研究者詳細 - 杉本　誠一郎

論文 - 杉本　誠一郎

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Novel pulmonary abdominal normothermic regional perfusion circuit for simultaneous in-donor evaluation and preservation of lungs and abdominal organs in donation after circulatory death.

Shin Tanaka, Masashi Umeda, Hiroyuki Ujike, Tsuyoshi Ryuko, Yasuaki Tomioka, Kentaroh Miyoshi, Mikio Okazaki, Seiichiro Sugimoto, Shinichi Toyooka

General thoracic and cardiovascular surgery 2025年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: To overcome limitations of traditional ex vivo lung perfusion (EVLP) for controlled donation after circulatory death (cDCD) lungs, this study aimed to evaluate a novel pulmonary abdominal normothermic regional perfusion (PANRP) technique, which we uniquely designed, for in situ assessment of lungs from cDCD donors. METHODS: We modified the abdominal normothermic regional perfusion circuit for simultaneous lung and abdominal organ assessment using independent extracorporeal membrane oxygenation components. Blood was oxygenated via a membrane oxygenator and returned to the body, with pulmonary flow adjusted to maintain pressure < 25 mmHg. Femoral cannulation was performed, and the lungs were ventilated with standard settings. Organ function was assessed over 2 h using PaO2/FiO2, AST, ALT, BUN, and Cr measurements to monitor perfusion and oxygen delivery. RESULTS: PANRP maintained stable lung function, with P/F ratios above 300, and preserved abdominal organ parameters, including stable AST, ALT, BUN, and Cr levels. Adequate urine output was observed, indicating normal renal function. Pulmonary artery pressure remained < 20 mmHg, and pulmonary vascular resistance was kept at 400 dyn・s/cm5, showing no signs of lung dysfunction or injury throughout the circuit. CONCLUSIONS: PANRP offers a promising alternative to traditional EVLP for cDCD lung evaluation, allowing in situ assessment of multiple organs simultaneously. This approach may overcome logistical and economic challenges associated with ex vivo techniques, enabling a more efficient evaluation process. Further studies are warranted to confirm its clinical applicability and impact on long-term outcomes.

DOI： 10.1007/s11748-025-02137-y

Nightmare case of repeated hemorrhagic pancreatitis due to pancreatic head cancer in the acute stage after two-stage lung transplantation

Tatsuya Hayashi, Shin Tanaka, Tsuyoshi Ryuko, Yasuaki Tomioka, Kentaroh Miyoshi, Mikio Okazaki, Seiichiro Sugimoto, Shinichi Toyooka

JHLT Open 100245 - 100245 2025年3月

Secondary Pneumothorax Due to Aspergillus welwitschiaein in a Lung Transplant Recipient. 国際誌

Shinnosuke Fukushima, Hideharu Hagiya, Sayaka Ban, Takashi Yaguchi, Akira Watanabe, Shin Tanaka, Seiichiro Sugimoto

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 107863 - 107863 2025年2月

Survival and functional outcomes after pediatric living-donor lobar lung transplantation and deceased-donor lung transplantation: A Japanese multicenter retrospective study. 国際誌

Yuki Morimura, Kei Matsubara, Satona Tanaka, Haruki Choshi, Shin Tanaka, Takashi Kanou, Yojiro Yutaka, Akihiro Ohsumi, Daisuke Nakajima, Yasushi Shintani, Seiichiro Sugimoto, Shinichi Toyooka, Hiroshi Date

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 2025年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: In pediatric living-donor lobar lung transplantation, whether transplanting adult lobes could result in satisfactory long-term survival and respiratory functional outcomes during and after the growth period in pediatric patients remains unclear. This study aimed to evaluate the long-term survival and functional prognosis after pediatric living-donor lobar lung transplantation and deceased-donor lung transplantation. METHODS: We retrospectively reviewed clinical data of pediatric patients (age: ≤17 years) who underwent lung transplantation between March 2001 and December 2022 at three institutions in Japan. RESULTS: Seventy and 24 patients who underwent living-donor and deceased-donor transplantation, respectively, were included. The 5-year and 10-year overall survival rates were 84.6% and 75.0% after living-donor transplantation and 85.8% and 85.8% after deceased-donor transplantation (p = 0.75), respectively. With a median follow-up period of 89.2 months, 48 living-donor cases (100%) and 16 deceased-donor cases (84.2%) had performance status 0-2 among 48 living-donor cases and 19 deceased-donor cases who were alive without re-transplantation. They showed height growth (median +9.7 cm, p < 0.01); however, the height standard deviation score decreased after transplantation (median -0.22, p = 0.03). The difference in height standard deviation score between the last follow-up and pre-transplantation was negative (median -0.42) in living-donor cases and significantly smaller than that in deceased-donor cases (median +0.19, p = 0.02). CONCLUSIONS: Pediatric living-donor lobar lung transplantation provided satisfactory long-term survival and functional prognosis that were comparable to those of deceased-donor lung transplantation. The limited post-transplant height growth in living-donor cases might be attributed to this favorable functional prognosis.

DOI： 10.1016/j.healun.2025.01.012

Long Short-Term Memory Algorithm for Personalized Tacrolimus Dosing: A Simple and Effective Time Series Forecasting Approach Post-Lung Transplantation. 査読国際誌

Haruki Choshi, Kentaroh Miyoshi, Maki Tanioka, Hayato Arai, Shin Tanaka, Kazuhiko Shien, Ken Suzawa, Mikio Okazaki, Seiichiro Sugimoto, Shinichi Toyooka

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 2024年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Management of tacrolimus trough levels influences morbidity and mortality after lung transplantation. Several studies have explored pharmacokinetic and artificial intelligence models to monitor tacrolimus levels. However, many models depend on a wide range of variables, some of which, like genetic polymorphisms, are not commonly tested for in regular clinical practice. This study aimed to verify the efficacy of a novel approach simply utilizing time series data of tacrolimus dosing, with the objective of accurately predicting trough levels in the variety of clinical settings. METHODS: Data encompassing 36 clinical variables for each patient were gathered, and a multivariate long short-term memory algorithm was applied to forecast subsequent tacrolimus trough levels based on the selected clinical variables. The tool was developed using a dataset of 87,112 data points from 117 patients and its efficacy was confirmed using six additional cases. RESULTS: Shapley Additive exPlanations revealed a significant correlation between trough levels and prior dose-concentration data. By using simple trend learning of dose, administration route, and previous trough levels of tacrolimus, we could predict values within 30% of the actual values for 88.5% of time points, which facilitated the creation of a tool for simulating tacrolimus trough levels in response to dosage adjustments. The tool exhibited the potential for rectifying clinical misjudgments in a simulation cohort. CONCLUSIONS: Utilizing our time series forecasting tool, precise prediction of trough levels is attainable independently of other clinical variables, through the analysis of historical tacrolimus dose-concentration trends alone.

DOI： 10.1016/j.healun.2024.10.026

Late living-donor kidney transplantation from the same donor after living-donor lobar lung transplantation. 査読国際誌

Tsuyoshi Ryuko, Seiichiro Sugimoto, Shin Tanaka, Kentaroh Miyoshi, Megumi Ishihara, Yuichi Shibuya, Shinichi Toyooka

JHLT open 6 100153 - 100153 2024年11月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Chronic kidney disease (CKD) is a common late complication associated with increased mortality after lung transplantation. Given the increased risk of infection in dialysis patients, late living-donor kidney transplantation (LDKT) provides excellent long-term survival in patients on dialysis after lung transplantation. However, recipients of living-donor lobar lung transplantation (LDLLT) might have scarce opportunity to receive LDKT due to the limited availability of living donors (LDs) for the second transplantation. We describe a successful case of late LDKT from the same donor after LDLLT. A 23-year-old woman with lymphangioleiomyomatosis underwent bilateral LDLLT of the right lower lobe from her brother and left lower lobe from her mother. Twelve years after LDLLT, she required hemodialysis for severe CKD. At the age of 37, she underwent LDKT from her mother, who was also an LD for the LDLLT. The postoperative courses of both the recipient and donor were uneventful, and the recipient remains in good physical condition (at the time of writing) despite developing recurrent lymphangioleiomyomatosis 23 years after the LDLLT, that is, 9 years after the LDKT. Her mother, the dual-organ LD, was able to return to her previous lifestyle. Late LDKT even from the same donor might be a viable option for patients developing severe CKD after LDLLT.

DOI： 10.1016/j.jhlto.2024.100153

Deep learning-based approach for acquisition time reduction in ventilation SPECT in patients after lung transplantation. 査読

Masahiro Nakashima, Ryohei Fukui, Seiichiro Sugimoto, Toshihiro Iguchi

Radiological physics and technology 2024年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

We aimed to evaluate the image quality and diagnostic performance of chronic lung allograft dysfunction (CLAD) with lung ventilation single-photon emission computed tomography (SPECT) images acquired briefly using a convolutional neural network (CNN) in patients after lung transplantation and to explore the feasibility of short acquisition times. We retrospectively identified 93 consecutive lung-transplant recipients who underwent ventilation SPECT/computed tomography (CT). We employed a CNN to distinguish the images acquired in full time from those acquired in a short time. The image quality was evaluated using the structural similarity index (SSIM) loss and normalized mean square error (NMSE). The correlation between functional volume/morphological volume (F/M) ratios of full-time SPECT images and predicted SPECT images was evaluated. Differences in the F/M ratio were evaluated using Bland-Altman plots, and the diagnostic performance was compared using the area under the curve (AUC). The learning curve, obtained using MSE, converged within 100 epochs. The NMSE was significantly lower (P < 0.001) and the SSIM was significantly higher (P < 0.001) for the CNN-predicted SPECT images compared to the short-time SPECT images. The F/M ratio of full-time SPECT images and predicted SPECT images showed a significant correlation (r = 0.955, P < 0.0001). The Bland-Altman plot revealed a bias of -7.90% in the F/M ratio. The AUC values were 0.942 for full-time SPECT images, 0.934 for predicted SPECT images and 0.872 for short-time SPECT images. Our findings suggest that a deep-learning-based approach can significantly curtail the acquisition time of ventilation SPECT, while preserving the image quality and diagnostic accuracy for CLAD.

DOI： 10.1007/s12194-024-00853-3

Loss of Nr4a1 ameliorates endothelial cell injury and vascular leakage in lung transplantation from circulatory-death donor. 査読国際誌

Shinichi Kawana, Mikio Okazaki, Tomohisa Sakaue, Kohei Hashimoto, Kentaro Nakata, Haruki Choshi, Shin Tanaka, Kentaroh Miyoshi, Shinji Ohtani, Toshiaki Ohara, Seiichiro Sugimoto, Akihiro Matsukawa, Shinichi Toyooka

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 2024年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Ischemia-reperfusion injury (IRI) stands as a major trigger for primary graft dysfunction (PGD) in lung transplantation (LTx). Especially in LTx from donation after cardiac death (DCD), effective control of IRI following warm ischemia (WIRI) is crucial to prevent PGD. This study aimed to identify the key factors affecting WIRI in LTx from DCD. METHODS: Previously reported RNA-sequencing dataset of lung WIRI was reanalyzed to identify nuclear receptor subfamily 4 group A member 1 (NR4A1) as the immediate early gene for WIRI. Dynamics of NR4A1 expression were verified using a mouse hilar clamp model. To investigate the role of NR4A1 in WIRI, a mouse model of LTx from DCD was established using Nr4a1 knockout (Nr4a1-/-) mice. RESULTS: NR4A1 was located around vascular cells, and its protein levels in the lungs increased rapidly and transiently during WIRI. LTｘ from Nr4a1-/- donors significantly improved pulmonary graft function compared to wild-type donors (P < 0.001). Histological analysis showed decreased microvascular endothelial cell death (P = 0.007), neutrophil infiltration (P < 0.001), and albumin leakage (P < 0.001). Evans blue permeability assay demonstrated maintained pulmonary microvascular barrier integrity in grafts from Nr4a1-/- donors, correlating with diminished pulmonary edema (P < 0.001). However, NR4A1 did not significantly affect the inflammatory response during WIRI, and IRI was not suppressed when a wild-type donor lung was transplanted into the Nr4a1-/- recipient. CONCLUSIONS: Donor NR4A1 plays a specialized role in the positive regulation of endothelial cell injury and microvascular hyperpermeability. These findings demonstrate the potential of targeting NR4A1 interventions to alleviate PGD and improve outcomes in LTx from DCD.

DOI： 10.1016/j.healun.2024.09.028

A Case of Single-lung Transplant in a Patient with Mycobacterium avium Pulmonary Disease Successfully Treated with Amikacin Liposome Inhalation Suspension. 査読

Taichi Ozeki, Hisao Higo, Hiroki Omori, Shunta Mori, Shin Tanaka, Go Makimoto, Kiichiro Ninomiya, Akihiko Taniguchi, Masanori Fujii, Kentaro Miyoshi, Kammei Rai, Eiki Ichihara, Kadoaki Ohashi, Seiichiro Sugimoto, Katsuyuki Hotta, Masahiro Tabata, Shinichi Toyooka, Yoshinobu Maeda, Nobuaki Miyahara

Internal medicine (Tokyo, Japan) 2024年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

A 55-year-old man presented to our hospital with idiopathic pulmonary fibrosis (IPF). He was registered with the Japan Organ Transplant Network the following year due to disease progression. Treatment with clarithromycin, ethambutol, and rifampicin for complications of Mycobacterium avium pulmonary disease was initiated, but sputum conversion could not be achieved. The administration of an amikacin liposome inhalation suspension (ALIS) resulted in sputum conversion, and single-lung transplantation was performed. ALIS therapy was continued after lung transplantation, and no M. avium disease was observed for 15 months. ALIS may cause M. avium pulmonary disease with additional indications for lung transplantation.

DOI： 10.2169/internalmedicine.3854-24

Prophylactic effect of tissue flap in the prevention of bronchopleural fistula after surgery for lung cancer. 査読

Tomohiro Habu, Hiromasa Yamamoto, Kentaro Nakata, Kohei Hashimoto, Shin Tanaka, Kazuhiko Shien, Ken Suzawa, Kentaroh Miyoshi, Mikio Okazaki, Seiichiro Sugimoto, Shinichi Toyooka

Surgery today 2024年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Bronchopleural fistula (BPF) is a serious complication of lung resection. To avoid BPF, the bronchial stump/anastomotic site is often covered with a flap of surrounding tissue. One risk factor for BPF is radical lung resection after induction chemoradiotherapy for lung cancer. We retrospectively reviewed our database to elucidate the characteristics of tissue flaps that prevent BPF. METHODS: This retrospective study included 152 patients treated between 1999 and 2019. We examined the clinicopathological characteristics, including the type and thickness of the tissue flap used to cover the bronchial stump/anastomotic site, and postoperative complications, including BPF. RESULTS: BPF occurred in 5 patients (3.3%). All 5 patients had complications that could have affected delayed wound healing, such as pneumonia. The covering tissue flap thickness was significantly greater in patients without BPF than in those who developed BPF (p = 0.0290). Additionally, the tissue flap thickness was significantly greater than in those with BPF (p = 0.0077), even in high-risk patients who developed pneumonia or radiation pneumonitis on the operative side within 6 months postoperatively. CONCLUSION: Perioperative management is crucial to avoid complications affecting the healing of the bronchial stump/anastomotic site, and the covering tissue flap thickness may be an important factor in avoiding or minimizing BPF.

DOI： 10.1007/s00595-024-02927-6

Augmented humoral response to third and fourth dose of SARS-CoV-2 mRNA vaccines in lung transplant recipients. 査読国際誌

Shinichi Kawana, Seiichiro Sugimoto, Kei Matsubara, Haruki Choshi, Shin Tanaka, Megumi Ishihara, Tomohiro Habu, Kohei Hashimoto, Ken Suzawa, Kazuhiko Shien, Kentaroh Miyoshi, Mikio Okazaki, Masanori Nakayama, Shinichi Toyooka

Respiratory investigation 62 ( 5 ) 804 - 810 2024年7月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Since lung transplant recipients (LTRs) exhibit low immunogenicity after two doses of SARS-CoV-2 mRNA vaccines, optimal vaccine strategies for SARS-CoV-2 are required in LTRs. This study aimed to investigate the efficacy and safety of the third and fourth doses of the SARS-CoV-2 mRNA vaccines in LTRs. METHODS: We conducted a single-center study of 73 LTRs and 23 healthy controls (HCs). Participants received two-to-four doses of SARS-CoV-2 mRNA vaccines. The LTRs were divided into three groups based on the number of vaccine dose. IgG titers against SARS-CoV-2 spike protein were measured, and adverse events were assessed. Factors associated with humoral response were analyzed using univariate and multivariate analyses. RESULTS: The Dose 4 group (n = 27) had a higher humoral response rate (P = 0.018) and higher levels of anti-SARS-CoV-2 IgG antibody (P = 0.04) than the Dose 2 group (n = 14). The Dose 3 group (n = 32) had lower humoral response rates (P = 0.005) and levels of anti-SARS-CoV-2 IgG antibody (P = 0.0005) than the HCs (n = 23) even after the same dose. Systemic adverse events were milder in the LTRs than in the HCs (P < 0.05). Increased number of vaccine dose was identified as a predictor of positive humoral response (P = 0.021). CONCLUSION: Booster doses of SARS-CoV-2 mRNA vaccines may enhance humoral response with mild adverse events in LTRs. Repeated vaccination might be warranted for LTRs to prevent SARS-CoV-2 infection.

DOI： 10.1016/j.resinv.2024.07.004

Pulmonary Vein Repair on Extracorporeal Life Support: A Potential Surgical Complication for 2-Staged Lung Transplantation: Case Report. 査読国際誌

Shin Tanaka, Kentaroh Miyoshi, Seiichiro Sugimoto, Shinichi Toyooka

Transplantation proceedings 2024年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Double-lung transplantation (DLT) is favored for enhanced long-term survival despite the risk of major complications, particularly in elderly patients or those with comorbidities. Two-stage contralateral single-lung transplantation (SLT) leading to DLT is considered a valuable option to combine the advantages of less invasive SLT with DLT survival benefits. This study detailed the intraoperative challenges encountered during the procedure. A 54-year-old patient with chronic lung allograft dysfunction after right SLT underwent contralateral (left) SLT because of left lung dysfunction. During surgery, unexpected complications arose from robust adhesions on the right side, a consequence of prior transplantation, causing difficulty in manipulating the heart position. The deep bifurcation of the left pulmonary vein posed challenges, leading to damage to the left atrium, necessitating extracorporeal circulation. Despite these complexities, successful anastomosis was achieved. This case highlights the importance of recognizing potential surgical difficulties in contralateral lung transplantation, particularly in cases with adhesions, and emphasizes the need for caution when managing deep pulmonary veins. This 2-stage approach holds promise for patients with poor health but emphasizes the significance of addressing the potential challenges inherent in the surgical procedure.

DOI： 10.1016/j.transproceed.2024.05.009

Utility of neutrophil-to-lymphocyte ratio as an indicator of tumor immune status in non-small cell lung cancer. 査読国際誌

Kazuma Iwata, Ken Suzawa, Kohei Hashimoto, Shin Tanaka, Kazuhiko Shien, Kentaroh Miyoshi, Hiromasa Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Shinichi Toyooka

Japanese journal of clinical oncology 2024年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has been reported as a prognostic biomarker in non-small cell lung cancer (NSCLC); however, the underlying biological rationale remains unclear. The present study aimed to explore the potential utility of NLR as a surrogate biomarker for immune response to cancer and to elucidate the underlying mechanism. METHODS: This retrospective study included the medical records of 120 patients with NSCLC who underwent surgery at the study institution in 2012. NLR in peripheral blood was determined from blood test within 30 days before surgery. Tumor immune status was evaluated using immunohistochemical staining to identify CD3+, CD8+ and FOXP3+ tumor-infiltrating lymphocytes (TILs), and the relationship of NLR, with clinicopathologic characteristics including 5-year overall survival (OS), and the tumor immune status was investigated. The median values of NLR and TIL count were used as cutoff points. RESULTS: The 5-year OS was significantly better in patients with low NLR (<2.2) than in those with high NLR (≥2.2) (70.1% vs. 56.8%, P = 0.042) and in patients with high CD3+ TIL count (≥242) than in those with low CD3+ TIL count (<242) (70% vs. 56.8%, P = 0.019). Additionally, the CD3+ TIL count was negatively correlated with preoperative NLR (P = 0.005). CONCLUSION: NLR might potentially reflect the immune status of tumor microenvironment, explaining its impact on prognosis of patients with NSCLC.

DOI： 10.1093/jjco/hyae058

Postoperative Complications in Living Donors for Lung Transplantation. 査読国際誌

Shin Tanaka, Kento Fujii, Megumi Ishihara, Haruki Choshi, Kei Matsubara, Kohei Hashimoto, Shuji Okahara, Kazuhiko Shien, Ken Suzawa, Kentaroh Miyoshi, Hiromasa Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Shinichi Toyooka

Transplantation direct 10 ( 5 ) e1617 2024年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Living donor lobar lung transplantation is a life-saving procedure for critically ill patients. This requires 2 healthy donors exposed to risks and without medical benefit. Therefore, the donor's safety and minimal postoperative complications are crucial. This study aimed to investigate the short-term outcomes and identify the risk factors affecting these outcomes. METHODS: The data of 175 living donors enrolled between 1998 and 2022 were analyzed. Donors were divided into era 1 (1998-2009) and era 2 (2010-2022). RESULTS: The overall incidence of postoperative complications was 39%, of which 7% were major complications. Donors who underwent surgery on the right side had a higher incidence of delayed pulmonary fistulae (P = 0.01) and elevated liver enzyme levels (P = 0.028). Living donor surgery on the right side (P = 0.01), era 2 (P = 0.01), and the need for plasty (P = 0.04) were predictors of postoperative complications. CONCLUSIONS: Updated data on complications and their correlation with postoperative quality of life from this study could aid in the selection of potential donors and facilitate informed consent.

DOI： 10.1097/TXD.0000000000001617

Effective division of the intersegmental plane using a robotic stapler in robotic pulmonary segmentectomy. 査読

Mikio Okazaki, Ken Suzawa, Kazuhiko Shien, Kohei Hashimoto, Shin Tanaka, Kentaroh Miyoshi, Hiromasa Yamamoto, Seiichiro Sugimoto, Shinichi Toyooka

Surgery today 2024年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSES: Robot-assisted thoracoscopic (RATS) segmentectomy is becoming increasingly common because of the expanded indications for segmentectomy and the widespread adoption of robotic surgery. The precise division of the intersegmental plane is necessary to ensure oncologic margins from the tumor and to preserve the lung function. In this study, we present a strategy for accurately dividing the intersegmental plane using a robotic stapler and review the surgical outcomes. METHODS: RATS portal segmentectomy was performed using the Da Vinci Xi system and the intersegmental plane was dissected using a robotic stapler. We evaluated the perioperative outcomes in 92 patients who underwent RATS portal segmentectomy between May 2020 and January 2023. These results were compared with those of 82 patients who underwent complete video-assisted thoracoscopic surgery (CVATS) during the same period. RESULTS: The operative and console times were 162 and 97 min, respectively. No intraoperative complications occurred, and postoperative complications were observed in four cases (4.3%). The operative time, blood loss, postoperative complications, and maximum incision size were significantly lower in the RATS group than in the CVATS group. However, RATS requires a significantly higher number of staplers than CVATS. CONCLUSIONS: The division of the intersegmental plane using a robotic stapler in RATS portal segmentectomy was, therefore, found to be safe and effective.

DOI： 10.1007/s00595-024-02840-y

Effect of revised organ transplant law in Japan on lung transplantation. 査読

Yoshito Imamura, Daisuke Nakajima, Takashi Kanou, Yasushi Shintani, Seiichiro Sugimoto, Shinichi Toyooka, Yasushi Hoshikawa, Keitaro Matsumoto, Takeshi Nagayasu, Hidemi Suzuki, Sumiko Maeda, Masayuki Chida, Takeshi Shiraishi, Toshihiko Sato, Masaaki Sato, Jun Nakajima, Hisashi Oishi, Yoshinori Okada, Hiroshi Date

Surgery today 2024年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To investigate how revision of the organ transplant law in Japan affected lung transplantation in this country. METHODS: Lung transplant candidates registered between January, 2000 and December, 2009 were designated as the pre-revision group (n = 396) and those registered between January, 2011 and December, 2020, as the post-revision group (n = 1326). Both groups were analyzed retrospectively using data collected by the Japanese Society of Lung and Heart-Lung Transplantation. RESULTS: The number of patients who underwent brain-dead donor lung transplantation (BDLT) increased significantly after the law amendment (32.2 vs. 13.8%, p < 0.01). The median waiting time for BDLT was significantly reduced (708 days vs. 1163 days, p < 0.01) and the mortality rate while waiting for BDLT improved significantly after the law amendment (33.1 vs. 42.6%, p < 0.01). In the post-revision group, 18 pediatric patients underwent BDLT. The 5-year survival rates after BDLT were comparable between the groups (73.5% in the pre-revision group vs. 73.2% in the post-revision group, p = 0.32). CONCLUSIONS: The organ transplant law revision shortened the waiting time for BDLT significantly and decreased the mortality rate while waiting for BDLT. The posttransplant outcomes in Japan remained favorable throughout the study period.

DOI： 10.1007/s00595-024-02839-5

Excess mortality in COVID-19-affected solid organ transplant recipients across the pandemic. 査読国際誌

Shigeyoshi Yamanaga, Keita Shimata, Satoko Ohfuji, Mikiko Yoshikawa, Yoichiro Natori, Taizo Hibi, Kenji Yuzawa, Hiroto Egawa

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2024年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

The excess mortality of coronavirus disease 2019 (COVID-19) solid organ transplant recipients (SOTRs) throughout the pandemic remains unclear. This prospective cohort study based on the Japanese nationwide registry included 1632 SOTRs diagnosed with COVID-19 between February 1, 2020, and July 31, 2022, categorized based on dominant phases of variants of concern (VOCs): Waves 1 to 3 (Beta), 4 (Alpha), 5 (Delta), 6 (Omicron BA.1/BA.2), and 7 (Omicron BA.5). Excess mortality of COVID-19-affected SOTRs was analyzed by calculating standardized mortality ratios (SMRs). Overall, 1632 COVID-19-confirmed SOTRs included 1170 kidney, 408 liver, 25 lung, 20 heart, 1 small intestine, and 8 multiorgan recipients. Although disease severity and all-cause mortality decreased as VOCs transitioned, SMRs of SOTRs were consistently higher than those of the general population throughout the pandemic, showing a U-shaped gap that peaked toward the Omicron BA.5 phase; SMR (95% CI): 6.2 (3.1-12.5), 4.0 (1.5-10.6), 3.0 (1.3-6.7), 8.8 (5.3-14.5), and 21.9 (5.5-87.6) for Waves 1 to 3 (Beta), Wave 4 (Alpha), Wave 5 (Delta), Wave 6 (Omicron BA.1/2), and Wave 7 (Omicron BA.5), respectively. In conclusion, COVID-19 SOTRs had greater SMRs than the general population across the pandemic. Vaccine boosters, immunosuppression optimization, and other protective measures, particularly for older SOTRs, are paramount.

DOI： 10.1016/j.ajt.2024.03.016

Impact of the neutrophil-to-lymphocyte ratio on patients with locally advanced non-small cell lung cancer who suffer radiation pneumonitis during the course of induction chemoradiotherapy followed by surgery. 査読

Yujiro Kubo, Hiromasa Yamamoto, Kei Matsubara, Kohei Hashimoto, Shin Tanaka, Kazuhiko Shien, Ken Suzawa, Kentaroh Miyoshi, Mikio Okazaki, Seiichiro Sugimoto, Kuniaki Katsui, Takao Hiraki, Katsuyuki Kiura, Shinichi Toyooka

Surgery today 2024年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Radiation pneumonitis (RP) is an obstacle for patients after surgery following induction chemoradiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC). We performed a comparative analysis of the association between clinicopathological factors, including the neutrophil-to-lymphocyte ratio (NLR) and prognosis, in LA-NSCLC patients with or without RP during induction chemoradiotherapy followed by surgery. METHODS: The subjects of this analysis were 168 patients undergoing trimodality therapy for LA-NSCLC between January, 1999 and May, 2019. Patients were divided into two groups: the RP group (n = 41) and the non-RP group (n = 127). We compared the clinicopathological factors including the NLR between the groups and analyzed the association between the NLR and prognosis. RESULTS: The RP group had more patients with tumors located in the lower lobe, more bilobar resections, shorter operative times, no implementation of postoperative adjuvant chemotherapy, and a higher postoperative NLR than the non-RP group. There were no significant differences in serious postoperative complications and the prognosis. Patients with a low postoperative NLR had a significantly better prognosis in the non-RP group, and a trend toward a better prognosis even in the RP group. CONCLUSION: Postoperative NLR may be a useful prognostic factor, even for patients who suffer RP after trimodality therapy for LA-NSCLC.

DOI： 10.1007/s00595-024-02816-y

肺移植後の抗体関連型拒絶反応に対する免疫グロブリン製剤使用の実態調査査読

中島大輔, 伊達洋至, 松原慧, 杉本誠一郎, 白石武史, 平間崇, 芳川豊史, 中川健, 江川裕人

移植 58 ( 4 ) 371 - 380 2024年3月

Plasma concentrations of histidine-rich glycoprotein in primary graft dysfunction after lung transplantation. 査読国際誌

Toshio Shiotani, Seiichiro Sugimoto, Yasuaki Tomioka, Shin Tanaka, Toshiharu Mitsuhashi, Ken Suzawa, Kazuhiko Shien, Kentaroh Miyoshi, Hiromasa Yamamoto, Mikio Okazaki, Shinichi Toyooka

Interdisciplinary cardiovascular and thoracic surgery 2024年2月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: Histidine-rich glycoprotein has been reported as an anti-inflammatory glycoprotein that inhibits acute lung injury in mice with sepsis and as a prognostic biomarker in patients with sepsis. We investigated the relationship between plasma concentrations of histidine-rich glycoprotein and the risk of occurrence of primary graft dysfunction. METHODS: According to the primary graft dysfunction grade at post-transplant 72 hours, patients who underwent lung transplantation were divided into three groups: non-primary graft dysfunction group (grade 0-1), moderate primary graft dysfunction group (grade 2), and severe primary graft dysfunction group (grade 3). The plasma concentrations of histidine-rich glycoprotein measured daily during the first post-transplant 7 days were compared among the three groups. Appropriate cutoff values of the concentrations were set for survival analyses after lung transplantation. RESULTS: A total of 68 patients were included. The plasma histidine-rich glycoprotein concentration at post-transplant 72 hours was significantly lower in the severe primary graft dysfunction group (n = 7) than in the other two groups (non-primary graft dysfunction group (n = 43), P = 0.042; moderate primary graft dysfunction group (n = 18), P = 0.040). Patients with plasma histidine-rich glycoprotein concentration ≥34.4 µg/mL at post-transplant 72 hours had significantly better chronic lung allograft dysfunction-free survival (P = 0.012) and overall survival (P = 0.037) than those with the concentration <34.4 µg/mL. CONCLUSIONS: Plasma histidine-rich glycoprotein concentrations at post-transplant 72 hours might be associated with the risk of development of primary graft dysfunction.

DOI： 10.1093/icvts/ivae021

Long-term outcomes of lung transplantation requiring renal replacement therapy: A single-center experience. 査読国際誌

Yasuaki Tomioka, Seiichiro Sugimoto, Toshio Shiotani, Kei Matsubara, Haruki Choshi, Megumi Ishihara, Shin Tanaka, Kentaroh Miyoshi, Shinji Otani, Shinichi Toyooka

Respiratory investigation 62 ( 2 ) 240 - 246 2024年1月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Life-long immunosuppressive therapy after lung transplantation (LT) may lead to end-stage renal disease (ESRD), requiring renal replacement therapy (RRT). We aimed to investigate the characteristics and long-term outcomes of patients undergoing LT and requiring RRT. METHODS: This study was a single-center, retrospective cohort study. The patients were divided into the RRT (n = 15) and non-RRT (n = 170) groups. We summarized the clinical features of patients in the RRT group and compared patient characteristics, overall survival, and chronic lung allograft dysfunction (CLAD)-free survival between the two groups. RESULTS: The cumulative incidences of ESRD requiring RRT after LT at 5, 10, and 15 years were 0.8 %, 7.6 %, and 25.2 %, respectively. In the RRT group, all 15 patients underwent hemodialysis but not peritoneal dialysis, and two patients underwent living-donor kidney transplantation. The median follow-up period was longer in the RRT group than in the non-RRT group (P < 0.001). The CLAD-free survival and overall survival did not differ between the two groups. The 5-year survival rate even after the initiation of hemodialysis was 53.3 %, and the leading cause of death in the RRT group was infection. CONCLUSIONS: Favorable long-term outcomes can be achieved by RRT for ESRD after LT.

DOI： 10.1016/j.resinv.2024.01.001

Successful Living-donor Lobar Lung Transplantation With BK Virus-related Hemorrhagic Cystitis Throughout the Perioperative Period. 査読国際誌

Yasuaki Tomioka, Shinji Otani, Shin Tanaka, Kentaroh Miyoshi, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka

Transplantation direct 10 ( 1 ) e1556 2024年1月

Corrigendum: Use of the index of pulmonary vascular disease for predicting longterm outcome of pulmonary arterial hypertension associated with congenital heart disease. 査読国際誌

Ayako Chida-Nagai, Naoki Masaki, Kay Maeda, Konosuke Sasaki, Hiroki Sato, Jun Muneuchi, Yoshie Ochiai, Hiroomi Murayama, Masahiro Tahara, Atsuko Shiono, Atsushi Shinozuka, Fumihiko Kono, Daisuke Machida, Shinichi Toyooka, Seiichiro Sugimoto, Kazufumi Nakamura, Satoshi Akagi, Maiko Kondo, Shingo Kasahara, Yasuhiro Kotani, Junichi Koizumi, Katsuhiko Oda, Masako Harada, Daisuke Nakajima, Akira Murata, Hazumu Nagata, Koichi Yatsunami, Tomio Kobayashi, Yoshikiyo Matsunaga, Takahiro Inoue, Hiroyuki Yamagishi, Naomi Nakagawa, Katsuki Ohtani, Masaki Yamamoto, Yushi Ito, Tatsunori Hokosaki, Yuta Kuwahara, Satoshi Masutani, Koji Nomura, Tsutomu Wada, Hirofumi Sawada, Masayuki Abiko, Tatsunori Takahashi, Yuichi Ishikawa, Seigo Okada, Atsushi Naitoh, Takako Toda, Tatsuya Ando, Akihiro Masuzawa, Shinsuke Hoshino, Masaaki Kawada, Yuichi Nomura, Kentaro Ueno, Naoki Ohashi, Tsuyoshi Tachibana, Yuchen Cao, Hideaki Ueda, Sadamitsu Yanagi, Masaaki Koide, Norie Mitsushita, Kouji Higashi, Yoshihiro Minosaki, Tomohiro Hayashi, Takashi Okamoto, Kenji Kuraishi, Eiji Ehara, Hidekazu Ishida, Hitoshi Horigome, Takashi Murakami, Kohta Takei, Taku Ishii, Gen Harada, Yasutaka Hirata, Jun Maeda, Shunsuke Tatebe, Chiharu Ota, Yasunobu Hayabuchi, Hisanori Sakazaki, Takashi Sasaki, Keiichi Hirono, Sayo Suzuki, Masahiro Yasuda, Atsuhito Takeda, Madoka Sawada, Kagami Miyaji, Atsushi Kitagawa, Yosuke Nakai, Nobuyuki Kakimoto, Kouta Agematsu, Atsushi Manabe, Yoshikatsu Saiki

Frontiers in cardiovascular medicine 11 1369831 - 1369831 2024年

PAI-1 mediates acquired resistance to MET-targeted therapy in non-small cell lung cancer. 査読国際誌

Yin Min Thu, Ken Suzawa, Shuta Tomida, Kosuke Ochi, Shimpei Tsudaka, Fumiaki Takatsu, Keiichi Date, Naoki Matsuda, Kazuma Iwata, Kentaro Nakata, Kazuhiko Shien, Hiromasa Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Shinichi Toyooka

PloS one 19 ( 5 ) e0300644 2024年

記述言語：英語掲載種別：研究論文（学術雑誌）

Mechanisms underlying primary and acquired resistance to MET tyrosine kinase inhibitors (TKIs) in managing non-small cell lung cancer remain unclear. In this study, we investigated the possible mechanisms acquired for crizotinib in MET-amplified lung carcinoma cell lines. Two MET-amplified lung cancer cell lines, EBC-1 and H1993, were established for acquired resistance to MET-TKI crizotinib and were functionally elucidated. Genomic and transcriptomic data were used to assess the factors contributing to the resistance mechanism, and the alterations hypothesized to confer resistance were validated. Multiple mechanisms underlie acquired resistance to crizotinib in MET-amplified lung cancer cell lines. In EBC-1-derived resistant cells, the overexpression of SERPINE1, the gene encoding plasminogen activator inhibitor-1 (PAI-1), mediated the drug resistance mechanism. Crizotinib resistance was addressed by combination therapy with a PAI-1 inhibitor and PAI-1 knockdown. Another mechanism of resistance in different subline cells of EBC-1 was evaluated as epithelial-to-mesenchymal transition with the upregulation of antiapoptotic proteins. In H1993-derived resistant cells, MEK inhibitors could be a potential therapeutic strategy for overcoming resistance with downstream mitogen-activated protein kinase pathway activation. In this study, we revealed the different mechanisms of acquired resistance to the MET inhibitor crizotinib with potential therapeutic application in patients with MET-amplified lung carcinoma.

