SHIONO Hiroyuki

    Kindai University Nara Hospital Professor/General Manager
Last Updated :2024/03/24

Researcher Information

J-Global ID

Research Interests

  • Chest surgery   Minimally invasive surgery   Endoscopic surgery   lung cancer   mediastinum   image guided surgery   Clinical Safety   surgical training   Thymoma   Myasthenia gravis   Thymus   

Research Areas

  • Life sciences / General surgery, pediatric surgery
  • Life sciences / Respiratory surgery

Academic & Professional Experience

  • 2012/04 - Today  Kindai UniversityFaculty of Medicine教授・部長
  • 2009/07 - 2012/03  Kindai UniversityFaculty of Medicine准教授・科長
  • 2007/11 - 2009/06  大阪警察病院呼吸器外科部長
  • 2005/03 - 2007/10  Osaka UniversityHospital特任准教授
  • 2002/07 - 2005/02  Osaka UniversityFaculty of Medicine助教
  • 2000/06 - 2002/06  大阪府立羽曳野病院呼吸器外科医長
  • 1997/11 - 2000/05  Oxford UniversityInstitute Molecular MedicineSeniro Research Fellow
  • 1995/09 - 1997/10  Osaka UniversityHospitalシニア非常勤医師
  • 1993/07 - 1995/08  Osaka UniversityHospital研究生
  • 1991/07 - 1993/06  国立療養所刀根山病院呼吸器外科医員
  • 1990/07 - 1991/06  国立呉病院胸部外科レジデント
  • 1988/07 - 1990/06  大阪府立病院消化器・一般外科レジデント
  • 1987/07 - 1988/06  Osaka UniversityHospital研修医

Education

  • 1981/04 - 1987/03  Osaka University  Faculty of Medicine  Medical School

Association Memberships

  • Japan Society of Clinical Safety   IASCL   JAPAN SOCIETY FOR MEDICAL EDUCATION   日本胸腺研究会   小切開・鏡視外科学会   日本呼吸器内視鏡学会   日本呼吸器学会   THE JAPAN LUNG CANCER SOCIETY   JSES   THE JAPANESE ASSOCIATION FOR CHEST SURGERY   THE JAPANESE ASSOCIATION FOR THORACIC SURGERY   JAPAN SURGICAL SOCIETY   

Published Papers

  • Takashi Iwazawa; Yoshihisa Kadota; Yukiyasu Takeuchi; Hideoki Yokouchi; Hiroyuki Shiono; Masanobu Hayakawa; Yasushi Sakamaki; Eiji Kurokawa; Kiyonori Nishioka; Yasushi Shintani
    General thoracic and cardiovascular surgery 69 (10) 1407 - 1413 2021/10 
    OBJECTIVE: Various surgical procedures have been performed to decrease the recurrence of primary spontaneous pneumothorax after video-assisted thoracic surgery. This study aimed to examine the efficiency of pleural coverage for the prevention of postoperative recurrence in relatively young patients. METHODS: Between January 2008 and December 2012, a total of 357 cases of 345 patients (age 15-29 years) with primary spontaneous pneumothorax who underwent bullectomy at 13 institutions were enrolled in this multi-institutional retrospective cohort study. A concurrent bilateral operation was counted as two cases. Polyglycolic acid sheets were used in 238 cases, and oxidized regenerated cellulose sheets were used in 37 cases to cover the visceral pleura, with no pleural coverage in 82 cases. The average observation period was 4.2 ± 2.0 years. RESULTS: Postoperative recurrence was observed in 50 cases (14.0%) after video-assisted thoracic surgery. Twenty-six cases (10.9%) in the polyglycolic acid group, eight (21.6%) in the oxidized regenerated cellulose group, and sixteen (19.5%) in the non-coverage group experienced postoperative recurrence. Kaplan-Meier analysis revealed that the rate of freedom from postoperative recurrence in the polyglycolic acid group was significantly higher than that in the non-coverage group. Multivariate analysis showed that age ≥ 20 years and coverage with polyglycolic acid sheets were associated with reduced risk factors for postoperative recurrence. CONCLUSION: Pleural coverage with a polyglycolic acid sheet is suggested to be effective in preventing postoperative recurrence of pneumothorax compared with non-coverage in relatively young patients.
  • Tomomi Isono; Tomoko Wakasa; Hidenori Kusumoto; Keiji Shimada; Takafumi Ogawa; Hiroyuki Shiono
    Medicine 100 (5) e24491  2021/02 [Refereed]
     
    RATIONALE: The relationship between thymic tumors and Sjögren syndrome (SjS) is unknown, and surgical resection has not been optimized. Especially, thymic carcinoma with autoimmune disease is rare. Analysis of SS-A52, germinal centers, plasma cells, and Foxp3+ Treg in thymic carcinoma has never been reported, and their pathological roles in causing SjS have not been studied. PATIENT CONCERNS: A 78-year-old man presented with sputum production and xerostomia while asleep. Chest computed tomography showed a homogeneous and hypodense mass in the anterosuperior mediastinum. Serum levels of the antinuclear antibody, antibody to SS-A, and antibody to SS-B were positive. DIAGNOSES: Thymic carcinoma (squamous cell carcinoma) and SjS. INTERVENTIONS: Video-assisted thoracoscopic resection of the mediastinal tumor and postoperative radiation therapy was performed. OUTCOMES: The histological diagnosis was thymic squamous cell carcinoma. Histologically, the squamous carcinomatous cells were arranged in nests and cords in the fibrohyaline stroma with capsular invasion. In the stroma, dense lymphoid tissues containing large reactive germinal centers and many plasma cells were also noted. In the involuted thymus, CD20-positive mature lymphocytes infiltrated, and germinal centers were noted. Double immunohistochemical staining revealed that SS-A52 antigen was positive in both the carcinoma component and CD20-positive mature B cells. Postoperatively, the xerostomia persisted, and serum SS-A and SS-B remained positive. No evidence of carcinoma recurrence with chest computed tomography scan was observed at 18-months follow-up. LESSONS: In the surgical treatment of thymic tumors with SjS, extended thymectomy might be worth considering to stop the progressive destruction of the targets of SjS-specific autoantibodies. However, the postoperative symptoms may not dramatically improve because the target organs might have changed irreversibly, and memory B cells might persist. This is the first report that demonstrated the SS-A52 antigen presentation in a thymic tumor to the best of our knowledge.
  • Naoko Ose; Yukiyasu Takeuchi; Naoto Kitahara; Akihide Matumura; Ken Kodama; Hiroyuki Shiono; Yoshiyuki Susaki; Yasunobu Funakoshi; Hiroyuki Takabatake; Yasushi Shintani
    Journal of thoracic disease 13 (2) 977 - 985 2021/02 [Refereed]
     
