.
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年08月, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

気管支充填術および持続陰圧吸引療法が有効であった有瘻性膿胸の一例
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, 13, 1, 58, 58, (NPO)小切開・鏡視外科学会, 2022年06月
日本語

気管支充填術および持続陰圧吸引療法が有効であった有瘻性膿胸の一例
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, 13, 1, 58, 58, (NPO)小切開・鏡視外科学会, 2022年06月
日本語

Presurgical assessment of flow variability in an azygos vein aneurysm using 4D-flow MRI.
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年04月06日, ［国内誌］
英語, 研究論文（学術雑誌）, 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, 122回, SF, 5, (一社)日本外科学会, 2022年04月
日本語

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, 122回, SF, 5, (一社)日本外科学会, 2022年04月
日本語

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, 122回, SF, 3, (一社)日本外科学会, 2022年04月
日本語

Elective Uniportal Video-Assisted Thoracoscopic Lobectomy for Congenital Cystic Lung Disease in a 2-Year-Old Child Using One-Lung Ventilation
Haruhiko Shiiya, Hideki Ujiie, Tatsuya Kato, Shohei Honda, Satoru Wakasa, Kichizo Kaga
INDIAN JOURNAL OF SURGERY, SPRINGER INDIA, 2022年04月
英語, 研究論文（学術雑誌）, 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.

Antibody responses induced by the BNT162b2 mRNA COVID-19 vaccine in healthcare workers in a single community hospital in Japan.
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年04月, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 6回, np20, np21, 日本メディカルイラストレーション学会, 2022年03月
日本語

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, 83, 3, 598, 598, 日本臨床外科学会, 2022年03月
日本語

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, 6回, np20, np21, 日本メディカルイラストレーション学会, 2022年03月
日本語

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, 83, 3, 598, 598, 日本臨床外科学会, 2022年03月
日本語

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, 62, 1, 72, 73, (NPO)日本肺癌学会, 2022年02月
日本語

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, 62, 1, 72, 73, (NPO)日本肺癌学会, 2022年02月
日本語

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, 26, 7, WS32, 3, (一社)日本内視鏡外科学会, 2021年12月
日本語

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, 26, 7, WS32, 3, (一社)日本内視鏡外科学会, 2021年12月
日本語

有瘻性膿胸に対し気管支充填術と持続陰圧吸引療法を併用した2症例
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, 43, 6, 689, 689, (NPO)日本呼吸器内視鏡学会, 2021年11月
日本語

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, 74回, SP5, 3, (一社)日本胸部外科学会, 2021年10月
日本語

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, 74回, LOD19, 5, (一社)日本胸部外科学会, 2021年10月
日本語

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, 61, 6, 613, 613, (NPO)日本肺癌学会, 2021年10月
日本語

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, 61, 6, 613, 613, (NPO)日本肺癌学会, 2021年10月
日本語

Surgical treatment for tracheal stent prolapse in a patient with blunt tracheal trauma.
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年09月28日, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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.

Elevated serum CYFRA 21-1 level as a diagnostic marker for thymic carcinoma.
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年09月27日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Intralobar pulmonary sequestration associated with left main coronary artery obstruction and mitral regurgitation.
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年09月21日, ［査読有り］, ［責任著者］, ［国内誌］
英語, 研究論文（学術雑誌）, 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.

A Novel Treatment of Widespread Empyema Necessitatis.
Shinya Otsuka, Hideki Ujiie, Kosuke Ishikawa, Takahiro Miura, Satoru Wakasa, Tatsuya Kato
The Annals of thoracic surgery, 112, 6, e471, 2021年09月04日, ［査読有り］, ［責任著者］, ［国際誌］
英語, 研究論文（学術雑誌）

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, 21, 2, 113, 113, 日本気胸・嚢胞性肺疾患学会, 2021年09月
日本語

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, 56, 総会臨時, P2, 7, (一社)日本移植学会, 2021年09月
日本語

Thymoma-Related Stiff-Person Syndrome with Successfully Treated by Surgery.
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年07月16日, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, 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.

Rare Diagnosis of a Multilobular Pulmonary Mass.
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年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Prediction of Pulmonary Embolism Following Resection of Pulmonary Infarction: A Case Series.
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年05月14日, ［査読有り］, ［責任著者］, ［国内誌］
英語, 研究論文（学術雑誌）, 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, 35, 3, SP2, 3, (NPO)日本呼吸器外科学会, 2021年05月
日本語

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, 35, 3, SP4, 6, (NPO)日本呼吸器外科学会, 2021年05月
日本語

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, 35, 3, PD1, 5, (NPO)日本呼吸器外科学会, 2021年05月
日本語

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, 35, 3, O14, 3, (NPO)日本呼吸器外科学会, 2021年05月
日本語

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, 35, 3, MO16, 5, (NPO)日本呼吸器外科学会, 2021年05月
日本語

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, 35, 3, MO54, 4, (NPO)日本呼吸器外科学会, 2021年05月
日本語

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, 35, 3, MO16, 5, (NPO)日本呼吸器外科学会, 2021年05月
日本語

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, 35, 3, MO54, 4, (NPO)日本呼吸器外科学会, 2021年05月
日本語

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, 35, 3, SP2, 3, (NPO)日本呼吸器外科学会, 2021年05月
日本語

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, 35, 3, SP4, 6, (NPO)日本呼吸器外科学会, 2021年05月
日本語

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, 35, 3, PD1, 5, (NPO)日本呼吸器外科学会, 2021年05月
日本語

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, 35, 3, O14, 3, (NPO)日本呼吸器外科学会, 2021年05月
日本語

Feasibility of limited resection for peripheral small-sized non-small cell lung cancer: a retrospective single-center-based study.
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年05月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 121回, SF, 2, (一社)日本外科学会, 2021年04月
日本語

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, 121回, SF, 2, (一社)日本外科学会, 2021年04月
日本語

Pneumatosis Intestinalis After Living Donor Lung Transplantation Associated With Alpha-Glucosidase Inhibitor Treatment: A Case Report.
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年03月09日, ［査読有り］, ［責任著者］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, (一社)日本内視鏡外科学会, 2021年03月
英語

肺メディカルコンサルタント業務の肺移植外科医以外への委嘱の展望
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, 55, 4, 504, 504, (一社)日本移植学会, 2021年03月
日本語

A novel Tn antigen epitope-recognizing antibody for MUC1 predicts clinical outcome in patients with primary lung adenocarcinoma.
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年03月, ［査読有り］, ［筆頭著者, 責任著者］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

血気胸を発症したPleuroparenchymal fibroelastosis(PPFE)合併肺癌の1切除例
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, 61, 1, 67, 67, (NPO)日本肺癌学会, 2021年02月
日本語

神経線維腫症I型に肺腺癌、内頸動静脈瘻を合併した1例
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, 61, 1, 67, 68, (NPO)日本肺癌学会, 2021年02月
日本語

血気胸を発症したPleuroparenchymal fibroelastosis(PPFE)合併肺癌の1切除例
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, 61, 1, 67, 67, (NPO)日本肺癌学会, 2021年02月
日本語

神経線維腫症I型に肺腺癌、内頸動静脈瘻を合併した1例
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, 61, 1, 67, 68, (NPO)日本肺癌学会, 2021年02月
日本語

Intraoperative real-time hemodynamics in intralobar pulmonary sequestration using indocyanine green and near-infrared thoracoscopy.
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年02月, ［査読有り］, ［責任著者］, ［国内誌］
英語, 研究論文（学術雑誌）, 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.

Developing a virtual reality simulation system for preoperative planning of thoracoscopic thoracic surgery.
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年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Primary pulmonary lymphoepithelioma-like carcinoma with positive expression of Epstein-Barr virus and PD-L1: A case report.
Akihiro Sasaki, Tatsuya Kato, Hideki Ujiie, Yasushi Cho, Masaaki Sato, Mitsuhito Kaji
International journal of surgery case reports, 79, 431, 435, 2021年02月, ［査読有り］, ［責任著者］, ［国際誌］
英語, 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.

Successful lung transplantation from lungs procured 12 hours after withdrawal of life-sustaining therapy: Changing the paradigm of controlled DCD donors?
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年01月23日, ［査読有り］, ［筆頭著者］, ［国際共著］, ［国際誌］
英語

降下性壊死性縦隔炎に対する大動脈弓部トンネリングによる左上縦隔ドレナージ
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, 17, 5, 482, 482, (一社)日本外科感染症学会, 2020年10月
日本語

肺移植患者における超音波気管支鏡の安全性および有効性の検討
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, 55, 総会臨時, 383, 383, (一社)日本移植学会, 2020年10月
日本語

巨大粘液栓を伴った肺粘表皮癌の1例
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, 42, 5, 441, 447, (NPO)日本呼吸器内視鏡学会, 2020年09月
日本語, 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)

Preoperative identification of clinicopathological prognostic factors for relapse-free survival in clinical N1 non-small cell lung cancer: a retrospective single center-based study.
Masato Aragaki, Tatsuya Kato, Aki Fujiwara-Kuroda, Yasuhiro Hida, Kichizo Kaga, Satoru Wakasa
Journal of cardiothoracic surgery, 15, 1, 229, 229, 2020年08月28日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, (一社)日本呼吸器外科学会, 2020年08月
英語

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, (一社)日本呼吸器外科学会, 2020年08月
英語

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, 120回, DP, 3, (一社)日本外科学会, 2020年08月
日本語

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, (NPO)日本呼吸器外科学会, 2020年08月
英語

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, (NPO)日本呼吸器外科学会, 2020年08月
英語

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, 34, 3, SP3, 3, (NPO)日本呼吸器外科学会, 2020年08月
日本語

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, 34, 3, RO10, 7, (NPO)日本呼吸器外科学会, 2020年08月
日本語

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, 34, 3, O36, 5, (NPO)日本呼吸器外科学会, 2020年08月
日本語

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, 34, 3, MO2, 1, (NPO)日本呼吸器外科学会, 2020年08月
日本語

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, 34, 3, MO26, 5, (NPO)日本呼吸器外科学会, 2020年08月
日本語

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, 34, 3, MO27, 2, (NPO)日本呼吸器外科学会, 2020年08月
日本語

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, 34, 3, MO60, 9, (NPO)日本呼吸器外科学会, 2020年08月
日本語

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, 34, 3, MO64, 4, (NPO)日本呼吸器外科学会, 2020年08月
日本語

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, 20, 1, 69, 69, 日本気胸・嚢胞性肺疾患学会, 2020年08月
日本語

A Novel Insertion Technique for the Extra-Long Montgomery T-Tube in Patients with a Large Mediastinal Tumor.
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年08月01日, ［査読有り］, ［筆頭著者, 責任著者］, ［国内誌］
英語, 研究論文（学術雑誌）, 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.

