Faculty Profiles - CHEN-YOSHIKAWA Toyofumi

Papers - CHEN-YOSHIKAWA Toyofumi

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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

PubMed

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

Scopus

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

PubMed

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

PubMed

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

PubMed

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

PubMed

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

Scopus

PubMed

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)

<p>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 %.</p>

DOI： 10.5687/iscie.33.123

CiNii Research

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

Scopus

PubMed

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

PubMed

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

PubMed

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

Scopus

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

Scopus

PubMed

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Papers - CHEN-YOSHIKAWA Toyofumi