研究者詳細 - 杉本　誠一郎

論文 - 杉本　誠一郎

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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

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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

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(, 10.32388/74e1v5)

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。

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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

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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

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

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

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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

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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

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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

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

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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

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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

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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

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

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

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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

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