DOI： 10.1371/journal.pone.0300644

(, 10.32388/74e1v5)

Ayako Chida-Nagai, Naoki Masaki, Kay Maeda, Konosuke Sasaki, Hiroki Sato, Jun Muneuchi, Yoshie Ochiai, Hiroomi Murayama, Masahiro Tahara, Atsuko Shiono, Atsushi Shinozuka, Fumihiko Kono, Daisuke Machida, Shinichi Toyooka, Seiichiro Sugimoto, Kazufumi Nakamura, Satoshi Akagi, Maiko Kondo, Shingo Kasahara, Yasuhiro Kotani, Junichi Koizumi, Katsuhiko Oda, Masako Harada, Daisuke Nakajima, Akira Murata, Hazumu Nagata, Koichi Yatsunami, Tomio Kobayashi, Yoshikiyo Matsunaga, Takahiro Inoue, Hiroyuki Yamagishi, Naomi Nakagawa, Katsuki Ohtani, Masaki Yamamoto, Yushi Ito, Tatsunori Hokosaki, Yuta Kuwahara, Satoshi Masutani, Koji Nomura, Tsutomu Wada, Hirofumi Sawada, Masayuki Abiko, Tatsunori Takahashi, Yuichi Ishikawa, Seigo Okada, Atsushi Naitoh, Takako Toda, Tatsuya Ando, Akihiro Masuzawa, Shinsuke Hoshino, Masaaki Kawada, Yuichi Nomura, Kentaro Ueno, Naoki Ohashi, Tsuyoshi Tachibana, Yuchen Cao, Hideaki Ueda, Sadamitsu Yanagi, Masaaki Koide, Norie Mitsushita, Kouji Higashi, Yoshihiro Minosaki, Tomohiro Hayashi, Takashi Okamoto, Kenji Kuraishi, Eiji Ehara, Hidekazu Ishida, Hitoshi Horigome, Takashi Murakami, Kohta Takei, Taku Ishii, Gen Harada, Yasutaka Hirata, Jun Maeda, Shunsuke Tatebe, Chiharu Ota, Yasunobu Hayabuchi, Hisanori Sakazaki, Takashi Sasaki, Keiichi Hirono, Sayo Suzuki, Masahiro Yasuda, Atsuhito Takeda, Madoka Sawada, Kagami Miyaji, Atsushi Kitagawa, Yosuke Nakai, Nobuyuki Kakimoto, Kouta Agematsu, Atsushi Manabe, Yoshikatsu Saiki

Frontiers in Cardiovascular Medicine 11 2024年

Correction to: Periostin secreted by cancer‑associated fibroblasts promotes cancer progression and drug resistance in non‑small cell lung cancer. 査読国際誌

Fumiaki Takatsu, Ken Suzawa, Shuta Tomida, Yin Min Thu, Masakiyo Sakaguchi, Tomohiro Toji, Masayoshi Ohki, Shimpei Tsudaka, Keiichi Date, Naoki Matsuda, Kazuma Iwata, Yidan Zhu, Kentaro Nakata, Kazuhiko Shien, Hiromasa Yamamoto, Akiko Nakayama, Mikio Okazaki, Seiichiro Sugimoto, Shinichi Toyooka

Journal of molecular medicine (Berlin, Germany) 2023年12月

【移植医療の最前線】肺移植招待査読

田中真, 石原恵, 三好健太郎, 杉本誠一郎, 豊岡伸一

Pharma Medica 40 ( 3 ) 133 - 138 2023年11月

記述言語：日本語出版者・発行元：(株)メディカルレビュー社

＜文献概要＞日本の肺移植は1998年に始まり、2022年末までに累計1,036例が行われてきた。改正臓器移植法の施行後、脳死ドナーの提供数は増加傾向ではあるが、依然としてドナー不足は深刻で肺移植待機患者の平均待機期間は2年半、待機中の死亡率は40%である。臓器提供が少ない現状のなか、日本では肺移植において世界とは異なる独自の取り組みが行われてきた。生体肺移植、ドナー肺利用率の向上、片肺移植がその特徴であり海外と比較しても遜色のない肺移植後生存率である。しかしこのような取り組みだけではドナープールのわずかな増加にしか貢献せず、近年増加する肺移植登録患者を救うことができない。より現実的に有望な新しいドナーソースとして、心臓死後のドナー提供が考えられる。心停止ドナー肺移植はすでに一部の欧米諸国で盛んに行われ、各国のドナー数の増加に寄与している。国際的なデータによれば、心停止ドナー肺移植の生存率は脳死肺ドナーと同等である。また他臓器を含めた心停止ドナー移植の導入には、腹部臓器常温局所灌流装置などの技術が寄与し、これによって臓器利用率が向上する可能性がある。今後、日本における心停止ドナー移植の導入には倫理的な課題は山積みであり、慎重な検討が必要である。

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01750&link_issn=&doc_id=20231207200004&doc_link_id=issn%3D0289-5803%26volume%3D40%26issue%3D3%26spage%3D133&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0289-5803%26volume%3D40%26issue%3D3%26spage%3D133&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

Impact of changes in skeletal muscle mass and quality during the waiting time on outcomes of lung transplantation. 査読国際誌

Akikazu Hagiyama, Seiichiro Sugimoto, Shin Tanaka, Kei Matsubara, Kentaroh Miyoshi, Yoshimi Katayama, Masanori Hamada, Masuo Senda, Shinichi Toyooka

Clinical transplantation e15169 2023年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: The association of changes in skeletal muscle mass and quality during the waiting time with outcomes of lung transplantation (LT) remains unclear. We aimed to examine the association of changes in skeletal muscle mass and quality during the waiting time, as well as preoperative skeletal muscle mass and quality, with outcomes of LT. METHODS: This study included individuals who underwent LT from brain-dead donors. Skeletal muscle mass (cm2 /m2 ) and quality (mean Hounsfield units [HU]) of the erector spinae muscle at the 12th thoracic level were evaluated using computed tomography. Preoperative skeletal muscle mass and quality, and their changes during the waiting time were calculated. We evaluated the associations among mechanical ventilation (MV) duration, intensive care unit (ICU) length of stay (LOS), hospital LOS, 6-minute walk distance at discharge, and 5-year survival after LT. RESULTS: This study included 98 patients. The median waiting time was 594.5 days (interquartile range [IQR], 355.0-913.0). The median changes in skeletal muscle mass and quality were -4.4% (IQR, -13.3-3.1) and -2.9% (IQR, -16.0-4.1), respectively. Severe low skeletal muscle mass at LT was associated with prolonged ICU LOS (B = 8.46, 95% confidence interval [CI]: .51-16.42) and hospital LOS (B = 36.00, 95% CI: 3.23-68.78). Pronounced decrease in skeletal muscle mass during the waiting time was associated with prolonged MV duration (B = 7.85, 95% CI: .89-14.81) and ICU LOS (B = 7.97, 95% CI: .83-15.10). CONCLUSION: Maintaining or increasing skeletal muscle mass during the waiting time would be beneficial to improve the short-term outcomes of LT.

DOI： 10.1111/ctr.15169

In vivo lung perfusion for prompt recovery from primary graft dysfunction after lung transplantation. 査読国際誌

Kei Matsubara, Kentaroh Miyoshi, Shinichi Kawana, Yujiro Kubo, Dai Shimizu, Yasuaki Tomioka, Toshio Shiotani, Haruchika Yamamoto, Shin Tanaka, Takeshi Kurosaki, Toshiaki Ohara, Mikio Okazaki, Seiichiro Sugimoto, Akihiro Matsukawa, Shinichi Toyooka

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 2023年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: No proven treatment after the development of primary graft dysfunction (PGD) is currently available. Here we established a novel strategy of in vivo lung perfusion (IVLP) for the treatment of PGD. IVLP involves the application of an in vivo isolated perfusion circuit to an implanted lung. This study aimed to explore the effectiveness of IVLP versus conventional post-lung transplant (LTx) extracorporeal membrane oxygenation (ECMO) treatment using an experimental swine LTx PGD model. METHODS: After 1.5-h warm ischemia of the donor lungs, a left LTx was performed. Following the confirmation of PGD development, pigs were divided into three groups (n = 5 each): control (no intervention), ECMO, and IVLP. After 2 h of treatment, a 4-h functional assessment was conducted and samples obtained. RESULTS: Significantly better oxygenation were achieved in the IVLP group (p ≤ 0.001). Recovery was confirmed immediately and maintained during the following 4-h observation. The IVLP group also demonstrated better lung compliance than the control group (p = 0.045). A histological evaluation showed that the lung injury score and terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed significantly fewer injuries and a better result in the wet-to-dry weight ratio in the IVLP group. CONCLUSIONS: A two-hour IVLP is technically feasible and allows for prompt recovery from PGD after LTx. The posttransplant short-duration IVLP strategy can complement or overcome the limitations of the current practice for donor assessment and PGD management.

DOI： 10.1016/j.healun.2023.10.011

Periostin secreted by cancer-associated fibroblasts promotes cancer progression and drug resistance in non-small cell lung cancer. 査読国際誌

Fumiaki Takatsu, Ken Suzawa, Shuta Tomida, Yin Min Thu, Masakiyo Sakaguchi, Tomohiro Toji, Masayoshi Ohki, Shimpei Tsudaka, Keiichi Date, Naoki Matsuda, Kazuma Iwata, Yidan Zhu, Kentaro Nakata, Kazuhiko Shien, Hiromasa Yamamoto, Akiko Nakayama, Mikio Okazaki, Seiichiro Sugimoto, Shinichi Toyooka

Journal of molecular medicine (Berlin, Germany) 2023年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Cancer-associated fibroblasts (CAFs) are important components in the tumor microenvironment, and we sought to identify effective therapeutic targets in CAFs for non-small cell lung cancer (NSCLC). In this study, we established fibroblast cell lines from the cancerous and non-cancerous parts of surgical lung specimens from patients with NSCLC and evaluated the differences in behaviors towards NSCLC cells. RNA sequencing analysis was performed to investigate the differentially expressed genes between normal fibroblasts (NFs) and CAFs, and we identified that the expression of periostin (POSTN), which is known to be overexpressed in various solid tumors and promote cancer progression, was significantly higher in CAFs than in NFs. POSTN increased cell proliferation via NSCLC cells' ERK pathway activation and induced epithelial-mesenchymal transition (EMT), which improved migration in vitro. In addition, POSTN knockdown in CAFs suppressed these effects, and in vivo experiments demonstrated that the POSTN knockdown improved the sensitivity of EGFR-mutant NSCLC cells for osimertinib treatment. Collectively, our results showed that CAF-derived POSTN is involved in tumor growth, migration, EMT induction, and drug resistance in NSCLC. Targeting CAF-secreted POSTN could be a potential therapeutic strategy for NSCLC. KEY MESSAGES: • POSTN is significantly upregulated in CAFs compared to normal fibroblasts in NCSLC. • POSTN increases cell proliferation via activation of the NSCLC cells' ERK pathway. • POSTN induces EMT in NSCLC cells and improves the migration ability. • POSTN knockdown improves the sensitivity for osimertinib in EGFR-mutant NSCLC cells.

DOI： 10.1007/s00109-023-02384-7

Author Correction: Identification of genetic loci associated with renal dysfunction after lung transplantation using an ethnic-specific single-nucleotide polymorphism array. 査読国際誌

Yasuaki Tomioka, Seiichiro Sugimoto, Haruchika Yamamoto, Shuta Tomida, Toshio Shiotani, Shin Tanaka, Kazuhiko Shien, Ken Suzawa, Kentaroh Miyoshi, Shinji Otani, Hiromasa Yamamoto, Mikio Okazaki, Masaomi Yamane, Shinichi Toyooka

Scientific reports 13 ( 1 ) 16721 - 16721 2023年10月

Long-term management and outcome of lung transplantation in Japan. 査読国際誌

Seiichiro Sugimoto, Kei Matsubara, Shin Tanaka, Kentaroh Miyoshi, Megumi Ishihara, Shinichi Toyooka

Journal of thoracic disease 15 ( 9 ) 5182 - 5194 2023年9月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

The long-term survival after lung transplantation (LT) is favorable in Japan. However, long-term survivors after LT are subject to late complications, including chronic lung allograft dysfunction (CLAD), malignancy, infection, and chronic kidney disease (CKD) because of the need for lifelong immunosuppression. The rates of single cadaveric LT (CLT) and living-donor lobar LT (LDLLT) are higher than that of bilateral CLT in Japan. Here, we will describe the management of late complications and long-term outcome after LT in Japan. Attention should be paid to not only the phenotype of CLAD but also the difference in CLAD after CLT and after LDLLT as well as the timing of lung re-transplantation for advanced CLAD, especially after single CLT. Since post-transplant lymphoproliferative disorder is the most common malignancy after LT, infection monitoring for infection-related malignancies and appropriate screening are keys to the early diagnosis and treatment of malignancy after LT. The long-term management of infection after LT is also important, especially with regard to community-acquired pathogens, Aspergillus, and cytomegalovirus. When providing long-term care after LT, physicians should be aware of CKD and the timing of renal replacement therapy in cases with severe CKD. The widespread use of computed tomography and dialysis in Japan are beneficial for long-term survivors of LT. The similar survival outcomes of single CLT and LDLLT, compared with bilateral CLT, might contribute to improved long-term survival in Japan. Pulmonologists are encouraged to become further involved in long-term management after LT in Japan.

DOI： 10.21037/jtd-22-1679

ASO Visual Abstract: Prognostic Impact of Tumor-Infiltrating Lymphocytes, Tertiary Lymphoid Structures, and Neutrophil-to-Lymphocyte Ratio in Pulmonary Metastases from Uterine Leiomyosarcoma. 査読国際誌

Naoki Matsuda, Hiromasa Yamamoto, Tomohiro Habu, Kazuma Iwata, Kei Matsubara, Shin Tanaka, Kohei Hashimoto, Kazuhiko Shien, Ken Suzawa, Kentaroh Miyoshi, Tomohiro Toji, Mikio Okazaki, Seiichiro Sugimoto, Katsuhito Takahashi, Shinichi Toyooka

Annals of surgical oncology 2023年9月

Successful management of temporary veno-venous extracorporeal membrane oxygenation for a pediatric lung transplant recipient with bronchiolitis obliterans syndrome awaiting lung re-transplantation: a case report. 査読国際誌

Yasuaki Tomioka, Kentaroh Miyoshi, Shin Tanaka, Seiichiro Sugimoto, Rie Kanai, Tetsuro Nikai, Shinichi Toyooka, Masaomi Yamane

Surgical case reports 9 ( 1 ) 163 - 163 2023年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation is an uncommon strategy in Japan owing to the severe donor shortage and absence of urgent allocation policy. Moreover, the use of veno-venous (VV) ECMO for immunosuppressed patients is controversial; thus, applying ECMO to patients who await lung re-transplantation is challenging. CASE PRESENTATION: A 16-year-old lung transplant recipient with grade 3 bronchiolitis obliterans syndrome was waitlisted for lung re-transplantation. Eleven months later, he fell into severe respiratory acidosis with hypercapnia, which were not resolved with mechanical ventilation. VV ECMO was introduced to minimize lung stress and strain. Tracheostomy was additionally performed on day 5 after the start of ECMO, and respiratory condition swiftly improved; hence, the weaning process from VV ECMO began on day 9. Rehabilitation became implementable, and bilateral re-lung transplantation was successfully performed 6 months after the ECMO treatment. No critical complication related to the precedent use of ECMO was noted. CONCLUSIONS: VV ECMO can be a feasible treatment option even for lung transplant candidates awaiting re-transplantation for a prolonged period. Introduction of ECMO and tracheostomy in the early deterioration stage may be crucial to successful subsequent patient management.

DOI： 10.1186/s40792-023-01742-4

Prognostic Impact of Tumor-Infiltrating Lymphocytes, Tertiary Lymphoid Structures, and Neutrophil-to-Lymphocyte Ratio in Pulmonary Metastases from Uterine Leiomyosarcoma. 査読国際誌

Naoki Matsuda, Hiromasa Yamamoto, Tomohiro Habu, Kazuma Iwata, Kei Matsubara, Shin Tanaka, Kohei Hashimoto, Kazuhiko Shien, Ken Suzawa, Kentaroh Miyoshi, Tomohiro Toji, Mikio Okazaki, Seiichiro Sugimoto, Katsuhito Takahashi, Shinichi Toyooka

Annals of surgical oncology 2023年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The presence of tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) in tumor tissue has been related to the prognosis in various malignancies. Meanwhile, neutrophil-to-lymphocyte ratio (NLR) as a systemic inflammation marker also has been associated with the prognosis in them. However, few reports have investigated the relationship between pulmonary metastases from sarcoma and these biomarkers. METHODS: We retrospectively recruited 102 patients undergoing metastasectomy for pulmonary metastases from uterine leiomyosarcoma at Okayama University Hospital from January 2006 to December 2019. TILs and TLSs were evaluated by immunohistochemical staining of surgically resected specimens of pulmonary metastases using anti-CD3/CD8/CD103/Foxp3/CD20 antibodies. NLR was calculated from the blood examination immediately before the most recent pulmonary metastasectomy. We elucidated the relationship between the prognosis and these factors. Because we considered that the status of tumor tissue and systemic inflammation were equally valuable, we also assessed the impact of the combination of TILs or TLSs and NLR on the prognosis. RESULTS: As for TILs, CD3-positive cells and CD8-positive cells were correlated with the prognosis. The prognosis was significantly better in patients with CD3-high group, CD8-high group, TLSs-high group, and NLR-low group, respectively. The prognosis of CD8-high/NLR-low group and TLSs-high/NLR-low group was significantly better than that of CD8-low/NLR-high group and TLSs-low/NLR-high group, respectively. CONCLUSIONS: CD3-positive TILs, CD8-positive TILs, TLSs, and NLR are correlated with the prognosis, respectively. The combination of CD8-positive TILs or TLSs and NLR may be the indicators to predict the prognosis of patients with pulmonary metastases from uterine leiomyosarcoma.

DOI： 10.1245/s10434-023-14176-x

Restrictive allograft dysfunction rather than bronchiolitis obliterans syndrome had a major impact on the overall survival after living-donor lobar lung transplantation. 査読

Kei Matsubara, Shinji Otani, Haruchika Yamamoto, Kohei Hashimoto, Shin Tanaka, Kazuhiko Shien, Ken Suzawa, Kentaroh Miyoshi, Hiromasa Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Shinichi Toyooka

Surgery today 2023年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Chronic lung allograft dysfunction (CLAD) is a known long-term fatal disorder after lung transplantation. In this study, we evaluated the CLAD classification of the International Society for Heart and Lung Transplantation (ISHLT) for living-donor lobar lung transplantation (LDLLT). METHODS: We conducted a single-center retrospective review of data from 73 patients who underwent bilateral LDLLT between 1998 and 2019. Factors related to opacity on computed tomography (CT) and restriction on pulmonary function tests (PFTs) were also analyzed. RESULTS: Overall, 26 (36%) patients were diagnosed with CLAD, including restrictive allograft syndrome (RAS), n = 10 (38.5%); bronchiolitis obliterans syndrome (BOS), n = 8 (30.8%); mixed, n = 1 (3.8%); undefined, n = 2 (7.7%); and unclassified, n = 5 (19.2%). The 5-year survival rate after the CLAD onset was 60.7%. The survival of patients with BOS was significantly better than that of patients with RAS (p = 0.012). In particular, patients with restriction on PFT had a significantly worse survival than those without restriction (p = 0.001). CONCLUSIONS: CLAD after bilateral LDLLT does not have a major impact on the recipient survival, especially in patients with BOS. Restriction on PFT may predict a particularly poor prognosis in patients with CLAD after bilateral LDLLT.

DOI： 10.1007/s00595-023-02729-2

Percentage of low attenuation area on computed tomography detects chronic lung allograft dysfunction, especially bronchiolitis obliterans syndrome, after bilateral lung transplantation. 査読国際誌

Yujiro Kubo, Seiichiro Sugimoto, Toshio Shiotani, Kei Matsubara, Kohei Hashimoto, Shin Tanaka, Kazuhiko Shien, Ken Suzawa, Kentaroh Miyoshi, Hiromasa Yamamoto, Mikio Okazaki, Shinichi Toyooka

Clinical transplantation e15077 2023年7月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: The percentage of low attenuation area (%LAA) on computed tomography (CT) is useful for evaluating lung emphysema, and higher %LAA was observed in patients with chronic lung allograft dysfunction (CLAD). This study investigated the relationship between the %LAA and the development of CLAD after bilateral lung transplantation (LT). METHODS: We conducted a single-center retrospective study of 75 recipients who underwent bilateral LT; the recipients were divided into a CLAD group (n = 30) and a non-CLAD group (n = 45). The %LAA was calculated using CT and compared between the two groups from 4 years before to 4 years after the diagnosis of CLAD. The relationships between the %LAA and the percent baseline values of the pulmonary function test parameters were also calculated. RESULTS: The %LAA was significantly higher in the CLAD group than in the non-CLAD group from 2 years before to 2 years after the diagnosis of CLAD (P < .05). In particular, patients with bronchiolitis obliterans syndrome (BOS) exhibited significant differences even from 4 years before to 4 years after diagnosis (P < .05). Significant negative correlations between the %LAA and the percent baseline values of the forced expiratory volume in 1 s (r = -.36, P = .0031), the forced vital capacity (r = -.27, P = .027), and the total lung capacity (r = -.40, P < .001) were seen at the time of CLAD diagnosis. CONCLUSION: The %LAA on CT was associated with the development of CLAD and appears to have the potential to predict CLAD, especially BOS, after bilateral LT.

DOI： 10.1111/ctr.15077

Elderly lung transplant recipients show acceptable long-term outcomes for lung transplantation: A propensity score-matched analysis. 査読

Yasuaki Tomioka, Shin Tanaka, Shinji Otani, Toshio Shiotani, Haruchika Yamamoto, Kentaroh Miyoshi, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka

Surgery today 2023年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Although the performance lung transplantation (LTx) in the elderly (≥ 60 years) has increased globally, the situation in Japan remains quite different, because the age limit at registration for cadaveric transplantation is 60 years. We investigated the long-term outcomes of LTx in the elderly in Japan. METHODS: This was a single-center retrospective study. We divided the patients into two groups according to age: the younger group (< 60 years; Y group; n = 194) and the elderly group (≥ 60 years; E group; n = 10). We performed three-to-one propensity score matching to compare the long-term survival between the E and Y groups. RESULTS: In the E group, the survival rate was significantly worse (p = 0.003), and single-LTx was more frequent (p = 0.036). There was a significant difference in the indications for LTx between the two groups (p < 0.001). The 5-year survival rate after single-LTx in the E group was significantly lower than that in the Y group (p = 0.006). After propensity score matching, the 5-year survival rates of the two groups were comparable (p = 0.55). However, the 5-year survival rate after single-LTx in the E group was significantly lower than that in the Y group (p = 0.007). CONCLUSION: Elderly patients showed acceptable long-term survival after LTx.

DOI： 10.1007/s00595-023-02699-5

Identification of genetic loci associated with renal dysfunction after lung transplantation using an ethnic-specific single-nucleotide polymorphism array. 査読国際誌

Yasuaki Tomioka, Seiichiro Sugimoto, Haruchika Yamamoto, Shuta Tomida, Toshio Shiotani, Shin Tanaka, Kazuhiko Shien, Ken Suzawa, Kentaroh Miyoshi, Shinji Otani, Hiromasa Yamamoto, Mikio Okazaki, Masaomi Yamane, Shinichi Toyooka

Scientific reports 13 ( 1 ) 8912 - 8912 2023年6月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Renal dysfunction is a long-term complication associated with an increased mortality after lung transplantation (LT). We investigated the association of single-nucleotide polymorphisms (SNPs) with the development of renal dysfunction after LT using a Japanese-specific SNP array. First, eligible samples of 34 LT recipients were genotyped using the SNP array and divided into two groups, according to the presence of homozygous and heterozygous combinations of mutant alleles of the 162 renal-related SNPs. To identify candidate SNPs, the renal function tests were compared between the two groups for each SNP. Next, we investigated the association between the candidate SNPs and the time course of changes of the estimated glomerular filtration rate (eGFR) in the 99 recipients until 10 years after the LT. ΔeGFR was defined as the difference between the postoperative and preoperative eGFR values. Eight SNPs were identified as the candidate SNPs in the 34 recipients. Validation analysis of these 8 candidate SNPs in all the 99 recipients showed that three SNPs, namely, rs10277115, rs4690095, and rs792064, were associated with significant changes of the ΔeGFR. Pre-transplant identification of high-risk patients for the development of renal dysfunction after LT based on the presence of these SNPs might contribute to providing personalized medicine.

DOI： 10.1038/s41598-023-36143-y

Pulmonary alveolar proteinosis after lung transplantation: Two case reports and literature review. 査読国際誌

Shinichi Kawana, Kentaroh Miyoshi, Shin Tanaka, Seiichiro Sugimoto, Dai Shimizu, Kei Matsubara, Mikio Okazaki, Noboru Hattori, Shinichi Toyooka

Respirology case reports 11 ( 6 ) e01160 2023年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Pulmonary alveolar proteinosis (PAP) affecting transplanted lungs is not well recognized. Herein, we report two cases of PAP after lung transplantation (LTx). The first case was a 4-year-old boy with hereditary pulmonary fibrosis who underwent bilateral LTx and presented with respiratory distress on postoperative day (POD) 23. He was initially treated for acute rejection, died due to infection on POD 248, and was diagnosed with PAP at autopsy. The second case involved a 52-year-old man with idiopathic pulmonary fibrosis who underwent bilateral LTx. On POD 99, chest computed tomography revealed ground-glass opacities. Bronchoalveolar lavage and transbronchial biopsy led to a diagnosis of PAP. Follow-up with immunosuppression tapering resulted in clinical and radiological improvement. PAP after lung transplantation mimics common acute rejection; however, is potentially transient or resolved with tapering immunosuppression, as observed in the second case. Transplant physicians should be aware of this rare complication to avoid misconducting immunosuppressive management.

DOI： 10.1002/rcr2.1160

Endobronchial Metastasis with Bloody Sputum 20 Years after Complete Resection of type A Non-Invasive Thymoma. 査読

Mototsugu Watanabe, Hiromasa Yamamoto, Kentaroh Miyoshi, Seiichiro Sugimoto, Shinichi Toyooka

Acta medica Okayama 77 ( 3 ) 331 - 334 2023年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Masaoka stage I type A thymomas rarely recur. We report the case of an 82-year-old man who developed endobronchial metastasis after thymothymectomy for Masaoka stage I type A thymoma. Twenty years after surgery, the patient developed bloody sputum, and chest computed tomography revealed a neoplasm obstructing the right upper lobe bronchus of the lung with enlarged mediastinal lymph nodes. He underwent right upper lobectomy and mediastinal lymph node dissection. Although preoperative pathological diagnosis was squamous cell carcinoma of the lung, postoperative histopathology revealed endobronchial metastasis of the thymoma. Nine years later, at age 89, the patient is alive and well.

DOI： 10.18926/AMO/65503

One-year change in the health status predicts the subsequent hospitalization and mortality in patients waitlisted for lung transplantation in Japan. 査読国際誌

Masaki Ikeda, Yusuke Wakatsuki, Toru Oga, Junko Tokuno, Seiichiro Sugimoto, Megumi Ishihara, Yoshinori Okada, Miki Akiba, Hidenao Kayawake, Satona Tanaka, Yoshito Yamada, Yojiro Yutaka, Akihiro Ohsumi, Daisuke Nakajima, Masatsugu Hamaji, Jumpei Kimura, Toyofumi F Chen-Yoshikawa, Hiroshi Date

Respiratory investigation 61 ( 4 ) 478 - 484 2023年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Poor health-related quality of life (HRQL) at the registration for lung transplantation is related to waitlist mortality. We investigated the relationship between 1-year change in HRQL and subsequent outcomes in patients waitlisted for lung transplantation. METHODS: In a 5-year longitudinal study, we analyzed the factors related to waitlist mortality in 197 lung transplant patients registered on the Japan Organ Transplant Network. HRQL was assessed using St. George's Respiratory Questionnaire (SGRQ), and factors related to changes in SGRQ scores were evaluated after 1 year. We assessed the relationship between the 1-year change in SGRQ score and subsequent mortality or hospitalization. RESULTS: Among 197 patients, 108 remained waitlisted during the first-year assessment. During the median follow-up period of 469 d, 28 patients died, and 54 underwent lung transplantation. Univariate Cox proportional hazards analysis revealed that the changes in all components and total score of the SGRQ after 1 year were associated with waitlist mortality (p < 0.05). Stepwise multivariate analysis revealed that the 1-year changes in SGRQ scores were significantly related to waitlist mortality. Forty-three patients with worsened HRQL after 1 year had higher likelihoods of hospitalization (p = 0.038) and mortality (p = 0.026) after 1 and 4 years of follow-up, respectively, than 61 patients without worsened HRQL. CONCLUSIONS: Patients with worsened health status during the first year after registration had higher likelihoods of hospitalization and mortality after 1 and 4 years of follow-up, respectively, than those without worsened HRQL. Strategies to improve health status while waiting are needed to reduce waitlist hospitalization or mortality.

DOI： 10.1016/j.resinv.2023.04.004

S100A8/A9 as a prognostic biomarker in lung transplantation. 査読国際誌

Kentaro Nakata, Mikio Okazaki, Shinichi Kawana, Yujiro Kubo, Dai Shimizu, Shin Tanaka, Kohei Hashimoto, Ken Suzawa, Kazuhiko Shien, Kentaroh Miyoshi, Hiromasa Yamamoto, Seiichiro Sugimoto, Shinichi Toyooka

Clinical transplantation e15006 2023年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: S100A8/A9 is a damage-associated molecule that augments systemic inflammation. However, its role in the acute phase after lung transplantation (LTx) remains elusive. This study aimed to determine S100A8/A9 levels after lung transplantation (LTx) and evaluate their impact on overall survival (OS) and chronic lung allograft dysfunction (CLAD)-free survival. METHODS: Sixty patients were enrolled in this study, and their plasma S100A8/A9 levels were measured on days 0, 1, 2, and 3 after LTx. The association of S100A8/A9 levels with OS and CLAD-free survival was assessed using univariate and multivariate Cox regression analyses. RESULTS: S100A8/A9 levels were elevated in a time-dependent manner until 3 days after LTx. Ischemic time was significantly longer in the high S100A8/9 group than in the low S100A8/A9 group (p = .017). Patients with high S100A8/A9 levels (> 2844 ng/mL) had worse prognosis (p = .031) and shorter CLAD-free survival (p = .045) in the Kaplan-Meier survival analysis than those with low levels. Furthermore, multivariate Cox regression analysis showed that high S100A8/A9 levels were a determinant of poor OS (hazard ratio [HR]: 3.7; 95% confidence interval [CI]: 1.2-12; p = .028) and poor CLAD-free survival (HR: 4.1; 95% CI: 1.1-15; p = .03). In patients with a low primary graft dysfunction grade (0-2), a high level of S100A8/A9 was also a poor prognostic factor. CONCLUSIONS: Our study provided novel insights into the role of S100A8/A9 as a prognostic biomarker and a potential therapeutic target for LTx.

DOI： 10.1111/ctr.15006

特集外科手術と感染症 II. 各論 4. 呼吸器外科 1)肺合併症を減らすための周術期対策招待査読

杉本誠一郎, 豊岡伸一

外科 85 ( 5 ) 557 - 564 2023年4月

Diagnostic value of circulating microRNA-21 in chronic lung allograft dysfunction after bilateral cadaveric and living-donor lobar lung transplantation. 査読国際誌

Toshio Shiotani, Seiichiro Sugimoto, Yasuaki Tomioka, Haruchika Yamamoto, Shin Tanaka, Kentaroh Miyoshi, Ken Suzawa, Kazuhiko Shien, Hiromasa Yamamoto, Mikio Okazaki, Shinichi Toyooka

Heliyon 9 ( 4 ) e14903 2023年4月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: MicroRNAs (miRNAs) involved in the pathogenesis of pulmonary fibrosis have been shown to be associated with the development of chronic lung allograft dysfunction (CLAD) after lung transplantation (LT). We investigated the role of circulating miRNAs in the diagnosis of CLAD after bilateral LT, including cadaveric LT (CLT) and living-donor lobar LT (LDLLT). METHODS: The subjects of this retrospective study were 37 recipients of bilateral CLT (n = 23) and LDLLT (n = 14), and they were divided into a non-CLAD group (n = 24) and a CLAD group (n = 13). The plasma miRNA levels of the two groups were compared, and correlations between their miRNAs levels and percent baseline forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and total lung capacity (TLC) values were calculated from one year before to one year after the diagnosis of CLAD. RESULTS: The plasma levels of both miR-21 and miR-155 at the time of the diagnosis of CLAD were significantly higher in the CLAD group than in the non-CLAD group (miR-21, P = 0.0013; miR-155, P = 0.042). The miR-21 levels were significantly correlated with the percent baseline FEV1, FVC, and TLC value of one year before and at the time of diagnosis of CLAD (P < 0.05). A receiver operating characteristic curve analysis of the performance of miR-21 levels in the diagnosis of CLAD yielded an area under the curve of 0.89. CONCLUSION: Circulating miR-21 appears to be of potential value in diagnosing CLAD after bilateral LT.

