2021/12/04 更新

写真a

ハシモト タケヒサ
橋本 毅久
HASHIMOTO Takehisa
所属
医歯学総合病院 魚沼地域医療教育センター 特任教授
職名
特任教授
外部リンク

学位

  • 医学博士 ( 2001年3月   新潟大学 )

研究キーワード

  • 肺癌

  • 遺伝子異常

  • 呼吸器外科

研究分野

  • ライフサイエンス / 呼吸器外科学  / 呼吸器外科

経歴

  • 新潟大学   医歯学総合病院 魚沼地域医療教育センター   特任教授

    2015年4月 - 現在

  • 新潟大学   医歯学総合研究科   講師

    2012年7月 - 2015年3月

  • 新潟大学   医学部 医学科   講師

    2012年7月 - 2015年3月

  • 新潟大学   医歯学総合病院   助教

    2003年10月 - 2012年6月

  • 新潟大学   助手

    2001年4月 - 2003年9月

  • 新潟大学   医学部   医員

    1993年4月 - 1997年3月

▶ 全件表示

取得資格

  • 医師

 

論文

  • Salvage surgery to treat tumor regrowth after stereotactic body radiotherapy in primary non-small cell lung cancer. 国際誌

    Takahisa Koizumi, Tadashi Aoki, Masayuki Saito, Yasushi Yamato, Go Furuyashiki, Akihiko Kitahara, Takehisa Hashimoto, Takehiro Watanabe, Masanori Tsuchida

    Journal of thoracic disease   12 ( 10 )   5289 - 5298   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: Stereotactic body radiotherapy (SBRT) is considered to be an effective and safe treatment in patients with primary lung cancer. If local recurrence is confirmed following SBRT, surgical treatment is a possibility. The present study aimed to clarify the safety and survival outcomes of salvage surgery in primary lung cancer patients with local recurrence following SBRT. Methods: All subjects were patients with primary lung cancer who underwent surgical treatment for local recurrence following SBRT during the period from July 2005 to July 2015. We evaluated the reason for SBRT selection, the surgical procedure, postoperative complications, and prognosis. Results: Of 932 patients underwent SBRT as treatment for primary lung cancer, 48 patients (5.2%) had local recurrence alone and 19 patients (2.0%) underwent salvage surgery. SBRT was selected in eight medically operable patients who refused surgery, and in 11 patients considered medically inoperable by their pulmonologist. Lobectomy was performed in 15 patients. Postoperative complications were documented in 4 patients (21.1%). Incomplete resection was performed in 2 patients. Stage progression was confirmed in 7 patients (36.8%). The 5-year overall survival (OS) was 72.5% and the 5-year disease-free survival (DFS) was 65.2%. Conclusions: We evaluated patients who underwent salvage surgery due to local recurrence of lung cancer following SBRT. We found that salvage surgery could be performed safely without affecting SBRT outcomes. We further infer that cases of complete resection are likely to be associated with good prognosis, and that SBRT should be selected only after careful consideration because complete resection is not possible in all cases.

    DOI: 10.21037/jtd-20-2253

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  • Isolated Adrenocorticotropin Deficiency due to Nivolumab-induced Hypophysitis in a Patient with Advanced Lung Adenocarcinoma: A Case Report and Literature Review.

    Nobumasa Ohara, Kazumasa Ohashi, Toshiya Fujisaki, Chiyumi Oda, Yohei Ikeda, Yuichiro Yoneoka, Takehisa Hashimoto, Go Hasegawa, Kazuo Suzuki, Toshinori Takada

    Internal medicine (Tokyo, Japan)   57 ( 4 )   527 - 535   2018年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A 63-year-old Japanese woman with advanced lung adenocarcinoma developed isolated adrenocorticotropin deficiency caused by immune checkpoint inhibitor (ICI)-related hypophysitis following 8 months of nivolumab therapy. Prompt corticosteroid replacement therapy effectively relieved her secondary adrenal insufficiency symptoms and allowed her to pursue nivolumab therapy, which had been effective for the control of lung adenocarcinoma. Human leukocyte antigen (HLA) typing revealed the presence of the DRB1*04:05-DQA1*03:03-DQB1*04:01 haplotype, which is associated with susceptibility to autoimmune polyglandular syndrome with pituitary disorder in the Japanese population. This case suggests that genetic factors, such as HLA, contribute to the development of endocrinopathies induced by ICIs.

    DOI: 10.2169/internalmedicine.9074-17

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  • Characteristics and timing of recurrence during postoperative surveillance after curative resection for lung adenocarcinoma.

    Terumoto Koike, Tatsuya Goto, Akihiko Kitahara, Seijiro Sato, Masayuki Saitoh, Takehisa Hashimoto, Osamu Namura, Masashi Takahashi, Shin-Ichi Toyabe, Masanori Tsuchida

    Surgery today   47 ( 12 )   1469 - 1475   2017年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: To establish the most effective methods of postoperative surveillance to detect early recurrence of lung adenocarcinoma. METHODS: The subjects of this retrospective study were 485 patients with p-stage I-III lung adenocarcinoma, who underwent postoperative surveillance. We examined the sites and detection modes of recurrence and calculated the recurrence-free probabilities. Patients with stage I disease were divided into low- and high-risk recurrence groups using a risk score calculated by assigning points proportional to risk factor regression coefficients. RESULTS: Of the 112 patients with recurrence, 86 had intrathoracic recurrence. Routine computed tomography (CT) revealed recurrence in 60 patients. The recurrence-free probability curves showed that 95% of recurrences were identified within the first 4 years after resection in patients with stage II/III disease. In patients with stage I disease, the predictors of recurrence included male sex, positive pleural lavage cytology, moderate-to-poor differentiation, and visceral pleural invasion. Postoperative recurrences were detected throughout the follow-up period in the high-risk group. CONCLUSIONS: Routine chest CT plays an important role in the postoperative surveillance of lung adenocarcinoma. We recommend intensive follow-up during the early post-resection period for patients with advanced stage disease and long-term follow-up for high-risk patients with stage I disease.

    DOI: 10.1007/s00595-017-1537-3

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  • Cardiac tamponade communicating with a posterior mediastinal chylocele after esophagectomy. 国際誌

    Shin-Ichi Kosugi, Takehisa Hashimoto, Yo Sato, Kenichiro Hirano, Eiji Sunami, Takeaki Matsuzawa, Motoko Takahashi, Hiroshi Ichikawa

    Journal of surgical case reports   2017 ( 10 )   rjx216   2017年10月

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    記述言語:英語  

    A 75-year-old male received neoadjuvant chemotherapy for locally advanced squamous cell carcinoma of the mid-thoracic esophagus, followed by right transthoracic esophagectomy with extended mediastinal lymphadenectomy. Cardiac tamponade developed on postoperative Days 1 and 13, for which emergency ultrasound-guided drainage was required. Pericardial drainage fluid became chylous after administration of polymeric formula. A computed tomography scan demonstrated the presence of a retrocardiac fluid collection, encompassed by the left pulmonary vein and left atrium, descending aorta and vertebral column. Based on these findings, the diagnosis of chylopericardial tamponade communicating with a posterior mediastinal chylocele was made. The ligation of the thoracic duct was successfully performed via the left-sided thoracoscopic approach on postoperative Day 20 and the clinical course after the second operation was uneventful. The possible mechanisms of this exceptionally rare complication after esophagectomy were discussed.

    DOI: 10.1093/jscr/rjx216

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  • Lobectomy and limited resection in small-sized peripheral non-small cell lung cancer. 国際誌

    Terumoto Koike, Teruaki Koike, Seijiro Sato, Takehisa Hashimoto, Tadashi Aoki, Katsuo Yoshiya, Yasushi Yamato, Takehiro Watanabe, Kohei Akazawa, Shin-Ichi Toyabe, Masanori Tsuchida

    Journal of thoracic disease   8 ( 11 )   3265 - 3274   2016年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Although lobectomy is the standard surgical procedure for non-small cell lung cancer (NSCLC), recent studies show favorable outcomes after limited resection in patients with small-sized peripheral tumors. We conducted a randomized controlled trial of such patients to estimate postoperative outcomes and pulmonary function following these surgical techniques. METHODS: Between 2005 and 2008, eligible patients with tumors of 2 cm or less were randomly assigned 1:1 to undergo lobectomy or limited resection; 32 and 33 NSCLC patients in each group, respectively, were analyzed. The primary end points were 5-year overall survival (OS) and disease-free survival (DFS), while the secondary end points were postoperative pulmonary function including forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). RESULTS: The 5-year OS rates were 93.8% and 90.9% in the lobectomy and limited resection groups, respectively (P=0.921). The 5-year DFS rates were 93.8% and 90.9% in the lobectomy and limited resection groups, respectively (P=0.714). These rates did not differ significantly between the two resection groups. The median postoperative/preoperative FVC ratios were 84.1% and 90.0% in the lobectomy and limited resection groups, respectively, while the median postoperative/preoperative FEV1 ratios were 81.9% and 89.1%, respectively. Both ratios were significantly higher in the limited resection group (P=0.032 and P=0.005 for FVC and FEV1 ratios, respectively). CONCLUSIONS: A similar outcome, with more preserved postoperative pulmonary function, was observed in patients who underwent limited resection compared to those who underwent lobectomy. Ongoing large-scale multi-institutional prospective randomized trials of lobar versus sublobar resection in patients with small peripheral NSCLCs will hopefully provide definitive information about intentional limited resection of small peripheral tumors.

