Faculty Profiles - TOYOOKA Shinichi

Papers - TOYOOKA Shinichi

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チームアプローチで実現するゲノム医療と薬剤師の役割ゲノム医療におけるデータサイエンティストの役割と育成

冨田秀太, 森田瑞樹, 山下範之, 平沢晃, 豊岡伸一

薬学雑誌 140 ( 5 ) 657 - 661 2020.5

Language：Japanese Publisher：(公社)日本薬学会

次世代シークエンサーを用いた遺伝子パネル検査とそのデータ解析はゲノム医療の根幹であるにもかかわらず、その担い手であるデータサイエンティストが極端に不足している。基本的なデータ解析の流れを理解し、解析結果の解釈ができる人材育成が喫緊の課題である。遺伝子パネル検査の流れを概説するとともに、遺伝子変異量(TMB)の概念と遺伝子パネル検査におけるTMBの算出方法について解説した。

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01459&link_issn=&doc_id=20200528480008&doc_link_id=%2Fcs7yakug%2F2020%2F014005%2F010%2F0657-0661%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcs7yakug%2F2020%2F014005%2F010%2F0657-0661%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Computed tomography fluoroscopy-guided cutting needle biopsy of pulmonary nodules ≤8 mm: A retrospective study including 117 nodules. International journal

Yanqing Zhao, Yusuke Matsui, Takao Hiraki, Toshihiro Iguchi, Koji Tomita, Mayu Uka, Hideo Gobara, Shinichi Toyooka, Susumu Kanazawa

European journal of radiology 125 108903 - 108903 2020.4

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To evaluate the diagnostic yield and safety of computed tomography (CT) fluoroscopy-guided cutting needle biopsy (CNB) for pulmonary nodules ≤ 8 mm. METHOD: Data of CT fluoroscopy-guided CNB for pulmonary nodules ≤ 8 mm performed in a single institution were retrospectively analyzed. One hundred and seventeen biopsy procedures for 117 pulmonary nodules (mean size, 7.4 mm) in 114 patients were included in the study. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall diagnostic accuracy were calculated. Univariate analyses were performed to elucidate the risk factors for diagnostic failure (i.e., non-diagnostic, false-positive, or false-negative results). Complications were graded per the Clavien-Dindo Classification. RESULTS: One (0.9 %) non-diagnostic biopsy result was found. The diagnostic accuracy was 95.7 % (112/117). The sensitivity and specificity were 95.8 % (91/95) and 95.5 % (21/22), respectively. PPV and NPV were 98.9 % (91/92) and 87.5 % (21/24), respectively. Univariate analyses showed that nodules in the lower lobes (p = 0.006) and prone biopsy position (p = 0.021) were the significant risk factors for diagnostic failure. The incidence of pneumothorax requiring chest tube placement (Grade IIIa) was 6.8 % (8/117). No Grade IIIb or higher complications were observed. CONCLUSION: CT fluoroscopy-guided CNB for pulmonary nodules ≤ 8 mm showed a high diagnostic yield without severe complications.

DOI： 10.1016/j.ejrad.2020.108903

Plasma micro-RNA Levels are Associated with the Development of Chronic Lung Allograft Dysfunction after Bilateral Living-Donor and Cadaveric Lung Transplantation

T. Shiotani, S. Sugimoto, H. Yamamoto, D. Shimizu, K. Miyoshi, S. Otani, M. Okazaki, M. Yamane, T. Oto, S. Toyooka

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 39 ( 4 ) S194 2020.4

Publishing type：Research paper (scientific journal)

