published_papers "タイトル(日本語)","タイトル(英語)","著者(日本語)","著者(英語)","担当区分","概要(日本語)","概要(英語)","出版者・発行元(日本語)","出版者・発行元(英語)","出版年月","誌名(日本語)","誌名(英語)","巻","号","開始ページ","終了ページ","記述言語","査読の有無","招待の有無","掲載種別","国際・国内誌","国際共著","DOI","ISSN","eISSN","URL","URL2","主要な業績かどうか","公開の有無" "Lung regeneration with rat fetal lung implantation and promotion of alveolar stem cell differentiation by corticosteroids","Lung regeneration with rat fetal lung implantation and promotion of alveolar stem cell differentiation by corticosteroids","Daisuke Matsumoto, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama, Shin-ichi Sakamoto, Mika Takashima, Naoya Kawakita, Hiromitsu Takizawa","Daisuke Matsumoto, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama, Shin-ichi Sakamoto, Mika Takashima, Naoya Kawakita, Hiromitsu Takizawa","null","The lung is a difficult organ to regenerate, and the development of functional lungs has still not been achieved. In this study, we investigated lung regeneration using a rat fetal lung tissue-implanted model. This study aimed to evaluate the functioning of the implanted fetal lung tissue and investigate the graft differentiation and maturation mechanism, focusing on alveolar stem cells. Fetal lung tissue fragments were obtained from Lewis rats on day 17 and implanted into adult lungs. Animals were divided into the following three groups: group 1, injection into the adult left lung parenchyma; group 2, injection with post-caval lobectomy; and group 3, injection with post-caval lobectomy and corticosteroid administration. Computed tomography was performed on weeks 1, 2, 4, and 8. The presence of alveolar pore, CD31 expression, and bipotential progenitor cell (podoplanin+/surfactant protein C+) localization were histologically evaluated. MiRNA expression was comprehensively compared among the three groups. The grafts comprised type I and type II alveolar cells connected to the recipient lungs with alveolar pores and capillary networks in the interstitial tissue. The alveolar space was the largest and the computed tomography value was the lowest in the grafts of the corticosteroid-administered group. The number of bipotential progenitor cells was the lowest in the corticosteroid administration group on day 7. Moreover, microRNA-487-3p, 374-5p, and 20b-5p expression was changed by more than 2-fold between the post-caval lobectomy and corticosteroid administration groups. Implanted fetal lung tissues established airway and capillary communication with the recipient lungs, and corticosteroids accelerated their maturation by promoting the differentiation of progenitor cells. The study findings provide new insights into lung regeneration research.","The lung is a difficult organ to regenerate, and the development of functional lungs has still not been achieved. In this study, we investigated lung regeneration using a rat fetal lung tissue-implanted model. This study aimed to evaluate the functioning of the implanted fetal lung tissue and investigate the graft differentiation and maturation mechanism, focusing on alveolar stem cells. Fetal lung tissue fragments were obtained from Lewis rats on day 17 and implanted into adult lungs. Animals were divided into the following three groups: group 1, injection into the adult left lung parenchyma; group 2, injection with post-caval lobectomy; and group 3, injection with post-caval lobectomy and corticosteroid administration. Computed tomography was performed on weeks 1, 2, 4, and 8. The presence of alveolar pore, CD31 expression, and bipotential progenitor cell (podoplanin+/surfactant protein C+) localization were histologically evaluated. MiRNA expression was comprehensively compared among the three groups. The grafts comprised type I and type II alveolar cells connected to the recipient lungs with alveolar pores and capillary networks in the interstitial tissue. The alveolar space was the largest and the computed tomography value was the lowest in the grafts of the corticosteroid-administered group. The number of bipotential progenitor cells was the lowest in the corticosteroid administration group on day 7. Moreover, microRNA-487-3p, 374-5p, and 20b-5p expression was changed by more than 2-fold between the post-caval lobectomy and corticosteroid administration groups. Implanted fetal lung tissues established airway and capillary communication with the recipient lungs, and corticosteroids accelerated their maturation by promoting the differentiation of progenitor cells. The study findings provide new insights into lung regeneration research.","null","null","2023-09-14","Regenerative Therapy","Regenerative Therapy","Vol.24","null","426","433","eng","true","null","scientific_journal","null","null","10.1016/j.reth.2023.09.006","2352-3204","null","null","null","null","null" "Effectiveness of surveillance by echocardiography for Cancer therapeutics-related cardiac dysfunction of patients with breast Cancer","Effectiveness of surveillance by echocardiography for Cancer therapeutics-related cardiac dysfunction of patients with breast Cancer","Yuichiro Okushi, Yoshihito Saijyo, Hirotsugu Yamada, Hiroaki Toba, Robert Zheng, Hiromitsu Seno, Tomonori Takahashi, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata, Kenya Kusunose","Yuichiro Okushi, Yoshihito Saijyo, Hirotsugu Yamada, Hiroaki Toba, Robert Zheng, Hiromitsu Seno, Tomonori Takahashi, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata, Kenya Kusunose","null","Cancer therapeutics-related cardiac dysfunction (CTRCD) affect the prognosis of patients with breast cancer. Echocardiographic surveillance of patients treated with anti-human epidermal growth factor receptor type 2 (HER2) antibodies has been recommended, but few reports have provided evidence on patients with breast cancer only. We aimed to evaluate the effectiveness of echocardiographic surveillance for breast cancer patients. We identified 250 patients with breast cancer who were treated with anti-HER2 antibodies from July 2007 to September 2021. We divided 48 patients with echocardiographic surveillance every 3 months into the surveillance group and 202 patients without echocardiographic surveillance into the non-surveillance group. In the surveillance group, patients with a considerable reduction in global longitudinal strain of 15 % were considered for the initiation of cardioprotective drugs. The composite outcome of CTRCD and acute heart failure was the study endpoint. The mean age was 59 ± 12 years. During the follow-up period of 15 months (12-17 months), 12 patients reached the endpoint. The surveillance group had significantly lower incidence of the composite outcome (2.1 % vs. 5.5 %, adjusted odds ratio: 0.28, 95 % confidential intervals: 0.09-0.94; p = 0.039) and higher rates of prescriptions of cardioprotective drugs than the non-surveillance group. The incidence of cardiac complications was significantly lower in the surveillance group than the non-surveillance group, which supports the effectiveness of echocardiographic surveillance in patients with breast cancer.","Cancer therapeutics-related cardiac dysfunction (CTRCD) affect the prognosis of patients with breast cancer. Echocardiographic surveillance of patients treated with anti-human epidermal growth factor receptor type 2 (HER2) antibodies has been recommended, but few reports have provided evidence on patients with breast cancer only. We aimed to evaluate the effectiveness of echocardiographic surveillance for breast cancer patients. We identified 250 patients with breast cancer who were treated with anti-HER2 antibodies from July 2007 to September 2021. We divided 48 patients with echocardiographic surveillance every 3 months into the surveillance group and 202 patients without echocardiographic surveillance into the non-surveillance group. In the surveillance group, patients with a considerable reduction in global longitudinal strain of 15 % were considered for the initiation of cardioprotective drugs. The composite outcome of CTRCD and acute heart failure was the study endpoint. The mean age was 59 ± 12 years. During the follow-up period of 15 months (12-17 months), 12 patients reached the endpoint. The surveillance group had significantly lower incidence of the composite outcome (2.1 % vs. 5.5 %, adjusted odds ratio: 0.28, 95 % confidential intervals: 0.09-0.94; p = 0.039) and higher rates of prescriptions of cardioprotective drugs than the non-surveillance group. The incidence of cardiac complications was significantly lower in the surveillance group than the non-surveillance group, which supports the effectiveness of echocardiographic surveillance in patients with breast cancer.","null","null","2023-07-20","Journal of Cardiology","Journal of Cardiology","Vol.82","No.6","467","472","eng","true","null","scientific_journal","null","null","10.1016/j.jjcc.2023.07.002","1876-4738","null","null","null","null","null" "Assessment of dyspnea, ADL, and QOL in the perioperative period in lung cancer patients treated with minimally invasive surgery","Assessment of dyspnea, ADL, and QOL in the perioperative period in lung cancer patients treated with minimally invasive surgery","Linwan Zhang, Kazuya Kondo, Takae Bando, Naoya Kawakita, Hiroaki Toba, Yoshie Imai, Hiromitsu Takizawa","Linwan Zhang, Kazuya Kondo, Takae Bando, Naoya Kawakita, Hiroaki Toba, Yoshie Imai, Hiromitsu Takizawa","null","Patients with lung cancer generally undergo minimally invasive surgery, such as video-assisted thoracoscopic surgery (VATS). This study examined the changes in health conditions and symptoms of patients with lung cancer using the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC QLQ) C-30 questionnaires after surgery. This was a longitudinal descriptive study. One hundred and three patients with lung cancer who underwent lung resection at Tokushima University Hospital between 2012 and 2021 were eligible. They completed EORTC QLQ-C30, QLQ-LC13, the Cancer Dyspnea scale (CDS), and pulmonary-ADL (P-ADL) before and 1, 3, and 6 months after surgery. Regarding functional scale scores, impairments in physical and role functions persisted for 6 months after surgery. In symptom scale scores, fatigue, pain, dyspnea, and appetite loss continued for 6 months after surgery. In CDS, sense of effort, discomfort, and total dyspnea scale scores were elevated for 6 months after surgery. In P-ADL, most ADL were impaired 1 month after surgery, but recovered by 3 months. The dyspnea index of ADL was lower for 6 months after surgery. Impairments in health conditions and symptoms persisted for 6 months after surgery despite its minimally invasive nature. J. Med. Invest. 70 : 388-402, August, 2023.","Patients with lung cancer generally undergo minimally invasive surgery, such as video-assisted thoracoscopic surgery (VATS). This study examined the changes in health conditions and symptoms of patients with lung cancer using the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC QLQ) C-30 questionnaires after surgery. This was a longitudinal descriptive study. One hundred and three patients with lung cancer who underwent lung resection at Tokushima University Hospital between 2012 and 2021 were eligible. They completed EORTC QLQ-C30, QLQ-LC13, the Cancer Dyspnea scale (CDS), and pulmonary-ADL (P-ADL) before and 1, 3, and 6 months after surgery. Regarding functional scale scores, impairments in physical and role functions persisted for 6 months after surgery. In symptom scale scores, fatigue, pain, dyspnea, and appetite loss continued for 6 months after surgery. In CDS, sense of effort, discomfort, and total dyspnea scale scores were elevated for 6 months after surgery. In P-ADL, most ADL were impaired 1 month after surgery, but recovered by 3 months. The dyspnea index of ADL was lower for 6 months after surgery. Impairments in health conditions and symptoms persisted for 6 months after surgery despite its minimally invasive nature. J. Med. Invest. 70 : 388-402, August, 2023.","null","null","2023-05","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.70","No.3.4","388","402","eng","true","null","scientific_journal","null","null","10.2152/jmi.70.388","1349-6867","null","null","null","null","null" "Absolute Lymphocyte Count Changes During Neoadjuvant Chemotherapy are Associated With Prognosis of Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Patients","Absolute Lymphocyte Count Changes During Neoadjuvant Chemotherapy are Associated With Prognosis of Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Patients","Naoki Miyamoto, Hiroaki Inoue, Tomohiro Inui, Souichiro Sasa, Mariko Aoyama, Kazumasa Okumura, Hiroaki Toba, Naoki Hino, Aya Nishisho, Yukishige Sawaka, Taeko Kawanaka, Hiromitsu Takizawa, Akira Tangoku","Naoki Miyamoto, Hiroaki Inoue, Tomohiro Inui, Souichiro Sasa, Mariko Aoyama, Kazumasa Okumura, Hiroaki Toba, Naoki Hino, Aya Nishisho, Yukishige Sawaka, Taeko Kawanaka, Hiromitsu Takizawa, Akira Tangoku","null","Some reports have shown that absolute lymphocyte count (ALC) is associated with prognosis in breast cancer; however, the impact of ALC changes remains unclear. This study aimed to investigate the relationship between ALC changes during neoadjuvant chemotherapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients and disease prognosis. This retrospective cohort study January 2010 to September 2020) included patients diagnosed with HER2-positive breast cancer and treated with trastuzumab-based neoadjuvant chemotherapy. The ALC ratio was defined as the ALC value after administration of the anti-HER2 drug divided by the ALC value before administration. The optimal ALC ratio cut-off value was identified using the receiver operating characteristic curve analysis and Youden's index. The relationship between the ALC ratio and disease-free survival was assessed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. Data from a total of 100 HER2-positive breast cancer patients were analyzed. The cut-off value of the ALC ratio was set as 1.142. The median follow-up period was 52.0 (range: 5.1-123.7) months. The 5-year disease-free survival rates were 88.4% and 60.9% in the high-and low-ALC ratio groups, respectively, and were significantly higher in the high-ALC ratio group (p = .0031). The ALC ratio was an independent prognostic factor in multivariate Cox proportional hazards analysis (p = .0032). HER2-positive breast cancer patients with a higher ALC ratio during trastuzumab-based neoadjuvant chemotherapy may have a better prognosis than their counterparts.","Some reports have shown that absolute lymphocyte count (ALC) is associated with prognosis in breast cancer; however, the impact of ALC changes remains unclear. This study aimed to investigate the relationship between ALC changes during neoadjuvant chemotherapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients and disease prognosis. This retrospective cohort study January 2010 to September 2020) included patients diagnosed with HER2-positive breast cancer and treated with trastuzumab-based neoadjuvant chemotherapy. The ALC ratio was defined as the ALC value after administration of the anti-HER2 drug divided by the ALC value before administration. The optimal ALC ratio cut-off value was identified using the receiver operating characteristic curve analysis and Youden's index. The relationship between the ALC ratio and disease-free survival was assessed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. Data from a total of 100 HER2-positive breast cancer patients were analyzed. The cut-off value of the ALC ratio was set as 1.142. The median follow-up period was 52.0 (range: 5.1-123.7) months. The 5-year disease-free survival rates were 88.4% and 60.9% in the high-and low-ALC ratio groups, respectively, and were significantly higher in the high-ALC ratio group (p = .0031). The ALC ratio was an independent prognostic factor in multivariate Cox proportional hazards analysis (p = .0032). HER2-positive breast cancer patients with a higher ALC ratio during trastuzumab-based neoadjuvant chemotherapy may have a better prognosis than their counterparts.","null","null","2023-04","Clinical Breast Cancer","Clinical Breast Cancer","Vol.23","No.3","e68","e76","eng","true","null","scientific_journal","null","null","10.1016/j.clbc.2023.01.005","1938-0666","null","null","null","null","null" "Aberrant methylation of dipeptidyl peptidaselike 6 as a potential prognostic biomarker for lung adenocarcinoma","Aberrant methylation of dipeptidyl peptidaselike 6 as a potential prognostic biomarker for lung adenocarcinoma","Batkhishig Munkhjargal, Kazuya Kondo, Soejima Shiho, Tegshee Bilguun, Chikako Takai, Naoya Kawakita, Hiroaki Toba, Hiromitsu Takizawa","Batkhishig Munkhjargal, Kazuya Kondo, Soejima Shiho, Tegshee Bilguun, Chikako Takai, Naoya Kawakita, Hiroaki Toba, Hiromitsu Takizawa","null","We previously performed the genome-wide screening of aberrantly methylated CpG islands (CGIs) using the paired tumorous and non-tumorous tissues of 12 lung adenocarcinomas (LADC). In comparisons with paired normal lung tissues, dipeptidyl peptidase-like 6 () has been identified as the most significantly hypermethylated CGI in LADC. is a protein that modulates A-type potassium channels in the somatodendritic compartments of neurons, which play a role in synaptic plasticity. Previous studies have showed that is downregulated in cancers, such as acute myeloid leukemia and melanoma, but upregulated in colon cancer, which is attributed to hyper- and hypomethylation, respectively. The present study investigated the methylation and expression levels of and its prognostic value in patients with LADC. The DNA methylation and mRNA expression levels of in surgically resected LADC tissues were examined by bisulfite pyrosequencing and reverse transcription-quantitative PCR, respectively. The DNA methylation and mRNA expression levels of were both significantly higher in LADC tissues compared with in normal lung tissues (n=25; P<0.0001). Overall and disease-free survival rates were significantly higher in LADC with high mRNA expression levels compared with those with low levels. In conclusion, epigenetic alterations in were significantly higher in LADC tissues compared with in normal lung tissues, which may contribute to the malignant features and worse prognosis of these patients.","We previously performed the genome-wide screening of aberrantly methylated CpG islands (CGIs) using the paired tumorous and non-tumorous tissues of 12 lung adenocarcinomas (LADC). In comparisons with paired normal lung tissues, dipeptidyl peptidase-like 6 () has been identified as the most significantly hypermethylated CGI in LADC. is a protein that modulates A-type potassium channels in the somatodendritic compartments of neurons, which play a role in synaptic plasticity. Previous studies have showed that is downregulated in cancers, such as acute myeloid leukemia and melanoma, but upregulated in colon cancer, which is attributed to hyper- and hypomethylation, respectively. The present study investigated the methylation and expression levels of and its prognostic value in patients with LADC. The DNA methylation and mRNA expression levels of in surgically resected LADC tissues were examined by bisulfite pyrosequencing and reverse transcription-quantitative PCR, respectively. The DNA methylation and mRNA expression levels of were both significantly higher in LADC tissues compared with in normal lung tissues (n=25; P<0.0001). Overall and disease-free survival rates were significantly higher in LADC with high mRNA expression levels compared with those with low levels. In conclusion, epigenetic alterations in were significantly higher in LADC tissues compared with in normal lung tissues, which may contribute to the malignant features and worse prognosis of these patients.","null","null","2023-03","Oncology Letters","Oncology Letters","Vol.25","No.5","206","206","eng","true","null","scientific_journal","null","null","10.3892/ol.2023.13792","1792-1082","null","null","null","null","null" "Cone-beam computed tomography-guided endobronchial ultrasound using an ultrathin bronchoscope for diagnosis of peripheral pulmonary lesions: a prospective pilot study","Cone-beam computed tomography-guided endobronchial ultrasound using an ultrathin bronchoscope for diagnosis of peripheral pulmonary lesions: a prospective pilot study","Naoya Kawakita, Hiroaki Toba, Shin-ichi Sakamoto, Naoki Miyamoto, Mika Takashima, Yukikiyo Kawakami, Kazuya Kondo, Hiromitsu Takizawa","Naoya Kawakita, Hiroaki Toba, Shin-ichi Sakamoto, Naoki Miyamoto, Mika Takashima, Yukikiyo Kawakami, Kazuya Kondo, Hiromitsu Takizawa","null","Multimodal transbronchial biopsy (TBB) may have improved diagnostic yield for peripheral pulmonary lesions suspected as lung cancer. Radial endobronchial ultrasound (R-EBUS) provides real-time imaging and confirmation of the location of the lesions. Cone-beam computed tomography (CBCT) can confirm that the forceps tip has reached the lesion before biopsy. Patients with peripheral pulmonary lesions and a positive computed tomography (CT) bronchus sign (based on slice thickness of 1 mm) were prospectively enrolled. An ultrathin bronchoscope (UTB) and R-EBUS probe were advanced to the target bronchus. Thereafter, forceps were advanced, and CBCT was performed. R-EBUS was performed for re-navigation, if possible. The obtained EBUS and CBCT images were classified into ""within"" (type 1), ""adjacent to"" (type 2), or ""far from"" (type 3), based on the probe or forceps tip. For 20 lesions, the diagnostic yield was 85%. The primary EBUS images were of types 1, 2, and 3 in 12, 6, and 2 cases, respectively. The primary CBCT images were of types 1, 2, and 3 in 12, 6, and 2 cases, respectively. Primary EBUS and CBCT image types were equivalent in 14 cases. Of the 12 cases with type 1 primary EBUS image, 9 cases had a type 1 primary CBCT image, while 3 cases exhibited positional misalignment of the forceps tip. Re-navigation was required in 8 cases with types 2 and 3 primary CBCT images. CBCT-guided TBB using an UTB and EBUS may enable real-time positioning guidance and better re-navigation in the diagnosis of peripheral pulmonary lesions.","Multimodal transbronchial biopsy (TBB) may have improved diagnostic yield for peripheral pulmonary lesions suspected as lung cancer. Radial endobronchial ultrasound (R-EBUS) provides real-time imaging and confirmation of the location of the lesions. Cone-beam computed tomography (CBCT) can confirm that the forceps tip has reached the lesion before biopsy. Patients with peripheral pulmonary lesions and a positive computed tomography (CT) bronchus sign (based on slice thickness of 1 mm) were prospectively enrolled. An ultrathin bronchoscope (UTB) and R-EBUS probe were advanced to the target bronchus. Thereafter, forceps were advanced, and CBCT was performed. R-EBUS was performed for re-navigation, if possible. The obtained EBUS and CBCT images were classified into ""within"" (type 1), ""adjacent to"" (type 2), or ""far from"" (type 3), based on the probe or forceps tip. For 20 lesions, the diagnostic yield was 85%. The primary EBUS images were of types 1, 2, and 3 in 12, 6, and 2 cases, respectively. The primary CBCT images were of types 1, 2, and 3 in 12, 6, and 2 cases, respectively. Primary EBUS and CBCT image types were equivalent in 14 cases. Of the 12 cases with type 1 primary EBUS image, 9 cases had a type 1 primary CBCT image, while 3 cases exhibited positional misalignment of the forceps tip. Re-navigation was required in 8 cases with types 2 and 3 primary CBCT images. CBCT-guided TBB using an UTB and EBUS may enable real-time positioning guidance and better re-navigation in the diagnosis of peripheral pulmonary lesions.","null","null","2023-02-08","Journal of Thoracic Disease","Journal of Thoracic Disease","Vol.15","No.2","579","588","eng","true","null","scientific_journal","null","null","10.21037/jtd-22-1369","2072-1439","null","null","null","null","null" "null","null","null","null","null","null","null","null","null","2023","null","null","Vol.49","No.5","272","273","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null" "Abscopal effect in a patient with solitary extramedullary plasmacytoma of the thyroid: case report","Abscopal effect in a patient with solitary extramedullary plasmacytoma of the thyroid: case report","Mariko Aoyama, Takashi Shono, Tomohiro INUI, Naoki Miyamoto, Shin-ichi Sakamoto, Seiya Inoue, Satoshi Fujiwara, Masakazu Goto, Hiroaki Toba, Hiromitsu Takizawa","Mariko Aoyama, Takashi Shono, Tomohiro INUI, Naoki Miyamoto, Shin-ichi Sakamoto, Seiya Inoue, Satoshi Fujiwara, Masakazu Goto, Hiroaki Toba, Hiromitsu Takizawa","null","The abscopal effect is a systemic antitumor response that occurs distant to the irradiation site and is induced by local irradiation. We herein describe a case of solitary extramedullary plasmacytoma (SEP) of the thyroid in which bone metastases disappeared after thyroidectomy and cervical radiotherapy (RT). A 68-year-old man with a right cervical swelling for approximately 10 years visited a hospital with left elbow pain that persisted for 5 months. He was referred to our hospital for more detailed examinations and treatment. An immobile mass of approximately 10 cm in diameter was palpable on the right side of the patient's neck. Computed tomography (CT) showed osteolytic changes in the left humerus and right scapula, and a tumor in the right lobe of the thyroid gland. The patient was diagnosed with widely invasive follicular carcinoma and multiple bone metastases and underwent total thyroidectomy. During surgery, tumor infiltration into the trachea was observed. Shaving between the tumor and trachea was performed. Based on the results of a pathological examination, the patient was diagnosed with primary extramedullary plasmacytoma of the thyroid. After surgery, external beam RT was performed on the neck, which also reduced the pain in the left elbow. Positron emission tomography (PET)-CT showed the decreased accumulation of fluorodeoxyglucose (FDG) in the left humerus and right scapula, and the amelioration of osteolytic changes on CT. SEP of the thyroid is rare, and to the best of our knowledge, this is the first case report in which the abscopal effect was observed after thyroidectomy and cervical RT.","The abscopal effect is a systemic antitumor response that occurs distant to the irradiation site and is induced by local irradiation. We herein describe a case of solitary extramedullary plasmacytoma (SEP) of the thyroid in which bone metastases disappeared after thyroidectomy and cervical radiotherapy (RT). A 68-year-old man with a right cervical swelling for approximately 10 years visited a hospital with left elbow pain that persisted for 5 months. He was referred to our hospital for more detailed examinations and treatment. An immobile mass of approximately 10 cm in diameter was palpable on the right side of the patient's neck. Computed tomography (CT) showed osteolytic changes in the left humerus and right scapula, and a tumor in the right lobe of the thyroid gland. The patient was diagnosed with widely invasive follicular carcinoma and multiple bone metastases and underwent total thyroidectomy. During surgery, tumor infiltration into the trachea was observed. Shaving between the tumor and trachea was performed. Based on the results of a pathological examination, the patient was diagnosed with primary extramedullary plasmacytoma of the thyroid. After surgery, external beam RT was performed on the neck, which also reduced the pain in the left elbow. Positron emission tomography (PET)-CT showed the decreased accumulation of fluorodeoxyglucose (FDG) in the left humerus and right scapula, and the amelioration of osteolytic changes on CT. SEP of the thyroid is rare, and to the best of our knowledge, this is the first case report in which the abscopal effect was observed after thyroidectomy and cervical RT.","null","null","2022-11","Translational Cancer Research","Translational Cancer Research","Vol.11","No.11","4200","4205","eng","true","null","scientific_journal","null","null","10.21037/tcr-22-1419","2219-6803","null","null","null","null","null" "F-FDG PET/CT Showing Rare Mediastinal Growing Teratoma Syndrome Following Chemotherapy.","F-FDG PET/CT Showing Rare Mediastinal Growing Teratoma Syndrome Following Chemotherapy.","Mihoko Sasahara, Takashi Abe, Youichi Otomi, Yumi Abe, Hiroaki Toba, Takayoshi Shinya, Hideki Otsuka, Masafumi Harada","Mihoko Sasahara, Takashi Abe, Youichi Otomi, Yumi Abe, Hiroaki Toba, Takayoshi Shinya, Hideki Otsuka, Masafumi Harada","null","F-FDG uptake.","F-FDG uptake.","null","null","2022-10-19","Molecular Imaging and Radionuclide Therapy","Molecular Imaging and Radionuclide Therapy","Vol.31","No.3","239","241","eng","true","null","scientific_journal","null","null","10.4274/mirt.galenos.2021.54775","2146-1414","null","null","null","null","null" "A case of papillary thyroid carcinoma with renal and pulmonary metastases","A case of papillary thyroid carcinoma with renal and pulmonary metastases","Mariko Aoyama, Tomohiro Inui, Naoki Miyamoto, Shin-ichi Sakamoto, Seiya Inoue, Satoshi Fujiwara, Masakazu Goto, Hiroaki Toba, Hiromitsu Takizawa","Mariko Aoyama, Tomohiro Inui, Naoki Miyamoto, Shin-ichi Sakamoto, Seiya Inoue, Satoshi Fujiwara, Masakazu Goto, Hiroaki Toba, Hiromitsu Takizawa","null","Distant metastases derived from papillary carcinoma are generally detected in the lungs and bones. However, renal metastasis is rare. We herein report a case of papillary thyroid carcinoma with renal and pulmonary metastases that had been initially diagnosed as primary renal carcinoma with pulmonary metastases. The lesions showed response to immune checkpoint inhibitors and tyrosine kinase inhibitor but not to radioactive iodine therapy.","Distant metastases derived from papillary carcinoma are generally detected in the lungs and bones. However, renal metastasis is rare. We herein report a case of papillary thyroid carcinoma with renal and pulmonary metastases that had been initially diagnosed as primary renal carcinoma with pulmonary metastases. The lesions showed response to immune checkpoint inhibitors and tyrosine kinase inhibitor but not to radioactive iodine therapy.","null","null","2022-08-13","Journal of Surgical Case Reports","Journal of Surgical Case Reports","Vol.2022","No.8","rjac366","rjac366","eng","true","null","scientific_journal","null","null","10.1093/jscr/rjac366","2042-8812","null","null","null","null","null" "Axillary lymphangioma that developed following COVID-19 vaccination: a case report","Axillary lymphangioma that developed following COVID-19 vaccination: a case report","Souichiro Sasa, Hiroaki Inoue, INUI Tomohiro, Naoki Miyamoto, Mariko Aoyama, Kazumasa Okumura, Hiroaki Toba, Takahiro Yoshida, Tezuka Miki, Hirose Chieko, Yasuyo Saijo, Hisanori Uehara, Izumori Ayumi, Takahashi Masako, Sasa Mitsunori, Hiromitsu Takizawa","Souichiro Sasa, Hiroaki Inoue, INUI Tomohiro, Naoki Miyamoto, Mariko Aoyama, Kazumasa Okumura, Hiroaki Toba, Takahiro Yoshida, Tezuka Miki, Hirose Chieko, Yasuyo Saijo, Hisanori Uehara, Izumori Ayumi, Takahashi Masako, Sasa Mitsunori, Hiromitsu Takizawa","null","Extensive vaccination programs are being implemented worldwide for coronavirus disease 2019 (COVID-19). With the spread of vaccination, swelling of the lymph nodes after vaccination is frequently seen. We encountered a patient who developed left axillary lymphadenoma following vaccine administration. The patient was a Japanese woman in her 80 s who had previously undergone surgery for right breast cancer. She received two injections of the Pfizer-BioNTech COVID-19 vaccine in her left arm. Approximately 3 months later, she complained of left axillary swelling, and imaging resulted in a diagnosis of left axillary lymphangioma. In accordance with the patient's wishes, we performed axillary mass resection. The pathological diagnosis was lymphangioma. Our examination findings indicated that congestion of the axillary lymph vessels might have been caused by upper-arm injections of the COVID-19 vaccine.","Extensive vaccination programs are being implemented worldwide for coronavirus disease 2019 (COVID-19). With the spread of vaccination, swelling of the lymph nodes after vaccination is frequently seen. We encountered a patient who developed left axillary lymphadenoma following vaccine administration. The patient was a Japanese woman in her 80 s who had previously undergone surgery for right breast cancer. She received two injections of the Pfizer-BioNTech COVID-19 vaccine in her left arm. Approximately 3 months later, she complained of left axillary swelling, and imaging resulted in a diagnosis of left axillary lymphangioma. In accordance with the patient's wishes, we performed axillary mass resection. The pathological diagnosis was lymphangioma. Our examination findings indicated that congestion of the axillary lymph vessels might have been caused by upper-arm injections of the COVID-19 vaccine.","null","null","2022-07-08","Surgical Case Reports","Surgical Case Reports","Vol.8","No.1","131","131","eng","true","null","scientific_journal","null","null","10.1186/s40792-022-01488-5","2198-7793","null","null","null","null","null" "Diversity of lymphatic flow in patients with lung cancer revealed by computed tomography lymphography","Diversity of lymphatic flow in patients with lung cancer revealed by computed tomography lymphography","Yukikiyo Kawakami, Hiromitsu Takizawa, Hiroaki Toba, Naoya Kawakita, Mitsuteru Yoshida, Kazuya Kondo, Akira Tangoku","Yukikiyo Kawakami, Hiromitsu Takizawa, Hiroaki Toba, Naoya Kawakita, Mitsuteru Yoshida, Kazuya Kondo, Akira Tangoku","null","This study was conducted to verify the optimal extent of lymph node dissection or sampling during lung cancer surgery based on the sentinel node (SN) map created by computed tomography (CT) lymphography. From April 2010 to January 2015, patients with clinical stage I non-small-cell lung cancer, who were candidates for lobectomy or segmentectomy with standard hilar and mediastinal lymph node dissection, and in whom bronchus reached the tumour, were enrolled. An ultrathin bronchoscope was inserted to the target bronchus under the guidance of virtual bronchoscopic navigation images. CT images of the chest were obtained 30 s after 2.5 ml of iopamidol was injected. SNs were identified when the maximum CT attenuation value of the lymph nodes on postcontrast CT images increased by 30 Hounsfield units or more compared with the precontrast images. Patients underwent lobectomy with standard lymph node dissection. SNs were identified in 36 (87.8%) of the 41 patients. The average number of SNs was 1.6 (range, 1-4). There was 1 false negative case; therefore, the accuracy of SN identification was 97.2% (35/36). In 5 (13.9%) of 36 patients, SNs were outside the lobe-specific lymph node station range (#11i from right S1, #7 from right S1, #4R from right S8, #12u from right S8, #7 and #12l from left S1 + 2). CT lymphography demonstrated the diversity of lymphatic spreading patterns and there were cases in which lymph flows are found outside the lymph node dissection range.","This study was conducted to verify the optimal extent of lymph node dissection or sampling during lung cancer surgery based on the sentinel node (SN) map created by computed tomography (CT) lymphography. From April 2010 to January 2015, patients with clinical stage I non-small-cell lung cancer, who were candidates for lobectomy or segmentectomy with standard hilar and mediastinal lymph node dissection, and in whom bronchus reached the tumour, were enrolled. An ultrathin bronchoscope was inserted to the target bronchus under the guidance of virtual bronchoscopic navigation images. CT images of the chest were obtained 30 s after 2.5 ml of iopamidol was injected. SNs were identified when the maximum CT attenuation value of the lymph nodes on postcontrast CT images increased by 30 Hounsfield units or more compared with the precontrast images. Patients underwent lobectomy with standard lymph node dissection. SNs were identified in 36 (87.8%) of the 41 patients. The average number of SNs was 1.6 (range, 1-4). There was 1 false negative case; therefore, the accuracy of SN identification was 97.2% (35/36). In 5 (13.9%) of 36 patients, SNs were outside the lobe-specific lymph node station range (#11i from right S1, #7 from right S1, #4R from right S8, #12u from right S8, #7 and #12l from left S1 + 2). CT lymphography demonstrated the diversity of lymphatic spreading patterns and there were cases in which lymph flows are found outside the lymph node dissection range.","null","null","2021-11-22","Interactive Cardiovascular and Thoracic Surgery","Interactive Cardiovascular and Thoracic Surgery","Vol.33","No.6","871","878","eng","true","null","scientific_journal","null","null","10.1093/icvts/ivab204","1569-9285","null","null","null","null","null" "XB130 deficiency causes congenital hypothyroidism in mice due to disorganized apical membrane structure and function of thyrocytes","XB130 deficiency causes congenital hypothyroidism in mice due to disorganized apical membrane structure and function of thyrocytes","Yingchun Wang, Hiroki Shimizu, Yun-Yan Xiang, Junichi Sugihara, Wei-Yang Lu, Xiao-Hui Liao, Hae-Ra Cho, 鳥羽 博明, Xiao-Hui Bai, Sylvia L Asa, Peter Arvan, Samuel Refetoff, Mingyao Liu","Yingchun Wang, Hiroki Shimizu, Yun-Yan Xiang, Junichi Sugihara, Wei-Yang Lu, Xiao-Hui Liao, Hae-Ra Cho, Hiroaki Toba, Xiao-Hui Bai, Sylvia L Asa, Peter Arvan, Samuel Refetoff, Mingyao Liu","null","Congenital hypothyroidism is often caused by genetic mutations that impair thyroid hormone (TH) production, resulting in growth and development defects. XB130 (actin filament associated protein 1 like 2) is an adaptor/scaffold protein that plays important roles in cell proliferation, migration, intracellular signal transduction, and tumorigenesis. It is highly expressed in thyrocytes, however, its function in the thyroid remains largely unexplored. mice and their littermates were studied. Postnatal growth and growth hormone levels were measured, and responses to low or high-iodine diet, and levothyroxine treatment were examined. TH and thyrotropin in the serum and TH in the thyroid glands were quantified. Structure and function of thyrocytes in embryos and postnatal life were studied with histology, immunohistochemistry, immunofluorescence staining, Western blotting, and quantitative reverse transcription polymerase chain reaction. mice exhibited transient growth retardation postnatally, due to congenital hypothyroidism with reduced TH synthesis and secretion, which could be rescued by exogenous thyroxine supplementation. The thyroid glands of mice displayed diminished thyroglobulin iodination and release at both embryonic and early postnatal stages. XB130 was found mainly on the apical membrane of thyroid follicles. Thyroid glands of embryonic and postnatal mice exhibited disorganized apical membrane structure, delayed folliculogenesis, and abnormal formation of thyroid follicle lumina. XB130 critically regulates folliculogenesis by maintaining apical membrane structure and function of thyrocytes, and its deficiency leads to congenital hypothyroidism.","Congenital hypothyroidism is often caused by genetic mutations that impair thyroid hormone (TH) production, resulting in growth and development defects. XB130 (actin filament associated protein 1 like 2) is an adaptor/scaffold protein that plays important roles in cell