智と技の伝承(鏡視外科手術トレーニングの将来像) ドライラボ、カダバーを用いた単孔式胸腔鏡手術(Uniportal VATS)トレーニングの経験
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, 11, 1, 38, 38, (NPO)小切開・鏡視外科学会, 2020年06月
日本語

先天性肺嚢胞性疾患に対する胸腔鏡手術の適応と成績
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, 11, 1, 50, 50, (NPO)小切開・鏡視外科学会, 2020年06月
日本語

胸腔鏡下手術における下位肋間経路による新しい切除肺の創外摘出法(eXtraction of resecting specimens through the Lower INterCostal route(XLINC) method、XLINC)について
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, 11, 1, 58, 58, (NPO)小切開・鏡視外科学会, 2020年06月
日本語

大網弁の積極利用による膿胸の治療と予防
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, 42, Suppl., S179, S179, (NPO)日本呼吸器内視鏡学会, 2020年06月
日本語

【小児の先天性嚢胞性肺疾患に対する胸腔鏡手術】
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, 65, 1, 2, 7, 北海道外科学会, 2020年06月
日本語, 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)

Endobronchial ultrasound-guided radiofrequency ablation of lung tumors and mediastinal lymph nodes: a preclinical study in animal lung tumor and mediastinal adenopathy models.
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年02月10日, ［査読有り］, ［国際誌］
英語, 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.

Changes in cerebral oxygen saturation during one-lung ventilation determined using spatially resolved spectroscopy and contributing factors.
Nobuhiro Tanaka, Ryoko Ito Katoh, Masataka Yamamoto, Koji Hoshino, Yuji Morimoto, Yoichi M Ito, Tatsuya Kato
Journal of clinical anesthesia, 59, 99, 100, 2020年02月, ［査読有り］, ［国際誌］
英語

A novel approach for the complete extraction of large tumours in video-assisted thoracoscopic surgery.
Masato Aragaki, Kichizo Kaga, Yasuhiro Hida, Tatsuya Kato, Yoshiro Matsui
Journal of minimal access surgery, 2020年01月28日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

肺移植患者における超音波気管支鏡の安全性および有効性の検討
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, 55, Supplement, 383_2, 383_2, 一般社団法人 日本移植学会, 2020年
日本語, 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, 24, 7, SY16, 1, (一社)日本内視鏡外科学会, 2019年12月
日本語

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, 24, 7, WS25, 3, (一社)日本内視鏡外科学会, 2019年12月
日本語

北海道「地域」肺メディカルコンサルタントと脳死ドナーあたりの肺臓提供数の推移
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, 54, 総会臨時, 211, 211, (一社)日本移植学会, 2019年09月
日本語

Feasibility and safety of reduced-port video-assisted thoracoscopic surgery using a needle scope for pulmonary lobectomy- retrospective study.
Masato Aragaki, Kichizo Kaga, Yasuhiro Hida, Tatsuya Kato, Yoshiro Matsui
Annals of medicine and surgery (2012), 45, 70, 74, 2019年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Lung cancer photothermal ablation by low-power near-infrared laser and topical injection of indocyanine green.
Hirohashi K, Anayama T, Wada H, Nakajima T, Kato T, Keshavjee S, Orihashi K, Yasufuku K
Interactive cardiovascular and thoracic surgery, 2019年07月, ［査読有り］, ［国際共著］, ［国際誌］

Downregulated expression of human leukocyte antigen class I heavy chain is associated with poor prognosis in non-small-cell lung cancer.
Kazuomi Ichinokawa, Yoshitsugu Nakanishi, Yasuhiro Hida, Takahiro Tsuchikawa, Tatsuya Kato, Tomoo Itoh, Mitsuhito Kaji, Kichizo Kaga, Satoshi Hirano
Oncology letters, 18, 1, 117, 126, 2019年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

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
小切開・鏡視外科学会雑誌, 10, 1, 54, 54, (NPO)小切開・鏡視外科学会, 2019年06月
日本語

肺移植未認定施設における肺移植トレーニングプログラムの有用性の検討 北海道での肺移植施設認定への取り組み
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, 64, 1, 43, 50, 北海道外科学会, 2019年06月, ［査読有り］
日本語, 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)

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
小切開・鏡視外科学会雑誌, 10, 1, 54, 54, (NPO)小切開・鏡視外科学会, 2019年06月
日本語

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, 80, 5, 1029, 1029, 日本臨床外科学会, 2019年05月
日本語

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, (一社)日本外科学会, 2019年04月
英語

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, (一社)日本外科学会, 2019年04月
英語

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, 33, 3, S, 2, (NPO)日本呼吸器外科学会, 2019年04月
日本語

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, 33, 3, V8, 1, (NPO)日本呼吸器外科学会, 2019年04月
日本語

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, 33, 3, O10, 4, (NPO)日本呼吸器外科学会, 2019年04月
日本語

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, 33, 3, P57, 2, (NPO)日本呼吸器外科学会, 2019年04月
日本語

Porphyrin-High-Density Lipoprotein: A Novel Photosensitizing Nanoparticle for Lung Cancer Therapy.
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, 2019年02月, ［査読有り］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Intraoperative Near-Infrared Fluorescence-Guided Peripheral Lung Tumor Localization in Rabbit Models.
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, 2019年01月, ［査読有り］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 23, 7, PD15, 4, (一社)日本内視鏡外科学会, 2018年12月
日本語

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, 23, 7, WS19, 3, (一社)日本内視鏡外科学会, 2018年12月
日本語

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, 23, 7, OS104, 1, (一社)日本内視鏡外科学会, 2018年12月
日本語

Preclinical investigation of folate receptor-targeted nanoparticles for photodynamic therapy of malignant pleural mesothelioma.
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, 2018年11月, ［査読有り］, ［筆頭著者］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

非移植認定施設における肺移植手術シミュレーションの有用性
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, 53, 総会臨時, 472, 472, (一社)日本移植学会, 2018年09月
日本語

Prognostic value of MAGEA4 in primary lung cancer depends on subcellular localization and p53 status.
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, 2018年08月, ［査読有り］, ［責任著者］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

インドシアニングリーン蛍光胸腔鏡を用いた胸腔鏡下複数肺区域切除
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, 9, 1, 22, 22, (NPO)小切開・鏡視外科学会, 2018年06月
日本語

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, 32, 3, O13, 1, (NPO)日本呼吸器外科学会, 2018年04月
日本語

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, 32, 3, O26, 2, (NPO)日本呼吸器外科学会, 2018年04月
日本語

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, 32, 3, O32, 1, (NPO)日本呼吸器外科学会, 2018年04月
日本語

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, 32, 3, P10, 6, (NPO)日本呼吸器外科学会, 2018年04月
日本語

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, 118回, 1796, 1796, (一社)日本外科学会, 2018年04月
日本語

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, 79, 3, 619, 620, 日本臨床外科学会, 2018年03月
日本語

Personalized siRNA-Nanoparticle Systemic Therapy using Metastatic Lymph Node Specimens Obtained with EBUS-TBNA in Lung Cancer.
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, 2018年01月, ［査読有り］, ［筆頭著者］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 57, 7, 917, 918, (NPO)日本肺癌学会, 2017年12月
日本語

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, 57, 7, 919, 919, (NPO)日本肺癌学会, 2017年12月
日本語

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, 22, 7, WS2, 2, (一社)日本内視鏡外科学会, 2017年12月
日本語

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, 22, 7, SF012, 03, (一社)日本内視鏡外科学会, 2017年12月
日本語

食道癌手術既往のある肺切除症例の検討
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, 62, 2, 182, 182, 北海道外科学会, 2017年12月
日本語

Nanoparticle targeted folate receptor 1-enhanced photodynamic therapy for lung cancer.
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, 2017年11月, ［査読有り］, ［筆頭著者］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

肺動脈性肺高血圧症における肺移植後の早期死亡率に関連する術前肝機能マーカーに関する検討
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, 52, 2-3, 275, 275, (一社)日本移植学会, 2017年09月
日本語

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, 17, 2, 96, 96, 日本気胸・嚢胞性肺疾患学会, 2017年08月
日本語

A novel minimally invasive near-infrared thoracoscopic localization technique of small pulmonary nodules: A phase I feasibility trial
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, MOSBY-ELSEVIER, 2017年08月, ［査読有り］, ［国際共著］
英語, 研究論文（学術雑誌）, 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.

Overexpression of MAGEA2 has a prognostic significance and is a potential therapeutic target for patients with lung cancer
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, SPANDIDOS PUBL LTD, 2017年06月, ［査読有り］, ［国際共著］
英語, 研究論文（学術雑誌）, 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.

Development of a novel ex vivo porcine laparoscopic Heller myotomy and Nissen fundoplication training model (Toronto lap-Nissen simulator)
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, +, AME PUBL CO, 2017年06月, ［査読有り］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, 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, 8, 1, 43, 43, (NPO)小切開・鏡視外科学会, 2017年05月
日本語

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, (一社)日本外科学会, 2017年04月
英語

First Evaluation of the New Thin Convex Probe Endobronchial Ultrasound Scope: A Human Ex Vivo Lung Study.
Patel P, Wada H, Hu HP, Hirohashi K, Kato T, Ujiie H, Ahn JY, Lee D, Geddie W, Yasufuku K
The Annals of thoracic surgery, 103, 4, 1158, 1164, ELSEVIER SCIENCE INC, 2017年04月, ［査読有り］
英語, 研究論文（学術雑誌）, 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

Evaluation of a New Ultrasound Thoracoscope for Localization of Lung Nodules in Ex Vivo Human Lungs.
Ujiie H, Kato T, Hu HP, Hasan S, Patel P, Wada H, Lee D, Fujino K, Hwang DM, Cypel M, de Perrot M, Pierre A, Darling G, Waddell TK, Keshavjee S, Yasufuku K
The Annals of thoracic surgery, 103, 3, 926, 934, ELSEVIER SCIENCE INC, 2017年03月, ［査読有り］
英語, 研究論文（学術雑誌）, 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

Gene Signature
Hideki Ujiie, Daiyoon Lee, Tatsuya Kato, Kazuhiro Yasufuku
Molecular Targeted Therapy of Lung Cancer, 279, 292, 2017年01月01日, ［査読有り］
論文集(書籍)内論文, © 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.

SORORIN and PLK1 as potential therapeutic targets in malignant pleural mesothelioma
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, SPANDIDOS PUBL LTD, 2016年12月, ［査読有り］, ［筆頭著者］
英語, 研究論文（学術雑誌）, 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.