    DOI: 10.21037/jtd.2016.11.106

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  • Surgical Outcomes of Lung Cancer Patients with Combined Pulmonary Fibrosis and Emphysema and Those with Idiopathic Pulmonary Fibrosis without Emphysema.

    Seijiro Sato, Terumoto Koike, Takehisa Hashimoto, Hiroyuki Ishikawa, Akira Okada, Takehiro Watanabe, Masanori Tsuchida

    Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia   22 ( 4 )   216 - 23   2016年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: Combined pulmonary fibrosis and emphysema (CPFE) is a unique disorder. The aim of this study was to compare the surgical outcomes of lung cancer patients with CPFE and those with idiopathic pulmonary fibrosis (IPF) without emphysema. METHODS: A total of 1548 patients who underwent surgery for primary lung cancer between January 2001 and December 2012 were retrospectively reviewed. RESULTS: Of the 1548 patients, 55 (3.6%) had CPFE on computed tomography (CT), and 45 (2.9%) had IPF without emphysema. The overall and disease-free 5-year survival rates for patients with CPFE were not significantly worse than those for patients with IPF without emphysema (24.9% vs. 36.8%, p = 0.814; 39.8% vs. 39.3%, p = 0.653, respectively). Overall, 21 (38.1%) patients with CPFE and nine patients (20.0%) with IPF without emphysema developed postoperative cardiopulmonary complications. Patients with CPFE had significantly more postoperative cardiopulmonary complications involving pulmonary air leakage for >6 days, hypoxemia, and arrhythmia than patients with IPF without emphysema (p = 0.048). CONCLUSIONS: There was no significant difference in survival after surgical treatment between CPFE patients and IPF patients without emphysema, but CPFE patients had significantly higher morbidity than IPF patients without emphysema.

    DOI: 10.5761/atcs.oa.15-00315

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  • Lobectomy Versus Segmentectomy in Radiologically Pure Solid Small-Sized Non-Small Cell Lung Cancer. 国際誌

    Terumoto Koike, Akihiko Kitahara, Seijiro Sato, Takehisa Hashimoto, Tadashi Aoki, Teruaki Koike, Katsuo Yoshiya, Shin-Ichi Toyabe, Masanori Tsuchida

    The Annals of thoracic surgery   101 ( 4 )   1354 - 60   2016年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The indication for limited resection of radiologically pure solid non-small cell lung cancer (NSCLC) is controversial owing to its invasive pathologic characteristics. This study was performed to compare the outcomes after lobectomy and segmentectomy in these NSCLC patients. METHODS: We retrospectively reviewed 251 patients with radiologically pure solid cT1a N0 M0 NSCLC who underwent lobectomy or segmentectomy, and the preoperative characteristics of the patients treated with the two operative techniques were matched using propensity score methods. Overall survival (OS) and disease-free survival (DFS) curves were compared using the log rank test, and differences in survival were also evaluated by the McNemar test. The preoperative factors and surgical procedure were analyzed with the multivariate Cox proportional hazards regression model to identify independent predictors of poor OS and DFS. RESULTS: In the propensity score matched lobectomy and segmentectomy groups (87 patients per group), the 5-year and 10-year OS rates were 85% versus 84% and 66% versus 63%, respectively; and the 5-year and 10-year DFS rates were 80% versus 77% and 64% versus 58%, respectively. There were no significant differences between the two groups in OS or DFS by the log rank test, and also no significant differences in 3-year, 5-year, or 7-year OS or DFS by the McNemar test. Although age, smoking status, pulmonary function, and carcinoembryonic antigen were identified as significant predictors of both OS and DFS, the surgical procedure was not identified. CONCLUSIONS: Similar oncologic outcomes after lobectomy and segmentectomy were indicated among patients with radiologically pure solid small-sized NSCLC.

    DOI: 10.1016/j.athoracsur.2015.10.048

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  • A Case of Ectopic ACTH-Producing Pulmonary Carcinoid Arising in an Extralobar Pulmonary Sequestration. 国際誌

    Seijiro Sato, Akihiko Kitahara, Terumoto Koike, Takehisa Hashimoto, Riuko Ohashi, Yoichi Kameda, Masanori Tsuchida

    International journal of surgical pathology   24 ( 2 )   130 - 4   2016年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Ectopic adrenocorticotrophic hormone (ACTH)-producing bronchopulmonary carcinoid arising in a bronchopulmonary sequestration is extremely rare. The case of a 67-year-old woman with a 1.7-cm nodule in the mediastinal side of the left lower lobe is presented. At 52 years of age, she was diagnosed as having ACTH-dependent Cushing's syndrome (CS). However, no ectopic source of ACTH-secretion was detected. Seven years later, she underwent a bilateral adrenalectomy because of aggravation of her health condition. This time, tumor excision was performed by thoracoscopic surgery. The tumor adhered sparsely to the mediastinal pleura and the left lower lobe and was bluntly separated from these tissues. Pathologically, the tumor was a typical carcinoid arising in an extralobar pulmonary sequestration. Immunohistochemical staining confirmed the secretion of ACTH by bronchopulmonary carcinoid tumor cells. After surgery, the serum ACTH level was almost normalized, and the dexamethasone (1 mg) suppression test showed significant suppression of ACTH.

    DOI: 10.1177/1066896915605615

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  • Resection of a large ectopic parathyroid adenoma: A case report. 国際誌

    Seijiro Sato, Akihiko Kitahara, Terumoto Koike, Takehisa Hashimoto, Riuko Ohashi, Noriko Motoi, Masanori Tsuchida

    International journal of surgery case reports   23   8 - 11   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    INTRODUCTION: Parathyroid adenomas are the most common cause of primary hyperparathyroidism. However, cases of parathyroid adenomas greater than 4cm with osteitis fibrosa cystica are extremely rare. Herein, we report a case of resection of a large ectopic mediastinal parathyroid adenoma. CASE PRESENTATIONS: A 46-year-old female with chief complaints of bone pain and gait disturbance was referred to our hospital. Physical examination revealed many mobile teeth in her oral cavity, distortion of the vertebral body, and bowlegs. Laboratory tests showed hypercalcemia, hypophosphatemia, and elevated serum levels of intact parathyroid hormone. Chest CT revealed a 42-mm well-defined, enhancing mass in front of the left-sided tracheal bifurcation. Her findings were diagnosed as primary hyperparathyroidism due to an ectopic mediastinal parathyroid tumor. We performed a median sternotomy and resected the tumor. The tumor was a solid, yellowish-brown mass measuring 42×42 mm. Pathologically, the tumor consisted mainly of chief cells with some oxyphil cells; there were no necrotic areas or nuclear atypia, and few mitotic figures. We diagnosed the tumor as an ectopic mediastinal parathyroid adenoma. Eight months after the resection, her serum calcium, phosphorus, and intact PTH levels were normal. DISCUSSION AND CONCLUSIONS: Parathyroid adenomas and parathyroid carcinomas have disparate natural histories, but they can be difficult to differentiate on the basis of preoperative clinical characteristics. We believe that long-term follow-up of these cases is required because there have been few reports on the postoperative natural history of large parathyroid adenomas.

    DOI: 10.1016/j.ijscr.2016.04.007

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  • [Simultaneous pulmonary resection and endovascular repair for patients with coexisting primary lung cancer and aneurysm].

    Terumoto Koike, Hiroki Sato, Seijiro Sato, Takeshi Okamoto, Takehisa Hashimoto, Kazuhiko Hanzawa, Masanori Tsuchida

    Kyobu geka. The Japanese journal of thoracic surgery   68 ( 4 )   293 - 7   2015年4月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    The surgical strategy for coexisting lung cancer and aneurysm is controversial owing to the risk of aneurysm rupture during the perioperative period of pulmonary resection. We performed simultaneous pulmonary resection and endovascular repair in 2 patients with coexisting lung cancer and aneurysm. Case 1:A 74-year-old man presented at our hospital with cT2aN0M0 lung cancer and a 5.0 cm abdominal aortic aneurysm. Because computed tomography indicated the possibility of advanced lung cancer, we decided to perform simultaneous surgery for lung cancer and the aneurysm. Under general anesthesia, endovascular aneurysm repair was performed before right lower lobectomy with lymphadenectomy. The postoperative course was uneventful, and the patient was discharged on postoperative day 12. Case 2:A 72-year-old man presented at our hospital with cT2aN1M0 lung cancer, a 5.0 cm left internal iliac artery aneurysm, and right renal cell carcinoma( RCC). Because the lung cancer was advanced and the patients needed following surgical treatment for RCC, we decided to perform simultaneous surgery for lung cancer and the aneurysm. Under general anesthesia, endovascular aneurysm repair was performed before right upper lobectomy with lymphadenectomy. The postoperative course was uneventful, and the patient was discharged on postoperative day 11.