DOI： 10.1016/j.heliyon.2023.e14903

Donor's long-term quality of life following living-donor lobar lung transplantation. 査読国際誌

Kento Fujii, Shin Tanaka, Megumi Ishihara, Kei Matsubara, Kohei Hashimoto, Shuji Okahara, Kazuhiko Shien, Ken Suzawa, Kentaroh Miyoshi, Shinji Otani, Hiromasa Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka

Clinical transplantation 37 ( 4 ) e14927 2023年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Living-donor lobar lung transplantation is an alternative procedure to deceased donation lung transplantation. It involves graft donation from healthy donors; however, only a few reports have discussed its long-term prognosis in living lung donors and their associated health-related quality of life. This study aimed to examine living lung donors' health-related quality of life. METHODS: In our cross-sectional survey of living lung donors, we assessed health-related quality of life based on three key aspects (physical, mental, and social health) using the 36-Item Short Form Health Survey. We also evaluated chronic postoperative pain and postoperative breathlessness using the numeric rating scale and the modified Medical Research Council Dyspnea scale, respectively. RESULTS: We obtained consent from 117 of 174 living lung donors. The average scores of the living lung donors on the 36-Item Short Form Health Survey were higher than the national average. However, some donors had poorer physical, mental, and social health, with lower summary scores than the national averages. Low mental component summary predictors included donor age (<40 years; odds ratio = 10.2; p<.001) and recipient age (<18 years; odds ratio = 2.73; p<.032). Low role-social component summary predictors included high lung allocation score (≥50; odds ratio = 3.94, p<.002) and recipient death (odds ratio = 3.64; p = .005). There were no predictors for physical component summary. Additionally, many donors did not complain of pain or dyspnea. CONCLUSIONS: Living lung donors maintained acceptable long-term health-related quality of life after surgery. Potential donors should be informed of relevant risk factors, and high-risk donors should receive appropriate support. This article is protected by copyright. All rights reserved.

DOI： 10.1111/ctr.14927

Use of the index of pulmonary vascular disease for predicting long-term outcome of pulmonary arterial hypertension associated with congenital heart disease. 査読国際誌

Ayako Chida-Nagai, Naoki Masaki, Kay Maeda, Konosuke Sasaki, Hiroki Sato, Jun Muneuchi, Yoshie Ochiai, Hiroomi Murayama, Masahiro Tahara, Atsuko Shiono, Atsushi Shinozuka, Fumihiko Kono, Daisuke Machida, Shinichi Toyooka, Seiichiro Sugimoto, Kazufumi Nakamura, Satoshi Akagi, Maiko Kondo, Shingo Kasahara, Yasuhiro Kotani, Junichi Koizumi, Katsuhiko Oda, Masako Harada, Daisuke Nakajima, Akira Murata, Hazumu Nagata, Koichi Yatsunami, Tomio Kobayashi, Yoshikiyo Matsunaga, Takahiro Inoue, Hiroyuki Yamagishi, Naomi Nakagawa, Katsuki Ohtani, Masaki Yamamoto, Yushi Ito, Tatsunori Hokosaki, Yuta Kuwahara, Satoshi Masutani, Koji Nomura, Tsutomu Wada, Hirofumi Sawada, Masayuki Abiko, Tatsunori Takahashi, Yuichi Ishikawa, Seigo Okada, Atsushi Naitoh, Takako Toda, Tatsuya Ando, Akihiro Masuzawa, Shinsuke Hoshino, Masaaki Kawada, Yuichi Nomura, Kentaro Ueno, Naoki Ohashi, Tsuyoshi Tachibana, Yuchen Cao, Hideaki Ueda, Sadamitsu Yanagi, Masaaki Koide, Norie Mitsushita, Kouji Higashi, Yoshihiro Minosaki, Tomohiro Hayashi, Takashi Okamoto, Kenji Kuraishi, Eiji Ehara, Hidekazu Ishida, Hitoshi Horigome, Takashi Murakami, Kohta Takei, Taku Ishii, Gen Harada, Yasutaka Hirata, Jun Maeda, Shunsuke Tatebe, Chiharu Ota, Yasunobu Hayabuchi, Hisanori Sakazaki, Takashi Sasaki, Keiichi Hirono, Sayo Suzuki, Masahiro Yasuda, Atsuhito Takeda, Madoka Sawai, Kagami Miyaji, Atsushi Kitagawa, Yosuke Nakai, Nobuyuki Kakimoto, Kouta Agematsu, Atsushi Manabe, Yoshikatsu Saiki

Frontiers in cardiovascular medicine 10 1212882 - 1212882 2023年

記述言語：英語掲載種別：研究論文（学術雑誌）

AIMS: Limited data exist on risk factors for the long-term outcome of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH). We focused on the index of pulmonary vascular disease (IPVD), an assessment system for pulmonary artery pathology specimens. The IPVD classifies pulmonary vascular lesions into four categories based on severity: (1) no intimal thickening, (2) cellular thickening of the intima, (3) fibrous thickening of the intima, and (4) destruction of the tunica media, with the overall grade expressed as an additive mean of these scores. This study aimed to investigate the relationship between IPVD and the long-term outcome of CHD-PAH. METHODS: This retrospective study examined lung pathology images of 764 patients with CHD-PAH aged <20 years whose lung specimens were submitted to the Japanese Research Institute of Pulmonary Vasculature for pulmonary pathological review between 2001 and 2020. Clinical information was collected retrospectively by each attending physician. The primary endpoint was cardiovascular death. RESULTS: The 5-year, 10-year, 15-year, and 20-year cardiovascular death-free survival rates for all patients were 92.0%, 90.4%, 87.3%, and 86.1%, respectively. The group with an IPVD of ≥2.0 had significantly poorer survival than the group with an IPVD <2.0 (P = .037). The Cox proportional hazards model adjusted for the presence of congenital anomaly syndromes associated with pulmonary hypertension, and age at lung biopsy showed similar results (hazard ratio 4.46; 95% confidence interval: 1.45-13.73; P = .009). CONCLUSIONS: The IPVD scoring system is useful for predicting the long-term outcome of CHD-PAH. For patients with an IPVD of ≥2.0, treatment strategies, including choosing palliative procedures such as pulmonary artery banding to restrict pulmonary blood flow and postponement of intracardiac repair, should be more carefully considered.

DOI： 10.3389/fcvm.2023.1212882

The impact of prognostic nutrition index on the waitlist mortality of lung transplantation. 査読

Kei Matsubara, Shinji Otani, Haruchika Yamamoto, Yasuaki Tomioka, Toshio Shiotani, Kentaroh Miyoshi, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka

General thoracic and cardiovascular surgery 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: The prognostic nutrition index (PNI), calculated using serum albumin and total lymphocyte count, is a recent topical index related to inflammation. Preoperative PNI is regarded as a new preoperative prognostic score in lung transplantation (LTx). This study aimed to investigate the impact of PNI at the time of registration as a prognostic parameter of mortality on the waiting list for LTx. METHODS: A retrospective review was conducted on the data of 132 adult patients registered for LTx in our department between January 2013 and June 2020. Patients who finally received LTx were analyzed as censored data. The overall survival was evaluated using the Kaplan-Meier method for pre-registered clinical factors including the PNI at the time of registration. Overall survival was calculated from the date of listing to the Japan Organ Transplant Network to the date of death. RESULTS: The low-PNI group had a significantly worse prognosis. Multivariate analysis demonstrated that age (p = 0.023), idiopathic interstitial pneumonia (p < 0.001), lung allocation score (LAS) (p < 0.001), and PNI (p < 0.001) were independent prognostic factors for waitlist mortality. CONCLUSIONS: PNI at the time of registration can be an independent prognostic parameter in registered candidates for LTx.

DOI： 10.1007/s11748-022-01895-3

Functional Blockage of S100A8/A9 Ameliorates Ischemia-Reperfusion Injury in the Lung. 査読国際誌

Kentaro Nakata, Mikio Okazaki, Tomohisa Sakaue, Rie Kinoshita, Yuhei Komoda, Dai Shimizu, Haruchika Yamamoto, Shin Tanaka, Ken Suzawa, Kazuhiko Shien, Kentaroh Miyoshi, Hiromasa Yamamoto, Toshiaki Ohara, Seiichiro Sugimoto, Masaomi Yamane, Akihiro Matsukawa, Masakiyo Sakaguchi, Shinichi Toyooka

Bioengineering (Basel, Switzerland) 9 ( 11 ) 2022年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

(1) Background: Lung ischemia-reperfusion (IR) injury increases the mortality and morbidity of patients undergoing lung transplantation. The objective of this study was to identify the key initiator of lung IR injury and to evaluate pharmacological therapeutic approaches using a functional inhibitor against the identified molecule. (2) Methods: Using a mouse hilar clamp model, the combination of RNA sequencing and histological investigations revealed that neutrophil-derived S100A8/A9 plays a central role in inflammatory reactions during lung IR injury. Mice were assigned to sham and IR groups with or without the injection of anti-S100A8/A9 neutralizing monoclonal antibody (mAb). (3) Results: Anti-S100A8/A9 mAb treatment significantly attenuated plasma S100A8/A9 levels compared with control IgG. As evaluated by oxygenation capacity and neutrophil infiltration, the antibody treatment dramatically ameliorated the IR injury. The gene expression levels of cytokines and chemokines induced by IR injury were significantly reduced by the neutralizing antibody. Furthermore, the antibody treatment significantly reduced TUNEL-positive cells, indicating the presence of apoptotic cells. (4) Conclusions: We identified S100A8/A9 as a novel therapeutic target against lung IR injury.

DOI： 10.3390/bioengineering9110673

本邦における肺移植時の一酸化窒素(NO)ガス使用状況に関する実態調査

吉安展将, 佐藤雅昭, 中島大輔, 富岡泰章, 渡辺有為, 白石武史, 舟木壮一郎, 前田寿美子, 朝重耕一, 中島崇裕, 土谷智史, 杉本誠一郎, 吉野一郎, 永安武, 千田雅之, 南正人, 岡田克典, 豊岡伸一, 伊達洋至, 中島淳

日本呼吸器外科学会雑誌 36 ( 7 ) 722 - 734 2022年11月

Inhibiting S100A8/A9 attenuates airway obstruction in a mouse model of heterotopic tracheal transplantation. 国際誌

Dai Shimizu, Mikio Okazaki, Seiichiro Sugimoto, Rie Kinoshita, Kentaro Nakata, Shin Tanaka, Kohei Hashimoto, Kentaroh Miyoshi, Masaomi Yamane, Akihiro Matsukawa, Masakiyo Sakaguchi, Shinichi Toyooka

Biochemical and biophysical research communications 629 86 - 94 2022年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Although bronchiolitis obliterans syndrome (BOS) is a major cause of death after lung transplantation, an effective drug therapy for BOS has not yet developed. Here, we assessed the effectiveness of a neutralizing anti-S100 calcium binding protein (S100) A8/A9 antibody against BOS. A murine model of heterotopic tracheal transplantation was used. Mice were intraperitoneally administered control IgG or the S100A8/A9 antibody on day 0 and twice per week until they were sacrificed. Tissue sections were used to evaluate the obstruction ratio, epithelium-preservation ratio, α-smooth muscle actin (SMA)-positive myofibroblast infiltration, and luminal cell death. Quantitative reverse transcriptase-polymerase chain reaction analysis was performed to analyze the mRNA-expression levels of collagen, inflammatory cytokines, and chemokines on days 7, 14, and 21. The anti-S100A8/A9 antibody significantly improved the obstruction ratio and epithelium-preservation ratio, with less α-SMA-positive myofibroblast infiltration compared to the control group. Antibody treatment reduced the type-III collagen: type-I collagen gene-expression ratio. The antibody also significantly suppressed the number of dead cells in the graft lumen. The expression levels of tumor growth factor β1 and C-C motif chemokine 2 on day 21, but not those of interleukin-1β, interleukin-6, and tumor necrosis factor α, were significantly suppressed by S100A8/A9 antibody treatment. These findings suggest that S100A8/A9 may be a potential therapeutic target for BOS after lung transplantation.

DOI： 10.1016/j.bbrc.2022.08.087

Lung recruitment after cardiac arrest during procurement of atelectatic donor lungs is a protective measure in lung transplantation. 国際誌

Eito Niman, Kentaroh Miyoshi, Toshio Shiotani, Tomohiro Toji, Takuro Igawa, Shinji Otani, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka

Journal of thoracic disease 14 ( 8 ) 2802 - 2811 2022年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: Brain-dead donors are susceptible to pulmonary atelectasis (AT). In procurement surgery, lung recruitment under circulatory conditions and cold-flushing for atelectatic donor lungs often provoke graft injury due to the acute blood inflow. We hypothesized that lung recruitment without blood circulation can mitigate graft injury. This study aimed to examine the benefits of lung recruitment subsequent to cardiac arrest using a porcine lung-transplant model. Methods: Thirteen donor pigs were categorized into the non-atelectatic (No-AT) group (n=3) representing a healthy control group; AT-BCR group (n=5), in which AT was reverted by conventional blood-circulated recruitment (BCR); and AT-no-BCR group (n=5), in which AT was reverted by no-BCR following circulatory arrest. In the atelectatic donor models, the left main bronchus was ligated for 24 hours prior to lung procurement. Left lung transplantation (LTx) was subsequently performed in the thirteen recipient pigs. After 6 hours evaluation, the recipients were euthanized and the lung grafts were excised. Results: The post-transplant PaO2/FiO2 ratio was significantly higher in the AT-no-BCR group than in the AT-BCR group (P=0.015). Wet/dry ratio, histological findings of graft injury and tissue interleukin-8 expression in the AT-no-BCR group were similar to those of the No-AT group. Conclusions: Lung recruitment without circulation after circulatory arrest could be more protective for atelectatic donor lung than the conventional procedure.

DOI： 10.21037/jtd-22-226

Drug repositioning of tranilast to sensitize a cancer therapy by targeting cancer-associated fibroblast. 国際誌

Kosuke Ochi, Ken Suzawa, Yin Min Thu, Fumiaki Takatsu, Shimpei Tsudaka, Yidan Zhu, Kentaro Nakata, Tatsuaki Takeda, Kazuhiko Shien, Hiromasa Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Tadahiko Shien, Yoshiharu Okamoto, Shuta Tomida, Shinichi Toyooka

Cancer science 113 ( 10 ) 3428 - 3436 2022年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment that mediate resistance of cancer cells to anticancer drugs. Tranilast is an antiallergic drug that suppresses the release of cytokines from various inflammatory cells. In this study, we investigated the inhibitory effect of tranilast on the interactions between non-small cell lung cancer (NSCLC) cells and the CAFs in the tumor microenvironment. Three EGFR-mutant NSCLC cell lines, two KRAS-mutant cell lines and three CAFs derived from NSCLC patients were used. To mimic the tumor microenvironment, the NSCLC cells were co-cultured with the CAFs in vitro, and the molecular profiles and sensitivity to molecular targeted therapy were assessed. Crosstalk between NSCLC cells and CAFs induced multiple biological effects on the NSCLC cells both in vivo and in vitro, including activation of the STAT3 signaling pathway, promotion of xenograft tumor growth, induction of epithelial-mesenchymal transition (EMT), and acquisition of resistance to molecular-targeted therapy, including of EGFR-mutant NSCLC cells to osimertinib and of KRAS-mutant NSCLC cells to selumetinib. Treatment with tranilast led to inhibition of IL-6 secretion from the CAFs, which, in turn, resulted in inhibition of CAF-induced phospho-STAT3 upregulation. Tranilast also inhibited CAF-induced EMT in the NSCLC cells. Finally, combined administration of tranilast with molecular-targeted therapy reversed the CAF-mediated resistance of the NSCLC cells to the molecular-targeted drugs, both in vitro and in vivo. Our results showed that combined administration of tranilast with molecular-targeted therapy is a possible new treatment strategy to overcome drug resistance caused by cancer- CAF interaction.

DOI： 10.1111/cas.15502

Robotic Mediastinal Tumor Resections: Position and Port Placement. 国際誌

Mikio Okazaki, Kazuhiko Shien, Ken Suzawa, Seiichiro Sugimoto, Shinichi Toyooka

Journal of personalized medicine 12 ( 8 ) 2022年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

This study aimed to determine the optimal position and port placement during robotic resection for various mediastinal tumors. For anterior mediastinal tumors, total or extended thymectomy is commonly performed in the supine position using the lateral or subxiphoid approach. Although it is unclear which approach is better during robotic thymectomy, technical advantages of subxiphoid approach are beneficial for patients with myasthenia who require extended thymectomy. Partial thymectomy is performed in the supine position using a lateral approach. Superior, middle, and posterior mediastinal tumors are resected in the decubitus position using the lateral approach, whereas dumbbell tumor resection, which requires a posterior approach, can be performed in the prone position. The position and port placement should be chosen depending on the size, location, and aggressiveness of the tumor. In this study, we describe how to choose which of these different robotic approaches can be used based on our experience and previous reports.

DOI： 10.3390/jpm12081195

One-step nucleic acid amplification for intraoperative diagnosis of lymph node metastasis in lung cancer patients: a single-center prospective study. 国際誌

Kei Namba, Ken Suzawa, Kazuhiko Shien, Akihiro Miura, Yuta Takahashi, Shunsaku Miyauchi, Kota Araki, Kentaro Nakata, Shuta Tomida, Shin Tanaka, Kentaroh Miyoshi, Shinji Otani, Hiromasa Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Junichi Soh, Masaomi Yamane, Shinichi Toyooka

Scientific reports 12 ( 1 ) 7297 - 7297 2022年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

One-step nucleic acid amplification (OSNA) is a rapid intraoperative molecular detection technique for sentinel node assessment via the quantitative measurement of target cytokeratin 19 (CK19) mRNA to determine the presence of metastasis. It has been validated in breast cancer but its application in lung cancer has not been adequately investigated. 214 LNs from 105 patients with 100 primary lung cancers, 2 occult primary lung tumors, and 3 metastatic lung tumors, who underwent surgical lung resection with LN dissection between February 2018 and January 2020, were assessed. Resected LNs were divided into two parts: one was snap-frozen for OSNA and the other underwent rapidly frozen histological examination. Intraoperatively collected LNs were evaluated by OSNA using loop-mediated isothermal amplification and compared with intraoperative pathological diagnosis as a control. Among 214 LNs, 14 were detected as positive by OSNA, and 11 were positive by both OSNA and intraoperative pathological diagnosis. The sensitivity and specificity of OSNA was 84.6% and 98.5%, respectively. The results of 5 of 214 LNs were discordant, and the remainder all matched (11 positive and 198 negative) with a concordance rate of 97.7%. Although the analysis of public mRNA expression data from cBioPortal showed that CK19 expression varies greatly depending on the cancer type and histological subtype, the results of the five cases, except for primary lung cancer, were consistent. OSNA provides sufficient diagnostic accuracy and speed and can be applied to the intraoperative diagnosis of LN metastasis for non-small cell lung cancer.

DOI： 10.1038/s41598-022-11064-4

Survival and prognostic factors in patients undergoing pulmonary metastasectomy for lung metastases from retroperitoneal sarcoma. 国際誌

Fumiaki Takatsu, Hiromasa Yamamoto, Yasuaki Tomioka, Shin Tanaka, Kazuhiko Shien, Ken Suzawa, Kentaroh Miyoshi, Shinji Otani, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Katsuhito Takahashi, Shinichi Toyooka

World journal of surgical oncology 20 ( 1 ) 114 - 114 2022年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Soft-tissue sarcomas are rare malignancies that consist of many different histologic subtypes and arise in various locations in the body. In patients with lung metastases from retroperitoneal sarcomas, the long-term outcomes and prognostic factors are unknown. This study is a retrospective review of patients undergoing pulmonary metastasectomy for retroperitoneal sarcoma metastases at one institution, with the purpose of determining prognostic factors and clinical outcomes. METHODS: This is a single-center, retrospective cohort study of patients undergoing pulmonary metastasectomy for lung metastases from various sarcomas at Okayama University Hospital from January 2006 to December 2018. The Kaplan-Meier method and log-rank test were used for the analyses, and cut-off values of continuous variables were determined by a receiver operating characteristic curve analysis. RESULTS: Twenty-four patients underwent the first pulmonary metastasectomy for lung metastases from retroperitoneal sarcoma in our hospital. Leiomyosarcoma was the most common histologic subtype of retroperitoneal sarcoma (79.2%, n = 19). Median overall survival was 49.9 months, and the 3-year and 5-year survival rates after the first pulmonary metastasectomy were 62.5% and 26.4% respectively. In univariate analysis, age ≥56 years, disease-free interval < 15 months, and size of metastasis (≥ 27 mm) were associated with poor survival. CONCLUSION: Pulmonary metastasectomy can be considered as an effective management strategy in retroperitoneal sarcoma patients with lung metastases in appropriately selected cases, just as it is for other sarcomas.

DOI： 10.1186/s12957-022-02552-y

【肺移植の現況と課題そして展望】生体肺移植後の慢性移植肺機能不全(CLAD)

杉本誠一郎, 田中真, 三好健太郎, 豊岡伸一

胸部外科 75 ( 4 ) 297 - 301 2022年4月

Paediatric lung transplantation: the impact of age on the survival.

Shinji Otani, Haruchika Yamamoto, Shin Tanaka, Yasuaki Tomioka, Kei Matsubara, Dai Shimizu, Toshio Shiotani, Ken Suzawa, Kentaroh Miyoshi, Hiromasa Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka

Surgery today 52 ( 11 ) 1540 - 1550 2022年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: We herein review the outcomes of paediatric lung transplantation (LTx) and analyse subgroups divided by age. METHODS: We retrospectively reviewed 43 consecutive paediatric LTx recipients (< 18 years old: cadaveric LTx [n = 9], living-donor lobar LTx [n = 34]). We also analysed subgroups of patients 1-6 years old (n = 10) and 7-17 years old (n = 33). RESULTS: The 1-, 5- and 10-year overall survival (OS) rates in paediatric recipients were 93%, 82% and 67%, respectively. The 1-, 5- and 10-year graft dysfunction (GD)-free survival rates in paediatric recipients were 85%, 59% and 31%, respectively. The 1- and 5-year OS in the 1- to 6-year-old vs. 7- to 17-year-old groups were 70% vs. 100% and 48% vs. 93%, respectively (p < 0.0001). The 1- and 5-year GD-free survival rates in the 1- to 6-year-old vs. 7- to 17-year-old groups were 60% vs. 93% and 24% vs. 69%, respectively (p = 0.024). The 1- to 6-year-old group showed higher rates of non-standard LTx (p = 0.0001), interstitial pneumonia (p = 0.004) and ventilator dependency (p = 0.007) than the 7- to 17-year-old group. CONCLUSION: Paediatric recipients under 7 years old seemed to have a higher risk of mortality and GD than those 7 years old and older.

DOI： 10.1007/s00595-022-02492-w

Identification of targetable kinases in idiopathic pulmonary fibrosis. 国際誌

Hisao Higo, Kadoaki Ohashi, Shuta Tomida, Sachi Okawa, Hiromasa Yamamoto, Seiichiro Sugimoto, Satoru Senoo, Go Makimoto, Kiichiro Ninomiya, Takamasa Nakasuka, Kazuya Nishii, Akihiko Taniguchi, Toshio Kubo, Eiki Ichihara, Katsuyuki Hotta, Nobuaki Miyahara, Yoshinobu Maeda, Shinichi Toyooka, Katsuyuki Kiura

Respiratory research 23 ( 1 ) 20 - 20 2022年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Tyrosine kinase activation plays an important role in the progression of pulmonary fibrosis. In this study, we analyzed the expression of 612 kinase-coding and cancer-related genes using next-generation sequencing to identify potential therapeutic targets for idiopathic pulmonary fibrosis (IPF). METHODS: Thirteen samples from five patients with IPF (Cases 1-5) and eight samples from four patients without IPF (control) were included in this study. Six of the thirteen samples were obtained from different lung segments of a single patient who underwent bilateral pneumonectomy. Gene expression analysis of IPF lung tissue samples (n = 13) and control samples (n = 8) was performed using SureSelect RNA Human Kinome Kit. The expression of the selected genes was further confirmed at the protein level by immunohistochemistry (IHC). RESULTS: Gene expression analysis revealed a correlation between the gene expression signatures and the degree of fibrosis, as assessed by Ashcroft score. In addition, the expression analysis indicated a stronger heterogeneity among the IPF lung samples than among the control lung samples. In the integrated analysis of the 21 samples, DCLK1 and STK33 were found to be upregulated in IPF lung samples compared to control lung samples. However, the top most upregulated genes were distinct in individual cases. DCLK1, PDK4, and ERBB4 were upregulated in IPF case 1, whereas STK33, PIM2, and SYK were upregulated in IPF case 2. IHC revealed that these proteins were expressed in the epithelial layer of the fibrotic lesions. CONCLUSIONS: We performed a comprehensive kinase expression analysis to explore the potential therapeutic targets for IPF. We found that DCLK1 and STK33 may serve as potential candidate targets for molecular targeted therapy of IPF. In addition, PDK4, ERBB4, PIM2, and SYK might also serve as personalized therapeutic targets of IPF. Additional large-scale studies are warranted to develop personalized therapies for patients with IPF.

DOI： 10.1186/s12931-022-01940-y

Completely Video-assisted Thoracoscopic Lobectomy for Congenital Lobar Emphysema in a Young Adult.

Tsuyoshi Ryuko, Hiromasa Yamamoto, Seiichiro Sugimoto, Ken Suzawa, Kentaroh Miyoshi, Shinji Otani, Mikio Okazaki, Masaomi Yamane, Shinichi Toyooka

Acta medica Okayama 76 ( 1 ) 89 - 92 2022年2月

記述言語：英語

Congenital lobar emphysema (CLE) is defined as the hyperinflation of pulmonary lobes due to obstruction of the flow of air via a known or unknown etiology, which causes pressure symptoms in the adjacent organs. CLE is mainly diagnosed in the neonatal period, and very few adult cases have been reported. Here we report a 34-year-old male with muscular dystrophy who was diagnosed with CLE on examination. He underwent a right lower lobectomy via 3-portal completely video-assisted thoracoscopic surgery, and his symptoms improved. Thoracoscopic surgery helped preserve the respiratory muscles and led to the improvement of respiratory function in this patient.

DOI： 10.18926/AMO/63217

Acute Pulmonary Edema Due to Arteriovenous Shunt Placement after Lung Transplant. 国際誌

Dai Shimizu, Kentaroh Miyoshi, Seiichiro Sugimoto, Tomoko Toma, Yusuke Matsuda, Yasuaki Tomioka, Toshio Shiotani, Shinji Otani, Masaomi Yamane, Shinichi Toyooka

The Annals of thoracic surgery 2022年1月

記述言語：英語

Lung transplant recipients are often complicated by immunosuppressant-induced nephropathy, which may require renal replacement therapy. We report a case of unilateral lung edema and pulmonary hypertension due to arteriovenous fistula placement in a patient with unilateral chronic lung allograft dysfunction after bilateral living-donor lobar lung transplantation. Lung transplant recipients with limited residual vascular beds, such as lobar graft or severe deviation in lung perfusion, are vulnerable to the acute increase in blood flow due to arteriovenous fistula placement and can easily develop pulmonary edema regardless of the left ventricular function. Hence, careful volume control is required.

DOI： 10.1016/j.athoracsur.2021.12.017

Pulmonary Enteric Adenocarcinoma Harboring a BRAF G469V Mutation.

Dai Shimizu, Hiromasa Yamamoto, Kazuhiko Shien, Kohei Taniguchi, Kentaroh Miyoshi, Kei Namba, Kumi Mesaki, Seiichiro Sugimoto, Junichi Soh, Masaomi Yamane, Shinichi Toyooka

Acta medica Okayama 75 ( 6 ) 759 - 762 2021年12月

記述言語：英語

Pulmonary enteric adenocarcinoma (PEAC) is a rare subtype of lung cancer that should be differentiated from colorectal cancer metastasis. Little is known about its genetic background. An 84-year-old male with adenocarcinoma of the lung underwent left upper lobectomy. The histology of the surgical specimen was suggestive of PEAC. Gastrointestinal and colorectal fiberscopy revealed no evidence of colorectal cancer. Next-generation sequencing of the tumor identified a G469V substitution in serine/threonine-protein kinase B-raf (BRAF). Based on the higher prevalence of the G469 substitution in BRAF-mutant lung adenocarcinoma than in BRAFmutant colorectal cancer, the tumor likely originated from the lung. Identification of mutational genotype may be of some help in distinguishing PEAC from the lung metastasis of colorectal cancer.

DOI： 10.18926/AMO/62819

Long-term outcomes of living-donor lobar lung transplantation. 査読国際誌

Seiichiro Sugimoto, Hiroshi Date, Kentaroh Miyoshi, Shinji Otani, Megumi Ishihara, Masaomi Yamane, Shinichi Toyooka

The Journal of thoracic and cardiovascular surgery 2021年11月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: Although living-donor lobar lung transplantation (LDLLT) enables an intermediate survival similar to cadaveric lung transplantation, the long-term outcome remains unknown. We examined the long-term outcomes of 30 patients who received LDLLT more than 16 years previously. METHODS: We retrospectively reviewed the clinical data of 30 patients who underwent LDLLT (bilateral LDLLT, 29 patients; single LDLLT, 1 pediatric patient) between October 1998 and April 2004. RESULTS: LDLLT was performed for 25 female and 5 male patients ranging in age from 8 to 55 years. The diagnoses included pulmonary hypertension (n = 11), pulmonary fibrosis (n = 7), bronchiolitis obliterans (n = 5), and others (n = 7). At a median follow-up of 205 months, 22 patients were alive and 8 were dead. The causes of death were infection (n = 3), malignancy (n = 2), acute rejection (n = 2), and chronic lung allograft dysfunction (CLAD; n = 1). Unilateral CLAD occurred in 17 patients (56.7%), but only 1 of these patients subsequently developed bilateral CLAD. Two patients underwent bilateral cadaveric lung retransplantations. The 5-, 10-, and 15-year CLAD-free survival rates were 80.0%, 62.8%, and 44.3%, respectively. Malignancy occurred in 7 patients. Two of 5 patients with chronic kidney disease requiring hemodialysis underwent living-donor kidney transplantation. The 5-, 10-, and 15-year overall survival rates were 96.7%, 86.7%, and 73.3%, respectively. CONCLUSIONS: Although only 2 lobes are implanted, LDLLT provides encouraging long-term outcomes. In patients with unilateral CLAD, the functioning contralateral graft might contribute to a favorable long-term outcome.

DOI： 10.1016/j.jtcvs.2021.08.090

Effect of preoperative long-term use of corticosteroids on the development of post-transplant lymphoproliferative disorders after lung transplantation: a single-center experience in Japan. 査読

Dai Shimizu, Shinji Otani, Seiichiro Sugimoto, Haruchika Yamamoto, Yasuaki Tomioka, Toshio Shiotani, Kentaroh Miyoshi, Mikio Okazaki, Masaomi Yamane, Shinichi Toyooka

Surgery today 52 ( 4 ) 697 - 704 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Post-transplant lymphoproliferative disorder (PTLD) is a major complication of lung transplantation (LTx). However, few studies on PTLD in Asian populations have been reported. We explored the characteristics of Japanese PTLD cases after LTx. METHODS: We retrospectively reviewed 195 cases of LTx at our institute. We summarized the clinical experiences of 7 PTLD cases and analyzed the patient characteristics and survival outcomes of patients with (n = 7) and without (n = 188) PTLD. RESULTS: All PTLD patients were taking corticosteroids preoperatively (p = 0.0030), and the duration of preoperative corticosteroid therapy was significantly longer in the PTLD group (p = 0.0064) than in the non-PTLD group. The overall survival after LTx was significantly worse in the PTLD group (p = 0.027) than in the non-PLTD group. Among the three patients who died within 1 year after the PTLD onset, two died of opportunistic infections without residual PTLD lesions. Chronic lung allograft dysfunction (CLAD) or bronchiolitis obliterans at an autopsy were diagnosed after PTLD treatment in four cases. CONCLUSIONS: Long-term preoperative corticosteroid therapy may be a risk factor for PTLD after LTx. Opportunistic infections are lethal complications of PTLD, regardless of the effectiveness of PTLD treatment. CLAD occurs at a high rate after PTLD treatment, and close monitoring is required.

DOI： 10.1007/s00595-021-02390-7

Meticulous closure of collateral vessels in the perihilar mediastinal pleura to control intraoperative bleeding during lung transplantation for pulmonary hypertension. 査読国際誌

Haruchika Yamamoto, Seiichiro Sugimoto, Kentaro Imanishi, Kohei Hashimoto, Kentaroh Miyoshi, Shinji Otani, Masaomi Yamane, Shinichi Toyooka

Journal of thoracic disease 13 ( 10 ) 5658 - 5669 2021年10月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Background: Massive blood transfusion compensating hemorrhage during lung transplantation (LT) results in primary graft dysfunction (PGD) and worse outcomes after LT. Collateral vessels in the perihilar mediastinal pleura could be the source of hemorrhage during LT in patients with pulmonary hypertension (PH). The purpose of this study was to examine the effect of closure with hemoclips of the vessels in the perihilar mediastinal pleura on the risk of intraoperative hemorrhage and outcomes after LT in patients with PH. Methods: We retrospectively reviewed 80 patients who underwent LT, including 13 patients with primary PH, 29 patients with secondary PH, and 38 patients with non-PH. Results: The median number of hemoclips was significantly higher in the primary PH group than in the non-PH group (P=0.0045) or secondary PH group (P=0.0060). The intraoperative blood loss, transfusion volume, maximum PGD grade, and the 30-day and 90-day mortality rates in the primary PH group were equivalent to those in the other two groups. Conclusions: Meticulous closure of collateral vessels in the perihilar mediastinal pleura during LT in patients with primary PH allowed intraoperative hemorrhage to be controlled and might be associated with acceptable mortality rate in these patients similar to that of LT in patients with other diseases.

DOI： 10.21037/jtd-21-1119

Lung transplantation for idiopathic multicentric Castleman disease: potential efficacy and tolerability of a humanized anti-interleukin-6 receptor monoclonal antibody. 査読国際誌

Yasuaki Tomioka, Shinji Otani, Shin Tanaka, Kazuhiko Shien, Ken Suzawa, Kentaroh Miyoshi, Hiromasa Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka

Surgical case reports 7 ( 1 ) 209 - 209 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Idiopathic multicentric Castleman disease (iMCD) is a rare polyclonal lymphoproliferative disease caused by the overrepresentation of interleukin-6 (IL-6). Tocilizumab (TCZ) is a humanized monoclonal antibody that binds to the IL-6 receptor and is approved for the treatment of iMCD. The efficacy and tolerability of TCZ in patients with iMCD undergoing lung transplantation (LTx) remain unknown. CASE PRESENTATION: We present the case of a 48-year-old iMCD patient with end-stage lung disease (ESLD) who was successfully treated with cadaveric single-LTx. Intravenous TCZ was used to stabilize the iMCD patient every 2 weeks, except for withdrawal immediately after LTx. At 32 month post-transplant, the patient remained asymptomatic without evidence of rejection, development of de novo donor-specific antibody (DSA), and recurrent iMCD in the native lung. CONCLUSIONS: Single-LTx can be a feasible treatment option for ESLD caused by iMCD. TCZ can be used safely and may be beneficial in recipients with iMCD, and TCZ in combination with usual immunosuppression can be helpful in stabilizing iMCD patients pre- and post-LTx.