    Background: Solitary pulmonary nodules caused by nontuberculous mycobacteriosis are included as a category of pulmonary nontuberculous mycobacterium disease. Clinical characteristics, treatments and prognosis are not fully known because there are a few related reports. Methods: This was a multi-center retrospective study of 101 cases diagnosed as solitary nodular type of nontuberculous mycobacteriosis from January 2000 to March 2017 that underwent resection at 9 related facilities belonging to the Thoracic Surgery Study Group of Osaka. Results: The most common pathogen was Mycobacterium avium complex (n=77, 87.5%), followed by Mycobacterium kansasii (n=8, 9.1%). Chest computed tomography results showed subpleural locations that were difficult to distinguish from lung cancer. Fluorodeoxyglucose positron emission tomography/computed tomography was performed in 58 cases and positive results were obtained in 35 (60.3%), with an average maximum standardized uptake value of 3.87. The purpose of resection in most cases was for diagnosis. The surgical procedure was wedge resection in 87, segmentectomy in 3, and lobectomy in 11, while 77 underwent thoracoscopic surgery. Postoperative complications occurred in 7 cases, though no infections caused by nontuberculous mycobacteriosis were noted. The median observation period was 27 months. A worsened condition occurred in 10 (9.9%) with Mycobacterium avium complex, though none had local recurrence. Conclusions: Solitary pulmonary nodules due to nontuberculous mycobacteriosis is difficult to diagnose based on preoperative examination results or distinguish from lung cancer. Among the present cases, none had local complications or recurrence, even in those that underwent a wedge resection, thus postoperative chemotherapy was not considered necessary if a complete resection was performed. On the other hand, some cases showed reinfection after a long period following resection, thus patients should be informed of that future possibility.
  • Ciliated muconodular papillary tumorの一例
    磯野 友美; 若狹 朋子; 大林 千穂; 楠本 英則; 塩野 裕之
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 34 (3) MO10 - 7 0919-0945 2020/08
  • Yoko Yamamoto; Ryu Kanzaki; Naoko Ose; Yasunobu Funakoshi; Naoki Ikeda; Koji Takami; Teruo Iwasaki; Takashi Iwazawa; Hideoki Yokouchi; Hiroyuki Shiono; Ken Kodama; Yasushi Shintani
    The Annals of thoracic surgery 109 (5) 1558 - 1565 2020/05 [Refereed]
     
    BACKGROUND: The clinical outcome of patients undergoing hemodialysis (HD) has not yet been clarified in lung cancer surgery. The aims of this study were to assess the clinical features, outcomes, and main cause of death after lung cancer surgery in patients undergoing HD and to evaluate the risk factors for postoperative complications. METHODS: The study identified 39 patients undergoing HD who had lung cancer surgery in 9 institutions under the Thoracic Surgery Study Group of Osaka University in Japan between 2007 and 2016. Study investigators retrospectively analyzed the surgical outcomes of these patients. RESULTS: Most patients were male and were smokers. Diabetes mellitus was the most common cause of primary renal disease. Lobectomy with systemic lymph node dissection was performed in 16 patients, and an extended operation was performed in 6 patients. Most patients had a diagnosis of pathologic stage IA (69.2%) lung cancer. The overall complication and mortality rates were 30.8% and 7.7%, respectively. Pneumonia was the most frequently observed complication. Extended operation was significantly associated with complications (P = .04). The 5-year overall survival rate was 57.9%, and the most common cause of death was not primary lung cancer but was a disease related to HD. CONCLUSIONS: Lung cancer surgery for patients undergoing HD provides favorable long-term outcomes despite higher postoperative mortality and morbidity rates. Because an extended operation is significantly associated with postoperative complications, thoracic surgeons should carefully select the type of resection on the basis of a balance between therapeutic benefit and invasiveness in these patients.
  • Tomomi Isono; Shigeshi Mori; Hidenori Kusumoto; Hiroyuki Shiono
    BMJ case reports 13 (2) 2020/02 [Refereed]
     
    Winged scapula is a rare condition caused by injuries to the long thoracic nerve (LTN) and accessory nerves. A 69-year-old man underwent surgery for right lung cancer. Video-assisted thoracic surgery was converted to axillary thoracotomy at the fourth intercostal space. The latissimus dorsi was protected, and the serratus anterior was divided on the side anterior to the LTN. Two months after discharge, he presented with difficulty in elevating his right arm and protrusion of the scapula from his back. Active forward flexion of the right shoulder was limited to 110° and abduction to 130°. He was diagnosed with winged scapula. After 6 months of occupational therapy, the symptoms improved. The LTN may have been overstretched or damaged by the electric scalpel. We recommend an increased awareness of the LTN, and to divide the serratus anterior at a site as far as possible from the LTN to avoid postoperative winged scapula.
  • Inoue M; Kusumoto H; Shiono H; Shintani Y; Ose N; Sakamaki Y; Okami J; Higashiyama M; Takeuchi Y
    Journal of chemotherapy (Florence, Italy) 31 (6) 343 - 348 1120-009X 2019/10 [Refereed]
     
