Faculty Profiles - CHEN-YOSHIKAWA Toyofumi

Managing recurrent thymic epithelial tumors after resection: outcomes and role of re-resection

Mizuno T., Chen-Yoshikawa T.F.

Mediastinum Vol. 8 2024.12

Publisher：Mediastinum

Thymic epithelial tumors (TETs) are rare neoplasms that include thymomas, thymic carcinomas (TCs), and thymic neuroendocrine neoplasms (TNENs). These three tumor categories differ in aggressiveness, the incidence of recurrence after resection, the pattern of recurrence, and survival outcomes. Owing to the tumor’s rarity, randomized trials have not been performed in the initial treatment setting. Furthermore, such trials have never been performed in recurrent cases after the initial resection. Thymomas have indolent characteristics, with a wide range of biological spectra compared to TCs and TNENs; therefore, several authors have reported favorable outcomes after re-resection for recurrent thymomas. Common recurrent sites are the local site and pleura, and recurrent disease progresses slowly after detection. Additionally, long-term survivors are sometimes observed after recurrence, and whether re-resections contribute to post-recurrent and cause-specific survival remains unclear. Multimodal therapies are indicated in patients with locally or regionally advanced recurrence, similar to those performed in the initial treatment settings. TCs and TNENs exhibit more aggressive behavior than thymomas. Surgical resection was performed on selected patients who experienced recurrence. Currently, there are no guidelines on selecting patients for re-resection. Therefore, it is most likely that each physician selects based on favorable factors, including the extent of disease, disease-free intervals, and histology. No evidence of nonsurgical treatments, such as radiotherapy or chemotherapy, has yet to be established. This review article summarizes the limited evidence on managing recurrent TETs after resection compared to thymomas, TCs, and TNENs, focusing on re-resection.

DOI： 10.21037/med-24-26

Adjuvant Chemotherapy Decisions in the Treatment of Lung Cancer Considering Nonrelapse Mortality: A Multicenter Study. International journal

Mitsue Kawahara, Yosuke Matsuura, Shota Nakamura, Fumie Kinoshita, Keiju Aokage, Tetsuhiko Asao, Toyofumi Fengshi Chen-Yoshikawa, Mingyon Mun

Clinical lung cancer 2024.12

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

BACKGROUND: Adjuvant chemotherapy (Adj) reduces recurrence and improves long-term survival in patients with surgically resected lung cancer. However, it has minimal impact on patients who die without relapsing. To optimize Adj indications, we aimed to identify factors associated with nonrelapse mortality (NRM). PATIENTS AND METHODS: This multicenter, retrospective, observational study enrolled patients with surgically resected with stages II-III non-small cell lung cancer. Multivariable Cox regression analysis was performed to identify the factors associated with NRM and early-NRM within 2 years of surgery and to stratify the enrolled patients. Adj administration rates and postoperative overall and recurrence-free survival rates were compared. Multivariable competing regression analysis with NRM as a competing risk was used to assess the cumulative incidence of lung cancer-associated death and recurrence. RESULTS: Through a scoring system assigning 1 point to each extracted factor (old age, male sex, poor performance status, nonadenocarcinoma, and occurrence of major complications), the 1,244 included patients were stratified into 3 groups based on scores of 0-5: A (0-1 points; n = 613), B (2-3 points; n = 549), and C (4-5 points; n = 62) with 53%, 26%, and 11% Adj administration, respectively. Although group A showed the highest overall and recurrence-free survival rates, competing regression analysis showed no significant differences in cumulative lung cancer-associated death and recurrence incidence between the groups. CONCLUSION: Better prognosis in group A was attributed to lower NRM and higher Adj administration rates. While proactive Adj may benefit group A, careful evaluation is warranted for group C to optimize Adj indication.

DOI： 10.1016/j.cllc.2024.12.009

症例感染巣切除後に再燃予防に抗真菌薬を投与した肺クリプトコッカス症の1例

藤村崇生, 中村彰太, 桐山亮太, 親松裕典, 岡川武日児, 深見惇, 新美誠次郎, 芳川豊史

胸部外科 Vol. 77 ( 13 ) page： 1135 - 1140 2024.12

[Pulmonary Cryptococcosis Treated with Antifungal Drugs After Surgical Resection:Report of a Case].

Takaki Fujimura, Shota Nakamura, Ryota Kiriyama, Hironori Oyamatsu, Takehiko Okagawa, Jun Fukami, Sejiro Niimi, Toyofumi Fengshi Chen-Yoshikawa

Kyobu geka. The Japanese journal of thoracic surgery Vol. 77 ( 13 ) page： 1135 - 1140 2024.12

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

The patient is an 81-year-old man. He underwent surgery for pancreatic body cancer in 201X and was followed up every six months with computed tomography (CT) imaging. A CT scan in 201X+5 showed a new nodule in S6 of the right lung. The nodule grew in the latter half of the year and was diagnostically resected on suspicion of being a metastatic lung tumor. A histopathological examination of the resected lung revealed pulmonary cryptococcosis. The postoperative course was uneventful, and the patient was treated with fluconazole 200 mg/day for six months. The patient is currently alive and recurrence-free three years after surgery. Pulmonary cryptococcosis can recur and may be complicated by meningitis. Postoperative antifungal therapy should be considered because of the poor prognosis of meningitis. Postoperative treatment should be performed with caution, especially in patients who are susceptible to infection, have positive preoperative serum cryptococcal antigen levels or have a high standardized uptake value (SUV) max on positron emission tomography (PET)-CT scanning, and are considered to have high fungal loads or activity.

Blood eosinophil count correlates with alveolar damage in emphysema-predominant COPD

Nakamura S., Wakahara K., Majima S., Yokoi E., Fukutani E., Otsuki R., Iwano S., Chen-Yoshikawa T.F., Kinoshita F., Abe T., Sashio T., Kimura T., Izuhara K., Hashimoto N., Ishii M., Hasegawa Y.

BMC Pulmonary Medicine Vol. 24 ( 1 ) 2024.12

Publisher：BMC Pulmonary Medicine

Background: Although blood eosinophil count is recognized as a useful biomarker for the management of chronic obstructive pulmonary disease (COPD), the impact of eosinophils in COPD has not been fully elucidated. Here we aimed to investigate the relationships between the blood eosinophil count and various clinical parameters including lung structural changes. Methods: Ninety-three COPD patients without concomitant asthma were prospectively enrolled in this study. Blood eosinophil count, serum IgE level, serum periostin level, and chest computed tomography (CT) scans were evaluated. Eosinophilic COPD was defined as COPD with a blood eosinophil count ≧ 300/µL. We examined the correlation between the blood eosinophil count and structural changes graded by chest CT, focusing specifically on thin airway wall (WT thin) and thick airway wall (WT thick) groups. In a separate cohort, the number of eosinophils in the peripheral lungs of COPD patients with low attenuation area (LAA) on chest CT was assessed using lung resection specimens. Results: The mean blood eosinophil count was 212.1/µL, and 18 patients (19.3%) were categorized as having eosinophilic COPD. In the whole group analysis, the blood eosinophil count correlated only with blood white blood cells, blood basophils, C-reactive protein level, and sputum eosinophils. However, the blood eosinophil count positively correlated with the percentage of LAA and negatively correlated with the diffusing capacity for carbon monoxide in the WT thin group. Lung specimen data showed an increased number of eosinophils in the peripheral lungs of COPD patients with LAA on chest CT scans compared to normal controls. Conclusions: Some COPD patients without concomitant asthma showed a phenotype of high blood eosinophils. Alveolar damage may be related to eosinophilic inflammation in patients with COPD without asthma and thickening of the central airway wall.

DOI： 10.1186/s12890-024-03320-2

A case of peribronchiolar metaplasia of the lung appearing as a solid nodule on computed tomography.

綜説小児の肺移植の現状と未来

芳川豊史

小児科 Vol. 65 ( 11 ) page： 1155 - 1163 2024.11

Yuri Takada, Shota Nakamura, Yoshito Imamura, Shoji Okado, Yuji Nomata, Hiroki Watanabe, Yuka Kadomatsu, Harushi Ueno, Taketo Kato, Tetsuya Mizuno, Iori Kojima, Toyofumi Fengshi Chen-Yoshikawa

Nagoya journal of medical science Vol. 86 ( 4 ) page： 720 - 725 2024.11

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

Peribronchiolar metaplasia is an uncommon lesion characterized by fibrosis and bronchiolar epithelial cell proliferation along the peribronchiolar alveolar walls, primarily in response to bronchiolar and peribronchiolar injuries. Peribronchiolar metaplasia usually appears as ground glass nodules or sub-solid nodules on computed tomography. However, we present an exceptional case of peribronchiolar metaplasia that appeared as a solitary solid nodule on computed tomography. A 62-year-old woman with conjunctival icterus was diagnosed with ampullary cancer and nodal metastasis. A solid predominant nodule (0.7 cm maximum diameter) in the left lower lobe was identified on computed tomography, requiring accurate differentiation between primary lung cancer and pulmonary metastasis. Due to the location, histological confirmation via transbronchial biopsy was not feasible. Hence, the patient underwent surgery for both diagnosis and treatment. The pathological findings revealed the growth of columnar epithelium containing ciliated cells replacing alveolar epithelium in the bronchioloalveolar wall with no malignant component. The final pathological diagnosis of the lesion was peribronchiolar metaplasia. This unique case highlights an atypical presentation of peribronchiolar metaplasia as a solitary solid nodule on computed tomography. Recognizing that peribronchiolar metaplasia can also manifest as solid nodules, as illustrated in our current case, is essential.

DOI： 10.18999/nagjms.86.4.720

Impact of the expanded indication of robot-assisted thoracic surgery for mediastinal tumors.

Taketo Kato, Hiroki Watanabe, Yuta Kawasumi, Yuka Kadomatsu, Harushi Ueno, Shota Nakamura, Tetsuya Mizuno, Toyofumi Fengshi Chen-Yoshikawa

General thoracic and cardiovascular surgery 2024.10

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

OBJECTIVE: Following the introduction of robot-assisted thoracoscopic surgery (RATS) as a health insurance-covered treatment in Japan, we investigated the current status and impact of the expansion of the indications for RATS for mediastinal tumors. METHODS: Between 2018 and 2022, 209 cases of total mediastinal tumor resection were performed in our hospital. The study period was divided into the first half (January 2018 to June 2020) and the second half (July 2020 to December 2022), and perioperative parameters were compared between the two groups. RESULTS: Ninety-six surgical procedures were performed in the first half and 113 in the second half. The percentage of RATS approach was significantly higher in the second half compared with the first half (P < 0.001). Indications for RATS in the second half compared with the first half were significantly increased in patients with stage II (P < 0.001) and stage III (P = 0.026) thymomas, tumor diameter ≥ 50 mm (P < 0.011), and patients undergoing extended thymectomy for myasthenia gravis (P < 0.009). In respect of short-term postoperative parameters, the estimated intraoperative blood loss (P < 0.035), postoperative drain duration (P < 0.037), and postoperative hospital stay (P < 0.011) were significantly lower in the second half than in the first half. CONCLUSIONS: RATS has recently been expanded for mediastinal tumors with improved short-term outcomes in our hospital after health insurance was applied in Japan. In the future, it will be necessary to discuss the further expansion of its indications by taking into account safety and long-term outcomes.

DOI： 10.1007/s11748-024-02093-z

Virtual thoracoscopic imaging for accurate pulmonary nodule localization: clinical experience.

Yuka Kadomatsu, Megumi Nakao, Shoji Okado, Harushi Ueno, Taketo Kato, Shota Nakamura, Toyofumi Fengshi Chen-Yoshikawa

Surgery today 2024.10

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

The increasing detection of small pulmonary nodules on computed tomography (CT) warrants simple and effective nodule localization methods. We describe our clinical experience using an experimental computer that displays virtual thoracoscopic images. This device constructs three-dimensional images from preoperative CT scans and simulates the deflated lung parenchyma in the lateral decubitus position. Five patients underwent lung resection using this technology. The device provided images that closely resembled actual thoracoscopic images in all cases. This method addresses the limitations of other localization techniques such as allergic reactions and mechanical marker-related complications. The method only requires preoperative CT images, and the process is semi-automatically performed by specifying the nodule location, thoracoscopic camera insertion site, and camera angle. This study is still in the preliminary phase and has several limitations. However, this method has the potential to accurately predict nodule locations and eliminate the many risks associated with other techniques.

DOI： 10.1007/s00595-024-02945-4

肺移植患者を取り巻く呼吸ケアの目標と実情

芳川豊史, 石塚全

日本呼吸ケア・リハビリテーション学会誌 Vol. 34 ( supplement ) page： 125s_2 - 125s_2 2024.10

Current Status and Future Perspectives of Preoperative and Intraoperative Marking in Thoracic Surgery. International journal

Toyofumi Fengshi Chen-Yoshikawa, Shota Nakamura, Harushi Ueno, Yuka Kadomatsu, Taketo Kato, Tetsuya Mizuno

Cancers Vol. 16 ( 19 ) 2024.9

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

The widespread implementation of lung cancer screening and thin-slice computed tomography (CT) has led to the more frequent detection of small nodules, which are commonly referred to thoracic surgeons. Surgical resection is the final diagnostic and treatment option for such nodules; however, surgeons must perform preoperative or intraoperative markings for the identification of such nodules and their precise resection. Historically, hook-wire marking has been performed more frequently worldwide; however, lethal complications, such as air embolism, have been reported. Therefore, several surgeons have recently attempted to develop novel preoperative and intraoperative markers. For example, transbronchial markings, such as virtual-assisted lung mapping and intraoperative markings using cone-beam computed tomography, have been developed. This review explores various marking methods that have been practically applied for a better understanding of preoperative and intraoperative markings in thoracic surgery. Recently, several attempts have been made to perform intraoperative molecular imaging and dynamic virtual three-dimensional computed tomography for the localization, diagnosis, and margin assessment of small nodules. In this narrative review, the current status and future perspectives of preoperative and intraoperative markings in thoracic surgery are examined for a better understanding of these techniques.

DOI： 10.3390/cancers16193284

2D/3D deformable registration for endoscopic camera images using self-supervised offline learning of intraoperative pneumothorax deformation Reviewed

Oya T., Kadomatsu Y., Chen-Yoshikawa T.F., Nakao M.

Computerized Medical Imaging and Graphics Vol. 116 2024.9

Language：English Publisher：Computerized Medical Imaging and Graphics

Shape registration of patient-specific organ shapes to endoscopic camera images is expected to be a key to realizing image-guided surgery, and a variety of applications of machine learning methods have been considered. Because the number of training data available from clinical cases is limited, the use of synthetic images generated from a statistical deformation model has been attempted; however, the influence on estimation caused by the difference between synthetic images and real scenes is a problem. In this study, we propose a self-supervised offline learning framework for model-based registration using image features commonly obtained from synthetic images and real camera images. Because of the limited number of endoscopic images available for training, we use a synthetic image generated from the nonlinear deformation model that represents possible intraoperative pneumothorax deformations. In order to solve the difficulty in estimating deformed shapes and viewpoints from the common image features obtained from synthetic and real images, we attempted to improve the registration error by adding the shading and distance information that can be obtained as prior knowledge in the synthetic image. Shape registration with real camera images is performed by learning the task of predicting the differential model parameters between two synthetic images. The developed framework achieved registration accuracy with a mean absolute error of less than 10 mm and a mean distance of less than 5 mm in a thoracoscopic pulmonary cancer resection, confirming improved prediction accuracy compared with conventional methods.

DOI： 10.1016/j.compmedimag.2024.102418

Excess mortality in COVID-19-affected solid organ transplant recipients across the pandemic Reviewed

特集低酸素に打ち克つ Ⅳ.低酸素に対する対処法-適応疾患と対処の実際肺移植 Invited

芳川豊史

呼吸器ジャーナル Vol. 72 ( 3 ) page： 478 - 484 2024.8

Yamanaga S., Shimata K., Ohfuji S., Yoshikawa M., Natori Y., Hibi T., Yuzawa K., Egawa H., Unagami K., Ishida H., Omoto K., Kasahara M., Uchida H., Sakamoto S., Futamura K., Nishikawa K., Imamura R., Nakazawa S., Hatano E., Ito T., Masano Y., Nishihira M., Hirata Y., Sakuma Y., Onishi Y., Yokoyama N., Yamamoto S., Yamada Y., Ogura Y., Kurata N., Uchida J., Kabei K., Iwamoto H., Ikeda C., Shinoda K., Yoshiike M., Hotta K., Hidaka Y., Iwami D., Ishii Y., Kamiyama M., Yoshizumi T., Kosai-Fujimoto Y., Kobayashi T., Motoyama K., Yamamoto M., Asai T., Tasaki M., Kenmochi T., Ito T., Tokodai K., Fujio A., Tsukamoto Y., Watanabe T., Akamatsu N., Yamashina S., Ishii D., Kitajima K., Yamada Y., Mitsuke A., Sakaguchi T., Nakamura M., Tomita Y., Nakamura Y., Ishimoto T., Ohdan H., Tanimine N., Fujiwara T., Yanagihara M., Hatakeyama S., Takai M., Nose K., Kikuchi T., Mori Y., Araki M., Sekito T., Nishimura S., Tanabe T., Igarashi Y., Hidaka S., Watanabe M., Ariyoshi Y., Hasegawa Y., Kamiyama M., Yoneda T., Shimizu T., Nishikawa K., Fukumoto T., Kuramitsu K., Kato M., Saito M., Shinkai M., Usui H., Sato M., Eguchi H., Imamura H., Kobayashi S., Soejima Y., Mita A., Kobayashi T.

American Journal of Transplantation Vol. 24 ( 8 ) page： 1495 - 1508 2024.8

Language：English Publisher：American Journal of Transplantation

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

Efficacy of Immune Checkpoint Inhibitors in Postoperative Recurrence of Wild-type EGFR Non-Small Cell Lung Cancer. Reviewed International journal

Yoshito Imamura, Taketo Kato, Yuji Nomata, Shoji Okado, Hiroki Watanabe, Yuta Kawasumi, Keita Nakanishi, Yuka Kadomatsu, Harushi Ueno, Shota Nakamura, Tetsuya Mizuno, Tetsunari Hase, Ichidai Tanaka, Makoto Ishii, Hiroshi Yatsuya, Toyofumi Fengshi Chen-Yoshikawa

Anticancer research Vol. 44 ( 8 ) page： 3451 - 3461 2024.8

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND/AIM: Immune checkpoint inhibitors (ICIs) have been widely used in the treatment of non-small cell lung cancer (NSCLC), but specific outcomes of ICIs treatment among patients with postoperative recurrence of NSCLC remain unclear. The objective of the study was to compare the efficacy of ICIs and chemotherapy with conventional chemotherapy only in patients with postoperative recurrence of epidermal growth factor receptor (EGFR) wild-type NSCLC. PATIENTS AND METHODS: A retrospective analysis was performed on patients who underwent anatomical lung resection at the Nagoya University Hospital and were treated for postoperative recurrence of wild-type EGFR NSCLC. This study evaluated the prognosis for postoperative recurrence, including ICIs treatment and other clinicopathological factors. RESULTS: Of the 83 patients included in the analysis, 20 patients underwent chemotherapy and 63 patients underwent chemotherapy combined with ICIs. The combination of ICIs and chemotherapy significantly prolonged survival after recurrence (median survival: 33.1 months vs. 22.0 months, p=0.01). In the ICIs group, no significant differences in survival were detected between patients with different programmed death ligand 1 (PD-L1) status (Tumor Proportion Scores: <1%, 1%-49%, ≥50%, p=0.27). Multivariate analysis revealed that postoperative distant recurrence was a significant poor prognostic factor for survival after recurrence (HR=1.85, 95% CI=1.06-3.25, p=0.03), and combining ICIs with chemotherapy significantly improved survival after recurrence (HR=0.43, 95% CI=0.24-0.78, p<0.01). CONCLUSION: Combination of ICIs with chemotherapy significantly prolonged survival of postoperative recurrence with wild-type EGFR NSCLC regardless of PD-L1 status.

DOI： 10.21873/anticanres.17165

Transcriptomic profiling of a late recurrent nuclear protein in testis carcinoma of the lung 14 years after the initial operation: a case report Reviewed

Taketo Kato, Hironori Oyamatsu, Yuki Hanamatsu, Heng Huang, Shoji Okado, Yoshito Imamura, Yuji Nomata, Hiroki Watanabe, Yuka Kadomatsu, Harushi Ueno, Shota Nakamura, Tetsuya Mizuno, Tetsunari Hase, Tamotsu Takeuchi, Toyofumi Fengshi Chen-Yoshikawa

Translational Lung Cancer Research Vol. 13 ( 7 ) page： 1756 - 1762 2024.7

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

Background: Nuclear protein in testis (NUT) carcinoma (NC) of the lung is a rare cancer that occurs mainly in young adolescents and adults. NC is genetically characterized by NUTM1 rearrangements, which usually take the form of BRD4-NUT fusions. The prognosis for NC is dismal, and treatment with conventional chemotherapeutic regimens is ineffective. Case Description: We herein describe the case of a 53-year-old woman with recurrent NC of the lung 14 years after surgery for nasal cavity cancer. Chest computed tomography revealed a 5.5-cm tumor in the lower lobe of the left lung. We completely resected the recurrent lung NC via thoracotomy. Immunohistochemistry (IHC) of the lung and nasal cavity cancers showed diffuse strong expression of NUT. RNA-seq of the lung NC revealed NUTM1 rearrangement, with a fusion of BRD4 exon 10 to NUTM1 exon 4. This breakpoint has never been reported before. In addition, IHC revealed elevated expression of parathyroid hormone-like hormone in the lung NC but not in the nasal cavity NC, indicating that the lung and nasal cavity NCs were metachronous multiple primary cancers. Conclusions: We experienced a rare recurrence of lung NC 14 years after the initial surgery. The BRD4-NUT fusion consisted of a new breakpoint. Furthermore, the expression pattern of parathyroid hormone-like hormone (PTHLH) suggested that the NCs in the nasal cavity and lung may be metachronous multiple lung cancers. This extremely rare case highlighted the possibility of identifying less malignant NCs in patients with poorly differentiated tumors via fusion gene analysis and the need to develop more effective treatment strategies for this malignancy.

DOI： 10.21037/tlcr-24-259

Endobronchial Closure for Peripheral Pulmonary Air Leakage. Reviewed International journal

Shoji Okado, Shota Nakamura, Keiyu Sato, Harushi Ueno, Takayasu Ito, Kazuhide Sato, Shotaro Okachi, Yohei Uehara, Misa Matsumoto, Natsumi Shimazaki, Katsuya Miyagawa, Toyofumi Fengshi Chen-Yoshikawa

Respiration 2024.7

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: A minimally invasive alternative to surgery for treating pneumothorax has been developed, aiming to reduce risks while maintaining efficacy. This study conducted basic experiments using Ex vivo and in vivo pig lung employing a super-thin catheter for treatment. This new device injects fibrin glue directly into the responsible lesion to close the air leak, which has two features; thin design and double-lumen. METHODS: The experimental setup involved utilizing trachea and both lung specimens from pigs under positive pressure ventilation. To simulate pneumothorax, artificial fistulas were created on the lung surfaces. The super-thin catheter, guided through a bronchoscope near the fistula, was used to embolize the peripheral bronchus by injecting a fibrin preparation. Then, an air leak test was conducted afterward to assess the efficacy of the treatment. Additionally, a similar pneumothorax model was induced in alive pig under general anesthesia to evaluate its curability. RESULTS: In the extracted pig lungs, embolization was performed in 21 cases, resulting in the cessation of air leaks in 19 cases, corresponding to a 90.5% cure rate. Notably, no major adverse events occurred with the treatment devices. Similarly, in living pigs, pneumothorax was successfully treated, with no recurrence observed up to the seventh postoperative day. CONCLUSION: The novel treatment device utilizing a super-thin catheter offers a minimally invasive and highly curative option for pneumothorax. These promising results suggest the potential for further development and human clinical trials, which could revolutionize the treatment of pneumothorax, reducing risks and improving outcomes.

DOI： 10.1159/000540652

Future directions for xenotransplantation in lungs. Invited Reviewed International journal

Hidetaka Hara, Hisashi Sahara, Toyofumi Fengshi Chen-Yoshikawa

Current opinion in organ transplantation Vol. 29 ( 5 ) page： 332 - 339 2024.7

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

PURPOSE OF REVIEW: Advancements in preclinical xenotransplant studies have opened doors for clinical heart and kidney xenotransplantation. This review assesses recent progress in lung xenotransplantation research and its potential clinical implications. RECENT FINDINGS: The efficacy of the humanized von Willebrand factor in reducing platelet sequestration in ex-vivo and in-vivo lung xenotransplant models was showcased. Combining human tissue factor pathway inhibitor and CD47 expression with selectin and integrin inhibition delayed neutrophil and platelet sequestration. Enhanced expression of human complement regulatory proteins and thrombomodulin in genetically engineered pig lungs improved graft survival by reducing platelet activation and modulating coagulation disruptions. Knocking out the CMAH gene decreased antibody-mediated inflammation and coagulation activation, enhancing compatibility for human transplantation. Furthermore, CMAH gene knockout in pigs attenuated sialoadhesin-dependent binding of human erythrocytes to porcine macrophages, mitigating erythrocyte sequestration and anemia. Meanwhile, in-vivo experiments demonstrated extended survival of xenografts for up to 31 days with multiple genetic modifications and comprehensive treatment strategies. SUMMARY: Experiments have uncovered vital insights for successful xenotransplantation, driving further research into immunosuppressive therapy and genetically modified pigs. This will ultimately pave the way for clinical trials designed to improve outcomes for patients with end-stage lung disease.

DOI： 10.1097/MOT.0000000000001161

Multidisciplinary treatment of giant thymoma, paving the way to complete surgical resection: a case report. Reviewed International journal

Ayaka Makita, Shota Nakamura, Tomohiro Setogawa, Yoshito Imamura, Shoji Okado, Yuji Nomata, Hiroki Watanabe, Yuta Kawasumi, Yuka Kadomatsu, Harushi Ueno, Taketo Kato, Tetsuya Mizuno, Toyofumi Fengshi Chen-Yoshikawa

Surgical case reports Vol. 10 ( 1 ) page： 170 - 170 2024.7

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: A multidisciplinary treatment approach is recommended for patients with extensive, advanced, or recurrent thymomas. However, detailed treatment strategies, such as chemotherapy regimens and optimal surgical procedures, are still under debate. CASE PRESENTATION: We report a case of gigantic locally advanced thymoma. A 70-year-old male was referred to our hospital following the detection of abnormal chest shadows. Chest X-ray and computed tomography (CT) scans revealed a 21-cm mass in the anterior mediastinum, encircling the pulmonary hilum and extending into the left thoracic cavity. PET/CT showed increased 18F-fluorodeoxyglucose uptake at the tumor site. Based on a trans-percutaneous CT-guided needle biopsy, the tumor was diagnosed as a Type B2 thymoma at the clinical IIIA stage. The patient underwent four cycles of preoperative induction chemotherapy, including cisplatin, doxorubicin, and methylprednisolone (CAMP), resulting in a partial response; the tumor shrank to 12 cm and FDG uptake decreased. Considering the patient's age and comorbidities, we performed total thymectomy, along with partial resections of the parietal, mediastinal and visceral pleura, pericardium, and left upper lobectomy. This approach achieved complete histological resection, mitigating the risk of recurrence. Pathological analysis confirmed a thymoma, ypT3 (lung) N0M0 stage IIIA, with no malignancy in the pericardial or pleural effusions. No recurrence was detected 9 months post-surgery. CONCLUSIONS: We report a case of giant thymoma successfully treated with multidisciplinary strategy. Surgical treatment alone may not have achieved complete resection, but after inducing significant tumor shrinkage with preoperative CAMP therapy, we were able to achieve complete resection. This treatment strategy may be effective in large thymoma cases.

DOI： 10.1186/s40792-024-01970-2

Development of a machine learning-based risk model for postoperative complications of lung cancer surgery. Reviewed

Yuka Kadomatsu, Ryo Emoto, Yoko Kubo, Keita Nakanishi, Harushi Ueno, Taketo Kato, Shota Nakamura, Tetsuya Mizuno, Shigeyuki Matsui, Toyofumi Fengshi Chen-Yoshikawa

Surgery today 2024.6

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To develop a comorbidity risk score specifically for lung resection surgeries. METHODS: We reviewed the medical records of patients who underwent lung resections for lung cancer, and developed a risk model using data from 2014 to 2017 (training dataset), validated using data from 2018 to 2019 (validation dataset). Forty variables were analyzed, including 35 factors related to the patient's overall condition and five factors related to surgical techniques and tumor-related factors. The risk model for postoperative complications was developed using an elastic net regularized generalized linear model. The performance of the risk model was evaluated using receiver operating characteristic curves and compared with the Charlson Comorbidity Index (CCI). RESULTS: The rate of postoperative complications was 34.7% in the training dataset and 21.9% in the validation dataset. The final model consisted of 20 variables, including age, surgical-related factors, respiratory function tests, and comorbidities, such as chronic obstructive pulmonary disease, a history of ischemic heart disease, and 12 blood test results. The area under the curve (AUC) for the developed risk model was 0.734, whereas the AUC for the CCI was 0.521 in the validation dataset. CONCLUSIONS: The new machine learning model could predict postoperative complications with acceptable accuracy. CLINICAL REGISTRATION NUMBER: 2020-0375.

DOI： 10.1007/s00595-024-02878-y

Updated outcomes of surgical treatment for recurrent thymic tumour: a report from the Japanese nationwide database Reviewed

Mizuno T., Chen-Yoshikawa T.F., Yoshino I., Okumura M., Ikeda N., Kuroda K., Maniwa Y., Kanzaki M., Suzuki M.

Interdisciplinary Cardiovascular and Thoracic Surgery Vol. 38 ( 6 ) 2024.6

Authorship：Corresponding author Language：English Publisher：Interdisciplinary Cardiovascular and Thoracic Surgery

OBJECTIVES: This study aimed to analyse the surgical outcomes for recurrent thymic epithelial tumours and identify the factors associated with post-recurrence survival, using an updated Japanese nationwide database. METHODS: The cohort that developed recurrence after the initial resection was extracted from an updated database of patients whose thymic epithelial tumours were treated surgically between 1991 and 2010. Furthermore, we reviewed clinicopathological and prognostic factors of re-resected cases. Post-recurrence survival outcomes and cause-specific deaths in non-re-resected cases were also reviewed. RESULTS: We enrolled 191 patients who underwent re-resection and 259 patients who did not. In the surgery group, more patients with early stage disease, less aggressive World Health Organization (WHO) histological classification, initial complete resection and shorter recurrence-free intervals were included. Non-thymic carcinoma, absence of preoperative treatment, longer recurrent-free interval, single-site recurrence and R0-1 re-resection were all significantly favourable prognostic factors for post-recurrence survival in the surgery group, according to univariable analyses. Non-thymic carcinoma histology, longer recurrence-free interval and R0-1 re-resection were identified as independent prognostic factors according to multivariable analysis. The post-recurrence survival of the entire cohort with R2 re-resection was significantly better than that of the non-surgery group, although it was not demonstrated that patients with thymoma who underwent R2 re-resection had significantly better post-recurrence and lower cause-specific death. CONCLUSIONS: R0-1 re-resection was newly identified as a prognostic factor after re-resection, in addition to non-thymic carcinoma histological classification and longer recurrence-free intervals, as documented in the initial report.

DOI： 10.1093/icvts/ivae064

Bronchial occlusion with endobronchial Watanabe spigots using a two-scope technique for massive haemoptysis. Reviewed International journal

Tomoya Baba, Takayasu Ito, Yoshiki Sato, Shunsaku Hayai, Junji Koyama, Shota Nakamura, Yoshiyuki Tokuda, Toyofumi Fengshi Chen-Yoshikawa, Makoto Ishii

Respirology case reports Vol. 12 ( 6 ) page： e01405 2024.6

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

Massive haemoptysis is a life-threatening condition whose cause needs to be identified rapidly so that prompt interventions can ensue. Bronchial occlusion with endobronchial Watanabe spigots (EWSs) may be useful when endovascular treatment or surgery proves to be difficult. An 84-year-old woman developed massive haemoptysis during percutaneous mitral valve repair for refractory heart failure due to severe mitral regurgitation (MR). Interventional radiology (IVR) and surgery were contraindicated, and bronchial occlusion with EWSs was attempted to control bleeding. The bleeding was so persistent that it was difficult to secure the visual field without aspiration with a bronchoscope. Herein, we report a two-scope technique, also used in cryobiopsy of peripheral lung lesions, to control bleeding and perform bronchial occlusion with EWSs.

DOI： 10.1002/rcr2.1405

The consecutive impact of COVID-19 on thoracic surgical procedures in Japan: an analysis of data from the National Clinical Database Reviewed

Sato Y., Yamamoto H., Ikeda N., Konishi H., Hibi T., Endo S., Inoue M., Okada Y., Shintani Y., Toyooka S., Nakamura H., Hoshikawa Y., Chen-Yoshikawa T.F., Uramoto H., Tsubochi Y., Kakizoe T., Chida M., Yoshino I.

Surgery Today Vol. 54 ( 6 ) page： 627 - 633 2024.6

Language：English Publisher：Surgery Today

Purpose: The current study was designed to analyze the impact of the COVID-19 pandemic on general thoracic surgeries in Japan. Methods: Changes in surgeries for lung cancer and metastatic lung tumors were evaluated based on National Clinical Database data regarding cancer screening. Results: In 2021, surgeries for primary lung cancer increased by 3.4% compared to 2020, which, given the increase from 2014 to 2019, indicates an overall 11.1% decrease. In contrast, surgeries for metastatic lung tumors in 2021 decreased by 5.8% compared to 2020, which, given the increase from 2014 to 2020, indicates an overall 9.2% decrease. Half of the primary diseases for metastatic lung tumor were cases of colorectal cancer. Low anterior resection procedures in 2020 decreased by 5.5% compared to 2019. Lung and colon cancer screening examinees in 2021 were increased compared to 2020; however, they still showed respective decreases of 11% and 9.0% compared to 2019. Conclusions: Surgeries for primary lung cancer still decreased substantially during the COVID-19 pandemic. The continued stagnation of screening was responsible for this decrease. Surgeries for metastatic lung tumors decreased profoundly, and the decrease in screening for primary tumors was responsible for this reduction. Our findings emphasize the significance of maintaining cancer screening efforts, even during a pandemic.

DOI： 10.1007/s00595-023-02763-0

Evolution of Three-Dimensional Computed Tomography Imaging in Thoracic Surgery Reviewed

Chen-Yoshikawa T.F.

Cancers Vol. 16 ( 11 ) 2024.6

Authorship：Lead author,　Corresponding author Language：English Publisher：Cancers

Radiologic reconstruction technology allows the wide use of three-dimensional (3D) computed tomography (CT) images in thoracic surgery. A minimally invasive surgery has become one of the standard therapies in thoracic surgery, and therefore, the need for preoperative and intraoperative simulations has increased. Three-dimensional CT images have been extensively used, and various types of software have been developed to reconstruct 3D-CT images for surgical simulation worldwide. Several software types have been commercialized and widely used by not only radiologists and technicians, but also thoracic surgeons. Three-dimensional CT images are helpful surgical guides; however, in almost all cases, they provide only static images, different from the intraoperative views. Lungs are soft and variable organs that can easily change shape by intraoperative inflation/deflation and surgical procedures. To address this issue, we have developed a novel software called the Resection Process Map (RPM), which creates variable virtual 3D images. Herein, we introduce the RPM and its development by tracking the history of 3D CT imaging in thoracic surgery. The RPM could help develop a real-time and accurate surgical navigation system for thoracic surgery.

DOI： 10.3390/cancers16112161

Extralobar Pulmonary Sequestration Diagnosed as a Mediastinal Tumor and Resected by Robotic Surgery. International journal

Harushi Ueno, Hiroki Watanabe, Shoji Okado, Yuka Kadomatsu, Taketo Kato, Shota Nakamura, Tetsuya Mizuno, Toyofumi Fengshi Chen-Yoshikawa

Annals of thoracic surgery short reports Vol. 2 ( 2 ) page： 185 - 188 2024.6

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

A 55-year-old woman with no significant medical history or symptoms was incidentally diagnosed with a mediastinal tumor during a routine health checkup. The intraoperative findings of robot-assisted thoracoscopic surgery led to the diagnosis of extralobar pulmonary sequestration (EPS), with multiple vessels connecting to the pulmonary artery and superior pulmonary vein. EPS, an extremely rare condition, is typically supplied with blood from the aorta. Whereas it is uncommon for blood to be supplied from the pulmonary artery and to drain into the pulmonary vein in EPS, it is safely excised through robot-assisted thoracoscopic surgery.

DOI： 10.1016/j.atssr.2024.01.009

A Case of Myelolipoma Diagnosed by an Endobronchial Biopsy Reviewed

Kiyotoshi Hiroko, Nakao Makoto, Hirata Yuya, Kinoshita Ryosuke, Sugihara Masahiro, Kuriyama Mamiko, Takeda Norihisa, Tsuyuki Takuji, Chen-Yoshikawa Toyofumi, Muramatsu Hideki

The Journal of the Japan Society for Respiratory Endoscopy Vol. 46 ( 3 ) page： 177 - 181 2024.5

Language：Japanese Publisher：The Japan Society for Respiratory Endoscopy

Background. Myelolipomas are rare and mostly occur in the adrenal glands. Their occurrence in the thoracic cavity, and particularly in the lungs, is very rare. Case. A 71-year-old man was referred to our hospital due to an abnormality detected on plain chest radiography. Chest computed tomography revealed an 18 mm nodule with adipose tissues in the right middle lobar bronchus and consequent atelectasis of the right middle lobe. The nodule was mildly enhanced following administration of intravenous contrast agents. Bronchoscopy revealed that a tumor had obstructed the lumen of the right middle lobar bronchus, and an endobronchial biopsy was performed. Pathologically, the tumor comprised adipose and hematopoietic tissues with myeloid, erythroid and megakaryocytic cells. Therefore, the patient was diagnosed with a myelolipoma. No abnormalities were detected in a bone-marrow aspiration sample. Because atelectasis is known to cause obstructive pneumonia, we recommended surgical resection of the nodule. However, the patient disagreed; therefore, we are currently practicing a "wait-and-see" approach. Conclusion. We encountered a rare case of a pulmonary myelolipoma diagnosed using an endobronchial biopsy.

DOI： 10.18907/jjsre.46.3_177

The Tumor Immune Microenvironment Is Associated With Recurrence in Early-Stage Lung Adenocarcinoma Reviewed

日本におけるsublobar切除とマーキング法の現状肺精密縮小手術研究会からの報告

小島史嗣, 分島良, 河北直也, 上田雄一郎, 豊洋次郎, 小林正嗣, 佐藤雅昭, 清水公裕, 新谷康, 滝沢宏光, 津谷康大, 中島崇裕, 芳川豊史, 佐藤寿彦

日本呼吸器外科学会雑誌 Vol. 38 ( 3 ) page： PS5 - 8 2024.4

Kanemura H., Yokoyama T., Nakajima R., Nakamura A., Kuroda H., Kitamura Y., Shoda H., Mamesaya N., Miyata Y., Okamoto T., Okishio K., Oki M., Sakairi Y., Chen-Yoshikawa T.F., Aoki T., Ohira T., Matsumoto I., Ueno K., Miyazaki T., Matsuguma H., Yokouchi H., Otani T., Ito A., Sakai K., Chiba Y., Nishio K., Yamamoto N., Okamoto I., Nakagawa K., Takeda M.

JTO Clinical and Research Reports Vol. 5 ( 4 ) 2024.4

Language：English Publisher：JTO Clinical and Research Reports

Introduction: Immune checkpoint inhibitors have recently been approved for the treatment of early-stage NSCLC in the perioperative setting on the basis of phase 3 trials. However, the characteristics of such patients who are susceptible to recurrence after adjuvant chemotherapy or who are likely to benefit from postoperative immunotherapy have remained unclear. Methods: This biomarker study (WJOG12219LTR) was designed to evaluate cancer stem cell markers (CD44 and CD133), programmed death-ligand 1 (PD-L1) expression on tumor cells, CD8 expression on tumor-infiltrating lymphocytes, and tumor mutation burden in completely resected stage II to IIIA NSCLC with the use of archived DNA and tissue samples from the prospective WJOG4107 trial. Tumors were classified as inflamed or noninflamed on the basis of the PD-L1 tumor proportion score and CD8+ tumor-infiltrating lymphocyte density. The association between each potential biomarker and relapse-free survival (RFS) during adjuvant chemotherapy was assessed by Kaplan-Meier analysis. Results: A total of 117 patients were included in this study. The median RFS was not reached (95% confidence intervals [CI]: 22.4 mo–not reached; n = 39) and 23.7 months (95% CI: 14.5–43.6; n = 41) in patients with inflamed or noninflamed adenocarcinoma, respectively (log-rank p = 0.02, hazard ratio of 0.52 [95% CI: 0.29–0.93]). Analysis of the combination of tumor inflammation category and TP53 mutation status revealed that inflamed tumors without TP53 mutations were associated with the longest RFS. Conclusions: PD-L1 expression on tumor cells, CD8+ T cell infiltration, and TP53 mutation status may help identify patients with early-stage NSCLC susceptible to recurrence after adjuvant chemotherapy.

DOI： 10.1016/j.jtocrr.2024.100658

Circulating microRNA Panel for Prediction of Recurrence and Survival in Early-Stage Lung Adenocarcinoma. Reviewed International journal

Mei-Chee Tai, Leonidas E Bantis, Gargy Parhy, Taketo Kato, Ichidai Tanaka, Chi-Wan Chow, Junya Fujimoto, Carmen Behrens, Tetsunari Hase, Koji Kawaguchi, Johannes F Fahrmann, Edwin J Ostrin, Kohei Yokoi, Toyofumi F Chen-Yoshikawa, Yoshinori Hasegawa, Samir M Hanash, Ignacio I Wistuba, Ayumu Taguchi

International journal of molecular sciences Vol. 25 ( 4 ) 2024.2

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

Early-stage lung adenocarcinoma (LUAD) patients remain at substantial risk for recurrence and disease-related death, highlighting the unmet need of biomarkers for the assessment and identification of those in an early stage who would likely benefit from adjuvant chemotherapy. To identify circulating miRNAs useful for predicting recurrence in early-stage LUAD, we performed miRNA microarray analysis with pools of pretreatment plasma samples from patients with stage I LUAD who developed recurrence or remained recurrence-free during the follow-up period. Subsequent validation in 85 patients with stage I LUAD resulted in the development of a circulating miRNA panel comprising miR-23a-3p, miR-320c, and miR-125b-5p and yielding an area under the curve (AUC) of 0.776 in predicting recurrence. Furthermore, the three-miRNA panel yielded an AUC of 0.804, with a sensitivity of 45.8% at 95% specificity in the independent test set of 57 stage I and II LUAD patients. The miRNA panel score was a significant and independent factor for predicting disease-free survival (p < 0.001, hazard ratio [HR] = 1.64, 95% confidence interval [CI] = 1.51-4.22) and overall survival (p = 0.001, HR = 1.51, 95% CI = 1.17-1.94). This circulating miRNA panel is a useful noninvasive tool to stratify early-stage LUAD patients and determine an appropriate treatment plan with maximal efficacy.

DOI： 10.3390/ijms25042331

CHST4 Gene as a Potential Predictor of Clinical Outcome in Malignant Pleural Mesothelioma. International journal

Shoji Okado, Taketo Kato, Yuki Hanamatsu, Ryo Emoto, Yoshito Imamura, Hiroki Watanabe, Yuta Kawasumi, Yuka Kadomatsu, Harushi Ueno, Shota Nakamura, Tetsuya Mizuno, Tamotsu Takeuchi, Shigeyuki Matsui, Toyofumi Fengshi Chen-Yoshikawa

International journal of molecular sciences Vol. 25 ( 4 ) 2024.2

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

Malignant pleural mesothelioma (MPM) develops primarily from asbestos exposures and has a poor prognosis. In this study, The Cancer Genome Atlas was used to perform a comprehensive survival analysis, which identified the CHST4 gene as a potential predictor of favorable overall survival for patients with MPM. An enrichment analysis of favorable prognostic genes, including CHST4, showed immune-related ontological terms, whereas an analysis of unfavorable prognostic genes indicated cell-cycle-related terms. CHST4 mRNA expression in MPM was significantly correlated with Bindea immune-gene signatures. To validate the relationship between CHST4 expression and prognosis, we performed an immunohistochemical analysis of CHST4 protein expression in 23 surgical specimens from surgically treated patients with MPM who achieved macroscopic complete resection. The score calculated from the proportion and intensity staining was used to compare the intensity of CHST4 gene expression, which showed that CHST4 expression was stronger in patients with a better postoperative prognosis. The median overall postoperative survival was 107.8 months in the high-expression-score group and 38.0 months in the low-score group (p = 0.044, log-rank test). Survival after recurrence was also significantly improved by CHST4 expression. These results suggest that CHST4 is useful as a prognostic biomarker in MPM.

DOI： 10.3390/ijms25042270

The efficacy of pulmonary rehabilitation training program for patients after lung transplantation Reviewed

Mei J., Hu J., Krause E.M., Chen-Yoshikawa T.F., Alvarez A., Wang X.

Journal of Thoracic Disease Vol. 16 ( 1 ) page： 530 - 541 2024.1

Language：English Publisher：Journal of Thoracic Disease

Background: Pulmonary rehabilitation is recognized widely as one of the most effective measures to promote postoperative recovery of lung transplant recipients (LTRs), and it has positive effects on both short- and long-term quality of life (QoL) and survival outcomes. However, no standardized pulmonary rehabilitation training programs exist specifically for LTRs. The pulmonary rehabilitation programs widely used in clinical practice focus mainly on exercise or respiratory training, to some extent neglecting other therapeutic methods that could promote patient health, such as nutrition support, pain control, spiritual comfort, and so on. This study aimed to develop a postoperative pulmonary rehabilitation training program for LTRs and evaluate its effectiveness. Methods: Using convenience sampling, all patients who underwent lung transplantation (LTx) at Shanghai Pulmonary Hospital from January 2021 to December 2022 were screened for inclusion and exclusion criteria, and a total of 68 patients were finally included in this study. A non-synchronous quasi-experimental design was used, with patients who underwent LTx in 2021 as the control group and patients who underwent LTx in 2022 as the experimental group. The control group received routine treatment, health education, and rehabilitation guidance when patients determined the date of surgery. In addition to this, the experimental group received pulmonary rehabilitation training. The incidence of postoperative pulmonary complications (pulmonary infections), duration of chest tube drainage, intensive care unit (ICU) length of stay, postoperative pain scores, postoperative QoL, pulmonary function, oxygenation index, and the distance in the 6-minute walking test (6MWD) were compared between the two groups. Results: The length of ICU stay and duration of chest tube drainage in the experimental group were lower than those in the control group, and the results of oxygenation index, 6MWD, and St. George’s Respiratory Questionnaire (reflecting the QoL) were better than those of the control group (P<0.05). There was no significant difference in the pain of the two groups 1 week after surgery and 3 months after surgery, and the pain score of the experimental group was lower than that of the control group at 1 month after surgery (P<0.05). There was no significant difference in the incidence of complications between the two groups (P>0.05). Conclusions: The postoperative pulmonary rehabilitation training program for LTRs is safe and effective. It can shorten both the duration of chest tube drainage and ICU stay, it can also improve patients’ exercise capacity and pulmonary function while also promote safety outcomes of LTRs, and improve QoL scores.

DOI： 10.21037/jtd-23-1774

Efficacy and safety of intraoperative partial spray of 50% glucose for patients with spontaneous pneumothorax. Reviewed International journal

Ryota Kiriyama, Shota Nakamura, Hironori Oyamatsu, Seijiro Niimi, Takaki Fujimura, Takehiko Okagawa, Toyofumi Fengshi Chen-Yoshikawa

Journal of cardiothoracic surgery Vol. 19 ( 1 ) page： 14 - 14 2024.1

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: The management for pneumothorax patients involves surgical intervention, nevertheless postoperative recurrences are often encountered. To reduce the rates of recurrence, thoracic surgeons have experimented with various novel techniques, such as pleural abrasion, chemical pleurodesis, and staple line coverage with absorbable sheets, in addition to bullectomy. And in recent years, there have been reports of the effectiveness of the use of intraoperative glucose intrapleural spray (GIS) containing 50 ml of 50% glucose solution in addition to bullectomy. However, information on the effects and adverse events of GIS is limited. Current study was aimed to assess the efficacy and safety of GIS in preventing recurrence of pneumothorax. PATIENTS AND METHODS: We conducted a retrospective study with 74 cases of bullectomy with or without GIS between 2018 and 2021 at Okazaki City Hospital. Of these cases, 50 received GIS (GIS group) while 24 were treated conservatively (C group). RESULT: The GIS group consisted of 46 males and 4 females, whereas the C group consisted of 23 males and 1 female, with mean ages of 38.5 ± 5.7 years and 30.5 ± 6.7 years, respectively. The GIS group exhibited a mean increase in blood glucose of 23.8 mg/dL postoperatively, and postoperative infections were observed in 2 cases in the GIS group (4.0%) and 2 cases in the C group (8.3%). The NRS scores of the patients in the GIS group and the C group three hours postoperatively were 4.0 and 3.1, respectively (p = 0.28). No prolongation of postoperative drainage period by GIS was observed (1.2 days and 1.4 days in the GIS and C groups, respectively). Postoperative recurrence occurred in two patients from the C group. The postoperative total drainage volumes were 341.8 ± 25.2 ml and 74.2 ± 25.5 ml in the GIS and C groups, respectively, showing a significant increase in drainage volume (p < 0.01). None of them presented dehydration-related symptoms. CONCLUSIONS: The use of intraoperative glucose intrapleural spray is effective and safe in terms of preventing recurrences and postoperative complications.