Copyright © 2020. Published by Elsevier Inc. PURPOSE: Micro-RNAs (miRNAs) regulate genes by selectively silencing their target messenger RNAs. Recently, serum levels of miRNA related to pulmonary fibrosis (miR-21 and miR-155), have been shown to be associated with the development of chronic lung allograft dysfunction (CLAD) after cadaveric lung transplantation (CLT). We investigated the relationship between miRNAs levels and CLAD after bilateral living-donor lobar lung transplantation (LDLLT) and CLT. METHODS: Blood samples were collected from a total of 70 patients who underwent bilateral LDLLT (n=39) and bilateral CLT (n=31), including patients with CLAD (the CLAD group, n=25) and those without CLAD (the non-CLAD group, n=45). Plasma miRNA levels (miR-21 and miR-155) were quantified using real-time PCR and compared between the two groups. The relationship between miRNA levels and the results of pulmonary function tests at the onset of CLAD was assessed. Appropriate cut-off values of miRNA levels were set for the diagnosis of CLAD. RESULTS: The median follow-up period was 3074 (1071-7523) days. Plasma miRNA levels of the CLAD group were significantly higher than those of the non-CLAD group (miR-21, P<0.001; miR-155, P=0.013) (Fig. 1). In the CLAD group, miRNA levels after LDLLT were comparable to those after CLT. Moreover, miRNA levels were significantly negatively correlated with the baseline values of forced expiratory volume in 1 second (FEV1) (miR-21, P<0.001; miR-155, P=0.039) and those of total lung cavity (TLC) (miR-21, P<0.001; miR-155, P=0.0012) (Fig. 2). An ROC analysis of the performance of miR-21 level as a marker of CLAD yielded an AUC of 0.94 at a threshold level of 6.51. Patients with miR-21 level≥6.51 showed significantly better CLAD-free survival than those with miR-21 level<6.51 (P<0.001) (Fig. 3). CONCLUSION: Plasma miRNA levels are associated with the development of CLAD after bilateral LDLLT and CLT, and might be a potential biomarker for the diagnosis of CLAD.

DOI： 10.1016/j.healun.2020.01.792

Prognostic Nutritional Index Negatively Correlates with Lung Allocation Score and Predicts Survival after Both Cadaveric and Living-Donor Lobar Lung Transplantation

H. Yamamoto, S. Sugimoto, T. Shiotani, K. Miyoshi, S. Otani, M. Okazaki, M. Yamane, T. Oto, S. Toyooka

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 39 ( 4 ) S311 2020.4

Publishing type：Research paper (scientific journal)

Copyright © 2020. Published by Elsevier Inc. PURPOSE: The preoperative nutritional status affects the clinical outcome of surgery. To predict the clinical outcome, a prognostic nutritional index (PNI) calculated using serum albumin levels (ALB) and total lymphocyte count (TLC) has been shown to be valuable in various fields of surgery. In this study, we investigated the relationship between PNI and lung allocation score (LAS) as well as the impact of PNI on outcomes of lung transplantation (LT), including cadaveric lung transplantation (CLT) and living-donor lobar lung transplantation (LDLLT). METHODS: Between June 2003 and August 2016, a total of 127 patients underwent LT at Okayama University Hospital, including 71 recipients of CLT and 56 recipients of LDLLT. The PNI was calculated by the following equation: PNI = (10 × ALB(g/dl)+(0.005 × TLC(/mm3)). The overall survival was evaluated by univariate analysis (the log rank test) and multivariate analysis (the Cox proportional hazard regression model) using preoperative factors, including sex, age, BMI, diagnosis, oxygen concentration, mechanical ventilation, tracheostomy, ECMO support, use of glucocorticoids, serum creatinine level, diabetes mellitus, LAS, and PNI. RESULTS: PNI was significantly negatively correlated with LAS (r=-0.3, P=0.00062) (Fig. 1A). The univariate analysis revealed that the overall survival was significantly worse in the patients with age>28 (P=0.047), BMI<24.2 (P=0.0098), LAS>58.04 (P=0.000072), PNI<46.35 (P=0.018) (Fig. 1B). The multivariate analysis demonstrated that age (P=0.00093), BMI (P=0.0024), and PNI (P=0.0047) were independent prognostic factors of worse outcome. In the subgroup analysis, low PNI is a significant prognostic factor of worse survival after CLT (P=0.015) (Fig. 1C) and LDLLT (P=0.041) (Fig. 1D). CONCLUSION: Preoperative nutritional evaluation using PNI could contribute to the assessment of LT recipient's severity and predict survival after both CLT and LDLLT.