proliferation, migration, intracellular signal transduction, and tumorigenesis. It is highly expressed in thyrocytes, however, its function in the thyroid remains largely unexplored. mice and their littermates were studied. Postnatal growth and growth hormone levels were measured, and responses to low or high-iodine diet, and levothyroxine treatment were examined. TH and thyrotropin in the serum and TH in the thyroid glands were quantified. Structure and function of thyrocytes in embryos and postnatal life were studied with histology, immunohistochemistry, immunofluorescence staining, Western blotting, and quantitative reverse transcription polymerase chain reaction. mice exhibited transient growth retardation postnatally, due to congenital hypothyroidism with reduced TH synthesis and secretion, which could be rescued by exogenous thyroxine supplementation. The thyroid glands of mice displayed diminished thyroglobulin iodination and release at both embryonic and early postnatal stages. XB130 was found mainly on the apical membrane of thyroid follicles. Thyroid glands of embryonic and postnatal mice exhibited disorganized apical membrane structure, delayed folliculogenesis, and abnormal formation of thyroid follicle lumina. XB130 critically regulates folliculogenesis by maintaining apical membrane structure and function of thyrocytes, and its deficiency leads to congenital hypothyroidism.","null","null","2021-11","Thyroid","Thyroid","Vol.31","No.11","1650","1661","jpn","true","null","scientific_journal","null","null","10.1089/thy.2021.0195","1557-9077","null","null","null","null","null" "GHSR methylation-dependent expression of a variant ligand and receptor of the ghrelin system induces thymoma tumorigenesis","GHSR methylation-dependent expression of a variant ligand and receptor of the ghrelin system induces thymoma tumorigenesis","Bilguun Tegshee, Kazuya Kondo, Shiho Soejima, Kyoka Muguruma, Mitsuhiro Tsuboi, Koichiro Kajiura, Yukikiyo Kawakami, Naoya Kawakita, Hiroaki Toba, Mitsuteru Yoshida, Hiromitsu Takizawa, Akira Tangoku","Bilguun Tegshee, Kazuya Kondo, Shiho Soejima, Kyoka Muguruma, Mitsuhiro Tsuboi, Koichiro Kajiura, Yukikiyo Kawakami, Naoya Kawakita, Hiroaki Toba, Mitsuteru Yoshida, Hiromitsu Takizawa, Akira Tangoku","null","Our previous study reported that the DNA methylation of growth hormone secretagogue receptor () was significantly higher in thymoma or thymic carcinoma (TC) than in normal thymic tissue samples. Thymic epithelial tumors (TETs) with higher DNA methylation were associated with significantly worse prognosis than those with lower levels of DNA methylation. Diversified components of the ghrelin- axis may exert opposing effects in cancer progression, depending on the cancer type in question. However, the precise function of the axis remains unclear. In the present study, the mRNA expression of five key components of the ghrelin system [native ligand ghrelin, variant ligand In-1 ghrelin, native receptor GHSR1a, variant receptor GHSR1b and acylation enzyme ghrelin O-acyltransferase (GOAT)] were examined in 58 TET samples by reverse transcription-quantitative PCR, and protein expression of GHSR1a and GHSR1b was assessed in 20 TETs using immunohistochemistry. The results revealed that In-1 ghrelin, GHSR1b (variant forms) and GOAT were more strongly expressed in thymoma compared with thymic-adjacent tissue. By contrast, no significant differences were observed in the expression of ghrelin and GHSR1a (native forms) between thymoma and thymic tissue. The mRNA expression of In-1 ghrelin and GHSR1b (variant forms) was positively associated with methylation in thymoma tissue samples. However, a relationship was not found between ghrelin, GHSR1a or GOAT expression (native forms) and methylation in thymoma. Immunohistochemical analysis revealed that mRNA expression of GHSR1a and GHSR1b generally correlated with expression of the corresponding protein, and that the expression of GHSR1b was increased in advanced-stage TETs. These results indicate that the DNA methylation of is associated with a shift from native expression (ghrelin and GHSR1a) to variant expression (In-1 ghrelin and GHSR1b), which induces the tumorigenesis of thymoma, but not TC.","Our previous study reported that the DNA methylation of growth hormone secretagogue receptor () was significantly higher in thymoma or thymic carcinoma (TC) than in normal thymic tissue samples. Thymic epithelial tumors (TETs) with higher DNA methylation were associated with significantly worse prognosis than those with lower levels of DNA methylation. Diversified components of the ghrelin- axis may exert opposing effects in cancer progression, depending on the cancer type in question. However, the precise function of the axis remains unclear. In the present study, the mRNA expression of five key components of the ghrelin system [native ligand ghrelin, variant ligand In-1 ghrelin, native receptor GHSR1a, variant receptor GHSR1b and acylation enzyme ghrelin O-acyltransferase (GOAT)] were examined in 58 TET samples by reverse transcription-quantitative PCR, and protein expression of GHSR1a and GHSR1b was assessed in 20 TETs using immunohistochemistry. The results revealed that In-1 ghrelin, GHSR1b (variant forms) and GOAT were more strongly expressed in thymoma compared with thymic-adjacent tissue. By contrast, no significant differences were observed in the expression of ghrelin and GHSR1a (native forms) between thymoma and thymic tissue. The mRNA expression of In-1 ghrelin and GHSR1b (variant forms) was positively associated with methylation in thymoma tissue samples. However, a relationship was not found between ghrelin, GHSR1a or GOAT expression (native forms) and methylation in thymoma. Immunohistochemical analysis revealed that mRNA expression of GHSR1a and GHSR1b generally correlated with expression of the corresponding protein, and that the expression of GHSR1b was increased in advanced-stage TETs. These results indicate that the DNA methylation of is associated with a shift from native expression (ghrelin and GHSR1a) to variant expression (In-1 ghrelin and GHSR1b), which induces the tumorigenesis of thymoma, but not TC.","null","null","2021-09-17","Oncology Letters","Oncology Letters","Vol.22","No.5","793","793","eng","true","null","scientific_journal","null","null","10.3892/ol.2021.13054","1792-1082","null","null","null","null","null" "HER2陽性乳癌患者における術前化学療法開始前の総リンパ球数は予後予測の指標となり得る","HER2陽性乳癌患者における術前化学療法開始前の総リンパ球数は予後予測の指標となり得る","宮本 直輝, 井上 寛章, 乾 友浩, 笹 聡一郎, 青山 万理子, 鳥羽 博明, 奥村 和正, 吉田 卓弘, 滝沢 宏光, 丹黒 章","宮本 直輝, Hiroaki Inoue, INUI Tomohiro, Soichiroh Sasa, Mariko Aoyama, Hiroaki Toba, Kazumasa Okumura, Takahiro Yoshida, Hiromitsu Takizawa, Akira Tangoku","null","Purpose : Several studies have shown that peripheral hematologic parameters, such as the absolute lymphocyte count(ALC)and neutrophil to lymphocyte ratio(NLR)can predict the prognosis for malignant tumor. We investigated the relation of these parameter and prognosis before neoadjuvant chemotherapy for human epidermal growth factor receptor-2(HER2)-positive breast cancer patients. Methods : From April 2009 to March 2019, 85 patients diagnosed with HER2‐positive breast cancer and treated with trastuzumab-based neoadjuvant chemotherapy were included in this retrospective cohort study. The optimal cut-off for the NLR and ALC was identified using the receiver operating characteristic(ROC)curve analysis and Youden's index. Results : The median age of patients at the start of treatment was 58.9(range 32‐81)years. The median follow-up time for HER2-positive breast cancer patients was 52.0(range:9.8‐114.3)months. In this period, 11 patients developed recurrence. The low-ALC group showed better disease free survival than the high-ALC group(p=0.0482). There was no significant difference in disease free survival between the low- and high-NLR groups. Conclusion : ALC before neoadjuvant chemotherapy may be a predictor of prolonged disease free survival in HER2‐positive breast cancer patients.","Purpose : Several studies have shown that peripheral hematologic parameters, such as the absolute lymphocyte count(ALC)and neutrophil to lymphocyte ratio(NLR)can predict the prognosis for malignant tumor. We investigated the relation of these parameter and prognosis before neoadjuvant chemotherapy for human epidermal growth factor receptor-2(HER2)-positive breast cancer patients. Methods : From April 2009 to March 2019, 85 patients diagnosed with HER2‐positive breast cancer and treated with trastuzumab-based neoadjuvant chemotherapy were included in this retrospective cohort study. The optimal cut-off for the NLR and ALC was identified using the receiver operating characteristic(ROC)curve analysis and Youden's index. Results : The median age of patients at the start of treatment was 58.9(range 32‐81)years. The median follow-up time for HER2-positive breast cancer patients was 52.0(range:9.8‐114.3)months. In this period, 11 patients developed recurrence. The low-ALC group showed better disease free survival than the high-ALC group(p=0.0482). There was no significant difference in disease free survival between the low- and high-NLR groups. Conclusion : ALC before neoadjuvant chemotherapy may be a predictor of prolonged disease free survival in HER2‐positive breast cancer patients.","null","null","2021-08-25","四国医学雑誌","Shikoku Acta Medica","Vol.77","No.3,4","131","136","jpn","true","null","scientific_journal","null","null","null","0037-3699","null","http://repo.lib.tokushima-u.ac.jp/116396","null","null","null" "Hypervascularized bronchial arteries as a risk factor for intraoperative bleeding and prolonged surgery","Hypervascularized bronchial arteries as a risk factor for intraoperative bleeding and prolonged surgery","Hiromitsu Takizawa, Naoki Miyamoto, Shinichi Sakamoto, Mika Takashima, Daisuke Matsumoto, Naoya Kawakita, Hiroaki Toba, Yukikiyo Kawakami, Mitsuteru Yoshida, Kazuya Kondo, Akira Tangoku","Hiromitsu Takizawa, Naoki Miyamoto, Shinichi Sakamoto, Mika Takashima, Daisuke Matsumoto, Naoya Kawakita, Hiroaki Toba, Yukikiyo Kawakami, Mitsuteru Yoshida, Kazuya Kondo, Akira Tangoku","null","The present study investigated whether highly vascularized bronchial arteries affect the intraoperative blood loss and the operative time of video-assisted thoracic surgery (VATS) lobectomy for patients with non-small cell lung cancer. We retrospectively collected data on consecutive pathological stage I to IIIA non-small cell lung cancer patients who underwent VATS lobectomy with systematic lymph node dissection between January 2017 and December 2019. Patients were divided into the following two groups according to bronchial artery diameters on preoperative enhanced contrast computed tomography (CT) findings: ≤2 and >2 mm groups. Among the 175 patients enrolled, risk factors for intraoperative blood loss >50 mL were being male (P=0.005), a history of smoking (P=0.01), percent forced expiratory volume in 1 s (FEV1.0%) <70% (P=0.012), squamous cell carcinoma (P=0.049), and a bronchial artery diameter >2.0 mm (P<0.001) in the unadjusted analysis, and a bronchial artery diameter >2.0 mm (P<0.001) in the multivariable analysis. Risk factors for an operative time >200 min were being male (P<0.001), a history of smoking (P=0.007), FEV1.0% <70% (P=0.011), squamous cell carcinoma (P=0.046), a bronchial artery diameter >2.0 mm (P<0.001), and experience of surgeon <10 years (P=0.011) in the unadjusted analysis, and being male (P=0.047), a bronchial artery diameter >2.0 mm (P=0.024), and experience of surgeon <10 years (P=0.047) in the multivariable analysis. Bronchial artery diameter was the most important risk factor of intraoperative bleeding and prolonged operative time during VATS lobectomy.","The present study investigated whether highly vascularized bronchial arteries affect the intraoperative blood loss and the operative time of video-assisted thoracic surgery (VATS) lobectomy for patients with non-small cell lung cancer. We retrospectively collected data on consecutive pathological stage I to IIIA non-small cell lung cancer patients who underwent VATS lobectomy with systematic lymph node dissection between January 2017 and December 2019. Patients were divided into the following two groups according to bronchial artery diameters on preoperative enhanced contrast computed tomography (CT) findings: ≤2 and >2 mm groups. Among the 175 patients enrolled, risk factors for intraoperative blood loss >50 mL were being male (P=0.005), a history of smoking (P=0.01), percent forced expiratory volume in 1 s (FEV1.0%) <70% (P=0.012), squamous cell carcinoma (P=0.049), and a bronchial artery diameter >2.0 mm (P<0.001) in the unadjusted analysis, and a bronchial artery diameter >2.0 mm (P<0.001) in the multivariable analysis. Risk factors for an operative time >200 min were being male (P<0.001), a history of smoking (P=0.007), FEV1.0% <70% (P=0.011), squamous cell carcinoma (P=0.046), a bronchial artery diameter >2.0 mm (P<0.001), and experience of surgeon <10 years (P=0.011) in the unadjusted analysis, and being male (P=0.047), a bronchial artery diameter >2.0 mm (P=0.024), and experience of surgeon <10 years (P=0.047) in the multivariable analysis. Bronchial artery diameter was the most important risk factor of intraoperative bleeding and prolonged operative time during VATS lobectomy.","null","null","2021-08","Journal of Thoracic Disease","Journal of Thoracic Disease","Vol.13","No.8","4731","4741","eng","true","null","scientific_journal","null","null","10.21037/jtd-21-616","2072-1439","null","null","null","null","null" "Diagnosis of visceral pleural invasion using confocal laser endomicroscopy during lung cancer surgery","Diagnosis of visceral pleural invasion using confocal laser endomicroscopy during lung cancer surgery","Toru Sawada, Hiromitsu Takizawa, Mariko Aoyama, Naoya Kawakita, Naoki Miyamoto, Shinichi Sakamoto, Mika Takashima, Daisuke Matsumoto, Hiroaki Toba, Yukikiyo Kawakami, Mitsuteru Yoshida, Kazuya Kondo, Akira Tangoku","Toru Sawada, Hiromitsu Takizawa, Mariko Aoyama, Naoya Kawakita, Naoki Miyamoto, Shinichi Sakamoto, Mika Takashima, Daisuke Matsumoto, Hiroaki Toba, Yukikiyo Kawakami, Mitsuteru Yoshida, Kazuya Kondo, Akira Tangoku","null","Visceral pleural invasion (VPI) in lung cancer is a significant prognostic factor; however, it is difficult to diagnose preoperatively or intraoperatively. In this study, we examined the possibility of intraoperative diagnosis of VPI using confocal laser endomicroscopy (CLE). Among patients with primary lung cancer who underwent surgery between April 2018 and August 2019, those in whom the tumor was in contact with the pleura on chest computed tomography and whose pleural changes were intraoperatively confirmed were enrolled in this study. In the 35 patients who underwent lung resection (6 cases with visceral pleural infiltration), the area where pleural change was noted was observed and a short video was recorded using CLE. Based on the video images, three evaluators determined the defect ratio (0%, 25%, 50%, 75%, and 100%) of the autofluorescence-positive structure. The area under the receiver operating characteristic curve was used to evaluate the diagnostic performance for VPI. In 15 cases (3 cases with VPI), a validation study was performed for intraoperative VPI according to the cutoff value of the defect ratio of the autofluorescence-positive structure. The areas under the receiver operating characteristic curve for the defect ratio of the autofluorescence-positive structure were 0.86-0.91 for the three readers. Using defect ratio of autofluorescence-positive structure cutoff of ≥50% as predictor of VPI, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 83.3-100.0%, 57.7-73.1%, 35.3-41.7%, 95.0-100.0%, and 75.0-78.1%, respectively, for the three readers. In the validation study, the sensitivity was 100%, the specificity was 83.3%, and the diagnostic accuracy rate was 86.7%. The diagnosis of VPI through CLE is simple, non-invasive, and has high diagnostic accuracy rates. This method may be applicable for determining surgical procedures.","Visceral pleural invasion (VPI) in lung cancer is a significant prognostic factor; however, it is difficult to diagnose preoperatively or intraoperatively. In this study, we examined the possibility of intraoperative diagnosis of VPI using confocal laser endomicroscopy (CLE). Among patients with primary lung cancer who underwent surgery between April 2018 and August 2019, those in whom the tumor was in contact with the pleura on chest computed tomography and whose pleural changes were intraoperatively confirmed were enrolled in this study. In the 35 patients who underwent lung resection (6 cases with visceral pleural infiltration), the area where pleural change was noted was observed and a short video was recorded using CLE. Based on the video images, three evaluators determined the defect ratio (0%, 25%, 50%, 75%, and 100%) of the autofluorescence-positive structure. The area under the receiver operating characteristic curve was used to evaluate the diagnostic performance for VPI. In 15 cases (3 cases with VPI), a validation study was performed for intraoperative VPI according to the cutoff value of the defect ratio of the autofluorescence-positive structure. The areas under the receiver operating characteristic curve for the defect ratio of the autofluorescence-positive structure were 0.86-0.91 for the three readers. Using defect ratio of autofluorescence-positive structure cutoff of ≥50% as predictor of VPI, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 83.3-100.0%, 57.7-73.1%, 35.3-41.7%, 95.0-100.0%, and 75.0-78.1%, respectively, for the three readers. In the validation study, the sensitivity was 100%, the specificity was 83.3%, and the diagnostic accuracy rate was 86.7%. The diagnosis of VPI through CLE is simple, non-invasive, and has high diagnostic accuracy rates. This method may be applicable for determining surgical procedures.","null","null","2021-08","Journal of Thoracic Disease","Journal of Thoracic Disease","Vol.13","No.8","4742","4752","eng","true","null","scientific_journal","null","null","10.21037/jtd-21-137","2072-1439","null","null","null","null","null" "GAD1 expression and its methylation as indicators of malignant behavior in thymic epithelial tumors","GAD1 expression and its methylation as indicators of malignant behavior in thymic epithelial tumors","Shiho Soejima, Kazuya Kondo, Mitsuhiro Tsuboi, Kyoka Muguruma, B Tegshee, Yukikiyo Kawakami, Koichiro Kajiura, Naoya Kawakita, Hiroaki Toba, Mitsuteru Yoshida, Hiromitsu Takizawa, Akira Tangoku","Shiho Soejima, Kazuya Kondo, Mitsuhiro Tsuboi, Kyoka Muguruma, B Tegshee, Yukikiyo Kawakami, Koichiro Kajiura, Naoya Kawakita, Hiroaki Toba, Mitsuteru Yoshida, Hiromitsu Takizawa, Akira Tangoku","null","Thymic epithelial tumors (TETs) comprise thymomas and thymic carcinoma (TC). TC has more aggressive features and a poorer prognosis than thymomas. Genetic and epigenetic alterations in thymomas and TC have been investigated in an attempt to identify novel target molecules for TC. In the present study, genome-wide screening was performed on aberrantly methylated CpG islands in thymomas and TC, and the glutamate decarboxylase 1 gene () was identified as the 4th significantly hypermethylated CpG island in TC compared with thymomas. catalyzes the production of γ-aminobutyric acid from L-glutamic acid. expression is abundant in the brain but rare in other tissues, including the thymus. A total of 73 thymomas and 17 TC tissues were obtained from 90 patients who underwent surgery or biopsy at Tokushima University Hospital between 1990 and 2017. DNA methylation was examined by bisulfite pyrosequencing, and the mRNA and protein expression levels of were analyzed using reverse transcription-quantitative PCR and immunohistochemistry, respectively. The DNA methylation levels of were significantly higher in TC tissues than in the normal thymus and thymoma tissues, and methylation exhibited high sensitivity and specificity for discriminating between TC and thymoma. The mRNA and protein expression levels of were significantly higher in TC tissues than in thymomas. Patients with TET with high DNA hypermethylation and high mRNA and protein expression levels had significantly shorter relapse-free survival rates than those with low levels. In conclusion, significantly more epigenetic alterations were observed in TC tissues compared with in thymomas, which may contribute to the clinical features and prognosis of patients.","Thymic epithelial tumors (TETs) comprise thymomas and thymic carcinoma (TC). TC has more aggressive features and a poorer prognosis than thymomas. Genetic and epigenetic alterations in thymomas and TC have been investigated in an attempt to identify novel target molecules for TC. In the present study, genome-wide screening was performed on aberrantly methylated CpG islands in thymomas and TC, and the glutamate decarboxylase 1 gene () was identified as the 4th significantly hypermethylated CpG island in TC compared with thymomas. catalyzes the production of γ-aminobutyric acid from L-glutamic acid. expression is abundant in the brain but rare in other tissues, including the thymus. A total of 73 thymomas and 17 TC tissues were obtained from 90 patients who underwent surgery or biopsy at Tokushima University Hospital between 1990 and 2017. DNA methylation was examined by bisulfite pyrosequencing, and the mRNA and protein expression levels of were analyzed using reverse transcription-quantitative PCR and immunohistochemistry, respectively. The DNA methylation levels of were significantly higher in TC tissues than in the normal thymus and thymoma tissues, and methylation exhibited high sensitivity and specificity for discriminating between TC and thymoma. The mRNA and protein expression levels of were significantly higher in TC tissues than in thymomas. Patients with TET with high DNA hypermethylation and high mRNA and protein expression levels had significantly shorter relapse-free survival rates than those with low levels. In conclusion, significantly more epigenetic alterations were observed in TC tissues compared with in thymomas, which may contribute to the clinical features and prognosis of patients.","null","null","2021-04-21","Oncology Letters","Oncology Letters","Vol.21","No.6","483","483","eng","true","null","scientific_journal","null","null","10.3892/ol.2021.12744","1792-1074","null","null","null","null","null" "Endobronchial Ultrasound Improves the Diagnosis of the Tracheobronchial Invasion of Advanced Esophageal Cancer","Endobronchial Ultrasound Improves the Diagnosis of the Tracheobronchial Invasion of Advanced Esophageal Cancer","Takeshi Nishino, Hiroaki Toba, Takahiro Yoshida, Seiya Inoue, Masakazu Goto, Naoya Kawakita, Hiromitsu Takizawa, Yoshihiro Tsuruo, Akira Tangoku","Takeshi Nishino, Hiroaki Toba, Takahiro Yoshida, Seiya Inoue, Masakazu Goto, Naoya Kawakita, Hiromitsu Takizawa, Yoshihiro Tsuruo, Akira Tangoku","null","Accurate diagnosis of the tracheobronchial invasion of advanced esophageal cancer is essential to select appropriate treatment and improve prognosis; however, it is difficult using the conventional modalities. This study aimed to clarify the diagnostic usefulness of convex probe endobronchial ultrasound (CP-EBUS) for the diagnosis of the tracheobronchial invasion of advanced esophageal cancer. We conducted a cadaveric study to clarify the changes in ultrasonic and histopathologic findings in the esophageal tumor and tracheal invasion models. Additionally, we examined CP-EBUS for patients with advanced thoracic esophageal cancer in whom tracheobronchial invasion was suspected on contrast-enhanced computed tomography (CE-CT) scan. We retrospectivity evaluated the diagnosis of CP-EBUS, comparing the pathological findings and treatment outcomes. Cadaveric esophageal tumor and tracheal invasion models showed the disappearance of the third layer observed with CP-EBUS and histologically proven interruption of the adventitia. This indicated that the third layer corresponded with the tracheal adventitia. We examined 40 patients with advanced thoracic esophageal cancer in whom tracheobronchial invasion was suspected. The precise diagnosis was pathologically confirmed in 9 of 14 patients diagnosed with cT3 who underwent radical surgery. 20 of 26 cases diagnosed with cT4b received definitive chemoradiotherapy, and 4 cases received salvage surgery and pathologically confirmed precise diagnosis. CP-EBUS is extremely useful for diagnosing the tracheobronchial invasion of advanced esophageal cancer. It could be an effective modality for determining treatment strategies in cases with a marginal surgical indication.","Accurate diagnosis of the tracheobronchial invasion of advanced esophageal cancer is essential to select appropriate treatment and improve prognosis; however, it is difficult using the conventional modalities. This study aimed to clarify the diagnostic usefulness of convex probe endobronchial ultrasound (CP-EBUS) for the diagnosis of the tracheobronchial invasion of advanced esophageal cancer. We conducted a cadaveric study to clarify the changes in ultrasonic and histopathologic findings in the esophageal tumor and tracheal invasion models. Additionally, we examined CP-EBUS for patients with advanced thoracic esophageal cancer in whom tracheobronchial invasion was suspected on contrast-enhanced computed tomography (CE-CT) scan. We retrospectivity evaluated the diagnosis of CP-EBUS, comparing the pathological findings and treatment outcomes. Cadaveric esophageal tumor and tracheal invasion models showed the disappearance of the third layer observed with CP-EBUS and histologically proven interruption of the adventitia. This indicated that the third layer corresponded with the tracheal adventitia. We examined 40 patients with advanced thoracic esophageal cancer in whom tracheobronchial invasion was suspected. The precise diagnosis was pathologically confirmed in 9 of 14 patients diagnosed with cT3 who underwent radical surgery. 20 of 26 cases diagnosed with cT4b received definitive chemoradiotherapy, and 4 cases received salvage surgery and pathologically confirmed precise diagnosis. CP-EBUS is extremely useful for diagnosing the tracheobronchial invasion of advanced esophageal cancer. It could be an effective modality for determining treatment strategies in cases with a marginal surgical indication.","null","null","2021-04-07","Annals of Surgical Oncology","Annals of Surgical Oncology","Vol.28","No.11","6398","6406","eng","true","null","scientific_journal","null","null","10.1245/s10434-021-09912-0","1534-4681","null","null","null","null","null" "気管支鏡の破損を分析する","Analyzing Bronchoscopic Damage","澤田 徹, 吉田 光輝, 梶浦 耕一郎, 河北 直也, 坪井 光弘, 鳥羽 博明, 川上 行奎, 滝沢 宏光, 近藤 和也, 丹黒 章","Toru Sawada, Mitsuteru Yoshida, Koichiro Kajiura, Naoya Kawakita, Mitsuhiro Tsuboi, Hiroaki Toba, Yukikiyo Kawakami, Hiromitsu Takizawa, Kazuya Kondo, Akira Tangoku","null","
背景.気管支鏡は超音波内視鏡,ステント,気管支充填術,また当科においては,術前コイルマーキングなど,様々な手技に使用されている.同時に,気管支鏡操作も複雑になり,様々な外力がかかることで破損が起こりやすくなる.気管支鏡の故障は医療経済面での不利益のみならず,合併症発生の増加や,修理期間中の検査・治療が中断されることによる患者側の不利益につながる.目的.当院で経験した気管支鏡の破損について検討し,その原因について探求し,今後の予防策や注意点に関して検討する.方法.2015年1月から2017年11月において当科で気管支鏡検査を施行した246例のうち,気管支鏡修理状況について,気管支鏡の種類や破損原因,修理費などについて検討した.結果.246例中3例(4本)の破損を認め,破損率は1.2%であった.気管内レーザー焼灼術による破損の1例(2本)は,吸引鉗子口の先端の熱損傷による破損であった.生検による破損の1例は湾曲部の鉗子操作によるものであり,超音波気管支鏡の破損の1例は,穿刺針による湾曲部の損傷によるものであった.結論.全例が手技的な要因で発生しており,機器の構造の理解不足や手技の不安定さが原因であった.気管支鏡破損は,経済面や安全面,時間的損失に影響を及ぼす.破損を起こさないためには,手技の向上や気管支鏡構造の理解が必要である.我々が取り組む方策は,気管支鏡内部構造の特性の理解,安定した手技の取得に至る講習,教育を常に意識して実行することである.
","Background. Bronchoscopy is used in many procedures, such as endoscopic ultrasonography, tracheal stent placement, placement of Endobronchial Watanabe Spigots, and preoperative coil marking. However, bronchoscopy is a complicated procedure, and breakage can occur due to external forces. Bronchoscope breakage is associated with both adverse economic effects and patient-related consequences, since these devices are expensive and their breakage may increase the rates of complications and cause interruptions in examinations and treatments, if repairs are necessary. Purpose. We considered the causes of bronchoscope damage at our hospital in order to design future preventive measures and precautions. Method. We examined the bronchoscope type, their breakage status, and the repair costs for the 246 bronchoscopes in our department between January 2015 and November 2017. Result. A bronchoscope was damaged in 3 of the 246 cases, resulting in a damage rate of 1.2%. Damage to the bronchoscope occurred during yttrium-aluminium-garnet laser resection (n=2) because of thermal damage to the suction forceps port, during a right upper lobe biopsy (n=1) because of the forceps contacting the curved part, and during an endobronchial ultrasound lymph node biopsy because of damage to the tube caused by the puncture needle (n=1). Conclusion. All cases of breakage occurred secondary to technical factors owing to a lack of understanding of the structure of the bronchoscope and procedural instability. Bronchoscope damage increases expenses and procedural time while potentially reducing safety. The bronchoscopy procedure must be improved. Furthermore, practitioners should increase their understanding of the bronchoscope structure in order to prevent damage. Precautionary measures can be communicated through short lecture courses and education programs in order to increase practitioners' understanding of the internal structure of the bronchoscope and measures to increase procedural stability.
","null","null","2021-03-25","気管支学","The Journal of the Japan Society for Respiratory Endoscopy","Vol.43","No.2","91","96","jpn","true","null","scientific_journal","null","null","10.18907/jjsre.43.2_91","0287-2137","null","https://search.jamas.or.jp/link/ui/2022060328","null","null","null" "Cone-beam computed tomography versus computed tomography-guided ultrathin bronchoscopic diagnosis for peripheral pulmonary lesions: A propensity score-matched analysis","Cone-beam computed tomography versus computed tomography-guided ultrathin bronchoscopic diagnosis for peripheral pulmonary lesions: A propensity score-matched analysis","Naoya Kawakita, Hiromitsu Takizawa, Hiroaki Toba, Shinichi Sakamoto, Naoki Miyamoto, Daisuke Matsumoto, Mika Takashima, Mitsuhiro Tsuboi, Mitsuteru Yoshida, Yukikiyo Kawakami, Kazuya Kondo, Akira Tangoku","Naoya Kawakita, Hiromitsu Takizawa, Hiroaki Toba, Shinichi Sakamoto, Naoki Miyamoto, Daisuke Matsumoto, Mika Takashima, Mitsuhiro Tsuboi, Mitsuteru Yoshida, Yukikiyo Kawakami, Kazuya Kondo, Akira Tangoku","null","CBCT-guided TBB using a UTB under VBN is a useful method for the diagnosis of peripheral small pulmonary lesions. CBCT-guided TBB using UTB under VBN has been used as an alternative to CT-guided TBB. However, the advantage of CBCT-guided TBB using UTB under VBN over CT-guided TBB is still unknown. This study aimed to compare the diagnostic yield of CT-guided TBB and CBCT-guided TBB using a propensity score-matched analysis. Patients with peripheral pulmonary lesions ≤30 mm were included. Lesions whose bronchus could not be determined by CT were excluded. A UTB and biopsy forceps were advanced to the target bronchus under VBN, 2D-fluoroscopy and CT or CBCT. The CT-guided and CBCT-guided groups were matched for their propensity scores based on patient characteristics. We retrospectively reviewed 93 patients in the CT-guided group and 79 patients in the CBCT-guided group for this study. Furthermore, 48 distinct examination pairs were generated by propensity score matching. In the overall diagnostic yield, the CBCT-guided group showed better results (72.9%) than did the CT-guided group (47.9%) (P = 0.012). The median examination time lasted for 43 (IQR: 37-51) min in the CBCT-guided group and 50 (IQR: 43-62) min in the CT-guided group. The examination time in the CBCT-guided group was significantly shorter than that of the CT-guided group (P = 0.001). CBCT-guided TBB had a better diagnostic yield and shorter examination time than did CT-guided TBB.","CBCT-guided TBB using a UTB under VBN is a useful method for the diagnosis of peripheral small pulmonary lesions. CBCT-guided TBB using UTB under VBN has been used as an alternative to CT-guided TBB. However, the advantage of CBCT-guided TBB using UTB under VBN over CT-guided TBB is still unknown. This study aimed to compare the diagnostic yield of CT-guided TBB and CBCT-guided TBB using a propensity score-matched analysis. Patients with peripheral pulmonary lesions ≤30 mm were included. Lesions whose bronchus could not be determined by CT were excluded. A UTB and biopsy forceps were advanced to the target bronchus under VBN, 2D-fluoroscopy and CT or CBCT. The CT-guided and CBCT-guided groups were matched for their propensity scores based on patient characteristics. We retrospectively reviewed 93 patients in the CT-guided group and 79 patients in the CBCT-guided group for this study. Furthermore, 48 distinct examination pairs were generated by propensity score matching. In the overall diagnostic yield, the CBCT-guided group showed better results (72.9%) than did the CT-guided group (47.9%) (P = 0.012). The median examination time lasted for 43 (IQR: 37-51) min in the CBCT-guided group and 50 (IQR: 43-62) min in the CT-guided group. The examination time in the CBCT-guided group was significantly shorter than that of the CT-guided group (P = 0.001). CBCT-guided TBB had a better diagnostic yield and shorter examination time than did CT-guided TBB.","null","null","2021-02-21","Respirology","Respirology","Vol.26","No.5","477","484","eng","true","null","scientific_journal","null","null","10.1111/resp.14016","1440-1843","null","null","null","null","null" "Diagnosis of recurrence and follow-up using FDG-PET/CT for postoperative non-small-cell lung cancer patients","Diagnosis of recurrence and follow-up using FDG-PET/CT for postoperative non-small-cell lung cancer patients","Hiroaki Toba, Naoya Kawakita, Mika Takashima, Daisuke Matsumoto, Hiromitsu Takizawa, Hideki Otsuka, Akira Tangoku","Hiroaki Toba, Naoya Kawakita, Mika Takashima, Daisuke Matsumoto, Hiromitsu Takizawa, Hideki Otsuka, Akira Tangoku","null","There is currently no consensus regarding the best program for postoperative follow-up and surveillance after a curative resection for non-small-cell lung cancer (NSCLC) patients. We examined the diagnostic capability of F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for detecting recurrence in postoperative NSCLC patients, and we evaluated the results of postoperative surveillance using FDG-PET/CT in asymptomatic patients. Between 2005 and 2013, 496 FDG-PET/CT examinations were performed to detect recurrences for 187 NSCLC patients who had undergone potentially curative operations at our institution. Follow-up FDG-PET/CT was performed ≥ 1 × /year in principle in 172 asymptomatic patients without clinical or radiological evidence of recurrence, and the results were retrospectively reviewed. FDG-PET/CT correctly diagnosed recurrence in 46 of 47 (97.9%) patients and 68 of 69 (98.6%) recurrent sites. The following were obtained: 97.9% sensitivity, 97.1% specificity, 92.0% positive predictive value, 99.3% negative predictive value, and 97.3% accuracy. In six patients, other diseases were detected and treated appropriately. In asymptomatic patients, the detection rate of recurrence in the stage III group was significantly higher than the detection rates in the stage I and II groups, and FDG-PET/CT performed ≤ 3 years post-resection detected significantly more FDG-positive lesions compared to that performed after 4 years. FDG-PET/CT is very useful for detecting recurrence in NSCLC patients after a potentially curative operation. It might be sufficient to perform follow-up FDG-PET/CT until 3 years post-resection for advanced-stage patients. Further randomized clinical trials are needed to determine whether the early detection of recurrences leads to better prognoses.","There is currently no consensus regarding the best program for postoperative follow-up and surveillance after a curative resection for non-small-cell lung cancer (NSCLC) patients. We examined the diagnostic capability of F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for detecting recurrence in postoperative NSCLC patients, and we evaluated the results of postoperative surveillance using FDG-PET/CT in asymptomatic patients. Between 2005 and 2013, 496 FDG-PET/CT examinations were performed to detect recurrences for 187 NSCLC patients who had undergone potentially curative operations at our institution. Follow-up FDG-PET/CT was performed ≥ 1 × /year in principle in 172 asymptomatic patients without clinical or radiological evidence of recurrence, and the results were retrospectively reviewed. FDG-PET/CT correctly diagnosed recurrence in 46 of 47 (97.9%) patients and 68 of 69 (98.6%) recurrent sites. The following were obtained: 97.9% sensitivity, 97.1% specificity, 92.0% positive predictive value, 99.3% negative predictive value, and 97.3% accuracy. In six patients, other diseases were detected and treated appropriately. In asymptomatic patients, the detection rate of recurrence in the stage III group was significantly higher than the detection rates in the stage I and II groups, and FDG-PET/CT performed ≤ 3 years post-resection detected significantly more FDG-positive lesions compared to that performed after 4 years. FDG-PET/CT is very useful for detecting recurrence in NSCLC patients after a potentially curative operation. It might be sufficient to perform follow-up FDG-PET/CT until 3 years post-resection for advanced-stage patients. Further randomized clinical trials are needed to determine whether the early detection of recurrences leads to better prognoses.","null","null","2021","General Thoracic and Cardiovascular Surgery","General Thoracic and Cardiovascular Surgery","Vol.69","No.2","311","317","eng","true","null","scientific_journal","null","null","10.1007/s11748-020-01477-1","1863-6713","null","null","null","null","null" "Long-term outcomes of sentinel node identification using indocyanine green in patients with lung cancer","Long-term outcomes of sentinel node identification using indocyanine green in patients with lung cancer","Yukikiyo Kawakami, Kazuya Kondo, Naoya Kawakita, Hisashi Matsuoka, Hiroaki Toba, Hiromitsu Takizawa, Mitsuteru Yoshida, Akira Tangoku","Yukikiyo Kawakami, Kazuya Kondo, Naoya Kawakita, Hisashi Matsuoka, Hiroaki Toba, Hiromitsu Takizawa, Mitsuteru Yoshida, Akira Tangoku","null","null","null","null","null","2021","Thoracic Cancer","Thoracic Cancer","Vol.12","No.2","165","171","eng","true","null","scientific_journal","null","null","10.1111/1759-7714.13737","1759-7706","null","null","null","null","null" "より良いがんの地域連携体制構築のための包括的な取り組み","Comprehensive Interventions for Building a Better Regional Cooperation for Cancer Patients","鳥羽 博明, 滝沢 宏光, 青山 万理子, 井上 寛章, 丹黒 章","Hiroaki Toba, Hiromitsu Takizawa, Mariko Aoyama, Hiroaki Inoue, Akira Tangoku","null","目的:より良いがんの地域連携体制を構築するための包括的な取り組みについて紹介する.方法:かかりつけ医を対象に行った,がん患者の連携の可否と役割分担できる診療内容に関するアンケート結果をもとに,情報の可視化,新たな連携クリティカルパス(連携パス)の導入,拠点病院内の環境整備を行った.結果:まず,アンケート結果の情報を整理し,誰もがアクセスできるよう病院ホームページにアップして可視化した.さらに,予防的G-CSF(Granulocyte-Colony Stimulating Factor)投与連携パスを運用し,少数だが4例に適用した.加えて,入院中に医療ソーシャルワーカーが介入してかかりつけ医を決定し,文書作成を1分以内に完遂できる簡便な電子カルテ運用にして医師の作業負担を減らし,連携件数を約10倍増加させた.結語:より早期から緊密に情報交換し,役割分担することで,患者にとって満足度の高いがん医療を提供できる.今回の取り組みは,より良い連携体制構築に寄与すると考える.