DOI： 10.1186/s13019-024-02486-4

Prognostic impact of adjuvant therapy for cisplatin-unfit patients with non-small-cell lung cancer: A multicenter analysis. Reviewed International journal

Osamu Noritake, Shota Nakamura, Fumie Kinoshita, Keiju Aokage, Tetsuhiko Asao, Yosuke Matsuura, Toyofumi Fengshi Chen-Yoshikawa

Lung cancer (Amsterdam, Netherlands) Vol. 188 page： 107470 - 107470 2024.1

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: No evidence exists for postoperative adjuvant therapy in elderly or renal dysfunction patients with non-small-cell lung cancer (NSCLC) who are unfit to receive cisplatin (CDDP). Herein, we evaluated the efficacy of postoperative adjuvant therapy for CDDP-unfit patients. MATERIALS AND METHODS: We defined CDDP-unfit patients as those aged ≥75 years or with renal dysfunction based on criteria established by expert panels and from prospective studies. CDDP-fit patients comprised all others. Between 2010 and 2020, among 1,423 patients with pathological stage II-III (8th edition of the AJCC-TNM Classification) NSCLC, 454 were identified as unfit for CDDP. Following propensity score matching in CDDP-unfit patients with and without postoperative adjuvant therapy, we analyzed the overall survival (OS) and disease-free survival (DFS) of each group and assessed the impact of adjuvant therapy on survival. RESULTS: OS was significantly better in patients who received adjuvant therapy than in those who did not (5-year OS rate: 76.1 % vs. 50.0 %, p < 0.01) among 255 propensity score-matched patients. DFS was also significantly better in patients who received adjuvant therapy than in those who did not (5-year OS: 54.6 % vs. 35.1 %, p < 0.01). CONCLUSIONS: Our findings suggest that postoperative adjuvant therapy could be beneficial for CDDP-unfit patients aged ≥75 years or with renal dysfunction. Future studies for CDDP-unfit patients should be designed based on the results of this study to determine the potential benefits of adjuvant therapy.

DOI： 10.1016/j.lungcan.2024.107470

Incidence of air leaks in patients undergoing robotic thoracic surgery and video-assisted thoracic surgery Reviewed

Ueno H., Takada Y., Imamura Y., Okado S., Nomata Y., Watanabe H., Nakanishi K., Kadomatsu Y., Kato T., Nakamura S., Mizuno T., Chen-Yoshikawa T.F.

Nagoya Journal of Medical Science Vol. 86 ( 3 ) page： 464 - 471 2024

Authorship：Last author Language：English Publisher：Nagoya Journal of Medical Science

Postoperative air leakage is the most common complication in surgery for malignant lung tumors, leading to extended hospital stays and substantial medical expenses. This study aimed to identify the incidence and characteristics of intraoperative and postoperative air leaks in both robotic-assisted thoracic surgery (RATS) and video-assisted thoracic surgery (VATS), as well as the causes of persistent air leakage following RATS. We conducted a retrospective analysis of patients who underwent lung resection for malignant lung tumors at our institution from October 2018 to August 2022. We compared the incidence rates of intraoperative air leak, postoperative air leak, and persistent air leak between patients who underwent RATS and those who underwent VATS. Background factors were adjusted using propensity score matching. A subanalysis was performed to compare unexpected air leaks, defined as air leaks not observed intraoperatively but confirmed postoperatively. The study included 295 cases of RATS and 227 cases of VATS. In both the overall population and the matched group (187 cases each for RATS and VATS), RATS demonstrated a significantly higher incidence of persistent air leaks compared to VATS (11% vs 3%, p < 0.01; 9% vs 3%, p = 0.02, respectively). RATS also had a significantly higher incidence of unexpected air leaks compared with VATS (29% vs 18%, p = 0.05). Although there was no statistically significant difference in hospital stays, RATS showed a higher incidence of postoperative persistent air leaks and unexpected postoperative air leaks than VATS.

DOI： 10.18999/nagjms.86.3.464

A Case of Incidentally Discovered Congenital Complete Pericardial Defect during Lobectomy for Lung Cancer: A Case Report and Literature Review. Reviewed

Tomohiro Setogawa, Taketo Kato, Hiroki Watanabe, Shota Nakamura, Tetsuya Mizuno, Toyofumi Fengshi Chen-Yoshikawa

Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia Vol. 30 ( 1 ) page： n/a 2024

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：The Editorial Committee of Annals of Thoracic and Cardiovascular Surgery

An 82-year-old male patient underwent a left upper lobectomy with anterolateral thoracotomy for lung cancer. Although a complete left-pericardial defect was observed during surgery, the pericardial repair was not performed because the left lower lobe remained and the heart was considered stable. Postoperative pathological examination revealed primary synchronous double-lung squamous-cell carcinoma (pathological stage pT2a(2)N0M0 stage IB). He was discharged without complications on postoperative day 8. Leftward displacement of the heart and left diaphragmatic elevation, suspected of phrenic-nerve paralysis, were found in the chest X-ray after discharge. However, the patient's overall condition remained unaffected at the 5-month postoperative follow-up. To assess the need for pericardial repair, we compared cases of complete pericardial defects observed during lobectomy or pneumonectomy reported in the literature. Only one of 12 cases occurred postoperative death despite pericardial repair, and that case combined pectus excavatum and pericardial defects. Our assessment indicated that pericardial repair might not be necessary, excluding complex cases.

DOI： 10.5761/atcs.cr.24-00041

Current status and future direction of pediatric lung transplantation Invited Reviewed

Fengshi Chen-Yoshikawa Toyofumi

Journal of Japanese Society of Pediatric Radiology Vol. 40 ( 1 ) page： 10 - 16 2024

Authorship：Lead author,　Corresponding author Language：Japanese Publisher：Japanese Society of Pediatric Radiology

Japan’s first living-donor lung transplant was successfully performed in 1998, 15 years after the world’s first successful lung transplant by the Toronto Group. More than 20 years have passed since then, and more than 1,000 lung transplants have now been performed in Japan. The results have been excellent, with a 5-year survival rate of over 70% and a 10-year survival rate of over 60%, which are some of the highest survival rates in the world. The number of lung transplants has been increasing globally over time, and in Japan, the number of lung transplants exceeded 100 cases per year for the first time in 2022. However, the annual number of pediatric lung transplants worldwide is only about 100, and only about 20 cases involve patients under 10 years of age. Japan is the only country in the world where living-donor lung transplantation continues to be performed, and living-donor lung transplantation for children is an essential treatment option because of the severe chronic cadaveric donor shortage in Japan. Therefore, in the hope that lung transplantation will become an established and increasingly used treatment option for pediatric patients suffering from chronic respiratory failure, the current status and future of lung transplantation are outlined in this article.

DOI： 10.20844/jspr.40.1_10

Urticaria induced by continuous intravenous epoprostenol treatment in a patient with pulmonary arterial hypertension Reviewed

Sawada T., Kuwai T., Nakajima S., Chen-Yoshikawa T.F., Nomura T., Date H., Kabashima K.

Journal of Dermatology 2024

Thoracoscopic Wedge Resection for Low-Grade Fibromyxoid Sarcoma (Evans Tumor) with Massive Calcification and Originating from the Lung: A Rare Case in an Unexpected Location Reviewed

Watanabe Hiroki, Nakanishi Keita, Ueno Harushi, Kato Taketo, Shimoyama Yoshie, Chen-Yoshikawa Toyofumi Fengshi

Annals of Thoracic and Cardiovascular Surgery Vol. 30 ( 1 ) page： n/a 2024

Authorship：Last author,　Corresponding author Language：English Publisher：The Editorial Committee of Annals of Thoracic and Cardiovascular Surgery

We encountered a rare case of low-grade fibromyxoid sarcoma, which is generally known as Evans tumor, with massive calcification originating from the lung. The patient was a 22-year-old man with Duchenne muscular dystrophy who was referred for a detailed investigation of an intrathoracic tumor with massive calcification. Although our preoperative diagnosis was a solitary fibrous tumor originating from the mediastinum or diaphragm, intraoperative thoracoscopy revealed the tumor arising from the left lower lobe without adhesion to the other organs. Considering his medical history, we aimed to preserve lung function and chose wedge resection, which completely removed the tumor. Based on the pathological findings, the tumor was diagnosed as low-grade fibromyxoid sarcoma with massive calcification originating from the lung. Although extremely rare, this tumor should be considered as a differential diagnosis for a solitary lung mass with massive calcification in young adults.

DOI： 10.5761/atcs.cr.23-00170

Lung cancer after kidney transplantation: a 50-year experience at a single institution Reviewed

Watanabe H., Kadomatsu Y., Hakiri S., Yoshioka H., Hiramitsu T., Futamura K., Okada M., Goto N., Narumi S., Watarai Y., Chen-Yoshikawa T.F.

Surgery Today 2024

Authorship：Last author Language：English Publisher：Surgery Today

Purpose: To investigate the clinical characteristics of lung cancer that develops after kidney transplantation. Methods: The clinical data of patients with lung cancer diagnosed after kidney transplantation were collected retrospectively. The medical records were extracted from our database. All patients underwent routine chest examination after kidney transplantation. Results: In total, 17 lung tumors were detected in 15 (0.6%) of 2593 patients who underwent kidney transplantation at our institution. Eleven lung tumors were completely resected from a collective 10 patients (surgical group). The remaining five patients did not receive surgical treatment (nonsurgical group). The surgical group underwent wedge resection (n = 5), segmentectomy (n = 1), lobectomy (n = 3), and bilobectomy (n = 1). The pathological stages were 0 (n = 1), IA1 (n = 2), IA2 (n = 4), IA3 (n = 2), and IB (n = 1). The surgical group had a significantly better prognosis than the nonsurgical group. There were no perioperative complications related to kidney transplantation in either group. Conclusions: Routine chest examination would be useful for the early diagnosis and treatment of lung cancer after kidney transplantation. Moreover, surgical resection for early-stage lung cancer was associated with a better prognosis for kidney transplantation patients.

DOI： 10.1007/s00595-024-02819-9

Effects of the COVID-19 pandemic on surgical treatment for thoracic malignant tumor cases in Japan: a national clinical database analysis

Commentary: Less is more in modified subxiphoid approach for thymic malignancy Invited Reviewed

Chen-Yoshikawa T.F.

Journal of Thoracic and Cardiovascular Surgery 2024

Shintani Y., Yamamoto H., Sato Y., Inoue M., Asakura K., Ito H., Uramoto H., Okada Y., Sato T., Fukui M., Hoshikawa Y., Chen-Yoshikawa T.F., Chida M., Ikeda N., Yoshino I.

Surgery Today 2024

Publisher：Surgery Today

Objective: Surgical care has been significantly affected by the COVID-19 pandemic. This study was conducted to evaluate the effects of the pandemic on lung cancer and mediastinal tumor surgery. Methods: Changes in the number of surgical procedures for lung cancer and mediastinal tumors were analyzed using the National Clinical Database of Japan. Patient characteristics, including disease stage and histological type, from 2019 to 2022 were evaluated using annual datasets. Results: Comparisons with 2019 showed that the number of patients who underwent surgery for primary lung cancer or a mediastinal tumor decreased in 2020 and then remained stable. There were no clinically significant changes in the trend over the four-year period regarding the number of patients for each clinical and pathological stage of lung cancer. Regarding mediastinal tumors, there was no significant difference in tumor size between years. There was a slight change in the selection of surgical indication during the second quarter of 2020, although its impact on annual trends in the stage distribution for lung cancer and primary disease for mediastinal tumors was minimal. Conclusions: Analyses of lung cancer and mediastinal tumor surgery cases in Japan during the COVID-19 pandemic showed no significant disease profile changes related to treatment delay.

DOI： 10.1007/s00595-024-02907-w

Immunosuppressive treatment for myasthenia gravis crises improve the taste disorder in patients with thymoma: two case reports Reviewed

Clinical, radiological, and pathological features of idiopathic and secondary interstitial pneumonia cases with pleuroparenchymal fibroelastosis undergoing lung transplantation Reviewed

Ikegami Naoya, Nakajima Naoki, Yoshizawa Akihiko, Handa Tomohiro, Chen-Yoshikawa Toyofumi, Kubo Takeshi, Tanizawa Kiminobu, Ohsumi Akihiro, Yamada Yoshito, Hamaji Masatsugu, Nakajima Daisuke, Yutaka Yojiro, Tanaka Satona, Watanabe Kizuku, Nakatsuka Yoshinari, Murase Yuko, Nakanishi Tomoko, Niwamoto Takafumi, Chin Kazuo, Date Hiroshi, Hirai Toyohiro

Tenri Medical Bulletin Vol. 26 ( 1 ) page： 56 - 57 2023.12

Yuko Ohara, Shoji Okado, Hiroki Watanabe, Osamu Noritake, Keita Nakanishi, Yuka Kadomatsu, Harushi Ueno, Taketo Kato, Shota Nakamura, Toyofumi Fengshi Chen-Yoshikawa, Koichi Fukumoto

Mediastinum Vol. 7 2023.12

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

Background: Taste disorders in patients with thymoma accompanied by myasthenia gravis (MG) is rare. Case Description: The first case was a male in his 50s who underwent surgery for Masaoka stage III type B3 thymoma. He experienced a loss of taste before surgery, which showed no improvement after surgery. Due to a MG crisis 44 days after surgery, the patient underwent intensive treatment with mechanical ventilation, steroid pulse therapy, and intravenous immunoglobulin (IVIG) therapy. The patient recovered taste when he started oral food intake after the treatment for the MG crisis (about 3 months after surgery). Despite the recovery of taste after steroid pulse therapy and IVIG therapy, taste disorder gradually worsened about 1 year and 9 months after surgery, resulting in an almost complete loss of sweet taste 2 years after surgery. The second case was a male in his 60s who underwent surgery for Masaoka stage II type B1 thymoma. He experienced loss of taste before surgery, which showed no improvement after surgery. Five years and two months after surgery, the patient was diagnosed with a MG crisis and underwent steroid pulse therapy. Along with improvements in MG symptoms, taste disorders gradually improved. After 6 years and 10 months of surgery, the patient is still alive without MG symptoms (only pyridostigmine, 180 mg/body/day), taste disorder, and thymoma recurrence. Conclusions: The autoimmune mechanism may contribute to taste disorders in patients with thymoma, which can be recovered by immunosuppressive treatment in our cases.

DOI： 10.21037/med-23-8

Influencing Factors on Intersegmental Identification Adequacy in Segmentectomy with Intraoperative Indocyanine Green (ICG) Intravenous Administration. Reviewed International journal

Harushi Ueno, Tomohiro Setogawa, Ayaka Makita, Yuko Ohara, Yoshito Imamura, Shoji Okado, Hiroki Watanabe, Yuta Kawasumi, Yuka Kadomatsu, Taketo Kato, Shota Nakamura, Tetsuya Mizuno, Toyofumi Fengshi Chen-Yoshikawa

Cancers Vol. 15 ( 24 ) 2023.12

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

Accurate identification of the intersegmental plane is essential in segmentectomy, and Indocyanine Green (ICG) assists in visualizing lung segments. Various factors, including patient-related, intraoperative, and technical issues, can influence boundary delineation. This study aims to assess the rate of unsuccessful intersegmental identification and identify the contributing factors. We analyzed cases of lung segmentectomy from April 2020 to March 2023, where intraoperative ICG was intravenously administered during robot-assisted or video-assisted thoracoscopic surgery. Cases where fluorescence extended beyond expected boundaries within 30 s were classified as the "unclear boundary group". This group was then compared to the "clear boundary group". The study encompassed 111 cases, 104 (94%) of which were classified under the "clear boundary group" and 7 (6%) under the "unclear boundary group". The "unclear boundary group" had a significantly lower DLCO (15.7 vs. 11.8, p = 0.03) and DLCO/VA (4.3 vs. 3.0, p = 0.01) compared to the "clear boundary group". All cases in the "unclear boundary group" underwent lower lobe segmentectomy. ICG administration effectively outlines pulmonary segments. Challenges in segment demarcation may occur in cases with low DLCO and DLCO/VA values, particularly during lower lobe segmentectomy.

DOI： 10.3390/cancers15245876

Perioperative changes in radiographic density in erector spinae muscle and mortality after lung transplantation. Reviewed International journal

Yohei Oshima, Susumu Sato, Toyofumi F Chen-Yoshikawa, Daisuke Nakajima, Yuji Yoshioka, Ryota Hamada, Taishi Kajimoto, Ayumi Otagaki, Manabu Nankaku, Naoya Tanabe, Ryosuke Ikeguchi, Hiroshi Date, Shuichi Matsuda

Respiratory medicine Vol. 221 page： 107482 - 107482 2023.12

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

RATIONALE: The radiographic density of the erector spinae muscle (ESM) is often decreased early after lung transplantation (LTx). The prognostic impact of this change has not been elucidated. OBJECTIVE: To investigate whether the decrease in the radiographic density of ESMs early after LTx is associated with a poor prognosis. METHODS: This study is a single center retrospective cohort study. Routine follow-up chest computed tomography scan data just before and 12 weeks after LTx were retrospectively retrieved for adult patients who underwent primary LTx at Kyoto University Hospital. The radiographic density of ESM was quantitatively evaluated as the mean attenuation of the ESM (ESMct), and the impact of the decreased ESMct during the 12 weeks after LTx on overall survival (OS) was examined by Cox proportional hazard regression. RESULTS: A total of 151 recipients (94 cadaveric LTx, 57 living-donor lobar LTx) were included in this study. The median duration of postoperative observation was 4.4 years, during which time 39 recipients (26%) died. Decreased postoperative ESMct was significantly associated with poor OS (HR, 1.64; 95% CI, 1.14-2.35, P = 0.008 per 1 Z score decrease) in the multivariate model adjusted for age, sex, episodes of acute rejection, and preoperative ESMct. Similar results were obtained when the subjects were limited to those with cadaveric LTx. CONCLUSION: A decreased perioperative ESMct was strongly associated with a poor prognosis after LTx in addition to low preoperative ESMct. Maintaining postoperative muscle radiographic density, which reflects muscle quality, may be important for a better prognosis after LTx.

DOI： 10.1016/j.rmed.2023.107482

Novel intrathoracic irrigation using ultrafine ozone bubbles in a rat empyema model Reviewed

Ikeda M., Yutaka Y., Chen-Yoshikawa T.F., Tanaka M., Yamamoto M., Tanaka S., Yamada Y., Ohsumi A., Nakajima D., Hamaji M., Yoshizawa A., Kusaka E., Nagao M., Date H.

Scientific Reports Vol. 13 ( 1 ) 2023.12

Language：English Publisher：Scientific Reports

Dissolved ozone is generally used for sanitization, but it has not been used for thoracic cavity sanitization because of its short half-life (< 20 min) and possible toxicity. We developed a novel solution containing ultrafine ozone bubbles (ozone-UFB) with a fivefold longer half-life than non-UFB ozone. Using an in vitro model, Staphylococcus aureus colonies were counted after exposure to ozone-UFB or non-UFB ozone at the same ozone concentration (0.4 mg/L). The colony count was significantly lower in the ozone-UFB group than in the non-UFB ozone group (p = 0.034). The effect of repeated pleural irrigation using ozone-UFB and saline was compared in a rat empyema model of S. aureus infection. The bacterial count in the pleural effusion was decreased by at least fivefold following intrathoracic lavage with ozone-UFB (3 mg/L). To examine the safety of ozone-UFB for intrathoracic use, ozone-UFB with a higher ozone concentration (10 mg/L) was injected into the thoracic cavities of normal rats. The treatment did not result in any specific pleural damage or elevated serum interleukin-6 concentrations. The findings highlighted the efficacy and safety of ozone-UFB for intrathoracic sanitization, but further studies are needed to determine the optimal therapeutic ozone concentration with appropriate safety margins.

DOI： 10.1038/s41598-023-43787-3

Postoperative Complications of Open Window Thoracostomy:Report of a Case. Reviewed

Toshinari Ito, Shota Nakamura, Shoji Okado, Keiyu Sato, Koichi Fukumoto, Toyofumi F Chen-Yoshikawa

Kyobu geka. The Japanese journal of thoracic surgery Vol. 76 ( 12 ) page： 1069 - 1072 2023.11

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

While open window thoracostomy is used to treat empyema with a high rate of infection control, it is an invasive procedure that leads to a decline in the quality of life. An 80-year-old man who had undergone wedge resection for pulmonary nodules subsequently developed postoperative empyema and underwent open window thoracostomy. After thoracostomy, the patient developed several complications, including bleeding from the lung surface and air leakage. Window closure was planned at this time;however, the plan was scuttled due to his low nutritional status and pulmonary air leakage. After the patient's condition improved with persistent conservative treatment, window closure was performed, and he overcame his complications. Patients with postoperative empyema requiring thoracostomy are at a high risk of developing postoperative complications. Therefore, it is important to manage the patients' condition persistently so that they can receive window closure at an appropriate time.

Complete visualization using indocyanine green in thoracic surgery for pulmonary sequestration. Reviewed International journal

Keita Nakanishi, Yuka Kadomatsu, Harushi Ueno, Taketo Kato, Shota Nakamura, Tetsuya Mizuno, Toyofumi Fengshi Chen-Yoshikawa

Journal of thoracic disease Vol. 15 ( 10 ) page： 5714 - 5722 2023.10

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

Preoperative three-dimensional computed tomography (CT) facilitates accurate identification of aberrant systemic arteries in thoracic surgery for pulmonary sequestration (PS). Furthermore, the boundary between normal and sequestrated lungs can be visualized using the spread of fluorescent indocyanine green (ICG) when performing surgery for PS. This study aimed to determine how to completely visualize anatomical variations, safely treat aberrant arteries, remove only sequestrated lungs, and perform minimally invasive surgery for PS. Seventeen patients underwent lung resection for intralobar PS at our institution between 2009 and 2022. We retrospectively reviewed the surgical outcomes and intraoperative images using ICG to assess the efficacy and feasibility of near-infrared fluorescence imaging. Since 2019, intraoperative near-infrared fluorescence imaging with ICG has been used in six patients, including four females and two males (median age, 56 years), to visualize the boundary between normal and sequestrated lungs. Aberrant arteries were identified using preoperative three-dimensional CT, and the boundary between sequestrated and normal lungs could be clearly delineated intraoperatively using ICG in all cases. The median operative time was 145 min (range, 88-167 min), and the median blood loss was 5 mL (range, 1-191 mL). The overlay mode using near-infrared thoracoscopy, which merges visible light images with fluorescent images, was safer and more useful than conventional thoracoscopy for delineating boundaries with electrocautery. No intraoperative or postoperative complications occurred. The median postoperative hospital stay was 5 days (range, 3-7 days). Intraoperative identification of the boundary between normal and sequestrated lungs using ICG was simple and feasible. We suggested that this technique was effective for lesion resection and normal lung preservation during surgery for intralobar PS.

DOI： 10.21037/jtd-23-892

NOTCH1 and CREBBP co-mutations negatively affect the benefit of adjuvant therapy in completely resected EGFR-mutated NSCLC: translational research of phase III IMPACT study. Reviewed International journal

Satoshi Ikeda, Masahiro Tsuboi, Kazuko Sakai, Toshihiro Misumi, Hiroaki Akamatsu, Hiroyasu Shoda, Noriaki Sakakura, Atsushi Nakamura, Yasuhisa Ohde, Hidetoshi Hayashi, Kyoichi Okishio, Morihito Okada, Ichiro Yoshino, Jiro Okami, Kazuhisa Takahashi, Norihiko Ikeda, Masayuki Tanahashi, Yuichi Tambo, Haruhiro Saito, Shinichi Toyooka, Hidetoshi Inokawa, Toyofumi Chen-Yoshikawa, Toshihide Yokoyama, Tatsuro Okamoto, Noriko Yanagitani, Masahide Oki, Makoto Takahama, Kenji Sawa, Hirohito Tada, Kazuhiko Nakagawa, Tetsuya Mitsudomi, Kazuto Nishio

Molecular oncology Vol. 18 ( 2 ) page： 305 - 316 2023.10

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

The phase III IMPACT study (UMIN000044738) compared adjuvant gefitinib with cisplatin plus vinorelbine (cis/vin) in completely resected epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Although the primary endpoint of disease-free survival (DFS) was not met, we searched for molecular predictors of adjuvant gefitinib efficacy. Of 234 patients enrolled in the IMPACT study, 202 patients were analyzed for 409 cancer-related gene mutations and tumor mutation burden using resected lung cancer specimens. Frequent somatic mutations included tumor protein p53 (TP53; 58.4%), CUB and Sushi multiple domains 3 (CSMD3; 11.8%), and NOTCH1 (9.9%). Multivariate analysis showed that NOTCH1 co-mutation was a significant poor prognostic factor for overall survival (OS) in the gefitinib group and cAMP response element binding protein (CREBBP) co-mutation for DFS and OS in the cis/vin group. In patients with NOTCH1 co-mutations, gefitinib group had a shorter OS than cis/vin group (Hazard ratio 5.49, 95% CI 1.07-28.00), with a significant interaction (P for interaction = 0.039). In patients with CREBBP co-mutations, the gefitinib group had a longer DFS than the cis/vin group, with a significant interaction (P for interaction = 0.058). In completely resected EGFR-mutated NSCLC, NOTCH1 and CREBBP mutations might predict poor outcome in patients treated with gefitinib and cis/vin, respectively.

DOI： 10.1002/1878-0261.13542

グローバルスタンダードを目指した肺がん縮小手術開発の現状と課題肺野末梢小型非小細胞肺がん例に対する実臨床での術式選択と術後成績

中村彰太, 高田裕里, 今村由人, 岡戸翔嗣, 野亦悠史, 渡邉裕樹, 門松由佳, 上野陽史, 加藤毅人, 水野鉄也, 芳川豊史

肺癌 Vol. 63 ( 5 ) page： 374 - 374 2023.10

充実性結節として描出され,転移性肺腫瘍や原発性肺癌との鑑別を要したperibronchiolar metaplasiaの1例

高田裕里, 中村彰太, 芳川豊史, 水野鉄也, 加藤毅人, 上野陽史, 門松由佳, 仲西慶太, 則竹統, 渡邉裕樹, 岡戸翔嗣, 野亦悠史, 今村由人, 岩清水寿徳

肺癌 Vol. 63 ( 5 ) page： 623 - 623 2023.10

New method for delineation of the intersegmental line in a deflated lung. Reviewed International journal

Shoji Okado, Yuka Kadomatsu, Megumi Nakao, Harushi Ueno, Koichi Fukumoto, Shota Nakamura, Toyofumi Fengshi Chen-Yoshikawa

Journal of thoracic disease Vol. 15 ( 9 ) page： 4736 - 4744 2023.9

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Preoperative three-dimensional (3D) computed tomography (CT) images have been widely used as surgical guides in lung surgery; however, the lungs tend to be deflated during surgery. Discrepancies between the preoperatively constructed 3D image and the intraoperative view of the deflated lungs often require preoperative and/or intraoperative marking methods for sublobar pulmonary resection. We have developed a lung deflation simulation algorithm in which 3D CT images of the deflated lungs can be predicted only based on the preoperative CT taken in an inflated phase of respiration. Using this system, we conducted a preliminary study to retrospectively compare the intersegmental line predicted by our lung deflation simulation algorithm with the intersegmental line delineated by the intravenous administration of indocyanine green. METHODS: Sixteen patients who underwent unilateral segmentectomy between January 1, 2020, and June 30, 2022, were included in the study. The identified intersegmental lines were confirmed intraoperatively using indocyanine green. These actual intersegmental lines were compared with those delineated on 3D images using the lung deflation simulation algorithm. RESULTS: Of the 16 patients who underwent pulmonary segmentectomy, the consistency of these intersegmental lines was in complete agreement in twelve patients, partial agreement in three patients, and disagreement in one patient. The concordance rate of the intersegmental lines was 75%. CONCLUSIONS: The lung deflation simulation algorithm provides a new surgical guide in addition to the currently utilized ones. Continuous innovation might lead to a less invasive surgical technique for delineating the intersegmental line.

DOI： 10.21037/jtd-23-421

Prognostic impact of highly solid component in early-stage solid lung adenocarcinoma. Reviewed International journal

Taketo Kato, Shingo Iwano, Yuki Hanamatsu, Masato Nakaguro, Ryo Emoto, Shoji Okado, Keiyu Sato, Osamu Noritake, Keita Nakanishi, Yuka Kadomatsu, Harushi Ueno, Naoki Ozeki, Shota Nakamura, Koichi Fukumoto, Tamotsu Takeuchi, Kennosuke Karube, Shigeyuki Matsui, Toyofumi Fengshi Chen-Yoshikawa

Quantitative imaging in medicine and surgery Vol. 13 ( 9 ) page： 5641 - 5652 2023.9

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Based on computed tomography (CT) findings of lung cancer, solid nodules have a much worse prognosis than subsolid nodules, even if the nodules are subcentimeter in size. There is, however, no systematic method for determining the prognosis of solid tumors on CT. This study aimed to discover the prognostic factor of early-stage solid lung adenocarcinoma using three-dimensional CT volumetry. METHODS: Patients with pathological stage I solid lung adenocarcinoma who underwent complete resection between 2007 and 2012 were selected in this retrospective study. Clinicopathological data and preoperative multidetector CT findings, such as tumor size on the two-dimensional axial image, three-dimensional tumor volume between -600 and 199 HU, and three-dimensional solid volume between 0 and 199 HU, which corresponded to highly solid components, were compared between recurrence and non-recurrence. Furthermore, these radiological values were compared to pathological invasive volume (PIV). RESULTS: During this time, 709 patients had their lung cancer completely removed. From this cohort, 90 patients with pathological stage I solid lung adenocarcinoma were selected. In addition, recurrence was found in 26 patients (28.9%). Although two-dimensional axial image, serum carcinoembryonic antigen (CEA) level, and SUVmax on 18F fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) did not differ statistically between recurrent and non-recurrent patients, three-dimensional tumor and solid tumor volume did. Multivariate analysis indicated that three-dimensional solid tumor volume [hazard ratio: 2.440; 95% confidence interval (CI): 1.110-5.361, P=0.026] and epidermal growth factor receptor (EGFR) mutation (hazard ratio: 4.307; 95% CI: 1.328-13.977, P=0.015) were significantly associated with disease-free survival (DFS). When three-dimensional tumor and solid tumor volume were compared to PIV, three-dimensional solid tumor volume (3,091 mm3 on average) showed a highly similar value with PIV (2,930 mm3 on average), whereas three-dimensional tumor volume (6,175 mm3 on average) was significantly larger than PIV (P<0.001). CONCLUSIONS: In patients with early-stage solid lung adenocarcinoma, the measurement of three-dimensional solid tumor volume, which is correlated with PIV, accurately predicted the postoperative outcome.

DOI： 10.21037/qims-23-36

Investigation of the Current Surgical Practice in Patients with Thymic Epithelial Tumors Among Board-certified Surgeons of the Japanese Association for Chest Surgery: Does a Discrepancy Exist Between Clinical Practice Guidelines and Clinical Practice?

Fukumoto Koichi, Mori Shoichi, Yoshioka Hiromu, Okasaka Toshiki, Taniguchi Tetsuo, Shigemitsu Kikuo, Narita Kunio, Fukui Takayuki, Nakamura Shota, Fengshi Chen-Yoshikawa Toyofumi

Haigan Vol. 63 ( 4 ) page： 280 - 284 2023.8

Language：Japanese Publisher：The Japan Lung Cancer Society

Purpose. According to the current Japanese clinical practice guidelines on thymic tumors, complete tumor resection accompanied by thymectomy is recommended in surgery for early-stage thymic epithelial tumors (TETs). However, in some cases of early-stage TETs, partial thymectomy is performed. In addition to surgical procedures, the extent to which clinical practice guidelines concerning thymic tumors are used as a reference for perioperative care is unclear. Methods. A questionnaire survey was conducted regarding clinical practice, such as surgical procedures, adjuvant therapy, and the postoperative follow-up period, in patients with TETs. Results. A total of 30 board-certified surgeons of the Japanese Association for Chest Surgery (JACS) in Nagoya University and affiliated hospitals responded to the questionnaire survey. Two-thirds of the board-certified surgeons of the JACS (20/30) selected thymectomy for early-stage TETs without myasthenia gravis. In contrast, the remaining board-certified surgeons of the JACS (10/30) selected partial thymectomy in such cases. Answers regarding adjuvant therapy and the postoperative follow-up period were in accordance with the clinical practice guidelines. Conclusion. This questionnaire revealed that one-third of board-certified surgeons of the JACS selected partial thymectomy for early-stage TETs, which is not recommended in the Japanese clinical practice guideline.

DOI： 10.2482/haigan.63.280

Risk stratification of postoperative pulmonary complications in elderly patients undergoing lung cancer resection: a propensity score-matched study Reviewed

Huang Q., Rauniyar R., Yang J., Zhou C., Cai D., Chen-Yoshikawa T.F., Yutaka Y., Orlandi R., Geraci T.C., Lin J., Hu H., Jiang Z., Zhao G., Ye L.

Journal of Thoracic Disease Vol. 15 ( 7 ) page： 3908 - 3918 2023.7

Language：English Publisher：Journal of Thoracic Disease

Background: In China, lung cancer mainly affects the elderly population. Surgery remains the standard treatment for lung cancer in elderly patients, however, postoperative pulmonary complications (PPCs) are major contributors to morbidity and mortality following lung resection. This study aimed to identify perioperative predictors of PPCs among elderly patients undergoing pulmonary resection for lung cancer to provide evidence for better prevention and intervention for PPCs. Methods: A retrospective study was conducted with 456 patients (age >65 years) undergoing pulmonary resection for lung cancer in Yunnan, China from January 2016 to March 2019. Propensity score matching (PSM) was performed to compare preoperative data and clinical characteristics between the PPC and non-PPC groups, followed by binary logistic regression to evaluate predictors of PPCs. Results: Pulmonary complications occurred in 142/456 (31.1%) patients age >65 years, with pneumonia being the most common event (21.7%). Both PSM and binary logistic regression analysis identified American Society of Anesthesiologists (ASA) class <II [odds ratio (OR): 0.177, 95% confidence interval (CI): 0.037–0.854] and video-assisted thoracoscopic surgery (VATS) (OR: 0.576, 95% CI: 0.334–0.992) as protective factors for PPCs. Conclusions: PPCs following lung cancer resection in elderly patients were associated with a higher ASA classification and open thoracotomy. An adequate and comprehensive evaluation of the operative strategies and enhanced recovery methods should be implemented among elderly patients undergoing lung resection with an ASA class > II or those undergoing an open thoracotomy to help prevent the occurrence of PPCs.

DOI： 10.21037/jtd-23-923

[Robot-assisted Extended Thymectomy via a Bilateral Approach for Patients with Myasthenia Gravis]. Reviewed

Shota Nakamura, Keita Nakanishi, Yuka Kadomatsu, Harushi Ueno, Taketo Kato, Toyofumi F Chen-Yoshikawa

Kyobu geka. The Japanese journal of thoracic surgery Vol. 76 ( 7 ) page： 523 - 527 2023.7

Authorship：Last author Language：Japanese Publishing type：Research paper (scientific journal)

Extended thymectomy is a procedure to remove the thymus gland and surrounding adipose tissue, while the traditional approach via a median sternotomy, minimally invasive approaches such as video-assisted thoracoscopic surgery (VATS) and robot-assisted thoracoscopic surgery (RATS) have been adopted. This report described the technique of bilateral approach for extended thymectomy in patients with myasthenia gravis (MG) by robot-assisted thoracoscopic surgery, and also showed the perioperative outcomes and postoperative exacerbation rates of 11 patients. In most patients, score of MG symptom were reduced and levels of anti-acetylcholine receptor antibodies declined postoperatively. In a small number of cases, the safety and efficacy of a RATS bilateral approach for extended thymectomy were confirmed.

One-year change in the health status predicts the subsequent hospitalization and mortality in patients waitlisted for lung transplantation in Japan. Reviewed International journal

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 Vol. 61 ( 4 ) page： 478 - 484 2023.7

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

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

Lingular-segment torsion after extended left-upper division segmentectomy by video-assisted thoracic surgery with indocyanine green fluorescence imaging. Reviewed

Taketo Kato, Yuko Ohara, Shoji Okado, Osamu Noritake, Keita Nakanishi, Yuka Kadomatsu, Harushi Ueno, Shota Nakamura, Koichi Fukumoto, Toyofumi Fengshi Chen-Yoshikawa

Asian journal of endoscopic surgery Vol. 16 ( 3 ) page： 584 - 587 2023.7

Authorship：Last author,　Corresponding author Language：English

Lingular-segment torsion after left-upper division segmentectomy (LUDS) is a rare complication, and the cause remains unclear. Here we report the case of a patient who developed lingular-segment torsion after LUDS for multiple lung metastases of breast cancer. One lung nodule was located in the S1 + 2 segment and another between the upper lobe and S6 on an incomplete interlobar fissure. The lung metastases were resected by extended LUDS using video-assisted thoracic surgery with indocyanine green fluorescence imaging. The staple line on the lingular segment was vertically tilted against the interlobar line because of the atypical defect of the fluorescence plane and nodule position. Chest X-ray and contrast-enhanced computed tomography indicated ischemia and torsion of the lingular segment on the second postoperative day, and completion of lingular segmentectomy was performed. This case showed the vertical intersegment staple line during LUDS was one of the important causes of postoperative torsion of the lingular segment.

DOI： 10.1111/ases.13189

【縦隔・胸壁腫瘍に対する低侵襲手術】ロボット支援下手術重症筋無力症に対する両側アプローチによるロボット支援下拡大胸腺全摘の術後成績

中村彰太, 仲西慶太, 門松由佳, 上野陽史, 加藤毅人, 芳川豊史

胸部外科 Vol. 76 ( 7 ) page： 523 - 527 2023.7

ABO blood type incompatible lung transplantation. Reviewed International journal

Toyofumi F Chen-Yoshikawa

Journal of thoracic disease Vol. 15 ( 6 ) page： 3437 - 3442 2023.6

Authorship：Lead author,　Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

ABO-incompatible transplantation has been successfully performed in the kidney and liver. However, lungs are subject to strong rejection and are vulnerable to infection because they are directly exposed to air. Therefore, lung transplantation from organs with incompatible blood types has been considered a significant challenge. Due to the severe shortage of donors, ABO-incompatible lung transplantation might be a viable method to save critically ill patients with end-stage respiratory diseases. Herein, we review the worldwide published reports about both minor and major ABO-incompatible lung transplantations. In North America, major ABO-incompatible lung transplants have been performed in cases with clerical errors in blood typing. But they were successful with additional treatments following the protocol for ABO-incompatible transplants in other organs (multiple plasma exchanges and additional immunosuppressive therapy such as anti-thymocyte globulin administration). In Japan, major ABO-incompatible living-donor lobar lung transplantations have also been performed successfully when the recipient does not have an ABO antibody against the donor. This unique situation sometimes occurs when the recipient undergoes hematopoietic stem cell transplantation before lung transplantation, in which the recipient's blood type changes after hematopoietic stem cell transplantation. One infant and one adult had successful intentional major ABO-incompatible lung transplantation with both induction therapy and aggressive maintenance antibody-depletion therapy. Furthermore, an experimental antibody-depletion study has also been conducted to overcome ABO incompatibility. Even though intentional major ABO-incompatible lung transplantation has rarely been performed, several significant pieces of evidence have been accumulated to prepare for ABO-incompatible lung transplantation in selected cases. In the future, this challenge can potentially expand the donor organ pool and lead to improvements in the fairness of organ allocation.

DOI： 10.21037/jtd-23-48

Robotic resection of ectopic mediastinal parathyroid adenoma in multiple endocrine neoplasia 1. Reviewed International journal

Yuko Ohara, Yuka Kadomatsu, Toyone Kikumori, Toyofumi F Chen-Yoshikawa

Surgical case reports Vol. 9 ( 1 ) page： 114 - 114 2023.6

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Hyperparathyroidism in patients with multiple endocrine neoplasia 1 is attributed to the excessive secretion of parathyroid hormone (PTH) from multiple parathyroid glands. This can be successfully treated through complete resection of the parathyroid glands; however, subsequent surgery is often required because of the presence of supernumerary or ectopic parathyroid glands. Therefore, identifying the locations of all functional glands is crucial for precise resection. Here, we report a case of ectopic mediastinal parathyroid adenoma that was successfully resected using robot-assisted thoracoscopic surgery. CASE PRESENTATION: A 53-year-old woman underwent a total parathyroidectomy with autotransplantation for multiple endocrine neoplasia 1-associated primary hyperparathyroidism. The patient previously underwent laparoscopic distal pancreatectomy for a pancreatic neuroendocrine tumor. She also presented with a mediastinal tumor and nonfunctional pituitary adenoma that could be followed up. Blood tests before total parathyroidectomy showed high levels of intact PTH (183 pg/mL) and calcium (Ca; 10.3 mg/dL); however, postoperative blood tests still revealed high levels of intact PTH (103 pg/mL) and Ca (11.4 mg/dL). Computed tomography and magnetic resonance imaging revealed a 45-mm-sized mass in the right upper mediastinum as a well-defined solid and cystic lesion, whereas 99mTc-methoxyisobutylisonitrile scintigraphy indicated a strong accumulation of tracers, suggesting an ectopic lesion in the mediastinum. Persistent hyperparathyroidism after total parathyroidectomy via neck incision was attributed to an ectopic parathyroid tumor in the mediastinum. Thus, we decided to resect the tumor using robot-assisted thoracoscopic surgery to perform the procedure gently and carefully. During surgery, a mediastinal tumor was identified as it was detected radiographically. Because it did not invade the surrounding tissues, it could be completely resected without injuring the capsule. The patient was discharged without complications. Postoperatively, Ca and intact PTH levels decreased back to normal. The final pathological diagnosis confirmed that the mass was an ectopic mediastinal parathyroid adenoma. CONCLUSIONS: Minimally invasive surgical resection of a remnant ectopic lesion was successfully performed in a patient with multiple endocrine neoplasia 1 using robot-assisted thoracoscopic surgery.

DOI： 10.1186/s40792-023-01694-9

シスプラチン投与困難な病理病期II-III期非小細胞肺癌症例の術後成績

則竹統, 中村彰太, 大原佑子, 岡戸翔嗣, 渡邉裕樹, 仲西慶太, 門松由佳, 上野陽史, 加藤毅人, 福本紘一, 芳川豊史

日本呼吸器外科学会雑誌 Vol. 37 ( 3 ) page： P4 - 6 2023.6

遷延する左気胸で発覚した悪性胸膜中皮腫の一例

岡戸翔嗣, 芳川豊史, 福本紘一, 中村彰太, 加藤毅人, 上野陽史, 門松由佳, 仲西慶太, 則竹統, 渡邉裕樹, 大原佑子

日本呼吸器外科学会雑誌 Vol. 37 ( 3 ) page： P78 - 6 2023.6

Development of panorama vision ring for thoracoscopy. Reviewed International journal

Takayuki Kitasaka, Shota Nakamura, Yuichiro Hayashi, Tsuyoshi Nakai, Yasuhiro Nakai, Kensaku Mori, Toyofumi Fengshi Chen-Yoshikawa

International journal of computer assisted radiology and surgery Vol. 18 ( 5 ) page： 945 - 952 2023.5

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Minimally invasive surgery (MIS) using a thoraco- or laparoscope is becoming a more common surgical technique. In MIS, a magnified view from a thoracoscope helps surgeons conduct precise operations. However, there is a risk of the visible area becoming narrow. To confirm that the operation field is safe, the surgeon will draw the thoracoscope back to check the marginal area of the target and insert it again many times during MIS. To reduce the surgeon's load, we aim to visualize the entire thoracic cavity using a newly developed device called "panorama vision ring" (PVR). METHOD: The PVR is used instead of a wound retractor or a trocar. It is a ring-type socket with one big hole for the thoracoscope and four small holes for tiny cameras placed around the big hole. The views from the tiny cameras are fused into one wider view that visualizes the entire thoracic cavity. A surgeon can proceed with an operation by checking what exists outside of the thoracoscopic view. Also, she/he can check whether or not bleeding has occurred from the image of the entire cavity. RESULTS: We evaluated the view-expansion ability of the PVR by using a three-dimensional full-scale thoracic model. The experimental results showed that the entire thoracic cavity could be visible in a panoramic view generated by the PVR. We also demonstrated pulmonary lobectomy in virtual MIS using the PVR. Surgeons could perform a pulmonary lobectomy while checking the entire cavity. CONCLUSION: We developed the PVR, which uses tiny auxiliary cameras to create a panoramic view of the entire thoracic cavity during MIS. We aim to make MIS safer for patients and more comfortable for surgeons through the development of the PVR.

DOI： 10.1007/s11548-023-02859-5

Clinical application of resection process map as a novel surgical guide in thoracic surgery. Reviewed International journal

Yuka Kadomatsu, Megumi Nakao, Harushi Ueno, Shota Nakamura, Koichi Fukumoto, Toyofumi Fengshi Chen-Yoshikawa

Interdisciplinary cardiovascular and thoracic surgery Vol. 36 ( 4 ) 2023.4

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

Resection Process Map (RPM) is a surgical simulation system that uses preoperative three-dimensional computed tomography. Unlike the usual static simulation, this system provides surgeons an individualized dynamic deformation of the lung parenchyma and vessels. RPM was first introduced in 2020. Although the intraoperative usefulness of this system has been evaluated experimentally, there have been no reports on its clinical use. Herein, we presented in detail the first experience on RPM during robot-assisted anatomical lung resection in the real clinical setting.

DOI： 10.1093/icvts/ivad059

連載未来の専門医を育てる! 名古屋大学の呼吸器外科教育-理想と現実のはざまで考えること

芳川豊史

胸部外科 Vol. 76 ( 4 ) page： 313 - 315 2023.4

Video-assisted thoracoscopic surgery for pleuroperitoneal communication. Reviewed

Hideki Tsubouchi, Shota Nakamura, Takayuki Fukui, Yuka Kadomatsu, Harushi Ueno, Naoki Ozeki, Koichi Fukumoto, Masashi Mizuno, Toyofumi F Chen-Yoshikawa

Asian journal of endoscopic surgery Vol. 16 ( 2 ) page： 262 - 265 2023.4

Authorship：Last author,　Corresponding author Language：English

Here we report the cases of five patients on continuous ambulatory peritoneal dialysis (CAPD) who developed hydrothorax because of pleuroperitoneal communication. Preoperative computed tomography (CT) peritoneography revealed penetrated sites on the diaphragm in all patients. All patients underwent video-assisted thoracoscopic surgery (VATS), and a dialysate containing indigo carmine was injected intraperitoneally through a CAPD catheter to confirm the fistula. In all patients, a thinned bleb was found at the center of the diaphragmatic tendon consistent with that noted on preoperative CT peritoneography. The bleb was resected using a surgical stapler in four patients, and the pleuroperitoneal communication did not recur. However, in one patient, the bleb was only covered with reinforcement agents and the hydrothorax recurred after CAPD. This study demonstrates that VATS treatment for pleuroperitoneal communication is safe and effective but that lesion resection would be more useful for preventing hydrothorax recurrence in patients undergoing CAPD.

DOI： 10.1111/ases.13127

術前に加えて周術期における脊柱起立筋CT値の低下も予後不良因子である

大島洋平, 佐藤晋, 芳川豊史, 中島大輔, 栢分秀直, 田中里奈, 山田義人, 豊洋次郎, 濱路政嗣, 大角明宏, 伊達洋至, 松田秀一

移植 Vol. 57 ( 4 ) page： 335 - 335 2023.4

生体肺移植後の健康関連QoLの実態調査脳死肺移植との比較

大島洋平, 佐藤晋, 芳川豊史, 中島大輔, 吉岡佑二, 濱田涼太, 梶本泰志, 太田垣あゆみ, 田中里奈, 山田義人, 豊洋次郎, 大角明宏, 濱路政嗣, 伊達洋至, 松田秀一

移植 Vol. 57 ( 4 ) page： 425 - 425 2023.4

Enteral liquid ventilation oxygenates a hypoxic pig model Reviewed

Fujii T., Yoneyama Y., Kinebuchi A., Ozeki N., Maeda S., Saiki N., Chen-Yoshikawa T.F., Date H., Nishiwaki K., Takebe T.

iScience Vol. 26 ( 3 ) 2023.3

Language：English Publisher：iScience

The potential of extrapulmonary ventilation pathways remains largely unexplored. Here, we assessed the enteral ventilation approach in hypoxic porcine models under controlled mechanical ventilation. 20 mL/kg of oxygenated perfluorodecalin (O2-PFD) was intra-anally delivered by a rectal tube. We simultaneously monitored arterial and pulmonary arterial blood gases every 2 min up to 30 min to determine the gut-mediated systemic and venous oxygenation kinetics. Intrarectal O2-PFD administration significantly increased the partial pressure of oxygen in arterial blood from 54.5 ± 6.4 to 61.1 ± 6.2 mmHg (mean ± SD) and reduced the partial pressure of carbon dioxide from 38.0 ± 5.6 to 34.4 ± 5.9 mmHg. Early oxygen transfer dynamics inversely correlate with baseline oxygenation status. SvO2 dynamic monitoring data indicated that oxygenation likely originated from the venous outflow of the broad segment of large intestine including the inferior mesenteric vein route. Enteral ventilation pathway offers an effective means for systemic oxygenation, thus warranting further clinical development.

DOI： 10.1016/j.isci.2023.106142

ASO Visual Abstract: Impact of Pleural Thickness on the Occurrence of Postoperative Complications in Patients with Malignant Pleural Mesothelioma

Ito T., Nakamura S., Kadomatsu Y., Ueno H., Kato T., Ozeki N., Fukumoto K., Chen-Yoshikawa T.F.

Annals of surgical oncology Vol. 30 ( 3 ) 2023.3

Impact of Pleural Thickness on Occurrence of Postoperative Complications in Patients with Malignant Pleural Mesothelioma Reviewed

Ito T., Nakamura S., Kadomatsu Y., Ueno H., Kato T., Ozeki N., Fukumoto K., Chen-Yoshikawa T.F.

