研究者詳細 - 芳川　豊史

Commentary: To know yourself is to know your neighbor

Nakanishi K., Chen-Yoshikawa T.F.

Journal of Thoracic and Cardiovascular Surgery 2021年

Commentary: Look Before You Leap

Fukumoto K., Chen-Yoshikawa T.F.

Seminars in Thoracic and Cardiovascular Surgery 2021年

Learning curve of robotic lobectomy for lung malignancies by certified thoracic surgeons

Fukui T., Kawaguchi K., Tsubouchi H., Ueno H., Sugiyama T., Mori S., Goto M., Ozeki N., Hakiri S., Nakamura S., Chen-Yoshikawa T.F.

Nagoya Journal of Medical Science 83 巻 ( 2 ) 頁： 227 - 237 2021年

記述言語：日本語出版者・発行元：Nagoya Journal of Medical Science

Video-assisted thoracic surgery (VATS) has become widespread in the last 20 years, followed by robot-assisted thoracic surgery (RATS). Few studies compared the learning curve between RATS lobectomy and conventional VATS. This study included 79 RATS lobectomy cases performed in our hospital from November 2015 to October 2019. To estimate the required number for learning, the cumulative sum method, which is to plot a value obtained by sequentially accumulating a difference from a mean value was applied. As a result, the median total operative time and the median console time for all cases were 167 minutes and 138 minutes, respectively. Firstly, for our team, 28 cases were estimated to be required for learning curve for RATS lobectomy. For individual, each surgeon might be learned in only 5 to 6 cases. By contrast, the number of cases for learning VATS lobectomy which was underwent by a ‘single' surgeon from 2009 was estimated to be 35 cases. The time to dock from start operation (median 14 minutes) reached plateau in 18 cases, but the time after rollout was median of 18 minutes and there was no significant change from the beginning. In conclusion, RATS lobectomy might be a technique that could be learned in a small number of cases compared to VATS. The results of this study might be helpful for certified surgeons who tried to get started with RATS and for establishing a learning program.

DOI： 10.18999/nagjms.83.2.227

Prognostic Value of Uncertain Resection for Overall Survival in Non-small Cell Lung Cancer

Kadomatsu Y., Nakamura S., Ueno H., Goto M., Ozeki N., Fukumoto K., Fukui T., Suzuki Y., Chen-Yoshikawa T.F.

Annals of Thoracic Surgery 2021年

記述言語：日本語出版者・発行元：Annals of Thoracic Surgery

Background: In this study we evaluated the R(un) category proposed by the International Association for the Study of Lung Cancer (IASLC) for non-small cell lung cancer (NSCLC). Methods: We retrospectively reviewed the medical records of patients with NSCLC who underwent segmentectomy or lobectomy between 2014 and 2015 at our institution. Residual tumor (R) status was reclassified from the Union for International Cancer Control designation to the IASLC-proposed R classification of R0 and R(un). The underlying reasons for the R(un) reclassification were analyzed according to pathologic stage, lymph node status, and resected lobe. A Cox proportional hazard model was used to evaluate the impacts of R(un) categorization on overall survival. Results: Of 355 patients, 44.5% were reclassified as R(un). The most common reason for the reclassification was insufficient number of harvested lymph nodes or no station 7 lymph nodes. When stratified by tumor location, the absence of station 7 lymph nodes was especially prominent in both the right and left upper lung resections. In the multivariate Cox regression model, the IASLC R classification was associated with poor overall survival in node-positive patients (hazard ratio, 2.657; P =.016). Conclusions: Various factors resulted in reclassification to R(un) because the R(un) group was highly heterogeneous. Careful consideration is required to determine whether the R(un) classification can be used as an indicator of lymph node dissection quality. For advanced cases, the R(un) definition may be useful in predicting poor prognosis.

DOI： 10.1016/j.athoracsur.2021.07.087

The importance of central airway dilatation in patients with bronchiolitis obliterans

Kogo M., Matsumoto H., Tanabe N., Chen-Yoshikawa T.F., Nakajima N., Yoshizawa A., Oguma T., Sato S., Nomura N., Morimoto C., Sunadome H., Gotoh S., Ohsumi A., Date H., Hirai T.