","Objectives : We introduce our comprehensive interventions for building a better regional cooperation for cancer patients. Methods : We have made a questionnaire survey for community physicians asking whether they can accept cancer patients and what types of medical treatments they can provide. Based on the questionnaire responses, we visualized the information, developed a new critical pathway, and improved the system in a basic hospital. Results : We first organized the information obtained from the questionnaire responses and uploaded the organized information to the basic hospital's homepage for public access. We then developed a new critical pathway for the cooperation among community physicians considering the prophylactic administration of a granulocyte-colony stimulating factor (G-CSF) formulation for treating cancer patients. This treatment was subsequently applied to four patients. Additionally, a community physician was matched with each patient by a medical social worker during the patients' hospitalization. We improved the basic hospital's simple electronic medical record system to reduce the physicians' workloads. As a result, the document creation could be completed within one minute, and so they could relate to approximately 10 times larger number of cases. Conclusions : Satisfactory cancer treatments can be provided for patients by building the better regional cooperative relationships and dividing the roles with community physicians in an earlier time.
","null","null","2021","日本臨床外科学会雑誌","Journal of Japan Surgical Association","Vol.82","No.7","1281","1285","jpn","true","null","scientific_journal","null","null","10.3919/jjsa.82.1281","1345-2843","null","http://id.ndl.go.jp/bib/031639179","null","null","null" "Ⅲ. N-1 Study","[ .N-1 Study].","丹黒 章, 鳥羽 博明, 井上 寛章, 笹 聡一郎, 奥村 和正, 青山 万理子, 乾 友浩, 滝沢 宏光","Akira Tangoku, Hiroaki Toba, Hiroaki Inoue, Soichiroh Sasa, Kazumasa Okumura, Mariko Aoyama, INUI Tomohiro, Hiromitsu Takizawa","null","null","null","null","null","2020-12","癌と化学療法","Japanese Journal of Cancer and Chemotherapy","Vol.47","No.12","1681","1686","jpn","true","null","scientific_journal","null","null","null","0385-0684","null","null","null","null","null" "Relationship between regional left ventricular dysfunction and cancer-therapy-related cardiac dysfunction","Relationship between regional left ventricular dysfunction and cancer-therapy-related cardiac dysfunction","Yoshihito Saijyo, Kenya Kusunose, Y Okushi, Hirotsugu Yamada, Hiroaki Toba, Masataka Sata","Yoshihito Saijyo, Kenya Kusunose, Y Okushi, Hirotsugu Yamada, Hiroaki Toba, Masataka Sata","null","The aim of our study was to assess the association between risk of cancer-therapy-related cardiac dysfunction (CTRCD) after first follow-up and the difference in echocardiographic measures from baseline to follow-up. We retrospectively enrolled 87 consecutive patients (58±14 years, 55 women) who received anthracycline and underwent echocardiographic examinations both before (baseline) and after initial anthracycline administration (first follow-up). We measured absolute values of global longitudinal strain (GLS), apical longitudinal strain (LS), mid-LS and basal-LS at baseline and first follow-up, and per cent changes (Δ) of these parameters were calculated. Among 61 patients who underwent further echocardiographic examinations (second follow-up, third follow-up, etc), we assessed the association between regional left ventricular (LV) systolic dysfunction from baseline to follow-up and development of CTRCD, defined as LV ejection fraction (LVEF) under 53% and more absolute decrease of 10% from baseline, after first follow-up. LVEF (65%±4% vs 63±4%, p=0.004), GLS (23.2%±2.6% vs 22.2±2.4%, p=0.005) and basal-LS (21.9%±2.5% vs 19.9±2.4%, p<0.001) at first follow-up significantly decreased compared with baseline. Among the 61 patients who had further follow-up echocardiographic examinations, 13% developed CTRCD. In the Cox-hazard model, worse Δbasal-LS was significantly associated with CTRCD. By Kaplan-Meier analysis, patients with Δbasal-LS decrease of more than the median value (-9.7%) had significantly worse event-free survival than those with a smaller decrease (p=0.015). Basal-LS significantly decreased prior to development of CTRCD, and worse basal-LS was associated with development of CTRCD in patients receiving anthracycline chemotherapy.","The aim of our study was to assess the association between risk of cancer-therapy-related cardiac dysfunction (CTRCD) after first follow-up and the difference in echocardiographic measures from baseline to follow-up. We retrospectively enrolled 87 consecutive patients (58±14 years, 55 women) who received anthracycline and underwent echocardiographic examinations both before (baseline) and after initial anthracycline administration (first follow-up). We measured absolute values of global longitudinal strain (GLS), apical longitudinal strain (LS), mid-LS and basal-LS at baseline and first follow-up, and per cent changes (Δ) of these parameters were calculated. Among 61 patients who underwent further echocardiographic examinations (second follow-up, third follow-up, etc), we assessed the association between regional left ventricular (LV) systolic dysfunction from baseline to follow-up and development of CTRCD, defined as LV ejection fraction (LVEF) under 53% and more absolute decrease of 10% from baseline, after first follow-up. LVEF (65%±4% vs 63±4%, p=0.004), GLS (23.2%±2.6% vs 22.2±2.4%, p=0.005) and basal-LS (21.9%±2.5% vs 19.9±2.4%, p<0.001) at first follow-up significantly decreased compared with baseline. Among the 61 patients who had further follow-up echocardiographic examinations, 13% developed CTRCD. In the Cox-hazard model, worse Δbasal-LS was significantly associated with CTRCD. By Kaplan-Meier analysis, patients with Δbasal-LS decrease of more than the median value (-9.7%) had significantly worse event-free survival than those with a smaller decrease (p=0.015). Basal-LS significantly decreased prior to development of CTRCD, and worse basal-LS was associated with development of CTRCD in patients receiving anthracycline chemotherapy.","null","null","2020-11","Heart","Heart","Vol.106","No.22","1752","1758","eng","true","null","scientific_journal","null","null","10.1136/heartjnl-2019-316339","1468-201X","null","null","null","null","null" "Bronchioalveolar stem cells derived from mouse-induced pluripotent stem cells promote airway epithelium regeneration","Bronchioalveolar stem cells derived from mouse-induced pluripotent stem cells promote airway epithelium regeneration","Naoya Kawakita, Hiroaki Toba, Keiko Miyoshi, Shinichi Sakamoto, Daisuke Matsumoto, Mika Takashima, Mariko Aoyama, Seiya Inoue, Masami Morimoto, Takeshi Nishino, Hiromitsu Takizawa, Akira Tangoku","Naoya Kawakita, Hiroaki Toba, Keiko Miyoshi, Shinichi Sakamoto, Daisuke Matsumoto, Mika Takashima, Mariko Aoyama, Seiya Inoue, Masami Morimoto, Takeshi Nishino, Hiromitsu Takizawa, Akira Tangoku","null","Bronchioalveolar stem cells (BASCs) located at the bronchioalveolar-duct junction (BADJ) are stem cells residing in alveoli and terminal bronchioles that can self-renew and differentiate into alveolar type (AT)-1 cells, AT-2 cells, club cells, and ciliated cells. Following terminal-bronchiole injury, BASCs increase in number and promote repair. However, whether BASCs can be differentiated from mouse-induced pluripotent stem cells (iPSCs) remains unreported, and the therapeutic potential of such cells is unclear. We therefore sought to differentiate BASCs from iPSCs and examine their potential for use in the treatment of epithelial injury in terminal bronchioles. BASCs were induced using a modified protocol for differentiating mouse iPSCs into AT-2 cells. Differentiated iPSCs were intratracheally transplanted into naphthalene-treated mice. The engraftment of BASCs into the BADJ and their subsequent ability to promote repair of injury to the airway epithelium were evaluated. Flow cytometric analysis revealed that BASCs represented ~ 7% of the cells obtained. Additionally, ultrastructural analysis of these iPSC-derived BASCs via transmission electron microscopy showed that the cells containing secretory granules harboured microvilli, as well as small and immature lamellar body-like structures. When the differentiated iPSCs were intratracheally transplanted in naphthalene-induced airway epithelium injury, transplanted BASCs were found to be engrafted in the BADJ epithelium and alveolar spaces for 14 days after transplantation and to maintain the BASC phenotype. Notably, repair of the terminal-bronchiole epithelium was markedly promoted after transplantation of the differentiated iPSCs. Mouse iPSCs could be differentiated in vitro into cells that display a similar phenotype to BASCs. Given that the differentiated iPSCs promoted epithelial repair in the mouse model of naphthalene-induced airway epithelium injury, this method may serve as a basis for the development of treatments for terminal-bronchiole/alveolar-region disorders.","Bronchioalveolar stem cells (BASCs) located at the bronchioalveolar-duct junction (BADJ) are stem cells residing in alveoli and terminal bronchioles that can self-renew and differentiate into alveolar type (AT)-1 cells, AT-2 cells, club cells, and ciliated cells. Following terminal-bronchiole injury, BASCs increase in number and promote repair. However, whether BASCs can be differentiated from mouse-induced pluripotent stem cells (iPSCs) remains unreported, and the therapeutic potential of such cells is unclear. We therefore sought to differentiate BASCs from iPSCs and examine their potential for use in the treatment of epithelial injury in terminal bronchioles. BASCs were induced using a modified protocol for differentiating mouse iPSCs into AT-2 cells. Differentiated iPSCs were intratracheally transplanted into naphthalene-treated mice. The engraftment of BASCs into the BADJ and their subsequent ability to promote repair of injury to the airway epithelium were evaluated. Flow cytometric analysis revealed that BASCs represented ~ 7% of the cells obtained. Additionally, ultrastructural analysis of these iPSC-derived BASCs via transmission electron microscopy showed that the cells containing secretory granules harboured microvilli, as well as small and immature lamellar body-like structures. When the differentiated iPSCs were intratracheally transplanted in naphthalene-induced airway epithelium injury, transplanted BASCs were found to be engrafted in the BADJ epithelium and alveolar spaces for 14 days after transplantation and to maintain the BASC phenotype. Notably, repair of the terminal-bronchiole epithelium was markedly promoted after transplantation of the differentiated iPSCs. Mouse iPSCs could be differentiated in vitro into cells that display a similar phenotype to BASCs. Given that the differentiated iPSCs promoted epithelial repair in the mouse model of naphthalene-induced airway epithelium injury, this method may serve as a basis for the development of treatments for terminal-bronchiole/alveolar-region disorders.","null","null","2020-10-02","Stem Cell Research & Therapy","Stem Cell Research & Therapy","Vol.11","No.1","430","430","eng","true","null","scientific_journal","null","null","10.1186/s13287-020-01946-7","1757-6512","null","null","null","null","null" "腋窩副乳発生と考えられる若年性線維腺腫の1例","A case of juvenile fibroadenoma arising from axillary accessory mammary gland","笹 聡一郎, 井上 寛章, 奥村 和正, 青山 万理子, 乾 友浩, 鳥羽 博明, 吉田 卓弘, 坂東 良美, 丹黒 章","Soichiroh Sasa, Hiroaki Inoue, Kazumasa Okumura, Mariko Aoyama, Tomohiro INUI, Hiroaki Toba, Takahiro Yoshida, Yoshimi Bando, Akira Tangoku","null","A case is20years old woman. She had previously noticed a mass in the left axilla. The mass grew, so she went to the hospital. Ultrasonography revealed a 71 × 51 mm well-defined tumor in the left axilla. We suspected a benign tumor but could not rule out axillary lymph node metastasis or accessory breast cancer. The findings of fine needle aspiration cytology suggested fibroadenoma or phyllodes tumor. Although we diagnosed fibroadenoma by needle biopsy, a definitive diagnosis was made by tumor resection because it is located in the axilla and large in size, and other diseases such as phyllodes tumors can be distinguished. The histopathological diagnosis of the excised specimen was juvenile fibroadenoma. We report a case of juvenile fibroadenoma arising from the axillary accessory mammary gland.","A case is20years old woman. She had previously noticed a mass in the left axilla. The mass grew, so she went to the hospital. Ultrasonography revealed a 71 × 51 mm well-defined tumor in the left axilla. We suspected a benign tumor but could not rule out axillary lymph node metastasis or accessory breast cancer. The findings of fine needle aspiration cytology suggested fibroadenoma or phyllodes tumor. Although we diagnosed fibroadenoma by needle biopsy, a definitive diagnosis was made by tumor resection because it is located in the axilla and large in size, and other diseases such as phyllodes tumors can be distinguished. The histopathological diagnosis of the excised specimen was juvenile fibroadenoma. We report a case of juvenile fibroadenoma arising from the axillary accessory mammary gland.","null","null","2020-08-25","四国医学雑誌","Shikoku Acta Medica","Vol.76","No.3,4","185","190","jpn","true","null","scientific_journal","null","null","null","0037-3699","null","https://ci.nii.ac.jp/naid/120006892839/","null","null","null" "Phase 1 Dose-Escalation Study of Triweekly Nab-Paclitaxel Combined With S-1 for HER2-Negative Metastatic Breast Cancer","Phase 1 Dose-Escalation Study of Triweekly Nab-Paclitaxel Combined With S-1 for HER2-Negative Metastatic Breast Cancer","Masami Morimoto, Hiroaki Toba, Mariko Aoyama, Misako Nakagawa, Hirokazu Takechi, Takahiro Yoshida, Akira Tangoku","Masami Morimoto, Hiroaki Toba, Mariko Aoyama, Misako Nakagawa, Hirokazu Takechi, Takahiro Yoshida, Akira Tangoku","null","To evaluate the efficacy, toxicity, maximum tolerated dose, and recommended dose of triweekly nab-paclitaxel (nab-PTX) and S-1 combination chemotherapy for patients with metastatic breast cancer. This phase 1 study was conducted with a standard 3 + 3 dose escalation design. Every 3 weeks, the patients received nab-PTX at 180-260 mg/m on day 1 and S-1 at 65-80 mg/m daily on days 1 to 14. Ten HER2-negative metastatic breast cancer patients were enrolled; their median number of prior chemotherapy regimens was 3. Dose-limiting toxicity was observed in the first patient assigned to level 4; grade 4 febrile neutropenia and grade 3 neurotoxicity such as needing a wheelchair occurred. Therefore, an additional patient was not assigned to level 4. The maximum tolerated dose was considered level 4 (260 mg/m nab-PTX with 80 mg/m S-1). The recommended dose determined was level 3 (220 mg/m nab-PTX with 80 mg/m S-1). The response rate was 60.0%. The disease control rate was 70.0%. This combination chemotherapy therapy was feasible and safe for patients with HER2-negative metastatic breast cancer.","To evaluate the efficacy, toxicity, maximum tolerated dose, and recommended dose of triweekly nab-paclitaxel (nab-PTX) and S-1 combination chemotherapy for patients with metastatic breast cancer. This phase 1 study was conducted with a standard 3 + 3 dose escalation design. Every 3 weeks, the patients received nab-PTX at 180-260 mg/m on day 1 and S-1 at 65-80 mg/m daily on days 1 to 14. Ten HER2-negative metastatic breast cancer patients were enrolled; their median number of prior chemotherapy regimens was 3. Dose-limiting toxicity was observed in the first patient assigned to level 4; grade 4 febrile neutropenia and grade 3 neurotoxicity such as needing a wheelchair occurred. Therefore, an additional patient was not assigned to level 4. The maximum tolerated dose was considered level 4 (260 mg/m nab-PTX with 80 mg/m S-1). The recommended dose determined was level 3 (220 mg/m nab-PTX with 80 mg/m S-1). The response rate was 60.0%. The disease control rate was 70.0%. This combination chemotherapy therapy was feasible and safe for patients with HER2-negative metastatic breast cancer.","null","null","2020-07-24","Clinical Breast Cancer","Clinical Breast Cancer","Vol.20","No.6","448","453","eng","true","null","scientific_journal","null","null","10.1016/j.clbc.2020.07.012","1938-0666","null","null","null","null","null" "Thoracoscopic lobectomy for lung cancer with unilateral absence of pulmonary artery","Thoracoscopic lobectomy for lung cancer with unilateral absence of pulmonary artery","Daisuke Matsumoto, Hiroaki Toba, Kazuya Kondo, Akira Tangoku","Daisuke Matsumoto, Hiroaki Toba, Kazuya Kondo, Akira Tangoku","null","null","null","null","null","2020-06-21","JTCVS Techniques","JTCVS Techniques","Vol.3","null","343","345","eng","true","null","scientific_journal","null","null","10.1016/j.xjtc.2020.06.024","2666-2507","null","https://doi.org/10.1016/j.xjtc.2020.06.024","null","null","null" "HER2陽性高齢者乳癌に対するAnthracycline系薬剤回避レジメンの忍容性と有効性についての検討","Tolerability and efficacy of a chemotherapy regimen avoiding Anthracycline for HER2 positive elderly and poor risked breast cancer patients","武知 浩和, 森本 雅美, 田代 善彦, 松山 和男, 宮内 隆行, 石川 正志, 笹 聡一郎, 青山 万理子, 井上 聖也, 鳥羽 博明, 吉田 卓弘, 丹黒 章","Hirokazu Takechi, Masami Morimoto, 田代 善彦, 松山 和男, 宮内 隆行, 石川 正志, Soichiroh Sasa, Mariko Aoyama, Seiya Inoue, Hiroaki Toba, Takahiro Yoshida, Akira Tangoku","null","Tolerability and efficacy of chemotherapy avoiding anthracycline regimen were examined histologically in ER negative and HER2positive elderly and poor risked breast cancer patients because of serious toxicity of Anthracycline regimen. Neo-adjuvant chemotherapy with 4 to 6 courses of Paclitaxel with Trastuzumab was given to 6 patients, Pertuzumab was added in 2 cases to obtain complete response. Adverse events were controllable, the primary treatment was completed without reducing the dose of drugs(RDI was 100%). Clinical CR rate was recognized in all 6 patients and pathological CR was proved in all of the operated5cases.","Tolerability and efficacy of chemotherapy avoiding anthracycline regimen were examined histologically in ER negative and HER2positive elderly and poor risked breast cancer patients because of serious toxicity of Anthracycline regimen. Neo-adjuvant chemotherapy with 4 to 6 courses of Paclitaxel with Trastuzumab was given to 6 patients, Pertuzumab was added in 2 cases to obtain complete response. Adverse events were controllable, the primary treatment was completed without reducing the dose of drugs(RDI was 100%). Clinical CR rate was recognized in all 6 patients and pathological CR was proved in all of the operated5cases.","null","null","2020-04-25","四国医学雑誌","Shikoku Acta Medica","Vol.76","No.1,2","69","72","jpn","true","null","scientific_journal","null","null","null","0037-3699","null","https://ci.nii.ac.jp/naid/120006860013/","null","null","null" "Use of a prognostic risk score that aggregates the FDG-PET/CT SUVmax, tumor size, and histologic group for predicting the prognosis of pStage I lung adenocarcinoma","Use of a prognostic risk score that aggregates the FDG-PET/CT SUVmax, tumor size, and histologic group for predicting the prognosis of pStage I lung adenocarcinoma","Naoya Kawakita, Hiroaki Toba, Yukikiyo Kawakami, Hiromitsu Takizawa, Yoshimi Bando, Hideki Otsuka, Daisuke Matsumoto, Mika Takashima, Mitsuhiro Tsuboi, Mitsuteru Yoshida, Kazuya Kondo, Akira Tangoku","Naoya Kawakita, Hiroaki Toba, Yukikiyo Kawakami, Hiromitsu Takizawa, Yoshimi Bando, Hideki Otsuka, Daisuke Matsumoto, Mika Takashima, Mitsuhiro Tsuboi, Mitsuteru Yoshida, Kazuya Kondo, Akira Tangoku","null","pStage I includes clinicopathologically diverse groups. This study aimed to identify the prognostic factors for pStage I lung adenocarcinoma. We retrospectively reviewed 208 patients with pStage I adenocarcinomas who underwent curative resection in our institute between 2006 and 2013. The maximum standardized uptake value (SUVmax) on [F18]-fluoro-deoxy-D-glucose positron emission tomography-computed tomography (PET/CT) was evaluated. Adenocarcinomas were categorized into the following histologic groups: group 0 (minimally invasive adenocarcinoma and lepidic predominant adenocarcinoma), group 1 (papillary predominant adenocarcinoma), and group 2 (acinar predominant adenocarcinoma and all the remaining subtypes). We assessed the relationship between disease-free survival (DFS) and clinicopathological factors. Multivariate analysis of DFS demonstrated that SUVmax > 3.0 (p < 0.001), total tumor size > 20 mm (p = 0.016), and histologic groups (p < 0.05) were independent prognostic factors. The prognostic risk score (PRS) was calculated using the following equation: PRS = SUVmax (≤ 3.0: 0 point, > 3.0: 2 points) + total tumor size (≤ 20 mm: 0 point, > 20 mm: 1 point) + histologic group (group 0: 0 point, group 1: 1 point, group 2: 2 points). Patients were divided into the following three risk groups: low-risk (PRS 0-2 points, n = 136), intermediate-risk (PRS 3-4 points, n = 49), and high-risk groups (PRS 5 points, n = 13). The 5-year DFS rates were 93.2%, 50.6%, and 30.8% for the low-, intermediate-, and high-risk groups, respectively (p < 0.001). The PRS aggregating the FDG-PET/CT SUVmax, total tumor size, and histologic group predicts the prognosis of pStage I lung adenocarcinoma.","pStage I includes clinicopathologically diverse groups. This study aimed to identify the prognostic factors for pStage I lung adenocarcinoma. We retrospectively reviewed 208 patients with pStage I adenocarcinomas who underwent curative resection in our institute between 2006 and 2013. The maximum standardized uptake value (SUVmax) on [F18]-fluoro-deoxy-D-glucose positron emission tomography-computed tomography (PET/CT) was evaluated. Adenocarcinomas were categorized into the following histologic groups: group 0 (minimally invasive adenocarcinoma and lepidic predominant adenocarcinoma), group 1 (papillary predominant adenocarcinoma), and group 2 (acinar predominant adenocarcinoma and all the remaining subtypes). We assessed the relationship between disease-free survival (DFS) and clinicopathological factors. Multivariate analysis of DFS demonstrated that SUVmax > 3.0 (p < 0.001), total tumor size > 20 mm (p = 0.016), and histologic groups (p < 0.05) were independent prognostic factors. The prognostic risk score (PRS) was calculated using the following equation: PRS = SUVmax (≤ 3.0: 0 point, > 3.0: 2 points) + total tumor size (≤ 20 mm: 0 point, > 20 mm: 1 point) + histologic group (group 0: 0 point, group 1: 1 point, group 2: 2 points). Patients were divided into the following three risk groups: low-risk (PRS 0-2 points, n = 136), intermediate-risk (PRS 3-4 points, n = 49), and high-risk groups (PRS 5 points, n = 13). The 5-year DFS rates were 93.2%, 50.6%, and 30.8% for the low-, intermediate-, and high-risk groups, respectively (p < 0.001). The PRS aggregating the FDG-PET/CT SUVmax, total tumor size, and histologic group predicts the prognosis of pStage I lung adenocarcinoma.","null","null","2020-03-04","International Journal of Clinical Oncology","International Journal of Clinical Oncology","Vol.25","No.6","1079","1089","eng","true","null","scientific_journal","null","null","10.1007/s10147-020-01637-6","1437-7772","null","null","null","null","null" "DNA methylation of GHSR, GNG4, HOXD9 and SALL3 is a common epigenetic alteration in thymic carcinoma","DNA methylation of GHSR, GNG4, HOXD9 and SALL3 is a common epigenetic alteration in thymic carcinoma","Reina Kishibuchi, Kazuya Kondo, Shiho Soejima, Mitsuhiro Tsuboi, Koichiro Kajiura, Yukikiyo Kawakami, Naoya Kawakita, Toru Sawada, Hiroaki Toba, Mitsuteru Yoshida, Hiromitsu Takizawa, Akira Tangoku","Reina Kishibuchi, Kazuya Kondo, Shiho Soejima, Mitsuhiro Tsuboi, Koichiro Kajiura, Yukikiyo Kawakami, Naoya Kawakita, Toru Sawada, Hiroaki Toba, Mitsuteru Yoshida, Hiromitsu Takizawa, Akira Tangoku","null","Thymic epithelial tumors comprise thymoma, thymic carcinoma and neuroendocrine tumors of the thymus. Recent studies have revealed that the incidence of somatic non-synonymous mutations is significantly higher in thymic carcinoma than in thymoma. However, limited information is currently available on epigenetic alterations in these types of cancer. In this study, we thus performed genome-wide screening of aberrantly methylated CpG islands in thymoma and thymic carcinoma using Illumina HumanMethylation450 K BeadChip. We identified 92 CpG islands significantly hypermethylated in thymic carcinoma in relation to thymoma and selected G protein subunit gamma 4 (GNG4), growth hormone secretagogue receptor (GHSR), homeobox D9 (HOXD9) and spalt like transcription factor 3 (SALL3), which are related to cancer. We examined the promoter methylation of 4 genes in 46 thymic epithelial tumors and 20 paired thymus tissues using bisulfite pyrosequencing. Promoter methylation was significantly higher in thymic carcinoma than in thymoma and revealed a high discrimination between thymic carcinoma and thymoma in all 4 genes. Promoter methylation was higher in thymic carcinoma than in the thymus. No significant differences were observed in the promoter methylation of GNG4, HOXD9, or SALL3 between thymoma and the thymus. The promoter methylation of the 4 genes was not significantly higher in advanced-stage tumors than in early-stage tumors in all thymic epithelial tumors. Among the 4 genes, relapse-free survival was significantly worse in tumors with a higher DNA methylation than in those with a lower DNA methylation in all thymic epithelial tumors. Moreover, relapse-free survival was significantly worse in thymomas with a higher DNA methylation of HOXD9 and SALL3 than in those with a lower DNA methylation. On the whole, the findings of this study indicated that the promoter methylation of cancer-related genes was significantly higher in thymic carcinoma than in thymoma and the thymus. This is a common epigenetic alteration of high diagnostic value in thymic carcinoma and may be involved in the carcinogenesis of thymic carcinoma. However, epigenetic alterations in the 3 genes, apart from GHSR, are not involved in the tumorigenesis of thymoma.","Thymic epithelial tumors comprise thymoma, thymic carcinoma and neuroendocrine tumors of the thymus. Recent studies have revealed that the incidence of somatic non-synonymous mutations is significantly higher in thymic carcinoma than in thymoma. However, limited information is currently available on epigenetic alterations in these types of cancer. In this study, we thus performed genome-wide screening of aberrantly methylated CpG islands in thymoma and thymic carcinoma using Illumina HumanMethylation450 K BeadChip. We identified 92 CpG islands significantly hypermethylated in thymic carcinoma in relation to thymoma and selected G protein subunit gamma 4 (GNG4), growth hormone secretagogue receptor (GHSR), homeobox D9 (HOXD9) and spalt like transcription factor 3 (SALL3), which are related to cancer. We examined the promoter methylation of 4 genes in 46 thymic epithelial tumors and 20 paired thymus tissues using bisulfite pyrosequencing. Promoter methylation was significantly higher in thymic carcinoma than in thymoma and revealed a high discrimination between thymic carcinoma and thymoma in all 4 genes. Promoter methylation was higher in thymic carcinoma than in the thymus. No significant differences were observed in the promoter methylation of GNG4, HOXD9, or SALL3 between thymoma and the thymus. The promoter methylation of the 4 genes was not significantly higher in advanced-stage tumors than in early-stage tumors in all thymic epithelial tumors. Among the 4 genes, relapse-free survival was significantly worse in tumors with a higher DNA methylation than in those with a lower DNA methylation in all thymic epithelial tumors. Moreover, relapse-free survival was significantly worse in thymomas with a higher DNA methylation of HOXD9 and SALL3 than in those with a lower DNA methylation. On the whole, the findings of this study indicated that the promoter methylation of cancer-related genes was significantly higher in thymic carcinoma than in thymoma and the thymus. This is a common epigenetic alteration of high diagnostic value in thymic carcinoma and may be involved in the carcinogenesis of thymic carcinoma. However, epigenetic alterations in the 3 genes, apart from GHSR, are not involved in the tumorigenesis of thymoma.","null","null","2019-11-18","International Journal of Oncology","International Journal of Oncology","Vol.56","No.1","315","326","eng","true","null","scientific_journal","null","null","10.3892/ijo.2019.4915","1791-2423","null","null","null","null","null" "Chromate exposure induces DNA hypermethylation of the mismatch repair gene MLH1 in lung cancer","Chromate exposure induces DNA hypermethylation of the mismatch repair gene MLH1 in lung cancer","Mitsuhiro Tsuboi, Kazuya Kondo, Shiho Soejima, Koichiro Kajiura, Naoya Kawakita, Hiroaki Toba, Yukikiyo Kawakami, Mitsuteru Yoshida, Hiromitsu Takizawa, Akira Tangoku","Mitsuhiro Tsuboi, Kazuya Kondo, Shiho Soejima, Koichiro Kajiura, Naoya Kawakita, Hiroaki Toba, Yukikiyo Kawakami, Mitsuteru Yoshida, Hiromitsu Takizawa, Akira Tangoku","null","Hexavalent chromium is recognized as a human carcinogen. Our previous studies revealed that lung cancer (LC) in chromate-exposed workers (chromate LC) had molecular features of frequent microsatellite instability (MSI), repression of MLH1 level, and aberrant DNA methylation of several tumor-suppressor genes, including MLH1. In the present study, we quantitatively investigated MLH1-promoter methylation status using bisulfite pyrosequencing of paired tumorous/nontumorous tissues from chromate and nonchromate LCs to determine the effect of chromate exposure on MLH1-promoter methylation. The methylation level of MLH1 promoter was significantly higher in chromate LC tumors (P < .001) than nonchromate LC tumors and, among chromate LC, significantly higher in tumorous tissue than nontumorous tissue (P = .004). Moreover, the methylation level of MLH1 promoter in normal lung tissue tended to be higher in chromate LC than nonchromate LC (P = .062). In addition, LC with reduced levels of MLH1 showed significantly higher methylation levels of MLH1 promoter than LC exhibiting normal MLH1 levels (P = .019). Moreover, immunohistochemical analyses determined that levels of SUV39H1, an H3K9me2-related methyltransferase, were higher in chromate LC than nonchromate LC (P = .076). Furthermore, we evaluated three DNA double-strand break-repair genes (MRE11, RAD50, and DNA-PKcs) as possible targets of MSI by fragment-length polymorphism analysis, revealing the mutation frequency of RAD50 as significantly higher in chromate LC than nonchromate LC (P = .047). These results suggest that chromate exposure might induce MLH1 hypermethylation in LC as a mechanism of chromate-induced carcinogenesis.","Hexavalent chromium is recognized as a human carcinogen. Our previous studies revealed that lung cancer (LC) in chromate-exposed workers (chromate LC) had molecular features of frequent microsatellite instability (MSI), repression of MLH1 level, and aberrant DNA methylation of several tumor-suppressor genes, including MLH1. In the present study, we quantitatively investigated MLH1-promoter methylation status using bisulfite pyrosequencing of paired tumorous/nontumorous tissues from chromate and nonchromate LCs to determine the effect of chromate exposure on MLH1-promoter methylation. The methylation level of MLH1 promoter was significantly higher in chromate LC tumors (P < .001) than nonchromate LC tumors and, among chromate LC, significantly higher in tumorous tissue than nontumorous tissue (P = .004). Moreover, the methylation level of MLH1 promoter in normal lung tissue tended to be higher in chromate LC than nonchromate LC (P = .062). In addition, LC with reduced levels of MLH1 showed significantly higher methylation levels of MLH1 promoter than LC exhibiting normal MLH1 levels (P = .019). Moreover, immunohistochemical analyses determined that levels of SUV39H1, an H3K9me2-related methyltransferase, were higher in chromate LC than nonchromate LC (P = .076). Furthermore, we evaluated three DNA double-strand break-repair genes (MRE11, RAD50, and DNA-PKcs) as possible targets of MSI by fragment-length polymorphism analysis, revealing the mutation frequency of RAD50 as significantly higher in chromate LC than nonchromate LC (P = .047). These