DOI： 10.1186/s40792-021-01297-2

Characterization of localized macrophages in bronchiolitis obliterans after allogeneic hematopoietic cell transplantation. 査読

Taiga Kuroi, Nobuharu Fujii, Koichi Ichimura, Keisuke Seike, Akira Yamamoto, Yui Kambara, Seiichiro Sugimoto, Shinji Otani, Kyosuke Saeki, Hideaki Fujiwara, Hisakazu Nishiomori, Takahiro Oto, Yoshinobu Maeda

International journal of hematology 114 ( 6 ) 701 - 708 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) remains one of the most devastating manifestations of chronic graft-versus-host disease in hematopoietic cell transplantation (HCT). Recent findings of BOS after lung transplantation indicate that donor (lung)-derived lung-resident macrophages contribute to BOS, suggesting that differences in the origin of immune cells and localized antigen-presenting cells cause the onset of BOS. METHODS: We identified the phenotype and origin of infiltrating macrophages using immunohistochemistry and fluorescence in situ hybridization in eight sex-mismatched HCT recipients who underwent lung transplantation for BOS after HCT. RESULTS: Most of the infiltrating macrophages appeared to be derived from donor (hematopoietic) cells in patients who developed BOS following HCT. Macrophages observed in the early-stage region of BOS were positive for cluster of differentiation (CD)68 and inducible nitric oxide synthase (iNOS) and negative for CD163 and CD206, suggesting an M1 phenotype. In the late-stage region, macrophages were negative for CD68 and iNOS in all patients, but also positive for CD163 and CD206 in some patients. CONCLUSIONS: Donor-derived M1-macrophages may be involved in the pathogenesis of the early-stage region of BOS. In addition, some macrophages in the late-stage region showed M2 polarization that might be involved in fibrosis.

DOI： 10.1007/s12185-021-03214-7

Protective effects of anti-HMGB1 monoclonal antibody on lung ischemia reperfusion injury in mice. 査読国際誌

Kentaro Nakata, Mikio Okazaki, Dai Shimizu, Ken Suzawa, Kazuhiko Shien, Kentaroh Miyoshi, Shinji Otani, Hiromasa Yamamoto, Seiichiro Sugimoto, Masaomi Yamane, Daiki Ousaka, Toshiaki Ohara, Akihiro Matsukawa, Masahiro Nishibori, Shinichi Toyooka

Biochemical and biophysical research communications 573 164 - 170 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

During ischemia reperfusion (IR) injury, high mobility group box 1 (HMGB1), a chromatin binding protein, is released from necrotic cells and triggers inflammatory responses. We assessed the therapeutic effect of a neutralizing anti-HMGB1 monoclonal antibody (mAb) on lung IR injury. A murine hilar clamp model of IR was used, where mice were divided into sham and IR groups with intravenous administration of anti-HMGB 1 mAb or control mAb. We analyzed the effect of anti-HMGB1 mAb against IR injury by assessing lung oxygenation, lung injury score, neutrophil infiltration, expression of proinflammatory cytokines and chemokines, levels of mitogen-activated protein kinase (MAPK) signaling, and measurement of apoptotic cells. Anti-HMGB1 mAb significantly decreased the plasma level of HMGB1 elevated by IR. The severity of IR injury represented by oxygenation capacity, lung injury score, and neutrophil infiltration was significantly improved by anti-HMGB1 mAb treatment. The expression of proinflammatory factors, including IL-1β, IL-6, IL-12, TNF-α, CXCL-1, and CXCL-2, and phosphorylation of p38 MAPK were both significantly reduced by anti-HMGB1 mAb treatment. Furthermore, anti-HMGB1 mAb treatment suppressed apoptosis, as determined through TUNEL assays. Overall, anti-HMGB1 mAb ameliorated lung IR injury by reducing inflammatory responses and apoptosis. Our findings indicate that anti-HMGB1 mAb has potential for use as a therapeutic to improve IR injury symptoms during lung transplantation.

DOI： 10.1016/j.bbrc.2021.08.015

Robot-assisted thoracoscopic lobectomy for severe incomplete interlober fissure. 査読国際誌

Mikio Okazaki, Ken Suzawa, Kazuhiko Shien, Kentaroh Miyoshi, Shinji Otani, Hiromasa Yamamoto, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka

Journal of surgical case reports 2021 ( 8 ) rjab336 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

An incomplete interlobar fissure makes thoracoscopic lobectomy difficult and is predictive of morbidity after thoracoscopic lobectomy. This report demonstrates the robot-assisted thoracoscopic (RATS) lobectomy technique for patients with severe incomplete interlobar fissures. A fissureless approach was chosen for pulmonary resection. Near-infrared fluorescence imaging with intravenous indocyanine green (ICG) was used to detect the interlobar line after transection of the bronchus, pulmonary artery and vein. Interlobar fissure was identified and divided by robotic staplers. This combined technique using ICG and fissureless lobectomy made RATS lobectomy safe for patients with severe incomplete interlobar fissures.

DOI： 10.1093/jscr/rjab336

Emphysematous changes and lower levels of plasma irisin are associated with bronchiolitis obliterans syndrome after bilateral living-donor lobar lung transplantation. 査読

Toshio Shiotani, Seiichiro Sugimoto, Haruchika Yamamoto, Kentaroh Miyoshi, Shinji Otani, Ken Suzawa, Hiromasa Yamamoto, Mikio Okazaki, Masaomi Yamane, Shinichi Toyooka

Surgery today 52 ( 2 ) 294 - 305 2021年7月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Decreased irisin levels may be associated with the development of emphysema. Similarly, emphysematous changes may develop in patients with chronic lung allograft dysfunction (CLAD) after living-donor lobar lung transplantation (LDLLT). We investigated the severity of emphysematous changes and the relationship between irisin levels and CLAD after bilateral LDLLT and cadaveric lung transplantation (CLT). METHODS: The subjects of this retrospective study were 59 recipients of bilateral LDLLT (n = 31) or CLT (n = 28), divided into a non-CLAD group (n = 41), a LDLLT-CLAD group (n = 11), and a CLT-CLAD group (n = 7). We compared the severity of emphysematous changes, the skeletal muscle mass, and the plasma irisin levels among the groups. RESULTS: The emphysematous changes were significantly more severe in the LDLLT-CLAD and CLT-CLAD groups (p = 0.046 and 0.036), especially in patients with bronchiolitis obliterans syndrome (BOS), than in the non-CLAD group. Although the skeletal muscle mass was similar in all the groups, the plasma irisin levels were significantly lower in the LDLLT-CLAD group (p = 0.022), especially in the patients with BOS after LDLLT, than in the non-CLAD group. CONCLUSION: Emphysematous changes and lower levels of plasma irisin were associated with CLAD, especially in patients with BOS, after bilateral LDLLT.

DOI： 10.1007/s00595-021-02339-w

Lung transplantation for bronchiectasis due to hyper-immunoglobulin E syndrome. 査読国際誌

Dai Shimizu, Shinji Otani, Seiichiro Sugimoto, Haruchika Yamamoto, Yasuaki Tomioka, Toshio Shiotani, Kentaroh Miyoshi, Mikio Okazaki, Masaomi Yamane, Shinichi Toyooka

The Annals of thoracic surgery 113 ( 4 ) e251-e253 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Hyper-immunoglobulin E syndrome (HIES) is one of the primary immunodeficiencies characterized by recurrent staphylococcal skin and lung infections that result in lung destruction and critically diminished pulmonary function. Despite the lack of definitive treatment, there have been no reports of successful lung transplantation (LTx) for HIES patients. We report the case of a 42-year-old female HIES patient with progressive bronchiectasis whose pulmonary infection was controlled prior to transplantation and subsequent LTx was uneventful. LTx may be feasible in HIES if the patient is immunologically stable preoperatively, and peri-operative infections, especially Aspergillus infections, are well-controlled.

DOI： 10.1016/j.athoracsur.2021.05.088

肺移植後の抗体関連拒絶に対するrituximab(遺伝子組換え) 査読

芳川豊史, 伊達洋至, 杉本誠一郎, 白石武史, 中川健, 江川裕人

移植 56 ( 1 ) 53 - 68 2021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：(一社)日本移植学会

日本国内で実施された肺移植525例を対象に、肺移植後に抗体関連型拒絶反応(AMR)を発症し、rituximabを使用した症例について検討した。その結果、肺移植後のAMRに対しrituximabを使用した症例は14例(2.7%)であった。移植時年齢は10歳が1例、23〜69歳が13例であった。rituximabは延べ20回投与され、うち11例は375mg/m2の単回投与であった。rituximab治療3ヵ月で移植肺は3例(21%)で生着したが、11例(79%)で廃絶した。重篤な有害事象は11例(79%)に認められ、うち rituximabとの関連性が否定できない事象は成人3例に発現し、肺炎2例、意識変容状態が1例であった。

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00083&link_issn=&doc_id=20210716280007&doc_link_id=10.11386%2Fjst.56.1_53&url=https%3A%2F%2Fdoi.org%2F10.11386%2Fjst.56.1_53&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

"Hybrid Lung Transplantation" Combining Living Donor and Cadaveric Lung Transplants: Report of 2 Cases. 査読国際誌

Takeshi Kurosaki, Takahiro Oto, Shinji Otani, Kentaroh Miyoshi, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka

Transplantation proceedings 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

We present 2 cases of "hybrid lung transplant," which included sequentially implanting a living lobar graft to 1 side and a cadaveric graft to the other side. This procedure was approved by the institutional review board at Okayama University Hospital. The 2 recipients were diagnosed with severe idiopathic pulmonary fibrosis, and living donor lobar lung transplant was considered; however, 2 appropriate donors were not available. Therefore, we accepted extended criteria donor lungs with a partial pressure of oxygen/fraction of inspired oxygen ratio of <251 mm Hg. However, 1 of the 2 patients developed grade 2 primary graft dysfunction. The living donor lobar lung had a low volume but was in good condition, which contributed to the patient's recovery after primary graft dysfunction during the perioperative period. The other patient's status of bronchiolitis obliterans syndrome had gradually progressed to grade 3, and only the living donor lung was functioning at that time. However, both patients are alive 5.5 and 4.2 years after lung transplant, respectively. Hybrid lung transplantation may increase patients' chances of receiving transplants because patients are not likely to survive while waiting for ideal donor lungs to become available.

DOI： 10.1016/j.transproceed.2021.04.019

Current status of inhaled nitric oxide therapy for lung transplantation in Japan: a nationwide survey. 査読

Nobuyuki Yoshiyasu, Masaaki Sato, Daisuke Nakajima, Yasuaki Tomioka, Yui Watanabe, Takeshi Shiraishi, Soichiro Funaki, Sumiko Maeda, Koichi Tomoshige, Takahiro Nakajima, Tomoshi Tsuchiya, Seiichiro Sugimoto, Ichiro Yoshino, Takeshi Nagayasu, Masayuki Chida, Masato Minami, Yoshinori Okada, Shinichi Toyooka, Hiroshi Date, Jun Nakajima

General thoracic and cardiovascular surgery 69 ( 10 ) 1421 - 1431 2021年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: Currently, inhaled nitric oxide (NO) therapy for lung transplantation is not covered by public health insurance in Japan. In this study, we evaluated the perioperative use and safety of inhaled NO therapy for lung transplantation. METHODS: Data regarding the duration of treatment and adverse events of inhaled NO therapy were collected for all lung transplantations performed from January 1, 2015, to December 31, 2019, at nine lung transplant facilities in Japan. RESULTS: During the study period, lung transplants were performed in 357 patients, among whom inhaled NO therapy was administered to 349 patients (98%). The median initial and median maximum inhaled NO doses were 10 and 20 ppm, respectively. Inhaled NO therapy was introduced during surgery and continued postoperatively in 313 patients (90%) for a median of 4 days. Significant improvements in oxygenation and decreases in pulmonary arterial pressure were observed in patients receiving inhaled NO therapy. Side effects of inhaled NO therapy, such as methemoglobinemia, were observed in 15 patients (4%), with a significant incidence in patients aged < 18 years. CONCLUSIONS: Inhaled NO therapy was performed in almost all patients who underwent lung transplantation in Japan and showed reasonable efficacy. Therefore, public health insurance coverage for inhaled NO therapy during lung transplantation is recommended.

DOI： 10.1007/s11748-021-01648-8

Circulating anti-human leukocyte antigen IgM antibodies as a potential early predictor of allograft rejection and a negative clinical outcome after lung transplantation. 査読

Kazuaki Miyahara, Kentaroh Miyoshi, Takeshi Kurosaki, Shinji Otani, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka

Surgery today 2021年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Anti-human leukocyte antigen (HLA) immunoglobulin (Ig) M production stimulated by an alloantigen is sensitive, making IgM a novel potential marker of allorejection after organ transplantation. This study examined the relationship between the serum levels of anti-HLA IgM early after clinical lung transplantation (LTx) and the post-transplant outcomes. METHODS: Thirty-one consecutive patients who underwent deceased LTx were included. Immunoreactivity against HLA was retrospectively analyzed by measuring the anti-HLA IgM levels in the serum sampled for the first 14 days after LTx. The flow panel reactive antibody technique was used. The ratio of the anti-class I IgM level at each day to baseline was obtained, and the peak IgM level was determined for each case. The correlation between the peak IgM level and subsequent development of acute rejection (AR), chronic lung allograft dysfunction (CLAD), and survival outcomes were examined. RESULTS: The peak IgM level was a significant risk factor for AR within 90 days in univariate and multivariate analyses. In the long term, the patients with positive IgM (peak level > 1.8) tended to have a poorer CLAD-free and overall survival than those with negative IgM. CONCLUSION: Elevation of anti-HLA IgM levels early after LTx may be correlated with a higher incidence of rejection and negative clinical outcomes.

DOI： 10.1007/s00595-021-02293-7

Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Locally Advanced Non-small-cell Lung Cancer Treated with Trimodality Therapy. 査読国際誌

Shimpei Tsudaka, Hiromasa Yamamoto, Hiroki Sato, Kuniaki Katsui, Ken Suzawa, Kazuhiko Shien, Kentaroh Miyoshi, Shinji Otani, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Katsuyuki Kiura, Susumu Kanazawa, Shinichi Toyooka

Annals of surgical oncology 28 ( 9 ) 4880 - 4890 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Current evidence suggests that the neutrophil-to-lymphocyte ratio (NLR) is a prognostic factor in several types of cancer. In this study, we aimed to evaluate the prognostic impact of clinicopathological factors, including postoperative NLR, in patients with locally advanced non-small-cell lung cancer (LA-NSCLC) who underwent surgery after chemoradiotherapy (CRT) with or without postoperative adjuvant chemotherapy. METHODS: The medical records of LA-NSCLC patients treated with trimodality therapy at our institution between June 1999 and May 2019 were reviewed. The association between several clinicopathological factors and overall survival (OS) was analyzed. RESULTS: A total of 168 patients were included in this study. Regarding the prognosis, the 5-year OS rate was 68.1%, and the 2-year recurrence-free survival rate was 66.1% in the entire population. In multivariate analysis, we identified that high postoperative NLR, not pretreatment or preoperative NLR, was one of the independent factors for unfavorable OS (NLR high vs NLR low; hazard ratio = 2.45, 95% confidence interval: 1.53-3.94, p < 0.001). In addition, among patients with high postoperative NLR, patients who received postoperative adjuvant chemotherapy showed significantly better 5-year OS compared with those who did not (p = 0.016). On the other hand, postoperative adjuvant chemotherapy had no impact on the prognosis in patients with low NLR (p = 0.19). CONCLUSIONS: Our results suggest that high postoperative NLR was not only an independent unfavorable prognostic factor in patients with LA-NSCLC who were treated with trimodality therapy, but also a promising indicator for postoperative treatment in this population.

DOI： 10.1245/s10434-021-09690-9

The prognostic nutritional index is correlated negatively with the lung allocation score and predicts survival after both cadaveric and living-donor lobar lung transplantation. 査読

Haruchika Yamamoto, Seiichiro Sugimoto, Junichi Soh, Toshio Shiotani, Kentaroh Miyoshi, Shinji Otani, Mikio Okazaki, Masaomi Yamane, Shinichi Toyooka

Surgery today 51 ( 10 ) 1610 - 1618 2021年2月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: The prognostic nutritional index (PNI), calculated based on the serum albumin levels and the total lymphocyte count, has been identified as a predictor of clinical outcomes in various fields of surgery. In this study, we investigated the relationship between the PNI and the lung allocation score (LAS) as well as the impact of the PNI on the outcomes of both cadaveric lung transplantation (CLT) and living-donor lobar lung transplantation (LDLLT). METHODS: We reviewed retrospective data for 127 recipients of lung transplantation (LT), including 71 recipients of CLT and 56 recipients of LDLLT. RESULTS: The PNI was correlated significantly and negatively with the LAS (r = - 0.40, P = 0.0000037). Multivariate analysis revealed that age (P = 0.00093), BMI (P = 0.00087), and PNI (P = 0.0046) were independent prognostic factors of a worse outcome after LT. In a subgroup analysis, survival after both CLT (P = 0.015) and LDLLT (P = 0.041) was significantly worse in the low PNI group than in the high PNI group. CONCLUSION: Preoperative nutritional evaluations using the PNI can assist with the assessment of disease severity in LT recipients and may predict survival after both CLT and LDLLT.

DOI： 10.1007/s00595-021-02244-2

The prognostic impact of sarcopenia on elderly patients undergoing pulmonary resection for non-small cell lung cancer. 査読

Akihiro Miura, Hiromasa Yamamoto, Hiroki Sato, Yasuaki Tomioka, Toshio Shiotani, Ken Suzawa, Kentaroh Miyoshi, Shinji Otani, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka

Surgery today 51 ( 7 ) 1203 - 1211 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: The number of elderly patients who undergo surgery is increasing, even though they are at a high risk due to a decreased physical strength. Furthermore, sarcopenia is generally associated with a poor prognosis in patients with non-small cell lung cancer (NSCLC). METHODS: This study included NSCLC patients ≥ 65 years old who underwent pulmonary resection in our hospital between 2012 and 2015. Sarcopenia was assessed using the psoas muscle mass index based on computed tomography at the level of the third lumbar vertebra. We elucidated the impact of sarcopenia on short- and long-term outcomes after surgery. RESULTS: We enrolled 259 patients, including 179 with sarcopenia. Patients with sarcopenia before surgery tended to have postoperative complications (p = 0.0521), although they did not show a poor prognosis. In patients with sarcopenia, a multivariate analysis revealed that postoperative complications and the progression of sarcopenia 1 year after surgery were significant risk factors for a poor prognosis (p = 0.0169 and 0.00370, respectively). CONCLUSIONS: The progression of sarcopenia after surgery is associated with a poor prognosis in elderly NSCLC patients with sarcopenia. A strategy to prevent postoperative progressive sarcopenia may be necessary for improving the clinical outcome of this population.

DOI： 10.1007/s00595-020-02221-1

Long-term Follow-up of Living-Donor Kidney Transplantation after Cadaveric Lung Transplantation. 査読

Toshio Shiotani, Seiichiro Sugimoto, Kota Araki, Yasuaki Tomioka, Kentaroh Miyoshi, Shinji Otani, Masaomi Yamane, Shinichi Toyooka

Acta medica Okayama 75 ( 1 ) 87 - 89 2021年2月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Although chronic kidney disease (CKD) commonly develops after lung transplantation (LT), living-donor kid-ney transplantation (LDKT) for CKD after LT is known to provide favorable outcomes. We describe the long-term follow-up findings of a patient who underwent LDKT after bilateral cadaveric LT. A 37-year-old male underwent LDKT for CKD 18 years after receiving bilateral cadaveric LT. He developed chronic lung allograft dysfunction (CLAD) 20 years after the LT; however, at 26 years after the initial LT, he is still alive with no pro-gression of CLAD or CKD. KT could be a viable option for CKD even after LT in Japan.

DOI： 10.18926/AMO/61439

Successful Bronchoscopic Treatment for Postoperative Bronchopleural Fistula Using N-butyl-2-cyanoacrylate (NBCA): Report of a Post-completion Pneumonectomy Case with a History of Induction Chemoradiotherapy Followed by Bilobectomy for Advanced Lung Cancer. 査読

Toshio Shiotani, Hiromasa Yamamoto, Riko Katsube, Yasuaki Tomioka, Ken Suzawa, Kentaroh Miyoshi, Shinji Otani, Mikio Okazaki, Seiichiro Sugimoto, Junichi Soh, Masaomi Yamane, Shinichi Toyooka

Acta medica Okayama 75 ( 1 ) 91 - 94 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Bronchopleural fistula (BPF) is a severe complication following lung resection. We present the case of a patient with a history of advanced lung cancer, who had undergone induction chemoradiotherapy followed by right middle and lower lobectomy, and who developed BPF after completion right pneumonectomy. Although we had covered the bronchial stump with an omental pedicled flap, BPF was found on postoperative day 19. We covered the fistula with n-butyl-2-cyanoacrylate (NBCA) using bronchoscopy. Although we had to repeat the NBCA treatment, we ultimately cured the patient's BPF and no recurrence was observed up to 15.2 months after surgery.

DOI： 10.18926/AMO/61440

Staged surgery for empyema and lung gangrene caused by pseudoaneurysm after radiofrequency ablation. 査読国際誌

Kentaro Nakata, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka

Interactive cardiovascular and thoracic surgery 32 ( 5 ) 831 - 833 2021年1月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Lung gangrene is a potentially fatal disease, and primary or staged surgery, depending on the patient's condition, is reported to be useful. We describe successful management, by staged surgery, of a rare case of empyema and lung gangrene complicating lung radiofrequency ablation. The patient, who was a diabetic with colorectal pulmonary metastases, underwent embolization of a pulmonary artery pseudoaneurysm in the right basal segment that developed after lung radiofrequency ablation. He subsequently developed lung gangrene caused by lung ischaemia, and empyema, necessitating pleural decortication followed by open-window thoracostomy. Subsequently, right basal segmentectomy was performed, with thoracostoma closure. Staged surgery might be beneficial for high-risk patients with empyema and lung gangrene caused by lung ischaemia.

DOI： 10.1093/icvts/ivaa331

The heterodimer S100A8/A9 is a potent therapeutic target for idiopathic pulmonary fibrosis. 査読国際誌

Kota Araki, Rie Kinoshita, Nahoko Tomonobu, Yuma Gohara, Shuta Tomida, Yuta Takahashi, Satoru Senoo, Akihiko Taniguchi, Junko Itano, Ken-Ichi Yamamoto, Hitoshi Murata, Ken Suzawa, Kazuhiko Shien, Hiromasa Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Kouichi Ichimura, Masahiro Nishibori, Nobuaki Miyahara, Shinichi Toyooka, Masakiyo Sakaguchi

Journal of molecular medicine (Berlin, Germany) 99 ( 1 ) 131 - 145 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

In patients with interstitial pneumonia, pulmonary fibrosis is an irreversible condition that can cause respiratory failure. Novel treatments for pulmonary fibrosis are necessary. Inflammation is thought to activate lung fibroblasts, resulting in pulmonary fibrosis. Of the known inflammatory molecules, we have focused on S100A8/A9 from the onset of inflammation to the subsequent progression of inflammation. Our findings confirmed the high expression of S100A8/A9 in specimens from patients with pulmonary fibrosis. An active role of S100A8/A9 was demonstrated not only in the proliferation of fibroblasts but also in the fibroblasts' differentiation to myofibroblasts (the active form of fibroblasts). S100A8/A9 also forced fibroblasts to upregulate the production of collagen. These effects were induced via the receptor of S100A8/A9, i.e., the receptor for advanced glycation end products (RAGE), on fibroblasts. The anti-S100A8/A9 neutralizing antibody inhibited the effects of S100A8/A9 on fibroblasts and suppressed the progression of fibrosis in bleomycin (BLM)-induced pulmonary fibrosis mouse model. Our findings strongly suggest a crucial role of S100A8/A9 in pulmonary fibrosis and the usefulness of S100A8/A9-targeting therapy for fibrosis interstitial pneumonia. HIGHLIGHTS: S100A8/A9 level is highly upregulated in the IPF patients' lungs as well as the blood. S100A8/A9 promotes not only the growth of fibroblasts but also differentiation to myofibroblasts. The cell surface RAGE acts as a crucial receptor to the extracellular S100A8/A9 in fibroblasts. The anti-S100A8/A9 antibody effectively suppresses the progression of IPF in a mouse model. In idiopathic pulmonary fibrosis (IPF), S100A8/A9, a heterodimer composed of S100A8 and S100A9 proteins, plays a crucial role in the onset of inflammation and the subsequent formation of a feed-forward inflammatory loop that promotes fibrosis. (1) The local, pronounced increase in S100A8/A9 in the injured inflammatory lung region-which is provided mainly by the activated neutrophils and macrophages-exerts strong inflammatory signals accompanied by dozens of inflammatory soluble factors including cytokines, chemokines, and growth factors that further act to produce and secrete S100A8/A9, eventually making a sustainable inflammatory circuit that supplies an indefinite presence of S100A8/A9 in the extracellular space with a mal-increased level. (2) The elevated S100A8/A9 compels fibroblasts to activate through receptor for advanced glycation end products (RAGE), one of the major S100A8/A9 receptors, resulting in the activation of NFκB, leading to fibroblast mal-events (e.g., elevated cell proliferation and transdifferentiation to myofibroblasts) that actively produce not only inflammatory cytokines but also collagen matrices. (3) Finally, the S100A8/A9-derived activation of lung fibroblasts under a chronic inflammation state leads to fibrosis events and constantly worsens fibrosis in the lung. Taken together, these findings suggest that the extracellular S100A8/A9 heterodimer protein is a novel mainstay soluble factor for IPF that exerts many functions as described above (1-3). Against this background, we herein applied the developed S100A8/A9 neutralizing antibody to prevent IPF. The IPF imitating lung fibrosis in an IPF mouse model was effectively blocked by treatment with the antibody, leading to enhanced survival. The developed S100A8/A9 antibody, as an innovative novel biologic, may help shed light on the difficulties encountered with IPF therapy in clinical settings.

DOI： 10.1007/s00109-020-02001-x

外科系新専門医制度のあるべきグランドデザイン地域枠医師に対する外科専門研修のあり方充実した地域医療の実現を目指して

黒田新士, 吉田龍一, 池田宏国, 岡崎幹生, 大澤晋, 小谷恭弘, 山根正修, 杉本誠一郎, 菊地覚次, 安井和也, 野田卓男, 笠原真悟, 豊岡伸一, 土井原博義, 藤原俊義

日本外科学会雑誌 122 ( 1 ) 83 - 85 2021年1月

Prognostic nutrition index affects the prognosis of patients undergoing trimodality therapy for locally advanced non-small cell lung cancer. 査読

Junichi Soh, Ken Suzawa, Kazuhiko Shien, Shinji Otani, Hiromasa Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Kuniaki Katsui, Masaomi Yamane, Katsuyuki Kiura, Susumu Kanazawa, Shinichi Toyooka

Surgery today 50 ( 12 ) 1610 - 1618 2020年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Trimodality therapy, comprised of induction chemoradiotherapy (iCRT) followed by surgery, is a highly invasive treatment option for locally advanced non-small cell lung cancers (LA-NSCLCs; defined as a heterogenous disease). We conducted this study to investigate the prognostic nutritional index (PNI) of LA-NSCLC patients undergoing trimodality therapy, which has not been studied in detail before. METHODS: The subjects of this retrospective study were 127 patients who underwent trimodality therapy between 1999 and 2016. We measured the PNI at three points: before iCRT (pre-iCRT), before the operation, and after the operation. RESULTS: PNIs decreased significantly as treatment progressed. Patients with clinical T3/4 (cT3/4) disease had a significantly lower PNI than those with cT1/2 disease, but the extent of lymph-node metastasis did not affect the PNI at any point. Using the cut-off values of receiver-operating curve analyses, multivariable analyses revealed that a high PNI pre-iCRT correlated significantly with a better survival of LA-NSCLC patients, especially those with cT3/4 disease (hazard ratio 3.84; 95% confidential interval 1.34-12.5, P = 0.012). CONCLUSIONS: Measuring the PNI before trimodality therapy is important for predicting the clinical outcome of patients with LA-NSCLC, with differing predictive ability according to the disease extent. Perioperative intensive nutritional intervention must be considered for patients who undergo trimodality therapy for LA-NSCLC.

DOI： 10.1007/s00595-020-02067-7

A Simple Prognostic Benefit Scoring System for Sarcoma Patients with Pulmonary Metastases: Sarcoma Lung Metastasis Score. 査読国際誌

Haruchika Yamamoto, Hiromasa Yamamoto, Junichi Soh, Etsuji Suzuki, Kei Namba, Ken Suzawa, Kentaroh Miyoshi, Shinji Otani, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Takashi Yorifuji, Katsuhito Takahashi, Shinichi Toyooka

Annals of surgical oncology 28 ( 7 ) 3884 - 3890 2020年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Pulmonary metastasectomy could be considered one of the treatment options for disease control in sarcoma patients with pulmonary metastases; however, there is little consensus regarding the suitable criteria for predicting the likely outcomes in these patients. The aim of this study was to establish a prognostic benefit scoring system based on preoperatively examined prognostic factors for sarcoma patients with pulmonary metastases. METHODS: This was a single-center, retrospective cohort study conducted in a cohort of 135 sarcoma patients who underwent a first pulmonary metastasectomy at Okayama University Hospital between January 2006 and December 2015. Based on the results of a multivariable logistic regression analysis performed to determine the factors influencing 3-year mortality, a Sarcoma Lung Metastasis Score was created and its correlation with 3-year survival was analyzed. RESULTS: The results of the multivariate analysis revealed significant differences in the disease-free interval (< 2 years vs. ≥ 2 years; odds ratio (OR) 4.22, 95% confidence interval (CI) 1.67-10.70), maximum tumor diameter (≥ 15 mm vs. < 15 mm; OR 3.86, 95% CI 1.75-8.52), and number of pulmonary metastases (≥ 6 vs. < 6; OR 2.65, 95% CI 1.06-6.620). The Sarcoma Lung Metastasis Score, which was defined as the total score of these three factors, reliably predicted 3-year survival (score: 0, 89.5%; 1, 63.2%; 2, 39.0%; 3, 10.5%). CONCLUSIONS: Our newly proposed simple Sarcoma Lung Metastasis Score appears to be a useful prognostic predictor for sarcoma patients with pulmonary metastases, in that it could be helpful for the selection of appropriate treatments for these patients.

DOI： 10.1245/s10434-020-09272-1

Long-term clinical follow-up after lung transplantation in patient with scoliosis: a case report. 査読

Haruchika Yamamoto, Shinji Otani, Kentaroh Miyoshi, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka

General thoracic and cardiovascular surgery 69 ( 4 ) 752 - 755 2020年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Severe scoliosis causes anatomical distortion of structures in the chest, which raises concerns about donor-recipient size-mismatch in lung transplantation (LT), so that severe scoliosis is considered as an absolute contraindication for LT. Also, postoperative right-side bronchial stenosis is one of the common complications in LT recipients with severe scoliosis. To date, the long-term outcomes in severe scoliosis patients with bronchial stenosis after LT have not been reported. A 14-year-old female patient with scoliosis and interstitial pneumonia underwent bilateral cadaveric LT. Although she developed bronchial stenosis post-LT, necessitating bronchoscopic intervention on three occasions, her lung function and perfusion recovered to the levels recorded prior to development of the obstruction, with the good condition maintained for more than 5 years after the LT. Therefore, while patients with severe scoliosis are at an elevated risk of postoperative transient bronchial stenosis, scoliosis should not always be considered as a contraindication to LT.

DOI： 10.1007/s11748-020-01539-4

Chronic lung injury after trimodality therapy for locally advanced non-small cell lung cancer. 査読国際誌

Junichi Soh, Seiichiro Sugimoto, Kei Namba, Akihiro Miura, Toshio Shiotani, Haruchika Yamamoto, Ken Suzawa, Kazuhiko Shien, Hiromasa Yamamoto, Mikio Okazaki, Kuniaki Katsui, Masaomi Yamane, Katsuyuki Kiura, Susumu Kanazawa, Shinichi Toyooka

The Annals of thoracic surgery 112 ( 1 ) 279 - 288 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Trimodality therapy is a treatment option for patients with locally advanced non-small cell lung cancer (LA-NSCLC). Thoracic radiation has both early (radiation pneumonitis) and late (chronic lung injury: CLI) adverse effects on the lung. While CLI is expected to result in various problems in long-term survivors, these manifestations have not been precisely investigated. METHODS: We enrolled 112 LA-NSCLC patients who had received induction chemoradiotherapy followed by surgery, and then undergone follow-up computed tomography (CT) every 6 months for >1 year. All chest CT images were reviewed to evaluate any injury of the pulmonary parenchyma. RESULTS: CLI at 1 year after surgery and its progression (pCLI) were observed in 94 (84%) and 38 (34%) patients, respectively. Progressive lung fibrosis (PLF) as the first manifestation of pCLI was most frequent after right middle and/or lower lobectomy. Cavity formation was the subsequent manifestation after PLF, and chronic infection was the final stage of CLI. The cumulative rate of chronic infection was 76.4% at 10 years in patients with cavity formation. Ten patients with chronic infection included seven cases of pulmonary aspergillosis and two cases of cavity infections with methicillin-resistant Staphylococcus aureus or Stenotrophomonas maltophili. Among them, 4 patients required surgical interventions including completion pneumonectomy or fenestration. CONCLUSIONS: CLI is a common incidence after trimodality therapy for LA-NSCLC. CLI frequently results in cavity formation, which is a precursor of highly refractory chronic infections requiring surgical intervention. Appropriate management needs to be established for CLI developing after trimodality therapy.

DOI： 10.1016/j.athoracsur.2020.07.068

Lung transplantation for Kartagener syndrome: technical aspects and morphological adaptation of the transplanted lungs. 査読

Haruchika Yamamoto, Seiichiro Sugimoto, Kentaroh Miyoshi, Shinji Otani, Masaomi Yamane, Shinichi Toyooka

General thoracic and cardiovascular surgery 69 ( 3 ) 588 - 592 2020年10月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

While technical considerations in lung transplantation for Kartagener syndrome have been discussed, little information is available about the postoperative morphological changes of the grafted lungs. Herein, we discuss both the technical aspects and postoperative morphological adaptation of the grafted lungs in a case of Kartagener syndrome. A 46-year-old male patient with Kartagener syndrome underwent bilateral cadaveric lung transplantation. The right arterial anastomosis for transplantation of the size-matched grafts required technical elaboration. After the transplantation, we found a free space in the cardiac notch of the left lung and partial collapse of the lower lobe of the right lung due to dextrocardia. Follow-up computed tomography performed on day 42 after the transplantation demonstrated resolution of the atelectasis and morphological adaptation of the grafts into the recipient's chest cavity with dextrocardia. Considering such early morphological adaptation of size-matched grafts, lobar reduction could be avoided in lung transplantation for Kartagener syndrome.

DOI： 10.1007/s11748-020-01509-w

Continuing surgical education of non-technical skills. 査読国際誌

Masaomi Yamane, Seiichiro Sugimoto, Etsuji Suzuki, Keiju Aokage, Mikio Okazaki, Junichi Soh, Makio Hayama, Yuji Hirami, Takashi Yorifuji, Shinichi Toyooka

Annals of medicine and surgery (2012) 58 177 - 186 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: The non-technical skills for surgeons (NOTSS) system was developed as a tool to assess surgical skills for patient safety during surgery. This study aimed to develop a NOTSS-based training system for surgical trainees to acquire non-technical skills using a chest surgery scenario in a wet lab. Materials and methods: Trainees were categorized into three subgroups according to the years of experience as follows: Level A: 6 years or more; Level B: 3-5 years; and Level C: 1-2 years. Three stages of surgical procedure were designed: 1. chest wall resection and right upper lobe lobectomy, 2. right middle lobe sleeve lobectomy, and 3. right lower lobe lobectomy. One instructor was assigned to each operation table, who evaluated each participant's NOTSS scores consisting of 16 elements. Results: When comparing average NOTSS score of all the three procedures, significant differences were observed between Level A, B, and C trainees. As an example of varying elements by procedure, Level A trainees demonstrated differences in Situation Awareness, and a significant difference was observed in Level C trainees regarding the elements of Decision Making. On the contrary, no significant difference was observed among Level B trainees. In the comparison between first-time and experienced participants, a significant improvement was observed in some elements in Level B and C trainees. Conclusion: This study highlights the usefulness and feasibility of the NOTSS scoring system for surgeons with different experiences and the effectiveness of providing feedback to trainees during intraoperative handoffs in a wet lab.