ERJ Open Research 7 巻 ( 4 ) 2021年

出版者・発行元：ERJ Open Research

Background Bronchiolitis obliterans (BO) is a clinical syndrome characterised by progressive small airway obstruction, causing significant morbidity and mortality. Central airway dilatation is one of its radiological characteristics, but little is known about the clinical and pathological associations between airway dilatation and BO. Methods This retrospective study consecutively included patients who underwent lung transplantation due to BO at Kyoto University Hospital from 2009 to 2019. Demographic and histopathological findings of the resected lungs were compared between patients with and without airway dilatation measured by chest computed tomography (CT) at registration for lung transplantation. Results Of a total of 38 included patients (median age, 30 years), 34 (89%) had a history of hematopoietic stem-cell transplantation, and 22 (58%) had airway dilatation based on CT. Patients with airway dilatation had a higher frequency of Pseudomonas aeruginosa isolation with greater residual volume than those without airway dilatation. Quantitative CT analysis revealed an increase in lung volume to predictive total lung capacity and a percentage of low attenuation volume <−950 HU at inspiration in association with the extent of airway dilatation. Airway dilatation on CT was associated with an increased number of bronchioles with concentric narrowing of the lumen and thickening of the subepithelium of the walls on histology. Conclusions In patients with BO, airway dilatation may reflect increased residual volume or air trapping and pathological extent of obstructive bronchioles, accompanied by a risk of Pseudomonas aeruginosa isolation. More attention should be paid to the development of airway dilatation in the management of BO.

DOI： 10.1183/23120541.00123-2021

肺移植後遠隔期における健康関連QoLの実態と関連因子の検討

大島洋平, 太田垣あゆみ, 吉岡佑二, 濱田涼太, 梶本泰志, 増本枝里子, 芳川豊史, 伊達洋至, 佐藤晋, 松田秀一

呼吸理学療法学 7th.Meeting 巻 ( 0 ) 頁： SJ-2 2021年

肺移植における術後早期栄養介入の試み

池田政樹, 中島大輔, 大島綾子, 大島洋平, 栢分秀直, 田中里奈, 山田義人, 豊洋次郎, 大角明宏, 濱路政嗣, 芳川豊史, 伊達洋至

移植 56 巻 ( Supplement ) 頁： s104 - s104 2021年

記述言語：日本語出版者・発行元：一般社団法人日本移植学会

背景：肺移植後の栄養管理では, 体外循環使用に伴う腸管浮腫, 誤嚥, 肺水腫に注意が必要で, 既存のプロトコルは無い. 今回プロトコルを作成, 導入したので, その成果を報告する.対象と方法：2019年1月から2020年12月に当院で実施した18歳以上の肺移植43例を対象とした. プロトコルは, 術後2-3日に経腸栄養または中心静脈栄養を開始し, 術後7日目の目標エネルギーを標準体重×25 kcal, 蛋白量を標準体重×1 gとし, 極端なやせは現体重を用いた. プロトコル開始前28例（前群）と開始後15例（後群）で, 栄養開始日, 術後7日目の栄養充足率, 体重・体組成の変化, 脊柱起立筋の筋量（CT断面積）を比較した.結果：経腸栄養は中央値で前群71%, 後群100%, 中心静脈栄養は前群79%, 後群100%に実施された. 栄養開始は後群で早かった（前群4日, 後群3日, p=0.004）. 術後7日目のエネルギー充足率は前群69%, 後群83%（p=0.010）, 蛋白充足率は前群74%, 後群95%（p=0.008）であった. 術後1か月, 3か月の体重減少は後群で有意に抑制された（-3.7 kg vs -1.4 kg, p=0.031; -4.4 kg vs -0.1 kg, p=0.013）. 術後2か月で細胞外水分率に差はなく, 体重に対する浮腫の影響は否定的であった. ICU退室時に見られた筋量減少（前群-16%, 後群-12%）は, 術後3か月で後群において有意に回復していた（前群-14%, 後群-4%, p=0.009）.結語：早期栄養介入により, 術後早期の体重減少, 筋量減少が抑制された可能性がある.