Annals of Surgical Oncology Vol. 30 ( 3 ) page： 1574 - 1583 2023.3

Authorship：Last author Language：English Publisher：Annals of Surgical Oncology

Objectives: The rates of postoperative mortality and morbidity are high in patients with malignant pleural mesothelioma (MPM). Therefore, it is important to identify variables that increase the risk of postoperative complications. Pleural thickness has recently been identified as a prognostic indicator in patients with MPM. The aim of this study was to investigate clinical variables, including pleural thickness, that contribute to postoperative complications in patients with MPM. Patients and Methods: A total of 47 patients who underwent surgical excision of MPM between 2005 and 2021 were enrolled in this study. Correlations between postoperative complications within 90 days of surgery and preoperative clinical factors were investigated. Results: A total of 27 patients underwent extrapleural pneumonectomy (EPP), and the remaining 20 underwent pleurectomy/decortication (P/D). Macroscopic complete resections were obtained in all but three patients. Of the 47 patients, 23 (49%) experienced postoperative complications of grade 3 or worse. The major complication in patients with EPP was respiratory failure (n = 6), whereas the major complication in patients with P/D was prolonged air leakage (n = 7). Univariate logistic regression analysis found a correlation between postoperative complications and age, surgical side, and pleural thickness, while multivariate logistic regression analysis found surgical side (p = 0.04, 95% Cl 1.10–21.71, OR 4.90) and pleural thickness (p = 0.03, 95% Cl 1.21–23.00, OR 5.26) to significantly influence the occurrence of postoperative complications. Conclusions: Pleural thickness has a significant effect on the occurrence of postoperative complications. Patients with thick pleura on the right side are at greater risk of postoperative complications.

DOI： 10.1245/s10434-022-12790-9

ASO Author Reflections: Pleural Thickness in Patients with Malignant Pleural Mesothelioma

Nakamura S., Ito T., Chen-Yoshikawa T.F.

Annals of Surgical Oncology Vol. 30 ( 3 ) page： 1584 - 1585 2023.3

Real-world evidence of safety and influence for lung cancer surgery under COVID-19 pandemic in Japan. Reviewed International journal

Taketo Kato, Ryotaro Katsuya, Shoji Okado, Keiyu Sato, Osamu Noritake, Keita Nakanishi, Misa Noguchi, Yuka Kadomatsu, Harushi Ueno, Naoki Ozeki, Shota Nakamura, Koichi Fukumoto, Toyofumi Fengshi Chen-Yoshikawa

Journal of thoracic disease Vol. 15 ( 2 ) page： 542 - 551 2023.2

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The COVID-19 pandemic has affected the clinical practice of lung cancer surgery in Japan, but few studies have revealed the real situation of surgical practice for lung cancer in this country. This latest information will help us to decide the future direction of lung cancer surgery under pandemic circumstances. METHODS: We collected data from patients with primary lung cancer who underwent thoracic surgery between 2018 and 2021. To investigate the impact of the COVID-19 pandemic on lung cancer surgery, we compared between 2018-2019 (prepandemic group) and 2020-2021 (pandemic group) in the respect of patient characteristics, pathological findings, and short-term outcome after lung cancer resection by Mann-Whitney and Fisher's exact tests. Moreover, the monthly number of surgeries for lung cancer in our institution during 2020-2021 was compared with the number of newly diagnosed COVID-19 patients in Japan by Spearman correlation analysis. RESULTS: From 2018 through 2021, 936 patients with primary lung cancer underwent surgical intervention in our institute and were included in this study. The number of surgeries did not decrease in the pandemic group (n=443) compared with that in the prepandemic group (n=493). Tumor and invasive size in stage I which was measured by pathologist were significantly larger in the pandemic group than in the prepandemic group (tumor size: P=0.031, invasive size: P<0.001). In terms of postoperative short-term outcome, the median hospital stay was 6 days, 30-day mortality was 2, and morbidity was around 20% in both groups. Only one patient suffered from COVID-19 infection 5 months after right upper lobectomy. An increased ratio of newly diagnosed COVID-19 cases in Japan was negatively correlated with the number of surgeries for lung cancer in our institution in the next month (r=-0.393, P=0.007), although there was no correlation in the present or the month after next. CONCLUSIONS: Even during the COVID-19 pandemic period, lung cancer surgery could be performed safely and in a sustainable manner. However, pathological findings of lung cancer tended to be progressive in early-stage lung cancer.

DOI： 10.21037/jtd-22-1289

The Clinical Application and Future Perspective of Fluorescence Imaging in the Treatment of Lung Cancer

Chen-Yoshikawa Toyofumi Fengshi

The Journal of Japan Society for Laser Surgery and Medicine Vol. 43 ( 4 ) page： 302 - 307 2023.1

Language：Japanese Publisher：Japan Society for Laser Surgery and Medicine

As radiological imaging has progressed, smaller nodules are more frequently detected. The trend of minimal invasiveness in thoracic surgery has paved the way for video-assisted thoracic surgery. In localization for small nodules and segmentectomy for such nodules, fluorescent dyes, such as indocyanine green (ICG) have been used more often. Therefore, we herein describe the utility of fluorescent imaging in the treatment of lung cancer, which is currently the mainstream of thoracic surgery, focusing on the clinical application of ICG.

DOI： 10.2530/jslsm.jslsm-43_0012

Dual inhibition of the MEK/ERK and PI3K/AKT pathways prevents pulmonary GVHD suppressing perivenulitis and bronchiolitis. Reviewed International journal

Hiroyuki Muranushi, Takero Shindo, Toyofumi F Chen-Yoshikawa, Akihiko Yoshizawa, Huong Thi Ngo, Fumiaki Gochi, Hiroshi Date, Akifumi Takaori-Kondo

Blood advances Vol. 7 ( 1 ) page： 106 - 121 2023.1

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

Patients with pulmonary graft-versus-host disease (pGVHD) have a poor prognosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Furthermore, pGVHD pathogenesis is not fully elucidated in humans, and currently available immunosuppressants are inadequately effective. We performed pathologic evaluation of lung specimens from 45 allo-HSCT recipients with pGVHD who underwent lung transplantation. Patient pathology was characterized by bronchiolitis and subpleural perivascular inflammation, with B-cell, monocyte, and T-cell accumulation around bronchioles. Bronchiolitis, perivascular inflammation, and peribronchial macrophage aggregation were also identified in a murine pGVHD model after transplant of bone marrow cells and splenocytes from C57BL/6 to B10.BR mice. Among mitogen-activated protein kinase kinase (MEK) inhibitors, cobimetinib, but not trametinib, improved survival rates. Cobimetinib attenuated bronchiolitis, improved airway resistance and lung compliance in the mice, and suppressed activation of B cells and tumor necrosis factor α production by monocytes in vitro; these features were not suppressed by trametinib or tacrolimus. Furthermore, cobimetinib suppressed activation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling, resulting in B-cell and monocyte suppression. Dual inhibition of the MEK/extracellular signal-regulated kinase (ERK) and PI3K/AKT pathways using a combination of trametinib and the PI3K inhibitor taselisib strongly suppressed B-cell activation in vitro and improved mouse survival rates compared with vehicle or monotherapy with trametinib or taselisib. Imaging mass cytometry of human pGVHD revealed that T cells around bronchioles were positive for phosphorylated ERK, whereas B cells were positive for phosphorylated AKT. Thus, perivascular inflammation and bronchiolitis mediated by activation of the MEK/ERK and PI3K/AKT pathways are essential for pGVHD and represent a potential novel therapeutic target in humans.

DOI： 10.1182/bloodadvances.2021006678

Cadaver surgical training for brain-dead donor lung procurement: Educational note Reviewed

Nakamura S., Ueno H., Mutsuga M., Chen-Yoshikawa T.F.

JTCVS Techniques 2023

Long-term outcomes following surgical treatment for thymic epithelial tumor in Japan and an analysis of prognostic factors based on the Japanese Association for Research on the Thymus nationwide database Reviewed

Okumura M., Yoshino I., Funaki S., Okuda K., Watanabe S.i., Tsuboi M., Shimizu K., Date H., Chen-Yoshikawa T.F., Nakajima J., Toyooka S., Asamura H.

Surgery Today 2023

Language：English Publisher：Surgery Today

Purpose: Patients with a thymic epithelial tumor (TET), comprising thymoma, thymic carcinoma (TC), and thymic neuroendocrine neoplasm (TNEN), are rarely encountered. The present study was conducted to determine the recent outcomes of surgical treatment for TET in Japan and clarify the significance of prognostic factors by analyzing a nationwide database created by the Japanese Association for Research on the Thymus (JART). Methods: The JART database includes records of 2471 thymoma, 285 TC, and 56 TNEN cases surgically treated between 1991 and 2010. At the time of the final follow-up examination, 439 patients had died, with tumor the cause of death in 188. The disease-specific survival was examined using the Kaplan–Meier method, with Cox’s proportional hazards model utilized to determine independent prognostic factors. Results: The 10-year survival rate according to TNM-based Stage I, II, IIIA, IIIB, IVA, and IVB classification was 98.7%, 76.8%, 85.0%, 68.9%, 66.2%, and 59.8%, respectively. The T factor, M factor, and tumor size were independent prognostic factors in both thymoma and thymic carcinoma cases, while the N factor had tendency to be a prognostic factor in thymoma but not in thymic carcinoma cases. The WHO histological type was an independent factor in thymoma cases. Conclusion: The significance of pathology and TNM classification as prognostic factors was confirmed.

DOI： 10.1007/s00595-023-02705-w

Impact of perioperative airway pathogens on living-donor lobar lung transplantation outcomes Reviewed

Oda H., Tanaka S., Chen-Yoshikawa T.F., Morimura Y., Yamada Y., Yutaka Y., Nakajima D., Hamaji M., Ohsumi A., Menju T., Nagao M., Date H.

Surgery Today 2023

Language：English Publisher：Surgery Today

Purpose: To elucidate the clinical impact of pathogenic organism (PO) positivity early after transplantation, we evaluated the impact of perioperative airway POs on outcomes after living-donor lobar lung transplantation (LDLLT), where the graft airway is supposed to be sterile from a healthy donor. Method: A retrospective review of 67 adult LDLLT procedures involving 132 living donors was performed. Presence of POs in the recipients’ airways was evaluated preoperatively and postoperatively in intensive-care units. Results: POs were detected preoperatively in 13 (19.4%) recipients. No POs were isolated from the donor airways at transplantation. POs were detected in 39 (58.2%) recipients postoperatively; most were different from the POs isolated preoperatively. Postoperative PO isolation was not associated with short-term outcomes other than prolonged postoperative ventilation. The 5-year overall survival was significantly better in the PO-negative group than in the PO-positive group (89.1% vs. 63.7%, P = 0.014). In the multivariate analysis, advanced age (hazard ratio [HR]: 1.041 per 1-year increase, P = 0.033) and posttransplant PO positivity in the airway (HR: 3.684, P = 0.019) significantly affected the survival. Conclusions: The airways of the living-donor grafts were microbiologically sterile. PO positivity in the airway early after transplantation negatively impacted long-term outcomes.

DOI： 10.1007/s00595-023-02730-9

Effectiveness and safety of rituximab in desensitization and for treatment of antibody-mediated rejection in a multicenter prospective study assessing liver, pancreas, lung, and heart transplantation

EGAWA Hiroto, ITO Taihei, ONO Minoru, CHEN-YOSHIKAWA Toyofumi, HASEGAWA Kiyoshi, NUNODA Shinichi, DATE Hiroshi, FUKUSHIMA Norihide, EGUCHI Susumu, HIBI Taizo, OGURA Yasuhiro, MIYAGI Shigehito, AKAMATSU Nobuhisa, ICHIDA Akihiko, HAGA Hironori, TERAMUKAI Satoshi

Japanese Journal of Transplantation Vol. 58 ( 1 ) page： 43 - 57 2023

Language：English Publisher：The Japan Society for Transplantation

【Background】 Few studies have assessed donor-specific antibodies (DSA) and anti-human leucocyte antigen (HLA) antibodies associated with the transplantation (Tx) of organs other than kidney.【Methods】 A total of 31 institutions participated in the current study. Patients who satisfied the study criteria were enrolled prospectively, and rituximab was used according to each institution’s clinical protocol for desensitization before Tx when patients had preexisting DSA or anti-HLA antibodies (desensitization cohort) or to treat post-Tx antibody-mediated rejection (ABMR) (ABMR treatment cohort). The desensitization cohort comprised four liver transplants, four kidney-pancreas transplants, and one heart transplant, and the ABMR treatment cohort contained two liver transplants, two heart transplants, and one lung transplant. In the desensitization cohort, organs ultimately were not allocated for the patient awaiting a heart transplant and one patient awaiting a kidney-pancreas transplant.【Results】 In the desensitization cohort, DSA or anti-HLA antibodies decreased in the four liver Tx patients and three of the kidney-pancreas Tx patients. Although T-cell mediated rejection occurred in two patients, they did not develop ABMR. One pancreatic graft was lost due to post-transplantation thrombosis; all other grafts and all patients survived. In the ABMR treatment cohort, DSA decreased after ABMR treatment in one heart Tx patient and two liver Tx patients. Acute ABMR was eliminated completely only in the patient who developed the complication early after liver Tx.【Conclusion】 Rituximab was well-tolerated, both during desensitization and as part of ABMR treatment for Tx of organs other than kidney.

DOI： 10.11386/jst.58.1_43

可変形3次元画像による大規模バーチャル手術手技アトラスと呼吸器外科手術ガイドシステムの創出

芳川豊史, 中尾恵

生体医工学 Vol. Annual61 ( Abstract ) page： 128_2 - 128_2 2023

Language：Japanese Publisher：公益社団法人日本生体医工学会

目的：低侵襲化の道を進む、匠の技である、無形の呼吸器外科手術手技について、可変形3次元画像と大規模なバーチャル手術手技アトラスを用いて有形化する。さらに、呼吸器外科手術ガイドシステムの創出により、呼吸器外科手術の高位平準化を図る。方法：本研究は、現有のシーズである画像変形推定技術と切離プロセスマッピングという技術を用いて、患者個人のCT情報をもとに、可変形3次元バーチャル画像を作成し研究開発を行う。結果：これまでの開発において達成し得たものを紹介する。まず、種々の手術術式において、可変形3次元バーチャル画像を作成し実際の手術画像と対比させたバーチャル手術手技アトラスを作成できた。次に、肺切除で最も肝要な、肺門や葉間というレベルでの血管や気管支という脈管構造の剥離のシミュレーションを、患者個人のCT情報をもとに、可変形3次元バーチャル画像を用いて行い得た。その際に、肺内を透見できる画像技術や手前の構造物を消去する技術を導入した。実際の手術において、患者個人のCT情報をもとに作成した可変形3次元バーチャル画像を自由に動かし、実際の手術における手術ガイドを10数例の解剖学的肺切除で行い得た。結語：我々が手掛けている可変形3次元バーチャル画像による手術ガイドについて進捗を紹介した。

DOI： 10.11239/jsmbe.annual61.128_2

Retrospective observation study of intravenous immunoglobulin therapy for antibody-mediated rejection in lung transplantation Reviewed

NAKAJIMA Daisuke, DATE Hiroshi, MATSUBARA Kei, SUGIMOTO Seiichiro, SHIRAISHI Takeshi, HIRAMA Takeshi, CHEN-YOSHIKAWA Toyofumi F., NAKAGAWA Ken, EGAWA Hiroto

Japanese Journal of Transplantation Vol. 58 ( 4 ) page： 371 - 380 2023

Authorship：Lead author Language：Japanese Publisher：The Japan Society for Transplantation

【Objective】 The aim of this study was to investigate the efficacy and safety of intravenous immunoglobulin (IVIG)-based therapy for antibody-mediated rejection (AMR) in lung transplantation in Japan.【Methods】 This retrospective observation study enrolled 48 patients, including 41 adults and 7 children, who underwent IVIG-based therapy for AMR in 4 lung transplant hospitals in Japan between April 2001 and March 2022.【Results】 AMR was treated by IVIG alone in 18 patients or IVIG combined with other therapies, including, in particular, steroid pulse therapy, plasma exchange, and/or rituximab. The total dose of IVIG was 0.15 g/kg-8.82 g/kg (median: 1.71 g/kg). Donor-specific antibody (DSA) developed in 33 patients after lung transplantation. Following IVIG-based therapy, DSA titer decreased in all DSA to human leukocyte antigen (HLA) class I and 90% of DSA to HLA class II, and AMR was ameliorated in 41 patients (85.4%). The 6- and 12-month graft survival after IVIG-based therapy were 85.4% and 83.0%, respectively. The 6- and 12-month overall survival rates after IVIG-based therapy were 93.8% and 87.5%, respectively. Serious adverse events related directly to IVIG administration were not observed in this study.【Conclusion】 IVIG-based therapy could be performed safely, could reduce circulating de novo DSA, and could improve AMR after lung transplantation.

DOI： 10.11386/jst.58.4_371

Cadaveric donor lung procurement for transplantation

HOSHIKAWA Yasushi, MATSUDA Yasushi, YOSHIKAWA Toyofumi

Japanese Journal of Transplantation Vol. 58 ( 2 ) page： 71 - 76 2023

Language：Japanese Publisher：The Japan Society for Transplantation

The key to cadaveric donor lung procurement is close collaboration with the other procurement teams, especially the donor heart procurement team which shares the surgical field throughout the entire process, local anesthesiologists, and the Japan Organ Transplant Network coordinators, reliable assessment of the donor lungs, and skillful and consistent surgical technique to complete the harvest without error within a limited time frame. In order to standardize these procurement procedures and present them to all lung procurement teams in Japan, a manual on cadaveric donor lung procurement has been published on the website of the Japan Society for Transplantation. The original version of this manual was prepared through a questionnaire survey conducted from March to May 2011 among seven lung transplant centers at that time to confirm surgical techniques and collect tips and pitfalls, followed by careful e-mail discussion and consensus building. From April to June 2021, another questionnaire was sent to 10 lung transplant centers, and after careful e-mail discussion, a revised version was created. In this process, the technique was reconfirmed and standardized among 10 centers. This article outlines the preparation, preoperative meeting, and procedure for donor lung procurement in the case of heart procurement, in accordance with the Lung Procurement Manual (revised edition 2021) of the Japan Society for Transplantation.

DOI： 10.11386/jst.58.2_71

Radiologic evaluation of compensatory lung growth using computed tomography by comparison with histological data from a large animal model Reviewed

脊柱起立筋の断面積は造血幹細胞移植後肺障害患者における肺移植待機中の生命予後と関連する

濱田涼太, 大島洋平, 吉岡佑二, 梶本泰志, 太田垣あゆみ, 堀江賢, 田辺直也, 池口良輔, 佐藤晋, 芳川豊史, 中島大輔, 伊達洋至, 松田秀一

呼吸理学療法学 Vol. 3 ( Suppl. ) page： 156 - 156 2023

Ohata K., Chen-Yoshikawa T.F., Hamaji M., Kubo T., Nakamura T., Date H.

Scientific Reports Vol. 12 ( 1 ) 2022.12

Language：English Publisher：Scientific Reports

Non-invasive analysis using computed tomography (CT) data may be a promising candidate to evaluate neo-alveolarization in adult lungs following lung resection. This study evaluates and compares the validity of CT analysis with histologic morphometry for compensatory lung growth in a large animal model. We calculated the radiologic tissue volume and the radiologic lung weight from CT data taken at 1, 3, and 6 months post-surgery on 15 male beagle dogs that had a right thoractotomy, bilobectomy, or pneumonectomy (n = 5 in each group). Results were analyzed using one-way ANOVA and were subsequently compared to histologic findings of tissue samples at 6 months post-surgery using Pearson’s correlation. An increase in radiologic tissue volume and radiologic lung weight was identified, which was positively correlated with histologic lung parenchymal amounts (correlation coefficient = 0.955 and 0.934, respectively, p < 0.001). Histology of lung specimens at 6 months post-surgery revealed an increase in the tissue amount in both Bilobectomy and Peumonectomy groups, which was consistent with compensatory lung growth. Radiologic tissue volume and radiologic lung weight reflected compensatory lung growth following lung resection. Radiologic assessment using CT data can be a promising clinical modality to evaluate postoperative lung growth.

DOI： 10.1038/s41598-022-06398-y

Adjuvant atezolizumab in Japanese patients with resected stage IB-IIIA non-small cell lung cancer (IMpower010) Reviewed

Kenmotsu H., Sugawara S., Watanabe Y., Saito H., Okada M., Chen-Yoshikawa T.F., Ohe Y., Nishio W., Nakagawa S., Nagao H.

Cancer Science Vol. 113 ( 12 ) page： 4327 - 4338 2022.12

Language：English Publisher：Cancer Science

The global phase 3 IMpower010 study evaluated adjuvant atezolizumab versus best supportive care (BSC) following platinum-based chemotherapy in patients with resected stage IB–IIIA non-small cell lung cancer (NSCLC). Here, we report a subgroup analysis in patients enrolled in Japan. Eligible patients had complete resection of histologically or cytologically confirmed stage IB (tumors ≥4 cm)–IIIA NSCLC. Upon completing 1–4 cycles of adjuvant cisplatin-based chemotherapy, patients were randomized 1:1 to receive atezolizumab (fixed dose of 1200 mg every 21 days; 16 cycles or 1 year) or BSC. The primary endpoint of the global IMpower010 study was investigator-assessed disease-free survival, tested hierarchically first in patients with stage II–IIIA NSCLC whose tumors expressed programmed death-ligand 1 (PD-L1) on ≥1% of tumor cells, then in all randomized patients with stage II–IIIA NSCLC, and finally in the intention-to-treat (ITT) population (stage IB–IIIA NSCLC). Safety was evaluated in all patients who received atezolizumab or BSC. The study comprised 149 enrolled patients in three populations: ITT (n = 117; atezolizumab, n = 59; BSC, n = 58), all-randomized stage II–IIIA (n = 113; atezolizumab, n = 56; BSC, n = 57), and PD-L1 tumor cells ≥1% stage II–IIIA (n = 74; atezolizumab, n = 41; BSC, n = 33). At the data cutoff date (January 21, 2021), a trend toward disease-free survival improvement with atezolizumab vs BSC was observed in the PD-L1 tumor cells ≥1% stage II–IIIA (unstratified hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.25–1.08), all-randomized stage II–IIIA (unstratified HR, 0.62; 95% CI, 0.35–1.11), and ITT (unstratified HR, 0.61; 95% CI, 0.34–1.10) populations. Atezolizumab-related grade 3/4 adverse events occurred in 16% of patients; no treatment-related grade 5 events occurred. Adjuvant atezolizumab showed disease-free survival improvement and a tolerable toxicity profile in Japanese patients in IMpower010, consistent with the global study results.

DOI： 10.1111/cas.15564

Prognostic impact of the number of peri-tumoral alveolar macrophages in patients with stage I lung adenocarcinoma Reviewed

Noritake Osamu, Aokage Keiju, Suzuki Ayako, Tane Kenta, Miyoshi Tomohiro, Samejima Joji, Yoshikawa Toyohumi, Murata Shawhay Charles, Nakai Tokiko, Tsuboi Masahiro, Ishii Genichiro

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY Vol. 148 ( 12 ) page： 3437 - 3447 2022.12

Language：English Publisher：Journal of Cancer Research and Clinical Oncology

Purpose: Intratumoral macrophages are reportedly involved in tumor progression in non-small cell lung cancer; however, little is known about the prognostic impact and function of alveolar macrophages (AMs). This study aims to investigate the prognostic impact of the number of peri-tumoral AMs in patients with stage I lung adenocarcinoma. Methods: We investigated 514 patients with pathological stage I lung adenocarcinoma who underwent complete resection with lobectomy or pneumonectomy. The numbers of peri-tumoral AMs were counted, and patients were classified into two groups based on the number of peri-tumoral AMs. Using the Cancer Genome Atlas (TCGA) database of stage I lung adenocarcinoma, we compared gene expression profiles of high and low peri-tumoral AM contents. Results: The median number of peri-tumoral AMs per alveolar space was 15.5. Patients with a high peri-tumoral AM content had significantly shorter disease-free survival and overall survival than patients with a low peri-tumoral AM content (both p < 0.01). In the multivariate analyses, a higher number of peri-tumoral AMs were an independent prognostic factor (p = 0.02). The analysis of TCGA database revealed that patients with a high peri-tumoral AM content had shorter disease-free survival than those with a low peri-tumoral AM content (p = 0.04). Gene expression analysis of TCGA stage I lung adenocarcinoma revealed enrichment of biological processes, such as chemotaxis and epithelial proliferation, in patients with a high peri-tumoral AM content. Conclusion: The number of peri-tumoral AMs had a strong impact on disease-free survival in patients with stage I lung adenocarcinoma.

DOI： 10.1007/s00432-022-04056-4

Assessing the development status of intraoperative fluorescence imaging for anatomy visualisation, using the IDEAL framework Reviewed

Ishizawa T., Mcculloch P., Stassen L., Van Den Bos J., Regimbeau J.M., Dembinski J., Schneider-Koriath S., Boni L., Aoki T., Nishino H., Hasegawa K., Sekine Y., Chen-Yoshikawa T., Yeung T., Berber E., Kahramangil B., Bouvet M., Diana M., Kokudo N., Dip F., White K., Rosenthal R.J.

BMJ Surgery, Interventions, and Health Technologies Vol. 4 ( 1 ) 2022.11

Language：English Publisher：BMJ Surgery, Interventions, and Health Technologies

Objectives Intraoperative fluorescence imaging is currently used in a variety of surgical fields for four main purposes: visualising anatomy, assessing tissue perfusion, identifying/localising cancer and mapping lymphatic systems. To establish evidence-based guidance for research and practice, understanding the state of research on fluorescence imaging in different surgical fields is needed. We evaluated the evidence on fluorescence imaging used to visualise anatomical structures using the IDEAL framework, a framework designed to describe the stages of innovation in surgery and other interventional procedures. Design IDEAL staging based on a thorough literature review. Setting All publications on intraoperative fluorescence imaging for visualising anatomical structures reported in PubMed through 2020 were identified for five surgical procedures: cholangiography, hepatic segmentation, lung segmentation, ureterography and parathyroid identification. Main outcome measures The IDEAL stage of research evidence was determined for each of the five procedures using a previously described approach. Results 225 articles (8427 cases) were selected for analysis. Current status of research evidence on fluorescence imaging was rated IDEAL stage 2a for ureterography and lung segmentation, IDEAL 2b for hepatic segmentation and IDEAL stage 3 for cholangiography and parathyroid identification. Enhanced tissue identification rates using fluorescence imaging relative to conventional white-light imaging have been documented for all five procedures by comparative studies including randomised controlled trials for cholangiography and parathyroid identification. Advantages of anatomy visualisation with fluorescence imaging for improving short-term and long-term postoperative outcomes also were demonstrated, especially for hepatobiliary surgery and (para)thyroidectomy. No adverse reactions associated with fluorescent agents were reported. Conclusions Intraoperative fluorescence imaging can be used safely to enhance the identification of anatomical structures, which may lead to improved postoperative outcomes. Overviewing current research knowledge using the IDEAL framework aids in designing further studies to develop fluorescence imaging techniques into an essential intraoperative navigation tool in each surgical field.

DOI： 10.1136/bmjsit-2022-000156

Comparison of international and Japanese predictive equations for maximal respiratory mouth pressures Reviewed

Hamada R., Oshima Y., Yoshioka Y., Chen-Yoshikawa T.F., Nakajima D., Nankaku M., Ikeguchi R., Date H., Matsuda S., Sato S.

Respiratory Investigation Vol. 60 ( 6 ) page： 847 - 851 2022.11

Language：Japanese Publisher：Respiratory Investigation

Respiratory muscle weakness has attracted attention because sarcopenia and respiratory muscle dysfunction may play a key role in the development of respiratory failure. To evaluate respiratory muscle strength appropriately, individual factors such as sex, age, body size, and ethnicity should be considered. This study aimed to compare equations available in Japan and other countries for predicting respiratory muscle strength. We tested 21 equations for maximal inspiratory pressure (MIP) and 17 for maximal expiratory pressure (MEP) for each sex (76 equations in total) in 159 normal, healthy subjects. We observed wide variations in the overall agreement among the MIP and MEP equations. Some equations showed a proper normal distribution, with median values of almost 100%, and the Japanese equations released in 1997 generally showed the best distributions of both %MIP and %MEP. We can conclude that it is better to use Japanese equations when evaluating respiratory muscle strength in Japanese subjects.

DOI： 10.1016/j.resinv.2022.07.003

Neoadjuvant Therapy for Patients with Non-small Cell Lung Cancer Complicated with Chest Wall Invasion Reviewed

Sato K., Nakamura S., Kadomatsu Y., Ueno H., Kato T., Ozeki N., Fukumoto K., Chen-Yoshikawa T.F.

Anticancer Research Vol. 42 ( 11 ) page： 5539 - 5546 2022.11

Authorship：Last author Language：English Publisher：Anticancer Research

Background/Aim: Multidisciplinary treatment including anatomical pulmonary and chest wall resection is recommended for lung cancer complicated by chest wall invasion. The present study aimed to investigate the survival benefit and safety of preoperative therapy followed by surgery for non-small cell lung cancer with chest wall invasion. Patients and Methods: Sixty-five patients who underwent surgical excision of lung cancer complicated with chest wall invasion between 2009 and 2020 were enrolled in this study. Results: The median age was 65 (37-81) years old, with 59 males and 6 females. Histological types included squamous cell carcinoma (n=32) and adenocarcinoma (n=21). The median tumor diameter was 5.5 cm (2.3-12.5 cm). The clinical nodal status was N0 in 49 cases and N positive in 16 cases. Of the 65 eligible patients, 5- and 10-year overall survival (OS) rates were 58.4% and 46.0%, respectively, and 5- and 10-year progression-free survival (PFS) rates were 54.2% and 41.7%, respectively. For patients receiving preoperative therapy followed by surgery (Pre-Tx), 5- and 10-year OS survival rates were 69.2% and 62.9%, and among patients receiving up-front surgery (UFS) were 48.5% and 29.1%, respectively (p=0.03). The 5- and 10-year PFS rates for pre-Tx were 65.8% and 59.2%, respectively, and 44.7% and 26.8% for UFS, respectively (p=0.02). Cox regression analysis preoperative therapy was significantly associated with OS and PFS. Conclusion: We demonstrate the survival benefit of preoperative therapy followed by surgery for patients with lung cancer and chest wall invasion.

DOI： 10.21873/anticanres.16059

Diagnostic value and safety of endobronchial ultrasonography with a guide sheath transbronchial biopsy for diagnosing peripheral pulmonary lesions in patients with interstitial lung disease Reviewed

Ito T., Okachi S., Iwano S., Kinoshita F., Wakahara K., Hashimoto N., Chen-Yoshikawa T.F.

Journal of Thoracic Disease Vol. 14 ( 11 ) page： 4361 - 4371 2022.11

Authorship：Last author Language：English Publisher：Journal of Thoracic Disease

Background: Radial endobronchial ultrasonography transbronchial biopsy with and without a guide sheath is a useful method for diagnosing peripheral pulmonary lesions (PPLs). However, the diagnostic yield and complications of radial endobronchial ultrasonography transbronchial biopsy for PPLs remains elusive in patients with interstitial lung disease (ILD). Methods: We retrospectively analysed 431 patients (69 with and 362 without ILD) who underwent radial endobronchial ultrasonography with a guide sheath transbronchial biopsy (EBUS-GS TBB) for PPLs from April 1, 2011, to March 31, 2020. We investigated the diagnostic yield and complications of the procedure for PPLs and compared them between patients with and without ILD. We also evaluated the factors contributing to successful diagnosis. Results: The diagnostic yield of radial endobronchial ultrasonography in patients with ILD was significantly lower than in those without ILD (62.3% vs. 75.4%, P=0.024). Multivariate analysis showed that the presence of ILD as background lung [odds ratio (OR) =0.517], probe position within the lesion (OR =4.654), and the presence of solid lesion (OR =1.946) significantly affected the diagnostic yield of PPLs. There was a significant difference in the rate of pneumothorax between the patients with ILD and those without ILD (4.3% vs. 0.6%, P=0.031). Conclusions: The presence of ILD as the background lung significantly affected the diagnostic yield of PPLs with radial EBUS-GS TBB. Regarding the complications, pneumothorax occurred more frequently in patients with ILD than in those without ILD.

DOI： 10.21037/jtd-22-809

A novel system applying artificial intelligence in the identification of air leak sites Reviewed

Kadomatsu Y., Nakao M., Ueno H., Nakamura S., Chen-Yoshikawa T.F.

JTCVS Techniques Vol. 15 page： 181 - 191 2022.10

Authorship：Last author Language：English Publisher：JTCVS Techniques

Objective: Prolonged air leak is the most common complication of thoracic surgery. Intraoperative leak site detection is the first step in decreasing the risk of leak-related postoperative complications. Methods: We retrospectively reviewed the surgical videos of patients who underwent lung resection at our institution. In the training phase, deep learning-based air leak detection software was developed using leak-positive endoscopic images. In the testing phase, a different data set was used to evaluate our proposed application for each predicted box. Results: A total of 110 originally captured and labeled images obtained from 70 surgeries were preprocessed for the training data set. The testing data set contained 64 leak-positive and 45 leak-negative sites. The testing data set was obtained from 93 operations, including 58 patients in whom an air leak was present and 35 patients in whom an air leak was absent. In the testing phase, our software detected leak sites with a sensitivity and specificity of 81.3% and 68.9%, respectively. Conclusions: We have successfully developed a deep learning-based leak site detection application, which can be used in deflated lungs. Although the current version is still a prototype with a limited training data set, it is a novel concept of leak detection based entirely on visual information.

DOI： 10.1016/j.xjtc.2022.06.011

The impact of COVID-19 on thoracic surgical procedures in Japan: Analysis of data from the National Clinical Database Reviewed

Is it true that less is more in thoracic surgery? Invited Reviewed

Chen-Yoshikawa T.F.

Journal of Thoracic Disease Vol. 14 ( 10 ) page： 3674 - 3676 2022.10

Sato Y., Yamamoto H., Ikeda N., Konishi H., Endo S., Okada Y., Kondo H., Shintani Y., Toyooka S., Nakamura H., Hoshikawa Y., Chen-Yoshikawa T.F., Yoshino I., Kakizoe T., Chida M.

Lung Cancer Vol. 172 page： 127 - 135 2022.10

Language：English Publisher：Lung Cancer

Objective: The COVID-19 pandemic has far-reaching collateral health impacts on the ongoing delivery of surgical care worldwide. The current study was designed to analyze the impact of the COVID-19 pandemic on the number of surgeries of general thoracic surgery in Japan. Methods: Changes in the number of surgeries for total and three representative tumors were analyzed using the National Clinical Database data with reference to the pandemic infection rate and lung cancer screening. Results: In 2020, the number of surgeries in total and for primary lung cancer and mediastinal lung tumor decreased by 4.9, 5.1, and 5.0 %, respectively. Considering the five-year trend towards a 5 % annual increase, there was a potential 10 % decrease in the number of primary lung cancer surgeries. The number of primary lung cancer surgeries bottomed in July 2020 but recovered towards the end of the year. In contrast, the number of metastatic lung tumor surgeries in 2020 increased by 3.2 %, following a similar trend observed over the previous five years. The number of lung cancer screening examinees decreased markedly with the lowest number in May. Our findings indicate that surgical triage had a limited impact on the decrease in primary lung cancer surgeries during the pandemic; rather, the decrease in lung cancer screening, which was a few months preceding, is most likely responsible. Conclusions: The decrease in primary lung cancer was mainly caused by the decrease in lung cancer screening, indicating that continuing screening is vital even during a pandemic.

DOI： 10.1016/j.lungcan.2022.08.011

Prevention of droplet dispersal with ‘e-mask’: A new daily use endoscopic mask during bronchoscopy Reviewed

Ito T., Okachi S., Sato K., Yasui H., Fukatsu N., Ando M., Chen-Yoshikawa T.F., Saka H.

Respirology Vol. 27 ( 10 ) page： 863 - 873 2022.10

Language：English Publisher：Respirology

Background and objective: Bronchoscopy is an airborne particle-generating procedure. However, few methods for safe bronchoscopy have been developed. To reduce airborne particles during bronchoscopy, we created an ‘e-mask’, which is a simple, disposable mask for patients. Our objective was to evaluate the e-mask's protective ability against airborne particles and to assess respiratory adverse events and complications. Methods: Patients with stage 2–4 chronic obstructive pulmonary disease were excluded. We performed visualization and quantifying experiments on airborne particles with and without the e-mask. We prospectively evaluated whether wearing the e-mask during bronchoscopy was associated with the incidence of patients requiring >5 L/min oxygen to maintain >90% oxygen saturation, and patients with >45 mm Hg end-tidal carbon dioxide (EtCO2) elevation, in addition to complications, compared to historical controls. Results: In the visualization experiment, more than ten thousand times of airborne particles were generated without the e-mask than with the e-mask. The volume of airborne particles was significantly reduced with the e-mask, compared to that without the e-mask (p = 0.011). Multivariate logistic regression analysis revealed that wearing the e-mask had no significant effect on the incidence of patients requiring >5 L/min oxygen to maintain >90% oxygen saturation, (p = 0.959); however, wearing the e-mask was a significant factor in >45 mm Hg EtCO2 elevation (p = 0.026). No significant differences in complications were observed between the e-mask and control groups (5.8% vs. 2.5%, p = 0.395). Conclusion: Wearing the e-mask during bronchoscopy significantly reduced the generation of airborne particles during bronchoscopy without increasing complications.

DOI： 10.1111/resp.14321

Skeletal muscle and related protein expression as prognostic factors in thymic squamous cell carcinoma Reviewed

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

Journal of Thoracic Disease Vol. 14 ( 9 ) page： 3245 - 3254 2022.9

Authorship：Last author Language：English Publisher：Journal of Thoracic Disease

Background: Sarcopenia and its marker, the psoas muscle index (PMI), have attracted attention as prognostic factors for various types of cancers. The fragile X-related 1 (FXR1) gene is highly expressed in myocytes, and FXR1 overexpression is a candidate biomarker for poor survival in several types of cancers. Thymic squamous cell carcinoma (TSQCC) is rare, and no studies assessing its prognostic factors, particularly in terms of skeletal muscle mass and FXR1 expression, are available. Methods: We retrospectively investigated the prognostic significance of PMI in 34 patients who underwent TSQCC resection, considering the status of FXR1 and tumor programmed death-ligand 1 (PD-L1). PMI was calculated from the bilateral psoas muscle using preoperative computed tomography (CT). Patients were divided into two groups: low PMI (<58.2%, n=17) and normal PMI (≥58.2%, n=17). Immunohistochemical analysis was performed to determine the FXR1 and PD-L1 expression levels. Results: Low PMI was significantly associated with worse overall survival (OS) (5-year survival rate; 86% vs. 100%; P=0.026) and marginally associated with worse disease-free survival (DFS) (5-year survival rate; 39% vs. 66%; P=0.090) compared with normal PMI. The immunohistochemical analysis revealed that the FXR1 intensity score (0–1+: 6% vs. 0%; 2+–3+: 94% vs. 100%; P=0.31), median FXR1 distribution (95% vs. 90%; P=0.63), and PD-L1 status (high: 47% vs. 59%; P=0.49) were not significantly different between the two groups. Conclusions: Our findings suggest that PMI might be considered as a potential prognostic factor in TSQCC and that FXR1 is widely expressed regardless of the PMI status. Skeletal muscle mass may play a role in the prognosis of TSQCC.

DOI： 10.21037/jtd-22-385

Chest three-dimensional-computed tomography imaging data analysis for the variation of exercise capacity after lung lobectomy Reviewed

Reply From Authors: How a cell dies matters and how to evaluate it also matters Reviewed

Ueda S., Chen-Yoshikawa T.F., Tanaka S., Yamada Y., Nakajima D., Ohsumi A., Date H.

JTCVS Open Vol. 11 2022.9

Long-term Follow-up Study of Thymic Epithelial Tumors. Report of the Updated Nation-wide Database in Japan Reviewed

Okumura M., Yoshino I., Shintani Y., Nakanishi R., Yoshikawa T., Date H., Toyooka S-I., Shimizu K., Nakajima J., Tsuboi M., Watanabe S-I., Asamura H.

JOURNAL OF THORACIC ONCOLOGY Vol. 17 ( 9 ) page： S78 - S79 2022.9

Ozeki N., Iwano S., Nakamura S., Kawaguchi K., Mizuno Y., Inoue T., Nagaya M., Chen-Yoshikawa T.F.

Clinical Physiology and Functional Imaging Vol. 42 ( 5 ) page： 362 - 371 2022.9

Authorship：Last author Language：English Publisher：Clinical Physiology and Functional Imaging

Background: Postoperative loss of exercise capacity and pulmonary function is a major concern among lung cancer patients. In this study, the time for a stair-climbing to 12-m height was used to investigate whether preoperative chest 3D-computed tomography (CT) could be a useful tool for predicting postoperative variations in exercise capacity and pulmonary function. Methods: Seventy-eight patients undergoing lobectomy for suspected stage I lung cancer were prospectively enroled. Preoperatively, lobe volume and low attenuation volume (LAV) were evaluated using the SYNAPSE VINCENT system. Preoperative data on stair-climbing time, spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) at baseline and 6-month postoperative data were used to evaluate variations in exercise capacity and pulmonary function. Maximal oxygen uptake (VO2t) was evaluated based on the stair-climbing time. Results: Significant differences in the variation of exercise capacity at 6 months postoperatively were found between the groups categorized by target lobe volume and LAV status: The large volume/LAV (+) group had a greater decline in VO2t. Mean loss of VO2t was −6.2%, −1.4%, −1.6% and −0.1% in the large volume/LAV (+), large volume/LAV (−), small volume/LAV (+) and small volume/LAV (−) groups, respectively. The large volume/LAV (−) group had a greater decline in forced expiratory volume in 1 s. The small volume/LAV (+) group showed a reduced decline in the DLCO. Conclusions: Analysis of chest 3D-CT scans is a potential tool for predicting the loss of exercise capacity and pulmonary function after lung lobectomy.

DOI： 10.1111/cpf.12777

Relationship of smoking cessation period with the incidence of complications in lung cancer surgery Reviewed

VAL-MAP14症例の検討

岡地祥太郎, 伊藤貴康, 若原恵子, 橋本直純, 中村彰太, 芳川豊史

気管支学 Vol. 44 ( 5 ) page： 400 - 400 2022.9

Kadomatsu Y., Sugiyama T., Sato K., Nakanishi K., Ueno H., Goto M., Ozeki N., Nakamura S., Fukumoto K., Chen-Yoshikawa T.F.

European journal of cardio-thoracic surgery Vol. 62 ( 3 ) 2022.8

Authorship：Last author Language：English Publisher：European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery

OBJECTIVES: The incidence of postoperative complications is relatively high in smokers. Although 4-week smoking cessation before surgery is generally recommended, it has not been sufficiently studied in lung cancer surgery. This study investigated whether smoking cessation for a short period of time significantly reduced complications after lung cancer surgery. METHODS: This was a retrospective, observational study that investigated the relationship between the smoking cessation period and the incidence of complications in lung cancer surgery. Patients who underwent curative-intent surgery for lung cancer at our institution between January 2014 and December 2017 were included. The smokers were classified into the following 4 categories of smoking cessation period before surgery: current (<4 weeks), recent (4 weeks to 12 months), distant (12 months to 5 years) and ex-smokers (>5 years). RESULTS: A total of 911 patients were included in this study. The incidence of pulmonary complications was 5 times higher in the smoker group than in the never smoker group (12.9% vs 2.5%, P < 0.001). On multivariable analysis in both models, the odds ratio for complications was significantly higher in distant smokers than in recent smokers and never smokers. Across all models, low lung function significantly predicted the development of postoperative complications. CONCLUSIONS: The evidence-based smoking cessation duration that reduces the incidence of complications after thoracic surgery remains unclear. The incidence of postoperative complications was more strongly affected by low pulmonary function than by the duration of preoperative smoking cessation. For patients with marginal indications for surgery, postponing surgery to accommodate a smoking cessation period seemed unnecessary.

DOI： 10.1093/ejcts/ezac163

Postoperative empyema complicated with descending necrotizing fasciitis: a case report. Reviewed International journal

Yuka Kadomatsu, Harushi Ueno, Masaki Goto, Naoki Ozeki, Shota Nakamura, Toyofumi Fengshi Chen-Yoshikawa

Surgical case reports Vol. 8 ( 1 ) page： 133 - 133 2022.7

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Empyema is a serious complication of lung surgery. CASE PRESENTATION: We report a case of Streptococcus anginosus empyema complicated by descending necrotizing fasciitis after surgery. Ten days after the initial surgery, the patient presented with arrhythmia and hypotension with septic shock. Pleural fluid analysis led to the diagnosis of empyema, and surgical debridement (second surgery) was performed. One week after the emergency surgery, a palpable pink erythematous skin change was observed on the ipsilateral iliac crest. Hence, the second emergency surgery (third surgery) was performed to debride the subcutaneous and intramuscular abscesses. CONCLUSIONS: The possibility of descending abscess and necrotizing fasciitis should be considered when Streptococcus anginosus is detected.

DOI： 10.1186/s40792-022-01492-9

Impact of inspiratory muscle strength on exercise capacity after lung transplantation Reviewed

Sato T., Sato S., Oshima Y., Yoshioka Y., Hamada R., Nankaku M., Ikeda M., Nakajima D., Chen-Yoshikawa T.F., Date H., Matsuda S., Tabira K.

Physiotherapy Research International Vol. 27 ( 3 ) 2022.7

Language：English Publisher：Physiotherapy Research International

Background and Purpose: Though inspiratory muscle strength is essential for patients with respiratory disease, it is unclear whether the recovery of inspiratory muscle strength contributes to an exemplary achievement of exercise tolerance after lung transplantation (LTx). We aimed to elucidate the inspiratory muscle strength affects the recovery of exercise capacity after LTx. Methods: Recipients who underwent LTx between June 2017 and September 2018 were enrolled, and 6-min walking distance (6MWD), quadriceps force, inspiratory muscle strength (maximal inspiratory pressure [MIP]), and spirometry were evaluated at 3, 6, and 12 months after LTx. The relationships between inspiratory muscle strength and changes in physical performance were analyzed. Results: Nineteen recipients (mean age: 44.8 years, male: 32%) who completed all follow-ups were analyzed. At 3 months after LTx, mean MIP (88.4% predicted) and vital capacity (60.9% predicted), quadriceps force (QF; 2.1 N*m/kg), and 6MWD (504 m) were lower than normal values. After LTx, 6MWD significantly improved up to 12 months. From 3 to 6 months after LTx, changes in MIP were significantly associated with increases in 6MWD by univariate (r = 0.55, p = 0.02) and multivariate (β = 0.59, p = 0.01) regression analyses, whereas changes of QF in place of MIP were significantly associated with the recoveries of 6MWD from 6 to 12 months. Discussion: Improvements in MIP may impact the recovery of exercise capacity in the early phase after LTx. Factors that determine the improvement in exercise capacity following LTx may vary with postoperative time.

DOI： 10.1002/pri.1951

Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade Reviewed

Miyai Y., Sugiyama D., Hase T., Asai N., Taki T., Nishida K., Fukui T., Chen-Yoshikawa T.F., Kobayashi H., Mii S., Shiraki Y., Hasegawa Y., Nishikawa H., Ando Y., Takahashi M., Enomoto A.

Life science alliance Vol. 5 ( 6 ) 2022.6

Language：English Publisher：Life science alliance

Cancer-associated fibroblasts (CAFs) are an integral component of the tumor microenvironment (TME). Most CAFs shape the TME toward an immunosuppressive milieu and attenuate the efficacy of immune checkpoint blockade (ICB) therapy. However, the detailed mechanism of how heterogeneous CAFs regulate tumor response to ICB therapy has not been defined. Here, we show that a recently defined CAF subset characterized by the expression of Meflin, a glycosylphosphatidylinositol-anchored protein marker of mesenchymal stromal/stem cells, is associated with survival and favorable therapeutic response to ICB monotherapy in patients with non-small cell lung cancer (NSCLC). The prevalence of Meflin-positive CAFs was positively correlated with CD4-positive T-cell infiltration and vascularization within non-small cell lung cancer tumors. Meflin deficiency and CAF-specific Meflin overexpression resulted in defective and enhanced ICB therapy responses in syngeneic tumors in mice, respectively. These findings suggest the presence of a CAF subset that promotes ICB therapy efficacy, which adds to our understanding of CAF functions and heterogeneity.

DOI： 10.26508/lsa.202101230

Impact of COVID-19 on living donor liver and kidney transplantation programs in Japan in 2020 Reviewed

『今日の治療薬2022-解説と便覧』

芳川豊史

胸部外科 Vol. 75 ( 6 ) page： 436 - 436 2022.6

Commentary: Less is more in thoracic surgery Invited Reviewed

Okado S., Chen-Yoshikawa T.F.

JTCVS Techniques Vol. 13 page： 242 - 243 2022.6

Kuramitsu K., Yamanaga S., Osawa R., Hibi T., Yoshikawa M., Toyoda M., Shimata K., Yosuke E., Ono M., Kenmochi T., Sogawa H., Natori Y., Yano H., Chen-Yoshikawa T., Yoshida K., Fukumoto T., Yuzawa K., Egawa H.

Transplant Infectious Disease Vol. 24 ( 3 ) 2022.6

Language：English Publisher：Transplant Infectious Disease

Background: Although many transplant programs have been forced to suspend living donor transplants due to the emergence of coronavirus disease (COVID-19), there are relatively few real-time databases to assess center-level transplant activities. We aimed to delineate the actual impact of COVID-19 on living donor transplant programs and the resumption process in Japan. Methods: In a nationwide survey, questionnaires were sent to 32 liver transplant programs that had performed at least more than one case of living donor liver transplantation in 2019 and 132 kidney transplant programs that had performed more than one living donor kidney transplantation in 2018. Results: Thirty-one (96.9%) and 125 (94.7%) liver and kidney transplant programs responded, respectively. In the early pandemic period, 67.7% (21/31) of liver programs and 29.8% (37/125) of kidney programs were able to maintain transplant activities similar to those during the pre-pandemic period. After temporal suspension, 58.1% of kidney programs resumed their transplant activity after the number of local COVID-19 cases peaked. Establishing institutional COVID-19 screening, triage, and therapeutic management protocols was mandatory to resume transplant activity for 64.5% and 67.7% of liver and kidney programs, respectively. In the future wave of COVID-19, 67.7% of liver programs would be affected by institutional COVID-19 intensive care unit-bound patient numbers, and 55.7% of kidney programs would stop if hospital-acquired severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection spreads. Conclusions: This nationwide survey revealed for the first time how living donor liver and kidney: transplant programs changed in response to the COVID-19 pandemic in a country where living donor transplantations are predominant.

DOI： 10.1111/tid.13845

Creation of a video library for education and virtual simulation of anatomical lung resection Reviewed

Tokuno J., Chen-Yoshikawa T.F., Nakao M., Iwakura M., Motoki T., Matsuda T., Date H.