    Feasibility is one of the major concerns during adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. A phase II clinical trial of adjuvant chemotherapy with four courses of carboplatin (AUC 5 at day 1) and S-1 (80 mg/m2/day for 2 weeks followed by a 2-week rest) was performed to evaluate the feasibility (UMIN 9101). The primary endpoint was the completion rate and the secondary endpoints were adverse events, 2-year overall survival and disease-free rates. Thirty-five non-small cell lung cancer patients were enrolled. The adjuvant chemotherapy completion rate was 85.3% (29/34); 17/34 (50%) patients completed 4 courses without dose reduction. There were no treatment-related deaths, and Grade 3/4 adverse events included neutropenia (38.2%), leukocytopenia (14.7%), anemia (20.6%), thrombocytopenia (20.6%), anorexia (5.9%), fatigue (5.9%), and oral mucositis (2.9%). Two-year overall and disease-free survival rates were 96.3% and 53.3%, respectively. Adjuvant chemotherapy with carboplatin plus S-1 is safe and feasible.
  • Tomomi Isono; Hirochiyo Sawaguchi; Hidenori Kusumoto; Hiroyuki Shiono
    The American journal of case reports 20 1440 - 1445 2019/09 [Refereed]
     
    BACKGROUND Herein, we describe a case of eosinophilic pneumonia that was likely to have been induced by vancomycin. CASE REPORT A 65-year-old man on maintenance hemodialysis presented with chest pain and dyspnea. He subsequently developed methicillin-resistant Staphylococcus aureus-positive acute pleural empyema in an evacuated right-sided pneumothorax. Surgical thoracoscopic curettage was ultimately performed, but dyspnea recurred postoperatively. Computed tomography depicted widespread reticular shadowing of the left lung, and peripheral eosinophilia was detected. The proportion of eosinophils found in bronchoalveolar lavage fluid was also remarkable (43%). All symptoms and the results of laboratory tests immediately improved after the discontinuation of vancomycin and initiation of prednisolone therapy. CONCLUSIONS We attribute this case of eosinophilic pneumonia to vancomycin, because all other candidate causes were ruled out, and only vancomycin fulfilled the criteria of both drug-induced eosinophilic pneumonia and drug-induced lung injury. If confirmed, this constitutes the first reported case of vancomycin-induced eosinophilic pneumonia.
  • Masanori Tsujie; Soichi Fumita; Hajime Ishikawa; Kotaro Kitani; Shumpei Satoi; Shuichi Fukuda; Hironobu Manabe; Yusaku Akashi; Tomoko Wakasa; Hiroyuki Shiono; Takao Tamura; Masao Yukawa; Masatoshi Inoue
    Gan to kagaku ryoho. Cancer & chemotherapy 46 (8) 1259 - 1263 0385-0684 2019/08 [Refereed]
     
    We retrospectively analyzed adverse effects(AEs), overall survival(OS), and progression-free survival(PFS)in 15 consecutive patients treated with FOLFIRINOX as the first-line treatment for recurrent or unresectable pancreatic ductal adenocarcinoma( PDAC)between February 2014 and December 2017 in our hospital. Eleven patients were treated for unresectable PDAC with distant metastases(UR-M), and 4 were treated for locally advanced unresectable PDAC(UR-LA). The median age was 56(range: 40-75)years. Nine patients were male, and 6 were female. The performance status was 0 or 1 in all patients. Tumors were located in the pancreas head in 8 cases and in the body-tail in 7 cases. Grade 5 AEs were observed in 1 case in which liver abscess causing sepsis resulted in mortality. The response rate was 20.0%, and the disease control rate was 66.7%. Two patients underwent conversion surgery after FOLFIRINOX treatment. Seven patients received a nab-paclitaxel plus gemcitabine regimen as second-line treatment. The median OS and PFS were 17.0 and 8.4 months, respectively, and the 1-year survival rate was 66.7%. FOLFIRINOX for recurrent and unresectable PDAC showed relatively good tumor control. However, strict attention is required for severe AEs. Conversion surgery might be effective in patients who are good responders even if they have metastatic disease.
  • Shimizu N; Akashi Y; Fujii T; Shiono H; Yane K; Kitahara T; Ohta Y; Kakudo K; Wakasa T
    Anticancer research 39 (1) 413 - 420 0250-7005 2019/01 [Refereed]
     
    BACKGROUND: Patients with adenocarcinoma of the lung are routinely screened for anaplastic lymphoma kinase (ALK) rearrangement because they can be treated by ALK-specific targeted therapy. The clinical and molecular characteristics of large-cell neuroendocrine carcinoma (LCNEC) associated with ALK rearrangement are still unclear. Herein, we assessed the ALK status in a series of patients with LCNEC by testing methods commonly used for adenocarcinoma. MATERIALS AND METHODS: ALK expression was first examined by immunohistochemistry. For a positively stained tumor, molecular analyses were then conducted. The ALK fusion partner found in a patient with ALK rearrangement was further identified by direct DNA sequencing. Patient clinicopathological features were also analyzed, focusing on the ALK rearrangement-positive case. RESULTS: Immunohistochemistry of seven patients identified strong ALK expression in one case of stage IV LCNEC. Molecular analysis identified a novel rearranged gene resulting from the fusion of kinesin family member 5B (KIF5B) exon 17 to ALK exon 20. The patient was treated with ALK-specific inhibitors, crizotinib and later, alectinib, and has remained alive for more than 24 months without disease progression. Three of the remaining six patients without ALK rearrangement had stage IV cancer and received cytotoxic chemotherapies. Their average overall survival was 5.4 months. CONCLUSION: To our knowledge, this is the first report of a KIF5B-ALK fusion gene in LCNEC. The patient was successfully treated with ALK inhibitors, suggesting that sensitivity to ALK inhibitor may define a specific LCNEC subtype. We propose that screening for ALK rearrangement in patients with LCNEC may assist in selecting potential candidates for targeted therapy.
  • Tomohiro Maniwa; Yasushi Shintani; Jiro Okami; Yoshihisa Kadota; Yukiyasu Takeuchi; Koji Takami; Hideoki Yokouchi; Eiji Kurokawa; Ryu Kanzaki; Yasushi Sakamaki; Hiroyuki Shiono; Teruo Iwasaki; Kiyonori Nishioka; Ken Kodama; Meinoshin Okumura
    Journal of thoracic disease 10 (12) 6828 - 6837 2018/12 [Refereed]
     