DOI： 10.11386/jst.56.supplement_s104

肺移植におけるEx Vivo Lung Perfusionの現状

中島大輔, 芳川豊史, 伊達洋至

移植 56 巻 ( Supplement ) 頁： s556 - s556 2021年

記述言語：日本語出版者・発行元：一般社団法人日本移植学会

脳死関連肺傷害を受けているマージナルドナー肺の使用には、移植前にその傷害を的確に評価することにより、移植後の虚血再灌流傷害を予防しうる、より優れた臓器保存法が必要である。Ex Vivo Lung Perfusion（EVLP）は、正常体温（37℃）下に換気と灌流が維持された状態で臓器を保存することにより、移植前の体外での的確な肺機能評価と臓器保存時間の延長を可能にした。2000年に初めて、スウェーデングループが心停止ドナー肺の評価のために、EVLPを臨床の現場に導入して以降、世界各国においてEVLPを用いた臨床試験が行われている。EVLP評価により、移植適応ありと判断されたマージナルドナー肺を用いた肺移植は、良好な移植後成績を示しただけでなく、ドナー肺の使用率を倍増させることに成功している。本邦では2015年に初めて、EVLPを用いた肺移植が１例のみ単発で行われ、その有用性が報告された。京都大学では、2018年よりEVLPの臨床導入の準備を進め、2020年に実症例を経験した。他施設にて移植が断念されたマージナル肺を、EVLPにより的確に評価することで救い上げ、移植に成功することができた。EVLPによる的確な移植前機能評価は、マージナルドナー肺の使用拡大による移植待機患者の予後改善だけでなく、移植後患者の移植後成績改善のために、本邦においても重要になってくると考えられる。

DOI： 10.11386/jst.56.supplement_s556

多職種チームで行う「献体を用いた臓器摘出トレーニング」in Clinical Anatomy Laboratory Nagoya (CALNA)

中村彰太, 六鹿雅登, 後藤和大, 仲西慶太, 杉山燈人, 門松由佳, 上野陽史, 後藤真輝, 尾関直樹, 福本紘一, 伊藤英樹, 小山富生, 碓氷章彦, 芳川豊史

移植 56 巻 ( Supplement ) 頁： s105 - s105 2021年

記述言語：日本語出版者・発行元：一般社団法人日本移植学会

【背景】脳死ドナー臓器摘出では、外科医だけでなく臨床工学技士（ME）・看護師・コーディネーター等多職種が関わる医療で、実際の手技を知っていればよりよい連携が可能かもしれない。献体されたご遺体の固定方法は進化しており、特殊な保存液で固定された状態は生体と類似しているため、手術トレーニングに用いることが可能となった。肺移植実施施設でない当院での実施施設へのとり組みの一貫として、心臓外科医・ME・医学生と合同で臓器摘出トレーニングを実行したので報告する。【トレーニング概要】開胸・心嚢切開し臓器評価方法を全員で確認した後、心灌流液注入用と肺灌流液ドレナージ用のカテーテルを各留置し、大血管を遮断し心臓摘出、続いて肺摘出を行った。続いてバックテーブルにて肺の植え込みができる状態にまで処理を行いトレーニング終了とした。心肺摘出に際して重要となる左房の処理については、操作を止め指導医にポイントを解説してもらいつつ、心臓外科・呼吸器外科の双方の考えを伝え、解剖を確認しながら行った。また、MEと肺灌流液ドレナージ経路の方法や肺灌流のタイミングなど細やかな部分まで共有できた。【結語】本トレーニングは多職種での手技と順序の確認に有用で、臓器摘出の際互いに心がけているポイントや考えも共有・理解できた。今後はプログラムを定型化し、実践に対応できるレベルに質を高めつつ、看護師やコーディネーターも含めて行う予定である。

DOI： 10.11386/jst.56.supplement_s105

Backtable bronchoplasty for donor tracheal bronchus in lung transplantation.