Validating Spectrum Image Analysis of Lymph Nodes During Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients With Lung Cancer
Ujiie, Hideki, Nakajima, Takahiro, Hu, Hsin-pei, Fujino, Kosuke, Kato, Tatsuya, Yasufuku, Kazuhiro
CHEST, 150, 4, 1045A, 1045A, AMER COLL CHEST PHYSICIANS, 2016年10月
英語

An Integrated Nanotechnology-Enabled Transbronchial Image-Guided Intervention Strategy for Peripheral Lung Cancer
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, AMER ASSOC CANCER RESEARCH, 2016年10月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

Multi-Modal Imaging in a Mouse Model of Orthotopic Lung Cancer
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, PUBLIC LIBRARY SCIENCE, 2016年09月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

Kinesin family members KIF11 and KIF23 as potential therapeutic targets in malignant pleural mesothelioma
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, SPANDIDOS PUBL LTD, 2016年08月, ［査読有り］, ［筆頭著者］, ［国際共著］
英語, 研究論文（学術雑誌）, 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.

Thoracoscopic ultrasonography for localization of subcentimetre lung nodules(aEuro)
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, OXFORD UNIV PRESS INC, 2016年02月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

Overexpression of KIF23 predicts clinical outcome in primary lung cancer patients
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, ELSEVIER IRELAND LTD, 2016年02月, ［査読有り］, ［筆頭著者］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Minimally Invasive Electro-Magnetic Navigational Bronchoscopy-Integrated Near-Infrared-Guided Sentinel Lymph Node Mapping in the Porcine Lung
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, PUBLIC LIBRARY SCIENCE, 2015年05月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

Photothermal ablation of human lung cancer by low-power near-infrared laser and topical injection of indocyanine green.
Hirohashi K, Anayama T, Wada H, Nakajima T, Kato T, Keshavjee S, Orihashi K, Yasufuku K
Journal of bronchology & interventional pulmonology, 22, 2, 99, 106, Lippincott Williams and Wilkins, 2015年04月24日, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

Thoracoscopic ultrasonography for localization of subcentimetre lung nodules†.
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, 2015年04月, ［査読有り］
日本語, Owner : NLM

Status : Publisher

PubModel : Print-Electronic

Language : ENG

Pagination :

Assessment of the new thin convex probe endobronchial ultrasound bronchoscope and the dedicated aspiration needle: a preliminary study in the porcine lung.
Wada H, Hirohashi K, Nakajima T, Anayama T, Kato T, Grindlay A, McConnell J, Yoshino I, Yasufuku K
Journal of bronchology & interventional pulmonology, 22, 1, 20, 27, Lippincott Williams and Wilkins, 2015年03月16日, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

A Case of Castleman's Disease with Myasthenia Gravis
Keidai Ishikawa, Tatsuya Kato, Masato Aragaki, Toshiro Ohbuchi, Sachiko Kimura, Yoshiro Matsui, Mitsuhito Kaji
ANNALS OF THORACIC AND CARDIOVASCULAR SURGERY, 20, 585, 588, MEDICAL TRIBUNE INC, 2014年, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

Reduced port video-assisted thoracoscopic surgery using a needle scope for lung and mediastinal lesions
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, OXFORD UNIV PRESS, 2013年08月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

RASEF is a Novel Diagnostic Biomarker and a Therapeutic Target for Lung Cancer
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, AMER ASSOC CANCER RESEARCH, 2013年08月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

Thrombosis in the pulmonary vein stump after left upper lobectomy as a possible cause of cerebral infarction.
Ohtaka K, Hida Y, Kaga K, Kato T, Muto J, Nakada-Kubota R, Sasaki T, Matsui Y
The Annals of thoracic surgery, 95, 6, 1924, 1928, Elsevier, 2013年06月, ［査読有り］
英語, 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

Optimal predictive value of preoperative serum carcinoembryonic antigen for surgical outcomes in stage I non-small cell lung cancer: differences according to histology and smoking status.
Tatsuya Kato, Keidai Ishikawa, Masato Aragaki, Masaaki Sato, Kenzo Okamoto, Tetsuya Ishibashi, Koji Oba, Mitsuhito Kaji
Journal of surgical oncology, 107, 6, 619, 24, 2013年05月, ［査読有り］, ［筆頭著者, 責任著者］, ［国際誌］
英語, 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, 27, 3, V01, 07, (NPO)日本呼吸器外科学会, 2013年04月
日本語

Limited resection and two-staged lobectomy for non-small cell lung cancer with ground-glass opacity.
Ohtaka K, Hida Y, Kaga K, Kato T, Muto J, Nakada-Kubota R, Hirano S, Matsui Y
Journal of cardiothoracic surgery, 8, 111, BioMed Central, 2013年04月, ［査読有り］
英語, 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.

Method for the validation of immunohistochemical staining using SCID mouse xenografts: Expression of CD40 and CD154 in human non-small cell lung cancer
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, SPANDIDOS PUBL LTD, 2013年04月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

Endobronchial closure of a bronchopleural fistula using a fibrin glue-coated collagen patch and fibrin glue
Keidai Ishikawa, Tatsuya Kato, Masato Aragaki, Ryunosuke Hase, Toyohiro Saikai, Yoshiro Matsui, Mitsuhito Kaji
Annals of Thoracic and Cardiovascular Surgery, 19, 6, 423, 427, 2013年, ［査読有り］
英語, 研究論文（学術雑誌）, 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, 17, 7, 268, 268, (一社)日本内視鏡外科学会, 2012年12月
日本語

【胸腔鏡を用いた縦隔疾患の手術適応とその手技】外科的アプローチの選択 縦隔腫瘤性病変に対する胸腔鏡手術の適応
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, 65, 11, 934, 938, (株)南江堂, 2012年10月
日本語

[Indication of video-assisted thoracic surgery for mediastinal mass lesions].
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, 2012年10月

Spontaneous pneumothorax in a patient with dendriform pulmonary ossification: report of a case
Tatsuya Kato, Keidai Ishikawa, Masatoshi Kadoya, Kenzo Okamoto, Mitsuhito Kaji
SURGERY TODAY, 42, 9, 903, 908, SPRINGER, 2012年09月, ［査読有り］, ［筆頭著者］
英語, 研究論文（学術雑誌）, 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.

Overexpression of CDC20 predicts poor prognosis in primary non-small cell lung cancer patients
Tatsuya Kato, Yataro Daigo, Masato Aragaki, Keidai Ishikawa, Masaaki Sato, Mitsuhito Kaji
JOURNAL OF SURGICAL ONCOLOGY, 106, 4, 423, 430, WILEY-BLACKWELL, 2012年09月, ［査読有り］, ［筆頭著者］
英語, 研究論文（学術雑誌）, 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.

Angiolymphatic invasion exerts a strong impact on surgical outcomes for stage I lung adenocarcinoma, but not non-adenocarcinoma
Tatsuya Kato, Keidai Ishikawa, Masato Aragaki, Masaaki Sato, Kenzo Okamoto, Tetsuya Ishibashi, Mitsuhito Kaji
LUNG CANCER, 77, 2, 394, 400, ELSEVIER IRELAND LTD, 2012年08月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）, 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, 26, 3, RS03, 02, (NPO)日本呼吸器外科学会, 2012年04月
日本語

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, 26, 3, RV10, 05, (NPO)日本呼吸器外科学会, 2012年04月
日本語

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, 26, 3, O02, 02, (NPO)日本呼吸器外科学会, 2012年04月
日本語

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, 26, 3, O12, 01, (NPO)日本呼吸器外科学会, 2012年04月
日本語

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, 26, 3, O13, 05, (NPO)日本呼吸器外科学会, 2012年04月
日本語

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, 26, 3, O29, 03, (NPO)日本呼吸器外科学会, 2012年04月
日本語

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, 26, 3, P16, 02, (NPO)日本呼吸器外科学会, 2012年04月
日本語

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, 26, 3, P45, 03, (NPO)日本呼吸器外科学会, 2012年04月
日本語

Overexpression of KIAA0101 predicts poor prognosis in primary lung cancer patients
Tatsuya Kato, Yataro Daigo, Masato Aragaki, Keidai Ishikawa, Masaaki Sato, Mitsuhito Kaji
LUNG CANCER, 75, 1, 110, 118, ELSEVIER IRELAND LTD, 2012年01月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）, 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.

Overexpression of MAD2 predicts clinical outcome in primary lung cancer patients
Tatsuya Kato, Yataro Daigo, Masato Aragaki, Keidai Ishikawa, Masaaki Sato, Satoshi Kondo, Mitsuhito Kaji
LUNG CANCER, 74, 1, 124, 131, ELSEVIER IRELAND LTD, 2011年10月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）, 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.

18F-FDG uptake in primary lung cancer as a predictor of intratumoral vessel invasion
Tetsuya Ishibashi, Mitsuhito Kaji, Tatsuya Kato, Keidai Ishikawa, Masatoshi Kadoya, Nagara Tamaki
ANNALS OF NUCLEAR MEDICINE, 25, 8, 547, 553, SPRINGER, 2011年10月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

Pleomorphic carcinoma of the lung arising in a patient with Li-Fraumeni syndrome: Report of a case
Tatsuya Kato, Keidai Ishikawa, Masaaki Satoh, Satoshi Kondo, Mitsuhito Kaji
SURGERY TODAY, 41, 6, 841, 845, SPRINGER, 2011年06月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）, 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, 日本癌学会, 2008年09月
英語

Up-regulation of CD40 with juxtacrine activity in human nonsmall lung cancer cells correlates with poor prognosis
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, JOHN WILEY & SONS INC, 2008年08月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

Activation of placenta-specific transcription factor distal-less homeobox 5 predicts clinical outcome in primary lung cancer patients
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, AMER ASSOC CANCER RESEARCH, 2008年04月, ［査読有り］, ［筆頭著者］
英語, 研究論文（学術雑誌）, 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.

cT2充実性結節陰影を呈しながらFDG-PET陰性であった肺腺癌の2例
上原 浩文, 加地 苗人, 加藤 達哉
日本呼吸器外科学会雑誌 = The journal of the Japanese Association for Chest Surgery, 22, 2, 169, 174, 特定非営利活動法人日本呼吸器外科学会, 2008年03月07日
日本語, FDG-PET（18F-fluorodeoxyglucose-positron emission tomography）は肺結節性病変の質的診断に有用とされているものの，偽陰性，偽陽性には注意する必要がある．今回我々は，胸部CTにて30mm以上（cT2）の充実性陰影を呈しながらFDG-PET陰性であった肺腺癌の2例を経験した．2例はともに，粘液産生型肺胞上皮癌であり，豊富な粘液産生によりCT画像上では充実性成分を主体としていたにもかかわらずFDGは低集積となっていた．FDG-PET陰性の充実性病変の診断にあたっては，粘液産生肺胞上皮癌である可能性を考慮し，慎重に考える必要がある．