Interactive Cardiovascular and Thoracic Surgery Vol. 34 ( 5 ) page： 808 - 813 2022.5

Authorship：Last author,　Corresponding author Language：English Publisher：Interactive Cardiovascular and Thoracic Surgery

OBJECTIVES: Recently, preoperative and intraoperative simulation using three-dimensional computed tomography (CT) has attracted much attention in thoracic surgery. However, because conventional three-dimensional CT only shows static images, dynamic simulation is required for a more precise operation. We previously reported on a resection process map for pulmonary resection, which we developed to generate virtual dynamic images from preoperative patient-specific CT scans. The goal of this study was to evaluate the feasibility of the clinical use of the resection process map for anatomical lung resection. METHODS: This study included 5 lobectomies for different lobes and 4 representative segmentectomies. Dissection of the pulmonary arteries, veins and bronchi were considered key parts of each procedure. To assess the description of images obtained from the resection process map, relevant clips from the actual surgical videos were collected, retrospectively replicated and superimposed on the resection process map to explain the procedures. RESULTS: In all surgical procedures, the resection process map successfully and semiautomatically generated a virtual dynamic image from the patient-specific CT data. Moreover, superimposition of the virtual images on the selected clips from the surgical videos showed no major differences. CONCLUSIONS: The resection process map could generate virtual images that corresponded to the actual surgical videos and has the potential for clinical use as preoperative and intraoperative simulation.

DOI： 10.1093/icvts/ivab379

Risk Assessment for Loss-of-Exercise Capacity After Lung Cancer Surgery: Current Advances in Surgery and Systemic Treatment Reviewed

Image Guidance in Thoracic Surgery: Current Status and Future Outlook

Chen-Yoshikawa T. F.

Nihon Kikan Shokudoka Gakkai Kaiho Vol. 73 ( 2 ) page： 112 - 113 2022.4

Ozeki N., Kadomatsu Y., Mizuno Y., Inoue T., Nagaya M., Goto M., Nakamura S., Fukumoto K., Chen-Yoshikawa T.F.

World Journal of Surgery Vol. 46 ( 4 ) page： 933 - 941 2022.4

Authorship：Last author Language：English Publisher：World Journal of Surgery

Background: Considering advances in current post-recurrence treatment, we examined the prognostic significance of the number of risk factors for loss-of-exercise capacity (LEC) after lung cancer surgery, which were identified by our previous prospective observational study. Methods: Risk factors for LEC were defined as a short baseline 6-min walk distance (<400 m), older age (≥75 years), and low predicted postoperative diffusing capacity for carbon monoxide (<60%). Patients were classified as Risk 0/I/II/III according to the number of risk factors. The survival data were retrospectively analyzed. Results: Between 2014 and 2017, 564 patients (n = 307, 193, 57, 7; Risk 0/I/II/III) who underwent lung cancer surgery were included in the study. The number of risk factors was associated with smoking status, predicted postoperative forced expiratory volume in 1 s, histology, pathological stage, and adjuvant therapy. In a multivariate Cox regression analysis, compared to Risk 0, Risk I/II/III showed significant associations with overall survival (hazard ratios: 1.92, 3.35, 9.21; 95% confidence interval: 1.27–2.92, 2.01–5.58, 3.64–23.35; Risk I/II/III, respectively). In 141 patients with recurrence, molecular targeted therapies (MTTs) or immune checkpoint inhibitors (ICIs) were included in 58%, 47%, 32%, and 0% (Risk 0/I/II/III) during the course of treatment. In patients with MTT/ICI treatment, the estimated 1-year and 3-year post-recurrence survival rates were 88% and 58%, respectively. Conclusions: Risk classification for LEC was associated with survival after lung cancer surgery, as well as post-recurrence treatment. The concept of physical performance-preserving surgery may contribute to improving the outcomes of current lung cancer treatment.

DOI： 10.1007/s00268-021-06427-3

Effect of Itraconazole and Its Metabolite Hydroxyitraconazole on the Blood Concentrations of Cyclosporine and Tacrolimus in Lung Transplant Recipients Reviewed

Matsuda Yuya, Nakagawa Shunsaku, Yano Ikuko, Masuda Satohiro, Imai Satoshi, Yonezawa Atsushi, Yamamoto Takashi, Sugimoto Mitsuhiro, Tsuda Masahiro, Tsuzuki Tetsunori, Omura Tomohiro, Nakagawa Takayuki, Chen-Yoshikawa Toyofumi Fengshi, Nagao Miki, Date Hiroshi, Matsubara Kazuo

Biological and Pharmaceutical Bulletin Vol. 45 ( 4 ) page： 397 - 402 2022.4

Language：English Publisher：The Pharmaceutical Society of Japan

Invasive Aspergillus infection is a major factor for poor prognosis in patients receiving lung transplantation (LT). An antifungal agent, itraconazole (ITCZ), that has antimicrobial activity against Aspergillus species, is used as a prophylactic agent against Aspergillus infection after LT. ITCZ and its metabolite, hydroxyitraconazole (OH-ITCZ), potently inhibit CYP3A and P-glycoprotein that metabolize or excrete calcineurin inhibitors (CNIs), which are the first-line immunosuppressants used after LT; thus, concomitant use of ITCZ and CNIs could induce an increase in the blood concentration of CNIs. However, no criteria for dose reduction of CNIs upon concomitant use with ITCZ in LT recipients have been defined. In this study, the effect of ITCZ and OH-ITCZ on the blood concentrations of two CNIs, tacrolimus and cyclosporine, after LT were retrospectively evaluated. A total of 39 patients who received LT were evaluated. Effects of ITCZ and OH-ITCZ on the concentration/dosage (C/D) ratio of tacrolimus and cyclosporine were analyzed using linear mixed-effects models. The plasma concentrations of OH-ITCZ were about 2.5-fold higher than those of ITCZ. Moreover, there was a significant correlation between the plasma concentrations of ITCZ and OH-ITCZ. Based on parameters obtained in the linear regression analysis, the C/D ratios of cyclosporine and tacrolimus increase by an average of 2.25- and 2.70-fold, respectively, when the total plasma concentration of ITCZ plus OH-ITCZ is 1000 ng/mL. In conclusion, the plasma levels of ITCZ and OH-ITCZ could be key factors in drawing up the criterion for dose reduction of CNIs.

DOI： 10.1248/bpb.b21-00738

Successful lung transplant cases with ex vivo lung perfusion assessment of extended criteria donor lungs. Reviewed

Daisuke Nakajima, Shunichi Nagata, Hidenao Kayawake, Satona Tanaka, Yoshito Yamada, Yojiro Yutaka, Akihiro Ohsumi, Masatsugu Hamaji, Toyofumi F Chen-Yoshikawa, Hiroshi Date

General thoracic and cardiovascular surgery Vol. 70 ( 4 ) page： 406 - 412 2022.4

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

We report our successful experience in two lung transplant cases in which ex vivo lung perfusion (EVLP) was used to evaluate the function of injured brain-dead donor lungs that were otherwise initially unacceptable. After the donor's lungs were declined for transplantation by all other transplant centers, the lungs were offered to the patients listed for lung transplantation in our hospital. The donor lung function was considered acceptable for transplantation after the 3-h EVLP assessment. In the first case, a 32-year-old man with bronchiolitis obliterans after hematopoietic stem cell transplantation underwent hybrid lung transplantation, that was right brain-dead donor lung transplantation, combined with native-upper lobe sparing living-donor lobar lung transplantation on the left side. In the second case, a 61-year-old woman received the right single lung transplantation for idiopathic pulmonary fibrosis. Both patients are doing well at one and a half years after lung transplantation.

DOI： 10.1007/s11748-022-01774-x

ASO Visual Abstract: Pleural Invasion Depth of Disseminated Nodules in Patients with Stage IVa or Recurrent Thymoma: Assessment, Curative Impact, and Surgical Outcomes Reviewed

Nakamura S., Tateyama H., Nakanishi K., Sugiyama T., Kadomatsu Y., Ueno H., Goto M., Ozeki N., Fukui T., Yokoi K., Chen-Yoshikawa T.F.

Annals of surgical oncology Vol. 29 ( 3 ) 2022.3

Clinical, radiological and pathological features of idiopathic and secondary interstitial pneumonia with pleuroparenchymal fibroelastosis in patients undergoing lung transplantation Reviewed

Ikegami N., Nakajima N., Yoshizawa A., Handa T., Chen-Yoshikawa T., Kubo T., Tanizawa K., Ohsumi A., Yamada Y., Hamaji M., Nakajima D., Yutaka Y., Tanaka S., Watanabe K., Nakatsuka Y., Murase Y., Nakanishi T., Niwamoto T., Chin K., Date H., Hirai T.

Histopathology Vol. 80 ( 4 ) page： 665 - 676 2022.3

Language：English Publisher：Histopathology

Aims: Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a rare type of idiopathic interstitial pneumonia, and pathological PPFE is also observed in patients with secondary interstitial pneumonia. This study aimed to evaluate the pathological findings associated with radiological PPFE-like lesions and the clinical and morphological features of patients with pathological PPFE. Methods and results: We retrospectively reviewed the pathology of the explanted lungs from 59 lung transplant recipients with radiological PPFE-like lesions. Pathological PPFE lesions were identified in 14 patients with idiopathic disease and in 12 patients with secondary disease. Pathological PPFE was associated with previous pneumothorax, volume loss in the upper lobes, and a flattened chest. Patients with idiopathic disease and those with secondary disease with pathological PPFE had similar clinical, radiological and pathological findings, whereas fibroblastic foci were more common in patients with idiopathic disease, and patients with secondary disease more frequently showed alveolar septal thickening with elastosis or fibrosis. Post-transplantation survival did not differ between patients with idiopathic and secondary disease with pathological PPFE (log-rank; P = 0.57) and was similar between patients with idiopathic disease with pathological PPFE and those with idiopathic pulmonary fibrosis (IPF) (log-rank; P = 0.62). Conclusions: Not all patients with interstitial pneumonia with radiological PPFE-like lesions have pathological PPFE. Characteristic clinical features can suggest the presence of pathological PPFE, and idiopathic and secondary cases with pathological PPFE are similar except for fibroblastic foci in idiopathic cases and alveolar septal thickening with elastosis or fibrosis in secondary cases. Patients with pathological PPFE have a similar prognosis to those with IPF after transplantation.

DOI： 10.1111/his.14595

Pleural Invasion Depth of Disseminated Nodules in Patients with Stage IVa or Recurrent Thymoma: Assessment, Curative Impact, and Surgical Outcomes Reviewed

Nakamura S., Tateyama H., Nakanishi K., Sugiyama T., Kadomatsu Y., Ueno H., Goto M., Ozeki N., Fukui T., Yokoi K., Chen-Yoshikawa T.F.

Annals of Surgical Oncology Vol. 29 ( 3 ) page： 1829 - 1837 2022.3

Authorship：Last author Language：English Publisher：Annals of Surgical Oncology

Background: Thymoma patients with pleural dissemination are difficult to manage, and their treatment strategy remains undefined. This study aimed to investigate the clinicopathologic features of these patients, focusing on the association between the depth of pleural invasion and prognosis. Methods: Between 2003 and 2019, the study identified 120 disseminated lesions in 20 thymoma patients. Seven patients had de novo stage IVa thymoma and 13 were recurrent cases. Extrapleural pneumonectomy was performed for 8 patients and debulking surgery for 12 patients. Invasion depth of pleural tumors was classified into two groups: when the disseminated tumors invaded the pleura beneath the elastic layer, the tumor was diagnosed as Da, and when the disseminated tumors invaded the pleura beyond the elastic layer, the tumor was diagnosed as Db. Results: Of 120 nodules, 31 (26%), found in eight patients with recurrent malignancies, were classified as Db. The pathologic status of the surgical margin (PSM) was positive in eight patients, seven of whom had Db nodules. The 5-year overall survival (OS) rate was 100% in the Da group and 75% in the Db group (P = 0.02). The 5-year progression-free survival (PFS) rate was 66.7% in the Da group and 25% in the Db group (P = 0.02). Cox univariate analysis showed that PFS was significantly influenced by the depth of invasion (P = 0.04) and PSM (P = 0.03). Conclusion: Depth of pleural invasion may influence survival outcomes for thymoma patients with pleural dissemination. The patients in this study with Da-disseminated nodules had an increased probability of a longer OS and PFS and tended to achieve negative PSM compared with the patients with Db.

DOI： 10.1245/s10434-021-10888-0

SRGN-Triggered Aggressive and Immunosuppressive Phenotype in a Subset of TTF-1-Negative Lung Adenocarcinomas Reviewed

Tanaka I., Dayde D., Tai M.C., Mori H., Solis L.M., Tripathi S.C., Fahrmann J.F., Unver N., Parhy G., Jain R., Parra E.R., Murakami Y., Aguilar-Bonavides C., Mino B., Celiktas M., Dhillon D., Casabar J.P., Nakatochi M., Stingo F., Baladandayuthapani V., Wang H., Katayama H., Dennison J.B., Lorenzi P.L., Do K.A., Fujimoto J., Behrens C., Ostrin E.J., Rodriguez-Canales J., Hase T., Fukui T., Kajino T., Kato S., Yatabe Y., Hosoda W., Kawaguchi K., Yokoi K., Chen-Yoshikawa T.F., Hasegawa Y., Gazdar A.F., Wistuba I.I., Hanash S., Taguchi A.

Journal of the National Cancer Institute Vol. 114 ( 2 ) page： 290 - 301 2022.2

Language：English Publisher：Journal of the National Cancer Institute

Background: Approximately 20% of lung adenocarcinoma (LUAD) is negative for the lineage-specific oncogene Thyroid transcription factor 1 (TTF-1) and exhibits worse clinical outcome with a low frequency of actionable genomic alterations. To identify molecular features associated with TTF-1-negative LUAD, we compared the transcriptomic and proteomic profiles of LUAD cell lines. SRGN, a chondroitin sulfate proteoglycan Serglycin, was identified as a markedly overexpressed gene in TTF-1-negative LUAD. We therefore investigated the roles and regulation of SRGN in TTF-1-negative LUAD. Methods: Proteomic and metabolomic analyses of 41 LUAD cell lines were done using mass spectrometry. The function of SRGN was investigated in 3 TTF-1-negative and 4 TTF-1-positive LUAD cell lines and in a syngeneic mouse model (n = 5 to 8 mice per group). Expression of SRGN was evaluated in 94 and 105 surgically resected LUAD tumor specimens using immunohistochemistry. All statistical tests were 2-sided. Results: SRGN was markedly overexpressed at mRNA and protein levels in TTF-1-negative LUAD cell lines (P <. 001 for both mRNA and protein levels). Expression of SRGN in LUAD tumor tissue was associated with poor outcome (hazard ratio = 4.22, 95% confidence interval = 1.12 to 15.86, likelihood ratio test, P =. 03), and with higher expression of Programmed cell death 1 ligand 1 (PD-L1) in tumor cells and higher infiltration of Programmed cell death protein 1-positive lymphocytes. SRGN regulated expression of PD-L1 as well as proinflammatory cytokines, including Interleukin-6, Interleukin-8, and C-X-C motif chemokine 1 in LUAD cell lines; increased migratory and invasive properties of LUAD cells and fibroblasts; and enhanced angiogenesis. SRGN was induced by DNA demethylation resulting from Nicotinamide N-methyltransferase-mediated impairment of methionine metabolism. Conclusions: Our findings suggest that SRGN plays a pivotal role in tumor-stromal interaction and reprogramming into an aggressive and immunosuppressive tumor microenvironment in TTF-1-negative LUAD.

DOI： 10.1093/jnci/djab183

Changes in the health-related quality of life and social reintegration status after lung transplantation following hematopoietic stem cell transplantation Reviewed

Hamada R., Oshima Y., Sato S., Yoshioka Y., Nankaku M., Kondo T., Chen-Yoshikawa T.F., Ikeguchi R., Nakajima D., Date H., Matsuda S.

Supportive Care in Cancer Vol. 30 ( 2 ) page： 1831 - 1839 2022.2

Language：English Publisher：Supportive Care in Cancer

Purpose: Late-onset non-infectious pulmonary complications (LONIPCs) after allogeneic hematopoietic stem cell transplantation are fatal; however, lung transplantation might achieve good survival. Nevertheless, improving the health-related quality of life (HRQoL) is still a major concern. This study aimed to investigate, in detail, the recovery in HRQoL and social reintegration status after lung transplantation in patients with LONIPC after allo-HSCT. Methods: This prospective cohort study involving 18 patients examined changes in the health and social reintegration status after lung transplantation following LONIPC. Results: Physical function and HRQoL were lowest before lung transplantation. Two years after lung transplantation, the dyspnea scores and performance status improved. Most patients had made a successful return to society, and patients who achieved social reintegration were significantly younger and had a good performance status. However, their Physical Functioning score and Physical Component Summary did not show significant improvement after lung transplantation. Moreover, recipients who were unemployed before lung transplantation were likely to remain unemployed and continued to show poor HRQoL. Conclusions: These results showed poor recovery of HRQoL, especially in terms of physical function, and the likelihood of failure to reintegrate into society within 2 years after lung transplantation. It is necessary to consider long-term follow-up and physical training to improve social reintegration and HRQoL.

DOI： 10.1007/s00520-021-06592-0

Protective effect of necrosulfonamide on rat pulmonary ischemia-reperfusion injury via inhibition of necroptosis Reviewed

Ueda S., Chen-Yoshikawa T.F., Tanaka S., Yamada Y., Nakajima D., Ohsumi A., Date H.

Journal of Thoracic and Cardiovascular Surgery Vol. 163 ( 2 ) page： e113 - e122 2022.2

Language：English Publisher：Journal of Thoracic and Cardiovascular Surgery

Background: Necroptosis plays an important role in cell death during pulmonary ischemia-reperfusion injury (IRI). We hypothesized that therapy with necrosulfonamide (NSA), a mixed-lineage kinase domain-like protein inhibitor, would attenuate lung IRI. Methods: Rats were assigned at random into the sham operation group (n = 6), vehicle group (n = 8), or NSA group (n = 8). In the NSA and vehicle groups, the animals were heparinized and underwent left thoracotomy, and the left hilum was clamped for 90 minutes, followed by reperfusion for 120 minutes. NSA (0.5 mg/body) and a solvent were administered i.p. in the NSA group and the vehicle group, respectively. The sham group underwent 210 minutes of perfusion without ischemia. After reperfusion, arterial blood gas analysis, physiologic data, lung wet-to-dry weight ratio, histologic changes, and cytokine levels were assessed. Fluorescence double immunostaining was performed to evaluate necroptosis and apoptosis. Results: Arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) was better, dynamic compliance was higher, and mean airway pressure and lung edema were lower in the NSA group compared with the vehicle group. Moreover, in the NSA group, lung injury was significantly alleviated, and the mean number of necroptotic cells (55.3 ± 4.06 vs 78.2 ± 6.87; P =.024), but not of apoptotic cells (P =.084), was significantly reduced compared with the vehicle group. Interleukin (IL)-1β and IL-6 levels were significantly lower with NSA administration. Conclusions: In a rat model, our results suggest that NSA may have a potential protective role in lung IRI through the inhibition of necroptosis.

DOI： 10.1016/j.jtcvs.2021.01.037

Meclozine Attenuates the MARK Pathway in Mammalian Chondrocytes and Ameliorates FGF2-Induced Bone Hyperossification in Larval Zebrafish Reviewed

Takemoto G., Matsushita M., Okamoto T., Ito T., Matsuura Y., Takashima C., Chen-Yoshikawa T.F., Ebi H., Imagama S., Kitoh H., Ohno K., Hosono Y.

Frontiers in Cell and Developmental Biology Vol. 9 2022.1

Language：English Publisher：Frontiers in Cell and Developmental Biology

Meclozine has been developed as an inhibitor of fibroblast growth factor receptor 3 (FGFR3) to treat achondroplasia (ACH). Extracellular signal regulated kinase (ERK) phosphorylation was attenuated by meclozine in FGF2-treated chondrocyte cell line, but the site of its action has not been elucidated. Although orally administered meclozine promoted longitudinal bone growth in a mouse model of ACH, its effect on craniofacial bone development during the early stage remains unknown. Herein, RNA-sequencing analysis was performed using murine chondrocytes from FGF2-treated cultured tibiae, which was significantly elongated by meclozine treatment. Gene set enrichment analysis demonstrated that FGF2 significantly increased the enrichment score of mitogen-activated protein kinase (MAPK) family signaling cascades in chondrocytes; however, meclozine reduced this enrichment. Next, we administered meclozine to FGF2-treated larval zebrafish from 8 h post-fertilization (hpf). We observed that FGF2 significantly increased the number of ossified vertebrae in larval zebrafish at 7 days post-fertilization (dpf), while meclozine delayed vertebral ossification in FGF2-induced zebrafish. Meclozine also reversed the FGF2-induced upregulation of ossified craniofacial bone area, including ceratohyal, hyomandibular, and quadrate. The current study provided additional evidence regarding the inhibitory effect of meclozine on the FGF2-induced upregulation of MAPK signaling in chondrocytes and FGF2-induced development of craniofacial and vertebral bones.

DOI： 10.3389/fcell.2021.694018

Predictive value of EGFR mutation in non–small-cell lung cancer patients treated with platinum doublet postoperative chemotherapy Reviewed

Takahashi T., Sakai K., Kenmotsu H., Yoh K., Daga H., Ohira T., Ueno T., Aoki T., Hayashi H., Yamazaki K., Hosomi Y., Chen-Yoshikawa T.F., Okumura N., Takiguchi Y., Sekine A., Haruki T., Yamamoto H., Sato Y., Akamatsu H., Seto T., Saeki S., Sugio K., Nishio M., Inokawa H., Yamamoto N., Nishio K., Tsuboi M.

Cancer Science Vol. 113 ( 1 ) page： 287 - 296 2022.1

Language：English Publisher：Cancer Science

The mutation status of tumor tissue DNA (n = 389) of resected stage II-III non-squamous non–small-cell lung cancer (Ns-NSCLC) was analyzed using targeted deep sequencing as an exploratory biomarker study (JIPANG-TR) for the JIPANG study, a randomized phase III study of pemetrexed/cisplatin (Pem/Cis) vs vinorelbine/cisplatin (Vnr/Cis). The TP53 mutation, common EGFR mutations (exon 19 deletion and L858R), and KRAS mutations were frequently detected. The frequency of the EGFR mutation was significant among female patients. Patients with an EGFR mutation-positive status had a significantly shorter recurrence-free survival (RFS) time (24 mo vs not reached) (HR, 1.64; 95% CI, 1.22-2.21; P =.0011 for EGFR mutation status). Multivariable analysis identified both the pathological stage and EGFR mutation status as independent prognostic factors for RFS (HR, 1.78; 95% CI, 1.30-2.44; P =.0003 for disease stage; and HR, 1.57; 95% CI, 1.15-2.16; P =.0050 for EGFR mutation status). This study demonstrated that the EGFR mutation has either a poor prognostic or predictive impact on a poor response to postoperative chemotherapy with platinum doublet chemotherapy for stage II-III Ns-NSCLC patients. This result supports a role for mandatory molecular diagnosis of early-stage Ns-NSCLC for precision oncology and signifies the importance of adjuvant for the 3rd generation tyrosine kinase inhibitor rather than platinum-based chemotherapy. This study is registered with the UMIN Clinical Trial Registry (UMIN 000012237).

DOI： 10.1111/cas.15171

Challenges in left sleeve pneumonectomy in the left lateral decubitus position Reviewed

Nakamura S., Fukui T., Ito H., Goto M., Ozeki N., Chen-Yoshikawa T.F.

Nagoya Journal of Medical Science Vol. 84 ( 3 ) page： 673 - 677 2022

Authorship：Last author,　Corresponding author Language：English Publisher：Nagoya Journal of Medical Science

We report the case of a 20-year-old woman with carinal adenoid cystic carcinoma who underwent left sleeve pneumonectomy in the left lateral decubitus position, during which severe desaturation was encountered. After transecting the left main bronchus, the left lung was selectively intubated and ventilated. However, oxygenation was inadequate. Hence, venoarterial extracorporeal membrane oxygenation (ECMO) was introduced. Initially, Barclay’s procedure was planned to preserve the left lung, but this plan was altered due to the extent of the tumor and unstable ventilation. After the lesion was removed, the trachea and right main bronchus were anastomosed end-to-end. During left pneumonectomy, the right lung was selectively ventilated, but oxygen saturation (SpO2) dropped to <70% despite ECMO. SpO2 improved on additionally ventilating the left lung using another breathing circuit. Temporary right chest closure was performed with ventilation of the left lung across the thoracotomy wound. The patient was turned to the semi-supine position, and tolerated selective right lung ventilation with ECMO. Subsequently, left thoracotomy and pneumonectomy were successfully performed. Careful management is required for desaturation in left sleeve pneumonectomy in the left lateral decubitus position.

DOI： 10.18999/nagjms.84.3.673

脳死下肺摘出・搬送法標準化の現状

星川康, 芳川豊史

移植 Vol. 57 ( Supplement ) page： s145_2 - s145_2 2022

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

本学会ホームページ上で提示されている脳死下肺摘出術のオリジナル版は、2011年3〜5月当時の肺移植実施7施設に対してアンケート調査を行い、慎重なメール審議とコンセンサス形成を経て、全施設の相違点を包括するものが作成された。本邦の肺摘出術の初めての標準化プロセスであった。2021年4〜6月共同演者の芳川豊史先生（本学会脳死・心停止下リカバリー環境改善委員会委員）が中心となり、日本肺および心肺移植研究会を通じて、肺移植実施10施設に「臓器搬送における手順標準化に向けたアンケート調査」を行い、慎重なメール審議の上、改訂がなされた。特に逆行性灌流に関して、従来の摘出後バックテーブルで行うものから術野で行う形に変更した施設が増えていたため、従来法と併記する形で加筆がなされた。事前に腹部チームとコンセンサスを得ること、呼吸循環管理医・日本臓器移植ネットワークコーディネーターと情報共有することも強調されている。この他、現状に合致させるよう複数の意見が出され、この過程で多施設間相互の手技の再確認、標準化が改めてなされた。臓器摘出・搬送の互助制度に関しては、2018年1〜2月日本肺および心肺移植研究会による肺移植実施9施設に対するアンケート調査の結果、肺移植では時期尚早と判断し、腹部臓器の状況をオブザーブする方針となっている。脳死下肺摘出・搬送法標準化の現状を提示し、今後の課題を議論したい。

DOI： 10.11386/jst.57.supplement_s145_2

生体肺移植術後の健康関連QoLの実態調査　―脳死肺移植との比較―

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

移植 Vol. 57 ( Supplement ) page： s342_1 - s342_1 2022

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

【背景と目的】生体肺移植（LDLLT）は本邦を中心に行われており，生命予後は脳死肺移植（CLT）とほぼ同等とされるが，健康関連QoL（HRQoL）に関しては定かでは無い．移植後5年までのHRQoLについて検討を行った．【方法】当院の肺移植患者を対象とし，術前，術後3ヶ月，6ヶ月，1年，以後1年毎に5年までのSF-36を調査し，3コンポーネント・サマリースコア（PCS, MCS, RCS）を算出した．CLTは術前評価の欠測値が多く，LDLLTとの術前比較にはmMRCを用いた．術後経過の比較では，術前mMRC，QoL評価時の慢性移植肺機能不全合併の有無を共変量とし，線形混合モデルを用いて解析した．なお，有意水準は5%とした．【結果】LDLLT68例，CLT148例が解析対象となり，全体では中央値4.4年まで経過観察され，5年後観察を完遂したのは94例（44%）だった．術前のmMRCはLDLLTで有意に高値であった（p＜0.001）．PCSは術後3ヶ月でLDLLT36点 vs. CLT40点，術後5年で41点 vs. 39点と同等になった．MCSは術前からLDLLT56点と高値であり，術後はLDLLT，CLT共に50点を超えて推移した．RCSは術前LDLLT27点と低値であり，術後3ヶ月においても低値が持続したが，術後5年ではCLT46点に対し，LDLLTは50点を超えた．線形混合モデルによる評価では，LDLLTとCLTの経過に有意な差は認められなかった．【結論】LDLLT患者はCLTと比較して，術前の呼吸器症状はより重度であったが，少なくとも術後のHRQoLは同等，もしくは一部でLDLLTが上回ると考えられた．

DOI： 10.11386/jst.57.supplement_s342_1

Setting a quality indicator for actual surgery time relative to scheduled surgery time in the context of increasing robotic-assisted thoracic surgery cases Reviewed

Ozeki N., Ueno H., Saeki J., Kadomatsu Y., Kato T., Nakamura S., Fukumoto K., Fukui T., Chen-Yoshikawa T.F.

General Thoracic and Cardiovascular Surgery 2022

Authorship：Last author Language：English Publisher：General Thoracic and Cardiovascular Surgery

Objective: This study aimed to demonstrate to the involved departments the goal of increasing the number of robotic-assisted thoracic surgery (RATS) cases/surgeons and acceptable surgery times. Methods: This retrospective study included 1572 patients who underwent thoracic surgery from fiscal year (FY) 2018 to FY 2021. The factors evaluated included the number of surgery cases and actual and scheduled surgery times. Results: The total number of RATS and total surgery cases increased after the quality indicator (QI) setting (n = 363, 360, 417, and 432 in FY 2018, 2019, 2020, and 2021, respectively). In FY 2020, 93.3% of the QI target was achieved, while in FY 2021, 88% was achieved. The number of RATS lobectomy/segmentectomy increased as the FY progressed (n = 31, 47, 58, and 116 in FY 2018, 2019, 2020, and 2021, respectively). The mean surgical time by RATS starters decreased in FY 2020 and 2021 (171.4 min.; 74 cases; seven RATS starters) compared with those in FY 2018 and 2019 (198.0 min.; 57 cases; six RATS starters) (P = 0.002). Conclusions: The goal of increasing the number of surgery cases and RATS cases/surgeons within the given framework was achieved by setting the QI.

DOI： 10.1007/s11748-022-01903-6

Multicentre, prospective, observational study investigating the most appropriate surgical option that can prevent the recurrence of primary spontaneous pneumothorax after surgery: The PATCH study, protocol Reviewed

Kadomatsu Y., Yoshioka H., Shigemitsu K., Nomata Y., Mori S., Hijiya K., Motoyama H., Ichikawa Y., Sueyoshi K., Okasaka T., Miyamoto E., Kobayashi M., Takahashi M., Fujinaga T., Takechi H., Yamagishi H., Takuwa T., Kobayashi J., Sakamoto J., Taniguchi T., Hanaoka N., Kubo Y., Chen-Yoshikawa T.F.

BMJ Open Vol. 11 ( 12 ) 2021.12

Authorship：Last author Language：English Publisher：BMJ Open

Introduction Thoracoscopic surgery is performed for refractory or recurrent primary spontaneous pneumothorax (PSP). To reduce postoperative recurrence, additional treatment is occasionally adopted during surgery after bulla resection. However, the most effective method has not been fully elucidated. Furthermore, the preference for additional treatment varies among countries, and its efficacy in preventing recurrence must be evaluated based on settings tailored for the conditions of a specific country. The number of registries collecting detailed data about PSP surgery is limited. Therefore, to address this issue, a prospective multicentre observational study was performed. Methods and analysis This multicentre, prospective, observational study will enrol 450 participants aged between 16 and 40 years who initially underwent PSP surgery. Data about demographic characteristics, disease and family history, surgical details, and CT scan findings will be collected. Follow-up must be conducted until 3 years after surgery or in the event of recurrence, whichever came first. Patients without recurrence will undergo annual follow-up until 3 years after surgery. The primary outcome is the rate of recurrence within 2 years after surgery. A multivariate analysis will be performed to compare the efficacy of different surgical options. Then, adverse outcomes correlated with various treatments and the feasibility of treatment methods will be compared. Ethics and dissemination This study was approved by the local ethics committee of all participating centres. The findings will be available in 2025, and they can be used as a basis for clinical decision-making regarding appropriate options for the initial PSP surgery. Trial registration number NCT04758143.

DOI： 10.1136/bmjopen-2021-052045

Updated long-term outcomes of salvage surgery after stereotactic body radiotherapy for early-stage non-small-cell lung cancer Reviewed

Yamanashi K.

Interactive cardiovascular and thoracic surgery Vol. 31 ( 6 ) page： 892 - 894 2021.12

Diagnostic utility of metabolic parameters on FDG PET/CT for lymph node metastasis in patients with cN2 non-small cell lung cancer Reviewed

Nakanishi K., Nakamura S., Sugiyama T., Kadomatsu Y., Ueno H., Goto M., Ozeki N., Fukui T., Iwano S., Chen-Yoshikawa T.F.

BMC Cancer Vol. 21 ( 1 ) 2021.12

Authorship：Last author Language：English Publisher：BMC Cancer

Background: The aim of this study was to assess the diagnostic utility of metabolic parameters on fluorine-18-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET)/computed tomography (CT) for predicting lymph node (LN) metastasis in patients with cN2 non-small cell lung cancer (NSCLC). Methods: We retrospectively reviewed patients who underwent surgery for cN2 NSCLC between 2007 and 2020. Those who had clinically diagnosed positive hilar and mediastinal LNs by routine CT and PET/CT imaging were investigated. To measure the metabolic parameters of LNs, the data according to maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and LN-to-primary tumor ratio of SUVmax (LPR) were examined. The diagnosis of each retrieved LN was confirmed based on histopathological examination of surgical tissue specimens. Receiver operating characteristics (ROC) curves with area under the curve (AUC) calculations and multivariate analysis by logistic regression were performed. Results: Forty-five patients with 84 clinically diagnosed positive hilar or mediastinal LNs were enrolled in the present study. Of the 84 LNs, 63 LNs were pathologically proven as positive (75%). The SUVmax, MTV, TLG, and LPR of LN metastasis were significantly higher than those of benign nodes. In the ROC analysis, the AUC value of LPR [AUC, 0.776; 95% confidence interval (CI), 0.640–0.913] was higher than that of LN SUVmax (AUC, 0.753; 95% CI, 0.626–0.880) or LN TLG3.5 (AUC, 0.746; 95% CI, 0.607–0.885). Using the optimal LPR cutoff value of 0.47, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 84.1, 66.7, 88.3, 58.3, and 79.8%, respectively. Multivariate analysis by logistic regression showed that LPR was an independent predictor for LN metastasis (odds ratio, 6.45; 95% CI, 1.785–23.301; P = 0.004). In the subgroup analysis of adenocarcinoma patients (n = 18; 32 LNs), TLG3.5 was a better predictor (AUC, 0.816; 95% CI, 0.639–0.985) than LPR (AUC, 0.792; 95% CI, 0.599–0.986) or LN SUVmax (AUC, 0.792; 95% CI, 0.625–0.959). Conclusions: Our findings suggest that LPR on FDG-PET is a useful predictor for LN metastasis in patients with cN2 NSCLC. TLG can be a good predictor for LN metastasis in patients with adenocarcinoma.

DOI： 10.1186/s12885-021-08688-6

Patient-reported dyspnea and health predict waitlist mortality in patients waiting for lung transplantation in Japan Reviewed

Ikeda M., Oga T., Chen-Yoshikawa T.F., Tokuno J., Oto T., Okawa T., Okada Y., Akiba M., Tanaka S., Yamada Y., Yutaka Y., Ohsumi A., Nakajima D., Hamaji M., Isomi M., Chin K., Date H.

Respiratory Research Vol. 22 ( 1 ) 2021.12

Language：English Publisher：Respiratory Research

Background: Waitlist mortality due to donor shortage for lung transplantation is a serious problem worldwide. Currently, the selection of recipients in Japan is mainly based on the registration order. Hence, scientific evidence for risk stratification regarding waitlist mortality is urgently needed. We hypothesized that patient-reported dyspnea and health would predict mortality in patients waitlisted for lung transplantation. Methods: We analyzed factors related to waitlist mortality using data of 203 patients who were registered as candidates for lung transplantation from deceased donors. Dyspnea was evaluated using the modified Medical Research Council (mMRC) dyspnea scale, and the health status was determined with St. George’s Respiratory Questionnaire (SGRQ). Results: Among 197 patients who met the inclusion criteria, the main underlying disease was interstitial lung disease (99 patients). During the median follow-up period of 572 days, 72 patients died and 96 received lung transplantation (69 from deceased donors). Univariable competing risk analyses revealed that both mMRC dyspnea and SGRQ Total score were significantly associated with waitlist mortality (p = 0.003 and p < 0.001, respectively) as well as age, interstitial lung disease, arterial partial pressure of carbon dioxide, and forced vital capacity. Multivariable competing risk analyses revealed that the mMRC and SGRQ score were associated with waitlist mortality in addition to age and interstitial lung disease. Conclusions: Both mMRC dyspnea and SGRQ score were significantly associated with waitlist mortality, in addition to other clinical variables such as patients’ background, underlying disease, and pulmonary function. Patient-reported dyspnea and health may be measured through multi-dimensional analysis (including subjective perceptions) and for risk stratification regarding waitlist mortality.

DOI： 10.1186/s12931-021-01715-x

Improved visualization of virtual-assisted lung mapping by indocyanine green Reviewed

Tokuno J., Chen-Yoshikawa T.F., Nakajima D., Aoyama A., Motoyama H., Sato M., Date H.

JTCVS Techniques Vol. 10 page： 542 - 549 2021.12

Language：English Publisher：JTCVS Techniques

Objectives: Virtual-assisted lung mapping (VAL-MAP) is a bronchoscopic marking method of dye application on the surface of the lungs before resecting nonpalpable nodules. However, in some cases, it can be difficult to identify the markings of VAL-MAP on computed tomography and intraoperative thoracoscopy. We developed and assessed the feasibility of indocyanine green VAL-MAP (ICG-VAL-MAP). Methods: A historical control trial was conducted to investigate the effectiveness of ICG-VAL-MAP for marking visualization compared with that of VAL-MAP. In ICG-VAL-MAP, instead of indigo carmine, ICG and computed tomography contrast agents were used for dye marking, and near-infrared fluorescence endoscopy was employed to visualize the ICG markings. The other processes in VAL-MAP were carried out. The marking visibility was assessed in 3 grades of easy, faint, or not identifiable. We compared the visibility of the markings on computed tomography images and during thoracoscopic operations between VAL-MAP (567 markings in 147 cases) and ICG-VAL-MAP (142 markings in 63 cases). Results: On the preoperative computed tomography images, ICG-VAL-MAP provided significantly better marking visualization than VAL-MAP (easy/faint/not identifiable = 142/0/0 vs 427/100/30; P <.0001). ICG-VAL-MAP provided significantly better intraoperative markings than VAL-MAP (easy/faint/not identifiable = 141/0/1, respectively, vs 475/50/42, respectively; P <.0001). Regarding complications, pneumothorax occurred in 8 (5.4%) cases of VAL-MAP and zero cases (0%) of ICG-VAL-MAP (P =.12); fever was observed in 7 (5.0%) cases of VAL-MAP and 2 (3.2%) cases of ICG-VAL-MAP (P =.72). Conclusions: ICG-VAL-MAP provided significantly better visibility of markings than VAL-MAP. It might be useful in the resection of nonpalpable small lung lesions.

DOI： 10.1016/j.xjtc.2021.07.019

Polyglycolic acid sheet covering to prevent recurrence after surgery for spontaneous pneumothorax: a meta-analysis Reviewed

Kadomatsu Y., Fukui T., Mori S., Chen-Yoshikawa T.F., Wakai K.

Scientific Reports Vol. 11 ( 1 ) 2021.12

Language：English Publisher：Scientific Reports

The coverage technique using absorbable mesh was first described in a European guideline published in 2015 as a preventive method for the recurrence of spontaneous pneumothorax. We performed a meta-analysis based on a literature search of primary studies that compared the postoperative recurrence rate of primary spontaneous pneumothorax between the use and nonuse of polyglycolic acid sheet coverage. Two reviewers independently selected and evaluated the quality of the relevant studies. The risk ratio in each study was calculated in a random-effect meta-analysis. Statistical heterogeneity among the included studies was quantitatively evaluated using the I2 index, and publication bias was assessed using a funnel plot. A total of 19 retrospective cohort studies were analyzed: 1524 patients who underwent wedge resection alone (the control group) and 1579 who received additional sheet coverage. Polyglycolic acid sheet coverage was associated with a lower recurrence rate than that in the control group (risk ratio: 0.27, 95% confidence interval 0.20–0.37, P < 0.001; I2 0%). The funnel plot suggested possible publication bias. The covering technique reduced the recurrence rate of pneumothorax after thoracoscopic surgery to one-fourth.

DOI： 10.1038/s41598-021-83103-5

Kernel-based framework to estimate deformations of pneumothorax lung using relative position of anatomical landmarks Reviewed

Commentary: Paving the way with visualization of the invisible craftsmanship Invited Reviewed

Nakamura S., Chen-Yoshikawa T.F.

JTCVS Open Vol. 8 page： 664 - 665 2021.12

Yamamoto U., Nakao M., Ohzeki M., Tokuno J., Chen-Yoshikawa T.F., Matsuda T.

Expert Systems with Applications Vol. 183 2021.11

Language：English Publisher：Expert Systems with Applications

In video-assisted thoracoscopic surgeries, successful procedures of nodule resection are highly dependent on the precise estimation of lung deformation between the inflated lung in the computed tomography (CT) images during preoperative planning and the deflated lung in the treatment views during surgery. Lungs in the pneumothorax state during surgery have a large volume change from normal lungs, making it difficult to build a mechanical model.The purpose of this study is to develop a deformation estimation method of 3D surface of a deflated lung from a few partial observations. To estimate deformations for a largely deformed lung, a kernel regression-based solution was introduced. The proposed method used a few landmarks to capture the partial deformation between the 3D surface mesh obtained from preoperative CT and the intraoperative anatomical positions. The deformation for each vertex of the entire mesh model was estimated per-vertex as a relative position from the landmarks. The landmarks were placed in the anatomical position of the lung's outer contour. The method was applied on nine datasets of the left lungs of live beagle dogs. Contrast-enhanced CT images of the lungs were acquired.The proposed method achieved a local positional error of vertices of 2.74 mm, Hausdorff distance of 6.11 mm, and Dice similarity coefficient of 0.94. Moreover, the proposed method achieved the estimation lung deformations from a small number of training cases and a small observation area.This study contributes to data-driven modeling of pneumothorax deformation of the lung.

DOI： 10.1016/j.eswa.2021.115288

Removal of hematoma due to massive hemoptysis after transbronchial biopsy: a case report. Reviewed International journal

Harushi Ueno, Hideki Tsubouchi, Keita Nakanishi, Tomoshi Sugiyama, Yuka Kadomatsu, Masaki Goto, Naoki Ozeki, Shota Nakamura, Takayuki Fukui, Toyofumi Fengshi Chen-Yoshikawa

Surgical case reports Vol. 7 ( 1 ) page： 237 - 237 2021.11

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Massive hemoptysis is a life-threatening complication after transbronchial biopsy (TBB). Reports on massive hemoptysis occurring several days after TBB are scarce. CASE PRESENTATION: A 62-year-old man presented with massive hemoptysis and was admitted to hospital as an emergency on the eighth day after TBB. On the 12th day after TBB, computed tomography showed complete atelectasis of the right middle and lower lobes. The patient underwent emergent right upper lobectomy. The right upper lobe bronchus was separated with a scalpel, the hematoma was pulled out with forceps, and the bronchus subsequently sutured shut. The patient was discharged from the hospital uneventfully. CONCLUSIONS: We experienced a case of massive hemoptysis on the eighth day after TBB, which required emergency surgery due to persistent bleeding into the airway and airway obstruction during follow-up. Postoperative pneumonia and atelectasis could be prevented by manual removal of the residual hematoma.

DOI： 10.1186/s40792-021-01323-3

Morphological and functional reserves of the right middle lobe: Radiological analysis of changes after right lower lobectomy in healthy individuals Reviewed

Yamagishi H.

Journal of Thoracic and Cardiovascular Surgery Vol. 162 ( 5 ) page： 1417 - 1423.e2 2021.11

Impacts of single nucleotide polymorphisms in Fc gamma receptor IIA (rs1801274) on lung transplant outcomes among Japanese lung transplant recipients Reviewed

Kayawake H., Chen-Yoshikawa T.F., Tanaka S., Tanaka Y., Ohdan H., Yutaka Y., Yamada Y., Ohsumi A., Nakajima D., Hamaji M., Egawa H., Date H.

Transplant International Vol. 34 ( 11 ) page： 2192 - 2204 2021.11

Language：English Publisher：Transplant International

This study aimed to analyze the influences of single nucleotide polymorphisms (SNPs) in Fc gamma receptor IIA (FCGR2A) on postoperative outcomes after lung transplantation (LTx). We enrolled 191 lung transplant recipients [80 undergoing living-donor lobar lung transplants (LDLLTs) and 111 undergoing deceased-donor lung transplants (DDLTs)] in this study. We identified SNPs in FCGR2A (131 histidine [H] or arginine [R]; rs1801274) and reviewed the infectious complication-free survival after ICU discharge. The SNPs in FCGR2A comprised H/H (n = 53), H/R (n = 24), and R/R (n = 3) in LDLLT and H/H (n = 67), H/R (n = 42), and R/R (n = 2) in DDLT. Recipients with H/H (H/H group) and those with H/R or R/R (R group) were compared in the analyses of infectious complications. In multivariate analyses, the R group of SNPs in FCGR2A was associated with pneumonia-free survival {HR: 2.52 [95% confidence interval (CI): 1.35–4.71], P = 0.004}, fungal infection-free survival [HR: 2.50 (95% CI: 1.07–5.84), P = 0.035], and cytomegalovirus infection-free survival [HR: 2.24 (95% CI: 1.07–4.69), P = 0.032] in LDLLT, but it was not associated with infectious complication-free survival in DDLT. Therefore, in LDLLT, more attention to infectious complications might need to be paid for LTx recipients with H/R or R/R than for those with H/H.

DOI： 10.1111/tri.13974

Left Upper Lobe Trisegmentectomy After Pulmonary Endarterectomy Reviewed

Tsubouchi H., Goto M., Terazawa S., Adachi S., Suzuki Y., Usui A., Kondo T., Chen-Yoshikawa T.F.

Annals of Thoracic Surgery Vol. 112 ( 5 ) page： e361 - e363 2021.11

Authorship：Last author,　Corresponding author Language：English Publisher：Annals of Thoracic Surgery

Major pulmonary resection has been successfully performed after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension in a few cases. A pulmonary nodule was detected in a 68-year-old man with a diagnosis of chronic thromboembolic pulmonary hypertension. After pulmonary hypertension was resolved with pulmonary endarterectomy, left upper lobe trisegmentectomy was performed for small lung cancer. Dissection of the pulmonary artery was carefully performed with a possibility of a fragile state on the arterial wall due to previous pulmonary endarterectomy. Pathologically, the arterial media with an uneven thickness was exposed to the vascular lumen in the resected pulmonary artery.

DOI： 10.1016/j.athoracsur.2021.02.022

Virtual-assisted lung mapping in sublobar resection of small pulmonary nodules, long-term results. Reviewed International journal

Hirokazu Yamaguchi, Masaaki Sato, Kazumichi Yamamoto, Keiko Ueda, Hiroshi Date, Toyofumi Chen-Yoshikawa, Yoshito Yamada, Junko Tokuno, Masahiro Yanagiya, Fumitsugu Kojima, Nobuyuki Yoshiyasu, Masashi Kobayashi, Yasuhiro Nakashima, Terumoto Koike, Jin Sakamoto, Shinji Kosaka, Ryuta Fukai, Tomoki Nishida, Hiroaki Sakai, Shinji Shinohara, Masaru Takenaka, Fumihiro Tanaka, Kenji Misawa, Jun Nakajima

European journal of cardio-thoracic surgery Vol. 61 ( 4 ) page： 761 - 768 2021.10

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

OBJECTIVES: The short-term efficacy of virtual-assisted lung mapping (VAL-MAP), a preoperative bronchoscopic multi-spot lung-marking technique, has been confirmed in 2 prospective multicentre studies. The objectives of this study were to analyse the local recurrence and survival of patients enrolled in these studies, long-term. METHODS: Of the 663 patients enrolled in the 2 studies, 559 patients' follow-up data were collected. After excluding those who did not undergo VAL-MAP, whose resection was not for curative intent, who underwent concurrent resection without VAL-MAP, or who eventually underwent lobectomy instead of sublobar resection (i.e. wedge resection or segmentectomy), 422 patients were further analysed. RESULTS: Among 264 patients with primary lung cancer, the 5-year local recurrence-free rate was 98.4%, and the 5-year overall survival (OS) rate was 94.5%. Limited to stage IA2 or less (≤2 cm in diameter; n = 238, 90.1%), the 5-year local recurrence-free and OS rates were 98.7% and 94.8%, respectively. Among 102 patients with metastatic lung tumours, the 5-year local recurrence-free rate was 93.8% and the 5-year OS rate was 81.8%. Limited to the most common (colorectal) cancer (n = 53), the 5-year local recurrence-free and OS rates were 94.9% and 82.3%, respectively. CONCLUSIONS: VAL-MAP, which is beneficial in localizing small barely palpable pulmonary lesions and determining the appropriate resection lines, was associated with reasonable long-term outcomes. SUBJ COLLECTION: 152, 1542.

DOI： 10.1093/ejcts/ezab421

Deformation analysis of surface and bronchial structures in intraoperative pneumothorax using deformable mesh registration Reviewed

綜説小児肺移植の現状

芳川豊史

小児科 Vol. 62 ( 11 ) page： 1364 - 1373 2021.10

Nakao M., Kobayashi K., Tokuno J., Chen-Yoshikawa T., Date H., Matsuda T.