    Background: Direct lymphatic drainage from a primary tumor to the right paratracheal or aortic window lymph nodes is often noted in pN2 disease. This multi-institutional retrospective study investigated the outcomes of upfront surgery in patients with clinical skip N2 disease (N2 disease without N1 disease) and a tumor in the right upper lobe or left upper segment based on results of modern radiological examinations, including positron emission tomography (PET). Methods: We identified 143 patients with cN2 disease who underwent upfront surgery in 12 institutions under the Thoracic Surgery Study Group of Osaka University between January 2006 and December 2013. Among 143 patients, 94 who underwent PET were analyzed. We classified these patients into Group A (n=39; clinical skip N2 disease and a tumor in the right upper lobe or left upper segment) and Group B (n=55; other). Results: The median follow-up was 56.5 months. Among the 94 patients, 50 (53.2%) had skip N2 disease and 65 (69.1%) had a tumor in the right upper lobe or left upper segment. The 5-year overall survival (OS) rates of the 94 patients with cN2 disease was 47.9%. The 5-year OS rates for the cN2pN0/1 (n=22) and cN2pN2 (n=70) groups were 74.9% and 41.2%, respectively (P=0.034). The univariate analysis of OS revealed no significant differences in age, sex, histology, carcinoembryonic antigen (CEA) level, tumor size, PET findings, and number of metastatic lymph nodes when these parameters were dichotomized. A significantly better 5-year OS rate was observed in Group A than in Group B (64.0% vs. 37.0%; P=0.039). The multivariate analysis of OS revealed that Group A was a significantly prognostic factor (P=0.030). Conclusions: Patients with cN2 disease in Group A had a more favorable prognosis. Upfront surgery may be a treatment option for such selected patients with non-small lung cancer in the specific group.
  • Sakurai T; Kusumoto H; Wakasa T; Ohta Y; Konishi E; Shiono H
    Surgical case reports 4 (1) 77 - 77 2018/07 [Refereed]
     
    BACKGROUND: Epithelioid sarcoma (ES) is a rare variant of soft tissue sarcoma. The proximal type of ES occurs in various locations. We present a resected case with proximal-type ES that occurred in the chest wall and discuss the relevant literature. CASE PRESENTATION: A 47-year-old woman was referred for a 6-month history of a right anterior chest mass with tenderness. Chest computed tomography showed an invasive chest wall mass with calcification surrounding the third rib. Aspiration biopsy cytology suggested malignancy. We performed wide resection, including the middle part of the pectoralis major muscle, the pectoralis minor muscle, the third and fourth ribs, and reconstruction of the chest wall, using a 2-mm polytetrafluoroethylene patch. Severe deformation of the chest wall was avoided. Postoperative physical therapy of the shoulder was effective for the continuous pain and weakness of the arm. She has remained alive for 1 year and 10 months without recurrence. Our literature review showed five previously reported cases of ES in the chest wall, and all of these were surgically resected. Two of these patients suffered from frequent local recurrence and died of disease. CONCLUSIONS: ES in the chest wall is rare. Previous reports have indicated that surgical resection with tumor-free margins is essential for treatment. We performed complete resection of the tumor in our case, and a polytetrafluoroethylene patch was effective for reconstructing the deficit in the chest wall.
  • 塩野 裕之; 楠本 英則; 櫻井 禎子; 岡部 崇記; 明石 雄策; 松浦 知弘; 岡嶋 馨
    肺癌 (NPO)日本肺癌学会 57 (5) 489 - 489 0386-9628 2017/09
  • Motoki Yano; Yoshitaka Fujii; Junji Yoshida; Tomoki Utsumi; Hiroyuki Shiono; Motoshi Takao; Masayuki Tanahashi; Yushi Saito
    WORLD JOURNAL OF SURGERY SPRINGER 41 (8) 2033 - 2038 0364-2313 2017/08 [Refereed]
     
    Background We believe the merit of preservation of a part of the thymus following surgery for thymoma. We evaluated the efficacy of partial or subtotal thymectomy for early-stage thymoma in the prospective study. Methods The Japanese Association for Research on the Thymus conducted a multiple institutional study of thymectomy for thymoma localized in the thymus without total thymectomy. Patients without autoimmune disease who had an anterior mediastinal tumor that had been clinically diagnosed as an early-stage thymoma were enrolled in the study. Patients who were positive for anti-acetylcholine receptor antibodies were excluded. Results Sixty-three patients were enrolled preoperatively; 27 patients were judged as being inappropriate based on the other thymic pathologies or tumor invasion. The remaining 36 cases were diagnosed as early-staged thymoma and analyzed. The mean age of the patients was 61 years. The mean maximal tumor diameter in the resected specimens was 3.6 cm. The most common pathological types of thymoma were AB (n = 10) and B1 (n = 10). The Masaoka stages were classified as stage I (n = 22) and II (n = 14). The mean observation period was 63 months. Two patients died due to respiratory dysfunction, which was not related to thymoma. One hundred percent of the patients remained recurrence-free. Conclusions This prospective study suggested the efficacy of partial or subtotal thymectomy for early-stage thymoma in patients without any apparent evidence of autoimmune disease. We can preserve a part of the thymus even following surgery for thymoma to prepare the possible second malignancies or diseases in future.
  • 坂本 鉄基; 櫻井 禎子; 井上 啓介; 若狭 朋子; 太田 善夫; 塩野 裕之
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 31 (4) 494 - 500 0919-0945 2017/05 [Refereed]
     