results suggest that chromate exposure might induce MLH1 hypermethylation in LC as a mechanism of chromate-induced carcinogenesis.","null","null","2019-10-03","Molecular Carcinogenesis","Molecular Carcinogenesis","Vol.59","No.1","24","31","eng","true","null","scientific_journal","null","null","10.1002/mc.23125","1098-2744","null","null","null","null","null" "Transbronchial Biopsy Using an Ultrathin Bronchoscope Guided by Cone-Beam Computed Tomography and Virtual Bronchoscopic Navigation in the Diagnosis of Pulmonary Nodules","Transbronchial Biopsy Using an Ultrathin Bronchoscope Guided by Cone-Beam Computed Tomography and Virtual Bronchoscopic Navigation in the Diagnosis of Pulmonary Nodules","A.A.Ali Eman, Hiromitsu Takizawa, Naoya Kawakita, Toru Sawada, Mitsuhiro Tsuboi, Hiroaki Toba, Mika Takashima, Daisuke Matsumoto, Mitsuteru Yoshida, Yukikiyo Kawakami, Kazuya Kondo, El-Badrawy Khairy Mohammad, Akira Tangoku","A.A.Ali Eman, Hiromitsu Takizawa, Naoya Kawakita, Toru Sawada, Mitsuhiro Tsuboi, Hiroaki Toba, Mika Takashima, Daisuke Matsumoto, Mitsuteru Yoshida, Yukikiyo Kawakami, Kazuya Kondo, El-Badrawy Khairy Mohammad, Akira Tangoku","null","Transbronchial biopsy is a safe diagnostic approach for patients with peripheral pulmonary lesions; however, the diagnostic yield is low. This study was conducted to evaluate the feasibility and diagnostic yield of transbronchial biopsy using the combination of an ultrathin bronchoscope, virtual bronchoscopic navigation (VBN), and cone-beam computed tomography (CBCT). Patients with peripheral pulmonary lesions, no >30 mm, with the responsible bronchus, were prospectively included. An ultrathin bronchoscope and biopsy forceps were advanced to the target bronchus under VBN, 2D-fluoroscopy, and CBCT. We categorized the CBCT findings before biopsy into 3 types according to positions of the target lesion and forceps (CBCT target-forceps sign). In type A, the forceps reached the inside of the target lesion. In type C, the forceps could not reach the lesion. When the CBCT findings could not be categorized into either type A or C, the sign was categorized as type B. Although the target lesions were invisible by conventional C-arm fluoroscopy in 29 patients, CBCT visualized all 40 lesions. The overall diagnostic yield was 90.0%, and diagnostic yields for malignant and benign lesions were 92.0 and 86.7%, respectively. Diagnostic yields for CBCT target-forceps sign types A, B, and C were 100, 75.0, and 0%, respectively. Four undiagnosed patients proceeded to other diagnostic procedures based on the CBCT target-forceps sign (type B: n = 2, type C: n = 2) and were correctly diagnosed without delay. Transbronchial biopsy using an ultrathin bronchoscope guided by CBCT and VBN showed a very high yield in the diagnosis of pulmonary nodules.","Transbronchial biopsy is a safe diagnostic approach for patients with peripheral pulmonary lesions; however, the diagnostic yield is low. This study was conducted to evaluate the feasibility and diagnostic yield of transbronchial biopsy using the combination of an ultrathin bronchoscope, virtual bronchoscopic navigation (VBN), and cone-beam computed tomography (CBCT). Patients with peripheral pulmonary lesions, no >30 mm, with the responsible bronchus, were prospectively included. An ultrathin bronchoscope and biopsy forceps were advanced to the target bronchus under VBN, 2D-fluoroscopy, and CBCT. We categorized the CBCT findings before biopsy into 3 types according to positions of the target lesion and forceps (CBCT target-forceps sign). In type A, the forceps reached the inside of the target lesion. In type C, the forceps could not reach the lesion. When the CBCT findings could not be categorized into either type A or C, the sign was categorized as type B. Although the target lesions were invisible by conventional C-arm fluoroscopy in 29 patients, CBCT visualized all 40 lesions. The overall diagnostic yield was 90.0%, and diagnostic yields for malignant and benign lesions were 92.0 and 86.7%, respectively. Diagnostic yields for CBCT target-forceps sign types A, B, and C were 100, 75.0, and 0%, respectively. Four undiagnosed patients proceeded to other diagnostic procedures based on the CBCT target-forceps sign (type B: n = 2, type C: n = 2) and were correctly diagnosed without delay. Transbronchial biopsy using an ultrathin bronchoscope guided by CBCT and VBN showed a very high yield in the diagnosis of pulmonary nodules.","null","null","2019-05-23","Respiration","Respiration","Vol.98","No.4","321","328","eng","true","null","scientific_journal","null","null","10.1159/000500228","1423-0356","null","null","null","null","null" "がんの地域連携 かかりつけ医との役割分担に関するアンケート調査","Regional cooperation for cancer patients : A questionnaire clarifying the roles of community doctor","鳥羽 博明, 滝沢 宏光, 吉田 卓弘, 森本 雅美, 青山 万理子, 西口 京子, 宮越 智寿, 武知 浩和, 丹黒 章","Hiroaki Toba, Hiromitsu Takizawa, Takahiro Yoshida, Masami Morimoto, Mariko Aoyama, 西口 京子, 宮越 智寿, Hirokazu Takechi, Akira Tangoku","null","It was suggested long ago that regional cooperation is necessary for cancer patients. Both doctors in base hospitals and community doctors understand the importance of such cooperation. Here we report the results of our widely distributed questionnaire designed to clarify the division of physicians' roles and to strengthen the relationships between base hospital and community doctors. The questionnaire asks whether community doctors can accept cancer patients and what types of medical treatment the doctors can provide for patients with esophageal cancer, lung cancer, breast cancer, and thyroid cancer. The doctors in 289 of 550 (53%) facilities completed and returned the questionnaire. About half of the community doctors responded that they can accept patients with any of the four cancers and can provide most types of the necessary medical examinations and treatments in their daily practices. Most of the community doctors indicated that they could not provide some anti-cancer drugs and supportive drug therapies for breast cancer patients. The development and implementation of a clinical pathway system could enable the participation of more community doctors and base hospital doctors. Although our findings are preliminary, they will contribute to a foundation for building better regional corporative relationships with community doctors who treat cancer patients.","It was suggested long ago that regional cooperation is necessary for cancer patients. Both doctors in base hospitals and community doctors understand the importance of such cooperation. Here we report the results of our widely distributed questionnaire designed to clarify the division of physicians' roles and to strengthen the relationships between base hospital and community doctors. The questionnaire asks whether community doctors can accept cancer patients and what types of medical treatment the doctors can provide for patients with esophageal cancer, lung cancer, breast cancer, and thyroid cancer. The doctors in 289 of 550 (53%) facilities completed and returned the questionnaire. About half of the community doctors responded that they can accept patients with any of the four cancers and can provide most types of the necessary medical examinations and treatments in their daily practices. Most of the community doctors indicated that they could not provide some anti-cancer drugs and supportive drug therapies for breast cancer patients. The development and implementation of a clinical pathway system could enable the participation of more community doctors and base hospital doctors. Although our findings are preliminary, they will contribute to a foundation for building better regional corporative relationships with community doctors who treat cancer patients.","null","null","2019-04-25","四国医学雑誌","Shikoku Acta Medica","Vol.75","No.1,2","49","54","jpn","true","null","scientific_journal","null","null","null","0037-3699","null","https://ci.nii.ac.jp/naid/120006729379/","null","null","null" "Indocyanine green fluorescence imaging for resection of pulmonary metastasis of hepatocellular carcinoma","Indocyanine green fluorescence imaging for resection of pulmonary metastasis of hepatocellular carcinoma","Naoya Kawakita, Hiromitsu Takizawa, Toru Sawada, Daisuke Matsumoto, Mitsuhiro Tsuboi, Hiroaki Toba, Mitsuteru Yoshida, Yukikiyo Kawakami, Kazuya Kondo, Akira Tangoku","Naoya Kawakita, Hiromitsu Takizawa, Toru Sawada, Daisuke Matsumoto, Mitsuhiro Tsuboi, Hiroaki Toba, Mitsuteru Yoshida, Yukikiyo Kawakami, Kazuya Kondo, Akira Tangoku","null","Indocyanine green (ICG) accumulates in hepatocellular carcinoma (HCC), and tumor fluorescence can be observed under irradiation with near infrared light (NIR). This study investigated the clinical utility of ICG fluorescence imaging during resection of pulmonary metastases of HCC. From April 2010 to June 2018, six patients with suspected pulmonary metastasis of HCC were enrolled prospectively. Prior to surgery, all patients underwent the ICG hepatic function test following intravenous administration of ICG (0.5 mg/kg body weight). During surgery, metastatic HCC was identified by observation of ICG fluorescence, allowing assessment of the surgical margin. Tumor fluorescence was also evaluated on cut sections. A total of 11 metastatic HCCs were resected in six patients at nine operations. Eight lesions were removed by wedge resection and 3 lesions were managed by lobectomy. During surgery, tumor fluorescence could be confirmed through the visceral pleura in 6 out of 7 lesions treated by wedge resection, while NIR irradiation was difficult for 1 lesion. For these 6 lesions, the median distance from the tumor to the visceral pleura and the median surgical margin were 0 mm (range, 0-2 mm) and 14 mm (range, 11-17 mm), respectively. When cut sections were examined, all tumors emitted fluorescence. All lesions were histologically confirmed to be metastatic HCC. In patients with pulmonary metastasis of HCC, ICG fluorescence imaging is useful for identifying the tumor and securing its margin when the lesion is peripheral and wedge resection is planned.","Indocyanine green (ICG) accumulates in hepatocellular carcinoma (HCC), and tumor fluorescence can be observed under irradiation with near infrared light (NIR). This study investigated the clinical utility of ICG fluorescence imaging during resection of pulmonary metastases of HCC. From April 2010 to June 2018, six patients with suspected pulmonary metastasis of HCC were enrolled prospectively. Prior to surgery, all patients underwent the ICG hepatic function test following intravenous administration of ICG (0.5 mg/kg body weight). During surgery, metastatic HCC was identified by observation of ICG fluorescence, allowing assessment of the surgical margin. Tumor fluorescence was also evaluated on cut sections. A total of 11 metastatic HCCs were resected in six patients at nine operations. Eight lesions were removed by wedge resection and 3 lesions were managed by lobectomy. During surgery, tumor fluorescence could be confirmed through the visceral pleura in 6 out of 7 lesions treated by wedge resection, while NIR irradiation was difficult for 1 lesion. For these 6 lesions, the median distance from the tumor to the visceral pleura and the median surgical margin were 0 mm (range, 0-2 mm) and 14 mm (range, 11-17 mm), respectively. When cut sections were examined, all tumors emitted fluorescence. All lesions were histologically confirmed to be metastatic HCC. In patients with pulmonary metastasis of HCC, ICG fluorescence imaging is useful for identifying the tumor and securing its margin when the lesion is peripheral and wedge resection is planned.","null","null","2019-03","Journal of Thoracic Disease","Journal of Thoracic Disease","Vol.11","No.3","944","949","eng","true","null","scientific_journal","null","null","10.21037/jtd.2019.01.107","2072-1439","null","null","null","null","null" "Evaluation of the components of mediastinal cystic lesions using imaging techniques","Evaluation of the components of mediastinal cystic lesions using imaging techniques","Koichiro Kajiura, Shoichiro Takao, Kawano Naoko, Toru Sawada, Mitsuhiro Tsuboi, Hiroaki Toba, Mitsuteru Yoshida, Hiromitsu Takizawa, Akira Tangoku, Kazuya Kondo","Koichiro Kajiura, Shoichiro Takao, Kawano Naoko, Toru Sawada, Mitsuhiro Tsuboi, Hiroaki Toba, Mitsuteru Yoshida, Hiromitsu Takizawa, Akira Tangoku, Kazuya Kondo","null","To identify and differentiate patients with mediastinal cysts from those with cystic tumors requiring surgery. A total of 36 patients with mediastinal cystic lesions were enrolled. The patients were separated into two groups based on pathological findings : those with mediastinal cysts (n=23) and those with mediastinal tumors (n=13). The cystic components were measured using imaging parameters including mean computed tomography (CT) value, apparent diffusion coefficient (ADC), T1 signal intensity ratio (T1SIratio), and T2 signal intensity ratio (T2SI-ratio), acquired from magnetic resonance imaging (MRI) ; and standardized maximum uptake value (SUVmax) fromF-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT). Both groups were statistically compared. Comparative parameters between the cysts and tumors revealed the following ratios : CT value, 40.9?21.2 versus (vs) 24.8?12.9 (p = 0.019) ;SUVmax, 1.18?0.50 vs 4.32?3.52 (p = 0.003) ; ADC, 3.46?0.96 vs 2.68?0.74 (p = 0.022) ; T1SI-ratio, 1.06?0.60 vs 1.35? 0.92 (p = 0.648) ; T2SI-ratio, 5.40?1.80 vs 4.33?1.58 (p = 0.194). However, there was no correlation between FDG uptake and ADC value. SUVmax fromF-FDG PET/CT and ADC derived from MRI were effective in facilitating preoperative diagnosis to differentiate mediastinal cysts from tumors. However, these examinations may be complementary to one another, not dominant. J. Med. Invest. 66 : 106-111, February, 2019.","To identify and differentiate patients with mediastinal cysts from those with cystic tumors requiring surgery. A total of 36 patients with mediastinal cystic lesions were enrolled. The patients were separated into two groups based on pathological findings : those with mediastinal cysts (n=23) and those with mediastinal tumors (n=13). The cystic components were measured using imaging parameters including mean computed tomography (CT) value, apparent diffusion coefficient (ADC), T1 signal intensity ratio (T1SIratio), and T2 signal intensity ratio (T2SI-ratio), acquired from magnetic resonance imaging (MRI) ; and standardized maximum uptake value (SUVmax) fromF-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT). Both groups were statistically compared. Comparative parameters between the cysts and tumors revealed the following ratios : CT value, 40.9?21.2 versus (vs) 24.8?12.9 (p = 0.019) ;SUVmax, 1.18?0.50 vs 4.32?3.52 (p = 0.003) ; ADC, 3.46?0.96 vs 2.68?0.74 (p = 0.022) ; T1SI-ratio, 1.06?0.60 vs 1.35? 0.92 (p = 0.648) ; T2SI-ratio, 5.40?1.80 vs 4.33?1.58 (p = 0.194). However, there was no correlation between FDG uptake and ADC value. SUVmax fromF-FDG PET/CT and ADC derived from MRI were effective in facilitating preoperative diagnosis to differentiate mediastinal cysts from tumors. However, these examinations may be complementary to one another, not dominant. J. Med. Invest. 66 : 106-111, February, 2019.","null","null","2019-02","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.66","No.1,2","106","111","eng","true","null","scientific_journal","null","null","10.2152/jmi.66.106","1349-6867","null","null","null","null","null" "Phase II Study of S-1 Combined With Low-Dose Docetaxel as Neoadjuvant Chemotherapy for Operable Breast Cancer Patients (N-1 Study)","Phase II Study of S-1 Combined With Low-Dose Docetaxel as Neoadjuvant Chemotherapy for Operable Breast Cancer Patients (N-1 Study)","Misako Nakagawa, Mayumi Ikeuchi, Masami Morimoto, Hirokazu Takechi, Hiroaki Toba, Takahiro Yoshida, Kazumasa Okumura, Naoki Hino, Aya Nishisho, Akira Tangoku","Misako Nakagawa, Mayumi Ikeuchi, Masami Morimoto, Hirokazu Takechi, Hiroaki Toba, Takahiro Yoshida, Kazumasa Okumura, Naoki Hino, Aya Nishisho, Akira Tangoku","null","To improve the pathological complete response (pCR) rate, we devised new neoadjuvant chemotherapy. Efficacy and safety of the oral fluoropyrimidine derivative S-1 (Taiho Pharmaceutical Co, Tokyo, Japan) combined with low-dose docetaxel (S-1+DOC) were evaluated. Patients were treated with docetaxel (40 mg/m intravenously on day 1) and S-1 (40 mg/m orally twice per day on days 1-14) every 3 weeks for 4 cycles. In accord with the Response Evaluation Criteria In Solid Tumors version 1.1 criteria, the patients who showed a complete response (CR) underwent surgery, and those who achieved a partial response (PR) underwent 4 more cycles of S-1+DOC. Patients who achieved stable disease (SD) or progressive disease (PD) received EC (epirubicin and cyclophosphamide) or HT (trastuzumab and paclitaxel) according to their HER2 status. The primary end point was the pCR rate. Ninety-four patients entered the study. After 4 cycles of S-1+DOC, CR was noted in 5 patients, PR in 57, SD in 18, and PD in 3. Of the patients who achieved SD and PD, 12 received EC, and 9 received HT. Among the 83 assessable patients, the pCR rate was 34.9%, and the response rate was 80.7%. The pCR rates were 19.5% in the luminal type group, 53.8% in the luminal HER2 group, 46.1% in the HER2 group, and 50.0% in the triple-negative group. The S-1+DOC regimen in this study could be well tolerated and a new candidate neoadjuvant chemotherapy in operable breast cancer patients. It is also expected to be effective even in patients with luminal type disease. However, further randomized control trials are needed to ascertain whether pCR can contribute to favorable outcomes.","To improve the pathological complete response (pCR) rate, we devised new neoadjuvant chemotherapy. Efficacy and safety of the oral fluoropyrimidine derivative S-1 (Taiho Pharmaceutical Co, Tokyo, Japan) combined with low-dose docetaxel (S-1+DOC) were evaluated. Patients were treated with docetaxel (40 mg/m intravenously on day 1) and S-1 (40 mg/m orally twice per day on days 1-14) every 3 weeks for 4 cycles. In accord with the Response Evaluation Criteria In Solid Tumors version 1.1 criteria, the patients who showed a complete response (CR) underwent surgery, and those who achieved a partial response (PR) underwent 4 more cycles of S-1+DOC. Patients who achieved stable disease (SD) or progressive disease (PD) received EC (epirubicin and cyclophosphamide) or HT (trastuzumab and paclitaxel) according to their HER2 status. The primary end point was the pCR rate. Ninety-four patients entered the study. After 4 cycles of S-1+DOC, CR was noted in 5 patients, PR in 57, SD in 18, and PD in 3. Of the patients who achieved SD and PD, 12 received EC, and 9 received HT. Among the 83 assessable patients, the pCR rate was 34.9%, and the response rate was 80.7%. The pCR rates were 19.5% in the luminal type group, 53.8% in the luminal HER2 group, 46.1% in the HER2 group, and 50.0% in the triple-negative group. The S-1+DOC regimen in this study could be well tolerated and a new candidate neoadjuvant chemotherapy in operable breast cancer patients. It is also expected to be effective even in patients with luminal type disease. However, further randomized control trials are needed to ascertain whether pCR can contribute to favorable outcomes.","null","null","2019-02","Clinical Breast Cancer","Clinical Breast Cancer","Vol.S1526-8209","No.18","30262","30263","eng","true","null","scientific_journal","null","null","10.1016/j.clbc.2018.09.008","1938-0666","null","null","null","null","null" "A case of thoracoscopic medial basal segmentectomy","A case of thoracoscopic medial basal segmentectomy","Naoya Kawakita, Hiroaki Toba, Shoji Sakiyama, Mitsuhiro Tsuboi, Hiromitsu Takizawa, Akira Tangoku","Naoya Kawakita, Hiroaki Toba, Shoji Sakiyama, Mitsuhiro Tsuboi, Hiromitsu Takizawa, Akira Tangoku","null","Isolated resection of the medial basal segment (S7) is uncommon because of its small volume, and S7 segmentectomy is considered to be difficult due to anatomical variation. We report a case of successful thoracoscopic S7 segmentectomy. A 56-year-old man was referred to our hospital with suspected pulmonary metastasis of rectal cancer. A 6-mm nodule was detected in S7. A7 and B7 branched from the basal segmental artery and bronchus, respectively, to run ventral to the inferior pulmonary vein. This made it possible to isolate A7 and B7 by an approach via the interlobar fissure. In addition, V7a and V7b were easily isolated from inferior pulmonary vein. The intersegmental plane was indicated by V7b and was transected along a demarcation line identified by using selective oxygenation via B7. B7 most commonly branches from the basal bronchus and A7 from the basal artery to run ventral to the inferior pulmonary vein. With this anatomical type, when the surgeon approaches via the interlobar fissure during surgery, A7 is identified first, B7 is seen behind A7, and the IPV is posterior to B7. Since the intersegmental plane is located ventral to the IPV, segmentectomy can be completed via the interlobar fissure approach. In patients with this pattern of pulmonary artery and bronchial anatomy, isolated S7 segmentectomy is a feasible treatment option.","Isolated resection of the medial basal segment (S7) is uncommon because of its small volume, and S7 segmentectomy is considered to be difficult due to anatomical variation. We report a case of successful thoracoscopic S7 segmentectomy. A 56-year-old man was referred to our hospital with suspected pulmonary metastasis of rectal cancer. A 6-mm nodule was detected in S7. A7 and B7 branched from the basal segmental artery and bronchus, respectively, to run ventral to the inferior pulmonary vein. This made it possible to isolate A7 and B7 by an approach via the interlobar fissure. In addition, V7a and V7b were easily isolated from inferior pulmonary vein. The intersegmental plane was indicated by V7b and was transected along a demarcation line identified by using selective oxygenation via B7. B7 most commonly branches from the basal bronchus and A7 from the basal artery to run ventral to the inferior pulmonary vein. With this anatomical type, when the surgeon approaches via the interlobar fissure during surgery, A7 is identified first, B7 is seen behind A7, and the IPV is posterior to B7. Since the intersegmental plane is located ventral to the IPV, segmentectomy can be completed via the interlobar fissure approach. In patients with this pattern of pulmonary artery and bronchial anatomy, isolated S7 segmentectomy is a feasible treatment option.","null","null","2019-01-11","International Journal of Surgery Case Reports","International Journal of Surgery Case Reports","Vol.55","null","15","17","eng","true","null","scientific_journal","null","null","10.1016/j.ijscr.2018.12.004","2210-2612","null","null","null","null","null" "CT lymphography for superficial esophageal cancer. Lymph Node Metastasis in Gastrointestinal Cancer"" Part IV. Sentinel node navigation surgery, Chapter 17, Methodology: CT lumphography","CT lymphography for superficial esophageal cancer. Lymph Node Metastasis in Gastrointestinal Cancer"" Part IV. Sentinel node navigation surgery, Chapter 17, Methodology: CT lumphography","丹黒 章, 吉田 卓弘, 鳥羽 博明, 武知 浩和, 奥村 和正, 西野 豪志, 井上 聖也, 中川 美砂子, 森本 雅美, 澤田 徹, 青山 万理子, 宮本 直輝, 西岡 康平, 藤本 啓介, 滝沢 宏光","Akira Tangoku, Takahiro Yoshida, Hiroaki Toba, Hirokazu Takechi, Kazumasa Okumura, Takeshi Nishino, Seiya Inoue, Misako Nakagawa, Masami Morimoto, Toru Sawada, 青山 万理子, 宮本 直輝, 西岡 康平, 藤本 啓介, Hiromitsu Takizawa","null","null","null","null","null","2019","Lymph Node Metastasis in Gastrointestinal Cancer. Ed. By Natsugoe S, Springer-Verlag, Tokyo","Lymph Node Metastasis in Gastrointestinal Cancer. Ed. By Natsugoe S, Springer-Verlag, Tokyo","null","null","323","333","jpn","true","null","scientific_journal","null","null","10.1007/978-981-10-4699-5_17","null","null","null","null","null","null" "乳癌頚椎転移による脊髄麻痺に対して迅速な集学的治療によりQOLの改善が得られた1例","Case reports : A case of advanced breast cancer with spinal palsy due to cervical bone metastasis who was improved a quality of life by emergent multidisciplinary oncological salvage","森本 雅美, 行重 佐和香, 池内 真由美, 中川 美砂子, 武知 浩和, 鳥羽 博明, 丹黒 章","Masami Morimoto, 行重 佐和香, 池内 真由美, Misako Nakagawa, Hirokazu Takechi, Hiroaki Toba, Akira Tangoku","null","A 60s female complained of right thigh pain caused by bone metastasis from advanced breast cancer. She was introduced to our ward for systemic therapy with palliative radiation to painful osteolytic lesion in the right femur. She suddenly complained of serious pain and motility disturbance in the right upper-extremity two days after her admission. Magnetic resonance imaging(MRI)suggested bone metastasis in the 3rd cervical vertebra which compressed spinal cord. We discussed about an optimal treatment with the orthopedic surgeon and the radiation therapeutic physician, and laminectomy was scheduled promptly. She also had a right femur fracture a day before her planed laminectomy, so she underwent osteosynthesis of the femur together with laminectomy of the cervical vertebra. She also received the irradiation to the 3rd cervical vertebra and the shaft of right femur. She became able to eat with a spoon by herself and her activity of daily living(ADL)have fully recovered by daily rehabilitation. She is receiving chemotherapy in our out-patient clinic now. We recognized that an emergent oncological treatment for the spinal decompression by the bone metastasis could improve the patients' quality of life(QOL)to avoid the permanent paralysis and also their prognoses.","A 60s female complained of right thigh pain caused by bone metastasis from advanced breast cancer. She was introduced to our ward for systemic therapy with palliative radiation to painful osteolytic lesion in the right femur. She suddenly complained of serious pain and motility disturbance in the right upper-extremity two days after her admission. Magnetic resonance imaging(MRI)suggested bone metastasis in the 3rd cervical vertebra which compressed spinal cord. We discussed about an optimal treatment with the orthopedic surgeon and the radiation therapeutic physician, and laminectomy was scheduled promptly. She also had a right femur fracture a day before her planed laminectomy, so she underwent osteosynthesis of the femur together with laminectomy of the cervical vertebra. She also received the irradiation to the 3rd cervical vertebra and the shaft of right femur. She became able to eat with a spoon by herself and her activity of daily living(ADL)have fully recovered by daily rehabilitation. She is receiving chemotherapy in our out-patient clinic now. We recognized that an emergent oncological treatment for the spinal decompression by the bone metastasis could improve the patients' quality of life(QOL)to avoid the permanent paralysis and also their prognoses.","null","null","2018-08-25","四国医学雑誌","Shikoku Acta Medica","Vol.74","No.3,4","119","124","jpn","true","null","scientific_journal","null","null","null","0037-3699","null","https://ci.nii.ac.jp/naid/120006531556/","null","null","null" "選択的肺葉ブロックを用いた肺切除の2例","Selective lobar blockade for lung resection : A report of two cases","河北 直也, 鳥羽 博明, 先山 正二, 澤田 徹, 坪井 光弘, 吉田 光輝, 川上 行奎, 滝沢 宏光, 近藤 和也, 丹黒 章","Naoya Kawakita, Hiroaki Toba, Shoji Sakiyama, Toru Sawada, Mitsuhiro Tsuboi, Mitsuteru Yoshida, Yukikiyo Kawakami, Hiromitsu Takizawa, Kazuya Kondo, Akira Tangoku","null","There are cases in which one-lung ventilation is difficult due to contralateral lung resection or low lung function. Selective lobar blockade can improve oxygenation compared with one-lung ventilation and secure a good operative field by inducing partial collapse. We report two cases of lung resection involving selective lobar blockade. (Case1) An 80-year-old female had previously undergone right upper and middle lobectomy for multiple lung tumors. Surgery was scheduled to remove a 7‐mm ground glass opacity from the upper left lobe. Oral intubation was performed (inner diameter of intubation tube:8mm). Next, the left upper lobe bronchus was blocked with a7Fr Arndt blocker under bronchoscopy, and partial resection of the left upper lobe was conducted. (Case2) A 75-year-old male had previously undergone right upper lobectomy for pulmonary tuberculosis and had developed right chronic empyema. Surgery was scheduled to remove a 22-mm nodule from the left lingular segment. Oral intubation was performed(inner diameter of intubation tube:8.5mm). Next, the left lingual bronchus was blocked with a7Fr Arndt blocker under bronchoscopy. Left lingular segmentectomy was carried out under thoracoscopic assistance. Intraoperative oxygenation was maintained in both cases, and the release of the block due to hypoxemia was not required in either case.","There are cases in which one-lung ventilation is difficult due to contralateral lung resection or low lung function. Selective lobar blockade can improve oxygenation compared with one-lung ventilation and secure a good operative field by inducing partial collapse. We report two cases of lung resection involving selective lobar blockade. (Case1) An 80-year-old female had previously undergone right upper and middle lobectomy for multiple lung tumors. Surgery was scheduled to remove a 7‐mm ground glass opacity from the upper left lobe. Oral intubation was performed (inner diameter of intubation tube:8mm). Next, the left upper lobe bronchus was blocked with a7Fr Arndt blocker under bronchoscopy, and partial resection of the left upper lobe was conducted. (Case2) A 75-year-old male had previously undergone right upper lobectomy for pulmonary tuberculosis and had developed right chronic empyema. Surgery was scheduled to remove a 22-mm nodule from the left lingular segment. Oral intubation was performed(inner diameter of intubation tube:8.5mm). Next, the left lingual bronchus was blocked with a7Fr Arndt blocker under bronchoscopy. Left lingular segmentectomy was carried out under thoracoscopic assistance. Intraoperative oxygenation was maintained in both cases, and the release of the block due to hypoxemia was not required in either case.","null","null","2018-04-25","四国医学雑誌","Shikoku Acta Medica","Vol.74","No.1,2","55","60","jpn","true","null","scientific_journal","null","null","null","0037-3699","null","https://ci.nii.ac.jp/naid/120006464493/","null","null","null" "The effects of the herbal medicine Daikenchuto (TJ-100) after esophageal cancer resection, open-label, randomized controlled trial","The effects of the herbal medicine Daikenchuto (TJ-100) after esophageal cancer resection, open-label, randomized controlled trial","Takeshi Nishino, Takahiro Yoshida, Masakazu Goto, Seiya Inoue, Takuya Minato, Satoshi Fujiwara, Yota Yamamoto, Yoshihito Furukita, Yasuhiro Yuasa, Hiromichi Yamai, Hirokazu Takechi, Hiroaki Toba, Hiromitsu Takizawa, Mitsuteru Yoshida, Jun-ichi Seike, Takanori Miyoshi, Akira Tangoku","Takeshi Nishino, Takahiro Yoshida, Masakazu Goto, Seiya Inoue, Takuya Minato, Satoshi Fujiwara, Yota Yamamoto, Yoshihito Furukita, Yasuhiro Yuasa, Hiromichi Yamai, Hirokazu Takechi, Hiroaki Toba, Hiromitsu Takizawa, Mitsuteru Yoshida, Jun-ichi Seike, Takanori Miyoshi, Akira Tangoku","null","Daikenchuto (TJ-100), a traditional Japanese herbal medicine, is widely used in Japan. Its effects on gastrointestinal motility and microcirculation and its anti-inflammatory effect are known. The purpose of this prospective randomized controlled trial was to investigate the effect of TJ-100 after esophagectomy in esophageal cancer patients. Forty patients for whom subtotal esophageal resection for esophageal cancer was planned at our institute from March 2011 to August 2013 were enrolled and divided into two groups at the point of determination of the operation schedule after informed consent was obtained: a TJ-100 (15 g/day)-treated group (n = 20) and a control group (n = 20). The primary efficacy end-points were maintenance of the nutrition condition and the recovery of gastrointestinal function. The secondary efficacy end-points were the serum C-reactive protein (CRP) level and adrenomedullin level during the postoperative course, the incidence of postoperative complications, and the length of hospital stay after surgery. We examined 39 patients because one patient in the TJ-100 group was judged as having unresectable cancer after surgery. The mean age of the TJ-100 group patients was significantly