P34-07 当科における肺孤立性病変に対するFDG-PET偽陽性・偽陰性症例の検討(肺癌・PET,第25回日本呼吸器外科学会総会)
加藤 達哉, 石川 慶大, 加地 苗人
日本呼吸器外科学会雑誌, 22, 3, 532, 532, 特定非営利活動法人 日本呼吸器外科学会, 2008年
日本語

Activation of holliday junction-recognizing protein involved in the chromosomal stability and immortality of cancer cells
Tatsuya Kato, Nagato Sato, Satoshi Hayama, Takumi Yamabuki, Tomoo Ito, Masaki Miyamoto, Satoshi Kondo, Yusuke Nakamura, Yataro Daigo
CANCER RESEARCH, 67, 18, 8544, 8553, AMER ASSOC CANCER RESEARCH, 2007年09月, ［査読有り］, ［筆頭著者］
英語, 研究論文（学術雑誌）, 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, 日本癌学会, 2007年08月
英語

Phosphorylation and activation of cell division cycle associated 8 by aurora kinase B plays a significant role in human lung carcinogenesis
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, AMER ASSOC CANCER RESEARCH, 2007年05月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

Dikkopf-1 as a novel serologic and prognostic biomarker for lung and esophageal carcinomas
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, AMER ASSOC CANCER RESEARCH, 2007年03月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

Identification of Myc-associated protein with JmjC domain as a novel therapeutic target oncogene for lung 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, AMER ASSOC CANCER RESEARCH, 2007年02月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

PS-070-5 多発癌家系に発症した若年者原発性肺多形癌の一例(肺癌症例8, 第24回日本呼吸器外科学会総会号)
加藤 達哉, 上原 浩文, 加地 苗人
日本呼吸器外科学会雑誌, 21, 3, 458, 458, 特定非営利活動法人 日本呼吸器外科学会, 2007年
日本語

PS-001-5 原発巣のCTおよびFDG-PET所見と病理学的リンパ節転移に関する検討(診断と手術適応1, 第24回日本呼吸器外科学会総会号)
上原 浩文, 加地 苗人, 加藤 達哉
日本呼吸器外科学会雑誌, 21, 3, 362, 362, 特定非営利活動法人 日本呼吸器外科学会, 2007年
日本語

RV-02-2 当科における完全鏡視下右肺上葉切除術(右上葉切除(2), 第24回日本呼吸器外科学会総会号)
加地 苗人, 加藤 達哉, 上原 浩文
日本呼吸器外科学会雑誌, 21, 3, 322, 322, 特定非営利活動法人 日本呼吸器外科学会, 2007年
日本語

Increased expression of insulin-like growth factor-II messenger RNA-binding protein 1 is associated with tumor progression in patients with lung cancer
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, AMER ASSOC CANCER RESEARCH, 2007年01月, ［査読有り］, ［筆頭著者］
英語, 研究論文（学術雑誌）, 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.

Activation of CDCA1-KNTC2, members of centromere protein complex, involved in pulmonary carcinogenesis
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, AMER ASSOC CANCER RESEARCH, 2006年11月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

The neuromedin U-growth hormone secretagogue receptor 1b/neurotensin receptor 1 oncogenic signaling pathway as a therapeutic target for lung cancer
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, AMER ASSOC CANCER RESEARCH, 2006年10月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

Characterization of SEZ6L2 cell-surface protein as a novel prognostic marker for lung cancer
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, BLACKWELL PUBLISHING, 2006年08月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

Genome-wide gene expression profile analysis of esophageal squamous cell carcinomas
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, PROFESSOR D A SPANDIDOS, 2006年06月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

ANLN plays a critical role in human lung carcinogenesis through the activation of RHOA and by involvement in the phosphoinositide 3-kinase/AKT pathway
C Suzuki, Y Daigo, N Ishikawa, T Kato, S Hayama, T Ito, E Tsuchiya, Y Nakamura
CANCER RESEARCH, 65, 24, 11314, 11325, AMER ASSOC CANCER RESEARCH, 2005年12月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

Increases of amphiregulin and transforming growth factor-alpha in serum as predictors of poor response to gefitinib among patients with advanced non-small cell 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, AMER ASSOC CANCER RESEARCH, 2005年10月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

Plakophilin 3 oncogene as prognostic marker and therapeutic target for lung cancer
C Furukawa, Y Daigo, N Ishikawa, T Kato, T Ito, E Tsuchiya, S Sone, Y Nakamura
CANCER RESEARCH, 65, 16, 7102, 7110, AMER ASSOC CANCER RESEARCH, 2005年08月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

A novel human tRNA-dihydrouridine synthase involved in pulmonary carcinogenesis
T Kato, Y Daigo, S Hayama, N Ishikawa, T Yamabuki, T Ito, M Myamoto, S Kondo, Y Nakamura
CANCER RESEARCH, 65, 13, 5638, 5646, AMER ASSOC CANCER RESEARCH, 2005年07月, ［査読有り］, ［筆頭著者］
英語, 研究論文（学術雑誌）, 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.

Difference of caveolin-1 expression pattern in human lung neoplastic tissue. Atypical adenomatous hyperplasia, adenocarcinoma and squamous cell carcinoma
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, ELSEVIER SCI IRELAND LTD, 2004年10月, ［査読有り］, ［筆頭著者］
英語, 研究論文（学術雑誌）, 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.

Inflammatory malignant fibrous histiocytoma of the gallbladder: Report of a case
T Kato, T Kojima, T Shimizu, H Sasaki, M Abe, S Okushiba, S Kondo, H Kato, H Sato
SURGERY TODAY, 32, 1, 81, 85, SPRINGER-VERLAG, 2002年, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）, 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.

Gastrectomy in combination with a distal splenorenal shunt in a patient with gastric cancer and portal hypertension: Report of a case
T Kato, H Kato, S Kondo, S Okushiba, T Morikawa
SURGERY TODAY, 32, 8, 727, 730, SPRINGER-VERLAG, 2002年, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）, 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.

Two cases of esophageal cancer with portal hypertension: Esophagectomy with venous shunt procedure
T Kato, T Motohara, Y Kaneko, H Shikishima, S Okushiba, S Kondo, H Kato
HEPATO-GASTROENTEROLOGY, 48, 42, 1656, 1658, H G E UPDATE MEDICAL PUBL LTD., 2001年11月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）, 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.

腹膜播種を伴ったgasurointestinal stromal tumorの2例
平岡 圭, 森田 高行, 加藤 達哉, 仙丸 直人, 宮坂 祐司, 藤田 美芳, 加藤 紘之
日本臨床外科学会雑誌 = The journal of the Japan Surgical Association, 61, 1, 204, 208, Japan Surgical Association, 2000年01月25日
日本語, 腹膜播種を伴ったgastrointestinal stromal tumor (GIST)の2切除例を経験したので報告する.症例1) 70歳,男性,腹部膨満感を主訴に来院.腹部CTにて胃に巨大な嚢胞性腫瘤を認め,胃粘膜下腫瘍の診断にて手術を施行した.症例2) 59歳,男性,下血を主訴に来院.腹部CT,腹部超音波検査にて小腸に5cm大の腫瘤を認め,小腸腫瘍の診断にて小腸部分切除術を施行した.いずれも,術中腹膜に多数の小結節を認め,病理組織学的所見,免疫染色より,腹膜播種を伴ったGIST uncommitted typeと診断された. GISTは良,悪性の鑑別が困難であるが,腹膜播種を生じるとその予後は不良であり早期の治療が望まれる.

肝転移,腹膜播種を来した回腸平滑筋芽細胞腫の1例
平岡 圭, 森田 高行, 藤田 美芳, 宮坂 祐司, 仙丸 直人, 加藤 達哉, 加藤 紘之
日本臨床外科学会雑誌, 61, 3, 689, 692, Japan Surgical Association, 2000年
症例は59歳,男性.下血,めまいを主訴に来院した.小腸造影X線検査にて回腸に直径約2cmの隆起性病変を認めたため回腸腫瘍の診断にて回腸切除術を施行した.腫瘍は1.8×1.8×1.5cm大で,回盲部より約60cm口側に認められた.術中,明らかな腹膜播種,肝転移,リンパ節転移は認められなかつた.病理組織学的所見より平滑筋芽細胞腫と診断された.その後,肝転移,腹膜転移が出現しいずれも切除を施行したが,初回手術より4年2カ月後,全身転移を来して死亡した.小腸の平滑筋芽細胞腫は比較的稀で,その良・悪性の判断は困難とされているが,本例のように予後不良な経過をたどるものも存在するため,慎重な経過観察が必要である.

Report of a case with crohn's disease presenting as acute appendicitis
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, Japanese Society of Gastroenterological Surgery, 2000年, ［査読有り］, ［筆頭著者］
日本語, 研究論文（学術雑誌）, 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.

Basaloid-squamous carcinoma of the esophagus: Report of a case
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, SPRINGER VERLAG, 2000年, ［査読有り］, ［筆頭著者］
英語, 研究論文（学術雑誌）, 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.

Case of retroperitoneal dedifferentiated mixed-type liposarcoma: comparison of proliferative activity in specimens from four operations.
Kato T, Motohara T, Kaneko Y, Shikishima H, Takahashi T, Okushiba S, Kondo S, Kato H
Journal of surgical oncology, 72, 1, 32, 36, WILEY-LISS, 1999年09月, ［査読有り］, ［筆頭著者］
英語, 研究論文（学術雑誌）, 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.

Ischemic stricture of the small intestine associated with acute pancreatitis
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, HUMANA PRESS INC, 1998年12月, ［査読有り］, ［筆頭著者］
英語, 研究論文（学術雑誌）, 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.