DOI： 10.1016/j.amsu.2020.07.062

A Giant Thymic Cyst Accompanied by Acute Mediastinitis. 査読

Akihiro Miura, Kazuhiko Shien, Tomohiro Toji, Shinji Otani, Hiromasa Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Junichi Soh, Masaomi Yamane, Shinichi Toyooka

Acta medica Okayama 74 ( 5 ) 431 - 433 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

We encountered a rare case of thymic cyst accompanied by mediastinitis. A 39-year-old Japanese male presented with fever and chest pain. The chest CT revealed a mass composed of a lobular cystic lesion with inflammation, suggesting the onset of mediastinitis. A definitive histological diagnosis was not obtained, and we performed a thymectomy. Pathologically, the thymic cyst was accompanied by multiple cavities, mimicking thymic cysts, caused by the inflammatory abscess. The surrounding adipose tissue showed inflammatory cell infiltrations with chronic fibrosis. These findings indicate that clinicians should be aware that thymic cysts may cause severe mediastinitis.

DOI： 10.18926/AMO/60804

Effectiveness of scheduled intravenous acetaminophen in the postoperative pain management of video-assisted thoracic surgery. 査読

Yoshinobu Shikatani, Junichi Soh, Kazuhiko Shien, Takeshi Kurosaki, Shinji Ohtani, Hiromasa Yamamoto, Arata Taniguchi, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Takahiro Oto, Hiroshi Morimatsu, Shinichi Toyooka

Surgery today 51 ( 4 ) 589 - 594 2020年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: The scheduled administration of intravenous acetaminophen (scheduled-IV-AcA) is one of the more effective multimodal analgesic approaches for postoperative pain in abdominal/orthopedic surgeries. However, there is little evidence concerning scheduled-IV-AcA after general thoracic surgery, especially when limited to video-assisted thoracoscopic surgery (VATS). We investigated the efficacy of scheduled-IV-AcA administration in patients after undergoing VATS. METHODS: Ninety-nine patients who underwent VATS lobectomy or segmentectomy via an 8-cm access window and 1 camera port were retrospectively reviewed by categorizing them into groups either with scheduled-IV-AcA (Group AcA: n = 29) or without it (Group non-AcA: n = 70). Group AcA received 1 g of IV-AcA every 6 h from the end of the operation until the end of POD2. Postoperative pain was measured using a numeric rating scale (NRS) three times per day until discharge. RESULTS: NRS scores were significantly lower in Group AcA with motion (on POD1 to the first point of POD2) than in Group non-AcA. Group non-AcA was also more likely to use additional analgesics than Group AcA (39% vs. 17%, p = 0.058). CONCLUSIONS: Scheduled-IV-AcA administration is a safe and effective multimodal analgesic approach in patients undergoing VATS pulmonary resection via an 8-cm access window.

DOI： 10.1007/s00595-020-02127-y

Overcoming epithelial-mesenchymal transition-mediated drug resistance with monensin-based combined therapy in non-small cell lung cancer. 査読国際誌

Kosuke Ochi, Ken Suzawa, Shuta Tomida, Kazuhiko Shien, Jui Takano, Shunsaku Miyauchi, Tatsuaki Takeda, Akihiro Miura, Kota Araki, Kentaro Nakata, Hiromasa Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Tadahiko Shien, Masaomi Yamane, Kazuo Azuma, Yoshiharu Okamoto, Shinichi Toyooka

Biochemical and biophysical research communications 529 ( 3 ) 760 - 765 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The epithelial-mesenchymal transition (EMT) is a key process in tumor progression and metastasis and is also associated with drug resistance. Thus, controlling EMT status is a research of interest to conquer the malignant tumors. MATERIALS AND METHODS: A drug repositioning analysis of transcriptomic data from a public cell line database identified monensin, a widely used in veterinary medicine, as a candidate EMT inhibitor that suppresses the conversion of the EMT phenotype. Using TGF-β-induced EMT cell line models, the effects of monensin on the EMT status and EMT-mediated drug resistance were assessed. RESULTS: TGF-β treatment induced EMT in non-small cell lung cancer (NSCLC) cell lines and the EGFR-mutant NSCLC cell lines with TGF-β-induced EMT acquired resistance to EGFR-tyrosine kinase inhibitor. The addition of monensin effectively suppressed the TGF-β-induced-EMT conversion, and restored the growth inhibition and the induction of apoptosis by the EGFR-tyrosine kinase inhibitor. CONCLUSION: Our data suggested that combined therapy with monensin might be a useful strategy for preventing EMT-mediated acquired drug resistance.

DOI： 10.1016/j.bbrc.2020.06.077

The neutrophil-to-lymphocyte ratio as a novel independent prognostic factor for multiple metastatic lung tumors from various sarcomas. 査読

Hiromasa Yamamoto, Kei Namba, Haruchika Yamamoto, Tomohiro Toji, Junichi Soh, Kazuhiko Shien, Ken Suzawa, Takeshi Kurosaki, Shinji Otani, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Katsuhito Takahashi, Toshiyuki Kunisada, Takahiro Oto, Shinichi Toyooka

Surgery today 51 ( 1 ) 127 - 135 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Sarcomas are among the most refractory malignant tumors and often recur as pulmonary metastasis. Although the presence of a high neutrophil-to-lymphocyte ratio (NLR) has been associated with the prognosis of several malignancies, the relationship between the NLR and sarcoma with pulmonary metastasis is unclear. We investigated the impact of the NLR in patients who underwent surgical resection for metastatic lung tumors from various sarcomas. METHODS: The subjects of this retrospective study were 158 patients with metastatic lung tumors from various sarcomas, who underwent initial pulmonary metastasectomy between 2006 and 2015. We examined the clinicopathological variables, including the NLR and the characteristics of surgical procedures. Survival was estimated by the Kaplan-Meier method and prognostic factors were evaluated by multivariate analysis. RESULTS: Multivariate analysis revealed significantly better survival of the group with an NLR < 2.26 immediately before the most recent pulmonary metastasectomy, in addition to such factors as the largest resected lesion being < 22 mm, a disease-free interval of > 2 years, and 3 or more pulmonary metastasectomies. CONCLUSION: The NLR immediately before the most recent pulmonary metastasectomy is a novel independent prognostic factor, which may be helpful when considering repeated pulmonary metastasectomy.

DOI： 10.1007/s00595-020-02093-5

Lung perfusion scintigraphy to detect chronic lung allograft dysfunction after living-donor lobar lung transplantation. 査読国際誌

Haruchika Yamamoto, Seiichiro Sugimoto, Takeshi Kurosaki, Kentaroh Miyoshi, Shinji Otani, Mikio Okazaki, Masaomi Yamane, Takahiro Oto, Shinichi Toyooka

Scientific reports 10 ( 1 ) 10595 - 10595 2020年6月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Because chronic lung allograft dysfunction (CLAD) develops predominantly on one side after bilateral living-donor lobar lung transplantation (LDLLT), lung perfusion scintigraphy (Q-scinti) was expected to show a perfusion shift to the contralateral unaffected lung with the development of CLAD. Our study examined the potential usefulness of Q-scinti in the diagnosis of CLAD after bilateral LDLLT. We conducted a single-center retrospective cohort study of 58 recipients of bilateral LDLLT. The unilateral shift values on Q-scinti were calculated and compared between the CLAD group (N = 27) and the non-CLAD group (N = 31) from 5 years before to 5 years after the diagnosis of CLAD. The unilateral shift values in Q-scinti were significantly higher in the CLAD group than in the non-CLAD group from 5 years before the diagnosis of CLAD to 5 years after the diagnosis (P < 0.05). The unilateral shift values in Q-scinti were significantly correlated with the percent baseline values of the forced expiratory volume in 1 s (P = 0.0037), the total lung capacity (P = 0.0028), and the forced vital capacity (P = 0.00024) at the diagnosis of CLAD. In patients developing unilateral CLAD after bilateral LDLLT, Q-scinti showed a unilateral perfusion shift to the contralateral unaffected lung. Thus, Q-scinti appears to have the potential to predict unilateral CLAD after bilateral LDLLT.

DOI： 10.1038/s41598-020-67433-4

Right single lung transplantation using an inverted left donor lung: interposition of pericardial conduit for pulmonary venous anastomosis - a case report. 査読国際誌

Haruchika Yamamoto, Kentaroh Miyoshi, Shinji Otani, Takeshi Kurosaki, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka, Motomu Kobayashi, Takahiro Oto

BMC pulmonary medicine 20 ( 1 ) 46 - 46 2020年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Lung transplantation (LTx) is still limited by the shortage of suitable donor lungs. Developing flexible surgical procedures can help to increase the chances of LTx by unfolding recipient-to-donor matching options based on the pre-existing organ allocation concept. We report a case in which a successful left-to-right inverted LTx was completed using the interposition of a pericardial conduit for pulmonary venous anastomosis. CASE PRESENTATION: A left lung graft was offered to a 59-year-old male who had idiopathic pulmonary fibrosis with predominant damage in the right lung. He had been prescribed bed rest with constant oxygen inhalation through an oxymizer pendant and had been on the waiting list for 20 months. Considering the condition of the patient (LAS 34.3) and the scarcity of domestic organ offers, the patient was highly likely to be incapable of tolerating any additional waiting time for another donor organ if he was unable to accept the presently reported offer of a left lung. Eventually, we decided to transplant the left donor lung into the right thorax of the recipient. Because of the anterior-posterior position gap of the hilar structures, the cuff lengths of the pulmonary veins had to be adjusted. The patient did not develop any anastomotic complications after the transplantation. CONCLUSIONS: A left-to-right inverted LTx is technically feasible using an autologous pericardial conduit for pulmonary venous anastomosis in selected cases. This technique provides the potential benefit of resolving challenging situations in which surgeons must deal with a patient's urgency and the logistical limitations of organ allocation.

DOI： 10.1186/s12890-020-1075-4

Pulmonary aspergillosis as a late complication after surgery for locally advanced non-small cell lung cancer treated with induction chemoradiotherapy. 査読

Seiichiro Sugimoto, Junichi Soh, Ken Suzawa, Kentaroh Miyoshi, Shinji Otani, Hiromasa Yamamoto, Mikio Okazaki, Masaomi Yamane, Takahiro Oto, Susumu Kanazawa, Katsuyuki Kiura, Shinichi Toyooka

Surgery today 50 ( 8 ) 863 - 871 2020年1月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Some long-term survivors after surgery for locally advanced non-small cell lung cancer (NSCLC) treated with induction chemoradiotherapy (trimodality treatment) develop chronic pulmonary aspergillosis (CPA). The aim of our study was to assess the characteristics and outcomes of CPA that develops after trimodality treatment. METHODS: We retrospectively reviewed the data of 187 NSCLC patients who underwent trimodality treatment between 1999 and 2018. RESULTS: Six male ever-smoker patients developed CPA. All 6 patients had undergone extended resection for NSCLC and had a history of either adjuvant chemotherapy (n = 3) or radiation pneumonitis (n = 4). Among the 4 patients with CPA localized in a single lung, 3 patients were treated surgically (completion pneumonectomy or cavernostomy) and 1 patient was treated with antifungal therapy alone. Both treatments led to the improved control of CPA. In contrast, patients with CPA in both lungs were not candidates for surgery, and died of CPA. The survival rates after trimodality treatment in the CPA group and the group without CPA were comparable (10-year survival rate, 50.0% vs. 57.6%, P = 0.59). CONCLUSION: The early diagnosis of CPA localized in a single lung after NSCLC surgery is critical to improving control and survival in patients with CPA.

DOI： 10.1007/s00595-020-01960-5

Surgical treatment for N2 non-small cell lung cancer

Seiichiro Sugimoto, Shinichi Toyooka

Japanese Journal of Lung Cancer 59 ( 7 ) 1129 - 1133 2019年12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：Japan Lung Cancer Society

Because the control of the local tumor and possible distant micrometastases is essential for curing N2 non-small cell lung cancer, multimodality approaches have been considered the preferred treatment for patients with N2 non-small cell lung cancer, including radiotherapy, surgery and chemotherapy. Although induction treatment followed by surgery has been shown to offer a possible survival benefit in select patients with N2 non-small cell lung cancer, randomized phase III trials have failed to demonstrate an advantage of induction treatment followed by surgery over definitive chemoradiotherapy. However, in patients with resectable N2 non-small cell lung cancer, induction chemoradiotherapy followed by surgery has been shown to contribute to improved outcomes in the subgroup of patients who underwent lobectomy. Therefore, induction chemoradiotherapy followed by surgery may be a viable option in a select subset of patients. Recently, the use of immune checkpoint inhibitors after concurrent chemoradiotherapy has been shown to demonstrate a survival advantage in patients with unresectable N2 non-small cell lung cancer, suggesting that the advent of immune checkpoint inhibitors has led to an increase in therapeutic options. In this review, we outline some clinical trials of induction treatment followed by surgery for N2 non-small cell lung cancer and describe our experience in the perioperative management and surgical treatment with induction chemoradiotherapy followed by surgery as well as discuss future perspectives.

DOI： 10.2482/haigan.59.1129

Airway bacteria of the recipient but not the donor are relevant to post-lung transplant pneumonia. 査読

Konishi Y, Miyoshi K, Kurosaki T, Otani S, Sugimoto S, Yamane M, Oto T, Toyooka S

General thoracic and cardiovascular surgery 68 ( 8 ) 833 - 840 2019年12月

Negative impact of recipient SPRED2 deficiency on transplanted lung in a mouse model. 査読国際誌

Hashimoto K, Yamane M, Sugimoto S, Hirano Y, Kurosaki T, Otani S, Miyoshi K, Ohara T, Okazaki M, Yoshimura T, Oto T, Matsukawa A, Toyooka S

Transplant immunology 57 101242 - 101242 2019年12月

N2非小細胞肺癌に対する外科治療招待査読

杉本誠一郎, 豊岡伸一

肺癌 59 ( 7 ) 1129 - 1133 2019年12月

担当区分：責任著者記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：(NPO)日本肺癌学会

N2陽性の非小細胞肺癌では、局所の制御を目的とした放射線治療や手術と、遠隔転移の制御を目的とした化学療法を組み合わせた集学的治療が行われてきた。N2非小細胞肺癌に対する導入療法後手術の有用性が示唆されていたが、第III相試験では、根治的化学放射線療法と比較した導入療法後手術の優越性は証明されていないのが現状である。しかし、切除可能なN2非小細胞肺癌で、特に肺葉切除術が可能な場合には、導入化学放射線療法後の手術の有用性が示唆されており、治療の選択肢として考慮すべきである。また、最近では新しい治療薬として免疫チェックポイント阻害剤が登場し、切除不能III期非小細胞肺癌に対して、化学放射線療法との逐次併用による有用性が示され、治療の選択肢が増えている。本稿では、N2非小細胞肺癌に対する導入療法後手術の臨床試験を概説し、当院における導入放射線化学療法後手術の周術期管理や手術の工夫を述べるとともに、今後の展望について述べる。(著者抄録)

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01244&link_issn=&doc_id=20200109370001&doc_link_id=130007775582&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130007775582&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

Twenty-year Follow-up of the First Bilateral Living-donor Lobar Lung Transplantation in Japan.

Masamichi Komatsu, Hiroshi Yamamoto, Toshitaka Shomura, Kei Sonehara, Takashi Ichiyama, Kazuhisa Urushihata, Atsuhito Ushiki, Masanori Yasuo, Toshihide Wakamatsu, Seiichiro Sugimoto, Takahiro Oto, Hiroshi Date, Tomonobu Koizumi, Masayuki Hanaoka, Keishi Kubo

Internal medicine (Tokyo, Japan) 58 ( 21 ) 3133 - 3137 2019年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Patients with end-stage lung disease can undergo living-donor lobar lung transplantation (LDLLT), with survival rates improving every year. We herein report the 20-year follow-up findings of the first patient who underwent LDLLT in Japan. A 24-year-old woman with primary ciliary dyskinesia became ventilator-dependent after severe respiratory failure and right-sided heart failure following repeated respiratory infections. In 1998, she underwent LDLLT and received her sister's right lower lobe and her mother's left lower lobe. Although the patient required 21 hospitalizations and developed unilateral bronchiolitis obliterans syndrome, she is in good physical condition and lives without restriction at 20 years after undergoing LDLLT.

DOI： 10.2169/internalmedicine.3160-19

Warm retrograde perfusion can remove more fat from lung grafts with fat embolism in a porcine model. 査読

Irie M, Otani S, Kurosaki T, Tanaka S, Ohki T, Miyoshi K, Sugimoto S, Yamane M, Oto T, Toyooka S

General thoracic and cardiovascular surgery 68 ( 4 ) 363 - 369 2019年11月

Favorable survival even with high disease-specific complication rates in lymphangioleiomyomatosis after lung transplantation - long-term follow-up of a Japanese center. 査読国際誌

Kurosaki T, Otani S, Miyoshi K, Okazaki M, Sugimoto S, Suno M, Yamane M, Kobayashi M, Oto T, Toyooka S

The clinical respiratory journal 14 ( 2 ) 116 - 123 2019年11月

Impact of chronic lung allograft dysfunction, especially restrictive allograft syndrome, on the survival after living-donor lobar lung transplantation compared with cadaveric lung transplantation in adults: a single-center experience. 査読

Sugimoto S, Yamamoto H, Kurosaki T, Otani S, Okazaki M, Yamane M, Toyooka S, Oto T

Surgery today 49 ( 8 ) 686 - 693 2019年8月

Lung transplantation via cardiopulmonary bypass: excellent survival outcomes from extended criteria donors. 査読

Taka H, Miyoshi K, Kurosaki T, Douguchi T, Itoh H, Sugimoto S, Yamane M, Kobayashi M, Kasahara S, Oto T

General thoracic and cardiovascular surgery 67 ( 7 ) 624 - 632 2019年7月

Prolonged warm ischemia exacerbated acute rejection after lung transplantation from donation after cardiac death in a mouse. 査読

Hirano Y, Sugimoto S, Yamamoto S, Okada M, Otani S, Ohara T, Yamane M, Matsukawa A, Oto T, Toyooka S

General thoracic and cardiovascular surgery 68 ( 1 ) 57 - 62 2019年7月

Cavernous hemangioma of the rib mimicking a chondrosarcoma: Diagnostic value of delayed phase MRI 査読

T. Tanaka, Y. Masaoka, S. Sugimoto, T. Iguchi, T. Hiraki, H. Yanai, S. Kanazawa

Diagnostic and Interventional Imaging 100 ( 7-8 ) 455 - 457 2019年7月

SOCS3 overexpression in T cells ameliorates chronic airway obstruction in a murine heterotopic tracheal transplantation model. 査読

Mesaki K, Yamane M, Sugimoto S, Fujisawa M, Yoshimura T, Kurosaki T, Otani S, Miyoshi S, Oto T, Matsukawa A, Toyooka S

Surgery today 49 ( 5 ) 443 - 450 2019年5月

Mitochondrial damage-associated molecular patterns released by lung transplants are associated with primary graft dysfunction. 国際誌

Davide Scozzi, Mohsen Ibrahim, Fuyi Liao, Xue Lin, Hsi-Min Hsiao, Ramsey Hachem, Laneshia K Tague, Alberto Ricci, Hrishikesh S Kulkarni, Howard J Huang, Seiichiro Sugimoto, Alexander S Krupnick, Daniel Kreisel, Andrew E Gelman

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 19 ( 5 ) 1464 - 1477 2019年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Primary graft dysfunction (PGD) is a major limitation in short- and long-term lung transplant survival. Recent work has shown that mitochondrial damage-associated molecular patterns (mtDAMPs) can promote solid organ injury, but whether they contribute to PGD severity remains unclear. We quantitated circulating plasma mitochondrial DNA (mtDNA) in 62 patients, before lung transplantation and shortly after arrival to the intensive care unit. Although all recipients released mtDNA, high levels were associated with severe PGD development. In a mouse orthotopic lung transplant model of PGD, we detected airway cell-free damaged mitochondria and mtDNA in the peripheral circulation. Pharmacologic inhibition or genetic deletion of formylated peptide receptor 1 (FPR1), a chemotaxis sensor for N-formylated peptides released by damaged mitochondria, inhibited graft injury. An analysis of intragraft neutrophil-trafficking patterns reveals that FPR1 enhances neutrophil transepithelial migration and retention within airways but does not control extravasation. Using donor lungs that express a mitochondria-targeted reporter protein, we also show that FPR1-mediated neutrophil trafficking is coupled with the engulfment of damaged mitochondria, which in turn triggers reactive oxygen species (ROS)-induced pulmonary edema. Therefore, our data demonstrate an association between mtDAMP release and PGD development and suggest that neutrophil trafficking and effector responses to damaged mitochondria are drivers of graft damage.

DOI： 10.1111/ajt.15232

Lung transplant candidates with idiopathic pulmonary fibrosis and long-term pirfenidone therapy: Treatment feasibility influences waitlist survival. 査読国際誌

Tanaka S, Miyoshi K, Higo H, Kurosaki T, Otani S, Sugimoto S, Yamane M, Kiura K, Toyooka S, Oto T

Respiratory investigation 57 ( 2 ) 165 - 171 2019年3月

Feasibility of lung transplantation from donors mechanically ventilated for prolonged periods. 査読

Seiichiro Sugimoto, Takeshi Kurosaki, Shinji Otani, Shin Tanaka, Yukiko Hikasa, Masaomi Yamane, Shinichi Toyooka, Motomu Kobayashi, Takahiro Oto

Surgery today 49 ( 3 ) 254 - 260 2019年3月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: When patients are mechanically ventilated for more than 5 days, they are usually declined as donors for lung transplantation (LTx); thus, the long-term outcomes of LTx from such donors remain unclear. We investigated the feasibility of LTx from donors that had been mechanically ventilated for prolonged periods. METHODS: The subjects of this retrospective comparative investigation were 31 recipients of LTx from donors who had been mechanically ventilated for < 5 days (short-term group) and 50 recipients of LTx from donors who had been mechanically ventilated for ≥ 5 days (long-term group). RESULTS: The median duration of donor mechanical ventilation was 3 days in the short-term group and 8.5 days in the long-term group. However, other than the difference in the duration of donor ventilation, there were no significant differences in the clinical characteristics of the donors or recipients between the groups. The overall survival rate after LTx was comparable between the long-term group and short-term group (5-year survival rate, 66.6% vs. 75.2%). CONCLUSION: The potential inclusion of donors who have been on mechanical ventilation for more than 5 days could be a feasible strategy to alleviate donor organ shortage.

DOI： 10.1007/s00595-018-1730-z

A single-nucleotide polymorphism in a gene modulating glucocorticoid sensitivity is associated with the decline in total lung capacity after lung transplantation. 査読

Haruchika Yamamoto, Seiichiro Sugimoto, Shin Tanaka, Takeshi Kurosaki, Shinji Otani, Masaomi Yamane, Naruto Taira, Takahiro Oto, Shinichi Toyooka

Surgery today 49 ( 3 ) 268 - 274 2019年3月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Glucocorticoids are used to prevent chronic lung allograft dysfunction (CLAD) after lung transplantation (LT). Our study was aimed at assessing the association between the glucocorticoid-induced transcript 1 gene (GLCCI1) variant, which modulates glucocorticoid sensitivity, and the postoperative lung function and development of CLAD after LT. METHODS: A total of 71 recipients of LT were genotyped for the GLCCI1 variant (rs37972) and divided into three groups: the homozygous mutant allele (TT) group, the heterozygous mutant allele (CT) group, and the wild-type allele (CC) group. The results of pulmonary function tests were compared with the postoperative baseline values. RESULTS: The total lung capacity (TLC) in the TT group was significantly lower than that in the CC group at 3 years after LT (P = 0.029). In the recipients of cadaveric LT, the TLC and forced expiratory volume in 1 s in the TT group were significantly lower than those in the CC groups, resulting in a significant worse CLAD-free survival at 3 years after LT (P = 0.016). CONCLUSION: The GLCCI1 variant was associated with a significant decrease of the TLC at 3 years after LT and the development of CLAD at 3 years, especially in patients undergoing cadaveric LT.

DOI： 10.1007/s00595-018-1717-9

Long-term outcomes of pneumonectomy, back-table lung preservation, double-sleeve resection and reimplantation for advanced central lung cancer: the Oto procedure. 査読国際誌

Tanaka S, Sugimoto S, Soh J, Oto T

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 56 ( 1 ) 213 - 214 2018年12月

SPRED2 deficiency may lead to lung ischemia-reperfusion injury via ERK1/2 signaling pathway activation. 査読

Masanori Okada, Masaomi Yamane, Sumiharu Yamamoto, Shinji Otani, Kentaroh Miyoshi, Seiichiro Sugimoto, Akihiro Matsukawa, Shinichi Toyooka, Takahiro Oto, Shinichiro Miyoshi

Surgery today 48 ( 12 ) 1089 - 1095 2018年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Inflammatory changes during lung ischemia-reperfusion injury (IRI) are related to the activation of the extracellular signal-regulated kinase (ERK)1/2 signaling pathway. Sprouty-related EVH1 (enabled/vasodilator-stimulated phosphoprotein homology 1)-domain-containing proteins (SPREDs) are known inhibitors of ERK1/2 signaling. The role of SPRED2 in lung IRI was examined in a left hilar clamp mouse model. METHODS: C57BL/6 wild-type (WT) and Spred2-/- mice were used in the left hilar clamp model. Experimental groups underwent 30 min of left hilar clamping followed by 1 h of reperfusion. U0126, an ERK1/2 inhibitor, was administered to Spred2-/- mice with reperfused lungs. RESULTS: The partial pressures of oxygen of the Spred2-/- mice after reperfusion were significantly worse than those of WT mice (p < 0.01). Spred2-/- mice displayed more severe injuries than WT mice with increased neutrophil infiltration observed by a histological evaluation and flow cytometry (p < 0.001). This severe inflammation was inhibited by U0126. In addition, the rate of ERK1 activation was significantly higher in the lungs of Spred2-/- mice after reperfusion than in WT mice according to a Western blot analysis (p < 0.05). CONCLUSION: The activation of the ERK1/2 signaling pathway influences the severity of lung IRI, causing inflammation with neutrophil infiltration. SPRED2 may be a promising target for the suppression of lung IRI.

DOI： 10.1007/s00595-018-1696-x

Donor-derived cell-free DNA is associated with acute rejection and decreased oxygenation in primary graft dysfunction after living donor-lobar lung transplantation. 査読国際誌

Shin Tanaka, Seiichiro Sugimoto, Takeshi Kurosaki, Kentaroh Miyoshi, Shinji Otani, Ken Suzawa, Shinsuke Hashida, Masaomi Yamane, Takahiro Oto, Shinichi Toyooka

Scientific reports 8 ( 1 ) 15366 - 15366 2018年10月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Donor-derived cell-free DNA (dd-cf-DNA) has been shown to be an informative biomarker of rejection after lung transplantation (LT) from deceased donors. However, in living-donor lobar LT, because small grafts from blood relatives are implanted with short ischemic times, the detection of dd-cf-DNA might be challenging. Our study was aimed at examining the role of dd-cf-DNA measurement in the diagnosis of primary graft dysfunction and acute rejection early after living-donor lobar LT. Immediately after LT, marked increase of the plasma dd-cf-DNA levels was noted, with the levels subsequently reaching a plateau with the resolution of primary graft dysfunction. Increased plasma levels of dd-cf-DNA were significantly correlated with decreased oxygenation immediately (p = 0.022) and at 72 hours (p = 0.046) after LT. Significantly higher plasma dd-cf-DNA levels were observed in patients with acute rejection (median, 12.0%) than in those with infection (median, 4.2%) (p = 0.028) or in a stable condition (median, 1.1%) (p = 0.001). Thus, measurement of the plasma levels of dd-cf-DNA might be useful to monitor the severity of primary graft dysfunction, and plasma dd-cf-DNA could be a potential biomarker for the diagnosis of acute rejection after LT.

DOI： 10.1038/s41598-018-33848-3

Low-risk donor lungs optimize the post-lung transplant outcome for high lung allocation score patients. 査読

Takeshi Kurosaki, Kentaroh Miyoshi, Shinji Otani, Kentaro Imanishi, Seiichiro Sugimoto, Masaomi Yamane, Motomu Kobayashi, Shinichi Toyooka, Takahiro Oto

Surgery today 48 ( 10 ) 928 - 935 2018年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: The lung allocation score (LAS) has been generally recognized as a contributor to the overall survival in lung transplant candidates. However, donor-related risks have never been taken into consideration in previous research that validated the LAS. This study aimed to determine whether or not the role of the LAS as a predictor of the posttransplant outcome is influenced by the quality of the donor lungs. METHODS: We retrospectively reviewed 108 patients who underwent lung transplantation at Okayama University Hospital since 1998. The cohort was divided into two groups based on the lung donor score (DS; ≤ 4/> 4). Correlations between the LAS and posttransplant outcomes were investigated in both groups. RESULTS: In the high-DS group, an elevated LAS was strongly associated with posttransplant PaO2/FiO2 (p = 0.018). However, in the low-DS group, no correlation was found between them. There was no significant difference in the long-term survival according to the LAS in the low-DS group. The LAS effectively predicted the posttransplant outcome only when lungs with DS > 4 were transplanted; the LAS was not reliable if high-quality lungs were transplanted. CONCLUSION: Lung transplantation can be feasible and provides a survival benefit even for high-LAS patients if lungs from a low-risk donor are transplanted.

DOI： 10.1007/s00595-018-1670-7

Can pretransplant computed-tomographic assessment predict outcomes after lung transplantation? 国際誌

Seiichiro Sugimoto

Journal of thoracic disease 10 ( 10 ) 5652 - 5654 2018年10月

Myoepithelioma occurring in the posterior mediastinum harboring EWSR1 rearrangement: a case report. 査読国際誌

Tomohiro Habu, Junichi Soh, Tomohiro Toji, Kazuhiko Shien, Eito Niman, Kei Namba, Hiroki Sato, Hiromasa Yamamoto, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka

Japanese journal of clinical oncology 48 ( 9 ) 851 - 854 2018年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Myoepithelioma is a rare neoplasm usually occurring in the salivary glands or the mammary glands but also, more rarely, in the thoracic cavity. The diagnosis of myoepithelioma is based on the presence of histological and immunohistochemical characteristics of myoepithelioma, but in unusual locations, the diagnosis is challenging. For such cases, cytogenetic approaches have been developed as helpful tools for the diagnosis. We report a surgical case of 51-year-old woman with myoepithelioma occurring in the posterior mediastinum that harbored the Ewing sarcoma breakpoint region1 (EWSR1) gene rearrangement. To the best of our knowledge, this is the first report of a myoepithelioma occurring in the posterior mediastinum. In this case, the patient underwent the thoracoscopic surgery for a diagnostic tumorectomy and was diagnosed as myoepithelioma based on the following immunohistological findings. Considering the unusual location, we additionally performed a cytogenetic analysis to confirm the presence of the EWSR1 gene rearrangement, which is a genetic characteristic of myoepithelioma.

DOI： 10.1093/jjco/hyy100

Airway complications have a greater impact on the outcomes of living-donor lobar lung transplantation recipients than cadaveric lung transplantation recipients. 査読

Seiichiro Sugimoto, Masaomi Yamane, Shinji Otani, Takeshi Kurosaki, Shuji Okahara, Yukiko Hikasa, Shinichi Toyooka, Motomu Kobayashi, Takahiro Oto

Surgery today 48 ( 9 ) 848 - 855 2018年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Airway complications (ACs) after living-donor lobar lung transplantation (LDLLT) could have different features from those after cadaveric lung transplantation (CLT). We conducted this study to compare the characteristics of ACs after LDLLT vs. those after CLT and investigate their impact on outcomes. METHODS: We reviewed, retrospectively, data on 163 recipients of lung transplantation, including 83 recipients of LDLLT and 80 recipients of CLT. RESULTS: The incidence of ACs did not differ between LDLLT and CLT. The initial type of AC after LDLLT was limited to stenosis in all eight patients, whereas that after CLT consisted of stenosis in three patients and necrosis in ten patients (p = 0.0034). ACs after LDLLT necessitated significantly earlier initiation of treatment than those after CLT (p = 0.032). The overall survival rate of LDLLT recipients with an AC was significantly lower than that of those without an AC (p = 0.030), whereas the overall survival rate was comparable between CLT recipients with and those without ACs (p = 0.25). CONCLUSION: ACs after LDLLT, limited to bronchial stenosis, require significantly earlier treatment and have a greater adverse impact on survival than ACs after CLT.

DOI： 10.1007/s00595-018-1663-6

Unilateral lung transplantation using intact bilateral upper lobes. 査読国際誌

Shinji Otani, Takeshi Kurosaki, Seiichiro Sugimoto, Masaomi Yamane, Takahiro Oto

The Journal of thoracic and cardiovascular surgery 156 ( 1 ) e35-e38 - e38 2018年7月

Favorable survival in lung transplant recipients on preoperative low-dose, as compared to high-dose corticosteroids, after hematopoietic stem cell transplantation. 査読

Seiichiro Sugimoto, Kentaroh Miyoshi, Takeshi Kurosaki, Shinji Otani, Masaomi Yamane, Motomu Kobayashi, Takahiro Oto

International journal of hematology 107 ( 6 ) 696 - 702 2018年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Although the number of patients developing pulmonary complications after hematopoietic stem cell transplantation (HSCT) necessitating lung transplantation (LT) is increasing, a little information is available about factors influencing the prognosis after LT in these patients. Corticosteroids represent the first-line therapy for pulmonary complications after HSCT; however, prolonged corticosteroid treatment prior to LT increases the potential risks of LT. In this study, we assessed the effect of preoperative corticosteroid therapy on long-term survival in patients undergoing LT after HSCT. We retrospectively investigated data from 13 patients who had received high-dose corticosteroid therapy and nine who had received low-dose corticosteroid therapy prior to LT for pulmonary complications after HSCT. Other than the preoperative corticosteroid dose, patient clinical characteristics did not differ. The incidence of postoperative complications within the first year after LT was significantly lower in the low-dose corticosteroid group (p = 0.026). Survival after LT was also significantly better in the low-dose corticosteroid group than in the high-dose corticosteroid group (p = 0.034). In recipients of LT after HSCT, preoperative low-dose corticosteroid use, as compared to preoperative high-dose corticosteroid use, could limit the risks of postoperative complications developing within the first year after the LT, leading to improved long-term survival after LT.

DOI： 10.1007/s12185-018-2417-3

Prognostic Factors in Lung Transplantation after Hematopoietic Stem Cell Transplantation 査読国際誌

Toyofumi F. Chen-Yoshikawa, Seiichiro Sugimoto, Takeshi Shiraishi, Masato Minami, Yasushi Matsuda, Masayuki Chida, Sumiko Maeda, Akihiro Aoyama, Yoshinori Okada, Meinoshin Okumura, Akinori Iwasaki, Shinichiro Miyoshi, Takahiro Oto, Hiroshi Date

Transplantation 102 ( 1 ) 154 - 161 2018年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Lippincott Williams and Wilkins

Background Lung transplantation is the final lifesaving option for patients with pulmonary complications after hematopoietic stem cell transplantation (HSCT). Patients undergoing HSCT for hematologic diseases are thought to be high-risk candidates for lung transplantation
therefore, few lung transplants are performed for these patients, and few studies have been reported. This study aimed to describe the characteristics and outcomes of lung transplantation in patients with pulmonary complications after HSCT. Methods We retrospectively investigated 62 patients who underwent lung transplantation after HSCT. All data were collected from 6 lung transplant centers in Japan. Results Seventeen patients underwent cadaveric lung transplantation, whereas 45 underwent living-donor lobar lung transplantation (LDLLT). In the LDLLT group, 18 patients underwent LDLLT after HSCT in which one of the donors had also served as a donor for HSCT. Seven patients underwent single LDLLT for which the donor was the same as the patient from whom stem cells were obtained for HSCT. Preoperative hypercapnia was observed in 52 patients (84%). Thirteen patients (21%) required mechanical ventilation preoperatively. Fifty-five patients underwent HSCT for hematologic malignancies, and 4 (7%) relapsed after lung transplantation. The 5-year survival rate was 64.2%. In a multivariable analysis, patients younger than 45 years and those with the same donor for both procedures exhibited significantly better survival (P = 0.012 and 0.041, respectively). Conclusions Lung transplantation for pulmonary complications after HSCT was performed safely and yielded better survival, especially in younger recipients for whom both lung transplantation and HSCT involved the same donor.