Medical Image Analysis Vol. 73 2021.10

Language：English Publisher：Medical Image Analysis

The positions of nodules can change because of intraoperative lung deflation, and the modeling of pneumothorax-associated deformation remains a challenging issue for intraoperative tumor localization. In this study, we introduce spatial and geometric analysis methods for inflated/deflated lungs and discuss heterogeneity in pneumothorax-associated lung deformation. Contrast-enhanced CT images simulating intraoperative conditions were acquired from live Beagle dogs. The images contain the overall shape of the lungs, including all lobes and internal bronchial structures, and were analyzed to provide a statistical deformation model that could be used as prior knowledge to predict pneumothorax. To address the difficulties of mapping pneumothorax CT images with topological changes and CT intensity shifts, we designed deformable mesh registration techniques for mixed data structures including the lobe surfaces and the bronchial centerlines. Three global-to-local registration steps were performed under the constraint that the deformation was spatially continuous and smooth, while matching visible bronchial tree structures as much as possible. The developed framework achieved stable registration with a Hausdorff distance of less than 1 mm and a target registration error of less than 5 mm, and visualized deformation fields that demonstrate per-lobe contractions and rotations with high variability between subjects. The deformation analysis results show that the strain of lung parenchyma was 35% higher than that of bronchi, and that deformation in the deflated lung is heterogeneous.

DOI： 10.1016/j.media.2021.102181

Various techniques for anastomosis of pulmonary arteries with size mismatch during lung transplantation Reviewed

Yokoyama Y., Chen-Yoshikawa T.F., Nakajima D., Ohsumi A., Date H.

JTCVS Techniques Vol. 9 page： 192 - 194 2021.10

【胸部外科手術の進歩と術前術後のリハビリテーション診療】肺移植サルコペニアと栄養・リハビリテーション治療

芳川豊史, 大島洋平, 大島綾子

MEDICAL REHABILITATION ( 266 ) page： 36 - 42 2021.10

Language：Japanese Publisher：(株)全日本病院出版会

肺移植は、内科的治療が尽くされた末期呼吸不全患者における唯一の治療手段として世界的に確立し、本邦でも、手術手技や一般的な周術期管理以外の患者管理に、焦点が当てられるようになってきた。肺移植適応患者は、末期の慢性呼吸不全患者であり、日常生活における活動性は低い。さらに、運動機能や日常生活動作能力も極めて低下するなど、いわゆるサルコペニアの病態である患者も多い。したがって、長い待機期間だけでなく周術期を生き抜くためにも、肺移植待機患者に対する術前リハビリテーション治療や栄養療法は重要である。また、肺移植によって肺機能は劇的に改善するが、肺の機能を活かすための身体機能は何も変化しない。したがって、肺移植後のリハビリテーション治療では、低下した身体機能の向上をはかり、日常生活動作能力を高めることで、早期社会復帰を目指すことが目標となる。肺移植患者や肺移植待機患者において、サルコペニアと栄養状態の管理の観点からの多角的なリハビリテーション治療が、今後さらに重要となる。(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J03505&link_issn=&doc_id=20211014130006&doc_link_id=%2Fap5meree%2F2021%2F000266%2F008%2F0036-0042%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fap5meree%2F2021%2F000266%2F008%2F0036-0042%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

特集胸部外科領域における再手術up to date II. 呼吸器領域 7. 生体肺移植後の再移植

芳川豊史, 伊達洋至

胸部外科 Vol. 74 ( 10 ) page： 850 - 855 2021.9

Differential impacts of postoperative complications on patients’ survival in completely resected non-small-cell lung cancer Reviewed

Kadomatsu Y., Tsubouchi H., Nakanishi K., Sugiyama T., Ueno H., Goto M., Ozeki N., Nakamura S., Fukui T., Chen-Yoshikawa T.F.

General Thoracic and Cardiovascular Surgery Vol. 69 ( 9 ) page： 1283 - 1290 2021.9

Authorship：Last author Language：English Publisher：General Thoracic and Cardiovascular Surgery

Objective: The aim of this study was to investigate the effects of inflammatory respiratory complications on long-term survival in patients with resected non-small cell lung cancer. We defined inflammatory respiratory complications to include the following six conditions: pneumonia, empyema, bronchial fistula, respiratory dysfunction, acute interstitial pneumonia, and atelectasis. Methods: Part of the National Clinical Database was linked to our prospective database from 2014 to 2017. Linkage was achieved for 866 patients. The Kaplan–Meier method was used to evaluate the overall, relapse-free, and cancer-related survival. The Cox proportional hazard model was used to analyze the impact of each complication. Results: Of the 736 patients included in the study, 149 had complications. The 5-year overall and cancer-specific survival rates were significantly lower in patients with inflammatory respiratory complications. The Cox proportional hazard model showed that the inflammatory respiratory complications had a significant impact on overall survival (hazard ratio 2.48, 95% confidence interval 1.41–4.38) but not air leak (hazard ratio 1.38, 95% confidence interval 0.70–2.70). Conclusions: Our study shows the differential impact of each complication on the survival of patients with non-small cell lung cancer. The presence of inflammatory respiratory complications was the only predictor of poor overall survival.

DOI： 10.1007/s11748-021-01619-z

Physical function after lung transplantation for late-onset noninfectious pulmonary complications after allogeneic hematopoietic stem cell transplantation Reviewed

Hamada R., Oshima Y., Sato S., Yoshioka Y., Sato T., Nankaku M., Kondo T., Chen-Yoshikawa T.F., Ikeguchi R., Nakajima D., Date H., Matsuda S.

Supportive Care in Cancer Vol. 29 ( 9 ) page： 5447 - 5454 2021.9

Language：English Publisher：Supportive Care in Cancer

Purpose: Late-onset noninfectious pulmonary complications (LONIPCs) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are fatal, and lung transplantation is the only curative treatment. Although lung transplantation for LONIPCs may confer good survival rates, it is unclear whether or how impaired physical functioning is restored. Thus, this study aimed to investigate the long-term course and associated changes in physical functions after lung transplantation in patients with LONIPCs after allo-HSCT. Methods: This prospective cohort study enrolled 15 patients who received lung transplantation for LONIPCs after allo-HSCT between 2012 and 2018. Dyspnea scores, performance status, physical function, and exercise tolerance were assessed before lung transplantation and up to 2 years after transplantation. Results: Two years after lung transplantation, the dyspnea scores and performance status improved, but did not recover completely. Physical function was assessed using the knee extensor strength (KES) and 6-min walk test (6MWT); the results were poor until 3 months after transplantation but improved over 2 years. The 6MWT distance showed improvement to a nearly healthy level (562.7 m). Recovery of exercise tolerance was associated with recovery in % vital capacity (%VC; r=0.5) and KES (r=0.4) from 3 months to 2 years after lung transplantation. Furthermore, a flat thorax, which is a characteristic of patients with LONIPCs, affected the %VC at 2 years after transplantation (r=0.8). Conclusion: Lung transplantation for LONIPCs may restore impaired physical function. A multifaceted rehabilitation program should be considered, especially to improve muscle weakness and pulmonary function.

DOI： 10.1007/s00520-021-06118-8

肺移植における多職種連携肺移植における術後早期栄養介入の試み

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

移植 Vol. 56 ( 総会臨時 ) page： SWS3 - 4 2021.9

[Retransplantation after Bilateral Living-donor Lobar Lung Transplantation]. Reviewed

Toyofumi F Chen-Yoshikawa, Hiroshi Date

Kyobu geka. The Japanese journal of thoracic surgery Vol. 74 ( 10 ) page： 850 - 855 2021.9

Authorship：Lead author,　Corresponding author Language：Japanese Publishing type：Research paper (scientific journal)

Living-donor lobar lung transplantation( LDLLT) is an established therapy for patients with end-stage lung disease, but living-donor lobar lung retransplantation (re-LDLLT) is rarely reported. We previously reported a case of unilateral antibody-mediated rejection (AMR) after bilateral LDLLT in the presence of newly formed donor-specific antibodies against a right-lobe donor. The same patient developed contralateral bronchiolitis obliterans syndrome (BOS), resulting in bilateral BOS. Re-LDLLT was performed under extracorporeal membrane oxygenation. Eight and a half years after re-LDLLT, the patient is doing well without any anti-human leukocyte antigen antibodies. Four lobes from four different donors were transplanted in this patient. Herein, we report this rare case and discuss several issues in comparison with the findings in the previously reported similar cases.

Lessons learned from hybrid surgery with preoperative coil embolization for an aberrant artery in pulmonary sequestration. Reviewed International journal

Keita Nakanishi, Masaki Goto, Shota Nakamura, Toyofumi Fengshi Chen-Yoshikawa

Surgical case reports Vol. 7 ( 1 ) page： 192 - 192 2021.8

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The optimal management of an aberrant artery in pulmonary sequestration (PS) is controversial. Several studies have shown that hybrid surgery with preoperative coil embolization for an aberrant artery and surgical resection of the sequestrated lung is effective. However, there are no clear indications for the procedure. CASE PRESENTATION: A 68-year-old woman without any complaints was diagnosed with right intralobar PS, which was supplied by an aberrant artery from the thoracic aorta, via computed tomography performed during a medical examination. In addition, lung adenocarcinoma was detected over the border between the right upper and middle lobes. Preoperative coil embolization was performed by an interventional radiologist the day before surgery to decrease the risk of severe intraoperative hemorrhage. On the following day, bi-lobectomy of the right upper and middle lobes for lung adenocarcinoma with systemic lymph node dissection and segmentectomy of the sequestrated lung with thoracotomy was performed. Although no active hemorrhage was observed during surgery, the aberrant artery was challenging to dissect using an energy device due to the presence of an intravascular coil. Eventually, the coil stump was exposed, and it was cut with scissors. The postoperative course was uneventful. CONCLUSIONS: We reported the pitfall of the hybrid surgery for intralobar PS. Preoperative coil embolization can prevent fatal intraoperative hemorrhage. If embolization is performed using a coil for an aberrant artery supplied from the thoracic aorta, where and how to dissect the aberrant artery should be cautiously determined based on preoperative images, with consideration of the presence of an intravascular coil.

DOI： 10.1186/s40792-021-01277-6

Commentary: Constant dripping wears a stone away Invited Reviewed

Ozeki N.

Journal of Thoracic and Cardiovascular Surgery Vol. 162 ( 2 ) page： e159 - e160 2021.8

Outcomes of lung transplantation for idiopathic pleuroparenchymal fibroelastosis Reviewed

Shiiya H., Nakajima J., Date H., Chen-Yoshikawa T.F., Tanizawa K., Handa T., Oto T., Otani S., Shiotani T., Okada Y., Matsuda Y., Shiraishi T., Moroga T., Minami M., Funaki S., Chida M., Yoshino I., Hatachi G., Uemura Y., Sato M.

Surgery Today Vol. 51 ( 8 ) page： 1276 - 1284 2021.8

Language：English Publisher：Surgery Today

Purpose: This study was performed to compare the outcome of lung transplantation (LT) for idiopathic pleuroparenchymal fibroelastosis (IPPFE) with that of LT for idiopathic pulmonary fibrosis (IPF). Methods: We reviewed, retrospectively, all adult patients who underwent LT for IPPFE or IPF in Japan between 1998 and 2018. Results: There were 100 patients eligible for this study (31 with IPPFE and 69 with IPF). Patients with IPPFE tended to have a significantly lower body mass index (BMI) than those with IPF (median, 16.7 vs. 22.6 kg/m2, respectively; P < 0.01). However, Kaplan–Meier survival curves showed no significant difference in overall survival between the groups. The BMI did not increase in patients with IPPFE, even 1 year after LT (pretransplant, 16.5 ± 3.2 kg/m2 vs. 1 year post-transplant, 15.6 ± 2.5 kg/m2; P = 0.08). The percent predicted forced vital capacity (%FVC) 1 year after LT was significantly lower in the IPPFE group than in the IPF group (48.4% ± 19.5% vs. 68.6% ± 15.5%, respectively; P < 0.01). Conclusions: Despite extrapulmonary problems such as a flat chest, low BMI, and associated restrictive impairment persisting in patients with IPPFE, patient survival after LT for IPPFE or IPF was equivalent.

DOI： 10.1007/s00595-021-02232-6

Thymic mucinous adenocarcinoma: A case report

Tsubouchi Hideki, Ozeki Naoki, Suzuki Yuka, Kawaguchi Koji, Fukui Takayuki, F. Chen-Yoshikawa Toyofumi

The Journal of the Japanese Association for Chest Surgery Vol. 35 ( 5 ) page： 547 - 552 2021.7

Language：Japanese Publisher：The Japanese Association for Chest Surgery

A 61-year-old woman presented with a 44-mm well-circumscribed tumor in the anterior mediastinum on chest computed tomography. 18F-Fluorodeoxyglucose positron emission tomography showed a high-level accumulation of 18F-Fluorodeoxyglucose (standardized uptake value: 12.07). She underwent thymectomy with combined resection of partial pericardium. Histopathological findings showed that the tumor was a thymic mucinous adenocarcinoma (pT2N0M0 Stage II, and Masaoka stage III). After receiving adjuvant radiotherapy, she was in good health without any tumor recurrence at 6 months after surgery.

DOI： 10.2995/jacsurg.35.547

Pulmonary benign metastasizing leiomyoma: A clinicopathological study of 10 cases

Maeda Jun, Higashiyama Masahiko, Nishio Wataru, Yoshikawa Toyofumi, Kadota Yoshihisa, Iwasaki Teruo, Terada Yasuji, Okami Jiro

The Journal of the Japanese Association for Chest Surgery Vol. 35 ( 5 ) page： 537 - 546 2021.7

Language：Japanese Publisher：The Japanese Association for Chest Surgery

Pulmonary benign metastasizing leiomyoma (BML) is a rare disease in which a benign uterine leiomyoma metastasizes to the lung. We herein report a clinicopathological study of 10 cases. The median interval between hysterectomy and lung resection for pulmonary nodules was 114 months (range: 15-240 months). The median tumor size was 11 mm (range: 5-16 mm). While nine patients with multiple nodules underwent wedge resection, one was treated with lobectomy. Hormonal treatment was administered to 3 patients with residual lesions and 1 patient as adjuvant therapy. During the follow-up periods (range: 26-192 months, median: 105 months), seven patients were alive with disease and two without evidence of disease. One patient died of systemic metastases due to atypical leiomyoma diagnosed by reviewing uterine and pulmonary specimens. Diagnostic, surgical, and therapeutic problems associated with this disease were discussed.

DOI： 10.2995/jacsurg.35.537

Multicellular modeling of ciliopathy by combining ips cells and microfluidic airway-on-a-chip technology Reviewed

Sone N., Konishi S., Igura K., Tamai K., Ikeo S., Korogi Y., Kanagaki S., Namba T., Yamamoto Y., Xu Y., Takeuchi K., Adachi Y., Chen-Yoshikawa T.F., Date H., Hagiwara M., Tsukita S., Hirai T., Torisawa Y.S., Gotoh S.

Science Translational Medicine Vol. 13 ( 601 ) 2021.7

Language：English Publisher：Science Translational Medicine

Mucociliary clearance is an essential lung function that facilitates the removal of inhaled pathogens and foreign matter unidirectionally from the airway tract and is innately achieved by coordinated ciliary beating of multiciliated cells. Should ciliary function become disturbed, mucus can accumulate in the airway causing subsequent obstruction and potentially recurrent pneumonia. However, it has been difficult to recapitulate unidirectional mucociliary flow using human-derived induced pluripotent stem cells (iPSCs) in vitro and the mechanism governing the flow has not yet been elucidated, hampering the proper humanized airway disease modeling. Here, we combine human iPSCs and airway-on-a-chip technology, to demonstrate the effectiveness of fluid shear stress (FSS) for regulating the global axis of multicellular planar cell polarity (PCP), as well as inducing ciliogenesis, thereby contributing to quantifiable unidirectional mucociliary flow. Furthermore, we applied the findings to disease modeling of primary ciliary dyskinesia (PCD), a genetic disease characterized by impaired mucociliary clearance. The application of an airway cell sheet derived from patient-derived iPSCs and their gene-edited counterparts, as well as genetic knockout iPSCs of PCD causative genes, made it possible to recapitulate the abnormal ciliary functions in organized PCP using the airway-on-a-chip. These findings suggest that the disease model of PCD developed here is a potential platform for making diagnoses and identifying therapeutic targets and that airway reconstruction therapy using mechanical stress to regulate PCP might have therapeutic value.

DOI： 10.1126/scitranslmed.abb1298

CEBPγ facilitates lamellipodia formation and cancer cell migration through CERS6 upregulation Reviewed

Shi H., Niimi A., Takeuchi T., Shiogama K., Mizutani Y., Kajino T., Inada K., Hase T., Hatta T., Shibata H., Fukui T., Chen-Yoshikawa T.F., Nagano K., Murate T., Kawamoto Y., Tomida S., Takahashi T., Suzuki M.

Cancer Science Vol. 112 ( 7 ) page： 2770 - 2780 2021.7

Language：English Publisher：Cancer Science

Ceramide synthase 6 (CERS6) promotes lung cancer metastasis by stimulating cancer cell migration. To examine the underlying mechanisms, we performed luciferase analysis of the CERS6 promoter region and identified the Y-box as a cis-acting element. As a parallel analysis of database records for 149 non–small-cell lung cancer (NSCLC) cancer patients, we screened for trans-acting factors with an expression level showing a correlation with CERS6 expression. Among the candidates noted, silencing of either CCAAT enhancer-binding protein γ (CEBPγ) or Y-box binding protein 1 (YBX1) reduced the CERS6 expression level. Following knockdown, CEBPγ and YBX1 were found to be independently associated with reductions in ceramide-dependent lamellipodia formation as well as migration activity, while only CEBPγ may have induced CERS6 expression through specific binding to the Y-box. The mRNA expression levels of CERS6, CEBPγ, and YBX1 were positively correlated with adenocarcinoma invasiveness. YBX1 expression was observed in all 20 examined clinical lung cancer specimens, while 6 of those showed a staining pattern similar to that of CERS6. The present findings suggest promotion of lung cancer migration by possible involvement of the transcription factors CEBPγ and YBX1.

DOI： 10.1111/cas.14928

Comparison of de novo donor-specific antibodies between living and cadaveric lung transplantation Reviewed

Gochi F., Chen-Yoshikawa T.F., Kayawake H., Ohsumi A., Tanaka S., Yamada Y., Yutaka Y., Nakajima D., Hamaji M., Yurugi K., Hishida R., Date H.

Journal of Heart and Lung Transplantation Vol. 40 ( 7 ) page： 607 - 613 2021.7

Language：English Publisher：Journal of Heart and Lung Transplantation

Background: Despite growing interest in donor-specific antibodies (DSAs) and antibody-mediated rejection (AMR) in lung transplantation (LTx), no study evaluating the outcomes in recipients with de novo DSAs (dnDSAs) in living-donor lobar LTx (LDLLT) exists. We compared various characteristics of DSAs in LDLLT with those in cadaveric LTx (CLT) based on prospectively collected data. Methods: Between October 2009 and September 2019, 211 recipients underwent LTx (128 CLTs and 83 LDLLTs). We reviewed 108 CLTs and 74 LDLLTs to determine the characteristics and clinical impact of dnDSAs. Eighteen data-deficient cases, 7 cases with preformed DSAs, and 4 re-transplants were excluded. Results: There were significant differences between CLT and LDLLT patients in age, primary disease, ischemic time, and number of human leukocyte antigen mismatches per donor. The dnDSA incidence in LDLLT (6.8%) was significantly lower than that in CLT (19.4%, p = 0.02). The dnDSAs appeared later in LDLLT (mean 1,256 days) than in CLT (mean 196 days, p = 0.003). According to Cox models analyzed using dnDSA as a time-dependent covariate, dnDSA positivity was significantly associated with a poor overall survival (OS; hazard ratio [HR] 3.46, 95% confidence interval [CI] 1.59-7.57, p = 0.002) and poor CLAD-free survival in case of CLT (HR: 2.23, 95% CI: 1.08-4.63, p = 0.003). However, no such significant associations were noted in case of LDLLT. Conclusions: The dnDSA occurrence was significantly lower and later in LDLLT than in CLT. Furthermore, dnDSA-positivity was significantly associated with worse OS and CLAD-free survival after CLT but not after LDLLT.

DOI： 10.1016/j.healun.2021.03.019

肺移植後の抗体関連拒絶に対するrituximab(遺伝子組換え)

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 Vol. 56 ( 1 ) page： 53 - 68 2021.7

Language：Japanese Publisher：(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。

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00083&link_issn=&doc_id=20210716280007&doc_link_id=%2Fcl8isoke%2F2021%2F005601%2F007%2F0053-0068%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcl8isoke%2F2021%2F005601%2F007%2F0053-0068%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

脳死肺移植術前における脊柱起立筋CT値の低下は術後の予後不良因子である

大島洋平, 佐藤晋, 芳川豊史, 中島大輔, 田中里奈, 山田義人, 豊洋次郎, 濱路政嗣, 大角明宏, 伊達洋至, 松田秀一

移植 Vol. 56 ( 1 ) page： 96 - 96 2021.7

Mammalian enteral ventilation ameliorates respiratory failure Reviewed

Okabe R., Chen-Yoshikawa T.F., Yoneyama Y., Yokoyama Y., Tanaka S., Yoshizawa A., Thompson W.L., Kannan G., Kobayashi E., Date H., Takebe T.

Med Vol. 2 ( 6 ) page： 773 - 783.e5 2021.6

Language：English Publisher：Med

Background: Several aquatic organisms such as loaches have evolved unique intestinal breathing mechanisms to survive under extensive hypoxia. To date, it is highly controversial whether such capability can be adapted in mammalian species as another site for gas exchange. Here, we report the advent of the intestinal breathing phenomenon in mammalians by exploiting EVA (enteral ventilation via anus). Methods: Two different modes of EVA were investigated in an experimental model of respiratory failure: intra-rectal oxygen O2 gas ventilation (g-EVA) or liquid ventilation (l-EVA) with oxygenated perfluorocarbon. After induction of type 1 respiratory failure, we analyzed the effectiveness of g-EVA and I-EVA in mouse and pig, followed by preclinical safety analysis in rat. Findings: Both intra-rectal O2 gas and oxygenated liquid delivery were shown to provide vital rescue of experimental models of respiratory failure, improving survival, behavior, and systemic O2 level. A rodent and porcine model study confirmed the tolerable and repeatable features of an enema-like l-EVA procedure with no major signs of complications. Conclusions: EVA has proven effective in mammalians such that it oxygenated systemic circulation and ameliorated respiratory failure. Due to the proven safety of perfluorochemicals in clinics, EVA potentially provides an adjunctive means of oxygenation for patients under respiratory distress conditions. Funding: This work is funded by the Research Program on Emerging and Re-emerging Infectious Diseases, Research Projects on COVID-19 (JP20fk0108278, 20fk0108506h0001), from the Japan Agency for Medical Research and Development (AMED), to T.T.; Strategic Promotion for Practical Application of Innovative Medical Technology, Seeds A (A145), to T.T.; and KAKENHI 19K22657, to T.C.-Y. This research is partially supported by the AMED Translational Research Program; Strategic Promotion for Practical Application of Innovative Medical Technology (TR-SPRINT), to T.C.-Y.; and AMED JP18bm0704025h0001 (Program for Technological Innovation of Regenerative Medicine), to T.T.

DOI： 10.1016/j.medj.2021.04.004

Association Between Pretransplant Serum Carcinoembryonic Antigen Levels and Immunohistochemical Staining of Explanted Native Lungs in Patients Who Underwent Lung Transplantation

Okabe R.

Seminars in Thoracic and Cardiovascular Surgery Vol. 33 ( 2 ) page： 608 - 615 2021.6

Combined surgical therapy for pulmonary sequestration and aberrant artery from the abdominal aorta

Hakiri S., Fukui T., Chen-Yoshikawa T.F.

General Thoracic and Cardiovascular Surgery Vol. 69 ( 6 ) page： 1031 - 1034 2021.6

Language：Japanese Publisher：General Thoracic and Cardiovascular Surgery

Pulmonary sequestration with feeding vessels from the abdominal aorta is relatively rare. A 56-year-old woman with chronic left thoracic pain was referred to our hospital. Computed tomography showed multiple pulmonary cysts in the left lung and an aberrant artery from the abdominal aorta. She was diagnosed with pulmonary sequestration. She underwent embolization of the aberrant artery and wedge resection of the sequestrated lung under indocyanine green guidance. The surgical treatment combining preoperative embolization of the artery and intraoperative indocyanine green-guided lung resection might be safe and minimally invasive for patients with lung sequestrations accompanied by feeding vessels from the abdominal aorta.

DOI： 10.1007/s11748-021-01612-6

Ischemia–reperfusion injury in lung transplantation

Chen-Yoshikawa T.F.

Cells Vol. 10 ( 6 ) 2021.6

Language：Japanese Publisher：Cells

Lung transplantation has been established worldwide as the last treatment for end-stage respiratory failure. However, ischemia–reperfusion injury (IRI) inevitably occurs after lung transplantation. The most severe form of IRI leads to primary graft failure, which is an important cause of morbidity and mortality after lung transplantation. IRI may also induce rejection, which is the main cause of mortality in recipients. Despite advances in donor management and graft preservation, most donor grafts are still unsuitable for transplantation. Although the pulmonary endothelium is the primary target site of IRI, the pathophysiology of lung IRI remains incompletely understood. It is essential to understand the mechanism of pulmonary IRI to improve the outcomes of lung transplantation. Therefore, we reviewed the state-of-the-art in the management of pulmonary IRI after lung transplantation. Recently, the ex vivo lung perfusion (EVLP) system has been clinically introduced worldwide. Various promising therapeutic strategies for the protection of the endothelium against IRI, including EVLP, inhalation therapy with therapeutic gases and substances, fibrinolytic treatment, and mesenchymal stromal cell therapy, are awaiting clinical application. We herein review the latest advances in the field of pulmonary IRI in lung transplantation.

DOI： 10.3390/cells10061333

Preoperative paraspinous muscle sarcopenia and physical performance as prognostic indicators in non-small-cell lung cancer

Tanaka S., Ozeki N., Mizuno Y., Nakajima H., Hattori K., Inoue T., Nagaya M., Fukui T., Nakamura S., Goto M., Sugiyama T., Nishida Y., Chen-Yoshikawa T.F.

Journal of Cachexia, Sarcopenia and Muscle Vol. 12 ( 3 ) page： 646 - 656 2021.6

Language：Japanese Publisher：Journal of Cachexia, Sarcopenia and Muscle

Background: Despite the associations of both preoperative sarcopenia and physical performance with post-operative mortality in non-small-cell lung cancer (NSCLC), there have been no comprehensive studies of the impact of physical status on prognosis. This study was performed to investigate the prognostic significance of preoperative sarcopenia and physical performance in NSCLC. Methods: This retrospective cohort study was performed in NSCLS patients undergoing curative lung resection at a university hospital between January 2014 and December 2017. The patients were divided into four groups according to the skeletal muscle index [sarcopenia (lowest sex-specific tertile) and non-sarcopenia] and 6 min walking distance (6MWD) [short distance (<400 m) and long distance (≥400 m)]. Sarcopenia was assessed by preoperative cross-sectional areas of right and left paraspinous muscles at the level of the 12th thoracic vertebra from computed tomography images, and physical performance was determined by preoperative 6MWD. The primary and secondary endpoints were post-operative overall survival (OS) and disease-free survival (DFS). Results: The 587 patients [mean age: 68.5 ± 8.8 years, 399 men (68%)] included in the study were divided into the non-sarcopenia/long-distance group (58%), sarcopenia/long-distance group (26%), non-sarcopenia/short-distance group (9%), and sarcopenia/short-distance group (7%). A total of 109 (18.6%) deaths and 209 (35.6%) combined endpoints were observed over a mean follow-up of 3.1 ± 1.3 years. After adjusting for other covariates, the sarcopenia/short-distance group showed significant associations with shorter OS (hazard ratio, 3.38; 95% confidence interval, 1.79–6.37; P < 0.001) and DFS (hazard ratio, 2.11; 95% confidence, 1.27–3.51; P = 0.004) compared with the non-sarcopenia/long-distance group on multivariate analyses. Although not significant, adding skeletal muscle index and 6MWD to the pre-existing risk model increased the area under the curve on time-dependent receiver operating characteristic curve analysis for OS and DFS, except within 2 years of surgery. Conclusions: The presence of both preoperative paraspinous muscle sarcopenia and short distance in 6MWD had an adverse effect on post-operative prognosis in patients with NSCLC, suggesting that preoperative assessment of thoracic sarcopenia and physical performance may be useful for risk stratification of surgical candidates with potential for targeted interventions.

DOI： 10.1002/jcsm.12691

Native lung complications after living-donor lobar lung transplantation

Mineura K., Chen-Yoshikawa T.F., Tanaka S., Yamada Y., Yutaka Y., Nakajima D., Ohsumi A., Hamaji M., Menju T., Date H.

Journal of Heart and Lung Transplantation Vol. 40 ( 5 ) page： 343 - 350 2021.5

Language：Japanese Publisher：Journal of Heart and Lung Transplantation

Background: Living-donor lobar lung transplantation (LDLLT) is viable for critically ill patients in situations of donor shortage. Because it is sometimes difficult to find 2 ideal living donors with suitable graft sizes, we developed native lung-sparing procedures, including single LDLLT and native upper lobe-sparing LDLLT. This study aimed to investigate native lung complications (NLCs) in native lung-sparing LDLLT. Methods: Between April 2002 and March 2019, 92 LDLLTs and 124 cadaveric lung transplantations (CLTs) were performed at the Kyoto University Hospital. Our prospectively maintained database and clinical records were reviewed to compare NLCs among recipients who underwent native lung-sparing LDLLT (n = 21) with those among recipients who underwent single CLT (n = 61). Results: Among 21 recipients who underwent native lung-sparing LDLLT, 11 NLCs occurred in 8 recipients. No fatal NLC was noted; however, 2 required surgical intervention. Post-transplant survival was not significantly different between native lung-sparing LDLLT recipients with NLCs and those without NLCs. The incidence of NLCs was comparable between native lung-sparing LDLLT recipients and single CLT recipients (8/21 vs 26/61, p = 0.80); however, NLCs occurred significantly later in LDLLT recipients than in CLT recipients (median: 665 vs 181.5 days after transplantation, p = 0.014). Conclusions: NLCs after native lung-sparing LDLLT had favorable outcomes. Therefore, native lung-sparing LDLLT is a useful treatment option for severely ill patients who cannot wait for CLT. However, it is important to recognize that NLCs may occur later in LDLLT than in CLT.

DOI： 10.1016/j.healun.2021.01.1562

Postoperative outcomes of lung transplant recipients with preformed donor-specific antibodies

Kayawake H., Chen-Yoshikawa T.F., Gochi F., Tanaka S., Yurugi K., Hishida R., Yutaka Y., Yamada Y., Ohsumi A., Hamaji M., Nakajima D., Date H.

Interactive cardiovascular and thoracic surgery Vol. 32 ( 4 ) page： 616 - 624 2021.4

Language：Japanese Publisher：Interactive cardiovascular and thoracic surgery

OBJECTIVES: Few studies have evaluated the outcomes of lung transplantation (LTx) in recipients with preformed donor-specific antibodies (DSAs). This study investigated the postoperative changes in preformed DSAs based on prospectively collected data of DSAs, and the influences of preformed DSAs on postoperative outcomes among LTx recipients. METHODS: Between July 2010 and December 2019, 216 recipients underwent LTx (81 living-donor lobar lung transplants and 135 deceased-donor lung transplants). We reviewed 8 cases with preformed DSAs to determine postoperative changes in DSAs and compared postoperative outcomes between recipients with and without DSAs. RESULTS: The preoperative mean fluorescence intensity of preformed DSAs ranged from 1141 to 14 695. Two recipients experienced antibody-mediated rejection within 2 weeks after LTx. DSAs disappeared in 7 recipients; however, 1 recipient experienced the relapse of DSAs and died from chronic lung allograft syndrome (CLAD), whereas 1 recipient had persisting DSAs within the study period and died from CLAD. Neither overall survival (OS) nor CLAD-free survival was significantly different between recipients with and without DSAs (P = 0.26 and P = 0.17, respectively). However, both OS and CLAD-free survival were significantly lower in recipients with DSAs against HLA class II than in those without these antibodies {5-year OS: 25.0% [95% confidence interval (CI): 0.9-66.5%] vs 72.1% (95% CI: 63.8-78.9%), P = 0.030 and 5-year CLAD-free survival: 26.7% (95% CI: 1.0-68.6%) vs 73.7% (95% CI: 66.5-79.5%), P = 0.002}. CONCLUSIONS: Prognosis in recipients experiencing the relapse of preformed DSAs and those with persisting DSAs may be poor. The recipients with anti-HLA class II preformed DSAs had a significantly worse prognosis.

DOI： 10.1093/icvts/ivaa311

胸部CT画像による脊柱起立筋の術前指標が術後の運動耐容能および生命予後に及ぼす影響

閉塞性細気管支炎における気管支拡張の意義について

古郷摩利子, 松本久子, 田辺直也, 芳川豊史, 中島直樹, 吉澤明彦, 小熊毅, 佐藤晋, 野村奈都子, 森本千絵, 砂留広伸, 後藤慎平, 大角明宏, 伊達洋至, 平井豊博

日本呼吸器学会誌 Vol. 10 ( 増刊 ) page： 195 - 195 2021.4

Fluorescence-guided thoracic surgery Invited Reviewed

Shota Nakamura, Masaki Goto, Toyofumi F. Chen-Yoshikawa

Journal of Visualized Surgery Vol. 7 page： 18 - 18 2021.4

Left brachiocephalic vein aneurysm: a case report

Ueno Harushi, Yazawa Mari, Tsubouchi Hideki, Nakanishi Keita, Sugiyama Tomoshi, Kadomatsu Yuka, Goto Masaki, Ozeki Naoki, Nakamura Shota, Fukui Takayuki, Mutsuga Masato, Yoshikawa Toyofumi Fengshi Chen

SURGICAL CASE REPORTS Vol. 7 ( 1 ) 2021.3

大島洋平, 佐藤晋, 芳川豊史, 田中里奈, 山田義人, 豊洋次郎, 中島大輔, 濱路政嗣, 大角明宏, 伊達洋至, 松田秀一

移植 Vol. 55 ( 4 ) page： 515 - 516 2021.3

胸部CT画像による脊柱起立筋の術前指標が術後の運動耐容能および生命予後に及ぼす影響

大島洋平, 佐藤晋, 芳川豊史, 田中里奈, 山田義人, 豊洋次郎, 中島大輔, 濱路政嗣, 大角明宏, 伊達洋至, 松田秀一

移植 Vol. 55 ( 4 ) page： 515 - 516 2021.3

Factors associated with changes in the 12-m stair-climbing time after lung lobectomy

Ozeki N.

General Thoracic and Cardiovascular Surgery Vol. 69 ( 2 ) page： 282 - 289 2021.2

Thymic lipofibroadenoma accompanied with largish calcifications

Hakiri S.

General Thoracic and Cardiovascular Surgery Vol. 69 ( 2 ) page： 394 - 397 2021.2

生体肺移植周術期における脊柱起立筋CT値の低下は予後不良因子である

大島洋平, 佐藤晋, 吉岡佑二, 濱田涼太, 佐藤達也, 太田垣あゆみ, 芳川豊史, 伊達洋至, 南角学, 松田秀一

日本呼吸ケア・リハビリテーション学会誌 Vol. 30 ( Suppl. ) page： 154s - 154s 2021.2

肺移植待機中の間質性肺疾患患者における運動耐容能に影響を及ぼす因子の検討

佐藤達也, 佐藤晋, 大島洋平, 吉岡佑二, 濱田涼太, 田平一行, 芳川豊史, 半田知宏, 伊達洋至, 松田秀一

日本呼吸ケア・リハビリテーション学会誌 Vol. 30 ( Suppl. ) page： 154s - 154s 2021.2

脳死肺移植における術前の脊柱起立筋CT値の低下は予後不良因子である

大島洋平, 佐藤晋, 吉岡佑二, 濱田涼太, 佐藤達也, 太田垣あゆみ, 芳川豊史, 伊達洋至, 南角学, 松田秀一

日本呼吸ケア・リハビリテーション学会誌 Vol. 30 ( Suppl. ) page： 154s - 154s 2021.2

Protective Effects of a Hydrogen-Rich Preservation Solution in a Canine Lung Transplantation Model

Kayawake H., Chen-Yoshikawa T.F., Saito M., Yamagishi H., Yoshizawa A., Hirano S.i., Kurokawa R., Date H.

Annals of Thoracic Surgery Vol. 111 ( 1 ) page： 246 - 252 2021.1

Language：Japanese Publisher：Annals of Thoracic Surgery

Background: Molecular hydrogen (H2) has protective effects against ischemia-reperfusion injury in various organs. Because they are easier to transport and safer to use than inhaled H2, H2-rich solutions are suitable for organ preservation. In this study, we examined the protective effects of an H2-rich solution for lung preservation in a canine left lung transplantation (LTx) model. Methods: Ten beagles underwent orthotopic left LTx after 23 hours of cold ischemia followed by reperfusion for 4 hours. Forty-five minutes after reperfusion, the right main pulmonary artery was clamped to evaluate the function of the implanted graft. The beagles were divided into two groups: control group (n = 5), and H2 group (n = 5). In the control group, the donor lungs were flushed and immersed during cold preservation at 4°C using ET-Kyoto solution, and in the H2 group, these were flushed and immersed using H2-rich ET-Kyoto solution. Physiologic assessments were performed during reperfusion. After reperfusion, the wet-to-dry ratios were determined, and histology examinations were performed. Results: Significantly higher partial pressure of arterial oxygen and significantly lower partial pressure of carbon dioxide were observed in the H2 group than in the control group (P =.045 and P <.001, respectively). The wet-to-dry ratio was significantly lower in the H2 group than in the control group (P =.032). Moreover, in histology examination, less lung injury and fewer apoptotic cells were observed in the H2 group (P <.001 and P <.001, respectively). Conclusions: Our results demonstrated that the H2-rich preservation solution attenuated ischemia-reperfusion injury in a canine left LTx model.

DOI： 10.1016/j.athoracsur.2020.05.076

Kernel-based framework to estimate deformations of pneumothorax lung using anatomical landmarks

Yamamoto Utako, Nakao Megumi, Ohzeki Masayuki, Tokuno Junko, Yoshikawa Toyofumi, Matsuda Tetsuya

Transactions of Japanese Society for Medical and Biological Engineering Vol. Annual59 ( Abstract ) page： 515 - 515 2021

Language：Japanese Publisher：Japanese Society for Medical and Biological Engineering

In video-assisted thoracoscopic surgeries, the precise estimation of lung deformation between the inflated lung in the computed tomography (CT) images during preoperative planning and the deflated lung in the treatment views during surgery is expected. The purpose of this study is to develop a deformation estimation method of the 3D surface of a deflated lung from a few partial observations. To estimate deformations for a largely deformed lung, a kernel regression-based solution was introduced. The proposed method used a few landmarks to capture the partial deformation between the 3D surface mesh obtained from preoperative CT and the intraoperative anatomical positions. The method was applied on nine datasets of the left lungs of live Beagle dogs. Contrast-enhanced CT images of the lungs were acquired. The proposed method achieved a local positional error of vertices of 2.74 mm, Hausdorff distance of 6.11 mm, and Dice similarity coefficient of 0.94.

DOI： 10.11239/jsmbe.annual59.515

Rituximab for antibody-mediated rejection after lung transplantation

CHEN-YOSHIKAWA Toyofumi F., DATE Hiroshi, SUGIMOTO Seiichiro, SHIRAISHI Takeshi, NAKAGAWA Ken, EGAWA Hiroto

Japanese Journal of Transplantation Vol. 56 ( 1 ) page： 53 - 68 2021

Language：Japanese Publisher：The Japan Society for Transplantation

【Objective】 We retrospectively surveyed the details of treatment with rituximab for antibody-mediated rejection (AMR) after lung transplantation.【Design】 Case series.【Methods】 This study was conducted to assess outcomes in patients who underwent lung transplantation in Japan from August 2001 to December 2016 and were treated with rituximab for AMR. A questionnaire was sent to medical institutions that had used rituximab for such treatment, and information on AMR treatment, including rituximab dosage, efficacy, and safety, was collected.【Results】 Among the 525 patients undergoing lung transplantation during the study period in Japan, fourteen patients (2.7%; 1 child and 13 adults) were enrolled. Records showed definite clinical AMR in 3 patients, probable clinical AMR in 2 patients, possible clinical AMR in 8 patients and suspected AMR in 1 patient. All patients had allograft dysfunction, and 13 adult patients were positive for donor-specific antibodies (DSA). Two patients experienced rejection more than twice. Rituximab was administered to all patients. In one patient who experienced AMR twice, rituximab was administered for each AMR. The rituximab dose was 375 mg/m2 in all but one patient, who received 348 mg/m2. Eight patients recovered from AMR. AMR treatments, including rituximab, were well tolerated. However, 11 patients developed graft loss due to rejection, and 10 patients died from chronic lung allograft syndrome or sepsis.【Conclusion】 Based on these findings, treatment containing rituximab was considered effective for AMR, but careful monitoring is needed to prevent or reduce the number of adverse events such as infection.

DOI： 10.11386/jst.56.1_53

Commentary: Change the temperature before we have to

Kadomatsu Y., Chen-Yoshikawa T.F.

Journal of Thoracic and Cardiovascular Surgery 2021

Commentary: To know yourself is to know your neighbor

Nakanishi K., Chen-Yoshikawa T.F.

Journal of Thoracic and Cardiovascular Surgery 2021

Commentary: Look Before You Leap

Fukumoto K., Chen-Yoshikawa T.F.

Seminars in Thoracic and Cardiovascular Surgery 2021

Electromagnetic navigation bronchoscopy versus virtual bronchoscopy navigation for improving the diagnosis of peripheral lung lesions: analysis of the predictors of successful diagnosis

Yutaka Y., Sato T., Isowa M., Murata Y., Tanaka S., Yamada Y., Ohsumi A., Nakajima D., Hamaji M., Menju T., Chen-Yoshikawa T.F., Date H.

Surgery Today 2021

Language：Japanese Publisher：Surgery Today

Purpose: To investigate if electromagnetic navigation bronchoscopy (ENB) improves the diagnostic yield for peripheral lung lesions from that achieved by virtual bronchoscopy navigation (VBN). Methods: This retrospective study compared the results of 100 ENB-transbronchial lung biopsies (TBLBs) with those of 50 VBN-TBLBs at a single institution. Results: ENB improved the diagnostic yield significantly compared with VBN (64.0% for 19.4 ± 9.0 mm tumors vs. 46.0% for 27.6 ± 8.9 mm tumors; p < 0.0001). Irrespective of the bronchus sign, ENB was more favorable than VBN, with 81.0% (47/58) achieved by ENB vs. 60.0% (21/35) achieved by VBN in the presence of the positive bronchus sign (p = 0.0283), and 40.5% (17/42) achieved by ENB vs. 13.3% (2/15) achieved by VBN in the absence of the bronchus sign (p = 0.0431). Univariate analysis identified tumor size (p = 0.0048), amount of intravenous sedation (p = 0.0182), registration time (p = 0.0111), minimum distance to target (p = 0.0244), and the bronchus sign (p < 0.0001) as factors that affected the yield significantly for ENB. Multivariate analysis identified the bronchus sign (odds ratio 6.74; 95% CI 1.84–24.7) and the registration time (OR 1.01; 95% CI 1.00–1.02) as significant factors. Conclusions: Despite the bronchus sign being a significant factor, ENB improved the diagnostic yield of smaller lesions significantly, compared with VBN, regardless of the bronchus sign.

DOI： 10.1007/s00595-021-02398-z

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

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

Nagoya Journal of Medical Science Vol. 83 ( 2 ) page： 227 - 237 2021

Language：Japanese Publisher：Nagoya Journal of Medical Science

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

DOI： 10.18999/nagjms.83.2.227

Kernel-based modeling of pneumothorax deformation using intraoperative cone-beam CT images

Nakao M., Maekawa H., Mineura K., Chen-Yoshikawa T.F., Matsuda T.

Progress in Biomedical Optics and Imaging - Proceedings of SPIE Vol. 11598 2021

Language：Japanese Publisher：Progress in Biomedical Optics and Imaging - Proceedings of SPIE

In this study, we introduce statistical modeling methods for pneumothorax deformation using paired cone-beam computed tomography (CT) images. We designed a deformable mesh registration framework for shape changes involving non-linear deformation and rotation of the lungs. The registered meshes with local correspondences are available for both surgical guidance in thoracoscopic surgery and building statistical deformation models with inter-patient variations. In addition, a kernel-based deformation learning framework is proposed to reconstruct intraoperative dfl ated states of the lung from the preoperative CT models. This paper reports the findings of pneumothorax deformation and evaluation results of the kernel-based deformation framework.

DOI： 10.1117/12.2581388

Erector spinae muscle radiographic density is associated with survival after lung transplantation

Oshima Y., Sato S., Chen-Yoshikawa T.F., Nakajima D., Nankaku M., Date H., Matsuda S.

Journal of Thoracic and Cardiovascular Surgery 2021

Language：Japanese Publisher：Journal of Thoracic and Cardiovascular Surgery

Objective: The study objective was to verify whether low preoperative radiographic density of erector spinae muscles is associated with poor prognosis after lung transplantation. Methods: Preoperative chest computed tomography scans for patients who underwent deceased-donor lung transplantation between 2013 and 2019 at Kyoto University Hospital were retrospectively retrieved. The radiographic density of erector spinae muscles was quantitatively evaluated as the mean attenuation of erector spinae muscles, and low mean radiographic density of the erector spinae muscles was defined as a mean radiographic density of the erector spinae muscles value below the median value for all patients. Overall survival and chronic lung allograft dysfunction-free survival with high and low mean radiographic density of the erector spinae muscles were estimated using the Kaplan–Meier method and evaluated by the log-rank test, as well as by univariate and multivariate Cox proportional hazard analyses. Results: Of the 107 adult patients who underwent primary transplantation, 96 underwent at least 1 chest computed tomography scan within 24 hours before lung transplantation. The median mean radiographic density of the erector spinae muscles in these 96 patients was 49.2 Hounsfield units. A low mean radiographic density of the erector spinae muscles value was significantly associated with decreased overall survival (hazard ratio, 4.50; P =.030) and chronic lung allograft dysfunction–free survival (hazard ratio, 3.18; P =.028) in the multivariate analysis. Additionally, patients with preoperative steroid use and a low mean radiographic density of the erector spinae muscles value had a worse overall survival (P <.001) and chronic lung allograft dysfunction–free survival (P <.001) than patients with preoperative steroid use and a high mean radiographic density of the erector spinae muscles value and those without preoperative steroid use. Conclusions: Low mean radiographic density of the erector spinae muscles was closely associated with a poor prognosis after lung transplantation. The prognosis was particularly poor in patients with preoperative steroid use and a low mean radiographic density of the erector spinae muscles. These results may be useful when considering the indications for lung transplantation or preoperative interventions. Video Abstract:[Figure presented]

DOI： 10.1016/j.jtcvs.2021.07.039

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

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

Annals of Thoracic Surgery 2021

Language：Japanese Publisher：Annals of Thoracic Surgery

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

DOI： 10.1016/j.athoracsur.2021.07.087

The importance of central airway dilatation in patients with bronchiolitis obliterans

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

ERJ Open Research Vol. 7 ( 4 ) 2021

Publisher：ERJ Open Research

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

DOI： 10.1183/23120541.00123-2021

肺移植後遠隔期における健康関連QoLの実態と関連因子の検討

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

呼吸理学療法学 Vol. 7th.Meeting ( 0 ) page： SJ-2 2021

肺移植における術後早期栄養介入の試み

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

移植 Vol. 56 ( Supplement ) page： s104 - s104 2021

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

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

DOI： 10.11386/jst.56.supplement_s104

肺移植におけるEx Vivo Lung Perfusionの現状

中島大輔, 芳川豊史, 伊達洋至

移植 Vol. 56 ( Supplement ) page： s556 - s556 2021

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

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

DOI： 10.11386/jst.56.supplement_s556

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

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

移植 Vol. 56 ( Supplement ) page： s105 - s105 2021

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

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

DOI： 10.11386/jst.56.supplement_s105

Backtable bronchoplasty for donor tracheal bronchus in lung transplantation.

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

General thoracic and cardiovascular surgery Vol. 68 ( 12 ) page： 1536 - 1538 2020.12

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

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

DOI： 10.1007/s11748-020-01305-6

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

Yogo N.

PLoS ONE Vol. 15 ( 11 November ) 2020.11

CT画像を用いた肺葉切除後の呼吸機能と運動耐容能の予測

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

日本胸部外科学会定期学術集会 Vol. 73回 page： LOO14 - 6 2020.10

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

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

日本胸部外科学会定期学術集会 Vol. 73回 page： LOO1 - 40 2020.10

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

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

EUROPEAN RESPIRATORY JOURNAL Vol. 56 2020.9

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

Okabe R.

European Journal of Cardio-thoracic Surgery Vol. 58 ( 3 ) page： 638 - 645 2020.9

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

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

Surgery today Vol. 50 ( 9 ) page： 1049 - 1055 2020.9

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

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

DOI： 10.1007/s00595-020-01989-6

Expanded indications for auto-lung transplant technique.

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

General thoracic and cardiovascular surgery Vol. 68 ( 8 ) page： 828 - 832 2020.8

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

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

DOI： 10.1007/s11748-020-01289-3

A case of right upper lobectomy for lung cancer with partial anomalous pulmonary venous connection and tracheal bronchus

Ito Toshinari, Fukui Takayuki, Hakiri Shuhei, Nakamura Shota, Kawaguchi Koji, Chen-Yoshikawa Toyofumi

The Journal of the Japanese Association for Chest Surgery Vol. 34 ( 5 ) page： 321 - 326 2020.7

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Association for Chest Surgery

A 76-year-old man presented with an abnormal shadow on a chest roentgenogram. After a comprehensive radiographic examination and transbronchial lung biopsy, the preoperative diagnosis was lung adenocarcinoma Stage IA2 (cT1bN0M0).Chest computed tomography showed a partial anomalous pulmonary venous connection from the right upper and middle lobe and a right B1 bronchus branching from the trachea simultaneously. We attempted to perform complete video-assisted thoracic surgery (VATS) for right upper lobectomy. However, we required a small window incision to complete VATS lobectomy to improve our understanding of the intraoperative anatomy. In cases with uncommon anomalies such as the present patient, enlargement of the port incision to improve intraoperative understanding of the anatomy is important to perform a safe and minimally invasive procedure.