DOI： 10.1016/j.healun.2020.01.700

Association between Histological Types and Enhancement of Dynamic CT for Primary Lung Cancer.

Shogo Fukuma, Takayoshi Shinya, Junichi Soh, Ryuichiro Fukuhara, Nanako Ogawa, Fumiyo Higaki, Takehiro Tanaka, Eiki Ichihara, Takao Hiraki, Shinichi Toyooka, Susumu Kanazawa

Acta medica Okayama 74 ( 2 ) 129 - 135 2020.4

Language：English Publishing type：Research paper (scientific journal)

The aim of this study was to explore enhancement patterns of different types of primary lung cancers on 2-phase dynamic computed tomography (CT). This study included 217 primary lung cancer patients (141 adenocarcinomas [ADs], 48 squamous cell carcinomas [SCCs], 20 small cell lung carcinomas [SCLCs], and 8 others) who were examined using a 2-phase dynamic scan. Regions of interest were identified and mean enhancement values were calculated. After excluding the 20 SCLCs because these lesions had different clinical stages from the other cancer types, the mean attenuation values and subtractions between phases were compared between types of non-small cell lung carcinomas (NSCLCs) using the Kruskal-Wallis test. Late phase attenuation and attenuation of the late minus unenhanced phase (LMU) of SCCs were significantly higher than those of ADs (p<0.05). To differentiate SCC and AD in the late phase, a threshold of 80.21 Hounsfield units (HU) gave 52.9% accuracy. In LMU, a threshold of 52.16 HU gave 59.3% accuracy. Dynamic lung CT has the potential to aid in differentiating among NSCLC types.

DOI： 10.18926/AMO/58271

Evaluation of Therapeutic Target Gene Expression Based on Residual Cancer Burden Classification After Neoadjuvant Chemotherapy for HER2-Negative Breast Cancer. International journal

Yuko Takahashi, Takayuki Iwamoto, Yoko Suzuki, Yukiko Kajiwara, Minami Hatono, Takahiro Tsukioki, Kengo Kawada, Mariko Kochi, Hirokuni Ikeda, Tadahiko Shien, Naruto Taira, Junji Matsuoka, Hiroyoshi Doihara, Shinichi Toyooka

Clinical breast cancer 20 ( 2 ) 117 - 124 2020.4

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Patients with residual disease usually have a poor prognosis after neoadjuvant chemotherapy for breast cancer. The aim of this study was to explore therapeutic targets and potential additional adjuvant treatments for patients with residual disease after standard neoadjuvant chemotherapy. PATIENTS AND METHODS: We retrieved publicly available complementary DNA microarray data from 399 human epidermal growth factor receptor 2 (HER2)-negative primary breast cancer samples from patients who underwent standard neoadjuvant chemotherapy. We analyzed the messenger RNA (mRNA) expression levels of key breast cancer markers and therapeutic target genes according to residual cancer burden (RCB) classification: RCB-0/I, RCB-II, and RCB-III. RESULTS: Among hormone receptor-positive samples, there were more luminal A tumors by PAM50 (Prediction Analysis of Microarray 50 [Prosigna], aka Prosigna Breast Cancer Prognostic Gene Signature Assay) in RCB-III than in RCB-0/I and RCB-II (P < .01). The mRNA expressions of ESR1 and PGR were significantly higher, and that of MKI67 was lower in RCB-II and RCB-III than in RCB-0/I. The mRNA expression of cyclin D1 was up-regulated in RCB-III and that of CDKN2A was down-regulated in RCB-III (P = .027 and < .01). Among triple-negative (TN) samples, RCB-III had higher clinical stage and more lymph node-positive samples than RCB-0/1 and RCB-II (P < .01). In both subtypes, VEGF-C expression was significantly higher in RCB-III than in RCB-0/I and RCB-II. CONCLUSION: In hormone receptor-positive breast cancer, biological features such as luminal A were associated with RCB; this trend was not observed in TN breast cancer. Further, some targeted therapies should be tested as new strategies after standard neoadjuvant chemotherapy in future clinical trials.