So Miyahara, Masatsugu Hamaji, Akihiro Aoyama, Daisuke Nakajima, Hideki Motoyama, Toyofumi F Chen-Yoshikawa, Hiroshi Date

General thoracic and cardiovascular surgery 68 巻 ( 12 ) 頁： 1536 - 1538 2020年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

The management of a tracheal bronchus in lung transplantation is poorly studied and ill-defined. We report a case of lung transplantation performed using a donor right lung graft with an apical tracheal bronchus and propose a novel anastomosis technique for this procedure. The neo-upper lobe bronchus created by suturing the apical tracheal bronchus and the upper lobe bronchus of the donor was anastomosed to the upper lobe bronchus of the recipient in a double-barrel fashion. A follow-up at 19 months demonstrated no stenosis of the anastomosis. The advantages and potential disadvantages of this procedure are discussed.

DOI： 10.1007/s11748-020-01305-6

Development of an immuno-wall device for the rapid and sensitive detection of EGFR mutations in tumor tissues resected from lung cancer patients

Yogo N., Hase T., Kasama T., Nishiyama K., Ozawa N., Hatta T., Shibata H., Sato M., Komeda K., Kawabe N., Matsuoka K., Chen-Yoshikawa T.F., Kaji N., Tokeshi M., Baba Y., Hasegawa Y.

PLoS ONE 15 巻 ( 11 November ) 2020年11月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：PLoS ONE

Detecting molecular targets in specimens from patients with lung cancer is essential for targeted therapy. Recently, we developed a highly sensitive, rapid-detection device (an immuno-wall device) that utilizes photoreactive polyvinyl alcohol immobilized with antibodies against a target protein via a streptavidin–biotin interaction. To evaluate its performance, we assayed epidermal growth factor receptor (EGFR) mutations, such as E746_A750 deletion in exon 19 or L858R substitution in exon 21, both of which are common in non-small cell lung cancer and important predictors of the treatment efficacy of EGFR tyrosine kinase inhibitors. The results showed that in 20-min assays, the devices detected as few as 1% (E746_A750 deletion) and 0.1% (L858R substitution) of mutant cells. Subsequent evaluation of detection of the mutations in surgically resected lung cancer specimens from patients with or without EGFR mutations and previously diagnosed using commercially available, clinically approved genotyping assays revealed diagnostic sensitivities of the immuno-wall device for E746_A750 deletion and L858R substitution of 85.7% and 87.5%, respectively, with specificities of 100% for both mutations. These results suggest that the immuno-wall device represents a good candidate next-generation diagnostic tool, especially for screening of EGFR mutations.

DOI： 10.1371/journal.pone.0241422

Orthotopic foetal lung tissue direct injection into lung showed a preventive effect against paraquat-induced acute lung injury in mice

CT画像を用いた肺葉切除後の呼吸機能と運動耐容能の予測

尾関直樹, 坪内秀樹, 仲西慶太, 杉山燈人, 門松由佳, 上野陽史, 後藤真輝, 中村彰太, 福井高幸, 芳川豊史

日本胸部外科学会定期学術集会 73回巻頁： LOO14 - 6 2020年10月

非小細胞肺癌Oligometastases例に対する局所治療を加えた集学的治療成績

杉山燈人, 中村彰太, 坪内秀樹, 仲西慶太, 門松由佳, 上野陽史, 後藤真輝, 尾関直樹, 福井高幸, 芳川豊史

日本胸部外科学会定期学術集会 73回巻頁： LOO1 - 40 2020年10月

Impact of inspiratory muscle strength on exercise capacity after lung transplantation.-a longitudinal study in early stage

Sato Tatsuya, Tabira Kazuyuki, Sato Susumu, Oshima Yohei, Yoshioka Yuji, Hamada Ryota, Tanimura Kazuya, Yoshikawa Toyofumi, Date Hiroshi, Matsuda Shuichi

EUROPEAN RESPIRATORY JOURNAL 56 巻 2020年9月

Okabe R., Chen-Yoshikawa T.F., Yoshizawa A., Hirashima T., Saito M., Date H., Takebe T.