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  • A combination of preoperative CT findings and postoperative serum CEA levels improves recurrence prediction for stage I lung adenocarcinoma. 国際誌

    Motohiko Yamazaki, Hiroyuki Ishikawa, Ryosuke Kunii, Akiko Tasaki, Suguru Sato, Yohei Ikeda, Norihiko Yoshimura, Takehisa Hashimoto, Masanori Tsuchida, Hidefumi Aoyama

    European journal of radiology   84 ( 1 )   178 - 184   2015年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: To assess the prognostic value of combined evaluation of preoperative CT findings and pre/postoperative serum carcinoembryonic antigen (CEA) levels for pathological stage I lung adenocarcinoma. METHODS: This retrospective study included 250 consecutive patients who underwent complete resection for ≤ 3-cm pathological stage I (T1-2aN0M0) adenocarcinomas (132 men, 118 women; mean age, 67.8 years). Radiologists evaluated following CT findings: maximum tumor diameter, percentage of solid component (%solid), air bronchogram, spiculation, adjacency of bullae or interstitial pneumonia (IP) around the tumor, notch, and pleural indent. These CT findings, pre/postoperative CEA levels, age, gender, and Brinkman index were assessed by Cox proportional hazards model to determine the best prognostic model. Prognostic accuracy was examined using the area under the receiver operating characteristic curve (AUC). RESULTS: Median follow-up period was 73.2 months. In multivariate analysis, high %solid, adjacency of bullae or IP around the tumor, and high postoperative CEA levels comprised the best combination for predicting recurrence (P<0.05). A combination of these three findings had a greater accuracy in predicting 5-year disease-free survival than did %solid alone (AUC=0.853 versus 0.792; P=0.023), with a sensitivity of 85.7% and a specificity of 74.3% at the optimal threshold. The best cut-off values of %solid and postoperative CEA levels for predicting high-risk patients were ≥ 48% and ≥ 3.7 ng/mL, respectively. CONCLUSION: Compared to %solid alone, combined evaluation of %solid, adjacency of bullae or IP change around the tumor, and postoperative CEA levels improves recurrence prediction for stage I lung adenocarcinoma.

    DOI: 10.1016/j.ejrad.2014.10.009

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  • Surgical resection for a second primary lung cancer originating close to the initial surgical margin for lung squamous cell carcinoma. 国際誌

    Seijiro Sato, Terumoto Koike, Takehisa Hashimoto, Masanori Tsuchida

    Case reports in surgery   2015   462193 - 462193   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Few reports have described surgical resection for second primary lung cancers originating close to the initial surgical margin for lung cancer. A 64-year-old man had undergone left segmentectomy with lymph node dissection for small peripheral squamous cell lung cancer using video-assisted thoracic surgery, with pathology confirming a small tumor 12 mm in diameter identified about 3 cm from the surgical margin. Eighteen months after initial surgery, computed tomography revealed a 30 mm pulmonary nodule close to the initial surgical margin in the residual left upper lobe and the serum level of carcinoembryonic antigen was found to be increased. Local recurrence on the staple-line of the surgical margin was suspected, and completion left upper lobectomy was performed. Histological examination identified not only a squamous cell carcinoma component but also a small cell carcinoma component. The immunohistochemical staining pattern of the second tumor differed from that of the initial resected lung squamous cell carcinoma. The final pathological diagnosis was a second primary tumor with mixed small cell carcinoma and squamous cell carcinoma histology.

    DOI: 10.1155/2015/462193

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  • [Detection of the communication site by dye injection method at the surgery for pleuroperitoneal communication].

    Seijiro Sato, Terumoto Koike, Takehisa Hashimoto, Masanori Tsuchida

    Kyobu geka. The Japanese journal of thoracic surgery   67 ( 11 )   967 - 70   2014年10月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 65-year-old male with end stage renal failure due to IgA nephritis commenced continuous ambulatory peritoneal dialysis (CAPD). Three weeks after initiation of CAPD, right hydrothorax developed. Then, we strongly assumed pleuroperitoneal communication( PPC) although the pleural effusion did not show high concentration of glucose. He underwent thoracoscopic surgery for PPC. On the inner, central tendons part of the diaphragm, there were a few blebs. One hour after 3 l of peritoneal dialysis solution containing 15 ml indigocarmine was instilled into the abdomen through a CAPD catheter, the blebs were tense and colored blue by the dye solution. The blebs were directly sutured and diaphragm was covered by polyglycolic acid sheet and fibrin glue all over. Since then, he resumed CAPD, without recurrence of hydrothorax. Then we investigated the treatment outcome of video-assisted thoracic surgery (VATS) for PPC in Japan. The outcome was poorer in cases in which communication was not detected intraoperatively. These patients should be given sufficient consideration for surgical procedure.

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  • 7. 血管塞栓用コイルにて治癒した術後気管支断端瘻の1例(第54回 日本呼吸器内視鏡学会北陸支部会)

    篠原 博彦, 橋本 毅久, 白戸 亨, 土田 正則

    気管支学   34 ( 4 )   408 - 408   2012年

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    記述言語:日本語   出版者・発行元:特定非営利活動法人 日本呼吸器内視鏡学会  

    DOI: 10.18907/jjsre.34.4_408_2

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  • 6.右肺癌に対し下葉切除後,早期に気管浮腫による狭窄を来し気管切開を要した1例(第53回 日本呼吸器内視鏡学会北陸支部会)

    篠原 博彦, 橋本 毅久, 白戸 亨, 土田 正則

    気管支学   34 ( 1 )   89 - 89   2012年

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    記述言語:日本語   出版者・発行元:特定非営利活動法人 日本呼吸器内視鏡学会  

    DOI: 10.18907/jjsre.34.1_89

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  • O2-3 当科での肺切除における気管支断端瘻発症例の検討(外科手術1,一般口演2,第35回日本呼吸器内視鏡学会学術集会)

    篠原 博彦, 橋本 毅久, 白戸 亨, 土田 正則

    気管支学   34   S139   2012年

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    記述言語:日本語   出版者・発行元:特定非営利活動法人 日本呼吸器内視鏡学会  

    DOI: 10.18907/jjsre.34.Special_S139_3

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  • The predominant expression of hepatocyte nuclear factor 4α (HNF4α) in thyroid transcription factor-1 (TTF-1)-negative pulmonary adenocarcinoma. 国際誌

    Ryosuke Kunii, Shuying Jiang, Go Hasegawa, Takashi Yamamoto, Hajime Umezu, Takehiro Watanabe, Masanori Tsuchida, Takehisa Hashimoto, Takao Hamakubo, Tatsuhiko Kodama, Keisuke Sasai, Makoto Naito

    Histopathology   58 ( 3 )   467 - 76   2011年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIMS: To investigate TTF-1-negative pulmonary adenocarcinoma, focusing upon mucin production and the expression of hepatocyte nuclear factor-4α (HNF4α). MATERIALS AND METHODS: Two hundred and sixty-two cases of pulmonary adenocarcinoma were examined histologically and immunohistochemically; TTF-1 was expressed in 222 cases (84.7%), and 40 cases (15.3%) were negative. Among TTF-1-negative cases there were 31 mucinous-type tumours, and HNF4α, MUC5AC and MUC2 were expressed in 34 cases (85%), 29 cases (72.5%) and four cases (10%), respectively. In contrast, their expression was rare in TTF-1-positive tumours. A statistically inverse correlation was confirmed between the expression of TTF-1 and that of HNF4α and MUC5AC. CONCLUSION: Most TTF-1-negative pulmonary adenocarcinomas are mucinous lesions with the predominant expression of HNF4α and MUC5AC.

    DOI: 10.1111/j.1365-2559.2011.03764.x

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  • [Surgical treatment for metachronous lung cancer].

    Hirohiko Shinohara, Masanori Tsuchida, Takehisa Hashimoto, Junichi Hayashi

    Kyobu geka. The Japanese journal of thoracic surgery   63 ( 11 )   952 - 5   2010年10月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    We performed a retrospective review of 45 consecutive patients with metachronous multiple primary lung cancer who underwent resection between 1990 and 2009. Surgical treatment of the 1st tumor consisted of 39 lobectomies and 3 segmentectomies, and 3 wedge resections. The 2nd tumor was removed by means of a lobectomy in 9 patients, a segmentectomy in 17 patients, a wedge resection in 19 patients. No postoperative mortality was observed. Histologic classification was similar in 86.4% of patients and different in 13.6%. Postoperative stage of the 2nd tumor was IA in 31 patients, IB in 7, IIA in 1, IIIA in 3, IIIB in 3. Median follow-up was 48.4 months after 2nd operation. The 5-year survival rate was 90.8% after 1st operation and 85.6% after 2nd operation. The 5-year survival rate in patients with p-stage IA was 96.4%. Patients with metachronous lung cancer could have a favorable outcome. Thus we need careful follow-up of the patients after treatment on the 1st lung cancer, and moreover an aggressive surgical treatment is recommended as long as their performance state or residual pulmonary function allows.

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  • Primary thymic adenocarcinoma coexisting with type AB thymoma: a rare case with long-term survival.

    Yasuko Hosaka, Masanori Tsuchida, Hajime Umezu, Tadaaki Eimoto, Takehisa Hashimoto, Hirohiko Shinohara, Jun-ichi Hayashi

    General thoracic and cardiovascular surgery   58 ( 9 )   488 - 91   2010年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Thymic carcinoma is a rare tumor. The most common histological subtype is squamous cell carcinoma, and only a few cases of thymic adenocarcinoma have been reported. A case of papillary adenocarcinoma of thymic origin that coexisted with type AB thymoma as a separate nodule is presented herein. The patient was found to have an abnormal mediastinal shadow on chest X-ray. A computed tomography scan revealed a round, 6.5-cm-diameter mass in the right anterior mediastinum. The preoperative diagnosis was thymoma, and thymothymectomy was performed. On pathological examination, two tumors, which were diagnosed as papillary adenocarcinoma and type AB thymoma, respectively, were present in the thymus without any connection with each other. The patient has been alive without any signs of recurrence for 11 years after surgery. We diagnosed the adenocarcinoma in this case was a primary thymic carcinoma.