    肺癌の大腸転移はまれであり、自覚症状に伴い発見されることが多い。肺癌術後の無症状経過中にPET-CTで病変を指摘し得た症例を経験したので報告する。症例は69歳、男性。右上葉肺癌(acinar adenocarcinoma、pT1aN0M0、pStage IA)に対して右肺上葉切除+ND2a-1施行後、外来経過観察中であった。自覚症状はなく、術後2年目の胸腹部CTにて左肺門リンパ節腫大および盲腸周囲リンパ節腫大を認めた。PET-CTで回盲部に集積を認め、下部消化管内視鏡検査を施行した。生検の結果Group5、腺癌を認め、大腸癌と診断し手術を施行した。病理組織学的検査結果にて肺癌盲腸転移と診断した。根治切除が行われた早期肺癌でも大腸転移を起こすことがあり、PET-CTでの全身検索の検討の余地がある。(著者抄録)
  • Teiko Sakurai; Tetsuki Sakamoto; Tomoko Wakasa; Yoshio Ohta; Hiroyuki Shiono
    International Journal of Surgery Case Reports Elsevier Ltd 30 186 - 189 2210-2612 2017 [Refereed]
     
    Background A thymoma, an epithelial neoplasm of the thymus, mainly occurs in the anterior mediastinum, while few are seen in the middle mediastinum. Case presentation An 83-year-old male was referred for an incidental mass in the middle mediastinum. He had severe dementia and denied symptoms. Our follow-up computed tomography (CT) examinations had revealed the progress of tracheal compression along with tumor enlargement for 2 years. At 85 years old, we performed a thymomectomy via a median sternotomy to avoid complete trachea obstruction. The pathological diagnosis was WHO type A thymoma, Masaoka stage II. One year after surgery, the patient was free of disease. Discussion Thymomas occurring in the middle mediastinum are rare. In our review of 13 such cases, none were Masaoka stage III or IV, while the majority (9/13, 69.2%) were WHO type A or AB. Conclusion We encountered a thymoma in the middle mediastinum that showed enlargement over a 2-year period, inducing severe tracheal compression. Thymomas can occur widely in pharyngeal pouch-derived locations and should be considered in differential diagnosis of a middle mediastinum tumor.
  • Okumura M; Shintani Y; Ohta M; Kadota Y; Inoue M; Shiono H
    Journal of visualized surgery 3 96  2017 [Refereed]
  • 矢野 智紀; 藤井 義敬; 吉田 純司; 内海 朝喜; 塩野 裕之; 高尾 仁二; 棚橋 雅幸; 齋藤 雄史
    肺癌 (NPO)日本肺癌学会 56 (6) 507 - 507 0386-9628 2016/11
  • Hiroyuki Shiono; Tetsuki Sakamoto; Teiko Sakurai
    General Thoracic and Cardiovascular Surgery Springer Tokyo 64 (9) 564 - 567 1863-6713 2016/09 [Refereed]
     
    Anterior chest wall lifting facilitates a wide view and allows easy access during thoracoscopic surgery in a supine position for anterior mediastinal lesions. We previously reported an anterior chest wall lifting method for a thymectomy that utilizes our original costal hooks. Here, we present a less invasive method that can be performed with only a needle puncture, i.e., a metal plate placed under the ribs is lifted with a wire inserted through the anterior chest wall. We have applied this novel ‘T bar-lifting method’ for 5 different cases with anterior mediastinal tumors, and found it to be simple and easy to perform, as well as less invasive for patients undergoing thoracoscopic surgery.
  • Shiono H
    Nihon Geka Gakkai zasshi 117 (3) 222 - 224 0301-4894 2016/05 [Refereed]
  • Tomoyuki Nakagiri; Masayoshi Inoue; Yasushi Shintani; Soichiro Funaki; Tomohiro Kawamura; Masato Minami; Mitsunori Ohta; Yoshihisa Kadota; Hiroyuki Shiono; Meinoshin Okumura
    SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES SPRINGER 29 (9) 2859 - 2865 0930-2794 2015/09 [Refereed]
     
    We previously introduced video-assisted thoracoscopic ET (VATS-ET) as a therapeutic option for MG with acceptable results. We have conducted further investigations to improve the procedure without deterioration of operative results, including myasthenia gravis (MG) remission rate and palliation rate. Here, we report the details of our current procedure, as well as surgical results and patient outcomes as compared with the original VATS-ET procedure. From January 2002 to September 2013, we performed a VATS-ET procedure with an anterior chest wall lifting method for 77 patients who had MG with or without a thymoma. During that period, we investigated the appropriate indications and improved the procedure. Our current indication for this procedure is MG with the anti-acetylcholine receptor antibody or sero-negative type, or MG with a thymoma < 5 cm in diameter without invasion to adjacent organs. With our procedure, the thymus and surrounding tissue are sufficiently resected using a bilateral thoracoscopic surgical method without neck incision. Remission and palliation rates were found to be equivalent to those obtained with the original VATS-ET procedure. VATS-ET is suitable for select patients with MG with or without a thymoma. In addition, our current method has shown to be effective while also offering cosmetic advantages as compared with the original, neck incision needed, VATS-ET method.
  • Yasushi Sakamaki; Tomofumi Oda; Go Kanazawa; Toshio Shimokawa; Tetsuo Kido; Hiroyuki Shiono
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY MOSBY-ELSEVIER 148 (4) 1230 - + 0022-5223 2014/10 [Refereed]
     