DOI： 10.2995/jacsurg.34.321

Model-based registration for pneumothorax deformation analysis using intraoperative cone-beam CT images. International journal

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

Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference Vol. 2020 page： 5818 - 5821 2020.7

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

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

DOI： 10.1109/EMBC44109.2020.9176729

Well-differentiated fetal adenocarcinoma of the lung: positron emission tomography features and diagnostic difficulties in frozen section analysis-a case report. International journal

Shuhei Hakiri, Takayuki Fukui, Hideki Tsubouchi, Ayako Sakakibara, Shingo Iwano, Toyofumi F Chen-Yoshikawa

Surgical case reports Vol. 6 ( 1 ) page： 152 - 152 2020.6

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

BACKGROUND: Well-differentiated fetal adenocarcinoma (WDFA) of the lung is a rare disease that resembles fetal lung tubules. Most of previous reports concerning WDFA have focused on histological features, while there are few reports describing radiological features. In addition, there are no reports evaluating the difficulty of intraoperative diagnosis of WDFA with frozen section. We report a case of WDFA and review the radiological features of WDFA including the findings of F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and assess the difficulty of intraoperative diagnosis with frozen section. CASE PRESENTATION: A chest radiography performed in a 20-year-old female revealed a mass in the hilum of the right lung. Computed tomography revealed a well-defined mass measuring 3.5 × 3.0 cm in diameter in the right upper lobe, whereas PET showed a high accumulation of FDG. The most likely diagnosis was clinical T2aN0M0 stage 1B non-small cell lung cancer. A right S3 segmentectomy was performed via thoracotomy, and a benign tumor that was possibly an adenoma was intraoperatively diagnosed based on frozen section analysis. The mass was a solid tumor measuring 2.9 × 2.5 cm in diameter. Microscopically, the tumor comprised abundant glands with single or double layers of nonciliated cells and bronchial structures resembling a fetal lung. Rounded morules of polygonal cells were frequently observed. Immunohistochemistry revealed that nuclei and cytoplasm of the tumor cell were positive for β-catenin. Finally, the postoperative pathological diagnosis was well-differentiated fetal adenocarcinoma of the lung, and completion right upper lobectomy and mediastinal lymph node dissection were conducted 1 month after the initial segmentectomy. No residual tumor or lymph node metastasis was identified, and the final pathological stage was pT1cN0M0 stage 1A3. The patient did not wish to receive any adjuvant therapy. At the 1-year follow-up, no evidence of recurrence was noted. CONCLUSIONS: Here, we report a rare case of well-differentiated fetal adenocarcinoma of the lung that was difficult to diagnose based on radiological evaluations including FDG-PET and intraoperative diagnosis using frozen section analysis.

DOI： 10.1186/s40792-020-00910-0

Tranilast inhibits TGF-β1-induced epithelial-mesenchymal transition and invasion/metastasis via the suppression of Smad4 in human lung cancer cell lines

Takahashi K

Anticancer Research Vol. 40 ( 6 ) page： 3287-3296 - 3296 2020.6

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

Background/Aim: Transforming growth factor β1 (TGF-β1) is an important epithelial-mesenchymal transition (EMT) activator that regulates the expression of E-cadherin and vimentin through Smad signalling. Tranilast is an antiallergic drug that inhibits TGF-β1, and is used in the treatment of keloids and hypertrophic scars. We investigated whether tranilast inhibits TGF-β1-induced EMT and invasiveness in human non-small cell lung cancer cell lines. Materials and Methods: We examined the effects of tranilast treatment on EMT markers, TGF-β1/Smad signalling, and cell invasiveness in A549 and PC14 cells. Tumours from a mouse orthotopic lung cancer model with or without tranilast treatment were also immunohistochemically evaluated. Results: Tranilast increased E-cadherin expression via Smad4 suppression and inhibited cell invasion in TGF-β1-stimulated cells. Tranilast treatment of the in vivo mouse model reduced the pleural dissemination of cancer cells and suppressed vimentin and Smad4 expression. Conclusion: Tranilast inhibited TGF-β1- induced EMT and cellular invasion/metastasis by suppressing Smad4 expression in cancer cells.

DOI： 10.2196/10.21873/anticanres.14311

Living-donor single-lobe lung transplantation for pulmonary hypertension due to alveolar capillary dysplasia with misalignment of pulmonary veins. International journal

Daisuke Nakajima, Hiromi Oda, Katsutaka Mineura, Tatsuya Goto, Itaru Kato, Shiro Baba, Tadashi Ikeda, Toyofumi F Chen-Yoshikawa, Hiroshi Date

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Vol. 20 ( 6 ) page： 1739 - 1743 2020.6

Language：English

This is a case report of a successful single-lobe lung transplantation for pulmonary hypertension secondary to alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV). A 6-year-old boy underwent living-donor single-lobe transplantation with the right lower lobe from his 31-year-old mother. The pretransplantation graft size matching was acceptable: the estimated graft forced vital capacity (FVC) was 96.5% of the recipient's predicted FVC, and the graft size measured by computed tomography (CT) volumetry was 166% of the recipient's chest cavity volume. Right pneumonectomy followed by implantation was performed under cardiopulmonary bypass (CPB). The pulmonary arterial pressure was significantly decreased to 31/12 mm Hg immediately after transplantation, and the first PaO2 /FiO2 in the intensive-care unit (ICU) was 422 mm Hg. Lung perfusion scintigraphy showed 97.5% perfusion to the right implanted lung 3 months after transplantation. Chest CT showed a mass rapidly growing in the native left upper lobe 6 months after transplantation, which was diagnosed as posttransplant lymphoproliferative disorder (PTLD) by a CT-guided biopsy. After immunosuppressant reduction and six courses of chemotherapy with rituximab, he underwent native left upper lobectomy for salvage lung resection 13 months after transplantation. Seven months after lobectomy, he has returned to normal school life without any sign of tumor recurrence.

DOI： 10.1111/ajt.15762

Tranilast Inhibits TGF-β1-induced Epithelial-mesenchymal Transition and Invasion/Metastasis via the Suppression of Smad4 in Human Lung Cancer Cell Lines. International journal

Koji Takahashi, Toshi Menju, Shigeto Nishikawa, Ryo Miyata, Satona Tanaka, Yojiro Yutaka, Yoshito Yamada, Daisuke Nakajima, Masatsugu Hamaji, Akihiro Ohsumi, Toyofumi Fengshi Chen-Yoshikawa, Toshihiko Sato, Makoto Sonobe, Hiroshi Date

Anticancer research Vol. 40 ( 6 ) page： 3287 - 3296 2020.6

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

BACKGROUND/AIM: Transforming growth factor β1 (TGF-β1) is an important epithelial-mesenchymal transition (EMT) activator that regulates the expression of E-cadherin and vimentin through Smad signalling. Tranilast is an anti-allergic drug that inhibits TGF-β1, and is used in the treatment of keloids and hypertrophic scars. We investigated whether tranilast inhibits TGF-β1-induced EMT and invasiveness in human non-small cell lung cancer cell lines. MATERIALS AND METHODS: We examined the effects of tranilast treatment on EMT markers, TGF-β1/Smad signalling, and cell invasiveness in A549 and PC14 cells. Tumours from a mouse orthotopic lung cancer model with or without tranilast treatment were also immunohistochemically evaluated. RESULTS: Tranilast increased E-cadherin expression via Smad4 suppression and inhibited cell invasion in TGF-β1-stimulated cells. Tranilast treatment of the in vivo mouse model reduced the pleural dissemination of cancer cells and suppressed vimentin and Smad4 expression. CONCLUSION: Tranilast inhibited TGF-β1-induced EMT and cellular invasion/metastasis by suppressing Smad4 expression in cancer cells.

DOI： 10.21873/anticanres.14311

LPS-induced Airway-centered Inflammation Leading to BOS-like Airway Remodeling Distinct From RAS-like Fibrosis in Rat Lung Transplantation. International journal

Akihiro Takahagi, Masaaki Sato, Toyofumi F Chen-Yoshikawa, Ei Miyamoto, Masao Saito, Fumiaki Gochi, Masatsugu Hamaji, Akihiko Yoshizawa, Yasuhiro Terasaki, Hirokazu Urushiyama, Akihiro Aoyama, Makoto Sonobe, Hiroshi Date

Transplantation Vol. 104 ( 6 ) page： 1150 - 1158 2020.6

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

BACKGROUND: Localization of inflammatory stimuli may direct lung allografts to different phenotypes of chronic dysfunction, such as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). We hypothesized that airway stimulation with lipopolysaccharide (LPS) in rats leads to airway-centered inflammation similar to human BOS. METHODS: Rat left lung transplantation was conducted (donor: Brown Norway, recipient: Lewis). Allotransplant recipients received cyclosporine A (CsA) until postoperative day 56 with airway instillation of LPS (Allo-LPS, n = 8), phosphate buffered saline (Allo-PBS, n = 5) from days 35 to 46 (3 times a wk), or no further treatment (n = 4). Some allotransplant recipients received CsA until day 14 and were immunosuppression free after day 15 until day 56. Bronchial and pleural fibrosis were semiquantified; alveolar fibrosis was evaluated with a histological scale. RESULTS: The Allo-LPS group had significantly increased International Society for Heart and Lung Transplantation rejection grades (grade A, P = 0.005; grade B, P = 0.004), bronchial obstructive proportion (0.34 ± 0.04% [Allo-LPS] versus 0.11 ± 0.04% [Allo-PBS], P = 0.006), and airway resistance (3.05 ± 1.78 cm H2O·s/mL [Allo-LPS] versus 0.83 ± 0.58 cm H2O·s/mL [Allo-PBS], P = 0.007) compared with other groups. Allotransplant recipients that underwent a short course of CsA developed RAS-like fibrosis involving the airways, alveoli, and pleura. CONCLUSIONS: Airway instillation of LPS in allografts under immunosuppression resulted in BOS-like airway-centered inflammation and fibrosis distinct from RAS-like diffuse fibrosis, which was induced by a shortened course of immunosuppression. We propose novel animal models for BOS and RAS after lung transplantation.

DOI： 10.1097/TP.0000000000003097

Psoas muscle mass in patients undergoing lung cancer surgery: a prognostic difference between squamous cell carcinoma and adenocarcinoma

Ozeki N

International Journal of Clinical Oncology Vol. 25 ( 5 ) page： 876-884 - 884 2020.5

Current trends in thoracic surgery

Chen-Yoshikawa T.F

Nagoya Journal of Medical Science Vol. 82 ( 2 ) page： 161-173 - 173 2020.5

Protective effects of a hydrogen-rich solution during cold ischemia in rat lung transplantation. Reviewed International journal

Masao Saito, Toyofumi F Chen-Yoshikawa, Mamoru Takahashi, Hidenao Kayawake, Yuhei Yokoyama, Ryosuke Kurokawa, Shin-Ichi Hirano, Hiroshi Date

J Thorac Cardiovasc Surg Vol. 159 ( 5 ) page： 2110 - 2118 2020.5

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

BACKGROUND: Molecular hydrogen can reduce the oxidative stress of ischemia-reperfusion injury in various organs for transplantation and potentially improve survival rates in recipients. This study aimed to evaluate the protective effects of a hydrogen-rich preservation solution against ischemia-reperfusion injury after cold ischemia in rat lung transplantation. METHODS: Lewis rats were divided into a nontransplant group (n = 3), minimum-ischemia group (n = 3), cold ischemia group (n = 6), and cold ischemia with hydrogen-rich (more than 1.0 ppm) preservation solution group (n = 6). The rats in the nontransplant group underwent simple thoracotomy, and the rats in the remaining 3 groups underwent orthotopic left lung transplantation. The ischemic time was <30 minutes in the minimum-ischemia group and 6 hours in the cold ischemia groups. After 2-hour reperfusion, we evaluated arterial blood gas levels, pulmonary function, lung wet-to-dry weight ratio, and histologic features of the lung tissue. The expression of proinflammatory cytokines was measured using quantitative polymerase chain reaction assays, and 8-hydroxydeoxyguanosine levels were evaluated using enzyme-linked immunosorbent assays. RESULTS: When compared with the nontransplant and minimum-ischemia groups, the cold ischemia group had lower dynamic compliance, lower oxygenation levels, and higher wet-to-dry weight ratios. However, these variables were significantly improved in the cold ischemia with hydrogen-rich preservation solution group. This group also had fewer signs of perivascular edema, lower interleukin-1β messenger RNA expression, and lower 8-hydroxydeoxyguanosine levels than the cold ischemia group. CONCLUSIONS: The use of a hydrogen-rich preservation solution attenuates ischemia-reperfusion injury in rat lungs during cold ischemia through antioxidant and anti-inflammatory effects.

DOI： 10.1016/j.jtcvs.2019.09.175

Targeted Phototherapy for Malignant Pleural Mesothelioma: Near-Infrared Photoimmunotherapy Targeting Podoplanin International journal

Nishinaga Y

Cells Vol. 9 ( 4 ) 2020.4

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

Malignant pleural mesothelioma (MPM) has extremely limited treatment despite a poor prognosis. Moreover, molecular targeted therapy for MPM has not yet been implemented; thus, a new targeted therapy is highly desirable. Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed cancer therapy that combines the specificity of antibodies for targeting tumors with toxicity induced by the photoabsorber after exposure to NIR-light. In this study, we developed a new phototherapy targeting podoplanin (PDPN) for MPM with the use of both NIR-PIT and an anti-PDPN antibody, NZ-1. An antibody-photosensitizer conjugate consisting of NZ-1 and phthalocyanine dye was synthesized. In vitro NIR-PIT-induced cytotoxicity was measured with both dead cell staining and luciferase activity on various MPM cell lines. In vivo NIR-PIT was examined in both the flank tumor and orthotopic mouse model with in vivo real-time imaging. In vitro NIR-PIT-induced cytotoxicity was NIR-light dose dependent. In vivo NIR-PIT led to significant reduction in both tumor volume and luciferase activity in a flank model (p < 0.05, NIR-PIT group versus NZ-1-IR700 group). The PDPN-targeted NIR-PIT resulted in a significant antitumor effect in an MPM orthotopic mouse model (p < 0.05, NIR-PIT group versus NZ-1-IR700 group). This study suggests that PDPN-targeted NIR-PIT could be a new promising treatment for MPM.

DOI： 10.3390/cells9041019

Deformation Estimation of Deflated Lung using Kernel Method based on the Relative Position of Some Landmarks

Yamamoto Utako, Nakao Megumi, Ohzeki Masayuki, Tokuno Junko, Yoshikawa Toyofumi, Matsuda Tetsuya

Transactions of the Institute of Systems, Control and Information Engineers Vol. 33 ( 4 ) page： 123 - 127 2020.4

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：THE INSTITUTE OF SYSTEMS, CONTROL AND INFORMATION ENGINEERS (ISCIE)

It is expected to grasp how the lung deform by the deaeration during surgery compared to the inflated lung. In this study we propose a method to estimate deformation of the deflated lung from the inflated one based on the relative position of some landmarks using dog lungs. The kernel method was employed for the estimation as a machine learning technique. We achieved mean local positional error of 2.96 mm for test data where the volume reduction by the deaeration was 40 %.

DOI： 10.5687/iscie.33.123

Analysis of the Change in Sleep Quality in Lung Transplant Recipients

Tokuno J

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

CD26/DPP4 Inhibitor: A Novel Prophylactic Drug for Chronic Allograft Dysfunction after Clinical Lung Transplantation

Yamada Y

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

Comparison of Characteristics of De Novo Donor-Specific Anti-HLA Antibodies (dnDSAs) in Living-Donor Lobar Lung Transplantation and Deceased-Donor Lung Transplantation

Kayawake H

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Vol. 39 ( 4 ) page： S307-S308 2020.4

Extrapulmonary Problems Limit the Outcome of Lung Transplantation in Idiopathic Pleuroparenchymal Fibroelastosis: A Multi-Center Study in Japan

Shiiya H

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Vol. 39 ( 4 ) page： S313-S314 - S314 2020.4

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

Copyright © 2020. Published by Elsevier Inc. PURPOSE: Idiopathic pleurparenchymal fibroelastosis (IPPFE) is a relatively new disease entity of interstitial pneumonia characterized by upper lobe dominant fibrosis and flat chest. The purpose of this study is to evaluate the outcome of lung transplantation for IPPFE in comparison with idiopathic pulmonary fibrosis (IPF). METHODS: We retrospectively reviewed patients with IPPFE and those with IPF aged 20 or over who underwent lung transplantation between 1998 and 2018. Data were collected from all nine lung transplant centers in Japan, under the support of Japanese Society of Lung and Heart-Lung Transplantation. RESULTS: One hundred patients were eligible, including 31 IPPFE and 69 IPF patients. Patients with IPPFE were more likely to be women (58% vs 28%; P < 0.01) and to have a significantly lower body mass index (BMI) (17.6±3.6 vs 22.6±4.2 kg/m2; P < 0.01) than those in the IPF group. Kaplan-Meier survival curves showed no significant difference in overall survival between groups (P = 0.66; Figure 1A). The stay in the intensive care unit (ICU) was significantly longer in the IPPFE group (22.8±19.15 vs 13.2±11.2 days; P < 0.01). In the IPPFE group, BMI did not improve even 1 year after transplant (pre-; 16.5±3.2 kg/m2 vs 2 years later; 15.6±2.5 kg/m2; P = 0.08). By two years after transplantation, percent predicted forced vital capacity in IPPFE group significantly improved (pre-; 36.9±17.2 vs 2 years later; 52.0±20.0 %; P = 0.03; Figure 1B). However, compared with the IPF group, the value was still significantly lower (52.0±20.0 vs 70.8±18.7 %; P < 0.01). CONCLUSION: The survival of patients with IPPFE after lung transplantation was comparable with those with IPF. However, patients with IPPFE showed longer ICU stay, limited improvement in pulmonary function, and no improvement in low BMI, suggesting systemic or extrapulmonary problems such as stiff chest wall in patients with IPPFE.

DOI： 10.1016/j.healun.2020.01.706

Protective Effects of Necrosulfonamide on Ischemia-Reperfusion Injury in Rat Lung

Ueda S

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

Prognostic factors related to postoperative survival in the newly classified clinical T4 lung cancer. Reviewed International journal

Keiji Yamanashi, Toshi Menju, Masatsugu Hamaji, Satona Tanaka, Yojiro Yutaka, Yoshito Yamada, Daisuke Nakajima, Akihiro Ohsumi, Akihiro Aoyama, Toshihiko Sato, Toyofumi Fengshi Chen-Yoshikawa, Makoto Sonobe, Hiroshi Date

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Vol. 57 ( 4 ) page： 754 - 761 2020.4

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

OBJECTIVES: T4 lung cancer has become a more heterogeneous group since the 8th edition of tumour, node, metastasis classification. The aim of this study was to identify predictive factors related to post-surgical survival in patients with clinical T4 non-small-cell lung cancer (NSCLC), based on the 8th edition of the classification. METHODS: We retrospectively reviewed consecutive patients with clinical T4 NSCLC who underwent resection between January 2006 and December 2016, to identify factors associated with overall survival. RESULTS: Ninety-three patients were identified. The criteria for clinical T4 disease included tumours larger than 7 cm (n = 54), great vessels or left atrial invasion (n = 22), mediastinal invasion (n = 11), vertebral invasion (n = 3), tracheal or carina invasion (n = 3), diaphragm invasion (n = 1) and ipsilateral different lobe pulmonary metastasis (n = 2). The postoperative nodal status was 0, 1, 2 and 3 in 59, 18, 15 and 1 patient, respectively. R0 resection was achieved in 80 patients, and the 30-day mortality was 0%. The median follow-up time was 37.6 months, and the 5-year overall survival rate was 56.3%. The multivariable analysis revealed that nodal status and R-status were significant prognostic factors for postoperative survival [hazard ratio (HR) 2.62, 95% confidence interval (CI) 1.20-5.72, P = 0.016 and HR 3.29, 95% CI 1.45-7.44, P = 0.004]. CONCLUSIONS: Surgery provided encouraging survival outcomes for clinical T4 NSCLC based on the 8th edition of classification. The nodal status and R-status were significant prognostic factors for postoperative survival.

DOI： 10.1093/ejcts/ezz288

Commentary: Development of a new concept is achieved only step-by-step

Chen-Yoshikawa T.F

Journal of Thoracic and Cardiovascular Surgery Vol. 159 ( 4 ) page： 1656-1657 - 1657 2020.4

Quantity and quality of antigravity muscles in patients undergoing living-donor lobar lung transplantation: 1-year longitudinal analysis using chest computed tomography images. International journal

Yohei Oshima, Susumu Sato, Toyofumi F Chen-Yoshikawa, Yuji Yoshioka, Nana Shimamura, Ryota Hamada, Manabu Nankaku, Akira Tamaki, Hiroshi Date, Shuichi Matsuda

ERJ open research Vol. 6 ( 2 ) 2020.4

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

BACKGROUND: Skeletal muscle dysfunction is a common feature in patients with severe lung diseases. Although lung transplantation aims to save these patients, the surgical procedure and disuse may cause additional deterioration and prolonged functional disability. We investigated the postoperative course of antigravity muscle condition in terms of quantity and quality using chest computed tomography. METHODS: 35 consecutive patients were investigated for 12 months after living-donor lobar lung transplantation (LDLLT). The erector spinae muscles (ESMs), which are antigravity muscles, were evaluated, and the cross-sectional area (ESMCSA) and mean attenuation (ESMCT) were analysed to determine the quantity and quality of ESMs. Functional capacity was evaluated by the 6-min walk distance (6MWD). Age-matched living donors with lower lobectomy were evaluated as controls. RESULTS: Recipient and donor ESMCSA values temporarily decreased at 3 months and recovered by 12 months post-operatively. The ESMCSA of recipients, but not that of donors, surpassed baseline values by 12 months post-operatively. Increased ESMCSA (ratio to baseline ≥1) may occur at 12 months in patients with a high baseline ESMCT. Although the recipient ESMCT may continuously decrease for 12 months, the ESMCT is a major determinant, in addition to lung function, of the postoperative 6MWD at both 3 and 12 months. CONCLUSION: The quantity of ESMs may increase within 12 months after LDLLT in recipients with better muscle quality at baseline. The quality of ESMs is also important for physical performance; therefore, further approaches to prevent deterioration in muscle quality are required.

DOI： 10.1183/23120541.00205-2019

Characteristics of incomplete endobronchial ultrasound-guided transbronchial needle aspiration cases

Kayawake H., Chen-Yoshikawa T.F., Takana S., Yamada Y., Yutaka Y., Nakajima D., Hamaji M., Menju T., Ohsumi A., Date H.

Journal of Thoracic Disease Vol. 12 ( 3 ) page： 573 - 580 2020.3

Language：Japanese Publisher：Journal of Thoracic Disease

Backgrounds: The number of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) cases is increasing due to its less-invasiveness and usefulness. However, there are several unresolved issues, including the existence of incomplete cases and complications. This study aimed to investigate the frequency and diagnostic management of incomplete EBUS-TBNA cases. Methods: Between July 2009 and December 2017, 424 patients underwent EBUS-TBNA for the diagnosis of suspected malignancy. Among them, we retrospectively reviewed the frequency, characteristics and diagnostic managements of incomplete cases of EBUS-TBNA. Results: EBUS-TBNA was not completed in 16 patients (3.8%), all of whom underwent EBUS-TBNA cases under conscious sedation. The factors for incompleteness of EBUS-TBNA under conscious sedation were divided into two groups: impossibility to perform EBUS-TBNA under conscious sedation (n=8) and impossibility to perform safe needle biopsy (n=8). The former factor consisted of strong coughing reflex and insufficient sedation (n=5), frequent desaturation during EBUS-TBNA (n=2), and allergy to lidocaine (n=1), while the latter factor consisted of anatomical reasons (n=4), abundant blood flow in the target lesion (n=3), and invisibility of the target lesion due to airway deformation (n=1). Eventually, 10 out of 16 cases were histologically diagnosed as having malignancy by a surgical approach (n=5) and EBUS-TBNA under general anesthesia (n=5). Conclusions: Although the number was small, we did note some incomplete cases of EBUS-TBNA under conscious sedation. In incomplete cases under conscious sedation, EBUS-TBNA under general anesthesia and other surgical approaches can be considered as additional options.

DOI： 10.21037/jtd.2019.12.133

Near infrared photoimmunotherapy targeting DLL3 for small cell lung cancer

Isobe Y

EBioMedicine Vol. 52 2020.2

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

© 2020 The Authors Background: Small cell lung cancer (SCLC) has a poor prognosis, and its treatment options are limited. Delta-like protein 3 (DLL3) is expressed specifically in SCLC and is considered a promising therapeutic target for patients with this disease. Rovalpituzumab tesirine (Rova-T) was the first antibody-drug conjugate targeting DLL3. Although Rova-T development was unfortunately terminated, DLL3 remains an ideal target for SCLC. Near infrared photoimmunotherapy (NIR-PIT) is a new form of cancer treatment that employs an antibody-photosensitiser conjugate followed by NIR light exposure and damage target cells specifically. In this study, we demonstrate DLL3-targeted NIR-PIT to develop a novel molecularly targeted treatment for SCLC. Methods: The anti-DLL3 monoclonal antibody rovalpituzumab was conjugated to an IR700 photosensitiser (termed ‘rova-IR700’). SCLC cells overexpressing DLL3 as well as non-DLL3-expressing controls were incubated with rova-IR700 and then exposed to NIR-light. Next, mice with SCLC xenografts were injected with rova-IR700 and irradiated with NIR-light. Findings: DLL3-overexpressing cells underwent immediate destruction upon NIR-light exposure, whereas the control cells remained intact. The xenograft in mice treated with rova-IR700 and NIR-light shrank markedly, whereas neither rova-IR700 injection nor NIR-light irradiation alone affected tumour size. Interpretation: Our data suggest that targeting of DLL3 using NIR-PIT could be a novel and promising treatment for SCLC. Funding: Research supported by grants from the Program for Developing Next-generation Researchers (Japan Science and Technology Agency), KAKEN (18K15923, JSPS), Medical Research Encouragement Prize of The Japan Medical Association, The Nitto Foundation, Kanae Foundation for the Promotion of Medical Science.

DOI： 10.1016/j.ebiom.2020.102632

Outcomes of combination therapy including rituximab for antibody-mediated rejection after lung transplantation. Reviewed

Keiji Yamanashi, Toyofumi Fengshi Chen-Yoshikawa, Masatsugu Hamaji, Kimiko Yurugi, Satona Tanaka, Yojiro Yutaka, Yoshito Yamada, Daisuke Nakajima, Akihiro Ohsumi, Hiroshi Date

General thoracic and cardiovascular surgery Vol. 68 ( 2 ) page： 142 - 149 2020.2

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

OBJECTIVES: This study assessed the outcomes of combination therapy including rituximab for antibody-mediated rejection after lung transplantation. METHODS: Retrospective chart reviews were performed for all patients who received combination therapy including rituximab for post-lung transplantation antibody-mediated rejection between June 2008 and October 2018. RESULTS: Among the 196 consecutive patients undergoing lung transplantation during the study period, eight (4.1%) were eligible for this study. Two patients (25.0%) were classified as having clinically definite antibody-mediated rejection and six (75.0%) as having possible antibody-mediated rejection. Prior to treatment, four patients (50.0%) met the definition of chronic lung allograft dysfunction; seven of the eight patients (87.5%) remained alive at 6 months and four (50.0%) at 12 months after antibody-mediated rejection. All patients identified as having chronic lung allograft dysfunction, prior to the treatment, died of allograft failure, or underwent re-transplantation. Decreases in the mean fluorescence intensities of the major donor-specific antibodies were observed in three patients. One patient, diagnosed with clinical antibody-mediated rejection but without pre-treatment chronic lung allograft dysfunction, began treatment relatively soon after lung transplantation, and demonstrated improved respiratory function at the 3-year follow-up. CONCLUSIONS: Our experience suggests that multimodality therapy that includes rituximab is feasible and may prevent progression of antibody-mediated rejection after lung transplantation in selected patients.

DOI： 10.1007/s11748-019-01189-1

A preliminary study on deformation analysis of collapsed lung using intraoperative CBCT images

MAEKAWA Hinako, NAKAO Megumi, MINEURA Katsutaka, CHEN-YOSHIKAWA Toyofumi F, MATSUDA Tetsuya

Vol. 119 ( 399 ) page： 31 - 36 2020.1

Unexpected metastasis of intraductal papillary neoplasm of the bile duct without an invasive component to the brain and lungs: A case report. International journal

Nguyen Hai Nam, Kojiro Taura, Masashi Kanai, Keita Fukuyama, Norimitsu Uza, Hirona Maeda, Yojiro Yutaka, Toyofumi F Chen-Yoshikawa, Manabu Muto, Shinji Uemoto

World journal of gastroenterology Vol. 26 ( 3 ) page： 366 - 374 2020.1

Language：English

BACKGROUND: Despite an expanding number of studies on intraductal papillary neoplasm of the bile duct (IPNB), distant metastasis remains unexplained especially in cases of carcinoma in situ. In the present study, we report a rare and interesting case of IPNB without invasive components that later metastasized to lungs and brain. CASE SUMMARY: A 69-year-old male was referred to our hospital due to suspected cholangiocarcinoma. Laboratory tests on admission reported a mild elevation of alkaline phosphatase, γ-glutamyl transpeptidase, and total bilirubin in serum. Endoscopic retrograde cholangiography revealed a ﬁlling defect in the common bile duct (CBD) extending to the left hepatic duct. Peroral cholangioscopy delineated a tumor in the CBD that had a papillary pattern. Multidetector computed tomography and magnetic resonance cholangiopancreatography detected partial blockage ot interlude in the CBD leading to cholestasis without evidence of metastasis. Therefore, a diagnosis of IPNB cT1N0M0 was established. Left hepatectomy with bile duct reconstruction was performed. Pathological examination confirmed an intraepithelial neoplasia pattern without an invasive component and an R0 resection achievement. The patient was monitored carefully by regular examinations. However, at 32 mo after the operation, a 26 mm tumor in the lungs and a 12 mm lesion in the brain were detected following a suspicious elevated CA 19-9 level. Video-assisted thoracoscopic surgery of left upper lobectomy and stereotactic radiotherapy are indicated. In addition to histopathological results, a genomic profiling analysis using whole exome sequencing subsequently confirmed lung metastasis originating from bile duct cancer. CONCLUSION: This case highlights the important role of genomic profiling analysis using whole exome sequencing in identifying the origin of metastasis in patients with IPNB.

DOI： 10.3748/wjg.v26.i3.366

Variations and surgical management of pulmonary vein in living-donor lobectomy. Reviewed International journal

Hidenao Kayawake, Toyofumi Fengshi Chen-Yoshikawa, Satona Tanaka, Yoshito Yamada, Yojiro Yutaka, Daisuke Nakajima, Akihiro Ohsumi, Masatsugu Hamaji, Hiroshi Date

Interactive cardiovascular and thoracic surgery Vol. 30 ( 1 ) page： 24 - 29 2020.1

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

OBJECTIVES: In a living-donor lobectomy, the donor undergoes a right or left lower lobectomy. The surgical procedures for living-donor lobectomy are sometimes influenced by the anatomical variations of the pulmonary vein (PV). The goal of this study was to analyse the PV variations in living donors and to review the influence of these variations on the surgical procedures used. METHODS: Between June 2008 and September 2018, 154 living donors underwent right or left lower lobectomy. The PV variations were analysed using 3-dimensional computed tomography (3D-CT), and the surgical management of these variations was reviewed. RESULTS: Among 154 donors, 21 PV variations that could influence the surgical procedure for a right lower lobectomy were found in 19 (12.3%) donors, whereas no such variations for a left lower lobectomy were found. Detected PV variations were dorsal branch of the right upper PV (n = 12), middle PV draining into the right lower PV (n = 6) and the superior segment branch of the right lower PV draining into the right upper PV (n = 3). Among 96 donors undergoing right lower lobectomy, 9 (9.4%) donors had PV variations that could influence the surgical procedure. In 2 donors, sparing of PV branches with multiple vascular clamps was required. Pulmonary venoplasty was not required in any donor, whereas pulmonary venoplasty in recipient surgery was required in 4 recipients. There were no complications related to the surgical procedures performed on the PV. CONCLUSIONS: Living-donor lobectomy was performed safely owing to the preoperative evaluation of PV on 3D-CT and the use of appropriate surgical approaches to PV.

DOI： 10.1093/icvts/ivz238

Results of a nationwide survey in Japan on the status of antibody-mediated rejection treatment and the use of rituximab in that treatment

NAKAGAWA Ken, SATOH Shigeru, EGAWA Hiroto, AKAMATSU Nobuhisa, ITO Taihei, UENO Takehisa, OKUMI Masayoshi, SAKAMOTO Seisuke, CHEN-YOSHIKAWA Toyofumi F, NAWATA Kan, FUKUSHIMA Norihide

Japanese Journal of Transplantation Vol. 55 ( 1 ) page： 51-59 2020

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

We retrospectively surveyed the status of rituximab use in treatment for antibody-mediated rejection (AMR) in Japan between 2013 and 2016 for kidney transplantation and between 2001 and 2016 for transplantation of other organs, including the liver, pancreas, heart, lung, and intestine.Two hundred twenty-seven institutions responded. AMR developed in 493 patients who underwent kidney transplantation; 288 of those patients were treated with rituximab. AMR developed in 81 patients for liver transplantation, 4 patients for pancreas transplantation, 16 patients for heart transplantation, 22 patients for lung transplantation, and 2 patients for small intestine transplantation; rituximab was used in 18, 4, 4, 14, and 1 of those patients, respectively.We also report on treatment details and rituximab dosage.

DOI： 10.11386/jst.55.1_51

Results of a nationwide survey in Japan on transplantation in patients with pre-formed anti-donor specific antibody against HLA antigen, and on the use of rituximab in this transplantation

NAKAGAWA Ken, SATOH Shigeru, EGAWA Hiroto, AKAMATSU Nobuhisa, ITO Taihei, UENO Takehisa, OKUMI Masayoshi, SAKAMOTO Seisuke, CHEN-YOSHIKAWA Toyofumi F, NAWATA Kan, FUKUSHIMA Norihide

Japanese Journal of Transplantation Vol. 55 ( 1 ) page： 39-50 2020

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

A retrospective survey was conducted to assess the status of organ transplantation in patients with pre-formed donor-specific anti-HLA antibodies and the implementation of desensitization with rituximab in Japan. We obtained the data from 227 institutions for procedures performed between 2013 and 2016 for kidney transplantation and between 2001 and 2016 for transplantation of other organs, including the liver, pancreas, heart, lung, and intestine.Results showed pre-formed donor-specific antibodies (DSA) in recipients of 529 transplanted kidneys; rituximab was used in 462 of those transplantations. Rituximab was used in 48 of 135 liver transplantations in recipients with pre-formed DSA and in 1 of 1 small intestine transplantation involving pre-formed DSA. Such DSA was also reported in 5 heart transplants and 4 lung transplants. However, rituximab was not used for desensitization in any of those procedures.We also report on detection and assay of anti-HLA antibodies and DSA, criteria for transplantation, dosage of rituximab, and concomitant immunosuppressive drugs used at the institutions.

DOI： 10.11386/jst.55.1_39

Survival outcomes of resection for pulmonary malignancies including non-small cell lung cancer and pulmonary metastasis after esophagectomy for esophageal carcinoma

Yamanashi K

General Thoracic and Cardiovascular Surgery Vol. 68 ( 10 ) page： 1179 - 1186 2020

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

OBJECTIVES: This study investigated survival outcomes of resection for pulmonary malignancies after esophagectomy for esophageal carcinoma, comparing non-small cell lung cancer and pulmonary metastases. METHODS: We retrospectively reviewed consecutive patients who underwent resection for pulmonary malignancies after esophagectomy for esophageal carcinoma between 2009 and 2018. The overall survival and relapse-free survival rate were assessed using Kaplan-Meier analysis. RESULTS: Eleven patients had non-small cell lung cancer and eight patients had pulmonary metastases from esophageal carcinoma. The 5-year overall survival rate was 92.9% in all patients with a median follow-up period of 50.4 (range: 9.1-130.2) months. While the 5-year overall survival rate was 100.0% in patients with non-small cell lung cancer, it was 85.7% in patients with pulmonary metastases from esophageal carcinoma. The 5-year relapse-free survival rate was 85.7% in patients with non-small cell lung cancer. CONCLUSIONS: Our data suggest that resection for pulmonary malignancies after esophagectomy for esophageal carcinoma is associated with favorable survival outcomes and should be considered in selected patients.

DOI： 10.1007/s11748-020-01373-8

Commentary: Infants Toddle Before They Ambulate. Where Are We Now?

Okabe R

Seminars in Thoracic and Cardiovascular Surgery Vol. 33 ( 1 ) page： 274 - 275 2020

Is left-side DaVinci™ procedure challenging? Initial experiences of a single institute.

Toshihiko Sato, Akinori Iwasaki, Yojiro Yutaka, Yoshito Yamada, Daisuke Nakajima, Akihiro Ohsumi, Masatsugu Hamaji, Toshi Menju, Toyofumi Fengshi Chen-Yoshikawa, Hiroshi Date

General thoracic and cardiovascular surgery Vol. 68 ( 11 ) page： 1285 - 1289 2020

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

OBJECTIVE: Among the standard techniques for anatomical lung cancer resection, left upper lobectomy has been regarded as challenging by thoracic surgeons. Thus, this study aimed to examine whether laterality of robot-assisted thoracoscopic procedures has any influence on the incidence of conversion to thoracotomy, operation time, amount of bleeding, and postoperative complications in the introduction phase of this procedure. METHODS: The first consecutive 65 patients (right upper/middle/lower lobe with 31/3/15 cases, left upper/lower lobe with 10/6 cases) who underwent robot-assisted thoracoscopic lobectomy from December 2011 to April 2019 in Kyoto University were retrospectively reviewed. RESULTS: Five cases were converted to open thoracotomy, including four for the left upper lobectomy and one for the right lower lobectomy (p = 0.011). The mean operation time was 229.9 ± 53.9 min (n = 12) and 192.8 ± 53.1 min (n = 48) for the left-sided and right-sided procedures, respectively (p = 0.043, conversion cases were not included). The mean bleeding amount was 29.1 ± 75.7 g (n = 49) and 136.8 ± 330.9 g (n = 16) for the right side and left side, respectively (p = 0.036). The mean operation time (min) for each lobe was as follows: 253.5 ± 73.9 for the left upper lobe (n = 6), 206.3 ± 41.3 for the left lower lobe (n = 6), 189.7 ± 51.3 for the right upper lobe (n = 31), 192.3 ± 57.5 for the right middle lobe (n = 3), and 199.9 ± 61.8 for the right lower lobe (n = 14). CONCLUSION: Robot-assisted thoracoscopic surgery on the left side was associated with higher conversion rate, longer operation time, and more blood loss than that on the right side.

DOI： 10.1007/s11748-020-01382-7

Commentary: Local chemotherapy with nanoparticles: A ray of light in the dark?

Nakamura S

Journal of Thoracic and Cardiovascular Surgery Vol. 160 ( 3 ) page： e169 - e170 2020

Analysis of Optimal Health-Related Quality of Life Measures in Patients Waitlisted for Lung Transplantation

Tokuno J

Canadian Respiratory Journal Vol. 2020 2020

Prognostic factors of stage I thymic epithelial tumors

Fukui T

General Thoracic and Cardiovascular Surgery Vol. 69 ( 1 ) page： 59 - 66 2020

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

Objective: According to the tumor-node-metastasis classification for thymic malignancies, the proportion of patients diagnosed with stage I is expected to increase significantly. However, whether those patients have homogenous clinicopathological features and survival has not been fully evaluated. Methods: We reviewed 153 consecutive patients with stage I thymic epithelial tumors (133 thymomas, 15 thymic carcinomas, and 5 neuroendocrine tumors) who underwent complete resection at our institution between 2001 and 2016 and evaluated the prognostic significance of their clinicopathological factors. Results: The stage I patients accounted for 78% of all thymic epithelial tumors. The 5-year overall survival and recurrence-free survival rates of the 153 patients were 94% and 80%, respectively. The patients with the histology of thymic carcinoma or neuroendocrine tumor and with a tumor larger than 5.0 cm showed significantly worse recurrence-free survival in multivariate analysis (p = 0.027 and 0.038, respectively). Only the tumor size was revealed as a significant prognostic factor for recurrence-free survival when limited in the 133 cases of thymoma (p = 0.048). Conclusions: Patients with large tumors showed significantly worse recurrence-free survival than those with small tumors both in stage I thymic epithelial tumors and thymomas.

DOI： 10.1007/s11748-020-01427-x

Sleep quality and its association with health-related quality of life of patients on lung transplantation waitlist in Japan

Tokuno J

Sleep and Breathing Vol. 25 ( 1 ) page： 219 - 225 2020

Expanded indications for lung transplantation for pulmonary complications after hematopoietic stem cell transplantation

Noguchi M.

Journal of Thoracic and Cardiovascular Surgery 2020

Commentary: Continuous steady development is made by taking 2 steps forward, 1 step back

Mutsuga M.

Journal of Thoracic and Cardiovascular Surgery 2020

臓器別パネルディスカッション「拡大基準ドナーに対するコンセンサス　肺」

星川康, 芳川豊史, 渡辺有為, 此枝千尋, 田中里奈

移植 Vol. 55 ( 3 ) page： 145 - 153 2020

移植医療とCOVID-19

山永成美, 江川裕人, 蛭子洋介, 大澤良介, 小野稔, 剣持敬, 十川博, 名取洋一郎, 日比泰造, 矢野晴美, 芳川豊史, 吉川美喜子, 吉田一成, 湯沢賢治

移植 Vol. 55 ( Supplement ) page： 194_1 - 194_1 2020

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

2019年末からの中国武漢での報告後、瞬く間に世界中に拡散した新型コロナウイルス感染症 (COVID-19)は、現在も収束することなく、2020年8月31日時点で全世界で2500万人以上が感染していると報告されている。COVID-19は、移植医療の在り方に大きな影響をもたらし、世界中の多くの移植施設で、生命に関わる臓器の移植を除き、生体移植を中心とした待機可能な移植は一時停止を余儀なくされた。ドナーからの伝播の可能性、院内感染の可能性、移植患者への感染対応など、様々な状況を想定し、院内のコンセンサスを得ることで、現状では多くの施設が移植医療の提供を再開した。しかし、安心安全な移植医療を提供するためには、COVID-19以前とは異なる、新しい移植医療の様式を実践していく必要がある。また、移植患者は免疫抑制剤を服用しており、ウイルス感染症に脆弱である一方、COVID-19は、感染後期での免疫抑制剤使用による重症化抑制も知られている。相反する病態を理解し、免疫抑制剤調整を含めた移植患者の管理を適切に行うことも重要である。これまでに得られたCOVID-19と移植医療に関する文献的報告をレビューし、新しい移植医療の様式について提言したい。

DOI： 10.11386/jst.55.supplement_194_1

Fcγ受容体IIAの一塩基多型と肺移植後の感染性合併症との相関

栢分秀直, 芳川豊史, 田中里奈, 田中友加, 大段秀樹, 豊洋次郎, 山田義人, 大角明宏, 中島大輔, 濱路政嗣, 江川裕人, 伊達洋至

移植 Vol. 55 ( Supplement ) page： 354_1 - 354_1 2020

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

【背景】固形臓器移植後の術後成績にFcγ受容体の一塩基多型（SNP）が与えうる影響についての研究はいくつかあるが、肺移植に関する研究はほとんどない。本研究の目的はFcγ受容体IIA（FCGR2A）のSNPが肺移植後の術後成績に与える影響を検討することである。【対象と方法】2008年から2018年までに201例の肺移植が施行された。この中から再肺移植症例、残余DNAサンプルがない症例、ICU退室不可症例を除いた191例を対象とした。この191例に関してFCGR2AのSNP（131 histidine [H] or arginine [R]）を解析し、術後成績とSNPとの関連について検討した。【結果】FCGR2AのSNPの内訳は、H/H（n=120）、H/R（n=66）、R/R（n=5）であった。H/H群（H/H）とR群（H/R or R/R）の2群で解析を行ったところ、ICU退室から術後1年以内の肺炎の頻度および真菌感染症の頻度は、R群で有意に高かった（p=0.004およびp=0.012）。全生存率に関しては2群間に有意差を認めなかった（p=0.67）。【結語】FCGR2AのSNPに関して、予後には2群間で有意な差を認めなかったが、R群では1年以内の肺炎および真菌感染症の頻度が有意に高かった。

DOI： 10.11386/jst.55.supplement_354_1

Impact of diabetes mellitus on postoperative outcomes in individuals with non-small-cell lung cancer: A retrospective cohort study. International journal

Teruya Komatsu, Toyofumi F Chen-Yoshikawa, Masaki Ikeda, Koji Takahashi, Akiko Nishimura, Shin-Ichi Harashima, Hiroshi Date

PloS one Vol. 15 ( 11 ) page： e0241930 2020

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

OBJECTIVES: Studies showing that individuals with non-small cell lung cancer (NSCLC) and diabetes mellitus (DM) have reported poor outcomes after pulmonary resection with varying results. Therefore, we investigated the clinical impact of preoperative DM on postoperative morbidity and survival in individuals with resectable NSCLC. PATIENTS AND METHODS: Data of individuals who underwent pulmonary resection for NSCLC from 2000 to 2015 were extracted from the database of Kyoto University Hospital. The primary endpoint was the incidence of postoperative complications, and secondary endpoints were postoperative length of hospital stay and overall survival. The survival rate was analyzed using the Kaplan-Meier method. RESULTS: A total of 2,219 patients were eligible for the study. The median age of participants was 67 years. Among them, 39.5% were women, and 259 (11.7%) presented with DM. The effect of DM on the incidence of postoperative complications and postoperative length of hospital stay was not significant. Although the 5-year survival rates were similar in both patients with and without DM (80.2% versus 79.4%; p = 0.158), those with DM who had a hemoglobin A1c level ≥ 8.0% had the worst survival. CONCLUSIONS: In individuals with resectable NSCLC, preoperative DM does not influence the acute phase postoperative recovery. However, poorly controlled preoperative DM could lead to low postoperative survival rates.

DOI： 10.1371/journal.pone.0241930

Nocturnal hypercapnia with daytime normocapnia in patients with advanced pulmonary arterial hypertension awaiting lung transplantation. Reviewed International journal

Yoshinari Nakatsuka, Toyofumi Chen-Yoshikawa, Hideyuki Kinoshita, Akihiro Aoyama, Hiroyasu Kubo, Kimihiko Murase, Satoshi Hamada, Hirofumi Takeyama, Takuma Minami, Naomi Takahashi, Kiminobu Tanizawa, Tomohiro Handa, Toyohiro Hirai, Hiroshi Date, Kazuo Chin

PloS one Vol. 15 ( 4 ) page： e0227775 2020

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

BACKGROUND: Pulmonary arterial hypertension (PAH) is frequently complicated by sleep disordered breathing (SDB), and previous studies have largely focused on hypoxemic SDB. Even though nocturnal hypercapnia was shown to exacerbate pulmonary hypertension, the clinical significance of nocturnal hypercapnia among PAH patients has been scarcely investigated. METHOD: Seventeen patients with PAH were identified from 246 consecutive patients referred to Kyoto University Hospital for the evaluation of lung transplant registration from January 2010 to December 2017. Included in this study were 13 patients whose nocturnal transcutaneous carbon dioxide partial pressure (PtcCO2) monitoring data were available. Nocturnal hypercapnia was diagnosed according to the guidelines of the American Academy of Sleep Medicine. Associations of nocturnal PtcCO2 measurements with clinical features, the findings of right heart catheterization and pulmonary function parameters were evaluated. RESULTS: Nocturnal hypercapnia was diagnosed in six patients (46.2%), while no patient had daytime hypercapnia. Of note, nocturnal hypercapnia was found for 5 out of 6 patients with idiopathic PAH (83.3%). Mean nocturnal PtcCO2 levels correlated negatively with the percentage of predicted total lung capacity (TLC), and positively with cardiac output and cardiac index. CONCLUSION: Nocturnal hypercapnia was prevalent among advanced PAH patients who were waiting for lung transplantation, and associated with %TLC. Nocturnal hypercapnia was associated with the increase in cardiac output, which might potentially worsen pulmonary hypertension especially during sleep. Further studies are needed to investigate hemodynamics during sleep and to clarify whether nocturnal hypercapnia can be a therapeutic target for PAH patients.

DOI： 10.1371/journal.pone.0227775

Primary peritoneal carcinoma with late-phase pulmonary metastases: a case report. International journal

Naoki Ozeki, Shuhei Hakiri, Hisashi Tateyama, Kohei Yokoi, Toyofumi Chen-Yoshikawa

Surgical case reports Vol. 5 ( 1 ) page： 194 - 194 2019.12

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

BACKGROUND: Primary peritoneal carcinoma (PPC) is a very rare and aggressive type of malignancy with a poor prognosis. CASE PRESENTATION: A 66-year-old woman was referred to our hospital with two pulmonary nodules that developed after PPC resection and postoperative adjuvant chemotherapy administered 5 years earlier. Computed tomography revealed a 1.3-cm-sized nodule in the left lung with a small airspace in the posterior basal segment and a 0.9-cm-sized solid nodule in the apico-posterior segment that grew slightly within a 2-month period. 18F-Fluorodeoxyglucose-positron emission tomography of these lesions revealed respective maximum standardized uptake values of 7.11 and 2.46. Her serum cancer antigen-125 level remained within the normal range, despite elevation before the first surgery. The posterior basal segment and superior division were subjected to anatomical segmentectomy. An intraoperative frozen section examination could not distinguish metastatic PPC from primary lung cancer. Immunopathologically, the two nodules were identified as metastatic PPC. CONCLUSIONS: Our findings suggest that PPC patients may develop late-phase thoracic recurrence that is difficult to diagnose clinically after initial treatment in a potentially resectable setting.