胃上部早期胃癌に対する臨床病理学的検討
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, 42, 2, 281, 281, 北海道外科学会, 1997年12月, ［査読有り］
日本語

肺孤立性毛細血管腫の2症例　　　　　　　　　　　　　　　
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, 64, 1, 58, 58, 2024年02月
(NPO)日本肺癌学会, 日本語

肺静脈初回肺葉切除は臨床的N0原発性肺癌患者における術後予後を改善する可能性がある: 多施設傾向スコアマッチング研究【JST機械翻訳】|||
SHIIYA Haruhiko, UJIIE Hideki, OTSUKA Shohei, YAMASAKI Hiroshi, SASAKI Akihiro, CHIBA Ryohei, NOMURA Shunsuke, OHTAKA Kazuto, FUJIWARA-KURODA Aki, ARAGAKI Masato, KATO Tatsuya, 薬理と臨床, 34, 2, 2024年

ロボット支援胸部手術における水平開胸視野による修正前方アプローチ【JST機械翻訳】|||
OHTAKA Kazuto, OTSUKA Shohei, YAMASAKI Hiroshi, SASAKI Akihiro, SHIIYA Haruhiko, FUJIWARA-KURODA Akli, UJIIE Hideki, ARAGAKI Masato, KATO Tatsuya, 薬理と臨床, 34, 2, 2024年

Reduced port Robot-assisted thoracic surgery(RATS)の未来
氏家秀樹, 大塚将平, 佐々木明洋, 山崎洋, 椎谷洋彦, 大高和人, 藤原晶, 新垣雅人, 江花弘基, 加藤達哉, 気管支学, 46, 2024年

薬物療法後の縦隔内再発に対してロボット支援下腫瘍摘除術を施行した二相型胸膜中皮腫の1例
岡村峻, 佐々木明洋, 大塚将平, 山崎洋, 椎谷洋彦, 大高和人, 藤原晶, 氏家秀樹, 新垣雅人, 加藤達哉, 日本呼吸器外科学会総会(Web), 41st, 2024年

TOUCHCLASSを用いた手術教育システムの構築
新垣雅人, 大塚将平, 佐々木明洋, 山崎洋, 椎谷洋彦, 大高和人, 藤原晶, 氏家秀樹, 加藤達哉, 日本呼吸器外科学会総会(Web), 41st, 2024年

Reduced port Robot-assisted thoracic surgery(RATS)の定型化の取り組み-利点および欠点の検討
氏家秀樹, 大塚将平, 佐々木明洋, 山崎洋, 椎谷洋彦, 大高和人, 藤原晶, 新垣雅人, 江花弘基, 加藤達哉, 日本呼吸器外科学会総会(Web), 41st, 2024年

北海道大学病院呼吸器外科における医師のオンコール体制の導入
藤原晶, 大塚将平, 佐々木明洋, 山崎洋, 椎谷洋彦, 大高和人, 氏家秀樹, 新垣雅人, 加藤達哉, 日本呼吸器外科学会総会(Web), 41st, 2024年

左上葉肺癌に対する肺葉切除と区域切除の傾向スコアマッチングを用いた長期成績比較
竹野巨樹, 野村俊介, 大塚将平, 山崎洋, 佐々木明洋, 椎谷洋彦, 大高和人, 藤原晶, 氏家秀樹, 新垣雅人, 千葉龍平, 椎名伸行, 加地苗人, 加藤達哉, 日本呼吸器外科学会総会(Web), 41st, 2024年

胸膜中皮腫術後のアスペルギルス膿胸に対し外用抗真菌薬の胸腔内塗布が有効であった1例
野村俊介, 藤原晶, 大塚将平, 竹野巨樹, 山崎洋, 佐々木明洋, 椎谷洋彦, 大高和人, 氏家秀樹, 新垣雅人, 長靖, 加藤達哉, 日本呼吸器外科学会総会(Web), 41st, 2024年

7気管輪の気管環状切除を施行した下部気管腺様嚢胞癌の1例
佐々木明洋, 大塚将平, 山崎洋, 椎谷洋彦, 大高和人, 藤原晶, 氏家秀樹, 新垣雅人, 加藤達哉, 日本呼吸器外科学会総会(Web), 41st, 2024年

肺孤立性毛細血管腫の2症例
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(Web), 64, 1, 2024年

当院におけるReduced port Robot-assisted thoracic surgery(RATS)の定型化の取り組み
氏家秀樹, 竹野巨樹, 佐々木明洋, 山崎洋, 野村俊介, 椎谷洋彦, 大高和人, 藤原晶, 新垣雅人, 加藤達哉, 日本外科学会定期学術集会(Web), 124th, 2024年

肺静脈先行処理は原発性肺癌術後の再発を抑制する可能性がある-多施設共同研究-
椎谷洋彦, 氏家秀樹, 新垣雅人, 藤原晶, 大高和人, 野村俊介, 千葉龍平, 加藤達哉, 日本外科学会定期学術集会(Web), 124th, 2024年

前方アプローチ(対面倒立視野)によるロボット支援下肺葉切除術
大高和人, 竹野巨樹, 佐々木明洋, 山崎洋, 野村俊介, 藤原晶, 氏家秀樹, 新垣雅人, 加藤達哉, 日本ロボット外科学会学術集会プログラム・抄録集, 16th, 2024年

肺類上皮血管内皮腫と肺腺癌が混在した多発肺結節影の1例
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, 若林健人, 松野吉宏, 加藤達哉, 日本臨床外科学会雑誌, 85, 2, 2024年

当院におけるReduced port RATSの取り組み
氏家秀樹, 竹野巨樹, 佐々木明洋, 山崎洋, 野村俊介, 大高和人, 藤原晶, 新垣雅人, 加藤達哉, 日本肺癌学会学術集会号, 64th (CD-ROM), 2023年

悪性胸膜中皮腫における免疫応答と免疫チェックポイント阻害剤の効果予測因子の解析
榊原里江, YIN Yuting, 本多隆行, 桐村進, 小林正嗣, 安藤耕平, 氏家秀樹, 加藤達哉, 加賀基知三, 三ツ村隆弘, 中野亮二, 坂下博之, 松毛伸一, 石橋洋則, 明石巧, 樋田泰浩, 諸星隆夫, 東みゆき, 大久保憲一, 宮崎泰成, 日本肺癌学会学術集会号, 64th (CD-ROM), 2023年

小児に対する胸腔鏡下肺切除術の成績と課題
加賀基知三, 河原仁守, 藤原晶, 新垣雅人, 氏家秀樹, 本多昌平, 武冨紹信, 加藤達哉, 日本内視鏡外科学会総会(Web), 36th, 2023年

胸腺癌27例の手術治療成績~2施設共同研究~
新垣雅人, 千葉龍平, 藤原晶, 氏家秀樹, 大高和人, 野村俊介, 佐々木明洋, 山崎洋, 竹野巨樹, 加地苗人, 加藤達哉, 日本胸部外科学会定期学術集会(Web), 76th, 2023年

Reduced port RATSの取り組み-Uniportal RATS確立へ向けて
氏家秀樹, 竹野巨樹, 佐々木明洋, 山崎洋, 野村俊介, 大高和人, 藤原晶, 新垣雅人, 加藤達哉, 日本胸部外科学会定期学術集会(Web), 76th, 2023年

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総会(Web), 40th, 2023年

ドナー肺を体外肺灌流と10°C保存した後に両側肺葉移植を施行した一例
新垣雅人, 新垣雅人, 稲毛輝長, 川島光明, 谷口大輔, 石綿司, 氏家秀樹, 藤原晶, 大高和人, 椎谷洋彦, 加藤達哉, 安福和弘, KESHAVJEE Shaf, CYPEL Mercelo, 日本移植学会総会プログラム抄録集, 59th (Web), 2023年

当科における単孔式複雑区域切除術の経験
藤原晶, 長島諒太, 千葉龍平, 田畑佑希子, 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総会(Web), 39th, 2022年

Hybrid手術室を利用した触知不能病変の同定と切除マージンの確認法の工夫
藤原晶, 樋田泰浩, 山崎雅久, 千葉龍平, 野村俊介, 武藤潤, 氏家秀樹, 加賀基知三, 加藤達哉, 日本胸部外科学会定期学術集会(Web), 75th, 2022年

化学放射線療法後の左主気管支腺様嚢胞癌の一手術例
幾島拓也, 氏家秀樹, 千葉龍平, 野村俊介, 田畑佑希子, 藤原晶, 樋田泰浩, 加賀基知三, 品川尚文, 高島雄太, 若狭哲, 松野吉宏, 加藤達哉, 日本胸部外科学会定期学術集会(Web), 75th, 2022年

バーチャル・リアリティー(VR)システムを用いた,ロボット外科リアルタイムナビゲーション手術法の開発
氏家秀樹, 野村俊介, 千葉龍平, 山崎雅久, 武藤潤, 藤原晶, 樋田泰浩, 加賀基知三, EITEL Chad, CLAPP Tod, 加藤達哉, 日本胸部外科学会定期学術集会(Web), 75th, 2022年

当院職員における新型コロナウイルスワクチン接種後の抗体価の検討
大塚慎也, 大塚慎也, 平岡圭, 平岡圭, 鈴置真人, 氏家秀樹, 加藤達哉, 横田勲, 米澤一也, 小熊恵二, 岩代望, 加藤元嗣, 大原正範, 北海道医学雑誌, 97, 2, 2022年

右主気管支狭窄に対し心膜吊り上げ法による縦隔授動とステント留置により救命し得た一例
長島諒太, 藤原晶, 千葉龍平, 田畑佑希子, 氏家秀樹, 加藤達哉, 樋田泰浩, 加賀基知三, 若狭哲, 品川尚文, 日本呼吸器外科学会総会(Web), 39th, 2022年

ロボット支援下後縦隔腫瘍切除術における,腹臥位アプローチの有用性の検討
氏家秀樹, 海老原裕麿, 長島諒太, 千葉龍平, 野村俊介, 田畑祐希子, 藤原晶, 加藤達哉, 樋田泰浩, 加賀基知三, 若狭哲, 日本ロボット外科学会学術集会プログラム・抄録集, 14th, 2022年

当科における胸腔鏡下全胸膜被覆術(VATS-TPC)
藤原晶, 樋田泰浩, 長島諒太, 千葉龍平, 田畑佑希子, 氏家秀樹, 加藤達哉, 加賀基知三, 日本肺および心肺移植研究会プログラム・抄録集, 38th, 2022年

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(Web), 62, 1, 2022年

腫瘍組織解析とctDNAを併用した肺癌術後のモニタリング法はMinimal residual disease検出率を向上させる
加藤達哉, MING Chin Yoon, LOW Siew-Kee, 清谷一馬, 林理絵, 藤原晶, 氏家秀樹, 加賀基知三, 中村祐輔, 日本呼吸器外科学会総会(Web), 39th, 2022年

α-グルコシダーゼ阻害薬内服中に発症した肺移植後の腸管嚢胞様気腫症の一例—Pneumatosis Intestinalis After Living Donor Lung Transplantation Associated With Alpha-Glucosidase Inhibitor Treatment : A Case Report
大塚 慎也, 氏家 秀樹, 加藤 達哉, 椎谷 洋彦, 藤原 晶, 樋田 泰浩, 加賀 基知三, 若狭 哲, 井上 玲, 飯村 泰昭, 北海道外科雑誌 = The Hokkaido journal of surgery / 北海道外科雑誌編集委員会 編, 66, 2, 131, 133, 2021年12月
北海道外科学会, 日本語