DOI： 10.1097/TP.0000000000001886

Pneumatosis intestinalis after lung transplantation for pulmonary graft-versus-host disease. 査読国際誌

Kumi Mesaki, Seiichiro Sugimoto, Shinji Otani, Takeshi Kurosaki, Kentaroh Miyoshi, Masaomi Yamane, Takahiro Oto

Journal of thoracic disease 10 ( 1 ) E42-E45 - E45 2018年1月

記述言語：英語

Pneumatosis intestinalis, which could complicate a spectrum of clinical conditions ranging from benign to life-threatening, is a rarely encountered complication after lung transplantation (LT). We describe two cases in which PI developed as a complication following LT for pulmonary graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). In addition to the long-term immunosuppression administered for pulmonary GVHD, the intense immunosuppression needed after LT might increase the risk of PI in lung transplant recipients after HSCT. Conservative therapy should be considered for the treatment of PI developing after LT.

DOI： 10.21037/jtd.2017.11.121

Postoperative pyoderma gangrenosum exacerbated by granulocyte-colony stimulating factor after lung cancer surgery 査読国際誌

Haruchika Yamamoto, Seiichiro Sugimoto, Shinji Otani, Shinichi Toyooka

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 47 ( 10 ) 991 - 992 2017年10月

Lung retransplantation in an adult 13 years after single lobar transplant in childhood. 査読

Sugimoto S, Otani S, Ohki T, Kurosaki T, Miyoshi K, Yamane M, Miyoshi S, Oto T

General thoracic and cardiovascular surgery 65 ( 9 ) 539 - 541 2017年9月

High Frequency of Acute Adverse Cardiovascular Events After Lung Transplantation in Patients With Pulmonary Arterial Hypertension Receiving Preoperative Long-Term Intravenous Prostacyclin. 査読

Satoshi Akagi, Takahiro Oto, Motomu Kobayashi, Kentaroh Miyoshi, Seiichiro Sugimoto, Masaomi Yamane, Kazufumi Nakamura, Toshihiro Sarashina, Shinichiro Miyoshi, Hiroshi Ito

International heart journal 58 ( 4 ) 557 - 561 2017年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Adverse cardiovascular events after lung transplantation (LT) increase the mortality in patients with pulmonary arterial hypertension (PAH). Long-term intravenous prostacyclin is the usual treatment in severe patients with PAH, but it may increase the risk of hemorrhage due to its antiplatelet aggregation effect or thrombocytopenia. We investigated the impact of length of intravenous prostacyclin therapy on acute adverse cardiovascular events including hemorrhagic complication after LT. We retrospectively compared the incidence of adverse events (death, intrathoracic hematoma and bleeding, cardiac congestion or shock, cerebral infarction and pulmonary embolism) within 30 days after LT between no/short-term (median 0.6 years, n = 13) and long-term (median 3.7 years, n = 15) intravenous prostacyclin groups. There were no differences in the dose of intravenous prostacyclin and pulmonary artery pressure between the two groups. Among 22 adverse events (0.8 ± 1.1 events/patient), 4 events occurred in the no/short-term intravenous prostacyclin group and 18 occurred in the long-term intravenous prostacyclin group. The event rate per patient in the long-term intravenous prostacyclin group (1.2 ± 1.3 events/patient) was significantly higher than that in the no/short-term intravenous prostacyclin group (0.3 ± 0.5 events/patient) (P < 0.05). Intrathoracic hematoma and bleeding was the most frequent adverse event (9 events, 41%). Preoperative long-term intravenous prostacyclin therapy increases acute adverse cardiovascular events after LT in patients with PAH.

DOI： 10.1536/ihj.16-389

Successful Lung Transplantation Using a Deceased Donor Mechanically Ventilated for Ten Months 査読国際誌

Shin Tanaka, Kentaroh Miyoshi, Seiichiro Sugimoto, Masaomi Yamane, Motomu Kobayashi, Takahiro Oto

ANNALS OF THORACIC SURGERY 104 ( 2 ) E177 - E179 2017年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE INC

A successful outcome after lung transplant was achieved using lungs donated from a teenage boy who underwent prolonged mechanical ventilation. The donor experienced hypoxic brain damage and was declared brain dead 324 days after tracheal intubation. At the time of referral, the donor's lungs revealed diffuse radiologic infiltration and atelectasis but excellent function, with a PaO2/FiO(2) ratio of 450. The lungs were transplanted to a 10-year-old girl with bronchiolitis obliterans. She developed grade 2 primary graft dysfunction, but recovered quickly. She is doing well and has not experienced any other critical adverse events 12 months after lung transplantation. (C) 2017 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2017.03.019

Prolonged Administration of Twice-Daily Bolus Intravenous Tacrolimus in the Early Phase After Lung Transplantation 査読国際誌

Yutaka Hirano, Seiichiro Sugimoto, Toshifumi Mano, Takeshi Kurosaki, Kentaroh Miyoshi, Shinji Otani, Masaomi Yamane, Motomu Kobayashi, Shinichiro Miyoshi, Takahiro Oto

ANNALS OF TRANSPLANTATION 22 484 - 492 2017年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：INT SCIENTIFIC LITERATURE, INC

Background: Although administration of tacrolimus, whether by the enteric, sublingual, or continuous intravenous routes, has some limitations, twice-daily bolus intravenous tacrolimus administration has been shown to be beneficial in optimizing efficacy and safety after lung transplantation. However, at present, the duration of bolus intravenous tacrolimus administration is limited, and the effects of prolonged bolus intravenous tacrolimus administration remain unknown. Our study was aimed at assessing the safety and efficacy of prolonged twice-daily bolus intravenous tacrolimus administration in the early phase after lung transplantation.
Material/Methods: We retrospectively investigated the data of 62 recipients of lung transplantation who had received twice-daily bolus intravenous administration of tacrolimus, followed by oral tacrolimus, after lung transplantation at our institution between January 2011 and October 2015.
Results: The median duration of bolus intravenous tacrolimus administration was 19 days (4-72 days). The target trough level was achieved in 89% of the patients by day 3. Acute kidney injury occurred in 27% of the patients during bolus intravenous tacrolimus. Two patients (3%) had neurotoxicity, necessitating discontinuation of tacrolimus. Suspected acute rejection requiring steroid pulse therapy occurred in 21% of patients during the followup period. Eight patients (13%) developed chronic lung allograft dysfunction during the follow-up period. The 1-year and 5-year survival rates after lung transplantation were 95% and 76%, respectively.
Conclusions: These results suggest that prolonged bolus intravenous tacrolimus administration in the early phase after lung transplantation is a safe and effective alternative to enteric, sublingual, or continuous intravenous administration.

DOI： 10.12659/AOT.904225

Successful Lung Transplantation for Pulmonary Disease Associated With Erdheim-Chester Disease 査読国際誌

Kohei Hashimoto, Kentaroh Miyoshi, Hisao Mizutani, Shinji Otani, Seiichiro Sugimoto, Masaomi Yamane, Takahiro Oto

ANNALS OF THORACIC SURGERY 104 ( 1 ) E13 - E15 2017年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE INC

A 53-year-old man with pulmonary fibrosis associated with Erdheim-Chester disease achieved long-term survival after lung transplantation. Major clinical manifestations included lung and bone injuries, and other vital organs were functionally unaffected by the disease. After a careful observation for the disease progression, he underwent bilateral deceased-donor lung transplantation. He has returned to his normal social life and is doing well without recurrence of Erdheim-Chester disease in the lung allograft or progression in other organs 5 years after transplant. Lung transplantation is a potentially reasonable treatment option for Erdheim-Chester disease involving the lungs if the functions of other vital organs remain stable. (C) 2017 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2017.02.020

Clinical characteristics of Japanese candidates for lung transplant for interstitial lung disease and risk factors for early death while on the waiting list. 査読国際誌

Hisao Higo, Takeshi Kurosaki, Eiki Ichihara, Toshio Kubo, Kentaroh Miyoshi, Shinji Otani, Seiichiro Sugimoto, Masaomi Yamane, Nobuaki Miyahara, Katsuyuki Kiura, Shinichiro Miyoshi, Takahiro Oto

Respiratory investigation 55 ( 4 ) 264 - 269 2017年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Lung transplants have produced very favorable outcomes for patients with interstitial lung disease (ILD) in Japan. However, because of the severe donor lung shortage, patients must wait approximately 2.5 years before they can undergo transplantation and many candidates die before allocation. We reveal the clinical characteristics of Japanese patients with ILD who are candidates for lung transplants and the risk factors for early death while on the waiting list. METHODS: We retrospectively reviewed the clinical data of patients registered in the Japan Organ Transplant Network from Okayama University Hospital who are candidates for cadaveric lung transplants for ILD between 1999 and 2015. RESULTS: Fifty-three patients with ILD were included (24 patients with idiopathic pulmonary fibrosis and 29 others). They had severe pulmonary dysfunction and low exercise tolerability. The median waiting time for transplantation was 462 days, and 22 patients died before allocation. Patients who died before 462 days without undergoing transplantation had more severe dyspnea, shorter 6-minute walk distance (6MWD), and lower performance status than those who waited ≥462 days. CONCLUSIONS: Japanese candidates for cadaveric lung transplants for ILD have severe pulmonary dysfunction. Severe dyspnea, short 6MWD, and low performance status are risk factors for early death while on the waiting list.

DOI： 10.1016/j.resinv.2017.03.002

Early postoperative complications after middle lobe-preserving surgery for secondary lung cancer 査読

Yuho Maki, Shinichi Toyooka, Junichi Soh, Hiromasa Yamamoto, Seiichiro Sugimoto, Masaomi Yamane, Takahiro Oto, Shinichiro Miyoshi

SURGERY TODAY 47 ( 5 ) 601 - 605 2017年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER

Purpose Preservation of the middle lobe during lung surgery is traditionally avoided, because its presence in the hemithoracic cavity is considered a cause of complications. We report a series of lung cancer patients who underwent a secondary pulmonary resection with the preservation of the middle lobe to explore the complications and feasibility of these procedures.
Methods We reviewed the clinical courses of six patients who underwent surgery for metachronous lung cancers. Five patients underwent right upper lobectomy, including one sleeve lobectomy, after having undergone prior right lower lobectomy. The remaining patient underwent a right lower lobectomy after having undergone a prior right upper lobectomy.
Results There were no treatment-related deaths. One patient was readmitted for surgery to treat delayed air leakage progressing to pyothorax. One patient was treated for persistent air leakage. Two patients required intermittent drainage of pulmonary effusion, because of middle lobe atelectasis. The postoperative forced vital capacity and forced expiratory volume in 1 s were greater than the values predicted post-pneumonectomy in four evaluable patients.
Conclusions While postoperative complications after middle lobe-preserving surgery are manageable, their high incidence should be considered when performing this surgery.

DOI： 10.1007/s00595-016-1413-6

Pulmonary artery patch for an inadequate donor atrial cuff in the absence of donor pericardium in lung transplantation 査読

Seiichiro Sugimoto, Masaomi Yamane, Kentaroh Miyoshi, Takeshi Kurosaki, Shinji Otani, Shinichiro Miyoshi, Takahiro Oto

SURGERY TODAY 47 ( 3 ) 399 - 401 2017年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER

In cadaveric lung transplantation (LTx), a donor lung with an inadequate donor left atrial cuff is considered a "surgically marginal donor lung". The donor pericardium is commonly applied to reconstruct the inadequate donor left atrial cuff; however, in some cases, the donor pericardium is inadvertently removed during the lung procurement. We devised an alternative technique for reconstruction to overcome the absence of pericardium in a donor lung with an inadequate atrial cuff, using a patch of the donor pulmonary artery (PA) in single lung transplantation. In a recent case of lung transplantation in which the donor pericardium had been removed, we harvested a segment of the right PA distal to the main PA of the donor and used a PA patch to repair the inadequate donor left atrial cuff. No vascular complications were encountered in the recipient, who remains in good health after the transplantation.

DOI： 10.1007/s00595-016-1370-0

Immunoglobulin G4-related disease presenting as an intrapericardial tumor 査読国際誌

Masanori Okada, Seiichiro Sugimoto, Masaomi Yamane, Shinichiro Miyoshi

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 47 ( 1 ) 88 - 89 2017年1月

Reconstruction of Anterior Chest Wall with Polypropylene Mesh: Two Primary Sternal Chondrosarcoma Cases 査読

Shinichi Kawana, Hiromasa Yamamoto, Yuho Maki, Seiichiro Sugimoto, Shinichi Toyooka, Shinichiro Miyoshi

ACTA MEDICA OKAYAMA 71 ( 3 ) 259 - 262 2017年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

Primary sternal chondrosarcoma is a rare malignant tumor that is refractory to chemotherapy and radiation. Effective therapy is radical resection of the tumor. We present two patients with primary sternal chondrosarcoma who underwent a radical resection of the lower half of the sternum and bilateral ribs, followed by reconstruction with 2 sheets of polypropylene mesh layered orthogonally. The patients have maintained almost the same pulmonary function as preoperative values, with stability of the chest wall. Although there are various ways to reconstruct the anterior chest wall, reconstruction with polypropylene mesh layered orthogonally is an easy-to-use and sufficient method.

DOI： 10.18926/AMO/55210

Visualization of bronchial circulation at bronchial anastomotic site using bronchial fluorescein angiography technique 査読国際誌

Norichika Iga, Kentaroh Miyoshi, Katsuyoshi Takata, Yutaka Hirano, Yusuke Konishi, Shinji Otani, Seiichiro Sugimoto, Masaomi Yamane, Shinichiro Miyoshi, Takahiro Oto

INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY 23 ( 5 ) 716 - 721 2016年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OXFORD UNIV PRESS

Successful bronchial healing after a bronchoplastic procedure mainly depends on bronchial circulation at the anastomostic site. We developed a bronchial fluorescein angiography (B-FAG) technique for visualizing circulation on the bronchial surface. The technique was evaluated in animals.
Fluorescein was used as a contrast agent and an autofluorescence imaging (AFI) bronchoscope as a detector. The left main pulmonary artery (PA) and main bronchus of 10 pigs were isolated. After transection of the left main bronchus and bronchial arteries and re-anastomosis of the bronchus, the pigs were randomly divided into two groups: the PA- group (n = 5), in which the pulmonary artery was transected; and the PA+ group (n = 5), in which the pulmonary artery was preserved. Following intravenous injection of fluorescein, the distal anastomotic site was observed for 30 min with autofluorescence imaging bronchoscopy. Bronchial specimens sampled 2 days after the surgical intervention were histologically evaluated.
In the PA- group, there was no fluorescein enhancement in the distal bronchus throughout the observation time. However, enhancement, which turned the bronchial surface from magenta to bright green, was clearly observed in less than 207 +/- 102.5 s in the PA+ group. The enhancement status detected by bronchial fluorescein angiography was related to the extent of tissue damage, as was proven histologically in the acute healing stage.
Bronchial fluorescein angiography clearly visualized the circulatory status promptly after the anastomosis procedure at the central bronchus. This technique is a potentially practical approach to predict ischaemic airway complications following bronchial anastomosis.

DOI： 10.1093/icvts/ivw210

Balloon-expandable Metallic Stents for Airway Diseases 査読

Takashi Ohki, Seiichiro Sugimoto, Takeshi Kurosaki, Shinji Otani, Kentaroh Miyoshi, Masaomi Yamane, Shinichiro Miyoshi, Takahiro Oto

ACTA MEDICA OKAYAMA 70 ( 5 ) 421 - 424 2016年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

Stent placement is an essential treatment for airway diseases. Although self-expandable metallic stents and silicone stents are commonly applied for the treatment of airway diseases, these stents are unsuitable for the treatment of small airway diseases encountered in pediatric patients and lung transplant recipients with airway complications. Currently, only vascular balloon-expandable metallic stents are available for the treatment of small airway diseases; however, little research has been conducted on the use of these stents in this field. We have launched a prospective feasibility study to clarify the safety and efficacy of balloon-expandable metallic stents for the treatment of airway diseases.

DOI： 10.18926/AMO/54606

The Feasibility of Median Sternotomy With or Without Thoracotomy for Locally Advanced Non-Small Cell Lung Cancer Treated With Induction Chemoradiotherapy 査読国際誌

Hiroki Sato, Shinichi Toyooka, Junichi Soh, Katsuyuki Hotta, Kuniaki Katsui, Hiromasa Yamamoto, Seiichiro Sugimoto, Takahiro Oto, Susumu Kanazawa, Katsuyuki Kiura, Shinichiro Miyoshi

ANNALS OF THORACIC SURGERY 102 ( 3 ) 985 - 992 2016年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE INC

Background. This study aimed to compare the morbidity and mortality of a median sternotomy approach and a lateral thoracotomy and to investigate the feasibility of a median sternotomy for locally advanced non-small cell lung cancer (NSCLC) after induction chemoradiotherapy.
Methods. The medical records of patients with locally advanced NSCLC who underwent induction chemoradiotherapy followed by surgery at our institution between January 1999 and September 2014 were reviewed. We compared the morbidity and mortality of a median sternotomy approach and a lateral thoracotomy.
Results. A total of 102 NSCLC patients were the subjects of this study. Among them, 31 patients underwent surgery with a median sternotomy approach and 71 patients underwent surgery with a lateral thoracotomy. Patients in the median sternotomy group had a significantly higher rate of postoperative arrhythmia than those in the lateral thoracotomy group (p = 0.0028). However, all the complications were manageable, and no treatment-related deaths occurred in the median sternotomy group. Regarding the prognosis, the 5-year overall survival rate was 72.7%, and the 2-year recurrence-free survival rate was 66.5% in the entire population. No significant differences in overall survival or recurrence-free survival were observed between the 2 approaches.
Conclusions. Whereas the lateral thoracotomy approach is a standard procedure, our experience suggests that a median sternotomy approach for locally advanced NSCLC after induction chemoradiotherapy is a feasible procedure and can be a surgical option. (C) 2016 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2016.03.092

Lung transplantation for diffuse panbronchiolitis: 5 cases from a single centre 査読国際誌

Seiichiro Sugimoto, Kentaroh Miyoshi, Masaomi Yamane, Takahiro Oto

INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY 22 ( 5 ) 679 - 681 2016年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OXFORD UNIV PRESS

Diffuse panbronchiolitis is a rare complex genetic disease predominantly affecting East Asians, and is characterized by chronic inflammation of the respiratory bronchioles and sinobronchial infection. Although long-term macrolide therapy has been shown to significantly improve the survival in patients with diffuse panbronchiolitis, some patients continue to deteriorate, eventually requiring lung transplantation. However, lung transplantation for diffuse panbronchiolitis has rarely been reported and the outcome in these patients remains unknown. We describe our experience of lung transplantation for diffuse panbronchiolitis. A total of 5 patients received long-term macrolide therapy and had airway colonization by Pseudomonas aeruginosa preoperatively. Three patients had undergone sinus surgery for chronic rhinosinusitis before the transplantation. Bilateral cadaveric lung transplantation was performed in 4 patients, and living-donor lung transplantation in 1. After the lung transplantation, 1 patient developed an A3 acute rejection episode; however, none of the recipients developed severe pneumonia or any fatal infections. One recipient developed chronic lung allograft dysfunction 3 years after the transplantation; however, none developed recurrence of diffuse panbronchiolitis. All of the 5 patients were still surviving after a median follow-up period of 4.9 years (3.7-12.3 years). Lung transplantation is a viable option for the treatment of progressive diffuse panbronchiolitis resistant to long-term macrolide therapy.

DOI： 10.1093/icvts/ivw008

Therapeutic Effect of Sirolimus for Lymphangioleiomyomatosis Remaining in the Abdominopelvic Region After Lung Transplantation: A Case Report. 査読

Ito T, Suno M, Sakamoto K, Yoshizaki Y, Yamamoto K, Nakanishi R, Hirano Y, Irie M, Kurosaki T, Otani S, Yamane M, Sugimoto S, Miyoshi K, Oto T

Transplantation proceedings 48 ( 1 ) 271 - 274 2016年1月

[Cross-sectoral Approach of a Perioperative Management Center for General Thoracic Surgery]. 査読

Atsushi Shimoda, Junichi Soh, Takako Ashiba, Naomichi Murata, Tomomi Fukuda, Motomu Kobayashi, Hidejiro Torigoe, Yuho Maki, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka, Takahiro Oto, Shinichiro Miyoshi

Kyobu geka. The Japanese journal of thoracic surgery 69 ( 1 ) 20 - 4 2016年1月

記述言語：日本語掲載種別：研究論文（学術雑誌）

Perioperative assessment and care, such as enhanced recovery after surgery (ERAS), is very important for improving the clinical outcomes of patients who have undergone surgery. However, professional assessments and care cannot be achieved through the actions of only 1 surgical department. We established a perioperative management center(PERIO) comprised of surgeons, dedicated nurses, anesthesiologists, dentists, physiotherapists, pharmacists, and nutritionists to perform intensive cross-sectoral perioperative management. In this manuscript, we investigated the impact of PERIO on the clinical outcomes of 127 elderly patients who underwent thoracic surgery for the resection of non-small cell lung cancer (NSCLC). We categorized these 127 patients into 3 groups:① those treated before the introduction of PERIO (between January 2006 to August 2008), ② those treated during the early phase after PERIO introduction (September 2008 to December 2011), and ③ those treated during the late phase after PERIO introduction( January 2012 to December 2014). Radical operations were performed significantly more frequently after PERIO introduction than before PERIO introduction, while the postoperative complication rates were similar among the 3 groups. The duration of postoperative hospitalization was reduced after the introduction of PERIO, and the hospital surplus increased after the introduction of PERIO. In conclusion, PERIO may play an important role in improving the clinical outcomes of thoracic surgery, especially for elderly patients with NSCLC.

A neutrophil elastase inhibitor improves lung function during ex vivo lung perfusion. 査読

Masaaki Harada, Takahiro Oto, Shinji Otani, Kentaroh Miyoshi, Masanori Okada, Norichika Iga, Hitoshi Nishikawa, Seiichiro Sugimoto, Masaomi Yamane, Shinichiro Miyoshi

General thoracic and cardiovascular surgery 63 ( 12 ) 645 - 51 2015年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: Ex vivo lung perfusion (EVLP) has been used not only for graft evaluation but also for graft reconditioning prior to lung transplantation. Inflammatory cells such as neutrophils may cause additional graft injury during EVLP. Neutrophil elastase inhibitors protect lungs against neutrophil-induced lung injury, such as acute respiratory distress syndrome. This study aimed to investigate the effect of a neutrophil elastase inhibitor during EVLP. METHODS: EVLP was performed for 4 h in bilateral pig lungs that had previously experienced warm ischemia for 2 h with or without a neutrophil elastase inhibitor (treated and control groups, respectively; n = 6). Following EVLP, the left lung was transplanted into a recipient pig, and this was followed by observation for 4 h. Pulmonary functions were observed both during EVLP and during the early post-transplant stage. RESULTS: During EVLP, decreases in neutrophil elastase levels (P < 0.001), the wet-dry weight ratio (P < 0.05), and pulmonary vascular resistance (P < 0.01) and increases in the PaO2/FiO2 ratio (P < 0.01) and pulmonary compliance (P < 0.05) were observed in the treated group. After transplantation, decreased pulmonary vascular resistance (P < 0.05) was observed in the treated group. CONCLUSIONS: A neutrophil elastase inhibitor attenuated the inflammatory response during EVLP and may decrease the incidence of lung reperfusion injury after transplantation.

DOI： 10.1007/s11748-015-0585-0

False-positive axillary lymph node on positron emission tomography/computed tomography in a thymoma patient with a tattoo 査読国際誌

Yuma Fukumoto, Seiichiro Sugimoto, Masanori Okada, Shinichiro Miyoshi

EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 48 ( 5 ) 804 - 804 2015年11月

Retained Short Hook Wires Used for Preoperative Localization of Small Pulmonary Lesions During Video-Assisted Thoracoscopic Surgery: A Report of 2 Cases 査読国際誌

Toshihiro Iguchi, Takao Hiraki, Hideo Gobara, Hiroyasu Fujiwara, Seiichiro Sugimoto, Shinichiro Miyoshi, Susumu Kanazawa

CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY 38 ( 5 ) 1376 - 1379 2015年10月

Extended sleeve lobectomy after induction chemoradiotherapy for non-small cell lung cancer 査読

Shinichi Toyooka, Junichi Soh, Hiromasa Yamamoto, Masaomi Yamane, Shigeru Hattori, Kazuhiko Shien, Kentaroh Miyoshi, Seiichiro Sugimoto, Takahiro Oto, Shinichiro Miyoshi

SURGERY TODAY 45 ( 9 ) 1121 - 1126 2015年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER

Extended sleeve lobectomy is a challenging surgery. While induction chemoradiotherapy (ChRT) followed by surgery is one of the therapeutic strategies used for locally advanced non-small cell lung cancer (NSCLC), ChRT can impair the anastomotic healing potential. We herein present our experience with cases who underwent an extended sleeve lobectomy after induction ChRT.
The medical records of patients who underwent a surgery for NSCLC after ChRT were reviewed.
Between December 2007 and January 2013, nine patients underwent an extended sleeve lobectomy; the left lingular division and lower lobe in four patients, the right upper lobe and trachea in one patient, the carina and trachea in one patient, the right middle and lower lobes in one patient, the right upper and middle lobes and carina in one patient and the right upper lobe and superior segment of the lower lobe in one patient. While no postoperative 90-day deaths occurred, one case developed a bronchopleural fistula on postoperative day (POD) 25 and one case developed a bronchovascular fistula on POD 163. No cases of local recurrence developed.
Our experience suggests that an extended sleeve lobectomy after induction ChRT is feasible, but careful patient selection and perioperative management are mandatory.

DOI： 10.1007/s00595-014-1025-y

Primary pulmonary melanoma: a report of two cases 査読国際誌

Mototsugu Watanabe, Hiromasa Yamamoto, Shinsuke Hashida, Junichi Soh, Seiichiro Sugimoto, Shinichi Toyooka, Shinichiro Miyoshi

WORLD JOURNAL OF SURGICAL ONCOLOGY 13 274 - 274 2015年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BIOMED CENTRAL LTD

Malignant melanoma is a refractory malignancy with a dismal prognosis. It generally arises from the skin in most cases, and cases of primary pulmonary malignant melanoma are rare and often behave aggressively. We have treated two cases of localized primary pulmonary malignant melanoma using surgical resection. Pulmonary malignant melanomas often metastasize to the brain and liver; one of our cases exhibited metastasis to the cecum at about 8 months after surgery. Because cutaneous melanomas often carry activating mutations in the BRAF gene (V600E), we performed a BRAF mutational analysis using direct sequencing for both of these tumors arising from the lung. However, no BRAF mutations were detected. We detected a p53 mutation, which was thought to be a potential somatic mutation, in one of the two cases using a sequencing panel targeting 20 lung cancer-related genes. Although we also checked the expression of programmed death ligand 1 (PD-L1) on the surface of the tumor cells by immunohistochemical testing, neither of our two cases expressed PD-L1. Further molecular analyses may uncover the characteristics of primary pulmonary malignant melanomas.

DOI： 10.1186/s12957-015-0695-2

Simultaneous Multiple Preoperative Localizations of Small Pulmonary Lesions Using a Short Hook Wire and Suture System 査読国際誌

Toshihiro Iguchi, Takao Hiraki, Hideo Gobara, Hiroyasu Fujiwara, Yusuke Matsui, Seiichiro Sugimoto, Shinichi Toyooka, Takahiro Oto, Shinichiro Miyoshi, Susumu Kanazawa

CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY 38 ( 4 ) 971 - 976 2015年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER

The aim of the study was to retrospectively evaluate simultaneous multiple hook wire placement outcomes before video-assisted thoracoscopic surgery (VATS).
Thirty-eight procedures were performed on 35 patients (13 men and 22 women; mean age, 59.9 years) with 80 lung lesions (mean diameter 7.9 mm) who underwent simultaneous multiple hook wire placements for preoperative localizations. The primary endpoints were technical success, complications, procedure duration, and VATS outcome; secondary endpoints included comparisons between technical success rates, complication rates, and procedure durations of the 238 single-placement procedures performed. Complications were also evaluated.
In 35 procedures including 74 lesions, multiple hook wire placements were technically successful; in the remaining three procedures, the second target placement was aborted because of massive pneumothorax after the first placement. Although complications occurred in 34 procedures, no grade 3 or above adverse event was observed. The mean procedure duration was 36.4 +/- A 11.8 min. Three hook wires dislodged during patient transport to the surgical suite. Seventy-four successfully marked lesions were resected. Six lesions without hook wires were successfully resected after detection by palpation with an additional mini-thoracotomy or using subtle pleural changes as a guide. The complication rates and procedure durations of multiple-placement procedures were significantly higher (P = 0.04) and longer (P < 0.001) than those in the single-placement group, respectively, while the technical success rate was not significantly different (P = 0.051).
Simultaneous multiple hook wire placements before VATS were clinically feasible, but increased the complication rate and lengthened the procedure time.

DOI： 10.1007/s00270-014-1028-5

肺移植後の気管支合併症に対する治療方針

杉本誠一郎, 大藤剛宏

今日の移植 28 ( 3 ) 257 - 265 2015年6月

Kissing-stents technique after living-donor lobar lung transplantation 査読国際誌

Seiichiro Sugimoto, Takahiro Oto, Shinichi Toyooka, Shinichiro Miyoshi

EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 47 ( 6 ) 1105 - 1106 2015年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OXFORD UNIV PRESS INC

Stent placement has become common practice for bronchial stenosis (BS) after lung transplantation (LT). Especially, segmental BS after lobar LT requires a complex stenting technique. We describe a case of multiple segmental bronchial stenoses treated by the kissing-stents technique using balloon-expandable metallic stents after living-donor lobar LT. Based on the vascular kissing-stents technique, we simultaneously placed two stents, side by side, in the superior segmental bronchus and the basal segmental bronchus of the right transplanted lobar lung. This technique may represent a valuable option for complex segmental BS after lobar LT.

DOI： 10.1093/ejcts/ezu314

Use of Extended-Criteria Lungs on a Lobe-by-Lobe Basis Through Ex Vivo Lung Perfusion Assessment 査読国際誌

Kentaroh Miyoshi, Takahiro Oto, Yusuke Konishi, Yutaka Hirano, Masanori Okada, Norichika Iga, Shin Hirayama, Seiichiro Sugimoto, Masaomi Yamane, Motomu Kobayashi, Shinichiro Miyoshi

ANNALS OF THORACIC SURGERY 99 ( 5 ) 1819 - 1821 2015年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE INC

Initially rejected and extended-criteria lungs were partially used through an ex vivo lung perfusion (EVLP) assessment that was first clinically applied in Asia. The truly injured lobe (left lower lobe) was identified during 89-minute normothermic EVLP and was excised, and the remaining lobes were successfully transplanted into a patient with lymphangioleiomyomatosis. The lung lobes showed heterogeneous changes on the ex vivo rig, and a brief duration of EVLP helped differentiate lung quality on a lobe-by-lobe basis. (C) 2015 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2014.06.115

呼吸器疾患 1 肺移植適応とその実際,ホスピタリストが遭遇し得る合併症

杉本誠一郎, 大藤剛宏

Hospitalist 3 ( 1 ) 220 - 225 2015年3月

Pneumocephalus and Chylothorax Complicating Vertebrectomy for Lung Cancer 査読国際誌

Seiichiro Sugimoto, Masato Tanaka, Ken Suzawa, Hitoshi Nishikawa, Shinichi Toyooka, Takahiro Oto, Toshifumi Ozaki, Shinichiro Miyoshi

ANNALS OF THORACIC SURGERY 99 ( 4 ) 1425 - 1428 2015年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE INC

Pneumocephalus is a rare, but potentially fatal complication of thoracic surgery. We describe a case of successful management of pneumocephalus complicated by persistent chylothorax developing after en bloc partial vertebrectomy performed after induction chemoradiotherapy for lung cancer invading the spine. Surgical treatment should be considered for pneumocephalus complicated by any condition requiring persistent chest drainage. (C) 2015 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2014.05.098

Living related donor middle lobe lung transplant in a pediatric patient 査読国際誌

Takahiro Oto, Kentaroh Miyoshi, Seiichiro Sugimoto, Masaomi Yamane

JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 149 ( 3 ) E42 - E44 2015年3月

Transfissural Route Used for Preoperative Localization of Small Pulmonary Lesions with a Short Hook Wire and Suture System 査読国際誌

Toshihiro Iguchi, Takao Hiraki, Hideo Gobara, Hiroyasu Fujiwara, Yusuke Matsui, Seiichiro Sugimoto, Shinichi Toyooka, Takahiro Oto, Shinichiro Miyoshi, Susumu Kanazawa

CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY 38 ( 1 ) 222 - 226 2015年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER

We retrospectively evaluated the results of the transfissural route for preoperative localization with a short hook wire and suture system for video-assisted thoracoscopic surgery (VATS).
Eleven patients with 11 tumors underwent CT-guided transfissural placement of a hook wire before VATS. This route was selected for all patients, because the distance between the tumor and interlobar fissure was much shorter than the required distance traversed using the conventional approach. Complications were evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0.
The hook wire was successfully placed using the transfissural route in all but one case. Of these ten successful placements, two tumors needed a second puncture for optimal placement, because the CT scan showed that the first hook wire was not properly placed in the lung. In one patient, we did not attempt replacement after the first placement was incorrect. In ten successful procedures, the mean distance traversed in the parenchyma of the unaffected lung lobe was 27.9 mm. The distance between the pleura and placed hook wire was significantly shorter than the estimated distance between the pleura and hook wire using the conventional route (mean 16.3 vs. 40.9 mm; P = 0.0002). Grade 1 adverse events occurred (11 pneumothoraxes and 4 pulmonary hemorrhages). No grade 2 or higher adverse event was observed.
The transfissural route used for preoperative localization before VATS is useful for selected patients because this route may allow for more limited lung parenchyma resection.

DOI： 10.1007/s00270-014-0862-9

肺移植周術期におけるECMO

杉本誠一郎, 三好健太郎, 大藤剛宏

救急・集中治療 26 ( 11-12 ) 1568 - 1572 2014年12月

Validity of using lobe-specific regional lymph node stations to assist navigation during lymph node dissection in early stage non-small cell lung cancer patients 査読

Shinichiro Miyoshi, Kazuhiko Shien, Shinichi Toyooka, Kentaroh Miyoshi, Hiromasa Yamamoto, Seiichiro Sugimoto, Junichi Soh, Makio Hayama, Masaomi Yamane, Takahiro Oto

SURGERY TODAY 44 ( 11 ) 2028 - 2036 2014年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER

Purpose The validity of our proposed lobe-specific regional lymph node stations (LSRLNS) was evaluated as a method for navigation during lymphadenectomy in patients with early stage non-small cell lung cancer (NSCLC).
Methods A total of 725 NSCLC patients with c-T2N1M0 or less extensive disease who had undergone a curative operation with complete mediastinal lymph node dissection (MLND) were studied. The LSRLNS were #2, #3, #4 and #10 for the right upper lobe, #11i, #11s, #7 and #8 for the right lower lobe, #4, #5 and #6 for the left superior division, #11, #5 and #7 for the left lingular division and #11, #7 and #8 for the left lower lobe.
Results If the LSRLNS were used for pathological examinations during surgery, 599 p-N0 and 39 p-N1 patients diagnosed with no metastasis would have been subjected to a selective MLND, while 20 p-N1 and 65 p-N2 patients who had a diagnosis of metastasis would have been navigated to a complete MLND. Two p-N2 patients with a diagnosis of no metastasis would have inappropriately undergone a selective MLND, resulting in the false negative rate at 0.3 %.
Conclusion Intra-operative pathological examination using our LSRLNS may accurately reveal the status of metastasis, and appropriately lead to a selective or complete MLND in patients with c-T2N1M0 or less extensive disease.