DOI： 10.1186/s40792-019-0752-0

Intermediate outcomes of right-to-left inverted living-donor lobar lung transplantation. International journal

Toyofumi F Chen-Yoshikawa, Satona Tanaka, Yoshito Yamada, Yojiro Yutaka, Daisuke Nakajima, Akihiro Ohsumi, Masatsugu Hamaji, Toshi Menju, Hiroshi Date

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Vol. 56 ( 6 ) page： 1046 - 1053 2019.12

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

OBJECTIVES: Owing to the severe donor shortage in Japan, living-donor lobar lung transplantation (LDLLT) remains a valuable option. As only lobes are implanted in LDLLT, grafts may be too small, especially for adult recipients. To overcome this obstacle, we developed right-to-left inverted LDLLT. In this procedure, the right lower lobe, which is 25% bigger than the left lower lobe, is used as the left-side graft instead of the left lower lobe. This study aimed to investigate the characteristics and intermediate outcomes of right-to-left inverted LDLLT. METHODS: Since the first right-to-left inverted LDLLT performed in 2014, 48 LDLLTs have been performed in our institution, of which 15 were right-to-left inverted LDLLTs. We reviewed their characteristics and intermediate outcomes. RESULTS: The reasons for choosing an inverted procedure instead of the standard LDLLT were small-for-size graft in 11 cases and anatomical variation of donor vessels in 4 cases. The first patient underwent left single LDLLT using a right lower lobe graft, and the following 14 patients underwent bilateral LDLLT using 2 right lower lobe grafts. A native upper lobe-sparing procedure was additionally applied in 2 patients. No complications occurred in the bronchial and vascular anastomoses. No operative mortality occurred, and all the patients were discharged home after LDLLT. The 3-year survival was 92.3%, with a median follow-up time of 40 months. The donor postoperative course was uneventful, and all the donors returned to their regular routine postoperatively. CONCLUSION: Right-to-left inverted LDLLT is a safe and useful option with encouraging intermediate outcome.

DOI： 10.1093/ejcts/ezz244

Diameter of the dilated main pulmonary artery in patients with pulmonary hypertension decreases after lung transplantation.

Kayawake H, Aoyama A, Kinoshita H, Yoneda T, Baba S, Teramoto Y, Miyagawa-Hayashino A, Yamazaki K, Motoyama H, Hamaji M, Nakajima D, Chen-Yoshikawa TF, Date H

Surgery today Vol. 50 ( 3 ) page： 275 - 283 2019.10

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

PURPOSE: The pulmonary artery (PA) in patients with pulmonary hypertension (PH) becomes dilated. We analyzed the postoperative changes of the main PA after lung transplantation (LuTx). METHODS: The subjects of this retrospective study were 68 LuTx recipients, divided into a PH group (n = 36) and a non-PH group (n = 32), based on preoperative right heart catheterization findings. The PA diameter was measured on chest computed tomography. We evaluated the correlation between the mean pulmonary arterial pressure (mPAP) and the main PA diameter and compared the main PA diameters before and 3 months after LuTx. RESULTS: The main PA diameter was significantly correlated with the mPAP (r = 0.423, P < 0.001). Preoperatively, the mean main PA diameter in the PH group was significantly greater than that in the non-PH group. However, by 3 months after LuTx, the main PA diameter in the PH group had decreased significantly from 32.4 ± 6.7 to 26.9 ± 4.8 mm (P < 0.001), while that in the non-PH group had decreased minimally from 28.3 ± 4.9 to 26.4 ± 4.6 mm (P < 0.001), resulting in no significant difference in postoperative main PA diameters between the two groups. CONCLUSIONS: The main PA diameter in recipients with PH was enlarged and correlated with the mPAP. The dilated main PA diameter in PH patients decreased shortly after LuTx.

DOI： 10.1007/s00595-019-01887-6

Trametinib Attenuates Delayed Rejection and Preserves Thymic Function in Rat Lung Transplantation.

Resection Process Map: A novel dynamic simulation system for pulmonary resection.

Tokuno J, Chen-Yoshikawa TF, Nakao M, Matsuda T, Date H

The Journal of thoracic and cardiovascular surgery 2019.9

Emergent surgical treatment for acute thrombosis caused by pulmonary artery kinking after left upper sleeve lobectomy.

Nakajima D, Oda H, Chen-Yoshikawa TF, Date H

Interactive cardiovascular and thoracic surgery Vol. 29 ( 3 ) page： 481-483 2019.9

Completion pneumonectomy and auto-transplantation for bronchopleural fistula.

Hamaji M, Chen-Yoshikawa TF, Date H

The Journal of thoracic and cardiovascular surgery Vol. 158 ( 3 ) page： e121-e123 2019.9

Takahagi A, Shindo T, Chen-Yoshikawa TF, Yoshizawa A, Gochi F, Miyamoto E, Saito M, Tanaka S, Motoyama H, Aoyama A, Takaori-Kondo A, Date H

American journal of respiratory cell and molecular biology Vol. 61 ( 3 ) page： 355-366 - 366 2019.9

臓器摘出合同シミュレーション実施6年間の総括アンケート結果を踏まえて Reviewed

古川博之, 福嶌教偉, 剣持敬, 松野直徒, 星川康, 江口晋, 伊藤泰平, 芳川豊史, 縄田寛, 山内治雄, 松田安史, 曽山明彦, 芦刈淳之介, 小野稔, 江川裕人

移植 Vol. 54 ( 総会臨時 ) page： 234 - 234 2019.9

Living-donor lobar lung transplants provide comparable pulmonary function to cadaveric lung transplants.

Nakajima D, Chen-Yoshikawa TF, Ohsumi A, Date H

The Journal of thoracic and cardiovascular surgery 2019.8

Use of a three-dimensional model in lung transplantation for a patient with giant pulmonary aneurysm. International journal

Oda H, Hamaji M, Motoyama H, Ikeda T, Minatoya K, Nakajima D, Chen-Yoshikawa TF, Date H

The Annals of thoracic surgery Vol. 109 ( 3 ) page： e183-e185 2019.8

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

Management of a giant pulmonary trunk aneurysm in lung transplantation is a challenge. Herein, we present a patient undergoing replacement of the giant pulmonary artery aneurysm with a donor's aorta in bilateral lung transplantation for idiopathic pulmonary arterial hypertension. A plastic three-dimensional model of the pulmonary artery aneurysm created accurately based on computed tomography data allowed us to simulate the procedure on the back table. Our intraoperative findings and management are discussed in this article.

DOI： 10.1016/j.athoracsur.2019.06.092

Salvage surgery after chemo- or chemoradiotherapy for initially unresectable lung carcinoma.

Sonobe M, Yutaka Y, Nakajima D, Hamaji M, Menju T, Ohsumi A, Chen-Yoshikawa TF, Sato T, Date H

The Annals of thoracic surgery 2019.8

Surgery and stereotactic body radiotherapy for early stage non-small cell lung cancer: review of meta-analyses. Reviewed International journal

Masatsugu Hamaji, Yukinori Matsuo, Toyofumi Fengshi Chen-Yoshikawa, Takashi Mizowaki, Hiroshi Date

Journal of thoracic disease Vol. 11 ( Suppl 13 ) page： S1646-S1652 2019.8

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

Observational or randomized studies on survival outcome following surgery versus stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) demonstrated various results, and several meta-analyses on this topic have been published. The PubMed database was queried for meta-analyses comparing surgery and SBRT for early stage NSCLC. Six meta-analyses on this comparison were identified and 4 (66.7%) suggested that surgery be associated with significantly more favorable overall survival than SBRT, using odds ratio or hazard ratio (HR) as measures of effect. Most of the included studies in the meta-analyses were observational studies and those meta-analyses should be interpreted with caution.

DOI： 10.21037/jtd.2018.10.35

Acquired recipient pulmonary function is better than lost donor pulmonary function in living-donor lobar lung transplantation. International journal

Kayawake H, Chen-Yoshikawa TF, Hamaji M, Nakajima D, Ohsumi A, Aoyama A, Date H

The Journal of thoracic and cardiovascular surgery Vol. 158 ( 6 ) page： 1710 - 1716 2019.7

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

OBJECTIVE: In standard bilateral living-donor lobar lung transplantation (LDLLT), the right and left lower lobes from 2 healthy donors are implanted in the recipient in place of whole right and left lungs. In other words, total 10 lobes (5 lobes in each donor) are shared by the 2 donors (4 lobes in each donor) and the recipient (2 lobes) in this transplant procedure. This study aimed to compare pulmonary function between donors and recipients before and after LDLLT. METHODS: We performed 76 LDLLT procedures between June 2008 and March 2017. After excluding 12 single LDLLT and 11 native-lung-sparing LDLLT procedures, we identified 38 recipients of bilateral LDLLT who survived >1 year and underwent routine pulmonary function testing. Acquired recipient pulmonary function was compared with lost donor pulmonary function at 1 year post-LDLLT. RESULTS: The median age of the 38 recipients was 44 years (range, 8-62 years); 14 were men. The median age of the 76 donors was 41.5 years (range, 20-60 years); 50 were men. One year post-LDLLT, acquired recipient forced vital capacity was significantly greater than lost donor forced vital capacity (1889.5 ± 581.3 mL vs 1073.9 ± 661.6 mL; P < .001). Similarly, acquired recipient forced expiratory volume in 1 second at 1 year post-LDLLT was significantly greater than lost donor forced expiratory volume in 1 second (1646.8 ± 483.0 mL vs 1064.2 ± 534.5 mL; P < .001). CONCLUSIONS: These results indicated that acquired recipient pulmonary function was better than lost donor pulmonary function in bilateral LDLLT.

DOI： 10.1016/j.jtcvs.2019.06.058

Surface deformation analysis of collapsed lungs using model-based shape matching.

In Vitro Disease Modeling of Hermansky-Pudlak Syndrome Type 2 Using Human Induced Pluripotent Stem Cell-Derived Alveolar Organoids. International journal

Yohei Korogi, Shimpei Gotoh, Satoshi Ikeo, Yuki Yamamoto, Naoyuki Sone, Koji Tamai, Satoshi Konishi, Tadao Nagasaki, Hisako Matsumoto, Isao Ito, Toyofumi F Chen-Yoshikawa, Hiroshi Date, Masatoshi Hagiwara, Isao Asaka, Akitsu Hotta, Michiaki Mishima, Toyohiro Hirai

Stem cell reports Vol. 13 ( 1 ) page： 235 - 235 2019.7

Living-donor lung transplantation after surgical repair of transposition of the great arteries.

Yoshinaga D, Baba S, Hirata T, Fukushima H, Hamaji M, Aoyama A, Chen-Yoshikawa TF, Yamagishi H, Date H, Heike T

General thoracic and cardiovascular surgery Vol. 67 ( 7 ) page： 640-643 2019.7

Pirfenidone alleviates lung ischemia-reperfusion injury in a rat model.

Saito M, Chen-Yoshikawa TF, Suetsugu K, Okabe R, Takahagi A, Masuda S, Date H

The Journal of thoracic and cardiovascular surgery Vol. 158 ( 1 ) page： 289-296 2019.7

Nakao M, Tokuno J, Chen-Yoshikawa T, Date H, Matsuda T

International journal of computer assisted radiology and surgery Vol. 14 ( 10 ) page： 1763 - 1774 2019.6

Nutrition-related factors associated with waiting list mortality in patients with interstitial lung disease: A retrospective cohort study. Reviewed International journal

Ayako Oshima, Akiko Nishimura, Toyofumi F Chen-Yoshikawa, Shin-Ichi Harashima, Teruya Komatsu, Tomohiro Handa, Akihiro Aoyama, Koji Takahashi, Masaki Ikeda, Yohei Oshima, Kohei Ikezoe, Susumu Sato, Maki Isomi, Kenichiro Shide, Hiroshi Date, Nobuya Inagaki

Clinical transplantation Vol. 33 ( 6 ) page： e13566 2019.6

Language：English

Japanese patients with interstitial lung disease (ILD) sometimes die waiting for lung transplantation (LTx) because it takes about 2 years to receive it in Japan. We evaluated nutrition-related factors associated with waiting list mortality. Seventy-six ILD patients were hospitalized in Kyoto University Hospital at registration for LTx from 2013 to 2015. Among them, 40 patients were included and analyzed. Patient background was as follows: female, 30%; age, 50.3 ± 6.9 years; body mass index, 21.1 ± 4.0 kg/m2 ; 6-minute walk distance (6MWD), 356 ± 172 m; serum albumin, 3.8 ± 0.4 g/dL; serum transthyretin (TTR), 25.3 ± 7.5 mg/dL; and C-reactive protein, 0.5 ± 0.5 mg/dL. Median observational period was 497 (range 97-1015) days, and median survival time was 550 (95% CI 414-686) days. Survival rate was 47.5%, and mortality rate was 38.7/100 person-years. Cox analyses showed that TTR (HR 0.791, 95% CI 0.633-0.988) and 6MWD (HR 0.795, 95% CI 0.674-0.938) were independently correlated with mortality and were influenced by body fat mass and leg skeletal muscle mass, respectively. It is suggested that nutritional markers and exercise capacity are important prognostic markers in waitlisted patients, but further study is needed to determine whether nutritional intervention or exercise can change outcomes.

DOI： 10.1111/ctr.13566

Commentary: Promising future solution for unmet needs in lung transplantation.

Chen-Yoshikawa TF

The Journal of thoracic and cardiovascular surgery Vol. 157 ( 5 ) page： 2107-2108 2019.5

Ex Vivo Sleeve Lobectomy and Autotransplantation After Chemoradiation.

Yamashita T, Hamaji M, Nakanobo R, Aoyama A, Chen-Yoshikawa TF, Sonobe M, Date H

The Annals of thoracic surgery Vol. 107 ( 5 ) page： e341-e343 2019.5

Long agonal period deteriorates cardiac death donor lung function in a rat EVLP model.

Hijiya K, Chen-Yoshikawa TF, Motoyama H, Ohsumi A, Nakajima D, Sakamoto J, Aoyama A, Date H

General thoracic and cardiovascular surgery Vol. 67 ( 5 ) page： 457-463 2019.5

Survival outcomes after minimally invasive thymectomy for early-stage thymic carcinoma.

Miyata R, Hamaji M, Omasa M, Nakagawa T, Sumitomo R, Huang CL, Ikeda M, Fujinaga T, Shoji T, Katakura H, Motoyama H, Nakajima D, Ohsumi A, Menju T, Aoyama A, Chen-Yoshikawa TF, Sato T, Sonobe M, Date H

Surgery today Vol. 49 ( 4 ) page： 357-360 2019.4

In Vitro Disease Modeling of Hermansky-Pudlak Syndrome Type 2 Using Human Induced Pluripotent Stem Cell-Derived Alveolar Organoids. Reviewed International journal

Stem cell reports Vol. 12 ( 3 ) page： 431 - 440 2019.3

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

It has been challenging to generate in vitro models of alveolar lung diseases, as the stable culture of alveolar type 2 (AT2) cells has been difficult. Methods of generating and expanding AT2 cells derived from induced pluripotent stem cells (iPSCs) have been established and are expected to be applicable to disease modeling. Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by dysfunction of lysosome-related organelles, such as lamellar bodies (LBs), in AT2 cells. From an HPS type 2 (HPS2) patient, we established disease-specific iPSCs (HPS2-iPSCs) and their gene-corrected counterparts. By live cell imaging, the LB dynamics were visualized and altered distribution, enlargement, and impaired secretion of LBs were demonstrated in HPS2-iPSC-derived AT2 cells. These findings provide insight into the AT2 dysfunction in HPS patients and support the potential use of human iPSC-derived AT2 cells for future research on alveolar lung diseases.

DOI： 10.1016/j.stemcr.2019.01.014

Low incidence of and mortality from a second malignancy after resection of thymic carcinoma†.

Hamaji M, Kawaguchi A, Omasa M, Nakagawa T, Sumitomo R, Huang CL, Fujinaga T, Ikeda M, Shoji T, Katakura H, Motoyama H, Menju T, Aoyama A, Sato T, Chen-Yoshikawa TF, Sonobe M, Date H

Interactive cardiovascular and thoracic surgery Vol. 28 ( 3 ) page： 375-379 2019.3

Dual approach for large mediastinal tumors in the thoracic outlet: transmanubrial osteomuscular sparing approach and video-assisted thoracoscopic surgery. International journal

Kayawake H, Chen-Yoshikawa TF, Date H

Journal of cardiothoracic surgery Vol. 14 ( 1 ) page： 42 - 42 2019.2

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

BACKGROUND: Selecting the proper surgical approach for mediastinal tumors in the thoracic outlet is difficult. Video-assisted thoracoscopic surgery is ideal because of the less invasiveness; however, it is often difficult to resect tumors only by video-assisted thoracoscopic surgery due to the poor visualization of the cranial side of tumors. We report two successfully treated cases by using a dual approach consisting of the transmanubrial osteomuscular sparing technique and video-assisted thoracoscopic surgery for aiming both the less invasiveness and the good visualization of the cranial side of tumors. CASE PRESENTATIONS: We present two resected cases of the mediastinal tumor in the thoracic outlet. The first case was a 28-year-old woman and the second case was a 37-year-old man. They had a mediastinal tumor in the thoracic outlet which was detected on the roentgenogram. A definitive preoperative diagnosis was unavailable. The surgical resection was started with video-assisted thoracoscopic surgery in the both cases. After the dissection of the caudal side of the tumor, the dissection of the cranial side was judged to be difficult and risky because the tumor was located adjacent to major vessels and the good visualization of this side couldn't be acquired. Therefore, the transmanubrial approach was sequentially performed and complete resection was safely achieved. Postoperatively, although transient Horner syndrome appeared in both cases, they recovered from this syndrome and were discharged. The final diagnosis was schwannoma for both cases. Neither of the cases had any functional restriction of the upper extremity. CONCLUSIONS: This dual approach for mediastinal tumors in the thoracic outlet is useful in terms of safety and lower invasiveness.

DOI： 10.1186/s13019-019-0863-5

Impact of flat chest on cadaveric lung transplantation: postoperative pulmonary function and survival.

Miyahara S, Chen-Yoshikawa TF, Motoyama H, Nakajima D, Hamaji M, Aoyama A, Date H

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Vol. 55 ( 2 ) page： 316-322 2019.2

Prognostic impact of microscopic vessel invasion and visceral pleural invasion and their correlations with epithelial-mesenchymal transition, cancer stemness, and treatment failure in lung adenocarcinoma. Reviewed International journal

Shinya Neri, Toshi Menju, Terumasa Sowa, Yojiro Yutaka, Daisuke Nakajima, Masatsugu Hamaji, Akihiro Ohsumi, Toyofumi F Chen-Yoshikawa, Toshihiko Sato, Makoto Sonobe, Akihiko Yoshizawa, Hironori Haga, Hiroshi Date

Lung cancer (Amsterdam, Netherlands) Vol. 128 page： 13 - 19 2019.2

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

OBJECTIVES: Microscopic vessel invasion (MVI) and visceral pleural invasion (VPI) have been recently reported as poor prognostic factors of non-small cell lung cancer. Epithelial-mesenchymal transition (EMT) and cancer stemness (CS) are known malignant phenotypes that induce resistance to cancer therapy. We aimed to assess the prognostic significance of MVI and the correlations among VPI/MVI, EMT, CS, and treatment failure for recurrent tumor. MATERIALS AND METHODS: From 2002 to 2013, 1034 consecutive patients with pathological T1-4N0-2M0 lung adenocarcinoma underwent complete resection. Moreover, we established 206 tissue microarray (TMA) samples from 2002 to 2007. We then evaluated the prognostic impact of MVI, including conventional clinicopathological factors, and analyzed the VPI/MVI, EMT, CS, and treatment failure by TMA immunohistochemical staining. RESULTS: Among the 1034 cases, the proportion of patients with a 5-year overall survival (OS) period was 63.9% and 88.2% (MVI: +/-; p < .001). Multivariate analysis revealed that both MVI and VPI were independent predictors of OS (HR 1.57 and 1.47, respectively). Significant separation of the OS rate curves was observed among the 3 groups [VPI/MVI: both positive (2), either positive (1), and both negative (0)]. Among the 206 TMA cases, these 3 groups of VPI/MVI were significantly correlated with EMT and CS. The median time to progression after recurrence were 3.8, 8.9, and 15.9 months, respectively (VPI/MVI: 2/1/0; p = 0.016). CONCLUSION: MVI and VPI are significant prognostic factors of lung cancer, and they are correlated with EMT, CS, and treatment failure for recurrent tumor.

DOI： 10.1016/j.lungcan.2018.12.001

Native upper lobe-sparing living-donor lobar lung transplantation maximizes respiratory function of the donor graft.

Takahagi A, Chen-Yoshikawa TF, Saito M, Okabe R, Gochi F, Yamagishi H, Hamaji M, Motoyama H, Nakajima D, Ohsumi A, Aoyama A, Sonobe M, Date H

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Vol. 38 ( 1 ) page： 66-72 2019.1

Novel insights into lung regenerative medicine.

Chen-Yoshikawa TF, Okabe R

The Journal of thoracic and cardiovascular surgery Vol. 157 ( 1 ) page： 421-422 2019.1

Statins may have double-edged effects in patients with lung adenocarcinoma after lung resection. International journal

Nishikawa S, Menju T, Takahashi K, Miyata R, Chen-Yoshikawa TF, Sonobe M, Yoshizawa A, Sabe H, Sato T, Date H

Cancer management and research Vol. 11 page： 3419-3432 - 3432 2019

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

Purpose: The epithelial to mesenchymal transition (EMT) is pivotal for driving metastasis and recurrence in lung cancer. Some in vitro reports have shown that statins suppress EMT by inactivating mutant p53 functions. Several clinical trials of conventional treatments with statins have been performed, but the effect of these drugs on prognosis is still uncertain. The purpose of this study is to examine the impact of statins on EMT and the prognosis of patients with lung adenocarcinoma. Materials and methods: Morphological changes were evaluated and EMT markers (E-cadherin, vimentin) were analyzed by Western blotting in p53-overexpressing H1650 and mutant p53-harboring H1975 lung adenocarcinoma cells, with and without simvastatin administration. The invasive ability of these cells was analyzed in a Matrigel chemoinvasion assay. A total of 250 lung adenocarcinoma specimens were also collected from patients who underwent surgery in our institute. EMT markers in these tumor specimens were evaluated by immunostaining and p53 mutation status was determined by direct sequencing. Associations among EMT status, p53 mutation status, and statin use were evaluated, and prognosis was analyzed using a marginal structural model. Results: Mutant p53 induced EMT and increased the invasive ability of H1650 cells. Simvastatin restored the epithelial phenotype and decreased the invasive ability of both H1650 and H1975 cells. Statin administration was associated with inactivation of EMT only in patients with mutant p53, which was consistent with the in vitro results. Moreover, in patients with mutant p53, statin users had significantly better survival than non-statin users. In contrast, statins significantly worsened the prognosis of patients with wild type p53 (HR 2.10, 95% CI 1.14-3.85). Conclusion: Statins suppress EMT and change the prognosis of patients with lung adenocarcinoma in a p53 mutation-dependent manner.

DOI： 10.2147/CMAR.S200819

Near-Infrared Imaging Using Intravenous Indocyanine Green at a Conventional Dose to Locate Pulmonary Metastases: A Pilot Study.

Hamaji M, Chen-Yoshikawa TF, Minami M, Date H

The Thoracic and cardiovascular surgeon 2018.11

Prognostic impact of preoperative comorbidities in geriatric patients with early-stage lung cancer: Significance of sublobar resection as a compromise procedure.

Yutaka Y, Sonobe M, Kawaguchi A, Hamaji M, Nakajima D, Ohsumi A, Menju T, Chen-Yoshikawa TF, Sato T, Date H

Lung cancer (Amsterdam, Netherlands) Vol. 125 page： 192-197 2018.11

Unilateral Chronic Lung Allograft Dysfunction Assessed by Biphasic Computed Tomographic Volumetry in Bilateral Living-donor Lobar Lung Transplantation. International journal

Saito M, Chen-Yoshikawa TF, Nakamoto Y, Kayawake H, Tokuno J, Ueda S, Yamagishi H, Gochi F, Okabe R, Takahagi A, Hamaji M, Motoyama H, Aoyama A, Date H

Transplantation direct Vol. 4 ( 11 ) page： e398 2018.11

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

Background: Early diagnosis of unilateral chronic lung allograft dysfunction (CLAD) is difficult because the unaffected contralateral lung functions as a reservoir in bilateral living-donor lobar lung transplantation (LDLLT). We previously reported the usefulness of 133Xe ventilation scintigraphy for detection of unilateral change, but the supply of 133Xe has been stopped globally. The present study aimed to examine the usefulness of inspiratory and expiratory computed tomography (I/E CT) volumetry for detection of unilateral change in CLAD patients. Methods: This was a retrospective single-center, observational study using prospectively collected data. A total of 58 patients who underwent bilateral LDLLT from August 2008 to February 2017 were analyzed. Respiratory function tests, I/E CT were prospectively conducted. ΔLung volume was defined as the value obtained by subtracting expiratory lung volume from inspiratory lung volume. Results: Fourteen (24%) cases were clinically diagnosed with CLAD, of which 10 (71%) were diagnosed as unilateral CLAD. ΔLung volume of bilateral lungs strongly correlated with forced vital capacity (r = 0.92, P < 0.01) and forced expiratory volume in 1 second (r = 0.80, P < 0.01). Regardless the phenotypes (bronchiolitis obliterans syndrome or restrictive allograft syndrome) of CLAD, Δlung volume onset/baseline significantly decreased compared with that in the non-CLAD group. Among the 10 unilateral CLAD patients, 3 with clinically suspected unilateral rejection yet did not show a 20% decline in forced expiratory volume in 1 second. In 2 of these, Δlung volume of unilateral lungs on the rejection side decreased by 20% or more. Conclusions: Our findings suggest that I/E CT volumetry may be useful for assessment and early diagnosis of unilateral CLAD after bilateral LDLLT.

DOI： 10.1097/TXD.0000000000000839

Thoracoscopic rebiopsy to detect the T790M mutation after postoperative recurrence. Reviewed

Hamaji M, Motoyama H, Menju T, Chen-Yoshikawa TF, Sonobe M, Kim YH, Date H

Interactive cardiovascular and thoracic surgery Vol. 27 ( 4 ) page： 606 - 608 2018.10

Gastrointestinal complications after lung transplantation in Japanese patients.

Kayawake H, Chen-Yoshikawa TF, Motoyama H, Hamaji M, Nakajima D, Aoyama A, Date H

Surgery today Vol. 48 ( 9 ) page： 883-890 - 890 2018.9

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

PURPOSE: Gastrointestinal complications after lung transplantation (LTx) are an important postoperative morbidity associated with malnutrition and the malabsorption of drugs. We reviewed our experience of managing gastrointestinal complications after LTx. METHODS: Between June, 2008 and April, 2017, 160 lung transplants were performed at our institution, as living-donor lobar lung transplants in 77 patients, and as deceased-donor lung transplants in 83. We reviewed, retrospectively, the incidence, type and management of gastrointestinal complications. RESULTS: Among the 160 LTx recipients, 58 (36.3%) suffered a collective 70 gastrointestinal complications, the most frequent being gastroparesis, followed by gastroesophageal reflux disease. Two complications were managed surgically, by Nissen fundoplication for gastroesophageal reflux disease in one recipient and Hartmann's operation for sigmoid colon perforation in one. The other 68 complications were managed medically. Two patients died of complications: one, of aspiration pneumonia caused by gastroparesis; and one, of panperitonitis caused by a gastric ulcer. There were no significant differences in overall survival or chronic lung allograft dysfunction-free survival between the patients with and those without gastrointestinal complications. CONCLUSIONS: Gastrointestinal complications are not uncommon in LTx recipients and may be serious; therefore, early detection and appropriate treatment are imperative. Surgical management is required for some complications, but most can be managed medically.

DOI： 10.1007/s00595-018-1666-3

Clinical significance of radiological pleuroparenchymal fibroelastosis pattern in interstitial lung disease patients registered for lung transplantation: a retrospective cohort study. Reviewed International journal

Kiminobu Tanizawa, Tomohiro Handa, Takeshi Kubo, Toyofumi F Chen-Yoshikawa, Akihiro Aoyama, Hideki Motoyama, Kyoko Hijiya, Akihiko Yoshizawa, Yohei Oshima, Kohei Ikezoe, Shinsaku Tokuda, Yoshinari Nakatsuka, Yuko Murase, Sonoko Nagai, Shigeo Muro, Toru Oga, Kazuo Chin, Toyohiro Hirai, Hiroshi Date

Respiratory research Vol. 19 ( 1 ) page： 162 - 162 2018.8

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

BACKGROUND: Radiological pleuroparenchymal fibroelastosis (PPFE) lesion is characterized by pleural thickening with associated signs of subpleural fibrosis on high-resolution computed tomography (HRCT). This study evaluated the clinical significance of radiological PPFE as an isolated finding or associated with other interstitial lung diseases (ILDs) in patients having fibrotic ILDs and registered for cadaveric lung transplantation (LT). METHODS: This retrospective study included 118 fibrotic ILD patients registered for LT. Radiological PPFE on HRCT was assessed. The impact of radiological PPFE on clinical features and transplantation-censored survival were evaluated. RESULTS: Radiological PPFE was observed in 30/118 cases (25%): definite PPFE (PPFE concentrated in the upper lobes, with involvement of lower lobes being less marked) in 12 (10%) and consistent PPFE (PPFE not concentrated in the upper lobes, or PPFE with features of coexistent disease present elsewhere) in 18 (15%). Of these, 12 had late-onset non-infectious pulmonary complications after hematopoietic stem-cell transplantation and/or chemotherapy (LONIPCs), 9 idiopathic PPFE, and 9 other fibrotic ILDs (idiopathic pulmonary fibrosis, IPF; other idiopathic interstitial pneumonias, other IIPs; connective tissue disease-associated ILD, CTD-ILD, and hypersensitivity pneumonia, HP). Radiological PPFE was associated with previous history of pneumothorax, lower body mass index, lower percentage of predicted forced vital capacity (%FVC), higher percentage of predicted diffusion capacity of carbon monoxide, less desaturation on six-minute walk test, and hypercapnia. The median survival time of all study cases was 449 days. Thirty-seven (28%) received LTs: cadaveric in 31 and living-donor lobar in six. Of 93 patients who did not receive LT, 66 (71%) died. Radiological PPFE was marginally associated with better survival after adjustment for age, sex, %FVC, and six-minute walk distance < 250 m (hazard ratio 0.51 [0.25-1.05], p = 0.07). After adjustment for covariates, idiopathic PPFE and LONIPC with radiological PPFE was associated with better survival than fibrotic ILDs without radiological PPFE (hazard ratio 0.38 [0.16-0.90], p = 0.03), and marginally better survival than other fibrotic ILDs with radiological PPFE (hazard ratio, 0.20 [0.04-1.11], p = 0.07). CONCLUSIONS: idiopathic PPFE and LONIPC with radiological PPFE has better survival on the wait list for LT than fibrotic ILDs without radiological PPFE, after adjustment for age, sex, %FVC, and six-minute walk distance.

DOI： 10.1186/s12931-018-0860-6

Adjuvant vinorelbine and cisplatin after complete resection of stage II and III non-small cell lung cancer: long-term follow-up of our study of Japanese patients Reviewed

Makoto Sonobe, Masatsugu Hamaji, Hideki Motoyama, Toshi Menju, Akihiro Aoyama, Toyofumi F. Chen-Yoshikawa, Toshihiko Sato, Hiroshi Date

Surgery Today Vol. 48 ( 7 ) page： 687 - 694 2018.7

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

Purpose: We reported previously a phase II study of adjuvant chemotherapy consisting of four cycles of vinorelbine (25 mg/m2) and cisplatin (40 mg/m2), given on days 1 and 8, every 4 weeks, to Japanese patients with completely resected stage II or III non-small cell lung cancer (NSCLC
UMIN 000005055). However, the follow-up was too short for us to evaluate a definitive 5-year overall survival rate and after-effects. Methods: Between December 2006 and January 2011, 60 patients were enrolled in this study. We analyzed relapse-free and overall survival, long-lasting adverse effects, the influence of treatment on recurrent tumors, and the development of a second primary cancer, in relation with the regimen. Results: After a median follow-up period of 95.8 months, the 5-year relapse-free and overall survival rates were 51.7 and 76.7%, respectively. Neuralgia developed in one patient and this was the only case of a long-lasting adverse effect. Recurrence developed in 31 patients, 29 of whom received intensive treatment. Although 16 s (or more) primary neoplasms developed among 13 patients, these were common carcinomas in Japan and did not include sarcoma or hematologic malignancies. Conclusion: Adjuvant vinorelbine and cisplatin chemotherapy showed encouraging relapse-free and overall survival rates, and long-term safety in Japanese patients with resected NSCLC.

DOI： 10.1007/s00595-018-1646-7

GATA6-positive lung adenocarcinomas are associated with invasive mucinous adenocarcinoma morphology, hepatocyte nuclear factor 4α expression, and KRAS mutations Reviewed

Naoki Nakajima, Akihiko Yoshizawa, Tomoyuki Nakajima, Masahiro Hirata, Ayako Furuhata, Shinji Sumiyoshi, Mariyo Rokutan-Kurata, Makoto Sonobe, Toshi Menju, Ei Miyamoto, Toyofumi F. Chen-Yoshikawa, Hiroshi Date, Hironori Haga

Histopathology Vol. 73 ( 1 ) page： 38 - 48 2018.7

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

Aims: GATA6 is known to play a role in lung development. However, its role in the carcinogenesis of lung cancer is not well studied. The aim of this study was to analyse GATA6 expression in lung adenocarcinomas (LAs) by immunohistochemistry (IHC) in order to define its association with clinicopathological characteristics. Methods and results: IHC analysis of GATA6 was performed with tissue microarray slides containing 348 LAs. The association between GATA6 expression and clinicopathological parameters was evaluated. GATA6 expression in epithelial tumours other than lung cancer was also evaluated. GATA6 expression was found in 47 LAs (13.5%). This occurred more frequently in younger patients (P = 0.005), and was associated with the absence of lymph node metastasis (P =0.024), well-differentiated to moderately differentiated tumours (P &lt
0.001), the absence of lymphatic invasion (P = 0.020), and the absence of vascular invasion (P = 0.011). GATA6 expression was associated with mucin production (P &lt
0.001), the invasive mucinous adenocarcinoma subtype (P &lt
0.001), KRAS mutations (P = 0.026), expression of MUC2 (P &lt
0.001), CDX2 (P = 0.049), and MUC5AC (P &lt
0.001), and absence of expression of TTF-1 (P = 0.002). GATA6 expression was also associated with hepatocyte nuclear factor 4α (HNF4α) expression (P &lt
0.001). GATA6 expression tended to indicate better prognoses, whereas patients with HNF4α expression had significantly worse prognoses (P = 0.033). Of 270 tumours other than lung cancer, 110 expressed GATA6. Conclusions: These findings suggest that GATA6 might interact with HNF4α and contribute to the development of mucinous-type LAs.

DOI： 10.1111/his.13500

Surgical management of bronchial stumps in lobar lung transplantation Reviewed

Hidenao Kayawake, Toyofumi F. Chen-Yoshikawa, Akihiro Aoyama, Hideki Motoyama, Masatsugu Hamaji, Kyoko Hijiya, Hiroshi Date

Journal of Thoracic and Cardiovascular Surgery Vol. 156 ( 1 ) page： 451 - 460 2018.7

Language：English Publishing type：Research paper (scientific journal) Publisher：Mosby Inc.

Background: The validity of lobar lung transplantation (LT) has been established in both living-donor lobar lung transplantation (LDLLT) and cadaveric-donor lung transplantation (CLT). However, bronchial stump management in lobar LT has not been precisely documented. Thus, we retrospectively analyzed our strategies for bronchial stump management in lobar LT. Methods: Between June 2008 and August 2016, 145 LTs (72 LDLLTs and 73 CLTs) were performed at our institution. Bronchial stumps were left in 14 LDLLTs. Eight patients underwent bilateral CLTs with downsizing lobectomy. We avoided leaving donor bronchial stumps by lobar-to-lobar bronchial anastomosis, and left recipient bronchial stumps if necessary. We retrospectively reviewed the bronchial stump management methods and outcomes in these 22 patients. Results: Among the 14 LDLLTs, right-to-left inverted lobar LT and right single-lobe LT with left pneumonectomy were performed in 12 and 2 patients, respectively. Among the 8 CLTs, 11 lobectomies were performed because of oversized grafts and/or localized pneumonia. Twenty-three lobar-to-lobar bronchial anastomoses were performed, and there were 21 recipient bronchial stumps in total. Three bronchial stumps were left in the donor graft, the middle bronchus in all cases. No complications related to lobar-to-lobar bronchial anastomoses were observed. All bronchial stumps healed well without developing a bronchopleural fistula. The 3-year overall survival rate was 88.1% (95% confidence interval, 58.8%-97.0%). Conclusions: We successfully avoided leaving bronchial stumps in the donor graft, except in the middle bronchus, by performing lobar-to-lobar bronchial anastomoses in lobar LTs. Excellent healing of lobar-to-lobar bronchial anastomoses and bronchial stumps was observed.

DOI： 10.1016/j.jtcvs.2017.10.150

Anterior mediastinal tissue volume is correlated with antiacetylcholine receptor antibody level in myasthenia gravis Reviewed

Akihiro Takahagi, Mitsugu Omasa, Toyofumi F. Chen-Yoshikawa, Masatsugu Hamaji, Akihiko Yoshizawa, Takashi Sozu, Makoto Sonobe, Hiroshi Date

Journal of Thoracic and Cardiovascular Surgery Vol. 155 ( 6 ) page： 2738 - 2744 2018.6

Language：English Publishing type：Research paper (scientific journal) Publisher：Mosby Inc.

Objectives: Extended thymectomy is a treatment option for myasthenia gravis (MG), but the surgical indications are controversial. Pathologic features of the thymus can be used to predict surgical outcomes, but there is no reliable method for evaluating these characteristics preoperatively. The purpose of this study was to determine whether anterior mediastinal tissue volume, as measured via 3-dimensional computed tomography (3DCT) volumetry, correlates with serum anti-acetylcholine receptor antibody (AChRAb) levels in patients undergoing thymectomy for myasthenia gravis. Therefore, we investigated the relationships among anterior mediastinal tissue volume determined by 3DCT volumetry and AChRAb levels. Methods: The subjects were 28 patients who underwent extended thymectomy and were enrolled retrospectively. We measured volume of the anterior mediastinum and calculated the volumes of more than −30 Hounsfield units (V−30) by using 3DCT volumetry and compared them with perioperative AChRAb levels. The significance of their volumes in MG was examined by comparison with 53 patients without MG. Results: V−30 values were related to age and were significantly greater in patients with MG than in patients without MG (P &lt
.001). V−30 values were correlated positively with preoperative AChRAb levels (ρ = 0.505, P =.006) and inversely with the post/preoperative AChRAb ratio (ρ = −0.453, P =.018). The histologic nonadipose tissue ratio was correlated with the V−30/volume of the anterior mediastinum (ρ = 0.700, P &lt
.001). Conclusions: This method for evaluation of the anterior mediastinal tissue volume and AChRAb production may be helpful in establishing a treatment plan for MG.

DOI： 10.1016/j.jtcvs.2017.10.082

Diagnostic yield of electromagnetic navigational bronchoscopy: Results of initial 35 cases in a Japanese institute Reviewed

Toshihiko Sato, Yojiro Yutaka, Yuichiro Ueda, Masatsugu Hamaji, Hideki Motoyama, Toshi Menju, Akihiro Aoyama, Toyofumi Fengshi Chen-Yoshikawa, Makoto Sonobe, Hiroshi Date

Journal of Thoracic Disease Vol. 10 ( Suppl 14 ) page： S1615 - S1619 2018.6

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

Background: Electromagnetic navigational bronchoscopy (ENB) is a new bronchoscopic technique for navigational transbronchial lung biopsy (TBLB) that guides the sheath to the target lesion in real time. Herein, we report our experience with this navigational system, its diagnostic yields, and associated complications. Methods: A single-center, single-operator retrospective chart review was performed. We included 35 consecutive patients who underwent ENB with superDimension™ (Medtronic, MN, USA) for the diagnosis of pulmonary lesions from February 2016 to May 2017 in Kyoto University Hospital. The size of the target lesion varied from 8 to 25 mm (median, 15.28±5.48 mm). All ENB procedures were performed under conscious sedation using 2 to 10 mg midazolam and 1 to 10 mg morphine hydrochloride. No fluoroscopic guide was employed except in three cases. Results: A total of 25 patients were diagnosed via ENB, yielding a diagnostic rate of 71.4% (25/35). The average lesion size of the diagnosed group was 16.44±5.44 mm (range, 8-25 mm). Eighteen cases were diagnosed as primary lung cancer, 3 were metastatic lung cancer, and 4 were inflammatory diseases. The average lesion size of the 10 undiagnosed cases was 12.40±5.21 mm (range, 8-24 mm). The lesion size of the undiagnosed group was significantly smaller than that of the diagnosed group (P=0.02). The average time required for the procedure was 16.78±9.57 minutes (range, 3-46 minutes), independent of the diagnosis, the lesion size, and the tumor location. We encountered one pneumothorax which required chest drainage and one hemopneumothorax which required non-elective thoracotomy and wedge resection. One patient developed high fever over 38 ° for one day following the procedure. Conclusions: In our initial series of 35 cases, ENB-guided TBLB showed an acceptable diagnostic yield.

DOI： 10.21037/jtd.2018.04.123

Lung transplantation after haematopoietic stem cell transplantation for Wiskott-Aldrich syndrome Reviewed

Satoshi Ueda, Toyofumi F. Chen-Yoshikawa, Kyoko Hijiya, Hiroshi Date

European Journal of Cardio-thoracic Surgery Vol. 53 ( 6 ) page： 1286 - 1287 2018.6

Language：English Publishing type：Research paper (scientific journal) Publisher：European Association for Cardio-Thoracic Surgery

The authors report the first case involving a patient with Wiskott-Aldrich syndrome who underwent single living-donor lobar lung transplantation after haematopoietic stem cell transplantation. Haematopoietic stem cell transplantation was performed at 1 year of age
however, he developed severe pulmonary complications. Although lung transplantation is generally contraindicated in patients with immunodeficiency disease, the patient was able to undergo living-donor lobar lung transplantation because his immunodeficiency and thrombocytopenia were well controlled as a result of haematopoietic stem cell transplantation. Currently, the patient is doing well and is free from oxygen supplementation.

DOI： 10.1093/ejcts/ezx461

Successful conservative management of an anastomotic airway dehiscence at the left main bronchus following bilateral cadaveric lung transplantation Reviewed

Ryo Miyata, Toyofumi F. Chen-Yoshikawa, Masatsugu Hamaji, Fumiaki Gochi, Hideki Motoyama, Toshi Menju, Akihiro Aoyama, Toshihiko Sato, Makoto Sonobe, Hiroshi Date

General Thoracic and Cardiovascular Surgery Vol. 66 ( 6 ) page： 368 - 371 2018.6

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

There is a dearth of data on management of anastomotic airway dehiscence following lung transplantation. Herein we report a case of successful conservative management of an anastomotic airway dehiscence after cadaveric donor lung transplantation. A 41-year-old woman with primary ciliary dyskinesia underwent cadaveric bilateral lung transplantation without cardiopulmonary bypass. On the postoperative day 25, left pneumothorax developed and bronchoscopy demonstrated a localized anastomotic dehiscence at the left main bronchus. The dehiscence was managed with 2 weeks of pleural drainage and was completely covered with regenerated bronchial epithelium at 4 months after transplantation. There is no finding suggestive of significant stenosis at 4 years of follow-up. Our case suggested asymptomatic and localized anastomotic dehiscence does not always require endobronchial stent placement or re-operation. Multiple factors that may contribute to the successful conservative management were discussed in this article.

DOI： 10.1007/s11748-017-0826-5

Transition of the programmed death 1 pathway from the primary colorectal cancer to its corresponding pulmonary metastasis.

Miyamoto E, Chen-Yoshikawa TF, Ueshima C, Yoshizawa A, Hamaji M, Yamamoto T, Kawada K, Haga H, Sakai Y, Date H

Journal of surgical oncology Vol. 117 ( 7 ) page： 1405-1412 2018.6

Effect of early tracheostomy on clinical outcomes in critically ill lung transplant recipients Reviewed

Ryo Miyoshi, Toyofumi F. Chen-Yoshikawa, Masatsugu Hamaji, Atsushi Kawaguchi, Hidenao Kayawake, Kyoko Hijiya, Hideki Motoyama, Akihiro Aoyama, Hiroshi Date

General Thoracic and Cardiovascular Surgery Vol. 66 ( 9 ) page： 1 - 8 2018.5

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

Objectives: The purpose of this study was to evaluate the effect of early tracheostomy in patients following lung transplantation and to determine its optimal timing and influence on clinical outcomes. Methods: We retrospectively reviewed records of 96 adult patients who underwent lung transplantation at our institution between August 2008 and January 2016. Time-to-tracheostomy was defined based on timing of the procedure: “early” if less than 3 days or “late” if 3 or more days after lung transplantation. Results: Forty-nine patients (51%) underwent tracheostomy 3.2 ± 1.8 days after lung transplantation. Among these patients, 21 patients (42.9%) underwent early tracheostomy and 28 patients (57.1%) underwent late tracheostomy. Multivariable logistic regression analysis indicated that preoperative performance status was a significant predictor for tracheostomy (p = 0.006, odds ratio 2.72). Patients in the early tracheostomy group began walking (p = 0.003) and oral feeding (p = 0.0006) earlier and had a shorter duration of mechanical ventilation (p = 0.04) and shorter length of intensive care unit (p = 0.01) and hospital stay (p = 0.04) than patients in the late tracheostomy group. No significant differences in postoperative walking (p = 0.06), oral feeding (p = 0.17), or length of hospital stay (p = 0.37) were observed between patients who underwent early tracheostomy and those who did not undergo tracheostomy. Conclusions: Early tracheostomy following lung transplantation decreased both intensive care and hospital stay, due to improved postoperative recovery, even in patients with poor preoperative conditions. Furthermore, length of hospital stay in patients with early tracheostomy was similar to that of patients without tracheostomy after lung transplantation.

DOI： 10.1007/s11748-018-0949-3

Nontuberculous mycobacterial and Aspergillus infections among cadaveric lung transplant recipients in Japan Reviewed

Kazunobu Tachibana, Yoshinori Okada, Yasushi Matsuda, Kentaroh Miyoshi, Takahiro Oto, Toyofumi F. Chen-Yoshikawa, Hiroshi Date, Masato Minami, Meinoshin Okumura, Akinori Iwasaki, Takeshi Shiraishi, Sumiko Maeda, Yuji Matsumura, Takahiro Nakajima, Ichiro Yoshino, Seiji Hayashi

Respiratory Investigation Vol. 56 ( 3 ) page： 243 - 248 2018.5

Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier B.V.

Background: Lung transplantation is an effective treatment modality for respiratory failure. Chronic lung infections, including infections caused by nontuberculous mycobacteria (NTM) and Aspergillus, are difficult to control, and uncontrolled infections are relative contraindications for lung transplantation. However, few reports have documented the incidence and outcome of these infections in lung transplant recipients. Methods: To quantify the incidence and outcomes of colonization and disease caused by NTM and aspergillosis in recipients before and after lung transplantation, we reviewed the medical records and microbiology data from 240 consecutive cadaveric lung transplant recipients between 2000 and 2014. Results: Before lung transplantation, NTM and Aspergillus species were isolated from five (2.1%) and six (2.5%) patients, respectively, out of the total 240 recipients. All patients with NTM infection received treatment, resulting in culture conversion. They had no recurrence after lung transplantation. All patients with aspergillosis received treatment, one of whom had recurrence after lung transplantation. Over a median follow-up period of 3.3 years, NTM species were isolated after transplantation from eight of 240 patients (3.3%). Five of these patients met the criteria for NTM disease, and four of them received treatment. Four patients survived without a worsening of NTM disease. Over the same median follow-up period, Aspergillus species were isolated from seven of 240 patients (2.9%), six of whom received treatment. Conclusions: Isolation of NTM or Aspergillus species from lung transplant recipients is uncommon. Adequate pre-transplant control and post-transplant management of NTM and Aspergillus infections allows for safe lung transplantation.

DOI： 10.1016/j.resinv.2017.12.010

Second malignancy versus recurrence after complete resection of thymoma. Reviewed

Hamaji M, Sozu T, Machida R, Omasa M, Menju T, Aoyama A, Sato T, Chen-Yoshikawa TF, Sonobe M, Date H

Asian cardiovascular & thoracic annals Vol. 26 ( 4 ) page： 290 - 295 2018.5

Inverted Lobes Have Satisfactory Functions Compared With Noninverted Lobes in Lung Transplantation Reviewed

Hidenao Kayawake, Toyofumi F. Chen-Yoshikawa, Hideki Motoyama, Masatsugu Hamaji, Kyoko Hijiya, Akihiro Aoyama, Yasufumi Goda, Hiromi Oda, Satoshi Ueda, Hiroshi Date

Annals of Thoracic Surgery Vol. 105 ( 4 ) page： 1044 - 1049 2018.4

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

Background: To overcome the problem of small-for-size grafts in standard living-donor lobar lung transplantation (LDLLT), we developed inverted LDLLT, in which a right lower lobe from 1 donor is implanted as a right graft and another right lower lobe from another donor is implanted as a left graft. We retrospectively analyzed the functions of inverted grafts vs noninverted grafts. Methods: Between 2008 and 2015, 64 LDLLTs were performed. Included were 35 LDLLTs whose recipients were adults and monitored for more than 6 months without developing chronic lung allograft dysfunction. Among them, 65 implanted lobes were eligible for this analysis. There were 31 right lower lobes implanted as right grafts (right-to-right group), 7 right lower lobes as inverted left grafts (right-to-left group), and 27 left lower lobes as left grafts (left-to-left group). We evaluated the graft forced vital capacity (G-FVC) and graft volume of the 65 lobes before and 6 months after LDLLT and compared them among the three groups. Results: Preoperatively, G-FVC in the right-to-left group (1,050 mL) was comparable to that in the right-to-right group (1,177 mL) and better than that in the left-to-left group (791 mL, p &lt
0.01). Six months after LDLLT, G-FVC in the right-to-left group (1,015 mL) remained comparable to that in the right-to-right group (1,001 mL) and better than that in the left-to-left group (713 mL, p = 0.047). The ratio of graft volume 6 months after LDLLT to the preoperative value was comparable. Conclusions: The functions of inverted grafts in inverted LDLLTs were satisfactory compared with those of noninverted grafts.