    Objective: To evaluate the impact on patient survival of video-assisted thoracoscopic surgery (VATS) thymectomy for the treatment of early-stage thymoma, by comparing the intermediate-term oncologic outcomes with outcomes after open thymectomy. Methods: Eighty-two patients who underwent complete resection of a Masaoka stage I or II thymoma between November 1998 and December 2011 were reviewed. Results: The patients included 32 men and 50 women (median age, 57 years; range, 20-90 years), of whom 44 had stage I thymoma and 38 had stage II thymoma. Seventy-one patients underwent VATS, of whom 4 (5.6%) underwent conversion to open thymectomy; the remaining 11 patients underwent planned open thymectomy. Thirty-six patients underwent total thymectomy and 46 underwent partial thymectomy. Operative mortality was nil. The tumor stage, tumor size, and proportion of patients who underwent total thymectomy were not significantly different between the open and VATS thymectomy groups. The median follow-up period was 49 months (VATS, 48 months; open, 52 months). There was a significant difference between the 2 groups for the estimated 5-year overall survival (VATS, 97.0%; open, 79.5%; P = .041) but not in the estimated 5-year recurrence-free survival. Conclusions: Our findings indicate that the intermediate-term oncologic outcomes after VATS thymectomy for early-stage thymoma are as favorable as outcomes after open thymectomy. Further follow-up is still required to evaluate the long-term outcomes after VATS thymectomy.
  • 気胸を契機に発見された炎症性筋線維芽細胞腫の1切除例
    三浦 健; 坂本 鉄基; 太田 善夫; 塩野 裕之
    日本呼吸器外科学会雑誌 (NPO)日本呼吸器外科学会 28 (3) 1 - 7 0919-0945 2014/04 [Refereed]
  • Tomoyuki Nakagiri; Soichiro Funaki; Yoshihisa Kadota; Yukiyasu Takeuchi; Hiroyuki Shiono; Akinori Akashi; Meinoshin Okumura
    ANNALS OF THORACIC AND CARDIOVASCULAR SURGERY MEDICAL TRIBUNE INC 20 674 - 676 1341-1098 2014 [Refereed]
     
    A 56-year-old woman heavily pretreated for a thymoma was referred to our hospital with recurrence. Following additional surgery, the tumor recurred again in the left thoracic cavity. Because of previous multiple operations and repeated chemotherapies, the patient was considered unable to tolerate additional surgery or chemotherapy. After we obtained positive evidence of epidermal growth factor receptor (EGFR) mutation, she was administrated gefitinib for 3 months. Although immunohistochemistry findings showed that the tumor was EGFR positive, gefitinib therapy led no reduction of the tumor size. After undergoing immunotherapy, the patient suffered from repeated occurrences of pneumonia, and died from respiratory failure.
  • Toru Kimura; Masayoshi Inoue; Yoshihisa Kadota; Hiroyuki Shiono; Yasushi Shintani; Tomoyuki Nakagiri; Soichiro Funaki; Noriyoshi Sawabata; Masato Minami; Meinoshin Okumura
    European Journal of Cardio-thoracic Surgery 3 44 (3) e214 - e218 1010-7940 2013/09 [Refereed]
     
    Objectives: Although video-assisted thoracoscopic thymectomy (VATS-Tx) for thymoma has been introduced, its oncological outcome remains unclear. Our institutional experience with early-stage thymoma was retrospectively reviewed to evaluate the oncological feasibility of thoracoscopic thymectomy. Methods: A retrospective review consisting of 74 patients with Masaoka Stage I and II thymomas who had undergone thymectomy was performed. Forty-five patients underwentthoracoscopic thymectomy, while 29 underwent thymectomy through the open sternotomy approach. The clinical factors associated with the surgical outcome, including tumour recurrence, were investigated. Results: Neither operative death nor major postoperative complications were observed. The median intraoperative blood loss and operative time of thoracoscopic thymectomy were 50 ml and 180 min, respectively. Among the patients with thymomas > 5 cm, the number of patients with operative time > 4 h was 9 of 26 (34.6%) in the thoracoscopic thymectomy and 1 of 21 (4.8%) in the open sternotomy groups. Pleural recurrence was observed in 3 (6.7%) patients with thymoma > 5 cm only in the thoracoscopic thymectomy group. Tumour capsule injury by manipulation during the operation was recorded in 2 of these 3 patients. In 2 of the 3 cases who had tumours with cystic portions on computed tomography, a tumour capsule injury occurred due to manipulation during thoracoscopic thymectomy. Conclusions: VATS-Tx for early-stage thymomas is feasible, while the indications should be carefully considered in patients with large or cystic tumours. The conventional open sternotomy approach could be recommended in patients with thymomas> 5 cm to avoid capsule injury. © The Author 2013. Published by Oxford University Presson behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
  • Toru Kimura; Toshiki Takemoto; Yoshinori Fujiwara; Katsunari Yane; Hiroyuki Shiono
    ANNALS OF THORACIC AND CARDIOVASCULAR SURGERY MEDICAL TRIBUNE INC 19 (4) 289 - 292 1341-1098 2013/08 [Refereed]
     
    We herein report a case of thoracic esophageal perforation caused by a fish bone. The patient was a 68-year-old female who presented with a persistent sore throat after eating sea bream four days previously. She was diagnosed with an esophageal perforation and posterior mediastinal abscess formation by chest computed tomography and inflammatory findings in her blood test. Surgically indwelling drainage was able to effectively control the leakage of contaminants and infection. Endoscopic injection of fibrin glue into the long-standing thoracic-esophageal fistula promoted closure of the esophageal wall defect and enabled her to restart oral intake. This case report suggests that effective drainage and the use of fibrin glue sealant may be one of the treatment options for esophageal perforation.
  • Toru Kimura; Hiroyuki Shiono; Toshiki Takemoto; Yoshio Ohta
    SURGERY TODAY SPRINGER 43 (2) 199 - 202 0941-1291 2013/02 [Refereed]
     