DOI： 10.1007/s00595-013-0772-5

[Open-chest management with Esmarch bandages after lung transplantation]. 査読

Eito Niman, Takahiro Oto, Shinji Otani, Seiichiro Sugimoto, Masaomi Yamane, Junichi Soh, Shinichiro Miyoshi

Kyobu geka. The Japanese journal of thoracic surgery 67 ( 10 ) 884 - 7 2014年9月

記述言語：日本語掲載種別：研究論文（学術雑誌）

There are patients in whom management in an open-chest state after lung transplantation is necessary due to over-sized grafts, heart failure, use of extracorporeal membrane oxygenation (ECMO), or bleeding. In such patients, we suture Esmarch bandages, which are used for orthopedic surgery, to the open chest wound and perform wound management. We report 3 patients in whom wound management using this method was performed due to postoperative cardiac failure, primary graft dysfunction, and a postoperative pulmonary edema, respectively. Due to improvement in the wound management method and use of appropriate antibiotics, each patient could be managed without developing wound infection. This method was also useful for the management of bleeding.

Hyaluronan contributes to bronchiolitis obliterans syndrome and stimulates lung allograft rejection through activation of innate immunity. 国際誌

Jamie L Todd, Xingan Wang, Seichiro Sugimoto, Vanessa E Kennedy, Helen L Zhang, Elizabeth N Pavlisko, Fran L Kelly, Howard Huang, Daniel Kreisel, Scott M Palmer, Andrew E Gelman

American journal of respiratory and critical care medicine 189 ( 5 ) 556 - 66 2014年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

RATIONALE: Although innate immunity is increasingly recognized to contribute to lung allograft rejection, the significance of endogenous innate ligands, such as hyaluronan (HA) fragments, in clinical or experimental lung transplantation is uncertain. OBJECTIVES: To determine if HA is associated with clinical bronchiolitis obliterans syndrome (BOS) in lung transplant recipients, and evaluate the effect of low- or high-molecular-weight HA on experimental lung allograft rejection, including dependence on innate signaling pathways or effector cells. METHODS: HA concentrations were measured in bronchoalveolar lavage and plasma samples from lung recipients with or without established BOS. BOS and normal lung tissues were assessed for HA localization and expression of HA synthases. Murine orthotopic lung recipients with established tolerance were treated with low- or high-molecular-weight HA under varied experimental conditions, including Toll-like receptor (TLR) 2/4 and myeloid differentiation protein 88 deficiency and neutrophil depletion. MEASUREMENTS AND MAIN RESULTS: HA localized within areas of intraluminal small airways fibrosis in BOS lung tissue. Moreover, transcripts for HA synthase enzymes were significantly elevated in BOS versus normal lung tissues and both lavage fluid and plasma HA concentrations were increased in recipients with BOS. Treatment with low-molecular-weight HA abrogated tolerance in murine orthotopic lung recipients in a TLR2/4- and myeloid differentiation protein 88-dependent fashion and drove expansion of alloantigen-specific T lymphocytes. Additionally, TLR-dependent signals stimulated neutrophilia that promoted rejection. In contrast, high-molecular-weight HA attenuated basal allograft inflammation. CONCLUSIONS: These data suggest that accumulation of HA could contribute to BOS by directly activating innate immune signaling pathways that promote allograft rejection and neutrophilia.

DOI： 10.1164/rccm.201308-1481OC

Detection of airway ischaemic damage after lung transplantation by using autofluorescence imaging bronchoscopy 査読国際誌

Norichika Iga, Takahiro Oto, Masanori Okada, Masaaki Harada, Hitoshi Nishikawa, Kentaroh Miyoshi, Shinji Otani, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka, Shinichiro Miyoshi

EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 45 ( 3 ) 509 - 513 2014年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OXFORD UNIV PRESS INC

OBJECTIVES: Airway complications related to ischaemia are a major cause of morbidity after lung transplantation. Early detection of airway ischaemia and optimal management of the anastomotic site could reduce the risk of airway complications. Autofluorescence imaging (AFI) bronchoscopy has been increasingly recognized as an effective technique for detecting abnormal mucosal thickening. The aim of this study was to investigate whether AFI bronchoscopy can facilitate the detection of airway ischaemic damage in lung transplant patients.
METHODS: Twenty Landrace pigs were used to create a tracheal autotransplantation model. A four-ring length of trachea was excised and implanted orthotopically. The tracheal autograft was observed on postoperative days 0, 2, 4 and 7 with AFI bronchoscopy. The extent and origin of graft autofluorescence were examined using histology and measured according to fluorescence intensity.
RESULTS: The lesions on the tracheal autografts appeared as bright green fluorescence on AFI bronchoscopy. On confocal fluorescence microscopy, high-intensity green fluorescence was observed in the elastin fibre layer of the submucosa. The fluorescence intensity of elastin was significantly higher in the graft showing fluorescence than the graft that did not show fluorescence and that at the control site.
CONCLUSIONS: Bright green fluorescence was seen in an elastin fibre layer in the submucosa, which was likely a result of epithelial sloughing. There is a close relationship between the bright green fluorescence pattern observed using AFI bronchoscopy and airway ischaemic damage. We conclude that AFI bronchoscopy may detect airway ischaemic damage after lung transplantation.

DOI： 10.1093/ejcts/ezt437

Use of a vessel sealing system versus conventional electrocautery for lung parenchymal resection: a comparison of the clinicopathological outcomes in porcine lungs 査読

Seiichiro Sugimoto, Shinichi Toyooka, Norichika Iga, Masashi Furukawa, Ryujiro Sugimoto, Kazuhiko Shien, Hitoshi Nishikawa, Junichi Soh, Masaomi Yamane, Takahiro Oto, Shinichiro Miyoshi

SURGERY TODAY 44 ( 3 ) 540 - 545 2014年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER

LigaSure, a vessel sealing system, has been shown to have excellent hemostatic properties; however, its use for lung parenchymal resection has been limited. We herein examined the hemostatic properties and potential for inducing histological lung injury of the LigaSure system in non-anatomic pulmonary resection to estimate the feasibility of its clinical application.
Non-anatomic pulmonary wedge resections of the right cranial, middle, and caudal lobes were performed in four pigs using the LigaSure system (Group A) or electrocautery (Group B). In each resection, the resection time, blood loss, and weight of the resected lung were measured. The thermal effect on the lung tissue was examined by means of intraoperative thermography and histology.
A total of 12 lung wedge resections were performed in each group. For an equivalent length of operation and weight of the resected lung parenchyma, Group A showed significantly lower blood loss and lower maximum and minimum temperatures of the lung tissue, as assessed by thermography, than Group B. The degree of thermal injury as estimated by a histological examination was lower in Group A than in Group B.
Our study suggests that the LigaSure system may be superior to conventional electrocautery, indicating its clinical usefulness for non-anatomic pulmonary resection.

DOI： 10.1007/s00595-013-0545-1

[The role of 18F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) in liposarcoma of the chest wall]. 査読

Haruchika Yamamoto, Seiichiro Sugimoto, Kentaroh Miyoshi, Hiromasa Yamamoto, Junichi Soh, Masaomi Yamane, Shinichi Toyooka, Takahiro Oto, Shinichiro Miyoshi

Kyobu geka. The Japanese journal of thoracic surgery 67 ( 1 ) 4 - 8 2014年1月

記述言語：日本語掲載種別：研究論文（学術雑誌）

18F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT)imaging is valuable in biopsy guidance, response assessment, grading, follow-up and prognostication for soft-tissue sarcoma. In liposarcoma, the maximum standardized uptake value (SUVmax) on PET/CT scan is correlated with the histological subtypes. We briefly review the role of FDG PET/CT in liposarcoma, and describe a case of chest wall liposarcoma treated based on the assessment with PET/CT. A 76-year-old man, with a 10-cm tumor at the thoracic outlet of the right chest wall, underwent the complete resection of the tumor according to the assessment with PET/CT that showed high FDG uptakeonly in the central area of the tumor with SUVmax of 5.89, but low uptake in the peripheral area. In accordance with the PET/CT findings, pathological examination revealed dedifferentiated liposarcoma in the central area and well-differentiated liposarcoma in the peripheral area. Pretherapy PET/CT should be performed for the appropriate treatment of liposarcoma.

Thoracoscopic Lobectomy as Salvage Surgery for Local Recurrence of Non-Small Cell Lung Cancer after Carbon Ion Radiotherapy in an Initially Operable Patient 査読

Seiichiro Sugimoto, Shinichi Toyooka, Ken Suzawa, Kouichi Ichimura, Osamu Fujii, Shinichiro Miyoshi

ANNALS OF THORACIC AND CARDIOVASCULAR SURGERY 20 501 - 504 2014年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MEDICAL TRIBUNE INC

Carbon ion radiotherapy (CIRT) for patients with early-stage non-small cell lung cancer (NSCLC) has recently provided favorable local control with very few toxic reactions. Because CIRT for NSCLC has been mostly performed for elderly or inoperable patients, salvage surgery for NSCLC after CIRT has rarely been reported. We describe a case of complete thoracoscopic right upper lobectomy with mediastinal lymphadenectomy performed as salvage surgery for local recurrence of stage IA NSCLC after CIRT in an initially operable patient who had refused surgery 27 months previously. Pleural adhesions caused by CIRT were localized to the pulmonary apex and the central pulmonary structures were intact at the time of the salvage surgery, which allowed us to successfully perform thoracoscopic lobectomy without any complications. Thus, salvage surgery for NSCLC after CIRT may be feasible in an initially operable patient, as CIRT appears to be unlikely to cause any difficulties in the salvage surgery.

DOI： 10.5761/atcs.cr.13-00223

Sacrificing the pulmonary arterial branch to the spared lobe is a risk factor of bronchopleural fistula in sleeve lobectomy after chemoradiotherapy 査読国際誌

Shinichi Toyooka, Junichi Soh, Kazuhiko Shien, Seiichiro Sugimoto, Masaomi Yamane, Takahiro Oto, Hiroshi Date, Shinichiro Miyoshi

EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 43 ( 3 ) 568 - 572 2013年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OXFORD UNIV PRESS INC

A sleeve lobectomy is a widely accepted procedure for enabling the pulmonary parenchyma to be spared. Induction chemoradiotherapy (CRT) followed by surgery is one treatment option for locally advanced non-small cell lung cancer (NSCLC), but CRT is considered to have a negative effect on subsequent surgery, especially for anastomotic healing. In this study, we describe our experience performing sleeve lobectomies and the associated anastomotic complications after induction CRT.
The medical records of NSCLC patients who underwent surgery after receiving CRT were reviewed. The relationships between anastomotic complications and clinicopathological factors were examined.
Between December 1998 and October 2011, a total of 104 patients received CRT followed by surgery. Among them, 14 NSCLC patients underwent a bronchial sleeve resection: nine patients underwent a right upper lobe resection, two patients underwent a left lingular division and lower lobe resection and one patient each underwent a right lower lobe, a right upper and middle lobe and a right middle and lower lobe resection. A bronchopleural fistula at the anastomosis occurred in two patients. A pulmonary arterial (PA) branch to the spared lobe had been sacrificed in both of these patients because of tumour involvement. In contrast, the PA branches to the spared lobes were preserved in 11 of the 12 patients who did not exhibit anastomotic complications (P = 0.033).
Our experience strongly suggests that the sacrifice of the PA branch to the spared lobe is a possible risk factor for anastomotic complications for a sleeve lobectomy after induction CRT.

DOI： 10.1093/ejcts/ezs323

「COPDの集学的治療」嚢胞性肺疾患に対する肺移植治療

岡田真典, 大藤剛宏, 伊賀徳周, 原田昌明, 西川仁士, 中谷文, 三好健太郎, 大谷真二, 杉本誠一郎, 宗淳一, 山根正修, 豊岡伸一, 三好新一郎

日本気胸・嚢胞性肺疾患学会雑誌 12 ( 2 ) 121 - 124 2012年11月

記述言語：日本語出版者・発行元：日本気胸・嚢胞性肺疾患学会

肺移植手術を施行した87例を嚢胞性肺疾患28例(男9例、女19例、平均32.4歳;A群)と非嚢胞性肺疾患59例(男18例、女42例、平均32.7歳;B群)に分け、成績を比較した。年齢、性別、術式(生体/脳死肺移植)は両群間で有意差がなかった。術後人工呼吸器管理日数およびICU滞在日数はA群が良好であったが、術後入院期間は両群間で有意差はなかった。術後ADL評価としてHugh-Johns分類の推移と6分間歩行値を比較したが、両群間で有意差はなく、共に術前より大幅に改善していた。呼吸機能については、術前にA群でFEV1.0、FEV1.0%、PaCO2が有意に悪化していたが、術後は両群間で有意差がなくなり、%VC、P/F ratioは術前後とも有意差はなかった。慢性拒絶反応(BOS)の無発症期間はA群中央値55ヵ月、B群43ヵ月、5年生存率はそれぞれ87.7%、74.6%で、有意差はなかった。A群では3例にBOSを認め、1例に再肺移植を施行した。

Intrathoracic irrigation with arbekacin for methicillin-resistant Staphylococcus aureus empyema following lung resection 査読国際誌

Tsuyoshi Ueno, Shinichi Toyooka, Junichi Soh, Kentaroh Miyoshi, Seiichiro Sugimoto, Masaomi Yamane, Takahiro Oto, Shinichiro Miyoshi

INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY 15 ( 3 ) 437 - 441 2012年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OXFORD UNIV PRESS

OBJECTIVES: Empyema is a well-known complication following lung resection. In particular, empyema caused by methicillin-resistant Staphylococcus aureus (MRSA) is difficult to treat. Here, we present our experience of MRSA empyema treated with local irrigation using arbekacin.
METHODS: Six patients consisted of 4 males and 2 females with an average age of 65.7 years. They developed MRSA empyema following lung resection and were treated at our institution between 2007 and 2011. Cases comprised four primary and one metastatic lung cancer, and 1 patient was a living lung transplantation donor. The surgical procedure consisted of four lobectomies, one segmentectomy and one wedge resection. After diagnosis of MRSA empyema, anti-MRSA drugs were administered intravenously in all cases. In addition, arbekacin irrigation at a dose of 100 mg dissolved in saline was performed after irrigation with saline only.
RESULTS: The average number of postoperative days for the diagnosis of MRSA empyema was 13 (range 4-19). The period of irrigation ranged from 6 to 46 days. Arbekacin irrigation did not induce nephrotoxicity or other complications, and no bacteria resistant to arbekacin was detected in the thoracic cavity. We re-operated on 1 case because he had pulmonary fistula and severe wound infection. At the time of removing the thoracic catheter, MRSA in the pleural effusion disappeared completely in 3 patients. The period until MRSA concentration in the pleural effusion became negative after starting arbekacin irrigation ranged from 4 to 9 days. In the remaining cases, in which MRSA did not disappear, the catheter was removed because of no inflammatory reaction after stopping irrigation and clamping the catheters. All patients were discharged from our institution without thoracic catheterization and no patients had relapsed during the follow-up period ranging from 6 to 44 months.
CONCLUSIONS: Irrigation of the thoracic cavity with arbekacin proved to be an effective, safe and readily available method for treating MRSA empyema following lung resection.

DOI： 10.1093/icvts/ivs285

Outcome of living-donor lobar lung transplantation using a single donor 査読国際誌

Hiroshi Date, Takeshi Shiraishi, Seiichiro Sugimoto, Tsuyoshi Shoji, Fengshi Chen, Masafumi Hiratsuka, Akihiro Aoyama, Masaaki Sato, Masaomi Yamane, Akinori Iwasaki, Shinichiro Miyoshi, Toru Bando, Takahiro Oto

JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 144 ( 3 ) 710 - 715 2012年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MOSBY-ELSEVIER

Objective: Living-donor lobar lung transplantation usually requires 2 healthy donors who donate either a right or a left lower lobe; however, finding 2 healthy donors is difficult. Several case reports have been published on successful living-donor lobar lung transplantation using a single donor; however, little is known about its outcome.
Methods: We retrospectively investigated 14 critically ill patients who had undergone single living-donor lobar lung transplantation at 3 lung transplant centers in Japan. There were 10 female and 4 male patients, including 10 children and 4 adults. Size matching was assessed by estimated graft forced vital capacity and 3-dimensional computed tomography volumetry. The diagnoses included complications of allogeneic hematopoietic stem cell transplantation (n = 6), pulmonary hypertension (n = 4), and others (n = 4).
Results: At a mean follow-up of 45 months (range, 2-128), the 3- and 5-year survival rate was 70% and 56%, respectively. There were 4 early deaths, for a hospital mortality of 29%, with 1 additional death at 40 months. The main cause of early death was primary graft dysfunction, most likely related to size mismatching. The survival among these 14 patients was significantly worse than the survival in a group of 78 patients undergoing bilateral living-donor lobar lung transplantation during the same period (P = .044).
Conclusions: Single living-donor lobar lung transplantation provides acceptable results for sick patients who would die soon otherwise. However, bilateral living-donor lobar lung transplantation appears to be a better option if 2 living donors are found. (J Thorac Cardiovasc Surg 2012; 144: 710-5)

DOI： 10.1016/j.jtcvs.2012.05.054

[Primary mediastinal lymphoma; a clinicopathologic case series]. 査読

Seiichiro Sugimoto, Junichi Soh, Yuho Maki, Takeshi Kurosaki, Masaomi Yamane, Shinichi Toyooka, Takahiro Oto, Shinichiro Miyoshi

Kyobu geka. The Japanese journal of thoracic surgery 65 ( 7 ) 527 - 31 2012年7月

記述言語：日本語掲載種別：研究論文（学術雑誌）

Treatment for primary mediastinal lymphoma generally involves chemotherapy and radiotherapy, and treatment regimens depend on histologic subtypes of lymphoma. The histologic subtype of lymphoma is mostly determined by computed tomography (CT)-guided core-needle biopsy or surgical procedures, including thoracotomy, thoracoscopy and mediastinoscopy. We describe the clinicopathologic features and diagnostic procedures of 8 cases of primary mediastinal lymphoma. The male-to-female ratio was 1:1, and median age at diagnosis was 27 years. The median size of the primary mediastinal tumor on CT was 8.5 cm. Five patients were diagnosed by CT-guided core-needle biopsy, 1 by open biopsy and 2 by surgery. Three patients were diagnosed with nodular sclerosis Hodgkin lymphoma, 3 with mediastinal diffuse large B-cell lymphoma, 1 with precursor T-lymphoblastic leukemia/lymphoma and 1 with thymic extranodal marginal zone B-cell lymphoma. According to their histological subtypes, 5 patients were treated with chemoradiotherapy, 2 patients with chemotherapy and 1 patient of thymic extranodal marginal zone B-cell lymphoma with surgery alone. All patients survived in the median follow-up of 34.5 months. Appropriate biopsy procedure should be performed in patients with suspected mediastinal lymphoma.

A Case of Delayed Massive Hemothorax Caused by the Rupture of a Pulmonary Artery Pseudoaneurysm after Radiofrequency Ablation of Lung Tumors 査読国際誌

Junichi Soh, Shinichi Toyooka, Hideo Gobara, Takao Hiraki, Seiichiro Sugimoto, Masaomi Yamane, Takahiro Oto, Susumu Kanazawa, Shinichiro Miyoshi

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 42 ( 7 ) 646 - 649 2012年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OXFORD UNIV PRESS

Radiofrequency ablation has been applied as a minimally invasive therapy for the local control of lung tumors, including primary and metastatic neoplasms. Hemorrhagic complications after radiofrequency ablation can usually be treated conservatively, but such complications can be massive and fatal in some cases. In this paper, we report the rare case of delayed massive hemothrax caused by the rupture of a pulmonary artery pseudoaneurysm after lung radiofrequency ablation that was treated using transcatheter coil embolization followed by a left lower lobectomy. A 75-year-old woman underwent radiofrequency ablation for the treatment of a metastatic lung tumor in the left lower lobe arising from a colorectal carcinoma located close to a branch of the pulmonary artery. Thirty-six hours later, hemothorax and hemorrhagic shock occurred as a result of a ruptured pulmonary artery pseudoaneurysm and radiofrequency ablation-induced damage to the interlobular pleura. After transcatheter coil embolization of the pulmonary artery pseudoaneurysm, she recovered from a state of shock and a left lower lobectomy was performed. Histological findings revealed the presence of residual tumor cells in the ablated lung tumor. The postoperative course was uneventful, and no evidence of recurrence of the primary disease was seen at 1 year after the surgery. Although hemothorax secondary to the rupture of a pulmonary artery pseudoaneurysm after lung radiofrequency ablation is a rare complication, it should be recognized as a serious potential complication of lung radiofrequency ablation for a tumor located close to the pulmonary artery branch.

DOI： 10.1093/jjco/hys068

「高齢化社会を迎えての臓器移植の展望:高齢ドナー移植の現状と問題」肺移植における高齢ドナー

大藤剛宏, 三好健太郎, 杉本誠一郎, 山根正修, 三好新一郎

移植 47 ( 2/3 ) 161 - 165 2012年6月

Five-year update on the mouse model of orthotopic lung transplantation: Scientific uses, tricks of the trade, and tips for success 査読国際誌

Xue Lin, Wenjun Li, Jiaming Lai, Mikio Okazaki, Seiichiro Sugimoto, Sumiharu Yamamoto, Xingan Wang, Andrew E. Gelman, Daniel Kreisel, Alexander Sasha Krupnick

JOURNAL OF THORACIC DISEASE 4 ( 3 ) 247 - 258 2012年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PIONEER BIOSCIENCE PUBL CO

It has been 5 years since our team reported the first successful model of orthotopic single lung transplantation in the mouse (1). There has been great demand for this technique due to the obvious experimental advantages the mouse offers over other large and small animal models of lung transplantation. These include the availability of mouse-specific reagents as well as knockout and transgenic technology. Our laboratory has utilized this mouse model to study both immunological and non-immunological mechanisms of lung transplant physiology while others have focused on models of chronic rejection (1-19). It is surprising that despite our initial publication in 2007 only few other laboratories have published data using this model (20-25). This is likely due to the technical complexity of the surgical technique and perioperative complications, which can limit recipient survival (9,26). As two of the authors (XL and WL) have a combined experience of over 2500 left and right single lung transplants, this review will summarize their experience and delineate tips and tricks necessary for successful transplantation. We will also describe technical advances made since the original description of the model (1,5,6).

DOI： 10.3978/j.issn.2072-1439.2012.06.02

Egr1: a novel target for ameliorating acute allograft rejection in an experimental lung transplant model 査読国際誌

Naohisa Waki, Masaomi Yamane, Sumiharu Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Akihiro Matsukawa, Takahiro Oto, Shinichiro Miyoshi

EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 41 ( 3 ) 669 - 675 2012年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OXFORD UNIV PRESS INC

Acute allograft rejection is one of the significant complications occurring in lung transplant recipients. Early growth response-1 (Egr-1), zinc-finger-type transcription factor, is known as a master switch regulator of diverse chemical mediators. We used an orthotopic mouse model of left lung transplant to elucidate the function of Egr-1 in acute pulmonary rejection.
Left lung grafts retrieved from C57BL/6 wild mice or C57BL/6 Egr-1-null mice were orthotopically transplanted into BALB/c mice; the lungs were harvested at day 1, 3, 5 or 7 after lung transplantation. The grade of acute rejection was histopathologically evaluated. The intragraft gene expression levels of Egr-1 and downstream target mediators were quantitatively measured by real-time polymerase chain reaction. Immunohistochemical analysis was used to determine the location and distribution of the Egr-1 protein in the pulmonary graft.
Severe acute rejection was observed in allografts from wild-type mice at 5 days after transplantation. Only minimal rejection was seen in the lung graft from Egr-1-null donor mice at 5 days after transplantation. Strong upregulation of Egr-1 mRNA transcripts was observed at day 1, which then decreased during the next 5 days. The mRNA of Egr-1 target mediators [interleukin-1-beta (IL-1 beta), monocyte chemotactic protein-1 (MCP-1) and plasminogen activator inhibitor-1] reached maximal levels at day 5. Egr-1-null allografts exhibited significantly lower expressions of IL-1 beta and MCP-1 mRNA (P < 0.05).
Our study showed that deletion of Egr-1 in lung allografts ameliorates severe acute rejection with the reduction of expression levels of chemical mediators, implying a new possible strategy for treating acute pulmonary allograft rejection.

DOI： 10.1093/ejcts/ezr030

「切除困難例」への化学療法後の手術―根治切除はどこまで可能か非小細胞肺癌に対する根治的放射線化学療法後の手術

豊岡伸一, 宗淳一, 枝園和彦, 牧佑歩, 三好健太郎, 上野剛, 杉本誠一郎, 山根正修, 大藤剛宏, 三好新一郎

臨床外科 67 ( 1 ) 12 - 16 2012年1月

記述言語：日本語出版者・発行元：(株)医学書院

＜ポイント＞◆局所進行非小細胞肺癌に対しては根治的放射線化学療法を行うことが多いが,その後,外科手術になることがある.◆根治的放射線化学療法の再発症例に対するサルベージ手術,あるいは高線量による導入放射線化学療法の有用性は確立していない.◆高線量の放射線照射後の手術はリスクが高くなることが考えられるが,手術が原病,あるいは治療による合併症を改善する症例があり,必要に応じて手術を考慮すべきである.(著者抄録)

DOI： 10.11477/mf.1407103898

Emergency granulopoiesis promotes neutrophil-dendritic cell encounters that prevent mouse lung allograft acceptance 査読国際誌

Daniel Kreisel, Seiichiro Sugimoto, Jihong Zhu, Ruben Nava, Wenjun Li, Mikio Okazaki, Sumiharu Yamamoto, Mohsen Ibrahim, Howard J. Huang, Kelsey A. Toth, Jon H. Ritter, Alexander S. Krupnick, Mark J. Miller, Andrew E. Gelman

BLOOD 118 ( 23 ) 6172 - 6182 2011年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER SOC HEMATOLOGY

The mechanisms by which innate immune signals regulate alloimmune responses remain poorly understood. In the present study, we show by intravital 2-photon microscopy direct interactions between graft-infiltrating neutrophils and donor CD11c(+) dendritic cells (DCs) within orthotopic lung allografts immediately after reperfusion. Neutrophils isolated from the airways of lung transplantation recipients stimulate donor DCs in a contact-dependent fashion to augment their production of IL-12 and expand alloantigen-specific IFN-gamma(+) T cells. DC IL-12 expression is largely regulated by degranulation and induced by TNF-alpha associated with the neutrophil plasma membrane. Extended cold ischemic graft storage enhances G-CSF-mediated granulopoiesis and neutrophil graft infiltration, resulting in exacerbation of ischemia-reperfusion injury after lung transplantation. Ischemia reperfusion injury prevents immunosuppression-mediated acceptance of mouse lung allografts unless G-CSF-mediated granulopoiesis is inhibited. Our findings identify granulopoiesis-mediated augmentation of alloimmunity as a novel link between innate and adaptive immune responses after organ transplantation. (Blood. 2011;118(23):6172-6182)

DOI： 10.1182/blood-2011-04-347823

縦隔リンパ節転移を伴った肺癌に対する外科的治療をめぐって 3.術前化学療法後外科的治療 1)術前放射線化学療法における外科治療の役割

豊岡伸一, 宗淳一, 杉本誠一郎, 山根正修, 大藤剛宏, 三好新一郎

日本胸部臨床 70 ( 9 ) 919 - 924 2011年9月

記述言語：日本語出版者・発行元：克誠堂出版(株)

縦隔リンパ節転移を伴う非小細胞肺癌に対する手術の意義が問われている。導入放射線化学療法後手術群と根治的放射線化学療法群の生存率を比較した第III相試験(Intergroup trail 1346)の結果が発表されたが、全症例に対する解析では手術の有用性は確認できなかった。しかしながらこの試験では肺全摘症例の術後早期の死亡例が多く、肺葉切除に限った場合では手術群が放射線抗癌薬のみの群より良好な成績であり、手術の有用性が示唆されている。当院ではN2肺癌に対し1995年より術前導入療法後手術療法を行ってきた。特に放射線化学療法後手術を行う症例の成績は良好であり、有用な治療法として位置付けている。(著者抄録)

法改正後の移植の現状と問題点:心肺領域マージナル肺ドナーとメディカルコンサルタント

大藤剛宏, 三好健太郎, 杉本誠一郎, 山根正修, 三好新一郎

移植 46 ( 4/5 ) 281 - 283 2011年9月

治療抵抗性特発性間質性肺炎に対する生体肺移植

三好健太郎, 大藤剛宏, 大谷真二, 杉本誠一郎, 宗淳一, 山根正修, 豊岡伸一, 三好新一郎

臨床呼吸生理 43 47 - 49 2011年6月

記述言語：日本語出版者・発行元：臨床呼吸生理研究会

生体肺移植を行った56例を難治性特発性間質性肺炎14例(男4例、女10例、平均41.8歳;IIP群)と他疾患42例(男9例、女33例、平均27.9歳;non-IIP群)に分け、急性期および慢性期評価を比較した。年齢、術前ステロイド使用頻度はIIP群で高い傾向であった。術後ICU滞在平均日数はIIP群20.4日、non-IIP群34.4日、術後3ヵ月の6分間歩行はそれぞれ371.7m、353.7mで、いずれも有意差はなかった。慢性拒絶反応無発症期間はIIP群中央値52ヵ月、non-IIP群56ヵ月、生存期間はそれぞれ67ヵ月、73ヵ月と有意差はなく、両群とも良好に経過している。肺移植後の呼吸機能は、1秒率は両群で同様の改善傾向を認めたが、%努力性肺活量はIIP群がnon-IIP群と比較して術後早期からの回復が認められた。

A novel technique for identification of the lung intersegmental plane using dye injection into the segmental pulmonary artery 査読国際誌

Seiichiro Sugimoto, Takahiro Oto, Kentaroh Miyoshi, Shinichiro Miyoshi

JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 141 ( 5 ) 1325 - 1327 2011年5月

Maintenance of IKKβ activity is necessary to protect lung grafts from acute injury. 査読国際誌

Huang HJ, Sugimoto S, Lai J, Okazaki M, Yamamoto S, Krupnick AS, Kreisel D, Gelman AE

Transplantation 91 ( 6 ) 624 - 631 2011年3月

Bcl3 prevents acute inflammatory lung injury in mice by restraining emergency granulopoiesis 査読国際誌

Daniel Kreisel, Seiichiro Sugimoto, Jeremy Tietjens, Jihong Zhu, Sumiharu Yamamoto, Alexander S. Krupnick, Ruaidhri J. Carmody, Andrew E. Gelman

JOURNAL OF CLINICAL INVESTIGATION 121 ( 1 ) 265 - 276 2011年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER SOC CLINICAL INVESTIGATION INC

Granulocytes are pivotal regulators of tissue injury However, the transcriptional mechanisms that regulate granulopoiesis under inflammatory conditions are poorly understood Here we show that the transcriptional coregulator B cell leukemia/lymphoma 3 (Bcl3) limits granulopoiesis under emergency e, inflammatory) conditions, but not homeostatic conditions Treatment of mouse myeloid progenitors with G-CSF serum concentrations of which rise under inflammatory conditions rapidly increased Bcl3 transcript accumulation in a STAT3-dependent manner Bcl3-deficient myeloid progenitors demonstrated an enhanced capacity to proliferate and differentiate into granulocytes following G-CSF stimulation, whereas the accumulation of Bcl3 protein attenuated granulopoiesis in an NF-kappa B p50-dependent manner In a clinically relevant model of transplant-mediated lung ischemia reperfusion injury, expression of Bcl3 in recipients inhibited emergency granulopoiesis and limited acute graft damage These data demonstrate a critical role for Bcl3 in regulating emergency granulopoiesis and suggest that targeting the differentiation of myeloid progenitors may be a therapeutic strategy for preventing inflammatory lung injury

DOI： 10.1172/JCI42596

Surgery after induction chemoradiotherapy

Toyooka, S., Soh, J., Sugimoto, S., Yamane, M., Oro, T., Miyoshi, S.

Japanese Journal of Chest Diseases 70 ( 9 ) 2011年

肺移植後に発症した小腸悪性リンパ腫穿孔の1例

村岡孝幸, 浅野博昭, 佃和憲, 澤田芳行, 野上智弘, 上野剛, 牧佑歩, 杉本誠一郎, 豊岡伸一, 内藤稔

日本消化器外科学会雑誌(Web) 44 ( 12 ) 1610 - 1617 2011年

乳糜胸水・腹水を考える―その原因と対策〔術後合併症としての乳糜胸水・腹水―対応に困ったこの症例〕胸部外科系術後の乳糜胸水肺リンパ脈管筋腫症(LAM)患者に合併した術後乳糜胸水

二萬英斗, 大藤剛宏, 杉本誠一郎, 宗淳一, 山根正修, 豊岡伸一, 三好新一郎

臨床外科 65 ( 10 ) 1372 - 1375 2010年10月

記述言語：日本語出版者・発行元：(株)医学書院

胸部外科系術後の乳糜胸水は,術中操作による胸管損傷に伴い発症する合併症である.胸腔ドレナージ,絶食・TPN管理(長鎖脂肪酸の制限・中鎖脂肪酸の投与),胸膜癒着術,胸管結紮術などがその治療法としてよく知られている.しかし,これらの治療法に反応せず,対応に難渋する乳糜胸水症例にも時に遭遇する.特に肺リンパ脈管筋腫症(LAM)を伴った患者に対する手術の際には注意を要する.本稿では,胸部外科術後の乳糜胸水に対する治療を中心に概説するとともに,LAM患者に対する両側生体肺移植術後の難治性乳糜胸腹水にシロリムス(ラパマイシン)の投与が有効であった症例を加え,報告する.(著者抄録)

DOI： 10.11477/mf.1407103212

Cutting Edge: MHC Class II Expression by Pulmonary Nonhematopoietic Cells Plays a Critical Role in Controlling Local Inflammatory Responses 査読国際誌

Daniel Kreisel, Steven B. Richardson, Wenjun Li, Xue Lin, Christopher G. Kornfeld, Seiichiro Sugimoto, Chyi-Song Hsieh, Andrew E. Gelman, Alexander S. Krupnick

JOURNAL OF IMMUNOLOGY 185 ( 7 ) 3809 - 3813 2010年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER ASSOC IMMUNOLOGISTS

The interaction of CD4(+) T cells with MHC class II (MHCII)-expressing hematopoietic APCs plays a critical role in both the generation of protective immune responses and maintenance of tolerance in the lung. The functional significance of MHCII expression by nonhematopoietic stromal cells, however, has not been defined in vivo. Using a novel mouse model of orthotopic left lung transplantation, we demonstrate that selective elimination of MHCII expression on nonhematopoietic cells leads to an inflammatory response as a result of reduced peripheral generation of regulatory CD4(+) T cells. Absence of MHCII expression on nonhematopoietic cells also inhibits local growth of metastatic pulmonary tumor. These findings indicate that nonhematopoietic cells play a previously unrecognized role in downregulating inflammatory responses in nonlymphoid tissues. The Journal of Immunology, 2010, 185: 3809-3813.