DOI： 10.1016/j.clbc.2019.07.001

CTガイド下生検では診断困難であった肺門部結節影

松原慧, 大谷真二, 高津史明, 富岡泰章, 津高慎平, 山本治慎, 塩谷俊雄, 難波圭, 諏澤憲, 三好健太郎, 山本寛斉, 岡崎幹雄, 杉本誠一郎, 山根正修, 大藤剛宏, 豊岡伸一

岡山医学会雑誌 132 ( 1 ) 46 - 46 2020.4

Pulmonary resection in a prone position for lung cancer invading the spine. Reviewed

Shunsaku Miyauchi, Junichi Soh, Kazuhiko Shien, Masato Tanaka, Hiromasa Yamamoto, Toshifumi Ozaki, Shinichi Toyooka

General thoracic and cardiovascular surgery 68 ( 3 ) 298 - 301 2020.3

Language：English Publishing type：Research paper (scientific journal)

The prone position is usually not selected for pulmonary resection. The intraoperative body position is an important issue in surgery for non-small cell lung cancer invading the spine because the standard intraoperative body position for a vertebrectomy is a prone position, while that for a pulmonary resection is a lateral decubitus position. Intraoperative changes in body position can cause several complications. Using an O-arm with a navigation system, a partial vertebrectomy was completed with the patient in a prone position thanks to the recognition of accurate surgical margins in the vertebral body; then, without changing the patient's body position, a lobectomy with systemic lymph node dissection was performed via a posterior approach. Especially for procedures requiring a wide resection of the chest wall, a prone position can be selected for a lobectomy with systemic lymph node dissection via a posterior approach without any significant difficulties.

DOI： 10.1007/s11748-019-01113-7

Influence of breast density on breast cancer risk: a case control study in Japanese women.

Keiko Nishiyama, Naruto Taira, Taeko Mizoo, Mariko Kochi, Hirokuni Ikeda, Takayuki Iwamoto, Tadahiko Shien, Hiroyoshi Doihara, Setuko Ishihara, Hiroshi Kawai, Kensuke Kawasaki, Yoichi Ishibe, Yutaka Ogasawara, Shinichi Toyooka

Breast cancer (Tokyo, Japan) 27 ( 2 ) 277 - 283 2020.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Mammography is the standard examination for breast cancer screening of woman aged ≥ 40 years. High breast density on mammography indicates that mammary gland parenchyma occupy a high percentage of the breast. The objective of this study was to investigate factors associated with breast density and the risk of high breast density for breast cancer. METHODS: A multicenter case-control study was performed in 530 patients and 1043 controls. Breast density was classified as C1-C4 using the Breast Imaging Reporting and Data System (BI-RADS). Clinical factors were obtained from questionnaires or medical records, and the influence of each factor (breast density, menopausal status, body mass index (BMI), parity, presence or absence of breastfeeding history, age at menarche, age at first birth, and familial history of breast cancer) on breast cancer risk in all patients was calculated as an age-adjusted odds ratio (OR). Multivariate logistic regression analyses were then performed in all patients and in pre- and postmenopausal and BMI-stratified groups using factors with a significant age-adjusted OR as adjustment factors. RESULTS: Age-adjusted ORs for breast cancer were significant for breast density, BMI, parity, and breast feeding, but not for age at menarche, age at first birth, or family history of breast cancer. In multivariate analysis, there was a significant correlation between breast density and breast cancer in postmenopausal women (OR for C1 vs. C2 1.90 [95% CI 1.34-2.70]; C1 vs. C4 2.85 [95% CI 1.10-7.16]). This correlation was also significant in patients in the third BMI quartile (22.3-24.5 kg/m2) (OR for C1 vs. C4 8.76 [95% CI 2.38-42.47]); and fourth BMI quartile (>24.5 kg/m2) (OR for C1 vs. C2 1.92 [95% CI 1.17-3.15]; C1 vs. C4 11.89 [95% CI 1.56-245.17]). CONCLUSION: Breast density on mammography is a risk factor for breast cancer after adjustment for other risk factors. This risk is particularly high in postmenopausal women and those with a high BMI.