    DOI: 10.1007/s11748-009-0580-4

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  • Predictive advantage of a cell type classification for pulmonary adenocarcinoma coupled with data for p53, K-ras and EGFR alterations. 国際誌

    Akira Okada, Takuo Shimmyo, Takehisa Hashimoto, Yasuhito Kobayashi, Yohei Miyagi, Yuichi Ishikawa, Ken Nakagawa, Junichi Hayashi, Eiju Tsuchiya

    Cancer science   101 ( 7 )   1745 - 53   2010年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We analyzed relationships between histological subtypes of pulmonary adenocarcinomas and three gene alterations (p53, K-ras, and epidermal growth factor receptor gene), or thyroid transcription factor-1 (TTF-1) expression, and also studied prognoses by the subtypes, with or without combined multiple gene mutation status. Our purpose was to clearly determine pathogenesis, along with the best predictive value for biology and therapy-related traits. A total of 223 consecutively resected pulmonary adenocarcinomas were sub-classified using either the World Health Organization (WHO) or our five-cell type (FCT) classification system (hobnail, columnar/cuboidal, mixed, polygonal/oval, and goblet cell types). DNAs extracted from frozen samples of the adenocarcinomas were examined for gene alterations, and TTF-1 expressions were determined using immunohistochemistry. Next, relationships among the various data and clinicopathological factors were analyzed. The most striking result was: while almost 70% of adenocarcinomas were sub-classified as a mixed subtype by WHO, the FCT classified many of them as other cell subtypes. The FCT closely reflected differences in etiological factors, cellular lineages, and frequencies of gene mutations; and whether the data from combined gene mutations were used or not, differences among the cell types in postoperative survivals appeared. In contrast, subtypes of WHO did not show any association with the gene alteration or prognosis, and the FCT more suitably indicated sensitivity to gefitinib therapy than did WHO. The FCT combined with multiple gene mutation status appears to be useful in indicating pathogenesis and predicting the biological nature of pulmonary adenocarcinomas, and it could facilitate development of new therapies for each subtype.

    DOI: 10.1111/j.1349-7006.2010.01585.x

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  • Large bronchial granular cell tumor.

    Hirohiko Shinohara, Masanori Tsuchida, Takehisa Hashimoto, Seijirou Satoh, Mariko Takeshige, Jun-ichi Hayashi

    General thoracic and cardiovascular surgery   57 ( 9 )   484 - 7   2009年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We report a 20-year-old woman who underwent complete resection of a granular cell tumor (GCT). On chest computed tomography (CT) scan, a mass with a maximum diameter of 36 mm at the lower bronchus with atelectasis of the right lower lobe was noted. Bronchoscopic examination revealed a whitish mass in the truncus intermedius, and the middle and lower bronchus were unable to be seen. A cytopathological examination of the mass revealed GCT. A right middle and lower lobectomy was performed via a posterolateral thoracotomy. Microscopically, the tumor was composed of polygonal cells with oxyphilic granular cytoplasm and small ovoid nuclei. The cytoplasm of the neoplastic cells was positive for S-100 protein and neuron-specific enolase. The patient's postoperative course was uneventful, and she was asymptomatic after 4 months. A large bronchial GCT is rare, which is why we report this case.

    DOI: 10.1007/s11748-009-0428-y

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  • Expression of 5-fluorouracil-related enzymes in lung cancer: ELISA characterizes enzyme activity and messenger RNA expression. 国際誌

    Masanori Tsuchida, Yasushi Yamato, Takehisa Hashimoto, Hirohiko Shinohara, Hajime Umezu, Katsuo Yoshiya, Teruaki Koike, Jun-Ichi Hayashi

    Oncology reports   21 ( 4 )   1037 - 43   2009年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The enzymes thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl transferase (OPRT) are involved in the metabolism of the anticancer drug 5-fluorouracil (FU). Expression of TS, DPD and OPRT in cancer tissue has been reported to be associated with sensitivity and/or resistance to 5-FU therapy. However, the role of TS, DPD and OPRT expression in lung cancer has not been fully established. Furthermore, among several measuring methods, it is not clear which method effectively predicts the response to 5-FU therapy. The aim of this study was to analyze the expression of 5-FU-related enzymes using enzyme-linked immunosorbent assay (ELISA) and to examine the correlation of ELISA and the results obtained using different measuring methods such as reverse transcript polymerase chain reaction (RT-PCR), immunohistochemistry, and enzymatic activity. Lung cancer specimens were obtained from 134 patients who underwent curative resection for lung cancer. As a pilot study, enzyme expression of 11 samples was measured using 4 different methods for DPD: RT-PCR, immunohistochemistry, enzymatic activity and ELISA. The relationships between pairs of results were compared, and then enzyme protein expression was measured using ELISA in 119 patients with adenocarcinoma. Of the 4 independent methods, the highest correlation was observed between protein expression measured by ELISA and enzyme activity. The correlation of gene expression and ELISA was also significant. The protein level in stage I adenocarcinoma measured using ELISA was 13.0+/-24.8 ng/mg protein for TS, 362.2+/-264.3 ng/mg protein for DPD and 4.5+/-2.0 ng/mg protein for OPRT. The predictive value of the enzymes for prognosis and the effectiveness of 5-FU was not determined as few recurrences were observed during the short follow-up period. In conclusion, ELISA is a simple and reliable method to measure key enzymes related to 5-FU therapy.

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  • Superior vena cava reconstruction via a posterolateral thoracotomy without venous occlusion for locally advanced lung cancer: report of a case.

    Hirohiko Shinohara, Masanori Tsuchida, Takehisa Hashimoto, Seijirou Satoh, Ai Takeuchi, Mariko Takeshige, Jun-ichi Hayashi

    Surgery today   39 ( 9 )   787 - 9   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We performed a right upper lobectomy with prosthetic replacement of the superior vena cava (SVC) through a posterolateral thoracotomy in a 65-year-old man undergoing complete resection of a locally advanced non-small-cell lung cancer with invasion of the SVC. Instead of using a vascular shunt, the right atrium and a right brachiocephalic vein (BCV) were anastomosed using a ringed polytetrafluoroethylene (PTFE) graft. During the anastomosis, vascular flow was maintained through the left BCV. By using this technique, SVC resection and reconstruction during lung cancer surgery can be safely performed through a posterolateral thoracotomy without blood flow interruption.

    DOI: 10.1007/s00595-008-3927-z

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  • Absence of gene mutations in KIT-positive thymic epithelial tumors. 国際誌

    Masanori Tsuchida, Hajime Umezu, Takehisa Hashimoto, Hirohiko Shinohara, Terumoto Koike, Yasuko Hosaka, Tadaaki Eimoto, Jun-ich Hayashi

    Lung cancer (Amsterdam, Netherlands)   62 ( 3 )   321 - 5   2008年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Overexpression of KIT, a tyrosine kinase receptor protein encoded by the proto-oncogene c-kit, is observed in human neoplasms such as gastrointestinal stromal tumors (GISTs), myeloproliferative disorders, melanoma and seminoma. In patients with GIST, overexpression of mutated KIT within the tumor is predictive of response to molecular targeted therapy using imatinib. However, the role of KIT expression in thymic carcinoma is not fully understood. METHODS: Thymic epithelial tumors from 37 patients (17 thymic carcinomas and 20 thymomas) were examined. Immunohistochemical staining with anti-KIT polyclonal antibody and anti-CD5 was performed. Mutation analyses in the juxtamembrane domains, exons 9 and 11, and in the tyrosine kinase domains, exons 13 and 17, were undertaken using polymerase chain reaction (PCR) and direct DNA sequencing in KIT-positive samples. RESULTS: KIT- and CD5-positive staining was observed only in thymic carcinoma. Percentage of positive staining was 100% in squamous cell carcinoma, with no positive staining in other histologies, including atypical carcinoid. Mutation analysis of the KIT gene was performed in 11 squamous cell carcinomas, 1 adenocarcinoma and 1 adenosquamous cell carcinoma. None of the tested samples showed mutations in any of the four exons. CONCLUSIONS: Squamous cell carcinoma of the thymus frequently expressed KIT and CD5 proteins, whereas other tumors did not. Unlike GIST, overexpression of KIT does not necessarily indicate gene mutation in thymic carcinoma. KIT and CD5 appear useful for evaluating and subtyping thymic epithelial tumors.

    DOI: 10.1016/j.lungcan.2008.03.035

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  • Segmentectomy for multiple adenocarcinoma presenting as ground-glass opacities after lung cancer surgery.

    Ai Takeuchi, Masanori Tsuchida, Takehisa Hashimoto, Hirohiko Shinohara, Jun-Ichi Hayashi

    General thoracic and cardiovascular surgery   56 ( 8 )   410 - 2   2008年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    During follow-up of patients after primary lung cancer resections, small nodules or ground-glass opacities (GGOs) are sometimes detected on chest computed tomography. We report a case with multiple GGOs that were noted after primary lung cancer resection. A 76-year-old woman, who had undergone right upper lobectomy, middle lobe partial resection, and mediastinal lymph node dissection 3 years earlier, was admitted owing to five GGOs in the right lower lobe that had been increasing in size or density. A right S6+10 segmentectomy was performed. On histology, one adenocarcinoma and four bronchioloalveolar carcinomas (BACs), as well as two additional BACs that had not been detected preoperatively, were identified. No complications occurred postoperatively. Three years 4 months later, no tumor recurrence or new lesions have been found. Given the high possibility of malignancy, the appearance of new GGOs in patients with a history of lung cancer requires appropriate investigation.