European Journal of Cardio-thoracic Surgery 58 巻 ( 3 ) 頁： 638 - 645 2020年9月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：European Journal of Cardio-thoracic Surgery

OBJECTIVES: Lung transplantation is the only effective therapy for patients with end-stage lung disease but an organ shortage crisis necessitates the development of alternative therapies. Recent studies have highlighted the potential of foetal tissue transplantation to facilitate the regeneration of vital organs such as liver that have been damaged by lethal diseases. Herein, with the aim of restoring pulmonary function, we hypothesized that allogenic foetal lung tissue implantation would attenuate severe respiratory failure. METHODS: Lung tissue from the foetuses of pregnant green fluorescent protein-C57BL/6 mice at 13.5 days of gestation was injected into the left lungs of recipient mice. Severe lung injury was induced by paraquat, and we analysed the survival rate and pathohistological findings after 1 month. RESULTS: The survival rate of the therapy group was 39%, which was significantly higher than the vehicle group at 5.9% (P = 0.034). Immunochemical staining showed that positive cytoplasmic stained cells with anti-interleukin-10 antibody were identified in the gland-like structure of embryonic day 13.5 foetal lung. At 4 weeks after orthotopic implantation, haematoxylin and eosin staining showed reduced lung inflammatory cells, reduced lung oedema and increased active cell proliferation of foetal lung cells. Lung injury score showed that the airway septal thickening revealed statistically significant differences between vehicle and foetal lung therapy (P < 0.001). CONCLUSIONS: Immature foetal lungs improved the survival rate of mice with paraquat-induced severe lung injury, establishing the need for systematic follow-up studies. The anti-inflammatory cytokine in the tissue from embryonic day 13.5 foetal lung might suppress severe lung injury.

DOI： 10.1093/ejcts/ezaa091

Diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration to assess tumor-programmed cell death ligand-1 expression in mediastinal lymph nodes metastasized from non-small cell lung cancer.

Katsutaka Mineura, Masatsugu Hamaji, Akihiko Yoshizawa, Naoki Nakajima, Hidenao Kayawake, Satona Tanaka, Yoshito Yamada, Yojiro Yutaka, Daisuke Nakajima, Akihiro Ohsumi, Toshi Menju, Toyofumi F Chen-Yoshikawa, Hiroshi Date

Surgery today 50 巻 ( 9 ) 頁： 1049 - 1055 2020年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: We investigated the utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to evaluate programmed cell death ligand-1 (PD-L1) expression in patients with advanced non-small cell lung cancer (NSCLC). METHODS: A retrospective chart review of patients who underwent EBUS-TBNA between April 2017 and April 2019 was conducted. Among patients diagnosed with NSCLC, we investigated the rate of successful evaluation of tumor PD-L1 expression, compared the relevant factors between patients with evaluable and those with unevaluable PD-L1 expression, and examined the response to immune checkpoint inhibitors (ICIs) after EBUS-TBNA. RESULTS: Of the 40 patients assessed, 32 (80%) had evaluable PD-L1 expression. Patients with evaluable PD-L1 expression were older than those with unevaluable PD-L1 expression (p = 0.017), and we noted a tendency for a larger diameter of the biopsied lymph node (p = 0.12). The response rate to ICIs was 100% in patients with a tumor proportion score (TPS) ≥ 50%, 33% in those with a TPS 1-49%, and 0% in those with a TPS < 1%. CONCLUSION: The diagnostic yield of EBUS-TBNA to evaluate PD-L1 expression in advanced NSCLC appeared acceptable in association with relevant clinical outcomes after treatment with ICIs. A further prospective study with a larger sample size is required to confirm our findings.