子供におけるニードルスコープを用いた減孔式ビデオ補助下胸腔鏡下手術(RP-VATS)
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総会(Web), 33rd, 2021年

定型カルチノイドの治療—TREATMENT OF TYPICAL CARCINOID TUMORS—特集 肺・胸腺神経内分泌腫瘍の治療
氏家 秀樹, 樋田 泰浩, 大塚 慎也, 佐々木 明洋, 山崎 洋, 藤原 晶, 加藤 達哉, 加賀 基知三, 若狭 哲, 松野 吉宏, 日本外科学会雑誌 = Journal of Japan Surgical Society / 日本外科学会 編, 122, 1, 18, 25, 2021年
日本外科学会, 日本語

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, 日本移植学会総会プログラム抄録集, 57th (Web), 2021年

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, 21, 2, 2021年

肺切除後難治性肺ろうの治療戦略
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総会(Web), 34th, 2021年

有瘻性膿胸に対し気管支充填術と持続陰圧吸引療法を併用した2症例
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, 43, 6, 2021年

神経線維腫症I型に肺腺癌,内頚動静脈瘻を合併した1例
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(Web), 61, 1, 2021年

血気胸を発症したPleuroparenchymal fibroelastosis(PPFE)合併肺癌の1切除例
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(Web), 61, 1, 2021年

バーチャル・リアリティー(VR)システムを用いた,呼吸器外科手術シミュレーション法の開発
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, 気管支学, 43, 2021年

肺移植後に発症したα-グルコシダーゼ阻害薬内服中の腸管嚢胞様気腫症の一例
大塚慎也, 大塚慎也, 氏家秀樹, 加藤達哉, 千葉龍平, 椎谷洋彦, 藤原晶, 樋田泰浩, 加賀基知三, 若狭哲, 井上玲, 飯村泰昭, 日本肺および心肺移植研究会プログラム・抄録集, 37th, 2021年

肺・胸腺神経内分泌腫瘍の治療 3.定型カルチノイドの治療
氏家秀樹, 樋田泰浩, 大塚慎也, 佐々木明洋, 山崎洋, 藤原晶, 加藤達哉, 加賀基知三, 若狭哲, 松野吉宏, 日本外科学会雑誌, 122, 1, 2021年

肺メディカルコンサルタント業務の肺移植外科医以外への委嘱の展望
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, 日本肺および心肺移植研究会プログラム・抄録集, 36th, 2020年

降下性壊死性縦隔炎に対する大動脈弓部トンネリングによる左上縦隔ドレナージ
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(Web), 17, 5, 2020年

ヘッドマウントディスプレイ(HMD)によるバーチャル・リアリティー(VR)システムを用いた,肺区域切除手術シミュレーション法の開発
氏家秀樹, 大塚慎也, 佐々木明洋, 山崎洋, 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(Web), 73rd, 2020年

気管ステント留置後の逸脱に対し気管形成術を行い救命できた外傷性気管損傷の一例
大塚慎也, 加藤達哉, 氏家秀樹, 山崎洋, 佐々木明洋, 藤原晶, 樋田泰浩, 加賀基知三, 若狭哲, 高島雄太, 品川尚文, 日本胸部外科学会定期学術集会(Web), 73rd, 2020年

肺移植患者におけるEBUS(超音波気管支鏡)の役割
氏家秀樹, 氏家秀樹, 加藤達哉, 稲毛輝長, 石綿司, 新垣雅人, 新垣雅人, 樋田泰浩, 加賀基知三, KESHAVJEE Shaf, YASUFUKU Kazuhiro, 日本肺および心肺移植研究会プログラム・抄録集, 36th, 2020年

EBUS-TBNAによる遺伝子解析に基づいたsiRNA-nanoparticleによる肺癌個別化治療法の確立
加藤 達哉, 氏家 秀樹, 藤野 孝介, 加地 苗人, Chen Juan, Zheng Gang, 加賀 基知三, 松居 喜郎, 安福 和弘, 日本外科学会定期学術集会抄録集, 117回, SF, 8, 2017年04月
(一社)日本外科学会, 日本語

悪性胸膜中皮腫における治療標的遺伝子としてのSORORINおよびPLK1遺伝子の役割
加藤 達哉, Lee Daiyoon, 氏家 秀樹, 和田 啓伸, 加地 苗人, 松毛 真一, 菅野 宏美, 畑中 豊, 畑中 佳奈子, 松野 吉宏, 加賀 基知三, 松居 喜郎, De Perrot Marc, 安福 和弘, 日本呼吸器外科学会雑誌, 31, 3, P67, 3, 2017年04月
(NPO)日本呼吸器外科学会, 日本語

First Evaluation of the New Thin Convex Probe Endobronchial Ultrasound (TCP-EBUS) in Human Ex-Vivo Lungs
Priya Patel, Hironobu Wada, Tatsuya Kato, Kentaro Hirohashi, Spencer Hu, Jin Young Ahn, Daiyoon Lee, Kazuhiro Yasufuku, CHEST, 148, 4, 2015年10月
AMER COLL CHEST PHYSICIANS, 英語, 研究発表ペーパー・要旨（国際会議）

Overexpression of KIF23 Predicts Clinical Outcome in Primary Lung Cancer Patients
Tatsuya Kato, Hironobu Wada, Priya Patel, Daiyoon Lee, Spencer Hu, Kentaro Hirohashi, Takahiro Nakajima, Mitsuhito Kaji, Kichizo Kaga, Yoshiro Matsui, Ming S. Tsao, Kazuhiro Yasufuku, JOURNAL OF THORACIC ONCOLOGY, 10, 9, S710, S710, 2015年09月
ELSEVIER SCIENCE INC, 英語, 研究発表ペーパー・要旨（国際会議）

悪性胸膜中皮腫の新規治療標的分子であるURST1の機能解析(Characterization of URST1 protein as a therapeutic target for malignant pleural mesothelioma)　　　　　　　　　　　　　　　
吉岡 佑一郎, 高野 淳, 加藤 達哉, 釣田 義一郎, 渡邉 聡明, 醍醐 弥太郎, 日本癌学会総会記事, 73回, E, 3042, 2014年09月
日本癌学会, 英語

悪性胸膜中皮腫の左腹直筋転移に対して右腹直筋前鞘翻転法にて腹壁再建した1例
石川慶大, 加賀基知三, 樋田泰浩, 加藤達哉, 久保田玲子, 佐藤大介, 阿部紘丈, 松居喜郎, 北海道外科雑誌, 58, 1, 66, 66, 2013年06月20日
北海道外科学会, 日本語

胸腔鏡補助下醸膿胸膜切除・胸郭形成術後のVAC(Vacuum-assisted closure)システムによる治療経験　　　　　　　　　　　　　　　
石川 慶大, 加賀 基知三, 樋田 泰浩, 加藤 達哉, 久保田 玲子, 宮崎 大, 佐藤 大介, 七戸 俊明, 平野 聡, 松居 喜郎, 日本呼吸器外科学会雑誌, 27, 3, V08, 09, 2013年04月
(NPO)日本呼吸器外科学会, 日本語

PS-151-5 当院における縦隔腫瘍の治療方針(PS ポスターセッション,第113回日本外科学会定期学術集会)
石川 慶大, 樋田 泰浩, 加賀 基知三, 加藤 達哉, 久保田 玲子, 宮崎 大, 松居 喜郎, 日本外科学会雑誌, 114, 2, 729, 729, 2013年03月05日
一般社団法人日本外科学会, 日本語

SY-5-4 根治的化学放射線療法後肺癌に対する"Adjuvant Surgery"(SY シンポジウム,第113回日本外科学会定期学術集会)
樋田 泰浩, 加賀 基知三, 加藤 達哉, 石川 慶大, 久保田(中田) 玲子, 宮崎 大, 松居 喜郎, 日本外科学会雑誌, 114, 2, 118, 118, 2013年03月05日
一般社団法人日本外科学会, 日本語

VSY-17-4 肺・縦隔疾患に対するneedle scopic surgeryの適応拡大(VSY ビデオシンポジウム,第113回日本外科学会定期学術集会)
加賀 基知三, 樋田 泰浩, 加藤 達哉, 石川 慶大, 中田 玲子, 高野 博信, 佐藤 彰記, 宮崎 大, 松居 喜郎, 日本外科学会雑誌, 114, 2, 217, 217, 2013年03月05日
一般社団法人日本外科学会, 日本語

根治的化学放射線療法後肺癌に対する“Adjuvant Surgery”
樋田泰浩, 加賀基知三, 加藤達哉, 石川慶大, 久保田(中田, 玲子, 宮崎大, 松居喜郎, 日本外科学会雑誌, 114, 臨増2, 118, 118, 2013年03月05日
(一社)日本外科学会, 日本語

肺・縦隔疾患に対するneedle scopic surgeryの適応拡大
加賀基知三, 樋田泰浩, 加藤達哉, 石川慶大, 中田玲子, 高野博信, 佐藤彰記, 宮崎大, 松居喜郎, 日本外科学会雑誌, 114, 臨増2, 217, 217, 2013年03月05日
(一社)日本外科学会, 日本語

当院における縦隔腫瘍の治療方針
石川慶大, 樋田泰浩, 加賀基知三, 加藤達哉, 久保田玲子, 宮崎大, 松居喜郎, 日本外科学会雑誌, 114, 臨増2, 729, 729, 2013年03月05日
(一社)日本外科学会, 日本語

小型肺癌に対する胸腔鏡下術中生検法の検討―針生検と部分切除の比較―
石川慶大, 加賀基知三, 樋田泰浩, 加藤達哉, 久保田玲子, 佐藤彰記, 高野博信, 松居喜郎, 日本臨床外科学会雑誌, 73, 827, 2012年10月20日
日本語

肺癌に対するReduced Port Video‐assisted Thoracoscopic Surgeryの安全性
高野博信, 樋田泰浩, 加賀基知三, 加藤達哉, 石川慶大, 中田玲子, 佐藤彰記, 松居喜郎, 日本臨床外科学会雑誌, 73, 440, 2012年10月20日
日本語

右肺癌に対する完全胸腔鏡下縦隔郭清
樋田泰浩, 加賀基知三, 加藤達哉, 石川慶大, 久保田, 中田, 玲子, 佐藤彰記, 高野博信, 松居喜郎, 日本臨床外科学会雑誌, 73, 381, 2012年10月20日
日本語

原発性肺腺癌と扁平上皮癌切除例における原発巣へのFDG集積の臨床病理学的検討
佐藤彰記, 樋田泰浩, 加賀基知三, 加藤達哉, 石川慶大, 久保田(中田, 玲子, 平野聡, 松居喜郎, 肺癌, 52, 5, 613, 613, 2012年10月05日
(NPO)日本肺癌学会, 日本語