    DOI: 10.1007/s11748-008-0257-4

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  • Etiologic value of p53 mutation spectra and differences with histology in lung cancers. 国際誌

    Takuo Shimmyo, Akira Okada, Takehisa Hashimoto, Yasuhito Kobayashi, Youhei Miyagi, Yuichi Ishikawa, Ken Nakagawa, Hiroaki Osada, Eiju Tsuchiya

    Cancer science   99 ( 2 )   287 - 95   2008年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A total of 297 resected Japanese non-small cell lung cancers (74 squamous cell carcinomas and 223 adenocarcinomas) were analyzed to evaluate the validity of the p53 mutation spectrum as a fingerprint for mutagenic substances as etiological factors. Frequencies of G-->T transversions in smokers were significantly higher than in non-smokers (P = 0.003) and the average incidence of G-->T at hot spot codons of adduct formation was higher than that in other codons in smokers and in the hot spots in non-smokers. Further, the mutation showed a marked strand bias. G-->A transitions at CpG sites (CpG-->CpA) were equally distributed in smokers and non-smokers, and on both strands. A-->G transitions did not show any variation with smoking status in terms of frequency, but exhibited a marked strand bias. Taken together, the G-->T may be a fingerprint of direct mutagenic action of tobacco-related compounds, the A-->G being a new marker for other environmental chemicals, while the CpG-->CpA may be attributable to endogenous spontaneous mutation, for active in lung carcinogenesis.

    DOI: 10.1111/j.1349-7006.2007.00686.x

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  • Quality of life after lung cancer surgery: video-assisted thoracic surgery versus thoracotomy. 国際誌

    Tadashi Aoki, Masanori Tsuchida, Takehisa Hashimoto, Masayuki Saito, Terumoto Koike, Jun-ichi Hayashi

    Heart, lung & circulation   16 ( 4 )   285 - 9   2007年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: To assess the benefit of video-assisted thoracic surgery (VATS), we compared time-related quality of life (QOL) after lobectomy performed by VATS to that performed by thoracotomy. METHODS: Thirty-three patients underwent surgery for lung cancer during the period April 2001 through November 2002 completed a mailed questionnaire after surgery. RESULTS: Over time, improved QOL was reported in six dimensions by VATS patients but in only two dimensions by thoracotomy patients. There was significant improvement in bodily pain subscores in both groups during the 36 months after surgery. At 3 months after surgery, QOL scores for all eight dimensions were lower in the VATS group, but QOL scores for all eight dimensions did not differ significant between groups at 3 or 12 months after surgery. At 36 months after surgery, QOL scores for six dimensions were higher in the VATS group, and the difference was significant in scores for two dimensions. CONCLUSION: We found recovery was quicker in patients who underwent VATS than in those who underwent thoracotomy.

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  • Lung resection combined with percutaneous coronary intervention using cypher stents: a case report.

    Masanori Tsuchida, Takeshi Okamoto, Takehisa Hashimoto, Tadashi Aoki, Takashi Saigawa, Akira Hirono, Jun-ichi Hayashi

    Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia   13 ( 1 )   56 - 9   2007年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Treatment of concomitant severe coronary artery disease and lung cancer is a complicated issue. The present study describes a case of a 65-year-old man with coronary artery disease and primary lung cancer that was successfully treated with lung resection and percutaneous coronary intervention (PCI) using Cypher stents. Prior to lung resection, the patient underwent a PCI for diffuse stenosis of the right coronary artery and the circumflex artery. Cypher stents were deployed for both lesions. Five days after stent implantation, a right lower lobectomy was performed successfully. To the best of our knowledge, this is the first report of lung resection and PCI using Cypher stents.

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  • p53 mutation spectra for squamous cell carcinomas at different levels of human bronchial branches. 国際誌

    Takuo Shimmyo, Takehisa Hashimoto, Yasuhito Kobayashi, Youhei Miyagi, Yuichi Ishikawa, Ken Nakagawa, Hiroaki Osada, Eiju Tsuchiya

    International journal of cancer   119 ( 3 )   501 - 7   2006年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The question of whether squamous cell carcinomas (SCCs) arising in different sites of lung are caused by different etiological factors is of obvious importance for prevention, early detection and effective treatment. We here subclassified a large series of resected SCCs (74 cases) into 3 tumor-sites, central (main to segmental bronchi), intermediate (subsegmental to sub-subsegmental) and peripheral (distal to sub-subsegmental bronchi), and examined relationships with p53 mutational spectra and smoking history to provide clues to etiological factors. The rate for G-->A transitions at CpG sites considered to be caused by endogenous mechanism was higher in central (40%) than in intermediate (0%) and peripheral (14%) lesions, in spite of highest percentage of heavy smokers. In contrast, G-->T transversions associated with tobacco smoke carcinogens were most frequent (50%) in the intermediate location, although proportions of heavy smoker's ratio were the same among the locations when confined to p53 mutation cases. In the periphery, other mutations were highest (67%) compared with 33 and 50% in the central and intermediate regions, respectively. Thus, different etiological factors may be playing causal roles in the development of SCCs in different locations of bronchial tree. Furthermore, the results suggest that more extensive study of the influence of tobacco smoke carcinogens on endogenous mechanisms is warranted.

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  • Analysis of the effect of surgical lung biopsy on serum KL-6 Levels in patients with interstitial pneumonia: surgical lung biopsy does not elevate serum KL-6 levels.

    Jun-ichi Narita, Takashi Hasegawa, Masanori Tsuchida, Masaki Terada, Toshinori Takada, Takehisa Hashimoto, Tadashi Aoki, Hiroki Tsukada, Ichiei Narita, Jun-Ichi Hayashi, Fumitake Gejyo, Eiichi Suzuki

    Internal medicine (Tokyo, Japan)   45 ( 9 )   615 - 9   2006年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: It is well known that the serum level of KL-6 can be an indicator of disease activity in patients with interstitial pneumonia (IP). However, surgical lung biopsy is often required for the diagnosis of IP, although this can result in IP exacerbation. METHODS: The effect of surgical lung biopsy on the serum level of KL-6 in patients with IP was analyzed. Thirty-two cases of IP were examined in this study. There were no cases showing exacerbation of IP. RESULTS: The serum level of KL-6 demonstrated 1067+/-550 U/ml (mean+/-SD) before lung biopsy, 991+/-471 U/ml a day, 824+/-377 U/ml 4 days and 826+/-384 U/ml 7 days after lung biopsy. The serum KL-6 levels on the 1st, 4th, 7th day after the lung biopsy were significantly lower than that before the lung biopsy (P<0.05, P<0.01 and P<0.01, respectively). The percent decrease of the serum KL-6 levels on the 4th day (the lowest level) was dependent on the urine volume, and the analysis of the urinary levels of KL-6 showed a transient increase in urinary KL-6 excretion, suggesting that the decrease in serum KL-6 levels associated with surgical lung biopsy may be caused by this increase in urinary KL-6 excretion. CONCLUSION: Surgical lung biopsy of patients with IP has little effect on the increase in serum KL-6 levels. An elevation of serum KL-6 after surgical lung biopsy may indicate exacerbation of IP.

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  • Histologically unique case of combined small cell and squamous cell carcinoma in a polypoid bronchial tumor. 国際誌

    Mitsuhiro Fukushima, Kei-Ichi Homma, Takehisa Hashimoto, Ryuta Suzuki, Teruaki Koike

    Pathology international   55 ( 12 )   785 - 91   2005年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Presented herein is a case of combined small cell and squamous cell carcinoma in a polypoid bronchial tumor, showing a histologically unique progression, in a 76-year-old Japanese man. A bronchofiberscopic examination revealed that the bronchus (left B3) was occluded by the polypoid tumor. Biopsies were performed, and the pathological diagnosis was poorly differentiated squamous cell carcinoma. The patient consequently underwent a left upper lung lobectomy. The surgical specimen was described as a 24 x 8 x 8 mm soft tumor, emanating from the bronchial wall (left B3). Histologically, the tumor had two distinct components: (i) nearly the entire tumor was composed of atypical small round cells, with a high nuclear-cytoplasmic ratio, in the lamina propria, under the basement membrane; and (ii) the surface of the tumor was composed of poorly differentiated squamous cell carcinoma that had proliferated primarily above the basement membrane but there was also some proliferation, seen as island-like formations, below the basement membrane. The histological diagnosis was combined small cell and squamous cell carcinoma. It was suspected that poorly differentiated squamous cell carcinoma, generated in the bronchial epithelium, had caused small cell carcinoma resulting from neuroendocrine differentiation during its invasion into the lamina propria.