DOI： 10.4049/jimmunol.1000971

診療に役立つ「呼吸器疾患外科治療」のすべて I 良性疾患 7.肺気腫に対するvolume reduction surgery

杉本誠一郎, 大藤剛宏, 宗淳一, 山根正修, 豊岡伸一, 三好新一郎

日本胸部臨床 69 ( 9 ) S40-S44 - S44 2010年9月

記述言語：日本語出版者・発行元：克誠堂出版(株)

肺気腫に対する肺容量減少手術(LVRS)は米国での大規模臨床試験により、特に上葉優位型肺気腫に対する有効性が示されたため、現在では適応を慎重に検討して施行されている。LVRSは姑息的治療であり、肺移植へのbridge therapyの側面をもつことは留意すべきである。(著者抄録)

肺癌肺癌の治療指針とその戦略非小細胞肺癌の治療戦略肺癌外科手術―適応,手術手技,治療成績―

杉本誠一郎, 豊岡伸一, 三好新一郎

Medical Practice 27 ( 7 ) 1181 - 1185 2010年7月

Orthotopic vascularized right lung transplantation in the mouse 査読国際誌

Wenjun Li, Seiichiro Sugimoto, Jiaming Lai, G. Alexander Patterson, Andrew E. Gelman, Alexander S. Krupnick, Daniel Kreisel

JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 139 ( 6 ) 1637 - 1643 2010年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MOSBY-ELSEVIER

Objectives: Orthotopic left lung transplantation in the mouse, as recently developed by our laboratory, represents a physiologic model for studies in transplantation biology. However, because of the limited overall respiratory contribution of the murine left lung, left lung transplant recipients remain healthy despite immune-mediated graft necrosis. We sought to develop a lung transplantation model in which animal survival depends on graft function.
Methods: Orthotopic vascularized right lung transplantations using cuff techniques were performed in syngeneic and allogeneic strain combinations. Grafts were assessed histologically or functionally by measuring arterial blood gases from 7 to 28 days after transplantation. In a parallel set of experiments, syngeneic and immunosuppressed allogeneic hosts underwent a left pneumonectomy 2 weeks after right lung transplantation, with assessment of graft function 1 week later.
Results: We performed 40 right lung transplantations, with a survival rate of 87.5%. Syngeneic grafts remain free of inflammation as far as 28 days after transplantation. On day 7, arterial oxygen levels in syngeneic recipients (481 +/- 90 mm Hg) are equivalent to those in naive mice (503 +/- 59 mm Hg) after left hilar occlusion. Alternatively, allogeneic grafts develop histologic evidence of acute rejection, and arterial oxygen levels are significantly decreased after left hilar clamping (53.3 +/- 10.3 mm Hg). Both syngeneic and immunosuppressed allogeneic right lung recipients tolerate a left pneumonectomy.
Conclusions: Right lung transplantation followed by left pneumonectomy represents the first survival model of vascularized lung transplantation in the mouse and will therefore allow for the design of novel studies in experimental lung transplantation. (J Thorac Cardiovasc Surg 2010;139:1637-43)

DOI： 10.1016/j.jtcvs.2009.11.019

CCR2 regulates monocyte recruitment as well as CD4⁺ T <inf>h</inf>1 allorecognition after lung transplantation

A. E. Gelman, M. Okazaki, S. Sugimoto, W. Li, C. G. Kornfeld, J. Lai, S. B. Richardson, F. H. Kreisel, H. J. Huang, J. R. Tietjens, B. H. Zinselmeyer, G. A. Patterson, M. J. Miller, A. S. Krupnick, D. Kreisel

American Journal of Transplantation 10 ( 5 ) 1189 - 1199 2010年5月

掲載種別：研究論文（学術雑誌）

Graft rejection remains a formidable problem contributing to poor outcomes after lung transplantation. Blocking chemokine pathways have yielded promising results in some organ transplant systems. Previous clinical studies have demonstrated upregulation of CCR2 ligands following lung transplantation. Moreover, lung injury is attenuated in CCR2-deficient mice in several inflammatory models. In this study, we examined the role of CCR2 in monocyte recruitment and alloimmune responses in a mouse model of vascularized orthotopic lung transplantation. The CCR2 ligand MCP-1 is upregulated in serum and allografts following lung transplantation. CCR2 is critical for the mobilization of monocytes from the bone marrow into the bloodstream and for the accumulation of CD11c+ cells within lung allografts. A portion of graft-infiltrating recipient CD11c+ cells expresses both recipient and donor MHC molecules. Two-photon imaging demonstrates that recipient CD11c+ cells are associated with recipient T cells within the graft. While recipient CCR2 deficiency does not prevent acute lung rejection and is associated with increased graft infiltration by T cells, it significantly reduces CD4+ Th1 indirect and direct allorecognition. Thus, CCR2 may be a potential target to attenuate alloimmune responses after lung transplantation. © 2010 The American Society of Transplantation and the American Society of Transplant Surgeons.

DOI： 10.1111/j.1600-6143.2010.03101.x

Volume reduction surgery for pulmonary emphysema

Sugimoto, S., Oto, T., Soh, J., Yamane, M., Toyooka, S., Miyoshi, S.

Japanese Journal of Chest Diseases 69 ( SUPPL. ) 2010年

Apyrase treatment prevents ischemia-reperfusion injury in rat lung isografts 査読国際誌

Seiichiro Sugimoto, Xue Lin, Jiaming Lai, Mikio Okazaki, Nitin A. Das, Wenjun Li, Alexander S. Krupnick, Ridong Chen, Soon Seog Jeong, G. A. Patterson, Daniel Kreisel, Andrew E. Gelman

JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 138 ( 3 ) 752 - 759 2009年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MOSBY-ELSEVIER

Objective: Endothelial cells express the ectoenzyme ectonucleoside adenosine triphosphate diphosphohydrolase, an apyrase that inhibits vascular inflammation by catalyzing the hydrolysis of adenosine triphosphate and adenosine diphosphate. However, ectonucleoside adenosine triphosphate diphosphohydrolase expression is rapidly lost following oxidative stress, leading to the potential for adenosine triphosphate and related purigenic nucleotides to exacerbate acute solid organ inflammation and injury. We asked if administration of a soluble recombinant apyrase APT102 attenuates lung graft injury in a cold ischemia reperfusion model of rat syngeneic orthotopic lung transplantation.
Methods: Male Fisher 344 donor lungs were cold preserved in a low-potassium dextrose solution in the presence or absence of APT102 for 18 hours prior to transplantation into syngeneic male Fisher 344 recipients. Seven minutes after reperfusion, lung transplant recipients received either a bolus of APT102 or vehicle (saline solution). Four hours after reperfusion, APT102- and saline solution-treated groups were evaluated for lung graft function and inflammation.
Results: APT102 significantly reduced lung graft extracellular pools of adenosine triphosphate and adenosine diphosphate, improved oxygenation, and protected against pulmonary edema. Apyrase treatment was associated with attenuated neutrophil graft sequestration and less evidence of tissue inflammation as assessed by myeloperoxidase activity, expression of proinflammatory mediators, and numbers of apoptotic endothelial cells.
Conclusions: Administration of a soluble recombinant apyrase promotes lung function and limits the tissue damage induced by prolonged cold storage, indicating that extracellular purigenic nucleotides play a key role in promoting ischemia-reperfusion injury following lung transplantation.

DOI： 10.1016/j.jtcvs.2009.04.049

Experimental orthotopic lung transplantation model in rats with cold storage 査読

Ryujiro Sugimoto, Atsunori Nakao, Itaru Nagahiro, Junichi Kohmoto, Seiichiro Sugimoto, Mikio Okazaki, Masaomi Yamane, Hidetoshi Inokawa, Takahiro Oto, Kazunori Tahara, Jianghua Zhan, Yoshifumi Sano, Kenneth R. McCurry

SURGERY TODAY 39 ( 7 ) 641 - 645 2009年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER

This report describes a new experimental procedure, a rat unilateral, orthotopic lung transplantation with cold storage, and evaluates its relevancy and reliability to study the early events during cold ischemia/reperfusion (I/R) injury. This model, using the cuff technique, does not require extensive training and is relatively easy to be established. The model can induce reproducible degrees of pulmonary graft injury including impaired gas exchange, proinflammatory cytokine upregulation, or inflammatory infiltrates, depending on the preservation time. The results are consistent with the previous clinical evidence, thus suggesting that this model is a valid and reliable animal model of cold I/R injury.

DOI： 10.1007/s00595-008-3929-x

Cutting Edge: Acute Lung Allograft Rejection Is Independent of Secondary Lymphoid Organs 査読国際誌

Andrew E. Gelman, Wenjun Li, Steven B. Richardson, Bernd H. Zinselmeyer, Jiaming Lai, Mikio Okazaki, Christopher G. Kornfeld, Friederike H. Kreisel, Seiichiro Sugimoto, Jeremy R. Tietjens, John Dempster, G. Alexander Patterson, Alexander S. Krupnick, Mark J. Miller, Daniel Kreisel

JOURNAL OF IMMUNOLOGY 182 ( 7 ) 3969 - 3973 2009年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER ASSOC IMMUNOLOGISTS

It is the prevailing view that adaptive immune responses are initiated in secondary lymphoid organs. Studies using alymphoplastic mice have shown that secondary lymphoid organs are essential to initiate allograft rejection of skin, heart, and small bowel. The high immunogenicity of lungs is well recognized and allograft rejection remains a major contributing factor to poor outcomes after lung transplantation. We show in this study that alloreactive T cells are initially primed within lung allografts and not in secondary lymphoid organs following transplantation. In contrast to other organs, lungs are acutely rejected in the absence of secondary lymphoid organs. Two-photon microscopy revealed that recipient T cells cluster predominantly around lung-resident, donor-derived CD11c(+) cells early after engraftment. These findings demonstrate for the first time that alloimmune responses following lung transplantation are initiated in the graft itself and therefore identify a novel, potentially clinically relevant mechanism of lung allograft rejection. The Journal of Immunology, 2009, 182: 3969-3973.

DOI： 10.4049/jimmunol.0803514

Orthotopic mouse lung transplantation as experimental methodology to study transplant and tumor biology 査読国際誌

Alexander S. Krupnick, Xue Lin, Wenjun Li, Mikio Okazaki, Jiaming Lai, Seiichiro Sugimoto, Steven B. Richardson, Christopher G. Kornfeld, Joel R. Garbow, G. Alexander Patterson, Andrew E. Gelman, Daniel Kreisel

NATURE PROTOCOLS 4 ( 1 ) 86 - 93 2009年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：NATURE PUBLISHING GROUP

Unlike transplantation of other solid organs, vascularized mouse lung transplantation has only recently been developed. In this protocol, we describe a detailed method for performing a vascularized and aerated mouse orthotopic lung transplant, which to date represents the most physiological mouse model of lung transplantation. The procedure is divided into two separate portions consisting of donor harvest followed by implantation using the cuff technique for bronchovascular anastomoses. After a training period spanning several months, the procedure can be successfully mastered and, in experienced hands, requires similar to 90 min to perform. After an initial learning curve, perioperative survival is close to 100%. As the donor hematopoietic cells in the transplanted lung are replaced by those of the host over time, thereby creating a 'chimeric lung,' this model represents a novel research tool for the study of transplantation biology as well as other disease processes, such as malignancies.

DOI： 10.1038/nprot.2008.218

Costimulatory Blockade-Mediated Lung Allograft Acceptance Is Abrogated by Overexpression of Bcl-2 in the Recipient

Okazaki, M., Sugimoto, S., Lai, J., Kornfeld, C.G., Hotchkiss, R.S., Richardson, S.B., Li, W., Kreisel, F.H., Huang, H.J., Patterson, G.A., Krupnick, A.S., Gelman, A.E., Kreisel, D.

Transplantation Proceedings 41 ( 1 ) 385 - 387 2009年

掲載種別：研究論文（学術雑誌）

Lung allografts are considered to be more immunogenic than other solid organs. Little is known about the effectiveness of immunosuppressive regimens after lung transplantation. Herein, we describe a novel model of murine vascularized orthotopic lung transplantation we used to study the effects of costimulatory blockade on lung rejection. Transplants were performed in the Balb → B6 strain combination. Recipients were either not immunosuppressed or received perioperative CD40/CD40L and CD28/B7 costimulatory blockade. Nonimmunosupressed Balb/c → B6 lung transplants had severe acute rejection 7 days after transplantation and CD8+ T cells outnumbered CD4+ T cells within the allografts. Alternatively, B6 recipients that received perioperative costimulatory blockade had minimal inflammation and there were nearly equal numbers of CD8+ and CD4+ T cells in these grafts. Approximately one third of graft-infiltrating CD4+ T cells expressed Foxp3. CD4+ T cells isolated from these grafts induced apoptosis of alloreactive CD8+ T cells that were stimulated with donor splenocytes in vitro. In contrast with wild-type B6 recipient mice, we observed severe rejection of Balb/c lungs 7 days after transplantation into Bcl-2 transgenic B6 recipients that had received costimulatory blockade. CD8+ T cells outnumbered CD4+ T cells in these immunosuppressed Bcl-2 transgenic recipients and, compared with immunosuppressed wild-type B6 recipients, a lower percentage of graft-infiltrating CD4+ T cells expressed Foxp3, and a higher percentage of graft-infiltrating CD8+ T cells expressed intereferon-γ. Thus, our results show that perioperative blockade of the CD40/CD40L and CD28/B7 costimulatory pathways markedly ameliorates acute rejection of lung allografts in wild type but not Bcl-2 transgenic recipients. © 2009 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.transproceed.2008.10.068

Monocyte Differentiation Is Controlled by MyD88 After Mouse Orthotopic Lung Transplantation

Sugimoto, S., Lin, X., Okazaki, M., Lai, J., Tietjens, J.R., Huang, H., Patterson, G.A., Krupnick, A.S., Kreisel, D., Gelman, A.E.

Transplantation Proceedings 41 ( 1 ) 388 - 390 2009年

掲載種別：研究論文（学術雑誌）

In lung grafts, ischemia-reperfusion signals rapidly induce the recruitment and differentiation of host monocytes into macrophages and dendritic cells. The nature of ischemia-reperfusion signals are antigen independent, but have been hypothesized to initiate Toll-like receptor (TLR) and interleukin (IL)-1R-mediated signaling pathways that are thought to potentiate alloimmune responses. We wondered whether MyD88, an adaptor molecule critical for both TLR and IL-1R-mediated inflammatory responses, regulated monocyte differentiation in a mouse model of vascularized orthotopic lung transplantation. Orthotopic left lung transplants were performed in the following syngeneic combinations: CD45.1+ B6 → CD45.2+ MyD88-/- and CD45.1+ B6 → CD45.2+ B6. One day later, recipient-derived dendritic cells and macrophage numbers were assessed in the bronchiolar lavage by FACS analysis. Compared with the bronchiolar lavage of wildtype recipients, MyD88-/- recipients had lower numbers of dendritic cells in lung graft airways that were of recipient origin. Lower numbers of newly differentiated lung graft dendritic cells was coincident with the appearance of higher numbers of undifferentiated monocytes in the lung airways of MyD88-/- recipients as compared with wild-type recipients. Moreover, adoptive transfer experiments demonstrated that MyD88-/- monocytes were poorer at differentiating into lung dendritic cells as compared with wild-type monocytes. Taken together, these data show that MyD88 regulates graft-infiltrating monocyte differentiation and suggests a mechanism by which TLR/IL-1R-signaling pathways control adaptive responses in lung allografts through controlling monocyte fate. © 2009 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.transproceed.2008.09.064

Native lung-sparing lobar transplantation for pulmonary emphysema 査読国際誌

Masaomi Yamane, Daisuke Okutani, Sciichiro Sugimoto, Shinichi Toyooka, Motoi Aoe, Megumi Okazaki, Yoshifumi Sano, Hiroshi Date

JOURNAL OF HEART AND LUNG TRANSPLANTATION 27 ( 9 ) 1046 - 1049 2008年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE INC

The living-donor lobar lung transplantation procedure has been developed clinically as an alternative approach for patients considered too ill to await cadaveric transplantation. With this procedure, 2 lobes are implanted in the recipient in place of whole right and left lungs, respectively. However, the shortage of graft volume can be a problem when compared with full-sized cadaveric grafts. In an attempt to solve this problem, we have developed a native lobe-preserving lobar transplant technique using a large animal model. We report a first successful case of a patient undergoing native lobe-preserving lobar lung transplantation for severe pulmonary emphysema.

DOI： 10.1016/j.healun.2008.05.025

The feasibility of diaphragmatic transplantation as potential therapy for treatment of respiratory failure associated with Duchenne muscular dystrophy: Acute canine model 査読国際誌

Alexander Sasha Krupnick, Andrew E. Gelman, Mikio Okazaki, Jiaming Lai, Nitin Das, Seiichiro Sugimoto, Thomas H. Tung, Steven B. Richardson, G. Alexander Patterson, Daniel Kreisel

JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 135 ( 6 ) 1398 - U336 2008年6月

CD4(+) T lymphocytes are not necessary for the acute rejection of vascularized mouse lung transplants 査読国際誌

Andrew E. Gelman, Mikio Okazaki, Jiaming Lai, Christopher G. Kornfeld, Friederike H. Kreisel, Steven B. Richardson, Seiichiro Sugimoto, Jeremy R. Tietjens, G. Alexander Patterson, Alexander S. Krupnick, Daniel Kreisel

JOURNAL OF IMMUNOLOGY 180 ( 7 ) 4754 - 4762 2008年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER ASSOC IMMUNOLOGISTS

Acute rejection continues to present a major obstacle to successful lung transplantation. Although CD4(+) T lymphocytes are critical for the rejection of some solid organ grafts, the role of CD4(+) T cells in the rejection of lung allografts is largely unknown. In this study, we demonstrate in a novel model of orthotopic vascularized mouse lung transplantation that acute rejection of lung allografts is independent of CD4(+) T cell-mediated allorecognition pathways. CD4(+) T cell-independent rejection occurs in the absence of donor-derived graft-resident hematopoietic APCs. Furthermore, blockade of the CD28/B7 costimulatory pathways attenuates acute lung allograft rejection in the absence of CD4(+) T cells, but does not delay acute rejection when CD4(+) T cells are present. Our results provide new mechanistic insight into the acute rejection of lung allografts and highlight the importance of identifying differences in pathways that regulate the rejection of various organs.

新しい生体肺移植術式:両側自己肺温存部分肺移植術 Bilateral native lung‐sparing lobar transplantation

杉本誠一郎, 伊達洋至, 杉本龍士郎, 山根正修, 豊岡伸一, 大藤剛宏, 青江基, 佐野由文

岡山医学会雑誌 119 ( 2 ) 107 - 112 2007年9月

記述言語：日本語出版者・発行元：岡山医学会

雑種成犬を用い、両側自己肺温存部分肺移植術を行った。ドナー犬の両肺ブロックから右グラフト(右中・下・縦隔葉)と左グラフト(左下葉)を分離し、レシピエント犬の解剖学的位置に移植した。手術は12例全例で成功した。急性期実験(〜180分)では、6頭全例が人工呼吸器下の3時間評価で良好な心肺機能を示し、3時間評価終了時の動脈血酸素分圧は589.0±14.4mmHg、平均肺動脈圧は35.8±3.9mmHgであった。慢性期実験(〜3週)は、6頭全例が気管内チューブを抜管でき、抜管後、レシピエントは正常の呼吸パターンを示した。5例(83%)は3週間生存した。胸部X線写真、肺動脈造影では、グラフトの拡張は良好で、動脈吻合部に狭窄を認めなかった。術後5日目に死亡した1例は肺静脈血栓症で、剖検時に止血部位の血栓形成を認めた。両側自己肺温存部分肺移植術は、脳死移植を待てず、かつ体格の大きい成人に対し、新たな選択肢になり得ることが示唆された。

DOI： 10.4044/joma.119.107

Bilateral native lung-sparing lobar transplantation in a canine model 査読国際誌

Seiichiro Sugimoto, Hiroshi Date, Ryujiro Sugimoto, Motoi Aoe, Yoshifumi Sano

JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 132 ( 5 ) 1213 - 1218 2006年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MOSBY, INC

Objective: Bilateral living-donor lobar lung transplantation has become an accepted approach in response to the cadaveric lung donor shortage. Because only one lobe is implanted in each chest cavity, this procedure is usually confined to patients of small size. The purpose of this study was to develop a technique of bilateral native lung - sparing lobar transplantation that can be applied to large adult patients.
Methods: Bilateral native lung - sparing lobar transplantation was performed in 12 pairs of dogs. In donor animals the right middle, lower, and cardiac lobes were separated as a right graft, and the left lower lobe was separated as a left graft. In recipient animals these 2 grafts were implanted in the natural anatomic position with sparing native right upper, left upper, and middle lobes. In an acute study (n = 6), transplanted graft function was assessed for 3 hours after ligation of the pulmonary artery branches to the native spared lobes. In a chronic study (n = 6) the immunosuppressed recipients were observed for 3 weeks to assess the quality of bronchial healing and long-term pulmonary function.
Results: Morphologic adaptation of the 2 grafts was found to be excellent. All 6 animals in the acute study showed excellent pulmonary function. Five of 6 animals in the chronic study survived for 3 weeks, with excellent pulmonary function and satisfactory bronchial healing.
Conclusion: Bilateral native lung - sparing lobar transplantation was technically possible and associated with excellent pulmonary function and good bronchial healing in a canine experimental model.

DOI： 10.1016/j.jtcvs.2006.07.012

Post-mortem administration of urokinase in canine lung transplantation from non-heart-beating donors 査読国際誌

Ryujiro Sugimoto, Hiroshi Date, Seiichiro Sugimoto, Mikio Okazaki, Keiju Aokage, Hidetoshi Inokawa, Motoi Aoe, Yoshifumi Sano

JOURNAL OF HEART AND LUNG TRANSPLANTATION 25 ( 9 ) 1148 - 1153 2006年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE INC

Background: We previously reported that post-mortem heparinization by closed-chest cardiac massage within 30 minutes after cardiac arrest is beneficial in lung transplantation (LTx) from non-heart-beating donors (NHBDs) by preventing formation of microthrombi. In this study, we evaluated the effects of post-mortem administration of urokinase 60 minutes after cardiac arrest.
Methods: Left LTx was performed in 12 pairs of mongrel dogs. Donors were sacrificed and left at room temperature for 2 hours. In Group I (n = 6), heparin sodium (1,000 U/kg) was administered intravenously 60 minutes after cardiac arrest, then closed-chest cardiac massage was performed for 1 minute to distribute the heparin. In Group 2 (n = 6), the donors were treated as in Group 1, except, in addition to heparin sodium, urokinase (120,000 U) was administered intravenously before and at the end of cardiac massage. After 2 hours of cardiac arrest, donor lungs were flushed with low-potassium dextran glucose solution. After left LTx, the right pulmonary artery was ligated, and recipients were followed up for 3 hours. Uni- and multivariate repeat analyses were performed to obtain statistical data.
Results: Group 2 had significantly better arterial oxygen tension, lower pulmonary vascular resistance and lower wet/dry weight ratio of the transplanted lung than Group 1. D-dimer level during the warm ischemia was significantly lower in Group 2 than in Group 1.
Conclusions: Post-mortem administration of urokinase along with heparin is beneficial in LTx from NHBDs by fibrinolytic action on already formed pulmonary microthrombi in the cadaver donor lungs.

DOI： 10.1016/j.healun.2006.07.005

Intraatrial extension of thyroid cancer: A case report 査読

S Sugimoto, H Doihara, Y Ogasawara, M Aoe, S Sano, N Shimizu

ACTA MEDICA OKAYAMA 60 ( 2 ) 135 - 140 2006年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

A 61-year-old man, who was diagnosed with superior vena cava syndrome by papillary thyroid carcinoma, was referred to our hospital. A bulky thyroid tumor with tracheal invasion extended from the left neck to the right atrium without distant metastases. The risk of sudden death due to airway occlusion, tumor embolism or obstruction of the tricuspid valve led us to elect surgery. Extended resection of thyroid cancer was performed with cardiopulmonary bypass. Peritoneal dissemination was found via laparotomy. A histologrical diagnosis of anaplastic carcinoma arising from transformation of papillary carcinoma was made. After the operation, bilateral ureteral occlusion by peritoneal dissemination and multiple lung metastases were detected. The patient died with acute renal failure on postoperative day 12. Intraatrial extension of thyroid cancer is rare, and only 12 cases have been reported in the literature. We present a case of thyroid cancer with intruatrial extension.

DOI： 10.18926/AMO/30734

出血性すい仮性嚢胞の破裂による腹腔内出血の1例

杉本誠一郎, 村上正和, 太田徹哉, 市原周治, 内藤稔, 清水信義

日本臨床外科学会雑誌 66 ( 12 ) 3053 - 3057 2005年12月

Thoracoscopic operation with local and epidural anesthesia in the treatment of pneumothorax after lung transplantation 査読国際誌

S Sugimoto, H Date, R Sugimoto, M Okazaki, M Aoe, Y Sano, N Shimizu

JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 130 ( 4 ) 1219 - 1220 2005年10月

長期追跡中(25年),リンパ節・骨転移再発治癒後に発症した乳癌肝転移の1例

杉本誠一郎, 土井原博義, 小笠原豊, 清水信義, 浜崎周次

乳癌の臨床 19 ( 5 ) 501 - 504 2004年10月

胸壁切除術にて診断の確定した甲状腺乳頭癌肋骨転移の1例

杉本誠一郎, 永広格, 青江基, 清水信義

日本呼吸器外科学会雑誌 18 ( 6 ) 751 - 754 2004年9月

記述言語：日本語出版者・発行元：特定非営利活動法人日本呼吸器外科学会

初回手術後16年目に胸壁切除術にて診断の確定した甲状腺乳頭癌肋骨転移の1切除例を経験したので報告する.症例は74歳, 男性.58歳時に他院で甲状腺良性腫瘍にて手術を施行された.2003年3月, 検診で胸部異常陰影を指摘され, 精査加療目的で当院へ紹介された.胸部X線写真では左第6肋骨の融解像を伴う長径6cmの腫瘤影を認め, 胸部CTでは径7.3×4.8cmの血流豊富な骨破壊性の腫瘤を認めた.CTガイド下針生検で転移性腺癌疑いと診断され, 全身を検索したが原発巣は認められなかった.左第6肋骨腫瘍と診断し, 胸壁切除・再建術 (メッシュ) を施行.病理組織学的に甲状腺濾胞型乳頭癌の肋骨転移と診断された.術後の経過は良好で術後18病日に退院した.甲状腺全摘・¹³¹I内照射を施行していないため, 今後も厳重な経過観察が重要である.

DOI： 10.2995/jacsurg.18.6_751

肺癌術後気管支断端ろうに対してフィブリン糊の粘膜下注入で閉鎖し得た1例

徳毛誠樹, 永広格, 杉本誠一郎, 田尾裕之, 源寛二, 清水信義

日本呼吸器外科学会雑誌 18 ( 6 ) 716 - 720 2004年9月

記述言語：日本語出版者・発行元：特定非営利活動法人日本呼吸器外科学会

症例は76歳, 男性.原発性肺癌に対して右上葉切除術施行後, 膿胸, MRSA肺炎, 急性呼吸不全を合併し人工呼吸管理を要した.人工呼吸管理中の術後28日目に気管支断端疲を発症したが, 全身状態不良で瘻孔が径約3mmと微小であったことから手術的加療ではなく内視鏡的加療を選択した.気管支鏡下に瘻孔周囲の健常粘膜下にフィブリン糊を注入し, 周囲粘膜を膨隆させることで瘻孔閉鎖を試みた.胸腔内洗浄も連日行い, 粘膜下注入を合計5回施行し, 最終的に約2週間で瘻孔を閉鎖し得た.瘻孔閉鎖後は人工呼吸器より離脱し, 膿胸も治癒したため術後174日目に近医に転院となった.<BR>この方法は術後の気管支断端瘻のうち微小瘻孔症例, 再手術不能症例においてまず試みられるべき有効な治療法であると考えられた.

DOI： 10.2995/jacsurg.18.6_716

乳房温存療法後に発症したBOOP様肺炎の3例

杉本誠一郎, 土井原博義, 高橋寛敏, 小笠原豊, 清水信義

乳癌の臨床 19 ( 4 ) 385 - 390 2004年8月

Mediastinal cyst with rim calcification 査読

Seiichiro Sugimoto, Takahiko Misao, Hideharu Nakano, Masataka Yamane

Japanese Journal of Thoracic and Cardiovascular Surgery 52 ( 5 ) 261 - 263 2004年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Japanese Association for Thoracic Surgery

A 58-year-old man who had been undergoing treatment for chronic pericarditis for 15 months was found to have a calcified mediastinal mass shadow on a chest X-ray and was referred to us for further study and treatment. Chest computed tomography and magnetic resonance imaging showed an anterior mediastinal multilocular tumor with rim calcification. Tumor markers were within normal limits. The patient was preoperatively diagnosed as having a calcified mediastinal cyst, and median sternotomy was performed to remove the cystic tumor and the surrounding thymic tissues. Histological examination revealed that the cyst wall consisted of dense fibrous tissue and calcification without epithelial cell lining on the inner surface. Thymic tissue was present around the cyst wall. Although we suspected a thymic cyst from the intraoperative findings, the final diagnosis was made as mediastinal cyst with rim calcification. We herein present a rare case of mediastinal cyst with rim calcification.

DOI： 10.1007/s11748-004-0121-0

CTにて術前診断しえた両側閉鎖孔ヘルニアの1例

杉本誠一郎, 萱野公一, 宮崎医津博, 西岡聖

日本臨床外科学会雑誌 64 ( 9 ) 2327 - 2332 2003年9月

記述言語：日本語出版者・発行元：Japan Surgical Association

患者は59歳,女性.下腹部痛,嘔吐を主訴に当院を受診した.下腹部全体に圧痛やBlumberg徴候,筋性防御を認めたが, Howship-Romberg徴候を認めなかった. CTにて腹水,小腸の拡張,両側閉鎖孔ヘルニアを認めた.両側閉鎖孔ヘルニア嵌頓による穿孔性腹膜炎と診断し,緊急開腹術を施行した.腹腔内には腹水を認め, Treitz靱帯から80cm肛門側の空腸が右閉鎖孔に嵌頓し穿孔していた.左側は容易に整復でき,穿孔を認めなかった.空腸楔状切除術を施行し,両側ヘルニア門を直接縫合閉鎖し卵巣を縫着した.経過は良好で術後24日目に退院した.<br>最近,閉鎖孔ヘルニアは術前診断される症例が増加しているが,両側閉鎖孔ヘルニアは稀で,本邦報告例は自験例を含め51例である.今回, CTにて術前診断しえた両側閉鎖孔ヘルニアの1例を経験したので報告した.

DOI： 10.3919/jjsa.64.2327

大網充填術を施行した吻合部潰よう穿孔の1例

杉本誠一郎, 萱野公一, 宮崎医津博, 西岡聖

日本臨床外科学会雑誌 64 ( 6 ) 1497 - 1501 2003年6月

記述言語：日本語出版者・発行元：Japan Surgical Association

最近,稀になった吻合部潰瘍穿孔を経験し,大網充填術にて良好な結果を得たので報告する.患者は40歳,男性. 18歳時に他院で十二指腸潰瘍穿孔にて胃切除術を施行. 2002年1月8日夕方から心窩部痛が出現し翌日21時に当院を受診.心窩部を中心に上腹部全体に圧痛・筋性防御を認めた. WBC 13,190/mm³, CRP 0.01mg/dlでgastrinは低値であった.胸部単純X線写真で左横隔膜下に腹腔内遊離ガス像を認め,腹部CTでは残胃や吻合部周囲に腹腔内遊離ガス像を認めた.汎発性腹膜炎と診断し緊急開腹術を施行.吻合部潰瘍穿孔(結腸前Billroth II法, Braun吻合後)を認め腹腔ドレナージ・大網充填術を施行した.術後プロトンポンプ阻害剤などを投与し,経過は良好で術後20病日に退院した.吻合部潰瘍穿孔に対し大網充填術は有用で緊急手術の選択肢の1つとなりうるが,成因に対する根治術ではなく再発の可能性があるため,再手術を念頭に置いた長期的な経過観察が重要である.

DOI： 10.3919/jjsa.64.1497

特発性小腸穿孔の1例

杉本誠一郎, 萱野公一, 宮崎医津博, 西岡聖, 内田発三

日本臨床外科学会雑誌 64 ( 1 ) 107 - 110 2003年1月

記述言語：日本語出版者・発行元：Japan Surgical Association

消化管穿孔の中で非外傷性小腸穿孔は比較的稀で,その原因も様々である.今回,われわれは稀な特発性小腸穿孔の1例を経験したので報告する.<br>症例は84歳,男性. 82歳時に胆嚢癌にて膵頭十二指腸切除術を施行された.腹部全体の圧痛・腹膜刺激症状を認め,胸部・腹部X線検査では腹腔内遊離ガス像,イレウス像を認めなかったが,腹部CTで腹腔内遊離ガス像を認めたため,汎発性腹膜炎と診断し緊急開腹術を施行した. Bauhin弁から約65cm口側に回腸穿孔を認め,回腸部分切除術を施行した.転移や再発を認めず,腹腔内の癒着やイレウスを認めなかった.組織学的にも粘膜,筋層,漿膜は断裂し,粘膜の漿膜側へのslidingを認めず,悪性所見や慢性の炎症所見を認めなかった.穿孔の原因を特定する所見はなく,特発性小腸穿孔と診断した.術後の経過は良好であったが,術後76日目に他病死した.

DOI： 10.3919/jjsa.64.107

へん平上皮癌を混在した肺原発大細胞性神経内分泌癌の1例

杉本誠一郎, 水谷尚雄, 萱野公一, 寺本滋

日本呼吸器外科学会雑誌 16 ( 4 ) 559 - 564 2002年5月

記述言語：日本語出版者・発行元：特定非営利活動法人日本呼吸器外科学会

症例は52歳男性.2000年1月, 胸部X線写真上, 右上肺野に急速に増大した腫瘤影を認め当院に紹介された.胸部CT上, 右上葉に11×10×9.0cm大の腫瘤を認め, 縦隔リンパ節の腫大は認めなかった.腫瘍マーカーはSLX, SCC, CYFRA, NSEが上昇していた.原発性肺癌を強く疑い, 同年1月25日に右上葉切除・ND2a・胸壁 (第3肋骨) 合併切除術を施行した.病理組織学的に扁平上皮癌の成分とLarge cell neuroendocrine carcinoma (LCNEC) の成分を混在しており, 扁平上皮癌を混在したLCNECと診断され, 術後病期はpT3N0M0, Stage II Bであった.術後経過は良好であり, 化学療法を施行せずに退院した.以後, 外来通院中であったが10カ月後に再発し死亡した.近年, LCNECの報告例は増加しているが, 扁平上皮癌を混在したLCNECは稀なため報告した.

DOI： 10.2995/jacsurg.16.4_559

再発・切除を繰り返した右胸壁原発spindle cell sarcomaの1例

杉本誠一郎, 萱野公一, 岩浅祐二郎, 水谷尚雄, 古城資久, 宮崎医津博, 長尾俊彦, 西岡聖, 内田発三

兵庫県全外科医会会誌 38 ( 1 ) 24 - 26 2002年3月

肺原発large cell neuroendocrine carcinomaの1例

杉本誠一郎, 中野秀治, 神野禎次, 多胡護, 山根正隆, 三竿貴彦

香川県立中央病院医学雑誌 20 45 - 48 2001年3月

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