化学放射線療法後肺切除時の気管支断端瘻の予防
樋田泰浩, 加賀基知三, 加藤達哉, 石川慶大, 中田(久保田, 玲子, 佐藤彰記, 高野博信, 松居喜郎, 肺癌, 52, 5, 544, 544, 2012年10月05日
(NPO)日本肺癌学会, 日本語

非小細胞肺癌におけるCDC20遺伝子の発現と臨床病理学的検討
加藤達哉, 醍醐弥太郎, 石川慶大, 新垣雅人, 久保田玲子, 樋田泰浩, 加地苗人, 加賀基知三, 松居喜郎, 肺癌, 52, 5, 629, 629, 2012年10月05日
(NPO)日本肺癌学会, 日本語

ソロサージャリー・テクニックによる胸腔鏡下肺葉切除術
樋田泰浩, 加賀基知三, 加藤達哉, 石川慶大, 久保田(中田, 玲子, 佐藤彰記, 松居喜郎, Gen Thorac Cardiovasc Surg, 60, Supplement, 378, 2012年09月10日
日本語

胸腔鏡下手術における触知困難肺腫瘍の同定とCTによる切除検体マージンの確認
樋田泰浩, 加賀基知三, 加藤達哉, 石川慶大, 久保田(中田, 玲子, 佐藤彰記, 松居喜郎, Gen Thorac Cardiovasc Surg, 60, Supplement, 303, 2012年09月10日
日本語

非小細胞肺癌におけるKIAA0101遺伝子の発現と臨床病理学的検討
加藤達哉, 石川慶大, 新垣雅人, 樋田泰浩, 加賀基知三, 松居喜郎, 加地苗人, 醍醐弥太郎, 日本呼吸器外科学会総会(Web), 29th, 3, P85-05 (WEB ONLY), 05, 2012年04月
(NPO)日本呼吸器外科学会, 日本語

HP-162-3 非小細胞肺癌症例においてHLA Class I H鎖分子発現低下は予後不良因子である(肺(臨床1),ハイブリッドポスター,第109回日本外科学会定期学術集会)
市之川 一臣, 宮本 正樹, 石川 慶大, 加藤 達哉, 吉岡 達也, Roshian Mishura, 東海林 安人, 松村 祥幸, 加賀 基知三, 平野 聡, 近藤 哲, 日本外科学会雑誌, 110, 2, 668, 668, 2009年02月25日
一般社団法人日本外科学会, 日本語

非小細胞肺癌細胞においてジャクスタクライン活性を伴うCD40の発現増大は不良な予後に相関する
石川慶大, 宮本正樹, 吉岡達也, ROSHAN Mishra, 市之川一臣, 東海林安人, 松村祥幸, 樋田泰浩, 加賀基知三, 加藤達哉, 加地苗人, 平野聡, 近藤哲, 日本外科学会雑誌, 110, 臨増2, 664, 664, 2009年02月25日
(一社)日本外科学会, 日本語

非小細胞肺癌におけるCD40発現の検討
石川慶大, 宮本正樹, 吉岡達也, 角谷昌俊, 李栗, ROSHAN Mishra, 市之川一臣, 東海林安人, 松村祥幸, 加藤達哉, 樋田泰浩, 加賀基地三, 平野聡, 近藤哲, 日本外科学会雑誌, 108, 臨増2, 672, 672, 2007年03月10日
(一社)日本外科学会, 日本語

肺癌の増殖に関与する癌―精巣抗原IMS‐CL54およびIMS‐CL81の機能解析と新規治療薬の開発
早馬聡, 醍醐弥太郎, 加藤達哉, 山吹匠, 中鶴修一, 土屋永寿, 近藤哲, 中村祐輔, 日本癌学会学術総会記事, 65th, 157, 2006年08月28日
日本語

肺癌,食道扁平上皮癌の新規バイオマーカーIMS‐ESO3の同定と臨床応用
山吹匠, 醍醐弥太郎, 早馬聡, 加藤達哉, 中鶴修一, 土屋永寿, 藤田昌宏, 細川正夫, 近藤哲, 中村祐輔, 日本癌学会学術総会記事, 65th, 436, 2006年08月28日
日本語

非小細胞肺癌で特異的に発現が上昇する分子標的遺伝子IMS‐CL13およびIMS‐KIFの同定と機能解析
加藤達哉, 醍醐弥太郎, 早馬聡, 山吹匠, 中鶴修一, 近藤哲, 中村祐輔, 日本癌学会学術総会記事, 65th, 156, 2006年08月28日
日本語

P-447 多発肺癌症例の検討(一般示説64 多発肺癌(2),世界をリードする呼吸器外科医に!,第23回日本呼吸器外科学会総会)
長 靖, 加賀 基知三, 樋田 泰浩, 加藤 達哉, 平野 聡, 近藤 哲, 日本呼吸器外科学会雑誌, 20, 3, 2006年05月15日
特定非営利活動法人日本呼吸器外科学会, 日本語

I期肺癌における胸腔鏡手術の位置づけと手術成績
加賀基知三, 樋田泰浩, 長靖, 加藤達哉, 平野聡, 近藤哲, 日本呼吸器外科学会雑誌, 20, 3, 833, 833, 2006年05月15日
(NPO)日本呼吸器外科学会, 日本語

術前因子から見た小型末梢型肺癌のリンパ節転移の予測と縮小手術の適応
樋田泰浩, 加賀基知三, 長靖, 道免寛充, 三井潤, 福田直也, 菊地健司, 宮本正樹, 七戸俊明, 加藤達哉, 平野聡, 近藤哲, 日本呼吸器外科学会雑誌, 20, 3, 868, 868, 2006年05月15日
(NPO)日本呼吸器外科学会, 日本語

多発肺癌症例の検討
長靖, 加賀基知三, 樋田泰浩, 加藤達哉, 平野聡, 近藤哲, 日本呼吸器外科学会雑誌, 20, 3, 952, 952, 2006年05月15日
(NPO)日本呼吸器外科学会, 日本語

右上下葉原発同時性多発肺癌症例に対し,胸腔鏡下右肺上下葉切除を施行した1例
長靖, 加賀基知三, 樋田泰浩, 加藤達哉, 秋元敏伸, 本間直健, 松井あや, 平野聡, 近藤哲, Jpn J Thorac Cardiovasc Surg, 54, 5, 32, 2006年05月10日
日本語

非小細胞肺癌の進展,増悪に関与する新規遺伝子IMS‐KN08の同定とその機能解析
鈴木千恵, 醍醐弥太郎, 石川暢久, 加藤達哉, 早馬聡, 中鶴修一, 土屋永寿, 中村祐輔, 日本癌学会学術総会記事, 64th, 239, 2005年08月15日
日本語

血清マーカーを用いた非小細胞肺癌のgefitinib感受性予測診断法の構築
石川暢久, 醍醐弥太郎, 高野淳, 谷脇雅也, 加藤達哉, 早馬聡, 土屋永寿, 河野修興, 中村祐輔, 日本癌学会学術総会記事, 64th, 41, 2005年08月15日
日本語

非小細胞肺癌特異的な癌―精巣抗原IMS‐CL54およびIMS‐CL81の同定と機能解析
早馬聡, 醍醐弥太郎, 加藤達哉, 中鶴修一, 土屋永寿, 近藤哲, 中村祐輔, 日本癌学会学術総会記事, 64th, 240, 2005年08月15日
日本語

食道へん平上皮癌において特異的に発現する新規治療標的遺伝子IMS‐ESO1の同定と機能解析
山吹匠, 醍醐弥太郎, 加藤達哉, 早馬聡, 中鶴修一, 藤田昌宏, 細川正夫, 近藤哲, 中村祐輔, 日本癌学会学術総会記事, 64th, 525, 2005年08月15日
日本語

非小細胞肺癌で特異的な発現増加を認める新規治療標的分子IMS‐RQ29の同定と機能解析
高橋浩治, 醍醐弥太郎, 古川千幸, 加藤達哉, 中鶴修一, 中村祐輔, 日本癌学会学術総会記事, 64th, 240, 2005年08月15日
日本語

非小細胞肺癌の進展に関与する新規遺伝子の同定とその機能解析
鈴木千恵, 醍醐弥太郎, 石川暢久, 加藤達哉, 早馬聡, 中鶴修一, 中村祐輔, 日本癌学会総会記事, 63rd, 54, 2004年08月25日
日本語

非小細胞肺癌に関与する新規癌遺伝子IMS‐E21の同定と機能解析
加藤達哉, 醍醐弥太郎, 早馬聡, 鈴木千恵, 石川暢久, 中鶴修一, 近藤哲, 中村祐輔, 日本癌学会総会記事, 63rd, 54, 2004年08月25日
日本語

非小細胞肺癌特異的な癌‐精巣抗原IMS‐CL54の同定と機能解析
早馬聡, 醍醐弥太郎, 加藤達哉, 鈴木千恵, 石川暢久, 中鶴修一, 近藤哲, 中村祐輔, 日本癌学会総会記事, 63rd, 54, 2004年08月25日
日本語

PS-076-3 非小細胞肺癌におけるMLH1,MSH2発現の検討
橋本 裕之, 宮本 正樹, 上原 浩文, 加藤 達哉, 村上 壮一, 海老原 裕磨, 金古 裕之, 村上 慶洋, 高橋 亮, 妻鹿 成治, 長谷 龍之介, 李 栗, 川原田 陽, 七戸 俊明, 森川 利昭, 奥芝 俊一, 近藤 哲, 大淵 俊朗, 加藤 紘之, 日本外科学会雑誌, 105, 457, 457, 2004年03月15日
一般社団法人日本外科学会, 日本語

非小細胞肺癌で発現上昇を認める新規遺伝子の同定とその機能解析
鈴木千恵, 醍醐弥太郎, 菊地剛史, 柿内聡司, 石川暢久, 加藤達哉, 古川千幸, 中村祐輔, 日本癌学会総会記事, 62nd, 247, 248, 2003年08月25日
日本語

非小細胞肺癌で発現上昇を認める新規腫ようマーカー,分子標的薬候補遺伝子の同定と機能解析
古川千幸, 醍醐弥太郎, 菊地剛史, 柿内聡司, 鈴木千恵, 石川暢久, 加藤達哉, 曽根三郎, 中村祐輔, 日本癌学会総会記事, 62nd, 247, 2003年08月25日
日本語

非小細胞肺癌におけるcaveolin-1発現の免疫組織学的検討
加藤 達哉, 大渕 俊朗, 宮本 正樹, 加地 苗人, 森川 利昭, 奥芝 俊一, 近藤 哲, 加藤 紘之, 日本外科学会雑誌, 103, 424, 424, 2002年03月10日
一般社団法人日本外科学会, 日本語