older than that of the control group patients.The rate of body weight decrease at postoperative day 21 was significantly suppressed in the TJ-100 group (3.6% vs. the control group: 7.0%, p = 0.014), but the serum albumin level was not significantly different between the groups. The recovery of gastrointestinal function regarding flatus, defecation, and oral intake showed no significant between-group differences, but postoperative bowel symptoms tended to be rare in the TJ-100 group. There was no significant between-group difference in the length of hospital stay after surgery. The serum CRP level at postoperative day 3 was 4.9 mg/dl in the TJ-100 group and 6.9 mg/dl in the control group, showing a tendency of a suppressed serum CRP level in the TJ-100 group (p = 0.126). The rate of increase in adrenomedullin tended to be high postoperatively, but there was no significant difference between the two groups. TJ-100 treatment after esophageal cancer resection has the effects of prompting the recovery of gastrointestinal motility and minimizing body weight loss, and it might suppress the excess inflammatory reaction related to surgery.","Daikenchuto (TJ-100), a traditional Japanese herbal medicine, is widely used in Japan. Its effects on gastrointestinal motility and microcirculation and its anti-inflammatory effect are known. The purpose of this prospective randomized controlled trial was to investigate the effect of TJ-100 after esophagectomy in esophageal cancer patients. Forty patients for whom subtotal esophageal resection for esophageal cancer was planned at our institute from March 2011 to August 2013 were enrolled and divided into two groups at the point of determination of the operation schedule after informed consent was obtained: a TJ-100 (15 g/day)-treated group (n = 20) and a control group (n = 20). The primary efficacy end-points were maintenance of the nutrition condition and the recovery of gastrointestinal function. The secondary efficacy end-points were the serum C-reactive protein (CRP) level and adrenomedullin level during the postoperative course, the incidence of postoperative complications, and the length of hospital stay after surgery. We examined 39 patients because one patient in the TJ-100 group was judged as having unresectable cancer after surgery. The mean age of the TJ-100 group patients was significantly older than that of the control group patients.The rate of body weight decrease at postoperative day 21 was significantly suppressed in the TJ-100 group (3.6% vs. the control group: 7.0%, p = 0.014), but the serum albumin level was not significantly different between the groups. The recovery of gastrointestinal function regarding flatus, defecation, and oral intake showed no significant between-group differences, but postoperative bowel symptoms tended to be rare in the TJ-100 group. There was no significant between-group difference in the length of hospital stay after surgery. The serum CRP level at postoperative day 3 was 4.9 mg/dl in the TJ-100 group and 6.9 mg/dl in the control group, showing a tendency of a suppressed serum CRP level in the TJ-100 group (p = 0.126). The rate of increase in adrenomedullin tended to be high postoperatively, but there was no significant difference between the two groups. TJ-100 treatment after esophageal cancer resection has the effects of prompting the recovery of gastrointestinal motility and minimizing body weight loss, and it might suppress the excess inflammatory reaction related to surgery.","null","null","2018-04","Esophagus","Esophagus","Vol.15","No.2","75","82","eng","true","null","scientific_journal","null","null","10.1007/s10388-017-0601-9","1612-9067","null","null","null","null","null" "A feasibility study of postoperative adjuvant chemotherapy with fluoropyrimidine S-1 in patients with stage II-IIIA non-small cell lung cancer.","A feasibility study of postoperative adjuvant chemotherapy with fluoropyrimidine S-1 in patients with stage II-IIIA non-small cell lung cancer.","Mitsuhiro Tsuboi, Kazuya Kondo, Hiromitsu Takizawa, Naoya Kawakita, Toru Sawada, Hiroaki Toba, Yukikiyo Kawakami, Mitsuteru Yoshida, Hisashi Ishikura, Suguru Kimura, Akira Tangoku","Mitsuhiro Tsuboi, Kazuya Kondo, Hiromitsu Takizawa, Naoya Kawakita, Toru Sawada, Hiroaki Toba, Yukikiyo Kawakami, Mitsuteru Yoshida, Hisashi Ishikura, Suguru Kimura, Akira Tangoku","null","Adjuvant chemotherapy with uracil tegafur (UFT) improved survival among patients with completely resected stage I lung adenocarcinoma. S-1, an oral dihydropyrimidine dehydrogenase (DPD)-inhibitory 5-fluorouracil, is a more potent DPD inhibitor than UFT;therefore, we hypothesized that postoperative adjuvant chemotherapy with S-1 would be effective for advanced non-small cell lung cancer (NSCLC). We conducted a feasibility study of S-1 as postoperative adjuvant chemotherapy in patients with curatively resected pathological stage bold I back 10 bold I and bold I back 10 bold I back 20 bold I A NSCLC. Adjuvant chemotherapy consisted of 9 courses (4-week administration, 2-week withdrawal) of S-1 at 80-120 mg/body per day. Twenty-four patients with completely resected NSCLC were enrolled in this study from November 2007 through December 2010. The primary endpoint was the rate of completion of the scheduled adjuvant chemotherapy. The secondary endpoints were safety, overall survival, and relapse-free survival. Five patients were censored because of disease recurrence. The planned 9 courses of S-1 were administered to completion in 8 patients. Twelve patients completed more than 70% of the planned courses. Grade 3 adverse reactions, such as elevated total bilirubin (4.2%) and pneumonitis (4.2%), were observed, but there were no Grade 4 adverse reactions. Patients who completed more than 70% of the 9 courses demonstrated better overall survival than those who completed less than 70%. Postoperative administration of S-1 may be possible with few severe adverse events as adjuvant chemotherapy for patients with curatively resected pathological stage bold I back 10 bold I -bold I back 10 bold I back 20 bold I A NSCLC. J. Med. Invest. 65:90-95, February, 2018.","Adjuvant chemotherapy with uracil tegafur (UFT) improved survival among patients with completely resected stage I lung adenocarcinoma. S-1, an oral dihydropyrimidine dehydrogenase (DPD)-inhibitory 5-fluorouracil, is a more potent DPD inhibitor than UFT;therefore, we hypothesized that postoperative adjuvant chemotherapy with S-1 would be effective for advanced non-small cell lung cancer (NSCLC). We conducted a feasibility study of S-1 as postoperative adjuvant chemotherapy in patients with curatively resected pathological stage bold I back 10 bold I and bold I back 10 bold I back 20 bold I A NSCLC. Adjuvant chemotherapy consisted of 9 courses (4-week administration, 2-week withdrawal) of S-1 at 80-120 mg/body per day. Twenty-four patients with completely resected NSCLC were enrolled in this study from November 2007 through December 2010. The primary endpoint was the rate of completion of the scheduled adjuvant chemotherapy. The secondary endpoints were safety, overall survival, and relapse-free survival. Five patients were censored because of disease recurrence. The planned 9 courses of S-1 were administered to completion in 8 patients. Twelve patients completed more than 70% of the planned courses. Grade 3 adverse reactions, such as elevated total bilirubin (4.2%) and pneumonitis (4.2%), were observed, but there were no Grade 4 adverse reactions. Patients who completed more than 70% of the 9 courses demonstrated better overall survival than those who completed less than 70%. Postoperative administration of S-1 may be possible with few severe adverse events as adjuvant chemotherapy for patients with curatively resected pathological stage bold I back 10 bold I -bold I back 10 bold I back 20 bold I A NSCLC. J. Med. Invest. 65:90-95, February, 2018.","null","null","2018","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.65","null","90","95","eng","true","null","scientific_journal","null","null","10.2152/jmi.65.90","1349-6867","null","null","null","null","null" "多職種連携による緩和治療が有効であった乳腺悪性葉状腫瘍の1例","多職種連携による緩和治療が有効であった乳腺悪性葉状腫瘍の1例","武知 浩和, 松岡 由江, 秋月 佐代, 森本 雅美, 中川 美砂子, 奥村 和正, 鳥羽 博明, 吉田 卓弘, 丹黒 章","Hirokazu Takechi, 松岡 由江, 秋月 佐代, 森本 雅美, Misako Nakagawa, Kazumasa Okumura, Hiroaki Toba, Takahiro Yoshida, Akira Tangoku","null","The case subject was a woman in her50s who consulted her local clinic for the chief complaint of pain extending from the left buttock to the lower leg. A sacral lesion and giant mass in the right breast were observed, and thus on suspicion of breast cancer the subject was referred to our department. The results of needle biopsy led to the definite diagnosis of malignant phyllodes tumor. At the start of treatment the subject presented markedly reduced activities of daily living due to the pain, and upon the introduction of opioids, and performing palliative irradiation for the sacral metastasis, the pain was successfully alleviated relatively quickly. During this period, the primary lesion became ulcerated and progression of anemia was also observed, and therefore upon applying metronidazole ointment and commencing irradiation for the right breast, therapeutic effects such as tumor regression and control of anemia progression were observed. After the initial consultation the subject expressed severe anxiety, and thus intervention was requested from a nurse specialist in cancer care, who sat with the patient when her condition was explained, and listened closely to her anxiety. Thereafter, 2 courses of epirubicin and cyclophosphamide therapy as systemic chemotherapy were administered, however the disease progressed. The subject desired to receive care at a local medical institution, and thus it was decided with the help of a social worker that she be transferred to a hospice in the short-term.","The case subject was a woman in her50s who consulted her local clinic for the chief complaint of pain extending from the left buttock to the lower leg. A sacral lesion and giant mass in the right breast were observed, and thus on suspicion of breast cancer the subject was referred to our department. The results of needle biopsy led to the definite diagnosis of malignant phyllodes tumor. At the start of treatment the subject presented markedly reduced activities of daily living due to the pain, and upon the introduction of opioids, and performing palliative irradiation for the sacral metastasis, the pain was successfully alleviated relatively quickly. During this period, the primary lesion became ulcerated and progression of anemia was also observed, and therefore upon applying metronidazole ointment and commencing irradiation for the right breast, therapeutic effects such as tumor regression and control of anemia progression were observed. After the initial consultation the subject expressed severe anxiety, and thus intervention was requested from a nurse specialist in cancer care, who sat with the patient when her condition was explained, and listened closely to her anxiety. Thereafter, 2 courses of epirubicin and cyclophosphamide therapy as systemic chemotherapy were administered, however the disease progressed. The subject desired to receive care at a local medical institution, and thus it was decided with the help of a social worker that she be transferred to a hospice in the short-term.","null","null","2017-08-25","四国医学雑誌","Shikoku Acta Medica","Vol.73","No.3,4","169","172","jpn","true","null","scientific_journal","null","null","null","0037-3699","null","http://repo.lib.tokushima-u.ac.jp/111048","null","null","null" "A case of atypical type A thymoma with vascular invasion and lung metastasis","A case of atypical type A thymoma with vascular invasion and lung metastasis","Naoya Kawakita, Kazuya Kondo, Hiroaki Toba, Akiko Yoneda, Hiromitsu Takizawa, Akira Tangoku","Naoya Kawakita, Kazuya Kondo, Hiroaki Toba, Akiko Yoneda, Hiromitsu Takizawa, Akira Tangoku","null","We present a case of type A thymoma with invasion of the left brachiocephalic vein and lung metastases. An 84-year-old man underwent extended thymectomy combined with left brachiocephalic vein reconstruction and resection of a lung metastasis. Histological examination showed vascular invasion by the tumor. The lung metastasis had high mitotic activity and slight nuclear enlargement, the so-called ""atypical"" features, but the main part of the primary tumor did not. However, the intravascular portion of the tumor had ""atypical"" histological features like the lung metastasis. It seems that ""atypical"" histological features are related to clinically malignant behavior.","We present a case of type A thymoma with invasion of the left brachiocephalic vein and lung metastases. An 84-year-old man underwent extended thymectomy combined with left brachiocephalic vein reconstruction and resection of a lung metastasis. Histological examination showed vascular invasion by the tumor. The lung metastasis had high mitotic activity and slight nuclear enlargement, the so-called ""atypical"" features, but the main part of the primary tumor did not. However, the intravascular portion of the tumor had ""atypical"" histological features like the lung metastasis. It seems that ""atypical"" histological features are related to clinically malignant behavior.","null","null","2017-06-24","General Thoracic and Cardiovascular Surgery","General Thoracic and Cardiovascular Surgery","Vol.66","No.4","239","242","eng","true","null","scientific_journal","null","null","10.1007/s11748-017-0794-9","1863-6713","null","null","null","null","null" "Frequent silencing of RASSF1A by DNA methylation in thymic neuroendocrine tumours","Frequent silencing of RASSF1A by DNA methylation in thymic neuroendocrine tumours","Koichiro Kajiura, Hiromitsu Takizawa, Yuki Morimoto, Kiyoshi Masuda, Mitsuhiro Tsuboi, Reina Kishibuchi, Nuliamina Wusiman, Toru Sawada, Naoya Kawakita, Hiroaki Toba, Mitsuteru Yoshida, Yukikiyo Kawakami, Takuya Naruto, Issei Imoto, Akira Tangoku, Kazuya Kondo","Koichiro Kajiura, Hiromitsu Takizawa, Yuki Morimoto, Kiyoshi Masuda, Mitsuhiro Tsuboi, Reina Kishibuchi, Nuliamina Wusiman, Toru Sawada, Naoya Kawakita, Hiroaki Toba, Mitsuteru Yoshida, Yukikiyo Kawakami, Takuya Naruto, Issei Imoto, Akira Tangoku, Kazuya Kondo","null","Aberrant methylation of promoter CpG islands (CGIs) of tumour suppressor genes is a common epigenetic mechanism underlying cancer pathogenesis. The methylation patterns of thymic tumours have not been studied in detail since such tumours are rare. Herein, we sought to identify genes that could serve as epigenetic targets for thymic neuroendocrine tumour (NET) therapy. Genome-wide screening for aberrantly methylated CGIs was performed in three NET samples, seven thymic carcinoma (TC) samples, and eight type-B3 thymoma samples. The methylation status of thymic epithelial tumours (TETs) samples was validated by pyrosequencing in a larger cohort. The expression status was analysed by quantitative polymerase chain reaction (PCR) and immunohistochemistry. We identified a CGI on a novel gene, RASSF1A, which was strongly hypermethylated in NET, but not in thymic carcinoma or B3 thymoma. RASSF1A was identified as a candidate gene statistically and bibliographically, as it showed frequent CGI hypermethylation in NET by genome-wide screening. Pyrosequencing confirmed significant hypermethylation of a RASSF1A CGI in NET. Low-grade NET tissue was more strongly methylated than high-grade NET. Quantitative PCR and immunohistochemical staining revealed that RASSF1A mRNA and protein expression levels were negatively regulated by DNA methylation. RASSF1A is a tumour suppressor gene epigenetically dysregulated in NET. Aberrant methylation of RASSF1A has been reported in various tumours, but this is the first report of RASSF1A hypermethylation in TETs. RASSF1A may represent an epigenetic therapeutic target in thymic NET.","Aberrant methylation of promoter CpG islands (CGIs) of tumour suppressor genes is a common epigenetic mechanism underlying cancer pathogenesis. The methylation patterns of thymic tumours have not been studied in detail since such tumours are rare. Herein, we sought to identify genes that could serve as epigenetic targets for thymic neuroendocrine tumour (NET) therapy. Genome-wide screening for aberrantly methylated CGIs was performed in three NET samples, seven thymic carcinoma (TC) samples, and eight type-B3 thymoma samples. The methylation status of thymic epithelial tumours (TETs) samples was validated by pyrosequencing in a larger cohort. The expression status was analysed by quantitative polymerase chain reaction (PCR) and immunohistochemistry. We identified a CGI on a novel gene, RASSF1A, which was strongly hypermethylated in NET, but not in thymic carcinoma or B3 thymoma. RASSF1A was identified as a candidate gene statistically and bibliographically, as it showed frequent CGI hypermethylation in NET by genome-wide screening. Pyrosequencing confirmed significant hypermethylation of a RASSF1A CGI in NET. Low-grade NET tissue was more strongly methylated than high-grade NET. Quantitative PCR and immunohistochemical staining revealed that RASSF1A mRNA and protein expression levels were negatively regulated by DNA methylation. RASSF1A is a tumour suppressor gene epigenetically dysregulated in NET. Aberrant methylation of RASSF1A has been reported in various tumours, but this is the first report of RASSF1A hypermethylation in TETs. RASSF1A may represent an epigenetic therapeutic target in thymic NET.","null","null","2017-05-25","Lung Cancer","Lung Cancer","Vol.111","null","116","123","eng","true","null","scientific_journal","null","null","10.1016/j.lungcan.2017.05.019","1872-8332","null","null","null","null","null" "悪性胸膜中皮腫に合併した難治性気胸に対し胸腔内フィブリン糊注入療法が有効であった1例","Malignant Pleural Mesothelioma Presenting Refractory Pneumothorax Successfully Treated by Intrapleural Administration of Diluted Fibrin Glue : Report of a Case","西野 豪志, 滝沢 宏光, 西岡 康平, 藤本 啓介, 宮本 直輝, 青山 万理子, 澤田 徹, 河北 直也, 梶浦 耕一郎, 鳥羽 博明, 川上 行奎, 吉田 光輝","Takeshi Nishino, Hiromitsu Takizawa, 西岡 康平, 藤本 啓介, 宮本 直輝, 青山 万理子, Toru Sawada, Naoya Kawakita, Koichiro Kajiura, Hiroaki Toba, Yukikiyo Kawakami, Mitsuteru Yoshida","null","null","null","null","null","2017-05","胸部外科","The Japanese Journal of Thoracic Surgery","Vol.70","No.5","393","396","jpn","true","null","scientific_journal","null","null","null","0021-5252","null","https://ci.nii.ac.jp/naid/40021199857/","null","null","null" "Autofluorescence for the diagnosis of visceral pleural invasion in non-small-cell lung cancer","Autofluorescence for the diagnosis of visceral pleural invasion in non-small-cell lung cancer","Hiromitsu Takizawa, Kazuya Kondo, Naoya Kawakita, Mitsuhiro Tsuboi, Hiroaki Toba, Koichiro Kajiura, Yukikiyo Kawakami, Shoji Sakiyama, Akira Tangoku, Atsushi Morishita, Yasushi Nakagawa, Toshiyuki Hirose","Hiromitsu Takizawa, Kazuya Kondo, Naoya Kawakita, Mitsuhiro Tsuboi, Hiroaki Toba, Koichiro Kajiura, Yukikiyo Kawakami, Shoji Sakiyama, Akira Tangoku, Atsushi Morishita, Yasushi Nakagawa, Toshiyuki Hirose","null","This study was conducted to evaluate the accuracy of autofluorescence as a mode of diagnosis for visceral pleural invasion of non-small-cell lung cancer compared with white-light by means of clinical questions to several thoracic surgeons. Eight independent thoracic surgeons evaluated visceral pleural invasion in 25 cases of non-small-cell lung cancer attached to the visceral pleura on lung windows of preoperative computed tomography images. At the first study meeting to evaluate the accuracy of visceral pleural invasion diagnosis using conventional white-light images, the surgeons diagnosed visceral pleural invasion based on information in preoperative computed tomography images, histological types and videos recorded with white-light mode using a thoracoscope. At the second study meeting to evaluate the accuracy of visceral pleural invasion diagnosis using autofluorescence, the same surgeons diagnosed visceral pleural invasion based on information in 2 videos recorded in white-light mode and in autofluorescence mode using the thoracoscope. The overall average sensitivity, specificity and accuracy of visceral pleural invasion diagnosis by white-light versus autofluorescence mode were 64.6% vs 83.3%, 53.9% vs 73.7% and 56.5% vs 76.0%, respectively. The sensitivity, specificity and accuracy of visceral pleural invasion diagnosis was improved through the additional use of the autofluorescence mode compared with the white-light mode alone.","This study was conducted to evaluate the accuracy of autofluorescence as a mode of diagnosis for visceral pleural invasion of non-small-cell lung cancer compared with white-light by means of clinical questions to several thoracic surgeons. Eight independent thoracic surgeons evaluated visceral pleural invasion in 25 cases of non-small-cell lung cancer attached to the visceral pleura on lung windows of preoperative computed tomography images. At the first study meeting to evaluate the accuracy of visceral pleural invasion diagnosis using conventional white-light images, the surgeons diagnosed visceral pleural invasion based on information in preoperative computed tomography images, histological types and videos recorded with white-light mode using a thoracoscope. At the second study meeting to evaluate the accuracy of visceral pleural invasion diagnosis using autofluorescence, the same surgeons diagnosed visceral pleural invasion based on information in 2 videos recorded in white-light mode and in autofluorescence mode using the thoracoscope. The overall average sensitivity, specificity and accuracy of visceral pleural invasion diagnosis by white-light versus autofluorescence mode were 64.6% vs 83.3%, 53.9% vs 73.7% and 56.5% vs 76.0%, respectively. The sensitivity, specificity and accuracy of visceral pleural invasion diagnosis was improved through the additional use of the autofluorescence mode compared with the white-light mode alone.","null","null","2017","European Journal of Cardio-Thoracic Surgery","European Journal of Cardio-Thoracic Surgery","Vol.53","No.5","987","992","eng","true","null","scientific_journal","null","null","10.1093/ejcts/ezx419","1873-734X","null","null","null","null","null" "Gender differences in clinicopathological features and prognosis of squamous cell carcinoma of the esophagus","Gender differences in clinicopathological features and prognosis of squamous cell carcinoma of the esophagus","Takeshi Nishino, Takahiro Yoshida, Seiya Inoue, Satoshi Fujiwara, Masakazu Goto, Takuya Minato, Yoshihito Furukita, Yota Yamamoto, Yasuhiro Yuasa, Hiromichi Yamai, Hirokazu Takechi, Hiroaki Toba, Hiromitsu Takizawa, Mitsuteru Yoshida, Jun-ichi Seike, Takanori Miyoshi, Akira Tangoku","Takeshi Nishino, Takahiro Yoshida, Seiya Inoue, Satoshi Fujiwara, Masakazu Goto, Takuya Minato, Yoshihito Furukita, Yota Yamamoto, Yasuhiro Yuasa, Hiromichi Yamai, Hirokazu Takechi, Hiroaki Toba, Hiromitsu Takizawa, Mitsuteru Yoshida, Jun-ichi Seike, Takanori Miyoshi, Akira Tangoku","null","null","null","null","null","2017","Esophagus","Esophagus","Vol.14","No.2","122","130","eng","true","null","scientific_journal","null","null","10.1007/s10388-016-0554-4","1612-9059","null","null","null","null","null" "肺癌手術における周術期口腔機能管理の術後肺炎予防効果","肺癌手術における周術期口腔機能管理の術後肺炎予防効果","西野 豪志, 滝沢 宏光, 澤田 徹, 河北 直也, 坪井 光弘, 梶浦 耕一郎, 鳥羽 博明, 吉田 光輝, 川上 行奎, 近藤 和也, 山村 佳子, 東 雅之","Takeshi Nishino, Hiromitsu Takizawa, Toru Sawada, Naoya Kawakita, Mitsuhiro Tsuboi, Koichiro Kajiura, Hiroaki Toba, Mitsuteru Yoshida, Yukikiyo Kawakami, Kazuya Kondo, Yoshiko Yamamura, Masayuki Azuma","null","null","null","null","null","2017","日本呼吸器外科学会雑誌","The Journal of the Japanese Association for Chest Surgery","Vol.31","No.4","432","438","jpn","true","null","scientific_journal","null","null","10.2995/jacsurg.31.432","1881-4158","null","null","null","null","null" "縦隔原発悪性胚細胞性腫瘍に対するBEP療法中に発症した間質性肺炎治療後に手術を施行した2例","Surgical resection after BEP therapy induced interstitial pneumonia during treatment for primary mediastinal malignant germ cell tumor","河北 直也, 先山 正二, 鳥羽 博明, 滝沢 宏光, 広瀬 敏幸","Naoya Kawakita, Shoji Sakiyama, Hiroaki Toba, Hiromitsu Takizawa, 広瀬 敏幸","null","ブレオマイシンによる間質性肺炎は総投与量依存性に頻度が増加する.高容量投与が必要となる縦隔胚細胞性腫瘍において,治療中に間質性肺炎を生じた場合は,その後の手術にも影響がおよぶ可能性がある.今回BEP(bleomycin+etoposide+cisplatin)療法中に生じた間質性肺炎を治療し,早期に手術を施行した2例を報告する.症例1は19歳の男性,症例2は24歳男性で,ともに前縦隔に約10 cmの腫瘍を認め,針生検で卵黄囊腫瘍と診断された.BEP療法を開始し,それぞれ,ブレオマイシン総投与量360,330 mgで間質性肺炎を発症した.化学療法開始103日目,109日目から3日間のステロイドパルスを行い,その後内服で維持療法を行った.画像上,間質性肺炎の改善を認めたため,手術はパルス療法開始後17日目と26日目に残存腫瘍切除と肺部分切除を行った.ともに術後呼吸不全の発症なく経過良好であった.
","The incidence of interstitial pneumonia caused by bleomycin is increasing, dependent on the total dose. Care should be taken in the treatment of a germ cell tumor requiring high-dose administration. If interstitial pneumonia occurs during treatment for a primary mediastinal malignant germ cell tumor, it may influence the subsequent surgical treatment. We report two surgical cases of interstitial pneumonia that occurred during BEP (bleomycin+etoposide+cisplatin) therapy for a primary mediastinal malignant germ cell tumor. Case 1 was a 19-year-old man and case 2 was a 24-year-old man. They both had an anterior mediastinal tumor of around 10 cm in diameter that was diagnosed as a yolk sac tumor by needle biopsy, and received BEP therapy. Interstitial pneumonia occurred at total bleomycin doses of 360 and 330 mg, respectively. They received steroid pulse treatment 103 and 109 days after starting therapy, respectively. Thereafter, they received steroid maintenance treatment by oral administration. Because they showed the improvement of interstitial pneumonia on imaging examinations, they received residual tumor resection and partial resection of the lung 17 and 26 days after starting steroid pulse treatment, respectively. Both post-operative courses were good, without the onset of respiratory failure.
","null","null","2017","日本呼吸器外科学会雑誌","The Journal of the Japanese Association for Chest Surgery","Vol.31","No.1","109","114","jpn","true","null","scientific_journal","null","null","10.2995/jacsurg.31.109","0919-0945","null","https://ci.nii.ac.jp/naid/130005289960/","null","null","null" "A case of subcutaneous emphysema induced by a portable thoracic drainage system after pneumonectomy","A case of subcutaneous emphysema induced by a portable thoracic drainage system after pneumonectomy","Koichiro Kajiura, Hiromitsu Takizawa, Kazuya Kondo, Hiroaki Toba, Yukikiyo Kawakami, Akira Tangoku","Koichiro Kajiura, Hiromitsu Takizawa, Kazuya Kondo, Hiroaki Toba, Yukikiyo Kawakami, Akira Tangoku","null","症例は62歳男性.右肺扁平上皮癌にて術前放射線化学療法後に胸腔鏡補助下右肺全摘術(ND2a-2)を施行した.ポータブル型胸腔ドレナージ装置であるThopazⓇ(トパーズ)にblakeドレーンⓇをつなげて術後胸腔内ドレナージした.術後,咳嗽が多く認められ,皮下気腫が増加した.トパーズのエアリーク表示量はほぼ0 ml/分であった.気管支鏡で気管支断端瘻がないことを確認した.トパーズのドレナージトラブルと判断し,ドレーン抜去すると皮下気腫は軽快した.トパーズには胸腔内圧調節機能があり,胸腔内が過陰圧になるとバルブが開き空気を吸い込ませる機能がある.本症例では咳嗽による急激な胸腔内圧上昇時に胸腔内の空気が皮下に漏れ,その結果起こった胸腔内圧の低下を感知したトパーズ経由で胸腔内へ空気が流入するという機序を繰り返したと考えられた.
","A 62-year-old man was admitted to our hospital for squamous cell lung carcinoma. We performed video-assisted right pneumonectomy after the induction chemoradiation therapy. We used portable thoracic drainage systems: Thopaz® and 19-Fr blake drain®. The patient had a severe cough and showed progressive subcutaneous emphysema. Thopaz® showed little air leakage. We confirmed the absence of a fistula at the bronchial stump via bronchoscopy and the absence of air suction from outside the drainage tube. We removed the thoracic drain because we believed Thopaz® caused the subcutaneous emphysema, and the subcutaneous emphysema subsequently fully resolved.
Thopaz® regulates the mean intrathoracic pressure by supplying air to the thoracic cavity when there is an excessive negative intrathoracic pressure. The mechanism of the increased subcutaneous emphysema by Thopaz® was considered as follows: sudden elevation of the intrathoracic pressure caused by the cough moved intrathoracic air into the subcutaneous space, instead of the blake drain®. Thopaz® supplied air into the thoracic cavity to restore the excessive negative intrathoracic pressure. This cycle was repeated and the subcutaneous emphysema worsened.
","null","null","2017","The Journal of the Japanese Association for Chest Surgery","The Journal of the Japanese Association for Chest Surgery","Vol.31","No.5","610","615","deu","true","null","scientific_journal","null","null","10.2995/jacsurg.31.610","0919-0945","null","https://ci.nii.ac.jp/naid/130005773861/","null","null","null" "FDG-PET/CT陽性を示した肺原発良性血管周囲類上皮細胞腫瘍の1例","A case report of perivascular epithelioid cell tumor of the lung: A benign tumor with intense FDG uptake","宮本 直輝, 河北 直也, 澤田 徹, 鳥羽 博明, 吉田 光輝, 滝沢 宏光","宮本 直輝, Naoya Kawakita, Toru Sawada, Hiroaki Toba, Mitsuteru Yoshida, Hiromitsu Takizawa","null","症例は36歳女性.3年前より近医の検診で縦隔腫瘤が疑われ,経過観察を行っていた.継時的に増大傾向を示し,精査加療目的に当院受診となった.胸部CTで左中縦隔に36 mmの腫瘤影を認め,FDG-PET/CTにて同部位にSUVmax 4.93の集積を認めた.胸腺腫などの縦隔腫瘍を疑い胸腔鏡下手術を施行したが,病変は広基性な肺内腫瘍であった.迅速病理にて低悪性度腫瘍の結果であり左肺上大区切除を行った.術後の病理結果より良性血管周囲類上皮細胞腫瘍(benign perivascular epithelioid cell tumor:PEComa)と診断した.PEComaはまれな疾患であり,PET/CTを使用した報告は極めて少ない.FDGの集積亢進を認めた良性PEComaの1例を報告する.
","The patient was a 36-year-old who was undergoing follow-up observation after a mediastinal mass was identified during a physical examination at a local clinic 3 years earlier. Over time, the mass showed a tendency to grow, and so the subject consulted our hospital for close examination and treatment. Chest CT revealed a mass shadow of 36 mm in the left middle mediastinum, and FDG-PET/CT revealed FDG uptake with an SUVmax of 4.93 at the same site. On suspicion of a mediastinal tumor such as a thymoma, video-assisted thoracoscopic surgery was performed; however, the lesion was a sessile intrapulmonary tumor. Rapid pathological diagnosis revealed low-grade malignancy, and left upper segmentectomy was performed. The postoperative pathology results led to the diagnosis of a benign perivascular epithelioid cell tumor (PEComa). PEComa is a rare condition, for which there are very few reports using PET/CT. We report a case of benign PEComa that showed elevated FDG uptake.
","null","null","2017","日本呼吸器外科学会雑誌","The Journal of the Japanese Association for Chest Surgery","Vol.31","No.5","638","642","jpn","true","null","scientific_journal","null","null","10.2995/jacsurg.31.638","0919-0945","null","https://ci.nii.ac.jp/naid/130005773841/","null","null","null" "胸腺腫摘出術後発症した再生不良性貧血の1例","A case of aplastic anemia after thymothymectomy","梶浦 耕一郎, 先山 正二, 近藤 和也, 鳥羽 博明, 滝沢 宏光, 丹黒 章","Koichiro Kajiura, Shoji Sakiyama, Kazuya Kondo, Hiroaki Toba, Hiromitsu Takizawa, Akira Tangoku","null","胸腺腫には自己免疫性疾患が合併しやすく,時に胸腺腫摘出後に症状が顕在化することがある.胸腺腫摘出後に再生不良性貧血を発症した症例を経験したので報告する.
73歳,女性.前縦隔腫瘍にて紹介され,胸骨正中切開で胸腺胸腺腫摘出術を施行した.正岡分類I期,WHO分類はB1であった.術後半年後,肺炎を発症した.術前には正常範囲内であった血液検査で,汎血球減少を認めた.骨髄穿刺にて骨髄の細胞密度は10∼20%,脂肪髄かつ骨髄球/赤芽球の比は5以上であった.Grade 5の再生不良性貧血と診断した.シクロスポリンAを中心とした加療を行ったが,発症4ヵ月後に多臓器不全にて永眠された.
胸腺腫摘出後の再生不良性貧血は非常に稀な病態であるが,易感染性となり致死的となりうる.胸腺腫摘出後の経過観察の際には再発のみならず,自己免疫疾患の合併にも注意を必要とする.
","Thymoma often leads to complications such as autoimmune disease, and symptoms of autoimmune disease are sometimes observed in patients even after thymothymectomy. Here, we encountered a case of aplastic anemia after thymothymectomy. A 73-year-old woman was admitted to our hospital for the treatment of an anterior mediastinal tumor. We performed thymothymectomy by median sternotomy. Histopathological findings showed type B1 thymoma when classified according to the World Health Organization system, and stage I thymoma when classified according to the Masaoka system. Six months after the surgery, the patient had pneumonia, and her hemogram showed pancytopenia; however, it had been normal before surgery. Puncture of the bone marrow showed the presence of fatty marrow, a cell density of 10-20%, and a myeloid/erythroid ratio of more than five. The patient was diagnosed with a very severe grade of aplastic anemia. Cyclosporine and supportive therapy were administered. However, the patient died of multiple organ failure 4 months after the onset of aplastic anemia.
The occurrence of aplastic anemia after thymothymectomy is a very rare complication. However, this complication is likely to be fatal since the patient becomes immunocompromised. Therefore, it is important to be careful regarding not only the recurrence of thymoma in the patient, but also the occurrence of autoimmune disease during follow-up after thymothymectomy.