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  • Molecular markers for reinforcement of histological subclassification of neuroendocrine lung tumors. 国際誌

    Yasuhito Kobayashi, Yoshio Tokuchi, Takehisa Hashimoto, Moriaki Hayashi, Hitoshi Nishimura, Yuichi Ishikawa, Ken Nakagawa, Yukitoshi Sato, Atsushi Takahashi, Eiju Tsuchiya

    Cancer science   95 ( 4 )   334 - 41   2004年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The degree of malignancy of neuroendocrine lung tumors (NEs) increases in this order: from typical carcinoids (TCs) through atypical carcinoids (ACs) to large cell neuroendocrine carcinomas (LCNECs) and small cell lung carcinomas (SCLCs). However, histological classification has sometimes proved difficult. We here investigated loss of heterozygosity (LOH) using eight microsatellite markers and expression of p53, Bcl-2 and Bax proteins using immunohistochemical methods in 57 NEs (19 TCs, 5 ACs, 14 LCNECs and 19 SCLCs), looking for objective genetic markers to distinguish between subtypes. The frequencies of LOHs on D3S1300, RBi2 and TP53, the combinations of LOH status for RBi2 and TP53, and the immunohistochemically demonstrated Bcl-2/Bax ratios and p53-positive rates significantly differed among histopathologically diagnosed NEs. Differentiation between TC and AC was possible with reference to LOH on D3S1300, RBi2 and TP53, and the combined LOH status on RBi2 and TP53 (i.e., both LOH(-) versus one LOH(+)). For comparison between AC and LCNEC + SCLC, LOH on TP53 or the combination of two markers--one LOH(+) versus both LOH(+)--was applied. Furthermore, in three discordant cases of diagnoses based on histology and LOH markers, diagnoses using the latter were considered to be more probable by survival analysis. The present study indicated that assessment of LOHs using microsatellite markers could provide objective markers that can distinguish subtypes of NEs, for which histological assessment may commonly result in disagreement.

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  • Surgical strategy for clinical stage I non-small cell lung cancer in octogenarians. 国際誌

    Tadashi Aoki, Masanori Tsuchida, Takehiro Watanabe, Takehisa Hashimoto, Teruaki Koike, Tatsuhiko Hirono, Jun-ichi Hayashi

    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery   23 ( 4 )   446 - 50   2003年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: The purpose of this study was to determine whether lobectomy without radical systematic mediastinal lymphadenectomy (LA) is a satisfactory alternative surgical treatment for octogenarians with clinical stage I non-small cell lung cancer (NSCLC). METHODS: From April 1985 through December 2001, 49 patients aged 80 years and older who underwent surgical treatment for clinical stage I NSCLC were reviewed. Lobectomy without radical systematic mediastinal LA was performed for 27 patients (LA0 group) and lobectomy with radical systematic mediastinal LA was performed for 22 patients (LA group). RESULTS: The mortality rate was 0% in the LA0 group and 4.5% in the LA group. Five-year survival rate according to the type of surgery was 44.8% in the LA0 group and 55.5% in the LA group, a difference that was not significant (P=0.88). Although there was no significant statistical difference, postoperative pulmonary complication was more frequent in the LA group than in the LA0 group (32% in the LA group versus 11% in the LA0 group P=0.07). Five-year survival rates according to serum carcinoembryonic antigen (CEA) levels were 0% for patients with elevated CEA levels (n=9) and 56.5% for patients with normal CEA levels (n=40) (P<0.01). CONCLUSION: Lobectomy without radical systematic mediastinal LA appears to be a satisfactory surgical procedure for octogenarians with clinical stage I NSCLC. However, mediastinoscopy is necessary in such octogenarians if their serum CEA level is elevated so that the precise clinical stage can be determined and an accurate prognosis can be given.

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  • [Genetic alteration in lung cancer].

    Takehisa Hashimoto, Moriaki Hayashi, Eiju Tsuchiya

    Nihon rinsho. Japanese journal of clinical medicine   60 Suppl 5   78 - 82   2002年5月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • cN0-pN1/2小型肺癌に対する低侵襲手術成績 臨床病期I期腺癌亜分類別のリンパ節転移の解析から縮小手術を考える

    渡辺 健寛, 北原 哲彦, 吉谷 克雄, 大和 靖, 古屋敷 剛, 橋本 毅久, 齋藤 正幸, 土田 正則, 新潟呼吸器外科研究グループ

    日本呼吸器外科学会雑誌   34 ( 3 )   PD2 - 1   2020年8月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器外科学会  

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  • 定位放射線治療後の再発肺癌に対する手術例の検討

    古泉 貴久, 吉谷 克雄, 斎藤 正幸, 尾嶋 紀洋, 保坂 靖子, 橋本 毅久, 大和 靖, 古屋敷 剛, 渡辺 健寛, 土田 正則, 新潟呼吸器外科研究グループ

    日本呼吸器外科学会雑誌   31 ( 3 )   RO5 - 6   2017年4月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器外科学会  

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  • 気管支形成術を併用して右S6区域切除術をおこなった定型カルチノイドの1例

    橋本 毅久, 北原 哲彦, 佐藤 征二郎, 小池 輝元, 土田 正則

    日本呼吸器外科学会雑誌   30 ( 3 )   O18 - 5   2016年4月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器外科学会  

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  • 肺癌に対する定位放射線照射と手術 定位放射線治療後の局所再発原発性肺癌に対する切除例の検討

    古泉 貴久, 吉谷 克雄, 斉藤 正幸, 岩浪 崇嗣, 本間 崇浩, 富樫 賢一, 古屋敷 剛, 保坂 靖子, 橋本 毅久, 渡辺 健寛, 土田 正則

    日本呼吸器外科学会雑誌   30 ( 3 )   PD2 - 8   2016年4月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器外科学会  

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  • siRNAおよびVerteporfinを用いたがん併用療法

    橋本 正寛, 浅井 知浩, 清水 広介, 小出 裕之, 出羽 毅久, 奥 直人

    日本薬学会年会要旨集   136年会 ( 4 )   60 - 60   2016年3月

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    記述言語:日本語   出版者・発行元:(公社)日本薬学会  

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  • 非小細胞肺癌pN1症例における外科治療成績

    佐藤 征二郎, 北原 哲彦, 小池 輝元, 橋本 毅久, 土田 正則

    肺癌   55 ( 5 )   482 - 482   2015年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 術前に胸壁腫瘍が疑われた肺葉外肺分画症の1切除例

    北原 哲彦, 佐藤 征二郎, 梅澤 麻以子, 小池 輝元, 橋本 毅久, 土田 正則

    気管支学   37 ( 4 )   480 - 480   2015年7月

  • 胸骨縦切開を追加して切除し得た無症候性進行甲状腺癌の1例

    庭野 稔之, 小山 諭, 永橋 昌幸, 長谷川 美樹, 利川 千絵, 土田 純子, 若井 俊文, 小池 輝元, 橋本 毅久, 土田 正則

    新潟医学会雑誌   129 ( 5 )   281 - 286   2015年5月

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    記述言語:日本語   出版者・発行元:新潟医学会  

    甲状腺癌のうち乳頭癌(papillary carcinoma)の頻度は90%と大部分を占め、頸部リンパ節転移の頻度が高く、高齢者では未分化癌に転化することもある。今回、結腸癌術後の全身検索で発見され、胸骨縦切開を追加して切除可能であった無症候性進行甲状腺癌の1例を経験したので文献的考察を加えて報告する。症例は76歳、女性。上行結腸癌手術後7年目にCA19-9値の上昇傾向を指摘され、CT検査では上縦隔へ進展した7cm大の甲状腺腫瘤と1.5cm大の右頸部リンパ節腫大を認めた。穿刺吸引細胞診ではclass IIIであったが甲状腺癌が強く疑われたため、手術目的に当科入院となった。術前の頸部CTおよびMRI検査では、甲状腺腫瘍は上縦隔まで進展していたが、明らかな血管への浸潤所見は認めず、気管支鏡検査では明らかな気管浸潤は認めなかった。手術を施行し、右頸部リンパ節を摘出し術中迅速病理診断に提出したところ乳頭癌の診断が得られたため、甲状腺全摘術および頸部リンパ節郭清の方針となった。術中所見では、上縦隔内の無名静脈および右頸動脈への浸潤が疑われ、切除可能か否かの判定が困難であった。視野を確保し、血管等への浸潤の有無を判定するために胸骨縦切開を追加した。その結果、良好な視野が得られ、無名静脈、右左総頸動脈への直接浸潤を認めず、腫瘍の切離が可能となり、甲状腺全摘術および頸部リンパ節郭清を施行した。甲状腺癌、特に乳頭癌は10年生存率が80〜90%と良好であり、また、放置した場合に気管浸潤、血管浸潤を伴うと、生命予後のみならず、患者QOLも著しく損なわれるので、可能であるならば積極的に切除を行うことが望ましい。(著者抄録)

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  • 右下葉気管支管状切除・気管支形成術

    橋本 毅久, 佐藤 征二郎, 小池 輝元, 土田 正則

    日本呼吸器外科学会雑誌   29 ( 3 )   V2 - 3   2015年4月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器外科学会  

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  • 【心・大血管疾患合併肺癌の治療戦略】大動脈疾患・大動脈浸潤 動脈瘤合併肺癌例に対するステントグラフト内挿術・肺切除同時手術

    小池 輝元, 佐藤 裕喜, 佐藤 征二郎, 岡本 竹司, 橋本 毅久, 榛沢 和彦, 土田 正則

    胸部外科   68 ( 4 )   293 - 297   2015年4月

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    記述言語:日本語   出版者・発行元:(株)南江堂  