DOI： 10.1016/j.athoracsur.2017.11.034

Surgery for metachronous second primary lung cancer versus surgery for primary lung cancer: A propensity score-matched comparison of postoperative complications and survival outcomes Reviewed

Yusuke Muranishi, Makoto Sonobe, Masatsugu Hamaji, Atsushi Kawaguchi, Kyoko Hijiya, Hideki Motoyama, Toshi Menju, Akihiro Aoyama, Toyofumi F Chen-Yoshikawa, Toshihiko Sato, Hiroshi Date

Interactive Cardiovascular and Thoracic Surgery Vol. 26 ( 4 ) page： 631 - 637 2018.4

Language：English Publishing type：Research paper (scientific journal) Publisher：Oxford University Press

OBJECTIVES: Surgical treatments for metachronous second primary lung cancer (MSPLC) may be increasing. It was thought that surgery for MSPLC is associated with high mortality and morbidity. However, recent diffusion of minimally invasive surgical procedures may improve the safety of surgery for MSPLC. The aim of this study was to clarify the safety and prognosis of surgery for MSPLC compared with that for primary lung cancer (PLC). METHODS: We reviewed medical records of 1340 patients who underwent pulmonary resection for non-small-cell lung cancer between 2006 and 2013. We identified patients with PLC and those with MSPLC, and surgical parameters and survival outcome were compared. To eliminate selection bias between the MSPLC group and the PLC group, propensity score-matched analysis on the basis of clinicopathological factors was performed. RESULTS: Fifty-three patients underwent resection for MSPLC. Propensity score matching identified 50 patients from each treatment group. Of the 50 MSPLC patients, 41 (82.0%) underwent segmentectomy or wedge resection, 44 (82.0%) had clinical Stage I tumour and 36 (72.0%) received resection via video-assisted thoracoscopic surgery approach. Postoperative complications with a severity of Grade II or more occurred in 11 (22.0%) patients. The incidence of postoperative complications in the MSPLC group was not different from that of the PLC group (P = 0.4894). The 5-year overall survival rates were 68.7% and 83.0% in the PLC and the MSPLC groups, respectively. There was no significant difference between the PLC and the MSPLC groups in terms of overall survival (P = 0.2018, log-rank test). CONCLUSIONS: Pulmonary resection for MSPLC was safely performed with low short-term morbidity similar to that of PLC, and its longterm overall survival was acceptable.

DOI： 10.1093/icvts/ivx389

Salvage Pulmonary Metastasectomy for Local Relapse After Stereotactic Body Radiotherapy. Reviewed

Hamaji M, Mitsuyoshi T, Yoshizawa A, Sato T, Matsuo Y, Chen-Yoshikawa TF, Sonobe M, Mizowaki T, Date H

The Annals of thoracic surgery Vol. 105 ( 4 ) page： e165 - e168 2018.4

Late-onset chest wall abscess due to a biodegradable rib pin infection after lung transplantation Reviewed

Yasufumi Goda, Toyofumi F. Chen-Yoshikawa, Masaaki Kusunose, Masatsugu Hamaji, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Hiroshi Date

General Thoracic and Cardiovascular Surgery Vol. 66 ( 3 ) page： 175 - 178 2018.3

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

A 55-year-old man with end-stage emphysema underwent a right single-lung transplantation through a posterolateral thoracotomy. The fifth rib was divided and fused back using a biodegradable pin made of polylactide acid and hydroxyapatite. Two weeks postoperatively, he suffered from central vein catheter-related sepsis due to methicillin-sensitive Staphylococcus aureus. After being successfully treated for sepsis, he was discharged. However, 3 months later, computed tomography revealed multiple loculated abscesses in the chest wall and the right pleural space. Reoperative thoracotomy revealed abscesses mainly located around the fifth rib, where the pin was inserted. Both cultures of the abscess and the fifth rib were positive for methicillin-sensitive S. aureus, which suggested that the rib pin was the cause of the secondary infection. This case suggests the rib pins, even if they are biodegradable, could have a risk of infections side effect especially for the immunosuppressed patients.

DOI： 10.1007/s11748-017-0768-y

Radiologic and Functional Analysis of Compensatory Lung Growth After Living-Donor Lobectomy. Reviewed International journal

Kei Shikuma, Toyofumi F Chen-Yoshikawa, Tsuyoshi Oguma, Takeshi Kubo, Keiji Ohata, Masatsugu Hamaji, Atsushi Kawaguchi, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Hisako Matsumoto, Shigeo Muro, Hiroshi Date

The Annals of thoracic surgery Vol. 105 ( 3 ) page： 909 - 914 2018.3

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

BACKGROUND: Whether compensatory lung growth occurs in adult humans is controversial. The aim of this study was to confirm compensatory lung growth by analyzing ipsilateral residual lung after lower lobectomy in living lung transplant donors with quantitative and qualitative computed tomography assessments. METHODS: Chest computed tomography and pulmonary function tests were performed in 31 eligible donors before and 1 year after donor lobectomy. Ipsilateral residual lung volume was measured with three-dimensional computed tomography volumetry. The computed tomography-estimated volumes of low, middle, and high attenuations in the lung were calculated. Assessment of the D value, a coefficient of the cumulative size distribution of low-density area clusters, was performed to evaluate the structural quality of the residual lung. RESULTS: Postoperative pulmonary function test values were significantly larger than preoperative estimated values. Although postoperative total volume, low attenuation volume, middle attenuation volume, and high attenuation volume of the ipsilateral residual lung were significantly larger than the preoperative volumes, with 50.2%, 50.0%, 41.5%, and 43.1% increase in the median values, respectively (all p < 0.0001), the differences in D values before and after donor lobectomy were not significant (p = 0.848). The total volume of ipsilateral residual lung was increased by more than 600 mL (50%). CONCLUSIONS: The volume of ipsilateral residual lung increased, but its structural quality did not change before and after donor lobectomy. The existence of compensatory lung growth in adult humans was suggested by quantitative and qualitative computed tomography assessments.

DOI： 10.1016/j.athoracsur.2017.09.060

Wise surgeons learn from others' experiences.

Chen-Yoshikawa TF

The Journal of thoracic and cardiovascular surgery Vol. 155 ( 3 ) page： e115 2018.3

A long-term follow-up report on adjuvant vinorelbine and cisplatin in Japanese patients with completely resected stage II and III non-small cell lung cancer Reviewed

Sonobe M, Hamaji M, Motoyama H, Menju T, Aoyama A, Chen-Yoshikawa TF, Sato T, Date H

Surg Today 2018.3

The synergistic role of ATP-dependent drug efflux pump and focal adhesion signaling pathways in vinorelbine resistance in lung cancer Reviewed

Takao Nakanishi, Toshi Menju, Shigeto Nishikawa, Koji Takahashi, Ryo Miyata, Kei Shikuma, Terumasa Sowa, Naoto Imamura, Masatsugu Hamaji, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Toshihiko Sato, Toyofumi F. Chen-Yoshikawa, Makoto Sonobe, Hiroshi Date

Cancer Medicine Vol. 7 ( 2 ) page： 408 - 419 2018.2

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

The vinorelbine (VRB) plus cisplatin regimen is widely used to treat non–small cell lung cancer (NSCLC), but its cure rate is poor. Drug resistance is the primary driver of chemotherapeutic failure, and the causes of resistance remain unclear. By focusing on the focal adhesion (FA) pathway, we have highlighted a signaling pathway that promotes VRB resistance in lung cancer cells. First, we established VRB-resistant (VR) lung cancer cells (NCI-H1299 and A549) and examined its transcriptional changes, protein expressions, and activations. We treated VR cells by Src Family Kinase (SFK) inhibitors or gene silencing and examined cell viabilities. ATP-binding Cassette Sub-family B Member 1 (ABCB1) was highly expressed in VR cells. A pathway analysis and western blot analysis revealed the high expression of integrins β1 and β3 and the activation of FA pathway components, including Src family kinase (SFK) and AKT, in VR cells. SFK involvement in VRB resistance was confirmed by the recovery of VRB sensitivity in FYN knockdown A549 VR cells. Saracatinib, a dual inhibitor of SFK and ABCB1, had a synergistic effect with VRB in VR cells. In conclusion, ABCB1 is the primary cause of VRB resistance. Additionally, the FA pathway, particularly integrin, and SFK, are promising targets for VRB-resistant lung cancer. Further studies are needed to identify clinically applicable target drugs and biomarkers that will improve disease prognoses and predict therapeutic efficacies.

DOI： 10.1002/cam4.1282

Prognostic Factors in Lung Transplantation after Hematopoietic Stem Cell Transplantation Reviewed

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 Vol. 102 ( 1 ) page： 154 - 161 2018.1

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

Three-dimensional image in lung transplantation Reviewed

Toyofumi F. Chen-Yoshikawa, Hiroshi Date

General Thoracic and Cardiovascular Surgery Vol. 66 ( 1 ) page： 19 - 26 2018.1

Language：English Publisher：Springer Tokyo

Three-dimensional computed tomography (3D-CT) technologies have been developed and, recently, high-speed and high-quality 3D-CT technologies have been introduced to the field of thoracic surgery. The purpose of this manuscript is to demonstrate the clinical application of 3D-CT technologies in lung transplantation. In Japan, because of the severe donor shortage, living-donor lobar lung transplantation (LDLLT) is essential, in addition to cadaveric lung transplantation. In LDLLT, size matching is a grave issue, since ideal size matching between donor and recipient is usually difficult because of the limited population of potential donor. Size matching using pulmonary function test results has been widely used as a gold standard, but anatomical size matching using 3D-CT volumetry data has also been utilized in LDLLT. In donor lobectomy, 3D-CT images provided a variety of information regarding anatomical variation of pulmonary vessels and bronchial trees preoperatively. These images ensure surgical quality and safety, and they also affect surgical procedures for the recipient. 3D-CT images are also utilized in various aspects of postoperative care, such as detection of chronic lung allograft dysfunction and clarification of its subtypes. Furthermore, preoperative 3D-CT simulation is useful in developing and performing a special surgical procedure, such as right-to-left inverted LDLLT. In conclusion, following the introduction of 3D-CT to the field of thoracic surgery, various 3D-CT images and their application to preoperative simulations have been introduced in lung transplantation. In the near future, this technique will become more prevalent, and frequent use by thoracic surgeons will be seen worldwide in daily practice.

DOI： 10.1007/s11748-017-0849-y

Pulmonary endothelial chimerism after hematopoietic stem cell transplantation Reviewed

Kyoko Hijiya, Toyofumi Fengshi Chen-Yoshikawa, Aya Miyagawa-Hayashino, Tadakazu Kondo, Akihiro Aoyama, Hironori Haga, Akifumi Takaori-Kondo, Hiroshi Date

Surgery Today Vol. 48 ( 1 ) page： 101 - 109 2018.1

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

Purpose: Few studies have investigated pulmonary endothelial chimerism after hematopoietic stem cell transplantation. In the present study, we investigated pulmonary endothelial chimerism using the ABH histo-blood group antigen as an identifying marker in cases of ABO-incompatible hematopoietic stem cell transplantation. Methods: Sixteen lung samples were analyzed. Of these, seven were explanted lungs from lung transplant recipients with severe pulmonary chronic graft-versus-host disease (GVHD). The remaining nine were autopsy samples from patients who died from various causes, and six of these nine cases had a diagnosis of pulmonary chronic GVHD. The ABH histo-blood group antigen was used to differentiate donor cells from recipient cells immunohistochemically. We estimated the percentage of vessels positive for donor blood group antigens in comparison with the total number of vessels. Results: Donor blood group antigens were expressed in the endothelium of 13 samples, all of which were pathologically diagnosed with pulmonary chronic GVHD. The proportion of vessels with donor group antigens ranged from 0.1 to 17.5%. In contrast, no chimeric vessels were observed in the three samples without pulmonary chronic GVHD. Conclusions: Our results demonstrate that circulating stem cells engraft into the endothelium to a considerable extent in pulmonary chronic GVHD.

DOI： 10.1007/s00595-017-1562-2

A preliminary study on analysis of deaeration deformation for ex-vivo animal lung

Kotaro Kobayashi, Megumi Nakao, Junko Tokuno, Toyofumi F. Chen-Yoshikawa, Tetsuya Matsuda

Transactions of Japanese Society for Medical and Biological Engineering Vol. 56 page： 40 - 41 2018

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japan Soc. of Med. Electronics and Biol. Engineering

This study aims to analyze deaeration deformation to develop intraoperative guidance of minute lung nodules. We measured lung CT data from ex-vivo animal lungs with different internal pressures, and analyzed surface displacement using Laplacian-based surface registration. We evaluated the registration results by comparing with reference points determined manually, and confirmed that the registration error was around 1mm. We found that the magnitude of surface displacement is orderly distributed based on the distance from the pulmonary hilum.

DOI： 10.11239/jsmbe.Annual56.40

Clinical application of projection mapping technology for surgical resection of lung metastasis Reviewed

Toyofumi F. Chen-Yoshikawa, Etsuro Hatano, Atsushi Yoshizawa, Hiroshi Date

INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY Vol. 25 ( 6 ) page： 1010 - 1011 2017.12

Language：English Publisher：OXFORD UNIV PRESS

Indocyanine green fluorescent image-guided surgery was developed to identify primary and metastatic nodules of various malignancies. However, currently, surgeons need to identify the fluorescent image on a monitor, which impedes surgical procedures. Herein, we developed a novel projection mapping device that can cast the real-time fluorescent image onto the surface of the targeted organ. We performed surgical resection of a lung metastasis of hepatoblastoma using this technique. The projection mapping technique clearly detected the pulmonary lesion, and no other lesions were identified in the ipsilateral thorax. The patient is well and free of recurrence 2 years after surgery.

DOI： 10.1093/icvts/ivx247

Physical activity level significantly affects the survival of patients with end-stage lung disease on a waiting list for lung transplantation Reviewed

Teruya Komatsu, Ayako Oshima, Toyofumi F. Chen-Yoshikawa, Shin-ichi Harashima, Akihiro Aoyama, Nobuya Inagaki, Hiroshi Date

SURGERY TODAY Vol. 47 ( 12 ) page： 1526 - 1532 2017.12

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

Purpose Our objective was to investigate the factors predicting the survival of patients on the waiting list for lung transplantation (LT) during the waiting period, with a special emphasis on the physical activity level.
Methods The study included 70 patients with end-stage pulmonary disease who were on the waiting list for LT at Kyoto University Hospital. We examined the association between the baseline characteristics, including the body mass index and body composition, serum albumin, serum C-reactive protein (CRP), steroid administration, physical activity level (calculated by the food frequency questionnaire) and survival during the waiting period using Kaplan-Meier curves and Cox proportional hazard regression models.
Results A physical activity level of <= 1.2 was correlated with significantly decreased survival (1-year survival: 68 vs. 90.9%, p = 0.0089), with a hazard ratio (HR) of 2.24 (95% confidence interval (CI) 1.22-4.19, p = 0.0001). Hypo-albumin (HR 2.024, 95% CI 1.339-6.009, p = 0.004), a high level of CRP (HR 2.551, CI 1.229-4.892, p = 0.02), and the administration of steroids (HR 2.258, CI 1.907-5.032, p = 0.024) were also significant predictors of survival.
Conclusions Low levels of physical activity during the waiting period for LT led to decreased survival times among LT candidates.

DOI： 10.1007/s00595-017-1542-6

Clamping improves your judgment Reviewed

Toyofumi F. Chen-Yoshikawa

JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Vol. 154 ( 5 ) page： E93 - E93 2017.11

Complications of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Reviewed

Hidenao Kayawake, Toyofumi F. Chen-Yoshikawa, Hiromi Oda, Hideki Motoyama, Masatsugu Hamaji, Toshi Menju, Akihiro Aoyama, Toshihiko Sato, Makoto Sonobe, Hiroshi Date

ANNALS OF THORACIC SURGERY Vol. 104 ( 5 ) page： E363 - E365 2017.11

Language：English Publisher：ELSEVIER SCIENCE INC

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is considered useful for the staging and diagnosis of lung cancer or thoracic lymph node enlargement; however, little is known about its complications. Between July 2009 and November 2016, 413 patients underwent EBUS-TBNA, and four complications (0.97%) occurred. Here we report four cases involving complications of EBUS-TBNA, including mediastinitis (n = 2), obstructive pneumonia (n = 1), and airway obstruction requiring admission to the intensive care unit (n = 1). All patients recovered with appropriate medical treatment. Despite their low incidence, the complications associated with EBUS-TBNA can be serious. (C) 2017 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2017.06.015

Cytomegalovirus infection in living-donor and cadaveric lung transplantations Reviewed

Keiji Ohata, Toyofumi F. Chen-Yoshikawa, Koji Takahashi, Akihiro Aoyama, Hideki Motoyama, Kyoko Hijiya, Masatsugu Hamaji, Toshi Menju, Toshihiko Sato, Makoto Sonobe, Shunji Takakura, Hiroshi Date

INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY Vol. 25 ( 5 ) page： 710 - 715 2017.11

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS

OBJECTIVES: Cytomegalovirus (CMV) infection remains a major cause of morbidity after lung transplantation. Some studies have reported prognostic factors for the postoperative development of CMV infection in cadaveric lung transplantation (CLT), but no research has been performed in living-donor lobar lung transplantation (LDLLT). Therefore, we analysed the possible risk factors of post-transplant CMV infection and the differences between LDLLT and CLT.
METHODS: The development of CMV disease and viraemia in 110 patients undergoing lung transplantation at Kyoto University Hospital in 2008-2015 were retrospectively assessed. The prognostic factors in the development of CMV infection and the differences between LDLLT and CLT were analysed.
RESULTS: Among 110 patients, 58 LDLLTs and 52 CLTs were performed. The 3-year freedom rates from CMV disease and viraemia were 92.0% and 58.5%, respectively. There was no difference in the development of CMV infection between LDLLT and CLT (disease: 94.6% vs 91.0%, P = 0.58 and viraemia: 59.3% vs 57.2%, P = 0.76). In preoperative anti-CMV immunoglobulin status, R-D+ recipients (recipient: negative, donor: positive) and R-D-recipients (recipient: negative, donor: negative) tended to have higher and lower cumulative incidences, respectively, of CMV infection (disease: P = 0.34 and viraemia: P = 0.24) than that with R+ recipients (recipient: seropositive). Significantly lower cumulative incidence of CMV viraemia was observed in patients receiving 12-month prophylactic medication (70.6% vs 36.8%, P < 0.001). Twenty-eight patients (25.5%) had early cessation of anti-CMV prophylaxis due to toxicity; however, the extended prophylaxis duration did not increase the incidence of early cessation (P = 0.88). These trends were seen in both LDLLT and CLT.
CONCLUSIONS: We found that there was no difference in the development of CMV infection between LDLLT and CLT. Twelve-month prophylaxis protocol provides beneficial effect without increased toxicity also in LDLLT.

DOI： 10.1093/icvts/ivx226

Pulmonary Function and Exercise Capacity in Patients With Flat Chests After Lung Transplantation Reviewed

Ryo Miyoshi, Toyofumi F. Chen-Yoshikawa, Akihiro Takahagi, Yohei Oshima, Kyoko Hijiya, Hideki Motoyama, Akihiro Aoyama, Hiroshi Date

ANNALS OF THORACIC SURGERY Vol. 104 ( 5 ) page： 1695 - 1701 2017.11

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Background. Severe chest wall deformation is generally a contraindication for lung transplantation; however, it is not known whether patients with flat chests have reduced postoperative exercise capacity and pulmonary function. This study's purpose was to investigate the relationship between preoperative thoracic shape and postoperative exercise capacity and pulmonary function in patients undergoing lung transplantation.& para;& para;Methods. Twenty recipients who underwent successful bilateral living-donor lobar lung transplantation were evaluated. To analyze postoperative graft function in relation to preoperative thoracic shape, 40 donor grafts implanted into 20 recipients were divided into two groups: flat chest group and normal chest group. Flat chest is diagnosed when the thoracic anteroposterior diameter to transverse diameter ratio is 1:3 or less.& para;& para;Results. The ratio of the postoperative forced vital capacity to the preoperatively estimated forced vital capacity was significantly lower in the flat chest group than in the normal chest group 1 year after lung transplantation (p = 0.002). However, there were no significant differences in postoperative 6-minute walk distances between the two groups. Furthermore, the thoracic anteroposterior diameter to transverse diameter ratio in the flat chest group significantly increased after lung transplantation (p = 0.02).& para;& para;Conclusions. Although postoperative pulmonary function was significantly poorer for patients with flat chests than for patients with normal chests, their postoperative exercise capacity was equivalent. We also found that flat chest severity significantly improved after lung transplantation. Our study, the first investigating post operative functional status in patients with flat chests, clearly shows that it is possible to perform lung transplantation in such patients with acceptable outcomes. (C) 2017 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2017.06.023

Pulmonary venoplasty with a pericardial conduit in living-donor lobar lung retransplantation Reviewed

Hidenao Kayawake, Toyofumi F. Chen-Yoshikawa, Hideki Motoyama, Hiroshi Date

INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY Vol. 25 ( 5 ) page： 830 - 831 2017.11

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS

In living-donor lobar lung transplantation, donor lobectomies must be performed carefully for both donors and recipients. Furthermore, the recipients undergo pneumonectomies rather than lobectomies. Occasionally, anastomosis of the pulmonary vessels is difficult in living-donor lobar lung transplantation because of the limited length of the pulmonary vessels in the graft. This report describes a successful case of pulmonary venoplasty using an autologous pericardial conduit, which was interposed between the superior pulmonary vein of the recipient and the inferior pulmonary vein of the donor in living-donor lobar lung retransplantation. This technique may be required for the success of living-donor lobar lung retransplantation.

DOI： 10.1093/icvts/ivx122

Superior mesenteric artery syndrome after lung transplantation: a rare early gastrointestinal complication of lung transplantation Reviewed

Hidenao Kayawake, Toyofumi F. Chen-Yoshikawa, Akihiro Aoyama, Jitian Zhang, Hiroshi Date

SURGERY TODAY Vol. 47 ( 11 ) page： 1415 - 1418 2017.11

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

Gastrointestinal complications sometimes occur after lung transplantation and remain a cause of postoperative morbidity. Superior mesenteric artery syndrome is caused by the compression of the duodenum by the superior mesenteric artery, but few reports have described superior mesenteric artery syndrome after lung transplantation. We herein report two cases of superior mesenteric artery syndrome as an early complication after lung transplantation. Both patients were emaciated and had lost weight before transplantation. They also lost an additional 2-4 kg early after transplantation. They were medically treated with enteral nutrition and recovered without recurrence of the syndrome. Since critically ill patients with pulmonary disease usually lose weight both before and early after lung transplantation, superior mesenteric artery syndrome is important to consider in the differential diagnosis of gastrointestinal complications after transplantation.

DOI： 10.1007/s00595-017-1513-y

Basiliximab for posterior reversible encephalopathy syndrome after lung transplantation Reviewed

Hiroya Yamagishi, Toyofumi F. Chen-Yoshikawa, Hiroshi Date

EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Vol. 52 ( 4 ) page： 823 - 824 2017.10

Language：English Publisher：OXFORD UNIV PRESS INC

Posterior reversible encephalopathy syndrome is a neurological complication associated with calcineurin inhibitors. There is no consensus regarding the continuation of calcineurin inhibitors in the event of posterior reversible encephalopathy syndrome. We report 3 cases of posterior reversible encephalopathy syndrome among 155 lung transplant recipients (1.9%). The calcineurin inhibitor trough level exceeded the therapeutic range in only 1 case. Our findings demonstrate that temporary cessation of calcineurin inhibitors and administration of basiliximab may be effective strategies for managing posterior reversible encephalopathy syndrome.

DOI： 10.1093/ejcts/ezx151

Severe underweight decreases the survival rate in adult lung transplantation Reviewed

Teruya Komatsu, Toyofumi F. Chen-Yoshikawa, Ayako Oshima, Shin-ichi Harashima, Akihiro Aoyama, Nobuya Inagaki, Hiroshi Date

SURGERY TODAY Vol. 47 ( 10 ) page： 1243 - 1248 2017.10

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

The body mass index (BMI) before lung transplantation (LT) is a benchmark of the post-LT survival. The aim of the study is to determine the BMI inadequate for the post-LT survival.
We examined the survival after LT in patients grouped into the following BMI categories: < 18.5 kg/m(2) (underweight), 18.5-24.9 kg/m(2) (normal weight), 25-29.9 kg/m(2) (overweight), and 30.0 kg/m(2) (obese) according to the World Health Organization (WHO) criteria. A more detailed categorization was made for further evaluation of the underweight group: mild (17.0 BMI < 18.5 kg/m(2)) and severely underweight (BMI < 17.0 kg/m(2)).
There was no statistically significant difference in the post-LT survival between underweight and normal-weight patients (5-year survival: 78.7 vs. 76.1%). Patients with BMI < 17.0 kg/m(2) had a worse prognosis than those with 17.0 BMI < 18.5 kg/m(2) (5-year survival: 70.3 vs. 90.0%).
Standard BMI categorization per the WHO criteria is inadequate for determining the post-LT survival, especially in underweight patients. For the nutritional evaluation of underweight pre-LT patients, BMI < 17.0 kg/m(2) should be used instead of BMI < 18.5 kg/m(2).

DOI： 10.1007/s00595-017-1508-8

Prognostic factors and outcomes in Japanese lung transplant candidates with interstitial lung disease Reviewed

Kohei Ikezoe, Tomohiro Handa, Kiminobu Tanizawa, Toyofumi F. Chen-Yoshikawa, Takeshi Kubo, Akihiro Aoyama, Hideki Motoyama, Kyoko Hijiya, Shinsaku Tokuda, Yoshinari Nakatsuka, Yuko Yamamoto, Ayako Oshima, Shin-ichi Harashima, Sonoko Nagai, Toyohiro Hirai, Hiroshi Date, Kazuo Chin

PLOS ONE Vol. 12 ( 8 ) page： e0183171 2017.8

Language：English Publishing type：Research paper (scientific journal) Publisher：PUBLIC LIBRARY SCIENCE

Objective
Young patients with advanced interstitial lung disease (ILD) are potential candidates for cadaveric lung transplantation. This study aimed to examine clinical features, outcomes, and prognostic factors in Japanese ILD patients awaiting lung transplantation.
Methods
We investigated the clinical features and outcomes of 77 consecutive candidates with ILD who were referred to Kyoto University Hospital and subsequently actively listed for lung transplant in the Japan Organ Transplant Network between 2010 and 2014.
Results
Of the 77 candidates, 33 had idiopathic pulmonary fibrosis (IPF) and 15 had unclassifiable ILD. During the observational period, 23 patients (30%) received lung transplantations and 49 patients (64%) died before transplantation. Of the 33 patients with IPF, 13 (39%) had a family history of ILD and 13 (39%) had an inconsistent with usual interstitial pneumonia pattern on high-resolution computed tomography (HRCT). The median survival time from registration was 16.7 months, and mortality was similar among patients with IPF, unclassifiable ILD, and other ILDs. Using a multivariate stepwise Cox proportional hazards model, 6-min walking distance was shown to be an independent prognostic factor in candidates with ILD (per 10 m, hazard ratio (HR): 0.97; 95% confidence interval (CI): 0.95-0.99, p < 0.01), while lower body mass index (HR: 0.83; 95% CI: 0.72-0.95, p < 0.01) independently contributed to mortality in patients with IPF.
Conclusions
Japanese patients with ILD awaiting transplantation had very poor outcomes regardless of their specific diagnosis. A substantial percentage of IPF patients had an atypical HRCT pattern. 6-min walking distance in ILD patients and body mass index in IPF patients were independent predictors of mortality.

DOI： 10.1371/journal.pone.0183171

Immune function monitoring in lung transplantation using adenosine triphosphate production: time trends and relationship to postoperative infection Reviewed

Mamoru Takahashi, Akihiro Ohsumi, Keiji Ohata, Takeshi Kondo, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Hiroshi Date, Toyofumi F. Chen-Yoshikawa

SURGERY TODAY Vol. 47 ( 6 ) page： 762 - 769 2017.6

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

Purpose The ImmuKnow (IK) assay is a comprehensive immune function test that involves measuring adenosine triphosphate produced by the cluster of differentiation 4+ T lymphocytes in peripheral blood. The aim of this study was to analyze the time trends of IK values and assess the relationship between IK values and infections in lung transplants.
Methods We prospectively collected 178 blood samples from 22 deceased-donor lung transplant (DDLT) recipients and 17 living-donor lobar lung transplant (LDLLT) recipients. A surveillance IK assay was performed postoperatively, then after 1 week and 1, 3, 6, and 12 months.
Results Time trends of IK values in stable recipients peaked 1 week after DDLT (477 +/- 247 ATP ng/ml), and 1 month after LDLLT (433 +/- 134 ng/ml), followed by a gradual decline over 1 year. The mean IK values in infections were significantly lower than those in the stable state (119 vs 312 ATP ng/ml, p = 0.0002).
Conclusions IK values increased sharply after lung transplantation and then decreased gradually over time in the first year, suggesting a natural history of immune function. IK values were also significantly reduced during infections. These results may provide new insights into the utility of immune monitoring after lung transplantation.

DOI： 10.1007/s00595-016-1440-3

Salvage video-assisted thoracoscopic lobectomy for isolated local relapse after stereotactic body radiotherapy for early stage non-small cell lung cancer: technical aspects and perioperative management. Reviewed

Hamaji M, Chen-Yoshikawa TF, Matsuo Y, Motoyama H, Hijiya K, Menju T, Aoyama A, Sato T, Sonobe M, Date H

J Vis Surg 2017.6

Association of Local Intrapulmonary Production of Antibodies Specific to Donor Major Histocompatibility Complex Class I With the Progression of Chronic Rejection of Lung Allografts Reviewed

Ei Miyamoto, Hideki Motoyama, Masaaki Sato, Akihiro Aoyama, Toshi Menju, Kei Shikuma, Terumasa Sowa, Akihiko Yoshizawa, Masao Saito, Akihiro Takahagi, Satona Tanaka, Mamoru Takahashi, Keiji Ohata, Takeshi Kondo, Kyoko Hijiya, Toyofumi F. Chen-Yoshikawa, Hiroshi Date

TRANSPLANTATION Vol. 101 ( 5 ) page： e156 - e165 2017.5

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Background Antibody-mediated rejection may lead to chronic lung allograft dysfunction, but antibody-mediated rejection may develop in the absence of detectable donor-specific antibody (DSA) in recipient serum. This study investigated whether humoral immune responses develop not only systemically but locally within rejected lung allografts, resulting in local production of DSA.
Methods Lewis rats received orthotopic left lung transplantation from Lewis (syngeneic control) or Brown-Norway (major histocompatibility complex-mismatched allogeneic) donor rats. Rats that underwent allogeneic lung transplantation were subsequently administered cyclosporine until day 14 (short immunosuppression) or day 35 (long immunosuppression). The lung grafts and spleens of recipient animals were tissue cultured for 4 days, and the titer of antibody against donor major histocompatibility complex molecules was assayed by flow cytometry. Explanted lung grafts were also evaluated pathologically.
Results By day 98, DSA titers in supernatants of lung graft (P = 0.0074) and spleen (P = 0.0167) cultures, but not serum, from the short immunosuppression group were significantly higher than titers in syngeneic controls. Cultures and sera from the long immunosuppression group showed no production of DSA. Microscopically, the lung grafts from the short immunosuppression group showed severe bronchiole obliteration and parenchymal fibrosis, along with lymphoid aggregates containing T and B cells, accompanying plasma cells. These findings suggestive of local humoral immune response were not observed by days 28 and 63.
Conclusions DSA can be locally produced in chronically rejected lung allografts, along with intragraft immunocompetent cells. Clinical testing of DSA in serum samples alone may underestimate lung allograft dysfunction.

DOI： 10.1097/TP.0000000000001665

Right-to-left inverted living-donor lobar lung transplantation combined with sparing of native right upper lobe Reviewed

Yasufumi Goda, Hideki Motoyama, Akihiro Aoyama, Masatsugu Hamaji, Kyoko Hijiya, Toyofumi F. Chen-Yoshikawa, Hiroshi Date

JOURNAL OF HEART AND LUNG TRANSPLANTATION Vol. 36 ( 5 ) page： 483 - 485 2017.5

Gastric motility and emptying assessment by magnetic resonance imaging after lung transplantation: correlation with gastric emptying scintigraphy Reviewed

Nobuyuki Hayakawa, Yuji Nakamoto, Toyofumi F. Chen-Yoshikawa, Aki Kido, Takayoshi Ishimori, Koji Fujimoto, Tetsu Yamada, Masaaki Sato, Akihiro Aoyama, Hiroshi Date, Kaori Togashi

ABDOMINAL RADIOLOGY Vol. 42 ( 3 ) page： 818 - 824 2017.3

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

Purpose: Gastroparesis is a frequent gastrointestinal complication after lung transplantation. Although gastric emptying scintigraphy (GES) is the standard technique to evaluate gastroparesis, magnetic resonance imaging (MRI) can also assess gastric motility and emptying. This study compared the results obtained by these two modalities.
Methods: Twenty-two lung transplant recipients underwent MRI and GES after ingesting a small pancake as a test meal. Parameters assessed on MRI included antral peristaltic wave velocity and frequency, and the ratios of gastric content volume at 15 and 35 min. GES parameters included retention rates (RR) in the stomach at 30, 60, and 120 min (RR30, RR60, and RR120) and half-time of emptying (T1/2) calculated by exponential curve fitting. Correlations between MRI and GES results were evaluated.
Results: Peristaltic wave velocity showed significant moderate negative correlations with RR120 (r = - 0.58, p < 0.05) and T1/2 (r = - 0.60, p < 0.05), indicating an association between reduced velocity and prolonged gastric emptying. Gastric content volume ratios on MRI showed significant moderate positive correlations with RR30 (r = 0.46, p < 0.05), RR60 (r = 0.60, p < 0.01), and T1/2 (r = 0.60, p < 0.01). There were no significant correlations between peristaltic wave frequency and GES parameters. MRI and GES parameters did not differ significantly between the six patients with and the 16 without upper gastrointestinal symptoms.
Conclusions: MRI-based determinations of gastric motility and gastric emptying correlate with GES-based gastric emptying in lung transplant recipients, suggesting that MRI is useful for evaluating patients with gastroparesis.

DOI： 10.1007/s00261-016-0959-5

Living-Donor Lung Transplantation After Bone Marrow Transplantation for Chediak-Higashi Syndrome Reviewed

Tetsu Yamada, Toyofumi F. Chen-Yoshikawa, Shigeharu Oh, Rieko Ito-Taniguchi, Fumiaki Gochi, Masaaki Sato, Akihiro Aoyama, Hiroshi Date

ANNALS OF THORACIC SURGERY Vol. 103 ( 3 ) page： E281 - E283 2017.3

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

An 8-year-old girl with Chediak-Higashi syndrome (CHS) had pulmonary complications after hematopoietic stem cell transplantation (HSCT) for hemophagocytic lymphohistiocytosis (HLH) and eventually underwent single living-donor lobar lung transplantation (LDLLT). Electron micrographic findings showed vagus nerve tissue in extracted lung having granular inclusions, which are pathognomonic for CHS. Because her mother was the donor for both hematopoietic stem cell and lung transplantations, she was weaned from immunosuppression and is doing well 3 years after lung transplantation. Furthermore, an induced pluripotent stem (iPS) cell line was established from her skin fibroblasts for investigation and potential future treatment for CHS. (C) 2017 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2016.08.049

Immersing lungs in hydrogen-rich saline attenuates lung ischaemia-reperfusion injury Reviewed

Mamoru Takahashi, Toyofumi F. Chen-Yoshikawa, Masao Saito, Satona Tanaka, Ei Miyamoto, Keiji Ohata, Takeshi Kondo, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Hiroshi Date

EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Vol. 51 ( 3 ) page： 442 - 448 2017.3

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS INC

OBJECTIVES: Anti-oxidant effects of hydrogen have been reported in studies examining ischaemia-reperfusion injury (IRI). In this study, we evaluated the therapeutic efficacy of immersing lungs in hydrogen-rich saline on lung IRI.
METHODS: Lewis rats were divided into three groups: (i) sham, (ii) normal saline and (iii) hydrogen-rich saline. In the first experiment, the left thoracic cavity was filled with either normal saline or hydrogen-rich saline for 1 h. Then, we measured the hydrogen concentration in the left lung using a sensor gas chromatograph (N = 3 per group). In the second experiment, lung IRI was induced by occlusion of the left pulmonary hilum for 1 h, followed by reperfusion for 3 h. During the ischaemic period, the left thoracic cavity was filled with either normal saline or hydrogen-rich saline. After reperfusion, we assessed lung function, histological changes and cytokine production (N = 5-7 per group).
RESULTS: Immersing lungs in hydrogen-rich saline resulted in an elevated hydrogen concentration in the lung (6.9 +/- 2.9 mu mol/1 g lung). After IRI, pulmonary function (pulmonary compliance and oxygenation levels) was significantly higher in the hydrogen-rich saline group than in the normal saline group (P < 0.05). Similarly, pro-inflammatory cytokine levels (interleukin-1 beta and interleukin-6) in the left lung were significantly lower in the hydrogen-rich saline group than in the normal saline group (P < 0.05).
CONCLUSIONS: Immersing lungs in hydrogen-rich saline delivered hydrogen into the lung and consequently attenuated lung IRI. Hydrogen-rich solution appears to be a promising approach to managing lung IRI.

DOI： 10.1093/ejcts/ezw342

Bronchodilator Inhalation During Ex Vivo Lung Perfusion Improves Posttransplant Graft Function After Warm Ischemia Reviewed

Kyoko Hijiya, Toyofumi F. Chen-Yoshikawa, Takeshi Kondo, Hideki Motoyama, Akihiro Ohsumi, Daisuke Nakajima, Jin Sakamoto, Keiji Ohata, Mamoru Takahashi, Satona Tanaka, Ei Miyamoto, Akihiro Aoyama, Hiroshi Date

ANNALS OF THORACIC SURGERY Vol. 103 ( 2 ) page： 447 - 453 2017.2

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Background. We hypothesized that an injured lung graft from donation after cardiac death donors could be reconditioned before transplantation using an ex vivo lung perfusion (EVLP) system and ventilation with highdose short-acting beta(2)-adrenergic receptor agonists.
Methods. Cardiac arrest was induced in a canine model by intravenous potassium chloride injection. Lungs were randomly assigned to two groups after 150 minutes of warm ischemia: inhalation of 1,400 mu g of procaterol (BETA group, n = 5) or control group receiving solvent (CON group, n = 5) during EVLP. Left lungs were transplanted after 120 minutes of EVLP. Functional variables, tissue adenosine 5 '-triphosphate levels, and tissue cyclic adenosine monophosphate levels were measured 240 minutes after transplantation.
Results. Physiologic pulmonary function was similar at the end of EVLP in both groups. However, significantly better graft oxygenation, dynamic pulmonary compliance, and reduced pulmonary vascular resistance were observed in the BETA group than in the CON group 240 minutes after transplantation. No severe adverse effects were observed after lung transplantation in the BETA group. Lung tissue adenosine 5 '-triphosphate levels and cyclic adenosine monophosphate levels were significantly higher in the BETA group than in the CON group at the end of EVLP and at 240 minutes after transplantation.
Conclusions. High-dose nebulized procaterol during EVLP ameliorated lung graft dysfunction at the early posttransplantation period without severe adverse effects. These data suggest that lung reconditioning with procaterol ventilation during EVLP improves lung graft function after transplantation. (C) 2017 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2016.07.066

Excellent outcome of donor lobectomy with various surgical techniques for the interlobar artery Reviewed

Hidenao Kayawake, Toyofumi F. Chen-Yoshikawa, Akihiro Aoyama, Hideki Motoyama, Kyoko Hijiya, Toshi Menju, Toshihiko Sato, Makoto Sonobe, Hiroshi Date

EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Vol. 51 ( 2 ) page： 279 - 283 2017.2

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS INC

OBJECTIVES: Donor lobectomies in living-donor lobar lung transplantation sometimes require additional surgical procedures on the interlobar pulmonary artery. We retrospectively reviewed the surgical techniques and outcomes of living-donor lobectomy.
METHODS: Between 2008 and 2015, 116 living-donor lobectomies were performed in 64 consecutive living-donor lobar lung transplantations (52 bilateral, 12 single). The surgical techniques and outcomes were reviewed retrospectively.
RESULTS: Right lower lobectomies were performed in 69 donors, left lower lobectomies in 45 and middle lobectomies in 2. In 61 living donors (52.6%), small branches of the pulmonary artery were sacrificed for anatomical reasons. Pulmonary arterioplasties to preserve the pulmonary artery branches were performed in 13 donors (11.2%). Thirteen left lower lobectomies with pulmonary arterioplasty were performed to preserve lingular branches, as the lingular branch originated far distal to the superior segmental branch of the left lower lobe. Pulmonary arterioplasty with an autologous pericardial patch in 10 donors and with an end-to-end anastomosis in three donors was performed. All surgical procedures had no complications. Three months after lobectomy, the ratio of the pulmonary function test results to the preoperative values and the complication rate showed no significant differences between donors with and without pulmonary arterioplasties, and donors with and without sacrifice of small branches. All living donors resumed their previous lifestyles without restriction.
CONCLUSIONS: Although additional surgical procedures were often required in living-donor lobectomies, the donor outcomes were satisfactory. Arterioplasty to close the interlobar artery in the donor was needed in left-sided cases only.

DOI： 10.1093/ejcts/ezw298

Outcomes of various transplant procedures (single, sparing, inverted) in living-donor lobar lung transplantation Reviewed

Hiroshi Date, Akihiro Aoyama, Kyoko Hijiya, Hideki Motoyama, Tomohiro Handa, Hideyuki Kinoshita, Shiro Baba, Toshiyuki Mizota, Kenji Minakata, Toyofumi F. Chen-Yoshikawa

JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Vol. 153 ( 2 ) page： 479 - 486 2017.2

Language：English Publishing type：Research paper (scientific journal) Publisher：MOSBY-ELSEVIER

Objectives: In standard living-donor lobar lung transplantation (LDLLT), the right and left lower lobes from 2 healthy donors are implanted. Because of the difficulty encountered in finding 2 donors with ideal size matching, various transplant procedures have been developed in our institution. The purpose of this retrospective study was to compare outcomes of nonstandard LDLLT with standard LDLLT.
Methods: Between June 2008 and January 2016, we performed 65 LDLLTs for critically ill patients. Functional size matching was performed by estimating graft forced vital capacity based on the donor's measured forced vital capacity and the number of pulmonary segments implanted. For anatomical size matching, 3dimensional computed tomography volumetry was performed. In cases of oversize mismatch, single-lobe transplant or downsizing transplant was performed. In cases of undersize mismatch, native upper lobe sparing transplant or rightleft inverted transplant was performed. In right-left inverted transplants, the donor's right lower lobe was inverted and implanted into the recipient's left chest cavity.
Results: Twenty-nine patients (44.6%) received nonstandard LDLLT, including 12 single-lobe transplants, 7 native upper lobe sparing transplants, 6 right-left inverted transplants, 2 sparing + inverted transplants, and 2 others. Thirty-six patients (57.4%) received standard LDLLT. Three-and five-year survival rates were similar between the 2 groups (89.1% and 76.6% after nonstandard LDLLT vs 78.0% and 71.1% after standard LDLLT, P = .712).
Conclusions: Various transplant procedures such as single, sparing and inverted transplants are valuable options when 2 donors with ideal size matching are not available for LDLLT.

DOI： 10.1016/j.jtcvs.2016.10.017

Loss of SMAD4 Promotes Lung Metastasis of Colorectal Cancer by Accumulation of CCR1(+) Tumor-Associated Neutrophils through CCL15-CCR1 Axis Reviewed

Takamasa Yamamoto, Kenji Kawada, Yoshiro Itatani, Susumu Inamoto, Ryosuke Okamura, Masayoshi Iwamoto, Ei Miyamoto, Toyofumi F. Chen-Yoshikawa, Hideyo Hirai, Suguru Hasegawa, Hiroshi Date, Makoto M. Taketo, Yoshiharu Sakai

CLINICAL CANCER RESEARCH Vol. 23 ( 3 ) page： 833 - 844 2017.2

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER ASSOC CANCER RESEARCH

Purpose: We have reported loss of SMAD4 promotes expression of CCL15 from colorectal cancer to recruit CCR1(+) myeloid cells through the CCL15-CCR1 axis, which contributes to invasion and liver metastasis. However, the molecular mechanism of lung metastasis is yet to be elucidated. Our purpose is to determine whether similar mechanism is involved in the lung metastasis of colorectal cancer.
Experimental Design: In a mouse model, we examined whether SMAD4 could affect the metastatic activity of colorectal cancer cells to the lung through the CCL15-CCR1 axis. We immunohistochemically analyzed expression of SMAD4, CCL15, and CCR1 with 107 clinical specimens of colorectal cancer lung metastases. We also characterized the CCR1(+) myeloid cells using several cell-type-specific markers.
Results: In a mouse model, CCL15 secreted from SMAD4-deficient colorectal cancer cells recruited CCR1(+) cells, promoting their metastatic activities to the lung. Immunohistochemical analysis of lung metastases from colorectal cancer patients revealed that CCL15 expression was significantly correlated with loss of SMAD4, and that CCL15-positive metastases recruited approximately 1.9 times more numbers of CCR1(+) cells than CCL15-negative metastases. Importantly, patients with CCL15-positive metastases showed a significantly shorter relapse-free survival (RFS) than those with CCL15-negative metastases, and multivariate analysis indicated that CCL15 expression was an independent predictor of shorter RFS. Immunofluorescent staining showed that most CCR1(+) cells around lung metastases were tumor-associated neutrophil, although a minor fraction was granulocytic myeloid-derived suppressor cell.
Conclusions: CCL15-CCR1 axis may be a therapeutic target to prevent colorectal cancer lung metastasis. CCL15 can be a bio-marker indicating poor prognosis of colorectal cancer patients with lung metastases. (C) 2016 AACR.

DOI： 10.1158/1078-0432.CCR-16-0520

Protective Effect of Inhaled Rho-Kinase Inhibitor on Lung Ischemia- Reperfusion Injury Reviewed

Keiji Ohata, Toyofumi F. Chen-Yoshikawa, Toshi Menju, Ei Miyamoto, Satona Tanaka, Mamoru Takahashi, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Hiroshi Date

ANNALS OF THORACIC SURGERY Vol. 103 ( 2 ) page： 476 - 483 2017.2

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Background. Rho-kinase, an intracellular serine/threonine kinase, is a key regulator of cytoskeletal dynamics. Recent studies have demonstrated that Rho-kinase is involved in the ischemia-reperfusion injury (IRI) pathogenesis of many organs; however, its involvement with lung IRI remains unclear. This study assessed the association of Rho-kinase with lung IRI and evaluated the protective effect of inhaled Rho-kinase inhibitors in lung IRI.
Methods. The study included isolated rat lung perfusion models, divided into three groups: sham, Rho-kinase inhibitor, and warm ischemia (n = 6 each). The lungs were exposed to 60 minutes of warm ischemia by perfusion cessation. At the onset of ischemia, nebulized fasudil, a novel Rho-kinase inhibitor, and saline were inhaled in the Rho-kinase inhibitor and warm ischemia groups, respectively. Perfusion was restarted after the ischemic period, and physiologic data were collected for 90 minutes. Lungs in the sham group were continuously perfused without ischemia or drug administrations. Protein expression in tissue specimens related to the Rho-kinase pathway was evaluated by Western blotting.
Results. Warm ischemia and subsequent reperfusion enhanced Rho-kinase activity, and this was suppressed by fasudil inhalation. Fasudil inhalation significantly attenuated IRI pathophysiology, including pulmonary vascular contraction, dynamic compliance, lung edema, and oxygenation. Molecular analysis showed that Rho-kinase suppressed myosin phosphatase and endothelial nitric oxide synthase activities, suggesting these are downstream targets of Rho-kinase during lung IRI pathogenesis.
Conclusions. The present study suggests that Rho-kinase activation is involved in lung IRI pathogenesis and that inhaled Rho-kinase inhibitors may attenuate this pathogenesis. (Ann Thorac Surg 2017; 103: 476-83) (C) 2017 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2016.07.067

Hypoxia-inducible factor 1 promotes chemoresistance of lung cancer by inducing carbonic anhydrase IX expression Reviewed

Terumasa Sowa, Toshi Menju, Toyofumi F. Chen-Yoshikawa, Koji Takahashi, Shigeto Nishikawa, Takao Nakanishi, Kei Shikuma, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Toshihiko Sato, Makoto Sonobe, Hiroshi Harada, Hiroshi Date

CANCER MEDICINE Vol. 6 ( 1 ) page： 288 - 297 2017.1

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

Lung cancer treatment is difficult owing to chemoresistance. Hypoxia-inducible factor 1 (HIF-1) and HIF-1-induced glycolysis are correlated with chemoresistance; however, this is not evident in lung cancer. We investigated the effect of HIF-1 and carbonic anhydrase IX (CAIX), a transmembrane protein neutralizing intracellular acidosis, on chemoresistance and prognosis of lung cancer patients after induction chemoradiotherapy. Associations of HIF-1, glucose transporter 1 (GLUT1), and CAIX with chemoresistance of lung cancer were investigated using A549 lung cancer cells under normoxia or hypoxia in vitro. HIF-1-induced reprogramming of glucose metabolic pathway in A549 cells and the effects of HIF-1 and CAIX on the cytotoxicity of vinorelbine were investigated. Immunohistochemical analyses were performed to determine HIF-1, GLUT1, and CAIX expression levels in cancer specimens from lung cancer patients after induction chemoradiotherapy. Hypoxia induced HIF-1 expression in A549 cells. Moreover, hypoxia induced GLUT1 and CAIX expression in A549 cells in a HIF-1-dependent manner. Glucose metabolic pathway was shifted from oxidative phosphorylation to glycolysis by inducing HIF-1 in A549 cells. HIF-1 and CAIX induced chemoresistance under hypoxia, and their inhibition restored the chemosensitivity of A549 cells. The expression levels of HIF-1, GLUT1, and CAIX were associated with poor overall survival of lung cancer patients after induction chemoradiotherapy. HIF-1 and CAIX affected the chemosensitivity of A549 cells and prognosis of lung cancer patients. Therefore, inhibition of HIF-1 and CAIX might improve prognosis of lung cancer patients after induction chemoradiotherapy. Further analysis might be helpful in developing therapies for lung cancer.

DOI： 10.1002/cam4.991