DOI： 10.1007/s12282-019-01018-6

Embolization using hydrogel-coated coils for pulmonary arteriovenous malformations. Reviewed International journal

T Iguchi, T Hiraki, Y Matsui, H Fujiwara, J Sakurai, K Baba, S Toyooka, H Gobara, S Kanazawa

Diagnostic and interventional imaging 101 ( 3 ) 129 - 135 2020.3

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To prospectively evaluate the efficacy and safety of embolization using hydrogel-coated coils for the treatment of pulmonary arteriovenous malformations (PAVMs). MATERIALS AND METHODS: The outcomes of 21 PAVMs in 19 patients (3 men and 16 women; mean age, 58.8±15.2 [SD] years; age range 14-78 years) treated by venous sac embolization (VSE) with additional feeding artery embolization were prospectively evaluated. For VSE, using one or more 0.018-inch hydrogel-coated coils was mandatory. Recanalization and/or reperfusion were evaluated by pulmonary arteriography 1 year after embolization. RESULTS: The mean feeding artery and venous sac sizes were 4.0mm and 8.5mm, respectively. Embolization was successfully completed in 20/21 PAVMs, yielding a technical success rate of 95%. The feeding artery was also embolized in 17/20 successful PAVMs (85%). A technical failure occurred in one PAVM, where embolization was abandoned because of migration of one bare coil to the left ventricle. The mean numbers of hydrogel-coated coils and bare platinum detachable coils used for VSE were 3.3±2.1 (SD) (range, 1-8) and 4.4±3.9 (SD) (range, 1-17), respectively. The mean percentages of hydrogel-coated coils in number, length, and estimated volume were 42.9%, 33.3%, and 72.7% respectively. One patient with one PAVM was lost to follow-up after 3 months. Neither recanalization nor reperfusion was noted in the remaining 19 PAVMs (success rate, 19/19 [100%]). One grade 4 (coil migration) adverse event occurred, and it was treated without any sequelae. CONCLUSION: VSE using hydrogel-coated coils with additional feeding artery embolization is a safe and effective treatment for PAVM.

DOI： 10.1016/j.diii.2019.10.008

Right single lung transplantation using an inverted left donor lung: interposition of pericardial conduit for pulmonary venous anastomosis - a case report. Reviewed International journal

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 2020.2

Language：English

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

A Surgical Instructor Training Course for the Next Generation. Reviewed

Masaomi Yamane, Yasuhiro Mandai, Hideo Ino, Akihiro Matsukawa, Shinichi Toyooka

Acta medica Okayama 74 ( 1 ) 73 - 76 2020.2

Language：English

In 2016, Gunma University Hospital's Medical Accident Investigation Committee released a report reiterating the necessity of medical education and the need for surgeons to master non-technical skills. We designed a 17-h training course for surgical instructors, designed to teach participants how to sufficiently educate surgeon trainees and encourage their professional identity formation. A post-training survey showed that participants improved their awareness, and their behavioral changes led to favorable team performances. We then began offering a 3-h workshop focusing on the participants' experiences. We propose that the training course using participant narratives is required and effective to establish surgeons' self-reflection and professional identity as surgeons.

DOI： 10.18926/AMO/57956

肺内Solitary fibrous tumorの1例

三道幹大, 正岡佳久, 岡本聡一郎, 小河七子, 福原隆一郎, 田中高志, 稲井良太, 松井裕輔, 新家崇義, 金澤右, 田中健大, 大谷真二, 豊岡伸一

Japanese Journal of Radiology 38 ( Suppl. ) 72 - 72 2020.2

DV200 index for assessing RNA integrity in next-generation sequencing Reviewed International journal

Takehiro Matsubara, Junichi Soh, Mizuki Morita, Takahiro Uwabo, Shuta Tomida, Toshiyoshi Fujiwara, Susumu Kanazawa, Shinichi Toyooka, Akira Hirasawa