    動脈瘤合併肺癌例に対するステントグラフト内挿術・肺切除同時手術の2例を経験した。症例1は74歳男で、腹部CTにて腎動脈分岐部以下に最大短径50.cmの腹部大動脈瘤1を指摘された。右胸水貯溜を指摘され、気管支鏡下細胞診で悪性細胞を検出し、右原発性肺癌、腹部大動脈瘤と診断した。肺切除、ステントグラフト内挿術の同時手術の方針となった。第12病日に軽快退院となった。症例2は72歳男で、胸部CTで右肺の異常陰影を指摘された。精査の胸腹部CTで右上葉に肺野弓リンパ節と一塊となった腫瘤性病変、右腎に腫瘍性病変、左内腸骨動脈瘤を指摘された。経皮的冠状動脈形成術後に、ステントグラフト内挿術と同時手術で肺癌外科治療を先行、その後腎細胞癌の外科治療を行う方針となった。第11病日に軽快退院となった。

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J00349&link_issn=&doc_id=20150330060012&doc_link_id=40020407763&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F40020407763&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

  • 呼吸器 間質性肺炎合併肺癌に対する再手術の意義

    佐藤 征二郎, 小池 輝元, 橋本 毅久, 北原 哲彦, 渡辺 健寛, 土田 正則

    日本外科学会定期学術集会抄録集   115回   PLS - 1   2015年4月

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    記述言語:日本語   出版者・発行元:(一社)日本外科学会  

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  • pN2 III期非小細胞肺癌における縦隔リンパ節転移様式による病期細分化の検討

    佐藤 征二郎, 小池 輝元, 橋本 毅久, 土田 正則

    日本呼吸器外科学会雑誌   29 ( 3 )   O35 - 3   2015年4月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器外科学会  

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  • 触知困難小型肺癌病変に対するVirtual-assisted Lung Mappingを用いた胸腔鏡補助下肺区域切除の初期経験

    小池 輝元, 佐藤 征二郎, 橋本 毅久, 佐藤 雅昭, 土田 正則

    日本呼吸器外科学会雑誌   29 ( 3 )   O16 - 6   2015年4月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器外科学会  

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  • 診断に苦慮した縦隔内異所性副甲状腺腫の1切除例

    佐藤 征二郎, 小池 輝元, 橋本 毅久, 土田 正則

    日本胸部外科学会関東甲信越地方会要旨集   ( 167回 )   29 - 29   2015年3月

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    記述言語:日本語   出版者・発行元:日本胸部外科学会-関東甲信越地方会  

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  • 【呼吸器外科の手術看護パーフェクトマニュアル】(第2章)実践編 術式別の術中看護マニュアル 肺癌に対する肺楔状切除術

    橋本 毅久, 土田 正則

    オペナーシング   ( 2015臨時増刊 呼吸器外科の手術看護パーフェクトマニュアル )   111 - 117   2015年3月

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    記述言語:日本語   出版者・発行元:(株)メディカ出版  

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  • Foregut cystに発生した異所性ACTH産生カルチノイドの1例

    佐藤 征二郎, 小池 輝元, 橋本 毅久, 土田 正則, 大橋 瑠子, 梅津 哉

    肺癌   54 ( 7 )   1003 - 1003   2014年12月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 間質性肺炎合併肺癌切除後再手術の経験

    土田 正則, 橋本 毅久, 小池 輝元, 佐藤 征二郎

    肺癌   54 ( 5 )   568 - 568   2014年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • V-V ECMO使用下胸骨正中切開アプローチにて切除した気管原発MALTリンパ腫の1例

    小池 輝元, 佐藤 征二郎, 橋本 毅久, 土田 正則

    肺癌   54 ( 5 )   380 - 380   2014年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 慢性血液透析患者に対する肺癌手術周術期及び長期予後の検討

    佐藤 征二郎, 小池 輝元, 橋本 毅久, 土田 正則

    肺癌   54 ( 5 )   683 - 683   2014年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 【胸壁・横隔膜の手術-その2】横隔膜交通症 横隔膜交通症手術における欠損孔同定の実際と工夫

    佐藤 征二郎, 小池 輝元, 橋本 毅久, 土田 正則

    胸部外科   67 ( 11 )   967 - 970   2014年10月

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    記述言語:日本語   出版者・発行元:(株)南江堂  

    症例は65歳男性で、IgA腎症により慢性腎不全となり、持続腹膜透析(CAPD)が導入され、3週間後より呼吸困難が出現し、胸部X線で大量の右胸水貯留を認め、横隔膜交通症が疑われた。聴診で収縮期雑音、右側呼吸音の減弱を認めた。胸部X線で右胸水貯留を、胸部CTで右側の大量胸水を認めたが横隔膜面に異常所見は認めなかった。胸水穿刺により胸水中のグルコース濃度は154mg/dlと血糖測定値118mg/dlと比べ高値でなかったが胸水ドレナージ後にCAPDをいったん中止したところ胸水貯留を認め、横隔膜交通症と診断し、交通部の閉鎖のため胸腔鏡下手術を行った。術後第3病日にドレーンを抜去し、CAPDを再開した。術後1年3ヵ月経過したが再発を認めていない。

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J00349&link_issn=&doc_id=20140926040004&doc_link_id=40020213025&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F40020213025&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

  • 巨大な胸壁腫瘍が主体の胸壁浸潤肺癌に対し、高位後側方切開(後方アプローチ)にて切除した1例

    佐藤 征二郎, 小池 輝元, 橋本 毅久, 土田 正則

    肺癌   54 ( 5 )   373 - 373   2014年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 胸壁浸潤病変が腫瘍の主体であった肺扁平上皮癌の一例

    佐藤 征二郎, 小池 輝元, 橋本 毅久, 土田 正則

    日本胸部外科学会関東甲信越地方会要旨集   ( 165回 )   27 - 27   2014年6月

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    記述言語:日本語   出版者・発行元:日本胸部外科学会-関東甲信越地方会  

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  • 区域切除後の断端近傍に発生した異時多発肺癌の1切除例

    佐藤 征二郎, 白戸 亨, 小池 輝元, 橋本 毅久, 土田 正則

    肺癌   54 ( 3 )   166 - 166   2014年6月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 高齢者肺癌の外科治療戦略 80歳以上の高齢者肺癌に対する外科治療戦略 624例の検討から

    大和 靖, 土田 正則, 保坂 靖子, 橋本 毅久, 吉谷 克雄, 渡辺 健寛, 金沢 宏, 古屋敷 剛, 諸 久永, 富樫 賢一, 吉井 新平, 斎藤 正幸, 鬼塚 貴光, 新潟呼吸器外科研究グループ

    日本呼吸器外科学会雑誌   28 ( 3 )   PD1 - 6   2014年4月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器外科学会  

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  • 若年性肺気腫に伴う巨大ブラを切除し著明な呼吸機能改善を得た1例

    小池 輝元, 白戸 亨, 佐藤 征二郎, 橋本 毅久, 土田 正則

    日本呼吸器外科学会雑誌   28 ( 3 )   1 - 8   2014年4月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器外科学会  

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  • 肺扁平上皮癌における幹細胞関連マーカー発現の検討

    佐藤 征二郎, 白戸 亨, 小池 輝元, 橋本 毅久, 土田 正則

    日本呼吸器外科学会雑誌   28 ( 3 )   O16 - 4   2014年4月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器外科学会  

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  • 嚢胞内吸引療法により人工呼吸器を離脱し手術することができた巨大気腫性肺嚢胞の1例

    橋本 毅久, 白戸 亨, 佐藤 征二郎, 小池 輝元, 土田 正則

    日本呼吸器外科学会雑誌   28 ( 3 )   RV4 - 2   2014年4月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器外科学会  

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  • PS-035-5 胸膜浸潤におけるupstagingの妥当性について(PS-035 肺 転移・再発,ポスターセッション,第114回日本外科学会定期学術集会)

    佐藤 征二郎, 白戸 亨, 小池 輝元, 橋本 毅久, 土田 正則

    日本外科学会雑誌   115 ( 2 )   645 - 645   2014年3月

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    記述言語:日本語   出版者・発行元:一般社団法人日本外科学会  

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  • 化学療法後に完全切除した混合型胚細胞腫瘍の小児切除例

    土田 正則, 白戸 亨, 佐藤 征二郎, 小池 輝元, 橋本 毅久

    日本胸部外科学会関東甲信越地方会要旨集   ( 164回 )   27 - 27   2014年3月

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    記述言語:日本語   出版者・発行元:日本胸部外科学会-関東甲信越地方会  

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  • 胸膜浸潤におけるupstagingの妥当性について

    佐藤 征二郎, 白戸 亨, 小池 輝元, 橋本 毅久, 土田 正則

    日本外科学会雑誌   115 ( 臨増2 )   645 - 645   2014年3月

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    記述言語:日本語   出版者・発行元:(一社)日本外科学会  

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  • 小型非小細胞肺癌に対する標準手術としての根治縮小手術の妥当性に関する研究

    小池 輝元, 佐藤 征二郎, 橋本 毅久, 土田 正則

    新潟県医師会報   ( 766 )   8 - 9   2014年1月

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    記述言語:日本語   出版者・発行元:新潟県医師会  

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  • 間質性肺炎合併肺癌の術後急性増悪予測因子としての肺動脈圧評価

    小池 輝元, 湯山 聡子, 佐藤 征二郎, 橋本 毅久, 土田 正則

    日本呼吸器外科学会雑誌 = The journal of the Japanese Association for Chest Surgery   27 ( 5 )   22 - 28   2013年7月

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  • 脈管浸潤(VI)とリンパ管浸潤(Ly)の組織分類別検討

    佐藤 征二郎, 小池 輝元, 橋本 毅久, 土田 正則

    日本呼吸器外科学会雑誌   27 ( 3 )   P07 - 04   2013年4月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器外科学会  