","null","null","2017","日本呼吸器外科学会雑誌","The Journal of the Japanese Association for Chest Surgery","Vol.31","No.6","815","822","jpn","true","null","scientific_journal","null","null","10.2995/jacsurg.31.815","0919-0945","null","https://ci.nii.ac.jp/naid/130006078046/","null","null","null" "A randomized, open label study of the efficacy of prophylactic 24-h low-dose landiolol for atrial fibrillation in transthoracic esophagectomy","A randomized, open label study of the efficacy of prophylactic 24-h low-dose landiolol for atrial fibrillation in transthoracic esophagectomy","Takahiro Yoshida, Yoshihito Furukita, Yota Yamamoto, Takeshi Nishino, Seiya Inoue, Masami Morimoto, Kazumasa Okumura, Hiroaki Toba, Mitsuteru Yoshida, Hiromitsu Takizawa, Akira Tangoku","Takahiro Yoshida, Yoshihito Furukita, Yota Yamamoto, Takeshi Nishino, Seiya Inoue, Masami Morimoto, Kazumasa Okumura, Hiroaki Toba, Mitsuteru Yoshida, Hiromitsu Takizawa, Akira Tangoku","null","null","null","null","null","2017","Esophagus","Esophagus","Vol.14","No.1","97","103","eng","true","null","scientific_journal","null","null","10.1007/s10388-016-0553-5","1612-9059","null","null","null","null","null" "Lung regeneration by fetal lung tissue implantation in a mouse pulmonary emphysema model","Lung regeneration by fetal lung tissue implantation in a mouse pulmonary emphysema model","宇山 攻, Shoji Sakiyama, Mitsuteru Yoshida, Koichiro Kenzaki, Hiroaki Toba, Yukikiyo Kawakami, Kazumasa Okumura, Hiromitsu Takizawa, Kazuya Kondo, Akira Tangoku","宇山 攻, Shoji Sakiyama, Mitsuteru Yoshida, Koichiro Kenzaki, Hiroaki Toba, Yukikiyo Kawakami, Kazumasa Okumura, Hiromitsu Takizawa, Kazuya Kondo, Akira Tangoku","null","The mortality and morbidity of chronic obstructive pulmonary disease are high. However, no radical therapy has been developed to date. The purpose of this study was to evaluate whether fetal mouse lung tissue can grow and differentiate in the emphysematous lung. Fetal lung tissue from green fluorescent protein C57BL/6 mice at 16 days' gestation was used as donor material. Twelve-month-old pallid mice were used as recipients. Donor lungs were cut into small pieces and implanted into the recipient left lung by performing thoracotomy under anesthesia. The recipient mice were sacrificed at day 7, 14, and 28 after implantation and used for histological examination. Well-developed spontaneous pulmonary emphysema was seen in 12-month-old pallid mice. Smooth and continuous connection between implanted fetal lung tissue and recipient lung was recognized. Air space expansion and donor tissue differentiation were observed over time. We could clearly distinguish the border zones between injected tissue and native tissue by the green fluorescence of grafts. Fetal mouse lung fragments survived and differentiated in the emphysematous lung of pallid mice. Implantation of fetal lung tissue in pallid mice might lead to further lung regeneration research from the perspective of respiratory and exercise function. J. Med. Invest. 63: 182-186, August, 2016.","The mortality and morbidity of chronic obstructive pulmonary disease are high. However, no radical therapy has been developed to date. The purpose of this study was to evaluate whether fetal mouse lung tissue can grow and differentiate in the emphysematous lung. Fetal lung tissue from green fluorescent protein C57BL/6 mice at 16 days' gestation was used as donor material. Twelve-month-old pallid mice were used as recipients. Donor lungs were cut into small pieces and implanted into the recipient left lung by performing thoracotomy under anesthesia. The recipient mice were sacrificed at day 7, 14, and 28 after implantation and used for histological examination. Well-developed spontaneous pulmonary emphysema was seen in 12-month-old pallid mice. Smooth and continuous connection between implanted fetal lung tissue and recipient lung was recognized. Air space expansion and donor tissue differentiation were observed over time. We could clearly distinguish the border zones between injected tissue and native tissue by the green fluorescence of grafts. Fetal mouse lung fragments survived and differentiated in the emphysematous lung of pallid mice. Implantation of fetal lung tissue in pallid mice might lead to further lung regeneration research from the perspective of respiratory and exercise function. J. Med. Invest. 63: 182-186, August, 2016.","null","null","2016","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.63","No.3-4","182","186","eng","true","null","scientific_journal","null","null","10.2152/jmi.63.182","1349-6867","null","null","null","null","null" "Thirty percent of ductal carcinoma in situ of the breast in Japan is extremely low-grade ER(+)/HER2(-) type without comedo necrosis","Thirty percent of ductal carcinoma in situ of the breast in Japan is extremely low-grade ER(+)/HER2(-) type without comedo necrosis","Miyuki Kanematsu, Masami Morimoto, Masako Takahashi, Junko Honda, Yoshimi Bando, Takuya Moriya, Yukiko Tadokoro, Misako Nakagawa, Hirokazu Takechi, Takahiro Yoshida, Hiroaki Toba, Mitsuteru Yoshida, Aiichiro Kajikawa, Akira Tangoku, Issei Imoto, Mitsunori Sasa","Miyuki Kanematsu, Masami Morimoto, Masako Takahashi, Junko Honda, Yoshimi Bando, Takuya Moriya, Yukiko Tadokoro, Misako Nakagawa, Hirokazu Takechi, Takahiro Yoshida, Hiroaki Toba, Mitsuteru Yoshida, Aiichiro Kajikawa, Akira Tangoku, Issei Imoto, Mitsunori Sasa","null","Background Overdiagnosis in mammography (MMG) is a problem. Combination of MMG and ultrasonography for breast cancer screening may increase overdiagnosis. Most cases of overdiagnosis are low-grade ductal carcinoma in situ (LGD), but no reports have focused on them. Materials and methods We immunostained 169 ductal carcinoma in situ (DCIS) cases for ER, PgR, HER2 and Ki67 and classified them into 4 subtypes: ER(+)/HER2(-), ER(+)/HER2(+), ER(-)/HER2(-) and ER(-)/HER2(+). The Ki67 index was used to evaluate the grade of malignancy and examined for correlations with each ER/HER2 subtype and the nuclear grade (NG), with/without comedo necrosis. Results The Ki67 index correlated significantly with NG, both with/without comedo necrosis, and reliably evaluated the grade of malignancy. The index for ER(+)/HER2(-) (n=117, 69.2%) was 7.45±7.10, which was significantly lower than for each of the other types. The index was 5.71±6.94 for ER(+)/HER2(-) without comedo necrosis (n=52, 30.8%), which was significantly lower than with comedo necrosis. This was considered LGD, characterized by absence of microcalcification in MMG and either presence of a solid mass or cystic lesion or absence of hypoechoic areas in ultrasound. Conclusion In Japan, ER(+)/HER2(-) without comedo necrosis accounts for about 30% of DCIS and is LGD. This may be being overdiagnosed. J. Med. Invest. 63: 192-198, August, 2016.","Background Overdiagnosis in mammography (MMG) is a problem. Combination of MMG and ultrasonography for breast cancer screening may increase overdiagnosis. Most cases of overdiagnosis are low-grade ductal carcinoma in situ (LGD), but no reports have focused on them. Materials and methods We immunostained 169 ductal carcinoma in situ (DCIS) cases for ER, PgR, HER2 and Ki67 and classified them into 4 subtypes: ER(+)/HER2(-), ER(+)/HER2(+), ER(-)/HER2(-) and ER(-)/HER2(+). The Ki67 index was used to evaluate the grade of malignancy and examined for correlations with each ER/HER2 subtype and the nuclear grade (NG), with/without comedo necrosis. Results The Ki67 index correlated significantly with NG, both with/without comedo necrosis, and reliably evaluated the grade of malignancy. The index for ER(+)/HER2(-) (n=117, 69.2%) was 7.45±7.10, which was significantly lower than for each of the other types. The index was 5.71±6.94 for ER(+)/HER2(-) without comedo necrosis (n=52, 30.8%), which was significantly lower than with comedo necrosis. This was considered LGD, characterized by absence of microcalcification in MMG and either presence of a solid mass or cystic lesion or absence of hypoechoic areas in ultrasound. Conclusion In Japan, ER(+)/HER2(-) without comedo necrosis accounts for about 30% of DCIS and is LGD. This may be being overdiagnosed. J. Med. Invest. 63: 192-198, August, 2016.","null","null","2016","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.63","No.3-4","192","198","eng","true","null","scientific_journal","null","null","10.2152/jmi.63.192","1349-6867","null","null","null","null","null" "急速に増大する巨大気腫性肺囊胞に対して囊胞内吸引後にEWSとフィブリン糊注入で軽快した1例","急速に増大する巨大気腫性肺囊胞に対して囊胞内吸引後にEWSとフィブリン糊注入で軽快した1例","鳥羽 博明, 監﨑 孝一郎, 滝沢 宏光, 先山 正二, 近藤 和也, 丹黒 章","Hiroaki Toba, Koichiro Kenzaki, Hiromitsu Takizawa, Shoji Sakiyama, Kazuya Kondo, Akira Tangoku","null","null","null","null","null","2016","気管支学","The Journal of the Japan Society for Respiratory Endoscopy","Vol.38","No.4","324","327","jpn","true","null","scientific_journal","null","null","10.18907/jjsre.38.4_324","2186-0149","null","null","null","null","null" "胸腔鏡下右上葉切除術の手術時間に影響する因子の検討","胸腔鏡下右上葉切除術の手術時間に影響する因子の検討","滝沢 宏光, 坪井 光弘, 梶浦 耕一郎, 鳥羽 博明, 中川 靖士, 川上 行奎, 吉田 光輝, 先山 正二, 近藤 和也, 丹黒 章","Hiromitsu Takizawa, Mitsuhiro Tsuboi, Koichiro Kajiura, Hiroaki Toba, Yasushi Nakagawa, Yukikiyo Kawakami, Mitsuteru Yoshida, Shoji Sakiyama, Kazuya Kondo, Akira Tangoku","null","null","null","null","null","2016","日本呼吸器外科学会雑誌","The Journal of the Japanese Association for Chest Surgery","Vol.30","No.1","2","7","jpn","true","null","scientific_journal","null","null","10.2995/jacsurg.30.2","1881-4158","null","null","null","null","null" "Assay of serum E2 concentration in postmenopausal breast cancer patients using a high-sensitivity RIA method is generally useful.","Assay of serum E2 concentration in postmenopausal breast cancer patients using a high-sensitivity RIA method is generally useful.","Masami Morimoto, Masako Takahashi, Junko Honda, Takahiro Yoshida, Mitsuteru Yoshida, Hiroaki Toba, Issei Imoto, Akira Tangoku, Mitsunori Sasa","Masami Morimoto, Masako Takahashi, Junko Honda, Takahiro Yoshida, Mitsuteru Yoshida, Hiroaki Toba, Issei Imoto, Akira Tangoku, Mitsunori Sasa","null","Serum E2 levels determined for postmenopausal women by RIA and LC-MS/MS generally correlated well. High-sensitivity RIA is a potentially useful clinical assay, but it overestimated serum E2 in some women. J. Med. Invest. 63: 236-240, August, 2016.","Serum E2 levels determined for postmenopausal women by RIA and LC-MS/MS generally correlated well. High-sensitivity RIA is a potentially useful clinical assay, but it overestimated serum E2 in some women. J. Med. Invest. 63: 236-240, August, 2016.","null","null","2016","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.63","No.3-4","236","240","eng","true","null","scientific_journal","null","null","10.2152/jmi.63.236","1349-6867","null","null","null","null","null" "Safe and successful treatment with afatinib in three postoperative non-small cell lung cancer patients with recurrences following gefitinib/erlotinib-induced hepatotoxicity.","Safe and successful treatment with afatinib in three postoperative non-small cell lung cancer patients with recurrences following gefitinib/erlotinib-induced hepatotoxicity.","Hiroaki Toba, Shoji Sakiyama, Hiromitsu Takizawa, Akira Tangoku","Hiroaki Toba, Shoji Sakiyama, Hiromitsu Takizawa, Akira Tangoku","null","Afatinib could be a well-tolerated EGFR-TKI that could be chosen for its relatively low hepatotoxicity, which is attributable to its having a different metabolic mechanism compared to other EGFR-TKIs. J. Med. Invest. 63: 149-151, February, 2016.","Afatinib could be a well-tolerated EGFR-TKI that could be chosen for its relatively low hepatotoxicity, which is attributable to its having a different metabolic mechanism compared to other EGFR-TKIs. J. Med. Invest. 63: 149-151, February, 2016.","null","null","2016","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.63","No.1-2","149","151","eng","true","null","scientific_journal","null","null","10.2152/jmi.63.149","1349-6867","null","null","null","null","null" "XB130 promotes bronchioalveolar stem cell and Club cell proliferation in airway epithelial repair and regeneration","XB130 promotes bronchioalveolar stem cell and Club cell proliferation in airway epithelial repair and regeneration","Hiroaki Toba, Y Wang, X Bai, R Zamel, HR Cho, H Liu, A Lira, S Keshavjee, M Liu","Hiroaki Toba, Y Wang, X Bai, R Zamel, HR Cho, H Liu, A Lira, S Keshavjee, M Liu","null","Proliferation of bronchioalveolar stem cells (BASCs) is essential for epithelial repair. XB130 is a novel adaptor protein involved in the regulation of epithelial cell survival, proliferation and migration through the PI3K/Akt pathway. To determine the role of XB130 in airway epithelial injury repair and regeneration, a naphthalene-induced airway epithelial injury model was used with XB130 knockout (KO) mice and their wild type (WT) littermates. In XB130 KO mice, at days 7 and 14, small airway epithelium repair was significantly delayed with fewer number of Club cells (previously called Clara cells). CCSP (Club cell secreted protein) mRNA expression was also significantly lower in KO mice at day 7. At day 5, there were significantly fewer proliferative epithelial cells in the KO group, and the number of BASCs significantly increased in WT mice but not in KO mice. At day 7, phosphorylation of Akt, GSK-3β, and the p85α subunit of PI3K was observed in airway epithelial cells in WT mice, but to a much lesser extent in KO mice. Microarray data also suggest that PI3K/Akt-related signals were regulated differently in KO and WT mice. An inhibitory mechanism for cell proliferation and cell cycle progression was suggested in KO mice. XB130 is involved in bronchioalveolar stem cell and Club cell proliferation, likely through the PI3K/Akt/GSK-3β pathway.","Proliferation of bronchioalveolar stem cells (BASCs) is essential for epithelial repair. XB130 is a novel adaptor protein involved in the regulation of epithelial cell survival, proliferation and migration through the PI3K/Akt pathway. To determine the role of XB130 in airway epithelial injury repair and regeneration, a naphthalene-induced airway epithelial injury model was used with XB130 knockout (KO) mice and their wild type (WT) littermates. In XB130 KO mice, at days 7 and 14, small airway epithelium repair was significantly delayed with fewer number of Club cells (previously called Clara cells). CCSP (Club cell secreted protein) mRNA expression was also significantly lower in KO mice at day 7. At day 5, there were significantly fewer proliferative epithelial cells in the KO group, and the number of BASCs significantly increased in WT mice but not in KO mice. At day 7, phosphorylation of Akt, GSK-3β, and the p85α subunit of PI3K was observed in airway epithelial cells in WT mice, but to a much lesser extent in KO mice. Microarray data also suggest that PI3K/Akt-related signals were regulated differently in KO and WT mice. An inhibitory mechanism for cell proliferation and cell cycle progression was suggested in KO mice. XB130 is involved in bronchioalveolar stem cell and Club cell proliferation, likely through the PI3K/Akt/GSK-3β pathway.","null","null","2015-10-13","Oncotarget","Oncotarget","Vol.6","No.31","30803","30817","eng","true","null","scientific_journal","null","null","10.18632/oncotarget.5062","1949-2553","null","null","null","null","null" "発症予測が困難であった肺癌術後間質性肺炎急性増悪の2例","Acute exacerbation of interstitial pneumonia after pulmonary resection for lung cancer : Analysis of two cases","坪井 光弘, 松本 大資, 河北 直也, 梶浦 耕一郎, 鳥羽 博明, 中川 靖士, 川上 行奎, 滝沢 宏光, 先山 正二, 近藤 和也, 丹黒 章","Mitsuhiro Tsuboi, 松本 大資, 河北 直也, Koichiro Kajiura, Hiroaki Toba, Yasushi Nakagawa, Yukikiyo Kawakami, Hiromitsu Takizawa, Shoji Sakiyama, Kazuya Kondo, Akira Tangoku","null","Acute exacerbation of interstitial pneumonia (IP) is one of the most severe and fatal postoperative complications in lung cancer patients underlying IP. We treated two patients suffered from acute exacerbation of IP after pulmonary resection for lung cancer. We analyzed their clinical findings. Thoracoscopic lobectomy with mediastinal lymph node dissection was performed in these cases. The patients were diagnosed with acute exacerbation 4 or 5 days after operation and treated with steroids. Both patients had not been diagnosed as IPs before surgery, however, IPs were diagnosed by retrospective analysis of pathological examination for the removal lungs. Chest CT before surgery showed an interstitial shadow in the lung field faintly in these cases. It should be considered that patients who show a faint interstitial shadow in chest CT could potentially cause an acute exacerbation of IP after lung cancer operation.","Acute exacerbation of interstitial pneumonia (IP) is one of the most severe and fatal postoperative complications in lung cancer patients underlying IP. We treated two patients suffered from acute exacerbation of IP after pulmonary resection for lung cancer. We analyzed their clinical findings. Thoracoscopic lobectomy with mediastinal lymph node dissection was performed in these cases. The patients were diagnosed with acute exacerbation 4 or 5 days after operation and treated with steroids. Both patients had not been diagnosed as IPs before surgery, however, IPs were diagnosed by retrospective analysis of pathological examination for the removal lungs. Chest CT before surgery showed an interstitial shadow in the lung field faintly in these cases. It should be considered that patients who show a faint interstitial shadow in chest CT could potentially cause an acute exacerbation of IP after lung cancer operation.","null","null","2015-08-25","四国医学雑誌","Shikoku Acta Medica","Vol.71","No.3,4","81","86","jpn","true","null","scientific_journal","null","null","null","0037-3699","null","http://repo.lib.tokushima-u.ac.jp/109923","null","null","null" "これからの遺伝子診療を考える 遺伝性乳がんについて","Hereditary breast cancer","丹黒 章, 田所 由紀子, 武知 浩和, 鳥羽 博明, 中川 美砂子","Akira Tangoku, Yukiko Tadokoro, Hirokazu Takechi, Hiroaki Toba, Misako Nakagawa","null","null","null","null","null","2015-05-15","四国医学雑誌","Shikoku Acta Medica","Vol.71","No.5,6","105","110","jpn","true","null","scientific_journal","null","null","null","0037-3699","null","null","null","null","null" "人工呼吸器管理中の慢性有瘻性膿胸に対してEWSを用いた気管支充填術を施行した1例","人工呼吸器管理中の慢性有瘻性膿胸に対してEWSを用いた気管支充填術を施行した1例","梶浦 耕一郎, 滝沢 宏光, 坪井 光弘, 鳥羽 博明, 中川 靖士, 川上 行奎, 先山 正二, 近藤 和也, 丹黒 章","Koichiro Kajiura, Hiromitsu Takizawa, Mitsuhiro Tsuboi, Hiroaki Toba, Yasushi Nakagawa, Yukikiyo Kawakami, Shoji Sakiyama, Kazuya Kondo, Akira Tangoku","null","null","null","null","null","2015","気管支学","The Journal of the Japan Society for Respiratory Endoscopy","Vol.37","No.4","409","413","jpn","true","null","scientific_journal","null","null","10.18907/jjsre.37.4_409","2186-0149","null","null","null","null","null" "胸腔鏡下気管支動脈結紮を施行した気管支動脈蔓状血管腫の1例","胸腔鏡下気管支動脈結紮を施行した気管支動脈蔓状血管腫の1例","坪井 光弘, 鳥羽 博明, 川上 行奎, 先山 正二, 近藤 和也, 丹黒 章","Mitsuhiro Tsuboi, Hiroaki Toba, Yukikiyo Kawakami, Shoji Sakiyama, Kazuya Kondo, Akira Tangoku","null","null","null","null","null","2015","日本臨床外科学会雑誌","Journal of Japan Surgical Association","Vol.76","No.10","2417","2421","jpn","true","null","scientific_journal","null","null","10.3919/jjsa.76.2417","1882-5133","null","null","null","null","null" "肺癌の術中胸膜浸潤診断の正確性についての検討","肺癌の術中胸膜浸潤診断の正確性についての検討","滝沢 宏光, 坪井 光弘, 梶浦 耕一郎, 鳥羽 博明, 中川 靖士, 川上 行奎, 吉田 光輝, 先山 正二, 近藤 和也, 森下 敦司, 河北 直也, 広瀬 敏幸","Hiromitsu Takizawa, Mitsuhiro Tsuboi, Koichiro Kajiura, Hiroaki Toba, Yasushi Nakagawa, Yukikiyo Kawakami, Mitsuteru Yoshida, Shoji Sakiyama, Kazuya Kondo, 森下 敦司, 河北 直也, 広瀬 敏幸","null","null","null","null","null","2015","日本呼吸器外科学会雑誌","The Journal of the Japanese Association for Chest Surgery","Vol.29","No.5","576","581","jpn","true","null","scientific_journal","null","null","10.2995/jacsurg.29.576","1881-4158","null","null","null","null","null" "Comprehensive evaluation of the response of genes to the administration of the antitumor drug S-1 using a low density array.","Comprehensive evaluation of the response of genes to the administration of the antitumor drug S-1 using a low density array.","Hisashi Matsuoka, Kazuya Kondo, Hiromitsu Takizawa, Haruhiko Fujino, Etsuko Sakamoto, Junji Uchida, Koh Uyama, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama, Akira Tangoku","Hisashi Matsuoka, Kazuya Kondo, Hiromitsu Takizawa, Haruhiko Fujino, Etsuko Sakamoto, Junji Uchida, Koh Uyama, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama, Akira Tangoku","null","S-1 is a newly developed dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine that exhibits high clinical efficacy against non-small cell lung cancers. To identify genes that may be associated with chemosensitivity to the antitumor drug S-1, we used a low density array representing 93 genes to analyze expression profiles in 4 orthotopically implanted lung cancers derived from human lung cancer cell lines (Lu99, Lu130, LC6 and A549). The tumor growth inhibition (TGI) rates of S-1 in orthotopically implanted tumors of the Lu99, Lu130, LC6 and A549 cell lines were 34.6, 37.5, 32.1 and 3.6%, respectively. The expression of the PRSS3, ABCC4, TXN, SHMT1 and CMPK genes was significantly promoted in the orthotopically implanted SCID mouse model of the 4 lung cancer cell lines by the administration of S-1, while the expression of the LMO7 and FOLH1 genes was significantly suppressed. The expression of the ABCC1, 2 and TST genes was negatively correlated with TGI. The expression of the TK1 and ERCC2 genes was positively correlated with TGI. The results of the present study suggest that the expression of the ABCC1, 2, TST, TK1 and ERCC2 genes is related to resistance to the antitumor drug S-1.","S-1 is a newly developed dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine that exhibits high clinical efficacy against non-small cell lung cancers. To identify genes that may be associated with chemosensitivity to the antitumor drug S-1, we used a low density array representing 93 genes to analyze expression profiles in 4 orthotopically implanted lung cancers derived from human lung cancer cell lines (Lu99, Lu130, LC6 and A549). The tumor growth inhibition (TGI) rates of S-1 in orthotopically implanted tumors of the Lu99, Lu130, LC6 and A549 cell lines were 34.6, 37.5, 32.1 and 3.6%, respectively. The expression of the PRSS3, ABCC4, TXN, SHMT1 and CMPK genes was significantly promoted in the orthotopically implanted SCID mouse model of the 4 lung cancer cell lines by the administration of S-1, while the expression of the LMO7 and FOLH1 genes was significantly suppressed. The expression of the ABCC1, 2 and TST genes was negatively correlated with TGI. The expression of the TK1 and ERCC2 genes was positively correlated with TGI. The results of the present study suggest that the expression of the ABCC1, 2, TST, TK1 and ERCC2 genes is related to resistance to the antitumor drug S-1.","null","null","2014-11-17","International Journal of Oncology","International Journal of Oncology","Vol.46","No.2","569","577","eng","true","null","scientific_journal","null","null","10.3892/ijo.2014.2754","1791-2423","null","null","null","null","null" "Holter ECG monitoring of sympathovagal fluctuation during bronchoscopy.","Holter ECG monitoring of sympathovagal fluctuation during bronchoscopy.","Khalil Abdellah Hamed Ali, Hiroaki Toba, Shoji Sakiyama, Ryo Yamamoto, Hiromitsu Takizawa, Koichiro Kenzaki, Kazuya Kondo, Akira Tangoku","Khalil Abdellah Hamed Ali, Hiroaki Toba, Shoji Sakiyama, Ryo Yamamoto, Hiromitsu Takizawa, Koichiro Kenzaki, Kazuya Kondo, Akira Tangoku","null","Heart rate increased significantly after pre-medication compared with that before pre-medication and increased further during bronchoscopy. The coefficient of variation (CVRR ) values after pre-medication and during bronchoscopy were significantly higher than those before pre-medication (P = 0.031 and P = 0.041, respectively). The low frequency (LF) power decreased during bronchoscopy. LF powers obtained after bronchoscopy were significantly lower than those obtained before bronchoscopy (P < 0.041). The high-frequency (HF) power was found to be decreased during bronchoscopy. In particular, HF powers obtained after bronchoscopy were significantly lower than those obtained before bronchoscopy (P < 0.019). Although the LF/HF ratios increased after pre-medication, they decreased temporarily during the bronchoscope insertion.","This study shows for the first time that Holter ECG monitoring during diagnostic bronchoscopy was associated with activation of cardiac sympathetic and withdrawal of cardiac parasympathetic regulation, which may contribute to the occurrence of cardiac events during bronchoscopic procedures. So, Holter ECG monitoring during bronchoscopic procedures may confer reduction in cardiovascular events.","null","null","2014-09-05","The Clinical Respiratory Journal","The Clinical Respiratory Journal","null","null","null","null","eng","true","null","scientific_journal","null","null","10.1111/crj.12204","1752-699X","null","null","null","null","null" "肺葉切除における電動式自動縫合器の使用経験","Evaluation of Powered ECHELON FLEX for pulmonary lobectomy","坪井 光弘, 先山 正二, 住友 弘幸, 坂本 晋一, 梶浦 耕一郎, 鳥羽 博明, 中川 靖士, 川上 行奎, 滝沢 宏光, 近藤 和也, 丹黒 章","Mitsuhiro Tsuboi, Shoji Sakiyama, 住友 弘幸, 坂本 晋一, Koichiro Kajiura, Hiroaki Toba, Yasushi Nakagawa, Yukikiyo Kawakami, Hiromitsu Takizawa, Kazuya Kondo, Akira Tangoku","null","Objective : It has been accepted to use staplers for open and video-assisted thoracic surgery, however there was a risk in stapling of the pulmonary vasculatures. A newly developed stapler, powered ECHELON FLEX (Ethicon) is an electrically-powered stapler. It may reduce tip movement during cutting and stapling, which results in reduction of the risk of trauma to surrounding tissue. The aim of this study was to evaluate powered ECHELON FLEX for pulmonary lobectomy. Methods : We reviewed 16 patients who underwent pulmonary lobectomy with powered ECHELON FLEX in our institution from December, 2013 to April, 2014. Results : There were 25 stapling for the pulmonary artery, 17 stapling for the pulmonary vein, 16 stapling for the bronchus, and 33 stapling for the pulmonary parenchyma. Though two case of oozing from the stamps of a pulmonary artery and pulmonary parenchyma, there were no serious complications related to use of the staplers. Conclusions : The powered ECHELON FLEX can be used for pulmonary lobectomy safely.","Objective : It has been accepted to use staplers for open and video-assisted thoracic surgery, however there was a risk in stapling of the pulmonary vasculatures. A newly developed stapler, powered ECHELON FLEX (Ethicon) is an electrically-powered stapler. It may reduce tip movement during cutting and stapling, which results in reduction of the risk of trauma to surrounding tissue. The aim of this study was to evaluate powered ECHELON FLEX for pulmonary lobectomy. Methods : We reviewed 16 patients who underwent pulmonary lobectomy with powered ECHELON FLEX in our institution from December, 2013 to April, 2014. Results : There were 25 stapling for the pulmonary artery, 17 stapling for the pulmonary vein, 16 stapling for the bronchus, and 33 stapling for the pulmonary parenchyma. Though two case of oozing from the stamps of a pulmonary artery and pulmonary parenchyma, there were no serious complications related to use of the staplers. Conclusions : The powered ECHELON FLEX can be used for pulmonary lobectomy safely.","null","null","2014-08-25","四国医学雑誌","Shikoku Acta Medica","Vol.70","No.3-4","57","60","jpn","true","null","scientific_journal","null","null","null","0037-3699","null","http://repo.lib.tokushima-u.ac.jp/109754","null","null","null" "肺癌ロボット手術の私費料金設定","Setting of fees for robotic surgery for lung cancer not covered by insurance","滝沢 宏光, 先山 正二, 梶浦 耕一郎, 森下 敦司, 西野 豪志, 坪井 光弘, 鳥羽 博明, 中川 靖士, 吉田 光輝, 川上 行奎, 近藤 和也, 丹黒 章","Hiromitsu Takizawa, Shoji Sakiyama, Koichiro Kajiura, 森下 敦司, 西野 豪志, Mitsuhiro Tsuboi, Hiroaki Toba, Yasushi Nakagawa, Mitsuteru Yoshida, Yukikiyo Kawakami, Kazuya Kondo, Akira Tangoku","null","In Japan, the only robot surgery covered by health insurance is prostatectomy. Robot surgery for pulmonary cancer has not been approved as advanced health care, and hospitals are required to set out-of-pocket fees for surgery on their own. We calculated the fee not covered by insurance to be 1.28million yen, taking into account expenses for : (1) the use of medical equipment, (2) maintenance, (3) labor costs, and (4) medical materials and drugs. Since the fees for surgery plus hospitalization are actually incurred by patients, whether or not the hospitalization fee should be included in out-of-pocket medical fees is decided by each health care institution. In any case, it is necessary to provide patients with a summary of medical fees prior to surgery. Hospitals are required to collect data on pulmonary robot surgical cases while operating the system with medical fees incurred by individual patients.","In Japan, the only robot surgery covered by health insurance is prostatectomy. Robot surgery for pulmonary cancer has not been approved as advanced health care, and hospitals are required to set out-of-pocket fees for surgery on their own. We calculated the fee not covered by insurance to be 1.28million yen, taking into account expenses for : (1) the use of medical equipment, (2) maintenance, (3) labor costs, and (4) medical materials and drugs. Since the fees for surgery plus hospitalization are actually incurred by patients, whether or not the hospitalization fee should be included in out-of-pocket medical fees is decided by each health care institution. In any case, it is necessary to provide patients with a summary of medical fees prior to surgery. Hospitals are required to collect data on pulmonary robot surgical cases while operating the system with medical fees incurred by individual patients.","null","null","2014-08-25","四国医学雑誌","Shikoku Acta Medica","Vol.70","No.3,4","51","56","jpn","true","null","scientific_journal","null","null","null","0037-3699","null","http://repo.lib.tokushima-u.ac.jp/109753","null","null","null" "肺癌におけるsentinel node navigation surgery","肺癌におけるsentinel node navigation surgery","滝沢 宏光, 先山 正二, 丹黒 章, 梶浦 耕一郎, 鳥羽 博明","Hiromitsu Takizawa, Shoji Sakiyama, Akira Tangoku, Koichiro Kajiura, Hiroaki Toba","null","null","null","null","null","2014-04-01","外科","Surgery","Vol.76","No.4","371","376","jpn","true","null","scientific_journal","null","null","10.15106/j00393.2014127367","0016-593X","null","http://id.ndl.go.jp/bib/025363316","null","null","null" "特集:Sentinel node navigation surgery Ⅱ.各論 3.肺癌におけるsentinel node navigation surgery","特集:Sentinel node navigation surgery Ⅱ.各論 3.肺癌におけるsentinel node navigation surgery","滝沢 宏光, 丹黒 章, 先山 正二, 梶浦 耕一郎, 森下 敦司, 坪井 光弘, 鳥羽 博明, 中川 靖士, 吉田 光輝, 川上 行奎, 近藤 和也","Hiromitsu Takizawa, Akira Tangoku, Shoji Sakiyama, Koichiro Kajiura, 森下 敦司, Mitsuhiro Tsuboi, Hiroaki Toba, Yasushi Nakagawa, Mitsuteru Yoshida, Yukikiyo Kawakami, Kazuya Kondo","null","null","null","null","null","2014-04","臨床整形外科","Clinical Orthopaedic Surgery","Vol.76","No.4","371","376","jpn","true","null","scientific_journal","null","null","10.15106/J00393.2014127367","0557-0433","null","null","null","null","null" "Methylation and expression profiles of MGMT gene in thymic epithelial tumors","Methylation and expression profiles of MGMT gene in thymic epithelial tumors","Mohamed Mokhtar, Kazuya Kondo, Toshiaki Namura, Abdellah H.K. Ali, Yui Fujita, Chikako Takai, Hiromitsu Takizawa, Yasushi Nakagawa, Hiroaki Toba, Koichiro Kajiura, Mitsuteru Yoshida, Yukikiyo Kawakami, Shoji Sakiyama, Akira Tangoku","Mohamed Mokhtar, Kazuya Kondo, Toshiaki Namura, Abdellah H.K. Ali, Yui Fujita, Chikako Takai, Hiromitsu Takizawa, Yasushi Nakagawa, Hiroaki Toba, Koichiro Kajiura, Mitsuteru Yoshida, Yukikiyo Kawakami, Shoji Sakiyama, Akira Tangoku","null","A key challenge in diagnosis and treatment of thymic epithelial tumors (TET) is in improving our understanding of the genetic and epigenetic changes of these relatively rare tumors. Methylation specific PCR (MSP) and immunohistochemistry were applied to 66 TET to profile the methylation status of DNA repair gene O6-methylguanine DNA methyltransferase (MGMT) and its protein expression in TET to clarify the association between MGMT status and clinicopathological features, response to chemotherapy and overall survival. MGMT methylation was significantly more frequent in thymic carcinoma than in thymoma (17/23, 74% versus 13/44, 29%; P<0.001). Loss of expression of MGMT protein was significantly more frequent in thymic carcinoma than in thymoma (20/23, 87% versus 10/44, 23%; P<0.0001). There is a significant correlation between of MGMT methylation and loss of its protein expression (P<0.0003). MGMT methylation and loss of expression were significantly more frequent in advanced thymic epithelial tumors (III/IV) than in early tumors (I/II). MGMT methylation plays a soul role in development of TET, especially in thymic carcinoma. Therefore, translation of our results from basic molecular research to clinical practice may have important implication for considering MGMT methylation as a marker and a target of future therapies in TET.","A key challenge in diagnosis and treatment of thymic epithelial tumors (TET) is in improving our understanding of the genetic and epigenetic changes of these relatively rare tumors. Methylation specific PCR (MSP) and immunohistochemistry were applied to 66 TET to profile the methylation status of DNA repair gene O6-methylguanine DNA methyltransferase (MGMT) and its protein expression in TET to clarify the association between MGMT status and clinicopathological features, response to chemotherapy and overall survival. MGMT methylation was significantly more frequent in thymic carcinoma than in thymoma (17/23, 74% versus 13/44, 29%; P<0.001). Loss of expression of MGMT protein was significantly more frequent in thymic carcinoma than in thymoma (20/23, 87% versus 10/44, 23%; P<0.0001). There is a significant correlation between of MGMT methylation and loss of its protein expression (P<0.0003). MGMT methylation and loss of expression were significantly more frequent in advanced thymic epithelial tumors (III/IV) than in early tumors (I/II). MGMT methylation plays a soul role in development of TET, especially in thymic carcinoma. Therefore, translation of our results from basic molecular research to clinical practice may have important implication for considering MGMT methylation as a marker and a target of future therapies in TET.","null","null","2014-02","Lung Cancer","Lung Cancer","Vol.83","No.2","279","287","eng","true","null","scientific_journal","null","null","10.1016/j.lungcan.2013.12.004","1872-8332","null","null","null","null","null" "Monitoring of exhaled carbon monoxide and carbon dioxide during lung cancer operation","Monitoring of exhaled carbon monoxide and carbon dioxide during lung cancer operation","Khasag Narmisheekh, Shoji Sakiyama, Hiroaki Toba, Mitsuteru Yoshida, Yasushi Nakagawa, Hiromitsu Takizawa, Yukikiyo Kawakami, Koichiro Kenzaki, Ali Hamed Khalil Abdellah, Kazuya Kondo, Akira Tangoku","Khasag Narmisheekh, Shoji Sakiyama, Hiroaki Toba, Mitsuteru Yoshida, Yasushi Nakagawa, Hiromitsu Takizawa, Yukikiyo Kawakami, Koichiro Kenzaki, Ali Hamed Khalil Abdellah, Kazuya Kondo, Akira Tangoku","null","Carbon monoxide (CO) is expelled mainly via the lungs, so that exhaled carbon monoxide (Ex-CO) concentration reflects endogenous production. Recent reports have shown that Ex-CO levels are increased in critically ill patients and after anaesthesia and surgery. However, there has been no investigation of the changes in Ex-CO level during a lung operation. We continuously monitored Ex-CO and exhaled carbon dioxide (Ex-CO2) concentrations during surgery for lung cancer. Eighteen lung cancer patients who underwent elective lung cancer lobectomy were enrolled in this study. All patients were endotracheally intubated and ventilated under general anaesthesia. Ex-CO and Ex-CO2 concentrations were separately monitored and recorded continuously using two sets of Carbolyzer® breath analysers (Taiyo Inc., Osaka, Japan). Ex-CO concentration increased rapidly in response to changes in body position from supine to decubitus and was significantly decreased when patients were once again lying back (supine 2). Upon restarting bilateral ventilation, Ex-CO concentration in the operated lung was significantly higher than that in the breathing lung. In the lateral decubitus position, Ex-CO2 concentration showed the same pattern of increase as seen for Ex-CO. In the operated lung, the Ex-CO2 concentrations changed significantly at clamping, declamping and supine 2. In the re-ventilated, operated lung, the Ex-CO2 concentration was significantly lower than in the breathing lung. In the breathing lung, the Ex-CO2 concentration did not exhibit any significant changes over the course of the operation. When breathing was restarted, the Ex-CO level of the target lung was significantly higher than that of the breathing lung. The Ex-CO concentration was also affected by the surgical body position and this change was marked and transient.","Carbon monoxide (CO) is expelled mainly via the lungs, so that exhaled carbon monoxide (Ex-CO) concentration reflects endogenous production. Recent reports have shown that Ex-CO levels are increased in critically ill patients and after anaesthesia and surgery. However, there has been no investigation of the changes in Ex-CO level during a lung operation. We continuously monitored Ex-CO and exhaled carbon dioxide (Ex-CO2) concentrations during surgery for lung cancer. Eighteen lung cancer patients who underwent elective lung cancer lobectomy were enrolled in this study. All patients were endotracheally intubated and ventilated under general anaesthesia. Ex-CO and Ex-CO2 concentrations were separately monitored and recorded continuously using two sets of Carbolyzer® breath analysers (Taiyo Inc., Osaka, Japan). Ex-CO concentration increased rapidly in response to changes in body position from supine to decubitus and was significantly decreased when patients were once again lying back (supine 2). Upon restarting bilateral ventilation, Ex-CO concentration in the operated lung was significantly higher than that in the breathing lung. In the lateral decubitus position, Ex-CO2 concentration showed the same pattern of increase as seen for Ex-CO. In the operated lung, the Ex-CO2 concentrations changed significantly at clamping, declamping and supine 2. In the re-ventilated, operated lung, the Ex-CO2 concentration was significantly lower than in the breathing lung. In the breathing lung, the Ex-CO2 concentration did not exhibit any significant changes over the course of the operation. When breathing was restarted, the Ex-CO level of the target lung was significantly higher than that of the breathing lung. The Ex-CO concentration was also affected by the surgical body position and this change was marked and transient.","null","null","2013-08-02","European Journal of