DOI： 10.1007/s00595-020-01989-6

Expanded indications for auto-lung transplant technique.

Daisuke Nakajima, Akihiro Ohsumi, Masatsugu Hamaji, Toyofumi F Chen-Yoshikawa, Hiroshi Date

General thoracic and cardiovascular surgery 68 巻 ( 8 ) 頁： 828 - 832 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: Lung autotransplantation was originally developed to avoid pneumonectomy for centrally located lung cancer. We herein report our experience with lung autotransplantation for the treatment of various types of lung diseases. METHODS: This is a single-center case series of lung autotransplantation with ex vivo bench surgery. Five patients underwent lung autotransplantation between September 2014 and October 2018. A common surgical technique was as follows: pneumonectomy was first completed. The intact lobes were then separated ex vivo, flushed using cold ET-Kyoto solution on a back table, and reimplanted. RESULTS: The indications for lung autotransplantation were postpneumonectomy-like syndrome, locally advanced lung cancer, pulmonary artery sarcoma, central lung cancer, and bronchopleural fistula after right upper bronchial sleeve lobectomy. No major post-transplant complications were observed except for mild stenosis of bronchial anastomosis in one case that required bronchial intervention. One patient died of recurrence of pulmonary artery sarcoma 14 months after surgery. The other patients are alive without any recurrence of the native respiratory diseases or symptoms. CONCLUSIONS: Lung autotransplantation following ex vivo bench surgery was found to be technically feasible for various lung diseases, showing a favorable early post-transplant outcome.

DOI： 10.1007/s11748-020-01289-3

部分肺静脈還流異常と気管気管支を認めた右上葉肺癌切除の1例

伊藤俊成, 福井高幸, 羽切周平, 中村彰太, 川口晃司, 芳川豊史

日本呼吸器外科学会雑誌 34 巻 ( 5 ) 頁： 321 - 326 2020年7月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：特定非営利活動法人日本呼吸器外科学会

76歳男性．下顎腫瘤精査中に胸部X線写真で右肺に結節影を指摘された．経気管支肺生検で腺癌と診断され，造影CTの結果原発性肺腺癌cT1bN0M0と診断し手術を行うこととなった．その際のCTで上葉肺静脈と中葉肺静脈が上大静脈に還流する部分肺静脈還流異常と右B1気管支が気管から分岐する転位気管支分岐異常を認めた．手術は胸腔鏡下に開始したが解剖学的位置関係の把握が困難となり，最終的には小開胸を併用し胸腔鏡補助下に右肺上葉切除およびリンパ節郭清を施行した．本例では術前に両異常の存在を予測して手術に臨んだが，術中に解剖学的把握が困難となり，小開胸の併用を要した．稀な解剖学的異常が疑われる症例では，術前のCT画像をより理解することが重要であるが，術中に解剖の把握が困難になった際には，直視での確認が安全な手術の遂行に有用であった．

DOI： 10.2995/jacsurg.34.321

Model-based registration for pneumothorax deformation analysis using intraoperative cone-beam CT images. 国際誌

Hinako Maekawa, Megumi Nakao, Katsutaka Mineura, Toyofumi F Chen-Yoshikawa, Tetsuya Matsuda

Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference 2020 巻頁： 5818 - 5821 2020年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Because the lung deforms during surgery because of pneumothorax, it is important to be able to track the location of a tumor. Deformation of the whole lung can be estimated using intraoperative cone-beam CT (CBCT) images. In this study, we used deformable mesh registration methods for paired CBCT images in the inflated and deflated states, and analyzed their deformation. We proposed a deformable mesh registration framework for deformations of partial organ shapes involving large deformation and rotation. Experimental results showed that the proposed methods reduced errors in point-to-point correspondence. As a result of registration using surgical clips placed on the lung surface during imaging, it was confirmed that an average error of 3.9 mm occurred in eight cases. The result of analysis showed that both tissue rotation and contraction had large effects on displacement.

DOI： 10.1109/EMBC44109.2020.9176729