BioMed Research International 2020 9349132 - 9349132 2020.2

Language：English Publishing type：Research paper (scientific journal) Publisher：Hindawi

Poor quality of biological samples will result in an inaccurate analysis of next-generation sequencing (NGS). Therefore, methods to accurately evaluate sample integrity are needed. Among methods for evaluating RNA quality, the RNA integrity number equivalent (RINe) is widely used, whereas the DV200, which evaluates the percentage of fragments of >200 nucleotides, is also used as a quality assessment standard. In this study, we compared the RINe and DV200 RNA quality indexes to determine the most suitable RNA index for the NGS analysis. Seventy-one RNA samples were extracted from formalin-fixed paraffin-embedded tissue samples (n = 30), fresh-frozen samples (n = 25), or cell lines (n = 16). After assessing RNA quality using the RINe and DV200, we prepared two kinds of stranded mRNA sequencing libraries. Finally, we calculated the correlation between each RNA quality index and the amount of library product (1st PCR product per input RNA). The DV200 measure showed stronger correlation with the amount of library product than the RINe (R 2 = 0.8208 for the DV200 versus 0.6927 for the RINe). Receiver operating characteristic curve analyses revealed that the DV200 was the better marker for predicting efficient library production than the RINe using a threshold of >10 ng/ng for the amount of the 1st PCR product per input RNA (cutoff value for the RINe and DV200, 2.3 and 66.1%; area under the curve, 0.99 and 0.91; sensitivity, 82% and 92%; and specificity, 93% and 100%, respectively). Our results indicate that NGS libraries prepared using RNA samples with the DV200 value > 66.1% exhibit greater sensitivity and specificity than those prepared with the RINe values > 2.3. These findings suggest that the DV200 is superior to the RINe, especially for low-quality RNA, because it is a more consistent assessment of the amount of the 1st NGS library product per input.

DOI： 10.1155/2020/9349132

多発小腸GISTに対し手術を施行した神経線維腫症1型の1例

母里淑子, 重安邦俊, 吉岡貴裕, 永坂岳司, 原賀順子, 香川俊輔, 寺石文則, 豊岡伸一, 平沢晃, 藤原俊義

家族性腫瘍 19 ( 2 ) 77 - 82 2020.2

Language：Japanese Publisher：(一社)日本遺伝性腫瘍学会

症例は54歳男性.大量出血を伴う小腸多発GIST(Gastrointestinal stromal tumor)を認めて緊急入院となった.姉が神経線維腫症1型(neurofibromatosis type 1:NF1)と診断されており,患者にもおよそ20個の神経線維腫を疑う腫瘤とcafe au lait斑を6個以上認めたためNF1と診断した.出血コントロール目的に開腹手術を行ったが,GISTはおよそ20個多発しており,大量小腸切除を避けるために10mm以上の腫瘍のみ外科的切除を行い,多発微小腫瘍は経過観察とした不完全切除を選択した.切除標本の病理検査では紡錘形核と好酸性胞体を有する紡錘形細胞が密に錯綜する腫瘍を認め,免疫染色でKIT陽性.核分裂数は5以下/50HPFsであり低悪性度GISTと診断した.NF1に伴うGISTは比較的予後が良いとの報告もあるが,このような多発微小病変については明らかな治療指針がない.今後さらなる症例の集積と検討を要する.(著者抄録)

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

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 2020.1

Language：English

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

[Training Medical Staff with Basic Skills for Data Science in Genomic Medicine].

Shuta Tomida, Mizuki Morita, Noriyuki Yamashita, Akira Hirasawa, Shinichi Toyooka

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan 140 ( 5 ) 657 - 661 2020

Language：Japanese Publishing type：Research paper (scientific journal)

The development of specialized training programs for medical personnel, particularly nurses, clinical laboratory technicians, and pharmacists, is considered critical for the promotion of genomic medicine throughout Japan. Specifically, medical personnel skilled at analyzing and understanding high-throughput genomic data are in high demand. In this symposium, we will introduce the basic knowledge and skills necessary for processing genomic data.