Cardio-Thoracic Surgery","European Journal of Cardio-Thoracic Surgery","Vol.45","No.3","531","536","eng","true","null","scientific_journal","null","null","10.1093/ejcts/ezt395","1873-734X","null","null","null","null","null" "18F-fluorodeoxyglucose positron emission tomography/computed tomography and the relationship between fluorodeoxyglucose uptake and the expression of hypoxia-inducible factor-1, glucose transporter-1 and vascular endothelial growth factor in thymic epithelial tumours.","18F-fluorodeoxyglucose positron emission tomography/computed tomography and the relationship between fluorodeoxyglucose uptake and the expression of hypoxia-inducible factor-1, glucose transporter-1 and vascular endothelial growth factor in thymic epithelial tumours.","Hiroaki Toba, Kazuya Kondo, Yohei Sadohara, Hideki Otsuka, Masami Morimoto, Koichiro Kajiura, Yasushi Nakagawa, Mitsuteru Yoshida, Yukikiyo Kawakami, Hiromitsu Takizawa, Koichiro Kenzaki, Shoji Sakiyama, Yoshimi Bando, Akira Tangoku","Hiroaki Toba, Kazuya Kondo, Yohei Sadohara, Hideki Otsuka, Masami Morimoto, Koichiro Kajiura, Yasushi Nakagawa, Mitsuteru Yoshida, Yukikiyo Kawakami, Hiromitsu Takizawa, Koichiro Kenzaki, Shoji Sakiyama, Yoshimi Bando, Akira Tangoku","null","OBJECTIVES: The objective of this study was to evaluate the usefulness of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and the relationships among the expressions of hypoxia-inducible factor-1 (HIF-1), glucose transporter-1 (Glut-1) and vascular endothelial growth factor (VEGF), histological type, other clinical factors and FDG uptake in thymic epithelial tumours. METHODS: Thirty-three patients who underwent FDG-PET/CT before treatment were reviewed. All types of tumours were reclassified into three subgroups: low-risk thymomas (types A, AB and B1), high-risk thymomas (types B2 and B3) and thymic carcinomas. Tumour contour, pattern of FDG uptake, tumour size and maximum standardized uptake value (SUVmax) were obtained. Expressions of HIF-1, Glut-1 and VEGF were analysed immunohistochemically, and these expressions were evaluated using grading scales. RESULTS: FDG uptake was visually recognized in all (100%) tumours. A homogeneous pattern of FDG uptake was increasingly observed in the order of low-risk thymomas to high-risk thymomas to thymic carcinomas (P = 0.016). SUVmax for thymic carcinomas was significantly higher than that for thymomas (P = 0.008). With the optimal cut-off value of SUVmax of 5.6, the sensitivity, specificity and accuracy for diagnosing thymic carcinoma were 0.75, 0.80 and 0.79, respectively. Regarding the mean scoring of HIF-1, Glut-1 and VEGF, increasing trends were observed in the order of low-risk thymomas to high-risk thymomas to thymic carcinomas. Tumour size revealed a significant correlation with SUVmax (r = 0.60, P < 0.001), and the expression of HIF-1 showed a moderate association, but the expression of Glut-1 showed no correlation with SUVmax. Regarding correlations between the expression of the three markers, there were moderate associations between HIF-1 and Glut-1, and HIF-1 and VEGF, and a significant correlation between Glut-1 and VEGF (r = 0.60, P < 0.001). In type B1 thymoma, HIF-1 and Glut-1 were partly expressed in non-neoplastic immature lymphocytes. CONCLUSIONS: FDG-PET/CT should be performed in patients with tumours in the anterior mediastinum because the pattern of FDG uptake and SUVmax are useful in the differential diagnosis of thymic epithelial tumours. Furthermore, the expressions of HIF-1, Glut-1 and VEGF might be associated with malignancy of thymic epithelial tumours. In contrast, FDG uptake might be dependent on tumour size rather than Glut-1 overexpression.","OBJECTIVES: The objective of this study was to evaluate the usefulness of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and the relationships among the expressions of hypoxia-inducible factor-1 (HIF-1), glucose transporter-1 (Glut-1) and vascular endothelial growth factor (VEGF), histological type, other clinical factors and FDG uptake in thymic epithelial tumours. METHODS: Thirty-three patients who underwent FDG-PET/CT before treatment were reviewed. All types of tumours were reclassified into three subgroups: low-risk thymomas (types A, AB and B1), high-risk thymomas (types B2 and B3) and thymic carcinomas. Tumour contour, pattern of FDG uptake, tumour size and maximum standardized uptake value (SUVmax) were obtained. Expressions of HIF-1, Glut-1 and VEGF were analysed immunohistochemically, and these expressions were evaluated using grading scales. RESULTS: FDG uptake was visually recognized in all (100%) tumours. A homogeneous pattern of FDG uptake was increasingly observed in the order of low-risk thymomas to high-risk thymomas to thymic carcinomas (P = 0.016). SUVmax for thymic carcinomas was significantly higher than that for thymomas (P = 0.008). With the optimal cut-off value of SUVmax of 5.6, the sensitivity, specificity and accuracy for diagnosing thymic carcinoma were 0.75, 0.80 and 0.79, respectively. Regarding the mean scoring of HIF-1, Glut-1 and VEGF, increasing trends were observed in the order of low-risk thymomas to high-risk thymomas to thymic carcinomas. Tumour size revealed a significant correlation with SUVmax (r = 0.60, P < 0.001), and the expression of HIF-1 showed a moderate association, but the expression of Glut-1 showed no correlation with SUVmax. Regarding correlations between the expression of the three markers, there were moderate associations between HIF-1 and Glut-1, and HIF-1 and VEGF, and a significant correlation between Glut-1 and VEGF (r = 0.60, P < 0.001). In type B1 thymoma, HIF-1 and Glut-1 were partly expressed in non-neoplastic immature lymphocytes. CONCLUSIONS: FDG-PET/CT should be performed in patients with tumours in the anterior mediastinum because the pattern of FDG uptake and SUVmax are useful in the differential diagnosis of thymic epithelial tumours. Furthermore, the expressions of HIF-1, Glut-1 and VEGF might be associated with malignancy of thymic epithelial tumours. In contrast, FDG uptake might be dependent on tumour size rather than Glut-1 overexpression.","null","null","2013-05-14","European Journal of Cardio-Thoracic Surgery","European Journal of Cardio-Thoracic Surgery","Vol.44","No.2","e105","e112","eng","true","null","scientific_journal","null","null","10.1093/ejcts/ezt263","1873-734X","null","null","null","null","null" "Fluoroscopy-assisted thoracoscopic resection after computed tomography-guided bronchoscopic metallic coil marking for small peripheral pulmonary lesions.","Fluoroscopy-assisted thoracoscopic resection after computed tomography-guided bronchoscopic metallic coil marking for small peripheral pulmonary lesions.","Hiroaki Toba, Kazuya Kondo, Takanori Miyoshi, Koichiro Kajiura, Mitsuteru Yoshida, Yukikiyo Kawakami, Hiromitsu Takizawa, Koichiro Kenzaki, Shoji Sakiyama, Akira Tangoku","Hiroaki Toba, Kazuya Kondo, Takanori Miyoshi, Koichiro Kajiura, Mitsuteru Yoshida, Yukikiyo Kawakami, Hiromitsu Takizawa, Koichiro Kenzaki, Shoji Sakiyama, Akira Tangoku","null","OBJECTIVES: To re-evaluate the efficacy of fluoroscopy-assisted thoracoscopic resection after computed tomography (CT)-guided bronchoscopic metallic coil marking (FATS-CM), which was our original method for small peripheral pulmonary lesions. METHODS: Fifty-eight patients with 63 lesions underwent FATS-CM. A metallic coil was installed in the bronchus nearest to the lesion under CT fluoroscopic guidance with ultrathin bronchoscopy. The virtual bronchoscopic navigation (VBN) system was used in 14 cases. Afterwards, we basically performed wide wedge resection (WWR) using a C-arm-shaped roentgenographic fluoroscope during thoracoscopic surgery initially, and then the final procedure was determined by intraoperative histological diagnosis. Moreover, we prospectively treated ground-glass opacity (GGO) lesions of <20 mm diameter according to our treatment protocol from September 2004. RESULTS: We could install coils in the objective bronchi in all cases. The average time required for the marking procedure was 38.9 (15-120) min. Pneumothorax was recognized in 1 (1.7%) case as a complication, but no fatal complications occurred. We could also install coils for each lesion in 4 cases (9 lesions) with multiple lesions. In 14 cases with the VBN system, the examination time and CT number were significantly reduced (P < 0.05 and <0.001, respectively), compared with those of 40 cases without the VBN system. The average interval between the CM and the operation was 5.6 (0-30) days. We never experienced a case of migration preoperatively. Sixty-two (98.4%) lesions were definitively identified, and WWRs were performed using three trocars in 58 (92.1%) cases during thoracoscopic surgery. Lobectomy was initially performed in only 1 case owing to coil migration. Thirty-seven of 40 cases (92.5%) were in line with the treatment protocol. There were no local-regional recurrences in all cases undergoing WWR. CONCLUSIONS: We could prospectively show that our method was suitable to perform WWR with a sufficient margin for small GGO lesions of <20 mm. Moreover, we reconfirmed that the advantages of our method were safety, permitting flexibility in scheduling operations and a high ability to deal with multiple lesions. Additionally, our method became a minimally invasive and mature technique by using a new VBN system.","OBJECTIVES: To re-evaluate the efficacy of fluoroscopy-assisted thoracoscopic resection after computed tomography (CT)-guided bronchoscopic metallic coil marking (FATS-CM), which was our original method for small peripheral pulmonary lesions. METHODS: Fifty-eight patients with 63 lesions underwent FATS-CM. A metallic coil was installed in the bronchus nearest to the lesion under CT fluoroscopic guidance with ultrathin bronchoscopy. The virtual bronchoscopic navigation (VBN) system was used in 14 cases. Afterwards, we basically performed wide wedge resection (WWR) using a C-arm-shaped roentgenographic fluoroscope during thoracoscopic surgery initially, and then the final procedure was determined by intraoperative histological diagnosis. Moreover, we prospectively treated ground-glass opacity (GGO) lesions of <20 mm diameter according to our treatment protocol from September 2004. RESULTS: We could install coils in the objective bronchi in all cases. The average time required for the marking procedure was 38.9 (15-120) min. Pneumothorax was recognized in 1 (1.7%) case as a complication, but no fatal complications occurred. We could also install coils for each lesion in 4 cases (9 lesions) with multiple lesions. In 14 cases with the VBN system, the examination time and CT number were significantly reduced (P < 0.05 and <0.001, respectively), compared with those of 40 cases without the VBN system. The average interval between the CM and the operation was 5.6 (0-30) days. We never experienced a case of migration preoperatively. Sixty-two (98.4%) lesions were definitively identified, and WWRs were performed using three trocars in 58 (92.1%) cases during thoracoscopic surgery. Lobectomy was initially performed in only 1 case owing to coil migration. Thirty-seven of 40 cases (92.5%) were in line with the treatment protocol. There were no local-regional recurrences in all cases undergoing WWR. CONCLUSIONS: We could prospectively show that our method was suitable to perform WWR with a sufficient margin for small GGO lesions of <20 mm. Moreover, we reconfirmed that the advantages of our method were safety, permitting flexibility in scheduling operations and a high ability to deal with multiple lesions. Additionally, our method became a minimally invasive and mature technique by using a new VBN system.","null","null","2013-04-18","European Journal of Cardio-Thoracic Surgery","European Journal of Cardio-Thoracic Surgery","null","null","null","null","eng","true","null","scientific_journal","null","null","10.1093/ejcts/ezt220","1873-734X","null","null","null","null","null" "右中下葉・瘻管切除を施行した低肺機能の成人先天性食道気管支瘻の1例","A CASE OF CONGENTIAL ESOPHAGOBRONCHIAL FISTULA IN AN ADULT WITH IMPAIRED PULMONARY FUNCTION WHO WAS TREATED USING FISTULECTOMY AND RIGHT MIDDLE AND LOWER LOBECTOMY","後藤 正和, 先山 正二, 鳥羽 博明, 監﨑 孝一郎, 近藤 和也, 丹黒 章","Masakazu Goto, Shoji Sakiyama, Hiroaki Toba, Koichiro Kenzaki, Kazuya Kondo, Akira Tangoku","null","null","null","null","null","2012-05-25","日本臨床外科学会雑誌","Journal of Japan Surgical Association","Vol.73","No.5","1075","1079","jpn","true","null","scientific_journal","null","null","10.3919/jjsa.73.1075","1345-2843","null","http://ci.nii.ac.jp/naid/10030988380/","null","null","null" "Computed tomography lymphography by transbronchial injection of iopamidol to identify sentinel nodes in preoperative patients with non-small cell lung cancer : A pilot study","Computed tomography lymphography by transbronchial injection of iopamidol to identify sentinel nodes in preoperative patients with non-small cell lung cancer : A pilot study","Hiromitsu Takizawa, Kazuya Kondo, Hiroaki Toba, Koichiro Kajiura, Ali Hamed Khalil Abdellah, Shoji Sakiyama, Akira Tangoku","Hiromitsu Takizawa, Kazuya Kondo, Hiroaki Toba, Koichiro Kajiura, Ali Hamed Khalil Abdellah, Shoji Sakiyama, Akira Tangoku","null","The objective of the present study was to assess the safety and feasibility of computed tomography lymphography by transbronchial injection of a water-soluble extracellular computed tomography contrast agent. From April 2010 to May 2011, patients with clinical stage I non-small cell lung cancer who were candidates for lobectomy were enrolled in the present study. An ultrathin bronchoscope was inserted to the target bronchus under the guidance of virtual bronchoscopic navigation images. Computed tomography images of the chest were obtained 0.5 and 5 minutes after 2 or 3 mL of iopamidol was injected through a microcatheter. Sentinel nodes were identified when the maximum computed tomography attenuation value of the lymph nodes on the postcontrast computed tomography images increased by 30 Hounsfield units or more compared with the precontrast images. Patients underwent lobectomy with standard lymph node dissection. The ultrathin bronchoscope could access the targeted bronchus, and iopamidol was delivered into the peritumoral area in all 13 patients without any complications. Sentinel nodes were identified in 12 (92.3%) of the 13 patients. The average number of sentinel nodes was 1.5 (range, 1-2). Pathologic examination revealed metastatic lymph nodes in 2 patients. Metastatic nodes were included with the sentinel nodes. Computed tomography lymphography by transbronchial injection of iopamidol was a safe and feasible method to identify the sentinel nodes in patients with clinical stage I non-small cell lung cancer.","The objective of the present study was to assess the safety and feasibility of computed tomography lymphography by transbronchial injection of a water-soluble extracellular computed tomography contrast agent. From April 2010 to May 2011, patients with clinical stage I non-small cell lung cancer who were candidates for lobectomy were enrolled in the present study. An ultrathin bronchoscope was inserted to the target bronchus under the guidance of virtual bronchoscopic navigation images. Computed tomography images of the chest were obtained 0.5 and 5 minutes after 2 or 3 mL of iopamidol was injected through a microcatheter. Sentinel nodes were identified when the maximum computed tomography attenuation value of the lymph nodes on the postcontrast computed tomography images increased by 30 Hounsfield units or more compared with the precontrast images. Patients underwent lobectomy with standard lymph node dissection. The ultrathin bronchoscope could access the targeted bronchus, and iopamidol was delivered into the peritumoral area in all 13 patients without any complications. Sentinel nodes were identified in 12 (92.3%) of the 13 patients. The average number of sentinel nodes was 1.5 (range, 1-2). Pathologic examination revealed metastatic lymph nodes in 2 patients. Metastatic nodes were included with the sentinel nodes. Computed tomography lymphography by transbronchial injection of iopamidol was a safe and feasible method to identify the sentinel nodes in patients with clinical stage I non-small cell lung cancer.","null","null","2012-04-14","Journal of Thoracic and Cardiovascular Surgery","Journal of Thoracic and Cardiovascular Surgery","Vol.144","No.1","94","99","eng","true","null","scientific_journal","null","null","10.1016/j.jtcvs.2012.03.040","1097-685X","null","null","null","null","null" "摘出時にラリンジアルマスクを使用した小児気管支異物の1例","A Pediatric Case of Removal of a Bronchial Foreign Body Using a Laryngeal Mask Airway","鳥羽 博明, 先山 正二, 森本 雅美, 梶浦 耕一郎, 中川 靖士, 川上 行奎, 滝沢 宏光, 監﨑 孝一郎, 近藤 和也, 丹黒 章","Hiroaki Toba, Shoji Sakiyama, 森本 雅美, Koichiro Kajiura, Yasushi Nakagawa, Yukikiyo Kawakami, Hiromitsu Takizawa, Koichiro Kenzaki, Kazuya Kondo, Akira Tangoku","null","背景.摘出時にラリンジアルマスクを使用した小児気管支異物の1例を経験したので報告する.症例.1歳6カ月の女児.ピーナッツを食べた際に誤嚥.その後,喘鳴が出現し,前医に入院.抗菌薬を投与されていたが,翌日施行された胸部CTにて気管支異物を疑われ,当院に搬送された.CTにて左主気管支に異物と思われる陰影を認め,気管支異物と診断し,同日全身麻酔下に異物除去を施行した.ラリンジアルマスク(サイズ2.0)を使用して気道を確保した後,外径4.0mmの軟性気管支鏡を挿入し,バルーン付きカテーテルにて摘出した.異物はピーナッツであった.結論.小児気管支異物に対して,ラリンジアルマスクの使用により,異物摘出時の有効な換気と軟性気管支鏡のスムーズな操作性を担保することができた.","Background. We report a pediatric case of remove of bronchial foreign body using a laryngeal mask airway and flexible bronchoscopy. Case. A 18-month-old girl accidentally inhaled a peanut. Afterwards she entered another hospital with a chief complaint of wheezing and received antibiotic treatment. On the next day, an abnormal shadow was pointed out, which was suspected to indicate a foreign body, in the left main bronchus. Chest computed tomography (CT) scan was carried to our hospital. On the same day, after the airway was cleared using a laryngeal mask airway (LMA size 2.0) under general anesthesia, a flexible bronchoscope (external diameter 4.0 mm) was inserted. The foreign body was successfully removed with a balloon-tip catheter. The foreign body was a peanut. Conclusion. By using a laryngeal mask airway, we could maintain available ventilation and enable a smooth procedure using a flexible bronchoscope while removing a pediatric bronchial foreign body.","null","null","2012-03-25","気管支学","The Journal of the Japan Society for Respiratory Endoscopy","Vol.34","No.2","180","183","jpn","true","null","scientific_journal","null","null","null","0287-2137","null","http://ci.nii.ac.jp/naid/110009437402/","null","null","null" "Implantation of fetal rat lung fragments into bleomycin-induced pulmonary fibrosis","Implantation of fetal rat lung fragments into bleomycin-induced pulmonary fibrosis","Hiroaki Toba, Shoji Sakiyama, Koichiro Kenzaki, Yukikiyo Kawakami, Koh Uyama, Yoshimi Bando, Akira Tangoku","Hiroaki Toba, Shoji Sakiyama, Koichiro Kenzaki, Yukikiyo Kawakami, Koh Uyama, Yoshimi Bando, Akira Tangoku","null","Pulmonary fibrosis is a life-threatening disease that results in progressive respiratory failure. We have suggested the possibility of fetal lung tissue as an option for further investigation into lung regeneration. The objective was to prove whether fetal lung fragments can survive and differentiate in fibrotic lung. Lewis rats were administered bleomycin and used as recipients after 3 or 4 weeks. Day 17 fetal lung tissue from green fluorescent protein Lewis rats was used as donor material. Donor lungs were removed, cut into small pieces, and implanted into the recipients' left lung. The recipients received cyclosporin to prevent immune response to green fluorescent protein and were killed after 1, 2, 4, 8, and 12 weeks and histologically evaluated. Furthermore, the expression of thyroid transcription factor-1 and Clara cell secretory protein in the implanted fetal lung tissue was immunohistologically evaluated. Fibrotic changes were recognized for a long period of time in the recipient lungs. The implanted fetal lung fragments could be clearly distinguished from recipient lungs because of the luminescence of grafts. Fetal lung fragments could survive in the recipient lungs with fibrotic changes. The air spaces of implanted fetal lungs were narrow at 1 and 2 weeks but expanded with the passage of time. The connection between the recipient lung and the implanted fetal lung was recognized, particularly in the peripheral grafts. The expression patterns of thyroid transcription factor-1 and Clara cell secretory protein in implanted lungs resembled those in the process of normal lung morphogenesis. Fetal rat lung fragments could survive and differentiate in bleomycin-induced completely fibrotic lung.","Pulmonary fibrosis is a life-threatening disease that results in progressive respiratory failure. We have suggested the possibility of fetal lung tissue as an option for further investigation into lung regeneration. The objective was to prove whether fetal lung fragments can survive and differentiate in fibrotic lung. Lewis rats were administered bleomycin and used as recipients after 3 or 4 weeks. Day 17 fetal lung tissue from green fluorescent protein Lewis rats was used as donor material. Donor lungs were removed, cut into small pieces, and implanted into the recipients' left lung. The recipients received cyclosporin to prevent immune response to green fluorescent protein and were killed after 1, 2, 4, 8, and 12 weeks and histologically evaluated. Furthermore, the expression of thyroid transcription factor-1 and Clara cell secretory protein in the implanted fetal lung tissue was immunohistologically evaluated. Fibrotic changes were recognized for a long period of time in the recipient lungs. The implanted fetal lung fragments could be clearly distinguished from recipient lungs because of the luminescence of grafts. Fetal lung fragments could survive in the recipient lungs with fibrotic changes. The air spaces of implanted fetal lungs were narrow at 1 and 2 weeks but expanded with the passage of time. The connection between the recipient lung and the implanted fetal lung was recognized, particularly in the peripheral grafts. The expression patterns of thyroid transcription factor-1 and Clara cell secretory protein in implanted lungs resembled those in the process of normal lung morphogenesis. Fetal rat lung fragments could survive and differentiate in bleomycin-induced completely fibrotic lung.","null","null","2012-02-02","Journal of Thoracic and Cardiovascular Surgery","Journal of Thoracic and Cardiovascular Surgery","Vol.143","No.6","1429","1435","eng","true","null","scientific_journal","null","null","10.1016/j.jtcvs.2012.01.002","1097-685X","null","null","null","null","null" "Follow-up using fluorescence bronchoscopy for the patients with photodynamic therapy treated early lung cancer.","Follow-up using fluorescence bronchoscopy for the patients with photodynamic therapy treated early lung cancer.","Abdellah Hamed Khalil Ali, Hiromitsu Takizawa, Kazuya Kondo, Yasushi Nakagawa, Hiroaki Toba, Narmisheekh Khasag, Koichiro Kenzaki, Shoji Sakiyama, Hamdy Ali Mohammadien, Essam Ahmed Mokhtar, Akira Tangoku","Abdellah Hamed Khalil Ali, Hiromitsu Takizawa, Kazuya Kondo, Yasushi Nakagawa, Hiroaki Toba, Narmisheekh Khasag, Koichiro Kenzaki, Shoji Sakiyama, Hamdy Ali Mohammadien, Essam Ahmed Mokhtar, Akira Tangoku","null","To evaluate the accuracy of fluorescence bronchoscopy by precise histological analysis of the photodynamic therapy (PDT) treated lesions.","To evaluate the accuracy of fluorescence bronchoscopy by precise histological analysis of the photodynamic therapy (PDT) treated lesions.","null","null","2011-02","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.58","No.1-2","46","55","eng","true","null","scientific_journal","null","null","10.2152/jmi.58.46","1349-6867","null","null","null","null","null" "5-Aminolevulinic acid-induced fluorescence diagnosis of pleural malignant tumor.","5-Aminolevulinic acid-induced fluorescence diagnosis of pleural malignant tumor.","Khalil Abdellah Hamed Ali, Hiromitsu Takizawa, Kazuya Kondo, Hisashi Matsuoka, Hiroaki Toba, Yasushi Nakagawa, Koichiro Kenzaki, Shoji Sakiyama, Soji Kakiuchi, Yoshitaka Sekido, Saburo Sone, Akira Tangoku","Khalil Abdellah Hamed Ali, Hiromitsu Takizawa, Kazuya Kondo, Hisashi Matsuoka, Hiroaki Toba, Yasushi Nakagawa, Koichiro Kenzaki, Shoji Sakiyama, Soji Kakiuchi, Yoshitaka Sekido, Saburo Sone, Akira Tangoku","null","BACKGROUND: It is known that endogenously synthesized protoporphyrin IX (PpIX) following the administration of 5-aminolevulinic acid (5-ALA) is an effective photosensitizer for photodynamic diagnosis (PDD). We tested in vivo and in vitro susceptibility of human lung cancer and mesothelioma cells to photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) as a photosensitizer. METHODS: Human lung cancer cell lines A549, Ma44-3, FT821 and human mesothelioma cell lines MSTO-211H, NCI-H290, Y-MESO-14 were incubated with 0.03% 5-ALA for 4h. After incubation, protoporphyrin IX (PpIX) fluorescence was detected using a fluorescence microscope. Pleural carcinosis was induced in severe combined immunodeficiency disease mice using the previous cell lines to test the efficacy of PDD in vivo. The mice were sacrificed 4h after oral administration of 400mg/kg of 5-ALA. We counted the visible tumors under white light then fluorescence light. RESULTS: In vitro, clear red fluorescence was observed in all cell lines. The mean fluorescence intensity was stronger in A549 and FT821 cells than Ma44-3 cells (165.59±26.49, 157.62±18.93 vs. 104.01±17.58). Also, MSTO-211H and NCI-H290 cells had stronger fluorescence intensity than Y-MESO-14 cells (142.51±26.85, 165.16±12.91 vs. 92.31±8.69). In vivo, the tumor detection rate of fluorescence diagnosis was 1.1-4.5 times higher than that of white light. The mean number of metastases detected by the PDD was significantly higher than that of white light for FT821 (p=0.004), Ma44-3 (p=0.006) and Y-MESO-14 cell lines (p=0.005), but not for A549, NCI-H290 and MSTO-211H cell lines. Small lesions were detected by fluorescence diagnosis even though the lesions were invisible macroscopically under white light. CONCLUSION: Our results suggest the possibility of clinical application of fluorescence diagnosis with intrapleural malignant tumors.","BACKGROUND: It is known that endogenously synthesized protoporphyrin IX (PpIX) following the administration of 5-aminolevulinic acid (5-ALA) is an effective photosensitizer for photodynamic diagnosis (PDD). We tested in vivo and in vitro susceptibility of human lung cancer and mesothelioma cells to photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) as a photosensitizer. METHODS: Human lung cancer cell lines A549, Ma44-3, FT821 and human mesothelioma cell lines MSTO-211H, NCI-H290, Y-MESO-14 were incubated with 0.03% 5-ALA for 4h. After incubation, protoporphyrin IX (PpIX) fluorescence was detected using a fluorescence microscope. Pleural carcinosis was induced in severe combined immunodeficiency disease mice using the previous cell lines to test the efficacy of PDD in vivo. The mice were sacrificed 4h after oral administration of 400mg/kg of 5-ALA. We counted the visible tumors under white light then fluorescence light. RESULTS: In vitro, clear red fluorescence was observed in all cell lines. The mean fluorescence intensity was stronger in A549 and FT821 cells than Ma44-3 cells (165.59±26.49, 157.62±18.93 vs. 104.01±17.58). Also, MSTO-211H and NCI-H290 cells had stronger fluorescence intensity than Y-MESO-14 cells (142.51±26.85, 165.16±12.91 vs. 92.31±8.69). In vivo, the tumor detection rate of fluorescence diagnosis was 1.1-4.5 times higher than that of white light. The mean number of metastases detected by the PDD was significantly higher than that of white light for FT821 (p=0.004), Ma44-3 (p=0.006) and Y-MESO-14 cell lines (p=0.005), but not for A549, NCI-H290 and MSTO-211H cell lines. Small lesions were detected by fluorescence diagnosis even though the lesions were invisible macroscopically under white light. CONCLUSION: Our results suggest the possibility of clinical application of fluorescence diagnosis with intrapleural malignant tumors.","null","null","2011-02","Lung Cancer","Lung Cancer","null","null","null","null","eng","true","null","scientific_journal","null","null","10.1016/j.lungcan.2011.01.031","1872-8332","null","null","null","null","null" "Aberrant DNA methylation of some tumor suppressor genes in lung cancers from workers with chromate exposure.","Aberrant DNA methylation of some tumor suppressor genes in lung cancers from workers with chromate exposure.","Abdellah H. K. Ali, Kazuya Kondo, Toshiaki Namura, Yoshitaka Senba, Hiromitsu Takizawa, Yasushi Nakagawa, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama, Akira Tangoku","Abdellah H. K. Ali, Kazuya Kondo, Toshiaki Namura, Yoshitaka Senba, Hiromitsu Takizawa, Yasushi Nakagawa, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama, Akira Tangoku","null","Our previous studies revealed a variety of genetic changes in lung cancers from chromate-exposed workers (chromate lung cancer). In the present study, we examined epigenetic changes in chromate lung cancers. Nested-methylation-specific PCR was employed in studying the methylation of CpG islands in the APC, MGMT, hMLH1 genes in 36 chromate lung cancers and 25 nonchromate lung cancers. Methylation in chromate lung cancers was detected at 86% for APC, 20% for MGMT, and 28% for hMLH1. Whereas, it occurred at lower frequencies in nonchromate lung cancers, particularly in APC (44%) and hMLH1 (0%) genes. Our previous study showed that methylation of p16 gene in chromate lung cancer and nonchromate lung cancer was 33% and 26%, respectively. The mean methylation index (MI), a reflection of the overall methylation status, was significantly higher in chromate lung cancers than nonchromate lung cancers (0.41 vs. 0.21, P=0.001). Methylation of multiple genes (particularly hMLH1, p16, and APC genes) had experienced more than 15 yr of chromate exposure in chromate lung cancer (MI: <15 yr; 0.19, ≥ 15 yr, 0.42). There is a significant correlation of p16 and hMLH1 methylation with the expressional decrease or loss of the corresponding gene products (P=0.037 and 0.024) respectively, and an inverse correlation between APC and MGMT methylation (P = 0.014). This study provides a novel evidence for the chromium carcinogenesis that chromate lung cancer is linked to the progressive methylation of some tumor suppressor genes, which may be related to genomic instability.","Our previous studies revealed a variety of genetic changes in lung cancers from chromate-exposed workers (chromate lung cancer). In the present study, we examined epigenetic changes in chromate lung cancers. Nested-methylation-specific PCR was employed in studying the methylation of CpG islands in the APC, MGMT, hMLH1 genes in 36 chromate lung cancers and 25 nonchromate lung cancers. Methylation in chromate lung cancers was detected at 86% for APC, 20% for MGMT, and 28% for hMLH1. Whereas, it occurred at lower frequencies in nonchromate lung cancers, particularly in APC (44%) and hMLH1 (0%) genes. Our previous study showed that methylation of p16 gene in chromate lung cancer and nonchromate lung cancer was 33% and 26%, respectively. The mean methylation index (MI), a reflection of the overall methylation status, was significantly higher in chromate lung cancers than nonchromate lung cancers (0.41 vs. 0.21, P=0.001). Methylation of multiple genes (particularly hMLH1, p16, and APC genes) had experienced more than 15 yr of chromate exposure in chromate lung cancer (MI: <15 yr; 0.19, ≥ 15 yr, 0.42). There is a significant correlation of p16 and hMLH1 methylation with the expressional decrease or loss of the corresponding gene products (P=0.037 and 0.024) respectively, and an inverse correlation between APC and MGMT methylation (P = 0.014). This study provides a novel evidence for the chromium carcinogenesis that chromate lung cancer is linked to the progressive methylation of some tumor suppressor genes, which may be related to genomic instability.","null","null","2010-11-23","Molecular Carcinogenesis","Molecular Carcinogenesis","Vol.50","No.2","89","99","eng","true","null","scientific_journal","null","null","10.1002/mc.20697","1098-2744","null","null","null","null","null" "左上下肺静脈が共通幹を形成していた肺癌の2例","[Lung cancer in patient with a common trunk of left pulmonary veins; report of two cases].","河北 直也, 鳥羽 博明, 先山 正二, 澤田 徹, 山本 洋太, 中川 靖士, 滝沢 宏光, 監﨑 孝一郎, 近藤 和也, 丹黒 章","Naoya Kawakita, Hiroaki Toba, Shoji Sakiyama, Toru Sawada, Yota Yamamoto, Yasushi Nakagawa, Hiromitsu Takizawa, Koichiro Kenzaki, Kazuya Kondo, Akira Tangoku","null","A 69-year-old man and a 53-year-old man with lung cancer of left upper lobe underwent pulmonary resection. A preoperative chest computed tomography (CT) scan showed the left superior and inferior pulmonary veins forming a common trunk. In the former case, the common trunk was misidentified as the superior pulmonary vein. The latter was recognized preoperatively by using 3-dimensional CT, and successfully performed left superior segmentectomy. This variation type is surgically important because of a potential risk of intraoperative bleeding and damage to pulmonary circulation during pulmonary resection.","A 69-year-old man and a 53-year-old man with lung cancer of left upper lobe underwent pulmonary resection. A preoperative chest computed tomography (CT) scan showed the left superior and inferior pulmonary veins forming a common trunk. In the former case, the common trunk was misidentified as the superior pulmonary vein. The latter was recognized preoperatively by using 3-dimensional CT, and successfully performed left superior segmentectomy. This variation type is surgically important because of a potential risk of intraoperative bleeding and damage to pulmonary circulation during pulmonary resection.","null","null","2010-09","胸部外科","The Japanese Journal of Thoracic Surgery","Vol.63","No.10","915","918","jpn","true","null","scientific_journal","null","null","null","0021-5252","null","null","null","null","null" "Diagnosis of the presence of lymph node metastasis and decision of operative indication using fluorodeoxyglucose-positron emission tomography and computed tomography in patients with primary lung cancer.","Diagnosis of the presence of lymph node metastasis and decision of operative indication using fluorodeoxyglucose-positron emission tomography and computed tomography in patients with primary lung cancer.","Hiroaki Toba, Kazuya Kondo, Hideki Otsuka, Hiromitsu Takizawa, Koichiro Kenzaki, Shoji Sakiyama, Akira Tangoku","Hiroaki Toba, Kazuya Kondo, Hideki Otsuka, Hiromitsu Takizawa, Koichiro Kenzaki, Shoji Sakiyama, Akira Tangoku","null","PET/CT is superior to CT scan in lymph node staging. However, because the false-positive rate is high in PET-positive lymph nodes measuring less than 1 cm in diameter, we think that clinical background should be considered and other modalities or histological examinations should be undertaken if necessary. J. Med. Invest. 57: 305-313, August, 2010.","PET/CT is superior to CT scan in lymph node staging. However, because the false-positive rate is high in PET-positive lymph nodes measuring less than 1 cm in diameter, we think that clinical background should be considered and other modalities or histological examinations should be undertaken if necessary. J. Med. Invest. 