8.80歳以上の高齢者肺癌手術症例の検討(第27回日本肺癌学会北海道支部会)
加藤 達哉, 大淵 俊朗, 藤田 智, 関根 球一郎, 藤田 昭久, 田垣 茂, 高畠 博嗣, 千野 英明, 加藤 達哉, 加藤 紘之, 肺癌, 41, 7, 790, 790, 2001年12月20日
日本肺癌学会, 日本語

VS03-03 グリソン一括処理法を用いた肝切除術 : 特にS1切除について
近藤 哲, 平野 聡, 安保 義恭, 田中 栄一, 加藤 達哉, 鈴木 善法, 森川 利昭, 奥芝 俊一, 加藤 紘之, 日本消化器外科学会雑誌, 34, 7, 853, 853, 2001年07月01日
一般社団法人日本消化器外科学会, 日本語

PP112097 Santorini's duct領域に発生した膵管内乳頭腫瘍(IPMT)の臨床病理学的検討
平野 聡, 近藤 哲, 清水 道生, 安保 義恭, 田中 栄一, 加藤 達哉, 鈴木 善法, 森川 利昭, 奥芝 俊一, 加藤 紘之, 日本消化器外科学会雑誌, 34, 7, 1005, 1005, 2001年07月01日
一般社団法人日本消化器外科学会, 日本語

PP707 呼吸器外科における胸腔鏡手術の適応と成績
森川 利昭, 加藤 達哉, 倉島 庸, 大竹 節之, 加地 苗人, 奥芝 俊一, 近藤 哲, 加藤 紘之, 日本外科学会雑誌, 102, 400, 400, 2001年03月10日
一般社団法人日本外科学会, 日本語

PP688 胸部異常陰影の診断におけるFDG-PETの有用性について
大竹 節之, 森川 利昭, 加地 苗人, 加藤 達哉, 倉島 庸, 奥芝 俊一, 近藤 哲, 加藤 紘之, 塚本 江利子, 日本外科学会雑誌, 102, 395, 395, 2001年03月10日
一般社団法人日本外科学会, 日本語

PP1259 縦隔腫瘍に対する胸腔鏡手術の検討
倉島 庸, 森川 利昭, 加地 苗人, 大竹 節之, 加藤 達哉, 伊藤 清高, 奥芝 俊一, 近藤 哲, 加藤 紘之, 日本外科学会雑誌, 102, 538, 538, 2001年03月10日
一般社団法人日本外科学会, 日本語

自己免疫性肝炎の経過中に発症し治癒切除しえた肝細胞癌の1例
敷島 裕之, 本原 敏司, 加藤 達哉, 金子 行宏, 加藤 紘之, 日本消化器外科学会雑誌, 34, 2, 105, 108, 2001年02月01日
自己免疫肝炎(autoimmune hepatitis;以下, AIH)の経過観察中に肝細胞癌を合併した1例を経験したので報告する.症例は66歳の女性で平成元年4月よりAIHの診断にてプレドニンの内服治療を受けていた.平成11年1月α-fetoprotein (AFP) の上昇と超音波検査にて肝S8に腫瘤を認め, 入院となった.輸血歴, 飲酒歴はなく肝炎ウイルスマーカーはすべて陰性であったが, 抗核抗体陽性であった.各種画像診断にてHCCと診断し, 同年3月肝亜区域切除 (S8) を施行した.腫瘍は3.3×3.0cmのEdmondsonII> III型のHCCで, tw(-)の治癒切除であった.AIHのHCC合併例は, 高度進行例として発見されることが多く, 腫瘍マーカーはもとより各種画像診断を積極的に行うことが重要であると考えられた., 一般社団法人日本消化器外科学会, 日本語

14.肺野末梢型微小腺癌症例に対する縮小手術の妥当性の検討(第26回 日本肺癌学会北海道支部会)
加地 苗人, 森川 利昭, 大渕 俊朗, 大竹 節之, 倉島 庸, 加藤 達哉, 田中 栄一, 安保 義恭, 近江 亮, 平野 聡, 伊藤 清高, 近藤 哲, 加藤 紘之, 肺癌, 40, 7, 798, 798, 2000年12月20日
日本肺癌学会, 日本語

示II-186 進行大腸癌に対するD3郭清を伴うつり上げ式腹腔鏡下大腸切除術(第52回日本消化器外科学会総会)
宮坂 祐司, 森田 高行, 加藤 達哉, 平岡 圭, 仙丸 直人, 藤田 美芳, 加藤 紘之, 日本消化器外科学会雑誌, 31, 6, 1673, 1673, 1998年06月01日
一般社団法人日本消化器外科学会, 日本語

示I-411 膵癌切除例の再発形式に関する検討(第52回日本消化器外科学会総会)
仙丸 直人, 加藤 達哉, 平岡 圭, 宮坂 祐司, 藤田 美芳, 森田 高行, 加藤 紘之, 日本消化器外科学会雑誌, 31, 6, 1599, 1599, 1998年06月01日
一般社団法人日本消化器外科学会, 日本語

示II-377 膵腸吻合術の安全性に対する検討(第52回日本消化器外科学会総会)
藤田 美芳, 森田 高行, 加藤 達哉, 平岡 圭, 仙丸 直也, 宮坂 祐司, 加藤 紘之, 日本消化器外科学会雑誌, 31, 6, 1721, 1721, 1998年06月01日
一般社団法人日本消化器外科学会, 日本語

胆道癌の再発危険因子に関する臨床病理学的検討
樋田 泰浩, 森田 高行, 藤田 美芳, 宮坂 祐司, 平岡 圭, 加藤 達哉, 加藤 紘之, 日本外科学会雑誌, 99, 0, 403, 403, 1998年03月10日
一般社団法人日本外科学会, 日本語

I-229 腹膜播種を認めた消化管stromal tumorの3例
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, 日本消化器外科学会雑誌, 31, 2, 612, 612, 1998年02月01日
一般社団法人日本消化器外科学会, 日本語

I-37 消化性潰瘍穿孔に対する腹腔鏡下大網被覆術の検討
藤田 美芳, 加藤 達哉, 平岡 圭, 樋田 泰浩, 宮坂 祐司, 森田 高行, 加藤 紘之, 日本消化器外科学会雑誌, 31, 2, 564, 564, 1998年02月01日
一般社団法人日本消化器外科学会, 日本語

高機能ゲルによるゲノム制御：がん幹細胞リプログラミングの空間情報解析と治療薬開発
科学研究費助成事業
2024年04月01日 - 2029年03月31日
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, 基盤研究(S), 北海道大学, 24H00037

蛍光スペクトル解析胸腔鏡と5-ALAを応用した新規肺腫瘍マーキング法の開発
科学研究費助成事業
2022年01月04日 - 2024年03月31日
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。
日本学術振興会, 基盤研究(C), 北海道大学, 18K08774

肺がん糖鎖抗原を用いた光免疫とiRGDナノ粒子によるsiRNA送達システムの開発
科学研究費助成事業
2021年04月01日 - 2024年03月31日
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。
日本学術振興会, 基盤研究(C), 北海道大学, 21K08876

マウス肺癌モデルを用いたCD73を標的とした赤外光線免疫療法の確立
科学研究費助成事業
2021年04月01日 - 2024年03月31日
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）．
日本学術振興会, 基盤研究(C), 北海道大学, 21K07189

胸部悪性疾患に対する腫瘍特異的細径ナノ粒子を用いた光線力学的治療法の確立
科学研究費助成事業
2017年08月25日 - 2019年03月31日
加藤 達哉
光線力学的療法（PDT）は癌細胞に集積する光感受性物質にレーザー照射し、活性酸素の酸化作用により腫瘍を変性壊死させる。本研究は光感受性物質タラポルフィン（以下NPe6）をナノ粒子へ含有し、腫瘍の深部へ高濃度でNPe6を到達させることをその目的とした。完成したナノ粒子を電子顕微鏡にて観察、粒子径を確認した。細胞株を用いたFlow cytometryと蛍光顕微鏡を用いた解析で、 ナノ粒子封入NPe6はがん細胞内への取り込みが優位に亢進していることが示され、さらにナノ粒子にがん細胞特異的な葉酸リガンドを付加することでさらなる取り込み増強が確認できた。
日本学術振興会, 研究活動スタート支援, 北海道大学, 17H06489

肺癌血管内皮細胞を標的とした分子標的治療とコンパニオン診断薬の開発
科学研究費助成事業
2012年04月01日 - 2016年03月31日
樋田 泰浩, 加賀 基知三, 松居 喜郎, 加藤 達哉, 樋田 京子
担癌マウスの腫瘍血管内皮細胞，特に転移能の高い腫瘍から分離された腫瘍血管内皮細胞でビグリカンの高発現が顕著であった． siRNAでビグリカンをノックダウンすると，腫瘍細胞の血管内皮細胞の接着や細胞シート下層への浸潤の低下が認められた．マウスの肺転移モデルでは腫瘍血管内皮細胞を共移植すると転移能を持たない腫瘍細胞が転移能を獲得した．これは腫瘍血管内皮細胞におけるビグリカンの発現を抑制するとキャンセルされた．ヒト癌組織の免疫では腫瘍血管に特異的にビグリカンの発現が認められた．血液検体のELISA検査で担癌患者，特に転移陽性例で血清中ビグリカン濃度が高い傾向が認められた．
日本学術振興会, 基盤研究(B), 北海道大学, 24390324

腫瘍血管の分泌するエクソソームによる肺転移促進機序の解明
科学研究費助成事業
2012年04月01日 - 2014年03月31日
樋田 泰浩, 加賀 基知三, 松居 喜郎, 加藤 達哉, 樋田 京子
腫瘍の中の血管細胞（腫瘍血管内皮細胞, TEC）が分泌するマイクロRNA(miRNA)が腫瘍の遠隔転移を促進するという仮説の元に研究を行った．実験動物に移植してもほとんど転移しない悪性黒色腫の細胞株A375と同株から樹立された良く転移するA375SM("super metastatic")を用いた．それらの細胞株を移植したマウスに出来た腫瘍からそれぞれTECを分離してmiRNAを抽出し，miRNAマイクロアレイで発現量の比較を行った．見出したA375SMのTECに特異的に多いmiRNAを皮膚から分離された正常血管内皮細胞に導入すると，A375SMのTECと同様の性質を持つようになった．
日本学術振興会, 挑戦的萌芽研究, 北海道大学, 24659623

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
科学研究費助成事業
2012年 - 2012年
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。
日本学術振興会, 基盤研究(C), 北海道大学, 24592078