DOI： 10.1248/yakushi.19-00217-2

肺移植におけるLiquid biopsy：ドナー由来血中遊離DNAとマイクロRNA

杉本誠一郎, 塩谷俊雄, 富岡泰章, 石上恵美, 石原恵, 諏澤憲, 三好健太郎, 大谷真二, 山本寛斉, 岡崎幹生, 山根正修, 豊岡伸一

移植 55 ( Supplement ) 242_2 - 242_2 2020

Language：Japanese Publisher：一般社団法人日本移植学会

【背景】低侵襲に血液や体液を採取し解析を行うLiquid biopsyは、癌領域では既に臨床応用され治療方針の決定に一役買っているが、移植領域ではまだ発展途上である。当科では肺移植におけるLiquid biopsyとして、ドナー由来血中遊離DNA（dd-cf-DNA）とマイクロRNA（miRNA）を標的にした研究を行ってきたため、その成果を報告する。【方法】ドナーとレシピエントの一塩基多型を比較してdd-cf-DNAを測定し、生体肺移植後の急性拒絶反応（AR）における診断的意義を検討した。次にレシピエントのみの検体で評価できるmiRNAを測定し、脳死・生体肺移植後の移植片慢性機能不全（CLAD）における診断的意義を検討した。【結果】dd-cf-DNAは、感染群（p=0.028）や安定群（p=0.001）よりAR群で有意に増加しており、生体肺移植後ARの診断に有用であった（Sci Rep 2018）。また線維化に関与するmiRNAが、非CLAD群よりCLAD群で有意に増加しており（p=0.008）、一秒量の変化率とも相関し（p=0.014）、CLAD診断に有用であった。【結論】肺移植のLiquid biopsy として、dd-cf-DNAは生体肺移植後ARの診断に、またmiRNAはCLADの診断に有用である。今後の臨床応用を目指して症例数の集積と簡便で精度の高い方法の開発が望まれる。

DOI： 10.11386/jst.55.supplement_242_2

当院における高齢者レシピエント症例の検討

富岡泰章, 大谷真二, 清水大, 松原慧, 山本治慎, 塩谷俊雄, 三好健太郎, 岡崎幹生, 杉本誠一郎, 山根正修, 豊岡伸一

移植 55 ( Supplement ) 253_1 - 253_1 2020

Language：Japanese Publisher：一般社団法人日本移植学会

【背景】日本における高齢者レシピエントの長期成績に関しての報告は少ない．今回当院における高齢者レシピエントの長期成績について後方視的に検討した.【対象と方法】1998年1月～2020年1月に施行した18歳以上の肺移植症例161例を対象とした.60歳以上の高齢群(H群：n=10)と18-59歳の非高齢群(L群:n=151)の2群に分けて,全生存期間(OS)およびCLAD発症までの期間(CFS)について解析を行った.【結果】H群ではL群と比較して片肺移植(p=0.03),間質性肺炎(p=0.02),男性(p=0.04)の割合が有意に多かった.BMI,ドナー年齢,総虚血時間,LASスコアには有意差は認めなかった.H群とL群の5年OSはそれぞれ51.9%と75.5%であり,有意差を認めた(p=0.02).H群とL群の5年CFSはそれぞれ53.3%と72.5%であった.サブグループ解析では，H群の片肺移植症例(5年:OS 25%)は両肺移植症例(5年OS:75%)と比較してOSが悪い傾向にあった(p=0.08)が，H群の両肺移植症例はL群の両肺移植症例(5年OS:74.2%)と比較しても同等の成績であった（p=0.5）.【結語】60歳以上のレシピエントの成績は60歳未満と比較し不良だが，両肺移植がより望ましい可能性が示唆された.

DOI： 10.11386/jst.55.supplement_253_1

Surgical treatment for N2 non-small cell lung cancer

Seiichiro Sugimoto, Shinichi Toyooka

Japanese Journal of Lung Cancer 59 ( 7 ) 1129 - 1133 2019.12

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：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

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