57: 305-313, August, 2010.","null","null","2010-08","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.57","No.3-4","305","313","eng","true","null","scientific_journal","null","null","10.2152/jmi.57.305","1349-6867","null","null","null","null","null" "胸部外科の指針 高齢者原発性肺癌における臨床的検討","[Clinical analysis of elderly patients with primary lung cancer].","監﨑 孝一郎, 先山 正二, 富本 英樹, 鳥羽 博明, 中川 靖士, 滝沢 宏光, 近藤 和也, 曽根 三郎, 丹黒 章","Koichiro Kenzaki, Shoji Sakiyama, Hideki Tomimoto, Hiroaki Toba, Yasushi Nakagawa, Hiromitsu Takizawa, Kazuya Kondo, Saburo Sone, Akira Tangoku","null","We clinically reviewed 33 surgery patients and 15 non-surgery patients aged 80 years or older with primary lung cancer treated at our hospital. The surgery group consisted of 21 males and 12 females (82.0 +/- 1.9 years old). The surgical procedures were 1 pneumonectomy, 19 lobectomies (1 bronchoplasty), 4 segmentectomies and 9 partial resections. The cancer types were 17 adenocarcinomas, 14 squamous cell carcinomas and 2 others. The stagings were 24 in stage I, 4 in stage II and 5 in stage III. There were no direct surgical deaths within 30 days post operatively. There have been 9 other disease-related deaths to date (27%). The non-surgery group consisted of 9 males and 6 females (81.7 +/- 1.5 years old). Treatment procedures consisted of radiationtherapy in 11, chemotherapy in 2 and best supportive care in 3. The cancer types were 2 adenocarcinomas, 11 squamous cell carcinomas and 2 others. The stagings were 7 in stage I, 4 in stage II and 4 in stage III. There have been 3 other disease-related deaths to date (20%). We must carefully select the therapeutic approach for elderly lung cancer patients, because the other disease-related death rates of both groups were high. The 5-year survival rate of stage I patients in the surgical group was relatively good (60.2%). There were long-term survival (7 5-year survivors) in the surgical group. Since there were some cases of radiation pneumonia in the group receiving radiation therapy, it would be better to perform surgery for elderly patients with lung cancer, especially those with stage I disease. For elderly patients, it is important to consider quality of life as well as the survival rate.","We clinically reviewed 33 surgery patients and 15 non-surgery patients aged 80 years or older with primary lung cancer treated at our hospital. The surgery group consisted of 21 males and 12 females (82.0 +/- 1.9 years old). The surgical procedures were 1 pneumonectomy, 19 lobectomies (1 bronchoplasty), 4 segmentectomies and 9 partial resections. The cancer types were 17 adenocarcinomas, 14 squamous cell carcinomas and 2 others. The stagings were 24 in stage I, 4 in stage II and 5 in stage III. There were no direct surgical deaths within 30 days post operatively. There have been 9 other disease-related deaths to date (27%). The non-surgery group consisted of 9 males and 6 females (81.7 +/- 1.5 years old). Treatment procedures consisted of radiationtherapy in 11, chemotherapy in 2 and best supportive care in 3. The cancer types were 2 adenocarcinomas, 11 squamous cell carcinomas and 2 others. The stagings were 7 in stage I, 4 in stage II and 4 in stage III. There have been 3 other disease-related deaths to date (20%). We must carefully select the therapeutic approach for elderly lung cancer patients, because the other disease-related death rates of both groups were high. The 5-year survival rate of stage I patients in the surgical group was relatively good (60.2%). There were long-term survival (7 5-year survivors) in the surgical group. Since there were some cases of radiation pneumonia in the group receiving radiation therapy, it would be better to perform surgery for elderly patients with lung cancer, especially those with stage I disease. For elderly patients, it is important to consider quality of life as well as the survival rate.","null","null","2010-07","胸部外科","The Japanese Journal of Thoracic Surgery","Vol.63","No.7","519","526","jpn","true","null","scientific_journal","null","null","null","0021-5252","null","null","null","null","null" "Gefitinib耐性後に切除した肺腺癌術後肺転移の1例","Gefitinib耐性後に切除した肺腺癌術後肺転移の1例","河北 直也, 滝沢 宏光, 鳥羽 博明, 監﨑 孝一郎, 先山 正二, 近藤 和也","河北 直也, Hiromitsu Takizawa, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama, Kazuya Kondo","null","null","null","null","null","2010","日本呼吸器外科学会雑誌","The Journal of the Japanese Association for Chest Surgery","Vol.24","No.2","42","45","jpn","true","null","scientific_journal","null","null","10.2995/jacsurg.24.166","1881-4158","null","null","null","null","null" "Late pulmonary metastases from malignant melanoma of the left planta.","Late pulmonary metastases from malignant melanoma of the left planta.","Hiroaki Toba, Kazuya Kondo, Koichiro Kenzaki, Takanori Miyoshi, Shoji Sakiyama, Akira Tangoku","Hiroaki Toba, Kazuya Kondo, Koichiro Kenzaki, Takanori Miyoshi, Shoji Sakiyama, Akira Tangoku","null","We report a patient treated for malignant melanoma of the left planta who developed pulmonary metastases after a disease-free interval of 10 years. Metastatectomy was performed after observing progress for 12 months. However, 18 months later, pretracheal and right axillary lymph node metastases occurred. Because pulmonary metastasis from malignant melanoma may occur after 10 years or more, we observe patients carefully. If it does occur, an operation should be considered under limited indications. We should also recognize that recurrence may occur within a short interval after metastatectomy as well.","We report a patient treated for malignant melanoma of the left planta who developed pulmonary metastases after a disease-free interval of 10 years. Metastatectomy was performed after observing progress for 12 months. However, 18 months later, pretracheal and right axillary lymph node metastases occurred. Because pulmonary metastasis from malignant melanoma may occur after 10 years or more, we observe patients carefully. If it does occur, an operation should be considered under limited indications. We should also recognize that recurrence may occur within a short interval after metastatectomy as well.","null","null","2009-10-16","General Thoracic and Cardiovascular Surgery","General Thoracic and Cardiovascular Surgery","Vol.57","No.10","558","561","eng","true","null","scientific_journal","null","null","10.1007/s11748-009-0438-9","1863-6713","null","null","null","null","null" "Fluorescence diagnosis of lymph node metastasis of lung cancer in a mouse model.","Fluorescence diagnosis of lymph node metastasis of lung cancer in a mouse model.","Hiromitsu Takizawa, Kazuya Kondo, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama, Akira Tangoku","Hiromitsu Takizawa, Kazuya Kondo, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama, Akira Tangoku","null","Fluorescence diagnosis of lymph node metastasis of non-small cell lung cancer has not been reported previously. This study was conducted to evaluate the feasibility of fluorescence detection using 5-aminolevulinic acid and mono-L-aspartyl chlorine e6 for lymph node metastasis in a lung cancer mouse model. Human lung cancer cell line Ma44-3, which forms metastatic lymph nodes in the mediastinum, was injected into the left lungs of 6 severe combined immunodeficiency disease mice. Two weeks after implantation, 2 groups of 3 mice received oral administration of 5-aminolevulinic acid (100 mg/kg) or intraperitoneal administration of mono-L-aspartyl chlorine e6 (5 mg/kg). Both lungs and mediastinal organs were removed en-bloc and illuminated with blue light (405 nm) to evaluate the detectability of lung tumors and metastatic lymph nodes in the mediastinum. These organs were evaluated histopathologically. Clear red fluorescence was observed in the lung tumors of all mice. Metastatic lymph nodes had formed in 5 of 6 mice and were detected by fluorescent detection in all 5 mice even though one of the lymph nodes was invisible macroscopically under white light. In conclusion, fluorescence diagnosis of lymph node metastasis is possible in a mouse model. The successful result with small lymph node metastasis suggests the possibility of clinical application.","Fluorescence diagnosis of lymph node metastasis of non-small cell lung cancer has not been reported previously. This study was conducted to evaluate the feasibility of fluorescence detection using 5-aminolevulinic acid and mono-L-aspartyl chlorine e6 for lymph node metastasis in a lung cancer mouse model. Human lung cancer cell line Ma44-3, which forms metastatic lymph nodes in the mediastinum, was injected into the left lungs of 6 severe combined immunodeficiency disease mice. Two weeks after implantation, 2 groups of 3 mice received oral administration of 5-aminolevulinic acid (100 mg/kg) or intraperitoneal administration of mono-L-aspartyl chlorine e6 (5 mg/kg). Both lungs and mediastinal organs were removed en-bloc and illuminated with blue light (405 nm) to evaluate the detectability of lung tumors and metastatic lymph nodes in the mediastinum. These organs were evaluated histopathologically. Clear red fluorescence was observed in the lung tumors of all mice. Metastatic lymph nodes had formed in 5 of 6 mice and were detected by fluorescent detection in all 5 mice even though one of the lymph nodes was invisible macroscopically under white light. In conclusion, fluorescence diagnosis of lymph node metastasis is possible in a mouse model. The successful result with small lymph node metastasis suggests the possibility of clinical application.","null","null","2009-07","Oncology Reports","Oncology Reports","Vol.22","No.1","17","21","eng","true","null","scientific_journal","null","null","10.3892/or_00000400","1021-335X","null","null","null","null","null" "経口フッ化ピリミジン系抗癌剤の補助療法にて3年の長期生存を得ている甲状腺未分化癌の1例","A case of anaplastic carcinoma of thyroid administered peroral fluorinated pyrimidine for long-term survival during three years","山井 礼道, 吉田 卓弘, 鳥羽 博明, 吉良 美砂子, 滝沢 宏光, 丹黒 章","Hiromichi Yamai, Takahiro Yoshida, Hiroaki Toba, Misako Kira, Hiromitsu Takizawa, Akira Tangoku","null","We report a case of anaplastic carcinoma of the thyroid administered peroral fluorinated pyrimidine, providing longterm survival during three years. Three years ago, a 70-year-old woman diagnosed with anaplastic carcinoma of the thyroid was admitted for chemoradiation therapy after tumor resection and tracheostomy. The tumor was confirmed to remain on the margin of resected specimens by postoperative histopathology. Combination chemotherapy, including docetaxel, 5-fluorouracil, cisplatin, and radiotherapy, was performed for four weeks. After completion of radiotherapy, CT scan showed residual tumor and lytic clavicular bone findings. But the patient did not desire the same heavy chemotherapy, wishing rather to undergo chemotherapy as an outpatient, if possible. She received chemotherapy with S-1 which was peroral fluorinated pyrimidine for 9 months. In this period, PET-CT showed that accumulation of FDG and lytic clavicular bone findings were continuously confirmed. She was changed to tegafur-uracil(UFT)from S-1, because of myelosuppression. She is alive at this writing in good physical condition. CT shows no tumor growth and no remote metastasis.","We report a case of anaplastic carcinoma of the thyroid administered peroral fluorinated pyrimidine, providing longterm survival during three years. Three years ago, a 70-year-old woman diagnosed with anaplastic carcinoma of the thyroid was admitted for chemoradiation therapy after tumor resection and tracheostomy. The tumor was confirmed to remain on the margin of resected specimens by postoperative histopathology. Combination chemotherapy, including docetaxel, 5-fluorouracil, cisplatin, and radiotherapy, was performed for four weeks. After completion of radiotherapy, CT scan showed residual tumor and lytic clavicular bone findings. But the patient did not desire the same heavy chemotherapy, wishing rather to undergo chemotherapy as an outpatient, if possible. She received chemotherapy with S-1 which was peroral fluorinated pyrimidine for 9 months. In this period, PET-CT showed that accumulation of FDG and lytic clavicular bone findings were continuously confirmed. She was changed to tegafur-uracil(UFT)from S-1, because of myelosuppression. She is alive at this writing in good physical condition. CT shows no tumor growth and no remote metastasis.","null","null","2009-06","癌と化学療法","Japanese Journal of Cancer and Chemotherapy","Vol.36","No.6","1021","1024","jpn","true","null","scientific_journal","null","null","null","0385-0684","null","null","null","null","null" "Functional evaluation of pallid mice with genetic emphysema.","Functional evaluation of pallid mice with genetic emphysema.","M Yoshida, Shoji Sakiyama, Koichiro Kenzaki, Hiroaki Toba, K Uyama, M Takehisa, Kazuya Kondo, Akira Tangoku","M Yoshida, Shoji Sakiyama, Koichiro Kenzaki, Hiroaki Toba, K Uyama, M Takehisa, Kazuya Kondo, Akira Tangoku","null","Studies on pallid mice models of genetic emphysema have conventionally focused on morphological or biochemical evaluations. However, it is important to consider the functional aspects. We evaluated the exercise capacity and respiratory function in male pallid mice and male C57BL/6J mice at 3, 6, 12, and 15 months of age. The functional evaluations were conducted using a treadmill and a pulmonary function analysis device. The morphology of the lungs was analyzed on the basis of mean linear intercept (Lm) values. The body weights of the pallid mice at 12 and 15 months were significantly lower than those of the age-matched C57BL/6J mice. The pallid mice showed deterioration in exercise capacity from 6 months, as indicated by the trends in running distance. At 6, 12, and 15 months, the pallid mice showed significantly higher pulmonary compliance and significantly lower forced expiratory volume in 20 ms (FEV(20 ms))/vital capacity (VC) values in comparison with the corresponding values for the C57BL/6J mice. In the morphological analysis of the pallid mice, emphysema was detected from 12 months, and the mice showed a significantly larger Lm at 12 months. The exercise capacity and lung function in the pallid mice significantly deteriorated from 6 months, at which time no pathological changes in the lung were detected. The deterioration in the exercise capacity and pulmonary function preceded the microscopic morphological changes.Laboratory Investigation advance online publication, 20 April 2009; doi:10.1038/labinvest.2009.34.","Studies on pallid mice models of genetic emphysema have conventionally focused on morphological or biochemical evaluations. However, it is important to consider the functional aspects. We evaluated the exercise capacity and respiratory function in male pallid mice and male C57BL/6J mice at 3, 6, 12, and 15 months of age. The functional evaluations were conducted using a treadmill and a pulmonary function analysis device. The morphology of the lungs was analyzed on the basis of mean linear intercept (Lm) values. The body weights of the pallid mice at 12 and 15 months were significantly lower than those of the age-matched C57BL/6J mice. The pallid mice showed deterioration in exercise capacity from 6 months, as indicated by the trends in running distance. At 6, 12, and 15 months, the pallid mice showed significantly higher pulmonary compliance and significantly lower forced expiratory volume in 20 ms (FEV(20 ms))/vital capacity (VC) values in comparison with the corresponding values for the C57BL/6J mice. In the morphological analysis of the pallid mice, emphysema was detected from 12 months, and the mice showed a significantly larger Lm at 12 months. The exercise capacity and lung function in the pallid mice significantly deteriorated from 6 months, at which time no pathological changes in the lung were detected. The deterioration in the exercise capacity and pulmonary function preceded the microscopic morphological changes.Laboratory Investigation advance online publication, 20 April 2009; doi:10.1038/labinvest.2009.34.","null","null","2009-04-20","Laboratory Investigation; a Journal of Technical Methods and Pathology","Laboratory Investigation; a Journal of Technical Methods and Pathology","Vol.89","No.7","760","768","eng","true","null","scientific_journal","null","null","10.1038/labinvest.2009.34","1530-0307","null","null","null","null","null" "Recurrent thymoma with a pleural dissemination invading the intervertebral foramen.","Recurrent thymoma with a pleural dissemination invading the intervertebral foramen.","Hiroaki Toba, Kazuya Kondo, Hiromitsu Takizawa, Akira Tangoku","Hiroaki Toba, Kazuya Kondo, Hiromitsu Takizawa, Akira Tangoku","null","We report a rare case of recurrent thymoma with pleural dissemination invading the intervertebral foramen. A woman with Masaoka's stage IVa thymoma with myasthenia gravis (MG) underwent macroscopically complete resection. After 45 months, she developed back pain. Computed tomography (CT) of the chest demonstrated a mass in the right thoracic cavity invading the intervertebral foramen between thoracic vertebrae 10 and 11. She underwent complete resection of the tumor and postoperative radiotherapy. The resected specimen was histologically diagnosed as a pleural dissemination from thymoma. There has been no local recurrence.","We report a rare case of recurrent thymoma with pleural dissemination invading the intervertebral foramen. A woman with Masaoka's stage IVa thymoma with myasthenia gravis (MG) underwent macroscopically complete resection. After 45 months, she developed back pain. Computed tomography (CT) of the chest demonstrated a mass in the right thoracic cavity invading the intervertebral foramen between thoracic vertebrae 10 and 11. She underwent complete resection of the tumor and postoperative radiotherapy. The resected specimen was histologically diagnosed as a pleural dissemination from thymoma. There has been no local recurrence.","null","null","2009-03-09","European Journal of Cardio-Thoracic Surgery","European Journal of Cardio-Thoracic Surgery","Vol.35","No.5","917","919","eng","true","null","scientific_journal","null","null","10.1016/j.ejcts.2009.01.036","1873-734X","null","null","null","null","null" "肺多形癌の3切除例","Surgically treated pleomorphic carcinoma of the lung","鳥羽 博明, 先山 正二, 森本 雅美, 滝沢 宏光, 監﨑 孝一郎, 近藤 和也, 坂東 良美, 丹黒 章","Hiroaki Toba, Shoji Sakiyama, M Morimoto, Hiromitsu Takizawa, Koichiro Kenzaki, Kazuya Kondo, Yoshimi Bando, Akira Tangoku","null","We experienced 3 resected cases of pleomorphic carcinoma of the lung. Each cases were 74-year-old man (case 1), 74-year-old woman (case 2) and 69-year-old man (case 3). Two patients (case 1 and 2) were histologically diagnosed as pleomorphic carcinoma composed of spindle cell carcinoma with giant cell carcinoma. One patient (case 3) was similarly diagnosed as pleomorphic carcinoma composed of spindle cell carcinoma with adenocarcinoma and squamous cell carcinoma. Although lymph nodes metastasis were not recognized in all patients, invasion to vessels were recognized in 2 patients (case 1 and 3). In one patient (case 1), recurrence was recognized at contralateral side 1 month after surgery and he died of other disease 2 months after surgery. The other 2 patients were alive without recurrence 24 and 5 months after surgery. Recently it is reported that recurrence is recognized at early phase after surgery and prognosis is poor in a case with vessel invasions in spite of pathological NO state. Since one patient (case 3) had nonmetastatic lymph nodes with vessel invasions, careful observation is considered to be necessary.","We experienced 3 resected cases of pleomorphic carcinoma of the lung. Each cases were 74-year-old man (case 1), 74-year-old woman (case 2) and 69-year-old man (case 3). Two patients (case 1 and 2) were histologically diagnosed as pleomorphic carcinoma composed of spindle cell carcinoma with giant cell carcinoma. One patient (case 3) was similarly diagnosed as pleomorphic carcinoma composed of spindle cell carcinoma with adenocarcinoma and squamous cell carcinoma. Although lymph nodes metastasis were not recognized in all patients, invasion to vessels were recognized in 2 patients (case 1 and 3). In one patient (case 1), recurrence was recognized at contralateral side 1 month after surgery and he died of other disease 2 months after surgery. The other 2 patients were alive without recurrence 24 and 5 months after surgery. Recently it is reported that recurrence is recognized at early phase after surgery and prognosis is poor in a case with vessel invasions in spite of pathological NO state. Since one patient (case 3) had nonmetastatic lymph nodes with vessel invasions, careful observation is considered to be necessary.","null","null","2009-03","胸部外科","The Japanese Journal of Thoracic Surgery","Vol.62","No.3","202","206","jpn","true","null","scientific_journal","null","null","null","0021-5252","null","null","null","null","null" "気管・気管支形成手術の現況 2.気管・気管支形成 原発性肺癌における気管・気管支形成手術の臨床的検討","Clinical analysis of tracheoplasty and bronchoplasty in primary lung cancer","監﨑 孝一郎, 先山 正二, 鳥羽 博明, 中川 靖士, 滝沢 宏光, 近藤 和也, 丹黒 章","Koichiro Kenzaki, Shoji Sakiyama, Hiroaki Toba, Yasushi Nakagawa, Hiromitsu Takizawa, Kazuya Kondo, Akira Tangoku","null","In our department, there were 482 thoracic surgeries for primary lung cancer between 1994 and 2007. We clinically reviewed cases that underwent tracheoplasty or bronchoplasty (n = 22, 4.6%). The patients consisted of 21 males and 1 female (66.5 +/- 12.0 years-old). All patients were smokers. The tissue forms were 19 squamous cell carcinomas, 2 adenocarcinomas, 1 large cell carcinoma, 1 adenoid cystic carcinoma and 1 carcinoid, including 2 multiple carcinomas. Sleeve resections involved the trachea in 1, upper lobes in 13, lower lobes in 3, upper-middle lobes in 2 and intermediate bronchus in 1. Wedge resections were performed in the upper lobes in 2. Fourteen reconstructions were performed. We ordinarily sutured the trachea and bronchus in any case, using a single outside knot. There was no leakage at the anastomosis. There were 2 hospital deaths. There were 4 cancer deaths, including 2 local recurrences. There were 4 patients demonstrating stenosis post operatively. There were 3 stenoses among 4 preoperative radiation therapies. We considered that radiation therapy disturbed the repair of the anastomosis. There were 8 pneumonia patients who developed post operatively. There were 2 operative hospital deaths among 3 angio-bronchoplasties without coverage. Recently, we have routinely covered the anastomosis at the reconstruction site and have not experienced any major complications.","In our department, there were 482 thoracic surgeries for primary lung cancer between 1994 and 2007. We clinically reviewed cases that underwent tracheoplasty or bronchoplasty (n = 22, 4.6%). The patients consisted of 21 males and 1 female (66.5 +/- 12.0 years-old). All patients were smokers. The tissue forms were 19 squamous cell carcinomas, 2 adenocarcinomas, 1 large cell carcinoma, 1 adenoid cystic carcinoma and 1 carcinoid, including 2 multiple carcinomas. Sleeve resections involved the trachea in 1, upper lobes in 13, lower lobes in 3, upper-middle lobes in 2 and intermediate bronchus in 1. Wedge resections were performed in the upper lobes in 2. Fourteen reconstructions were performed. We ordinarily sutured the trachea and bronchus in any case, using a single outside knot. There was no leakage at the anastomosis. There were 2 hospital deaths. There were 4 cancer deaths, including 2 local recurrences. There were 4 patients demonstrating stenosis post operatively. There were 3 stenoses among 4 preoperative radiation therapies. We considered that radiation therapy disturbed the repair of the anastomosis. There were 8 pneumonia patients who developed post operatively. There were 2 operative hospital deaths among 3 angio-bronchoplasties without coverage. Recently, we have routinely covered the anastomosis at the reconstruction site and have not experienced any major complications.","null","null","2008-10","胸部外科","The Japanese Journal of Thoracic Surgery","Vol.61","No.11","951","956","jpn","true","null","scientific_journal","null","null","null","0021-5252","null","null","null","null","null" "Aberrant methylation of tumour-related genes in thymic epithelial tumours.","Aberrant methylation of tumour-related genes in thymic epithelial tumours.","Yukiko Hirose, Kazuya Kondo, Hiromitsu Takizawa, Taeko Nagao, Yasushi Nakagawa, Haruhiko Fujino, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama, Akira Tangoku","Yukiko Hirose, Kazuya Kondo, Hiromitsu Takizawa, Taeko Nagao, Yasushi Nakagawa, Haruhiko Fujino, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama, Akira Tangoku","null","BACKGROUND: Thymoma is an uncommon neoplasm derived from epithelial cells of the thymus. Few studies have addressed the genetic alterations that occur in the tumourigenesis of thymoma. METHODS: We examined aberrant DNA methylation of DAP-K, p-16, MGMT and HPP1 genes in 26 thymomas and 6 thymic carcinoma to clarify the association between aberrant DNA methylation and clinicopathological features. RESULTS: Fifteen (47%) of 32 thymic epithelial tumours showed aberrant methylation. Aberrant methylation was more frequent in thymic carcinoma (86%) than in thymoma (29%). Moreover, the frequency of tumours with methylation of multiple genes in thymic carcinoma was higher than in thymoma (60% vs 20%). In thymoma, the frequency of tumour methylation, including the type A tumour component (28%), was lower than that of tumours with type B tumour component (42%). MGMT methylation was detected in 23% of thymoma and in 83% of thymic carcinoma. The frequency of methylation of the MGMT gene in both tumours was high compared with the other 3 genes. CONCLUSIONS: Aberrant DNA methylation was more frequent in thymic carcinoma than in thymoma, and the frequency of DNA methylation in thymic epithelial tumours is roughly parallel to their malignant behaviour.","BACKGROUND: Thymoma is an uncommon neoplasm derived from epithelial cells of the thymus. Few studies have addressed the genetic alterations that occur in the tumourigenesis of thymoma. METHODS: We examined aberrant DNA methylation of DAP-K, p-16, MGMT and HPP1 genes in 26 thymomas and 6 thymic carcinoma to clarify the association between aberrant DNA methylation and clinicopathological features. RESULTS: Fifteen (47%) of 32 thymic epithelial tumours showed aberrant methylation. Aberrant methylation was more frequent in thymic carcinoma (86%) than in thymoma (29%). Moreover, the frequency of tumours with methylation of multiple genes in thymic carcinoma was higher than in thymoma (60% vs 20%). In thymoma, the frequency of tumour methylation, including the type A tumour component (28%), was lower than that of tumours with type B tumour component (42%). MGMT methylation was detected in 23% of thymoma and in 83% of thymic carcinoma. The frequency of methylation of the MGMT gene in both tumours was high compared with the other 3 genes. CONCLUSIONS: Aberrant DNA methylation was more frequent in thymic carcinoma than in thymoma, and the frequency of DNA methylation in thymic epithelial tumours is roughly parallel to their malignant behaviour.","null","null","2008-09-07","Lung Cancer","Lung Cancer","Vol.64","No.2","155","159","eng","true","null","scientific_journal","null","null","10.1016/j.lungcan.2008.07.015","1872-8332","null","null","null","null","null" "手術の工夫 両側転移性肺腫瘍に対するclamshell incisionによるアプローチ","Approach by clamshell incision for bilateral pulmonary metastasis","吉田 光輝, 先山 正二, 監﨑 孝一郎, 鳥羽 博明, 近藤 和也, 丹黒 章","Mitsuteru Yoshida, Shoji Sakiyama, Koichiro Kenzaki, Hiroaki Toba, Kazuya Kondo, Akira Tangoku","null","In recent years thoracotomy by ""clamshell incision"" has frequently been chosen for heart-lung transplantation, bilateral lung tumors and mediastinal tumor merging into lung tumor because this approach provides very good visibility to access the whole bilateral lung including the lower lobe and mediastinal organs. In our hospital, 4 patients underwent bilateral thoracotomy by clamshell incision for pulmonary metastasectomy between 2001 and 2005. All cases had bilateral pulmonary metastases, and multiple wedge resection was performed. All lesions that were planned for resection on preoperative computed tomography (CT) could be resected. Regarding the surgical approach to bilateral pulmonary metastases that did not need lobectomy, clamshell incision is one of the useful approaches that can allow wedge resection anywhere in the whole lung. In cases that are expected multiple procedures, bilateral thoracotomy by clamshell incision is recommended because it allows another route for thoracotomy at reoperation.","In recent years thoracotomy by ""clamshell incision"" has frequently been chosen for heart-lung transplantation, bilateral lung tumors and mediastinal tumor merging into lung tumor because this approach provides very good visibility to access the whole bilateral lung including the lower lobe and mediastinal organs. In our hospital, 4 patients underwent bilateral thoracotomy by clamshell incision for pulmonary metastasectomy between 2001 and 2005. All cases had bilateral pulmonary metastases, and multiple wedge resection was performed. All lesions that were planned for resection on preoperative computed tomography (CT) could be resected. Regarding the surgical approach to bilateral pulmonary metastases that did not need lobectomy, clamshell incision is one of the useful approaches that can allow wedge resection anywhere in the whole lung. In cases that are expected multiple procedures, bilateral thoracotomy by clamshell incision is recommended because it allows another route for thoracotomy at reoperation.","null","null","2008-03","胸部外科","The Japanese Journal of Thoracic Surgery","Vol.61","No.3","206","209","jpn","true","null","scientific_journal","null","null","null","0021-5252","null","null","null","null","null" "縦隔悪性リンパ腫の臨床的検討","Clinical experience with 16 cases of mediastinal lymphoma","鳥羽 博明, 近藤 和也, 吉田 光輝, 監﨑 孝一郎, 三好 孝典, 先山 正二, 丹黒 章","Hiroaki Toba, Kazuya Kondo, Mitsuteru Yoshida, Koichiro Kenzaki, Takanori Miyoshi, Shoji Sakiyama, Akira Tangoku","null","Sixteen cases of mediastinal lymphoma in our hospital were reviewed clinically. There were 7 men and 9 women, whose mean age is 35 years old. The histological types were non-Hodgkins' disease in 12 (B-cell type in 6 and T-cell type in 6), Hodgkins' disease in 2, mucosa-associated lymphoid tissue (MALT) lymphoma in 2. All cases except 1 in which percutaneous needle biopsy was performed were diagnosed histologically. Even small specimens by percutaneous needle biopsy can be helpful in diagnosing histological type and subtype with immunohistlogy, recommending percutaneous needle biopsy as an mitial step for diagnosis. When histological diagnosis can not be made by needle biopsy, open biopsy should be done.","Sixteen cases of mediastinal lymphoma in our hospital were reviewed clinically. There were 7 men and 9 women, whose mean age is 35 years old. The histological types were non-Hodgkins' disease in 12 (B-cell type in 6 and T-cell type in 6), Hodgkins' disease in 2, mucosa-associated lymphoid tissue (MALT) lymphoma in 2. All cases except 1 in which percutaneous needle biopsy was performed were diagnosed histologically. Even small specimens by percutaneous needle biopsy can be helpful in diagnosing histological type and subtype with immunohistlogy, recommending percutaneous needle biopsy as an mitial step for diagnosis. When histological diagnosis can not be made by needle biopsy, open biopsy should be done.","null","null","2008-02","胸部外科","The Japanese Journal of Thoracic Surgery","Vol.61","No.2","97","101","jpn","true","null","scientific_journal","null","null","null","0021-5252","null","null","null","null","null" "Effect of mediastinal lymph nodes sampling in patients with clinical stage I non-small cell lung cancer","Effect of mediastinal lymph nodes sampling in patients with clinical stage I non-small cell lung cancer","Hiromitsu Takizawa, Kazuya Kondo, Hisashi Matsuoka, Koh Uyama, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama, Akira Tangoku, Kazumasa Miura, Kiyoshi Yoshizawa, Junji Morita","Hiromitsu Takizawa, Kazuya Kondo, Hisashi Matsuoka, Koh Uyama, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama, Akira Tangoku, Kazumasa Miura, Kiyoshi Yoshizawa, Junji Morita","null","Systematic nodal dissection has been recommended for patients with resectable non-small cell lung cancer because of its staging accuracy. However, in patients with clinical stage I non-small cell lung cancer whether systematic nodal dissection provides more benefits than mediastinal lymph node sampling or not is controversial. In this retrospective study, we evaluated the effect of mediastinal lymph node sampling in patients with clinical stage I NSCLC. One hundred and nineteen consecutive patients with clinical stage I NSCLC, who underwent curative operation between January 1994 and December 2000, were retrospectively reviewed (dissection group = 58: sampling group= 61). Systematic nodal dissection was defined as complete removal of mediastinal lymph node, and mediastinal lymph node sampling was defined as removal of lymph node levels 3, 4, and 7 for right-sided tumors and levels 5, 6, and 7 for left-sided tumors. The total number of removed mediastinal lymph nodes in patients who underwent systematic nodal dissection was 22.1 +/- 9.7, which was significantly higher than that in patients who underwent mediastinal lymph node sampling of 11.4 +/- 7.0 (p < 0.001). Postoperatively N2 disease was detected in 8 patients (13.8%) in the dissection group and 7 (11.5%) in the sampling group. After the median follow up of 79 months, the cancer specific survival rate at 5 year was 78.0% in the dissection group and 76.2% in the sampling group (p = 0.60). Mediastinal lymph node sampling showed the similar effect to systematic nodal dissection in patients with clinical stage I non-small cell lung cancer.","Systematic nodal dissection has been recommended for patients with resectable non-small cell lung cancer because of its staging accuracy. However, in patients with clinical stage I non-small cell lung cancer whether systematic nodal dissection provides more benefits than mediastinal lymph node sampling or not is controversial. In this retrospective study, we evaluated the effect of mediastinal lymph node sampling in patients with clinical stage I NSCLC. One hundred and nineteen consecutive patients with clinical stage I NSCLC, who underwent curative operation between January 1994 and December 2000, were retrospectively reviewed (dissection group = 58: sampling group= 61). Systematic nodal dissection was defined as complete removal of mediastinal lymph node, and mediastinal lymph node sampling was defined as removal of lymph node levels 3, 4, and 7 for right-sided tumors and levels 5, 6, and 7 for left-sided tumors. The total number of removed mediastinal lymph nodes in patients who underwent systematic nodal dissection was 22.1 +/- 9.7, which was significantly higher than that in patients who underwent mediastinal lymph node sampling of 11.4 +/- 7.0 (p < 0.001). Postoperatively N2 disease was detected in 8 patients (13.8%) in the dissection group and 7 (11.5%) in the sampling group. After the median follow up of 79 months, the cancer specific survival rate at 5 year was 78.0% in the dissection group and 76.2% in the sampling group (p = 0.60). Mediastinal lymph node sampling showed the similar effect to systematic nodal dissection in patients with clinical stage I non-small cell lung cancer.","null","null","2008-02","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.55","No.1,2","37","43","eng","true","null","scientific_journal","null","null","10.2152/jmi.55.37","1343-1420","null","null","null","null","null" "Two cases of bronchogenic cyst with severe adhesion to the trachea","Two cases of bronchogenic cyst with severe adhesion to the trachea","Mitsuteru Yoshida, Kazuya Kondo, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama, Akira Tangoku","Mitsuteru Yoshida, Kazuya Kondo, Hiroaki Toba, Koichiro Kenzaki, Shoji Sakiyama, Akira Tangoku","null","We experienced two bronchogenic cysts with severe adhesion to the trachea. Both cysts were located on the right side of the trachea. The surgical procedure was changed to thoracotomy from thoracoscopic surgery due to strong adhesion to the trachea. In case 1, sharp separation of the cystic wall from the trachea led to tracheal wall damage. In case 2, the cystic wall except a portion which was adhered to the trachea was resected. The inner side of the residual cystic wall underwent dull curettage to remove the epithelial component. There were no postoperative complications in either case.","We experienced two bronchogenic cysts with severe adhesion to the trachea. Both cysts were located on the right side of the trachea. The surgical procedure was changed to thoracotomy from thoracoscopic surgery due to strong adhesion to the trachea. In case 1, sharp separation of the cystic wall from the trachea led to tracheal wall damage. In case 2, the cystic wall except a portion which was adhered to the trachea was resected. The inner side of the residual cystic wall underwent dull curettage to remove the epithelial component. There were no postoperative complications in either case.","null","null","2007-02","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.54","No.1-2","187","190","eng","true","null","scientific_journal","null","null","10.2152/jmi.54.187","1343-1420","null","null","null","null","null" "Predictive Value of Thymidylate Synthase and Dihydropyrimidine Dehydrogenase Expression in Tumor Tissue, Regarding the Efficacy of Postoperatively Administered UFT(Tegafur+Uracil) in Patients with Non-small Cell Lung Cancer","Predictive Value of Thymidylate Synthase and Dihydropyrimidine Dehydrogenase Expression in Tumor Tissue, Regarding the Efficacy of Postoperatively Administered UFT(Tegafur+Uracil) in Patients with Non-small Cell Lung Cancer","Takanori Miyoshi, Kazuya Kondo, Hiroaki Toba, Mitsuteru Yoshida, Haruhiko Fujino, Koichiro Kenzaki, Shoji Sakiyama, Masatsugu Takehisa, Akira Tangoku","Takanori Miyoshi, Kazuya Kondo, Hiroaki Toba, Mitsuteru Yoshida, Haruhiko Fujino, Koichiro Kenzaki, Shoji Sakiyama, Masatsugu Takehisa, Akira Tangoku","null","UFT (tegafur + uracil) has been reported to be effective as an adjuvant in postoperative chemotherapy for non-small cell lung cancer (NSCLC) in a randomized prospective study. Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression were investigated in resected tumors and the relationship between their expression and clinical factors in NSCLC patients was examined. Fifty-four NSCLC patients had undergone complete surgical resection and lymph node dissection, and had been administered UFT post-surgery. The TS and DPD expression in the tumor tissues was evaluated by immunohistochemical staining. The relationship between TS and/or DPD expression and clinicopathological factors was examined. There were 38 TS-negative and 16 TS-positive cases, and 22 DPD-negative and 32 DPD-positive cases. There was no significant difference between the patients with TS or DPD and those without TS or DPD in age, gender, histological type or p-stage. The 5-year survival rates of patients positive and negative for TS were 50.0 and 89.5%, while 10-year survival rates were 23.3 and 79.7%, respectively (p<0.001). The 5-year survival rates of TS-positive and TS-negative patients in p-stage I were 54.6 and 95.5%, while 10-year survival rates were 22.7 and 95.5%, respectively (p<0.001). There was no significant difference between DPD-positive and DPD-negative patients in prognosis. The oral administration of UFT after surgery might improve the survival of NSCLC patients when TS levels in tumor tissues are low. Immunohistochemical evaluation of TS and DPD expression may be useful for predicting the efficacy of UFT after complete resection in NSCLC.","UFT (tegafur + uracil) has been reported to be effective as an adjuvant in postoperative chemotherapy for non-small cell lung cancer (NSCLC) in a randomized prospective study. Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression were investigated in resected tumors and the relationship between their expression and clinical factors in NSCLC patients was examined. Fifty-four NSCLC patients had undergone complete surgical resection and lymph node dissection, and had been administered UFT post-surgery. The TS and DPD expression in the tumor tissues was evaluated by immunohistochemical staining. The relationship between TS and/or DPD expression and clinicopathological factors was examined. There were 38 TS-negative and 16 TS-positive cases, and 22 DPD-negative and 32 DPD-positive cases. There was no significant difference between the patients with TS or DPD and those without TS or DPD in age, gender, histological type or p-stage. The 5-year survival rates of patients positive and negative for TS were 50.0 and 89.5%, while 10-year survival rates were 23.3 and 79.7%, respectively (p<0.001). The 5-year survival rates of TS-positive and TS-negative patients in p-stage I were 54.6 and 95.5%, while 10-year survival rates were 22.7 and 95.5%, respectively (p<0.001). There was no significant difference between DPD-positive and DPD-negative patients in prognosis. The oral administration of UFT after surgery might improve the survival of NSCLC patients when TS levels in tumor tissues are low. Immunohistochemical evaluation of TS and DPD expression may be useful for predicting the efficacy of UFT after complete resection in NSCLC.","null","null","2007","Anticancer Research","Anticancer Research","Vol.27","No.4C","2641","2648","eng","true","null","scientific_journal","null","null","null","0250-7005","null","null","null","null","null" "臨床と研究 腎癌肺転移巣の組織学的異型度が画像診断に及ぼす影響","Pulmonary Resection in Renal Cell Carcinoma Metastasis : the Influence of Histologic Atypia of the Metastatic Focus on Preoperative or Perioperative Diagnosis","吉田 光輝, 先山 正二, 梶浦 耕一郎, 鳥羽 博明, 川上 行奎, 滝沢 宏光, 近藤 和也, 丹黒 章","Mitsuteru Yoshida, Shoji Sakiyama, Koichiro Kajiura, Hiroaki Toba, Yukikiyo Kawakami, Hiromitsu Takizawa, Kazuya Kondo, Akira Tangoku","null","null","null","null","null","2013-10","胸部外科","The Japanese Journal of Thoracic Surgery","Vol.66","No.11","996","999","jpn","null","null","research_institution","null","null","null","0021-5252","null","http://ci.nii.ac.jp/naid/40019810151/","null","null","null"