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  • 虚血性心疾患・心房細動合併肺癌患者の周術期管理と合併症

    橋本 毅久, 佐藤 征二郎, 小池 輝元, 土田 正則

    日本呼吸器外科学会雑誌   27 ( 3 )   P68 - 10   2013年4月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器外科学会  

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  • pI期非小細胞肺癌PLC(+)症例に対する術中CDDP胸腔内散布の有用性の検討

    篠原 博彦, 吉谷 克雄, 白戸 亨, 小池 輝明, 橋本 毅久, 青木 正, 岩浪 崇嗣, 金沢 宏, 斎藤 正幸, 富樫 賢一, 古屋敷 剛, 諸 久永, 吉井 新平, 渡辺 健寛, 土田 正則, 新潟県呼吸器外科研究グループ

    日本呼吸器外科学会雑誌   27 ( 3 )   P07 - 12   2013年4月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器外科学会  

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  • PS-027-1 充実陰影を呈する肺野末梢cT1aN0M0非小細胞肺癌に対する外科治療成績(PS ポスターセッション,第113回日本外科学会定期学術集会)

    小池 輝元, 佐藤 征二郎, 橋本 毅久, 白戸 亨, 篠原 博彦, 吉谷 克雄, 小池 輝明, 鳥谷部 真一, 土田 正則

    日本外科学会雑誌   114 ( 2 )   555 - 555   2013年3月

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    記述言語:日本語   出版者・発行元:一般社団法人日本外科学会  

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  • 13 S^6を温存した肺底動脈大動脈起始症の1切除例(一般演題, 第272回新潟外科集談会)

    白戸 亨, 篠原 博彦, 橋本 毅久, 土田 正則

    新潟医学会雑誌   127 ( 3 )   160 - 161   2013年3月

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    記述言語:日本語   出版者・発行元:新潟医学会  

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    その他リンク: http://search.jamas.or.jp/link/ui/2013333098

  • 14 ECMOを使用して手術を行った右気胸の1手術例(一般演題, 第273回新潟外科集談会)

    白戸 亨, 佐藤 征二郎, 小池 輝元, 橋本 毅久, 土田 正則

    新潟医学会雑誌   127 ( 3 )   169 - 169   2013年3月

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    記述言語:日本語   出版者・発行元:新潟医学会  

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  • 18 胸膜肺全摘術における人工物を用いない心膜, 横隔膜の再建法(一般演題, 第270回新潟外科集談会)

    橋本 毅久, 土田 正則, 北原 哲彦, 篠原 博彦, 林 純一

    新潟医学会雑誌   127 ( 2 )   113 - 113   2013年2月

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    記述言語:日本語   出版者・発行元:新潟医学会  

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    その他リンク: http://search.jamas.or.jp/link/ui/2013320262

  • ECMOを使用した呼吸器外科手術症例の経験

    白戸 亨, 篠原 博彦, 橋本 毅久, 土田 正則

    日本呼吸器外科学会雑誌   26 ( 3 )   P36 - 06   2012年4月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器外科学会  

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  • 肺分画症に対する区域切除術

    橋本 毅久, 白戸 亨, 篠原 博彦, 土田 正則

    日本呼吸器外科学会雑誌   26 ( 3 )   V20 - 05   2012年4月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器外科学会  

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  • 同時性両側肺癌に対する右上葉切除後の左胸腔鏡下上区切除術 3DCTによる血管把握の有用性

    橋本 毅久, 土田 正則, 三村 慎也, 篠原 博彦, 林 純一

    日本呼吸器外科学会雑誌   25 ( 3 )   RV07 - 01   2011年4月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器外科学会  

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  • 当科での胸膜肺全摘術症例の検討

    篠原 博彦, 土田 正則, 橋本 毅久, 林 純一

    日本呼吸器外科学会雑誌   25 ( 3 )   P52 - 06   2011年4月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器外科学会  

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  • 肺手術のための臨床局所解剖--外科医に必要な開胸操作の解剖と手技 (特集 手術のための臨床局所解剖)

    土田 正則, 青木 正, 橋本 毅久

    臨床外科   61 ( 5 )   573 - 578   2006年5月

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    記述言語:日本語   出版者・発行元:医学書院  

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    その他リンク: http://search.jamas.or.jp/link/ui/2006208631

▶ 全件表示

共同研究・競争的資金等の研究

  • 腫瘍特異的遺伝子異常による肺癌再発予測バイオマーカーの開発と補助化学療法の効果

    研究課題/領域番号:16K10674  2016年4月 - 2020年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    橋本 毅久, 佐藤 征二郎, 土田 正則, 小池 輝元

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    本研究の目的は肺癌手術症例の血清から癌由来DNAの検出を試み、再発予後との関係を調べて再発ハイリスク症例を選別することである。
    methylation-specific PCR(MS-PCR)法を工夫し、検出感度を10の-6乗まで高めた。50例の非小細胞肺癌原発巣でp16遺伝子プロモーター領域のメチル化を検索した。正常肺でもメチル化が検出された7症例を除外した43例中18例でメチル化が検出された。術前血清中からDNAを抽出し同様にMS-PCR法をおこなうと18例中6例(33%)で原発巣と同じメチル化DNAが検出された。しかし術後再発や補助化学療法の効果との有意な相関関係は認めなかった。

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  • 血清中の癌特異的遺伝子異常及びプロテオミクスを利用した新しい肺癌再発予測法の開発

    研究課題/領域番号:16790796  2004年 - 2005年

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    橋本 毅久

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    配分額:3400000円 ( 直接経費:3400000円 )

    1)methylation-specific PCR(MS-PCR)法の検出感度についての検討
    方法:陽性コントロールの希釈系列を作成しp16遺伝子プロモーター領域のprimerを用いてMS-PCRをおこなった。
    結果:MS-PCR法はnested PCRとすることによって陽性コントロールの10^<-5>以上の検出感度にすることが可能であった。
    2)原発巣腫瘍組織におけるメチル化の検出
    対象・方法:連続的に切除された非小細胞肺癌83例の凍結保存された正常肺、腫瘍からそれぞれDNAを抽出し、sodium bisulfite処理を加えた後、MS-PCR法を試みた。
    結果:腫瘍組織におけるプロモーター領域のメチル化は83例中39例(47%)に認められた。
    3)血清中からのメチル化DNAの検出
    対象・方法:原発巣腫瘍組織においてメチル化が認められた39例を対象とした。それぞれの症例の血清中からDNAを抽出して同様にsodium bisulfite処理を加えた後、MS-PCR法を試みた。
    結果:39例中14例(36%)において血清中から腫瘍組織と同様のメチル化DNAが検出された。
    4)血清中からメチル化DNAが検出された症例の予後、臨床病理学的因子の検討
    結果:血清中のメチル化DNA陽性14症例と陰性25症例の間で喫煙、病理病期、組織型、分化度などの臨床病理学的因子の違いの有無を検討したが、陽性症例はCEAが高値であった。再発は陽性6例(42.8%)と陰性4例(16%)に認め、また遠隔転移を陽性4例(28.6%)、陰性1例(4%)に認めた。
    5)まとめ・今後
    メチル化DNAを指標としたnested MS-PCR法は簡便であり、且つ検出感度も高かった。血清中からメチル化DNAが検出された症例はCEAが高く、再発・遠隔転移が多い傾向を認めた。今後は更に多種類の遺伝子での検索を検討したい。また血清蛋白での検索は更なる検討が必要である。

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  • 癌特異的遺伝子異常を利用した肺癌患者血清による新しい遺伝子診断

    研究課題/領域番号:14770674  2002年 - 2003年

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    橋本 毅久

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    配分額:2800000円 ( 直接経費:2800000円 )

    本研究ではDNAのCpG配列のメチル化を特異的に検出できるmethylation-specific PCR(MS-PCR)法を用いてその特異性と感度を高めるととによって微小転移の検出が可能であるかについて検討した。
    (1)初めにMS-PCR法の検出感度・特異性に関して検討した。メチル化DNAの希釈系列を作成した後、DNAをSodium bisulfite処理し、DNAのチミンをウラシルに変換した。CpG配列でのチミンはメチル化されているとウラシルには変換されないことを利用し、p16遺伝子のプロモーター領域のメチル化を特異的に検出できるプライマーを設計してPCRをおこない検出感度と特異性を調べた。特異性と感度を高めるためにnested PCRとし、2nd PCRではアニーリング温度を高く(72℃)設定した。更に各サイクル時間を短くし(15秒)且つサイクル数を多くした(35サイクル)。その結果メチル化DNAを10^<-6>まで希釈したサンプルでもp16遺伝子のプロモーター領域のメチル化を検出することが可能となった。
    (2)次に完全切除された50例の原発性非小細胞肺癌の原発巣でのメチル化の有無を検索した。凍結保存された肺癌と正常肺組織からDNAを抽出し、Sodium bisulfite処理をおこなった後にMS-PCR法を用いてp16遺伝子プロモーター領域のメチル化の有無を検索した。正常肺でもメチル化が検出される症例を対象から除外すると原発性肺癌43例中18例(41.9%)でメチル化が検出された。
    (3)現在手術前後の血清からDNAを抽出し上記の方法で血清中に含まれるメチル化遺伝子の検出を試みている。またp16遺伝子のみではメチル化の頻度が高くないことから今後は他の遺伝子(MGMT、DAP kinase、RASSF1A遺伝子など)も利用して検索を進める予定である。

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