    This report presents the case of a late relapse of an ovarian granulosa cell tumor (GCT) that metastasized to the lung 36 years after the initial diagnosis. A 72-year-old female demonstrated multiple nodules with extrapleural signs on chest computed tomography. Positron emission tomography with F-18-fluorodeoxyglucose ([F-18]FDG-PET) showed that the nodules had no FDG avidity. The nodules, which appeared as polypoid lesions of the visceral pleura on thoracoscopy, were resected and diagnosed as pulmonary metastases from the GCT. This case report indicates that thorough thoracoscopic exploration of the pleural cavity is essential when intrathoracic nodules are seen on postoperative imaging examinations in GCT patients, even when the [F-18]FDG-PET results are negative.
  • Sakamaki Y; Shiono H; Miura T
    Kyobu geka. The Japanese journal of thoracic surgery 10 65 (10) 926 - 929 0021-5252 2012/09 [Refereed]
  • Atsunari Kawashima; Masashi Nakayama; Daizo Oka; Mototaka Sato; Koji Hatano; Masatoshi Mukai; Akira Nagahara; Yasutomo Nakai; Hitoshi Takayama; Masayoshi Inoue; Hiroyuki Shiono; Kazuo Nishimura; Meinoshin Okumura; Norio Nonomura
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY SPRINGER TOKYO 16 (6) 660 - 665 1341-9625 2011/12 [Refereed]
     
    Pulmonary metastasectomy in patients with renal cell carcinoma (RCC) remains controversial. The purpose of our analysis was to explore the outcome of patients with RCC who underwent pulmonary metastasectomy at our institution. We reviewed data on 25 patients who underwent resection of lung metastasis from 1998 to 2008 at our institution. All patients were treated by radical nephrectomy for primary RCC. Progression-free survival (PFS) ranged from 0.3 to 198.8 months (median 7.4 months), and overall survival (OS) ranged from 2.4 to 198.8 months (median 33.9 months). The 5-year PFS rate was 24.9%, and the OS rate was 35.5%. Although differences in the resectability of the metastasectomy and OS were not significant in univariate or multivariate analyses, the relationship between PFS and the radicality of pulmonary metastasectomy was significant in both the univariate and multivariate analyses (P = 0.004, 0.012, respectively). The results of pulmonary metastasectomy for patients with RCC at our institution indicate that pulmonary metastasectomy should be performed only when the pulmonary metastasis can be completely resected. Additional studies are therefore necessary to evaluate the prognostic factors and to determine the selection criteria for pulmonary metastasectomy in the new era of molecular-targeted agents.
  • Toshiro Obuchi; Hiroyuki Shiono; Junichi Shimada; Kichizo Kaga; Masatoshi Kurihara; Akinori Iwasaki
    SURGERY TODAY SPRINGER 41 (11) 1579 - 1581 0941-1291 2011/11 [Refereed]
     
    Surgical teleconferences using advanced academic networks are becoming common; however, reports regarding Internet teleconferencing using free software packages such as Skype, USTREAM, and Dropbox are very rare. Teleconferences concerning mainly surgical techniques were held five times between Fukuoka University Hospital and other institutions from April to September 2010. These teleconferences used Skype and USTREAM as videophones to establish communication. Both PowerPoint presentations and surgical videos were made. These presentation files were previously sent to all stations via mail, e-mail, or Dropbox, and shared. A slide-show was simultaneously performed following the presenter's cue in each station. All teleconferences were successfully completed, even though there were minor instances of the Skype link being broken for unknown reasons during the telecommunication. Internet surgical teleconferences using ordinary software are therefore considered to be sufficiently feasible. This method will become more convenient and common as the Internet environments advance.
  • Hiroyuki Shiono; Kohei Nishiki; Mitsunori Ikeda
    SURGICAL LAPAROSCOPY ENDOSCOPY & PERCUTANEOUS TECHNIQUES LIPPINCOTT WILLIAMS & WILKINS 21 (5) E225 - E227 1530-4515 2011/10 [Refereed]
     
    Infrasternal mediastinoscopic single-incision surgery is a minimally invasive surgical option for patients with anterior mediastinal lesions. The main drawback of the procedure is difficultly when handling the endoscopic instruments through the small infrasternal incision. Herein, we report our initial experience with use of the procedure in 2 patients with bronchogenic cysts in the anterior mediastinum. We found that use of an SILS Port, now widely available for single-incision laparoscopic surgery, can decrease the difficulty of this approach.
  • 同時多発肺癌(6病変)の1切除例
    武本 智樹; 池田 直樹; 塩野 裕之; 明石 雄策; 尾崎 智博; 寺嶋 応顕; 植田 勲人; 田村 孝雄; 岡嶋 馨; 太田 善夫; 中川 勝裕
    肺癌 (NPO)日本肺癌学会 51 (4) 296 - 297 0386-9628 2011/08
  • Okumura M; Shiono H
    Kyobu geka. The Japanese journal of thoracic surgery 1 64 (1) 79 - 89 0021-5252 2011/01 [Refereed]
  • Meinoshin Okumura; Masayoshi Inoue; Yoshihisa Kadota; Akio Hayashi; Toshiteru Tokunaga; Takashi Kusu; Noriyoshi Sawabata; Hiroyuki Shiono
    SURGERY TODAY SPRINGER 40 (2) 102 - 107 0941-1291 2010/02 [Refereed]
     
    Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies to the striated muscle tissue. It is often treated by thymectomy. We review recent studies to investigate the biological implications of thymectomy. In anti-acetylcholine receptor antibody (anti-AchR Ab)-positive patients without a thymoma, abnormal germinal center formation in the thymus seems to play an essential role in the pathogenesis of MG. Specific differentiation of B cells producing anti-AchR Ab takes place uniquely in the thymus, and thymectomy is thought to assist in terminating the provision of high-affinity anti-AchR antibody-producing cells to peripheral organs. Thymectomy is not indicated for anti-AchR Ab-negative MG patients who are antimuscle specific kinase antibody (anti-MuSK Ab)-positive, although some anti-MuSK Ab-negative patients may benefit from the procedure. A thymoma can be considered as an acquired thymus with insufficient function of negative selection. The resection of a thymoma is thought to terminate the production of selfreactive T cells. Thus, the biological implications of thymectomy for MG have been partially revealed. Nevertheless, additional studies are needed to elucidate the ontogeny of T cells that recognize AchR and the mechanism of the activation of anti-AchR antibodies producing B cells.
  • Masayoshi Inoue; Mutsushi Matsuyama; Hiroyuki Shiono; Osamu Honda; Hiromitsu Sumikawa; Noriyuki Tomiyama; Meinoshin Okumura
    INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY E-CENTURY PUBLISHING CORP 3 (6) 587 - 592 1936-2625 2010 [Refereed]
     
    BUF/Mna rats develop thymomas spontaneously, which histologically mimic human thymomas. Although neoplasms in this rat strain contain a large number of immature lymphocytes, the phenotype has not been sufficiently assessed. We characterized T cell phenotypes in tumors from BUF/Mna rats in the present study. We also analyzed BUF/Mna-Rnu/+ rats, a heterozygous strain with suppressive thymomagenesis, and compared the histology and T cell maturation with those from the BUF/Mna rats. A total of 11 BUF/Mna and 10 BUF/Mna-Rnu/+ rats were used. Three-color flow cytometry was performed with anti-CD3, CD4, and CD8 antibodies to identify infiltrated lymphocytes, while tumor histology was evaluated with hematoxylin-eosin staining. The weight ratios of the entire thymic tissue including thymoma as compared to the BUF/Mna and BUF/Mna-Rnu/+ rat bodies were 0.8 +/- 0.8% and 1.2 +/- 1.8%, respectively. Histological findings for both rat congenic strains showed abundant lymphocytes surrounding large polygonal neoplastic thymic epithelia, which was compatible with the type B1 classification of the World Health Organization for human thymoma. CD4+CD8+ T cells accounted for 73.7 +/- 8.0% of the cells in tumors from BUF/Mna and 67.2 +/- 9.4% in those from BUF/Mna-Rnu/+ rats. Further, CD3-CD4-CD8+ T cells, intermediate between CD4-CD8-and CD4+CD8+ cells, accounted for 47.7 +/- 17.5% and 38.0 +/- 14.0% of the cells in tumors from the BUF/Mna and BUF/Mna-Rnu/+ strains, respectively. Thus, the proportion of developing thymic lymphocytes in and histology of thymomas from BUF/Mna and BUF/Mna-Rnu/+ rats were similar. These results suggest that both BUF/Mna and BUF/Mna-Rnu/+ strains are suitable animal models for human thymoma to understand the development of immature thymic lymphocytes.
  • Tomoki Utsumi; Hiroyuki Shiono; Yoshihisa Kadota; Akihide Matsumura; Hajime Maeda; Mitsunori Ohta; Yasuo Yoshioka; Masahiko Koizumi; Takehiro Inoue; Meinoshin Okumura
    CANCER JOHN WILEY & SONS INC 115 (23) 5413 - 5420 0008-543X 2009/12 [Refereed]
     
    BACKGROUND: Postoperative radiation therapy for thymoma is widely used, although the clinical benefits are controversial. Furthermore, to the authors' knowledge, the relation between postoperative radiation therapy and cell type classified by the World Health Organization (WHO) is not known. METHODS: The records of 324 patients (ages 17-83 years; mean, 51 years; 160 males and 164 females) who underwent complete resection of a thymoma between 1970 and 2005 were reviewed. Mediastinum postoperative radiation therapy was performed for 134 patients. Survival rates and patterns of recurrence were determined according to Masaoka stage and WHO cell type. RESULTS: The 10-year disease-specific survival rates for patients with and without postoperative radiation therapy were 92.8% and 94.4%, respectively (P = .22). Subset analyses after stratifying by Masaoka stage and WHO cell type demonstrated that the 10-year disease-specific survival rate for patients without postoperative radiation therapy with Masaoka stage I and II, as well as those with WHO cell types A, AB, or B1, was 100%, which was satisfactory. Furthermore, the rates for patients with Masaoka stage III/IV and those with WHO cell types B2/B3 with or without postoperative radiation therapy were not found to be significantly different. In 24 patients with disease recurrence, pleural dissemination was observed most often, followed by distant metastases; local disease recurrence without other recurrence occurred in 2. CONCLUSIONS: The authors concluded that surgical resection alone is sufficient for thymoma patients with Masaoka stage I and II, and those with WHO cell types A, AB, and B1. Furthermore, an optimal treatment strategy should be established for patients with Masaoka stage III/IV and WHO cell type B2/B3 thymomas. Cancer 2009;115:5413-20. (C) 2009 American Cancer Society.
  • Hiroyuki Shiono; Yoshihisa Kadota; Akio Hayashi; Meinoshin Okumura
    SURGICAL LAPAROSCOPY ENDOSCOPY & PERCUTANEOUS TECHNIQUES LIPPINCOTT WILLIAMS & WILKINS 19 (6) 424 - 427 1530-4515 2009/12 [Refereed]
     
    Minimally invasive thymectomy procedures have been proposed for nonthymomatous myasthenia gravis. However, few reports stressed that the lower invasiveness or cosmetic benefits also evaluated the rationale of a thymectomy, which is performed to remove as much thymic tissue as possible. We retrospectively reviewed 30 consecutive patients who underwent a bilateral video-assisted thoracoscopic extended thymectomy (VATET) and compared the results with those of 26 patients who underwent a transsternal extended thymectomy (TSET) to determine the amount of removed thymic tissue and clinical prognosis. The amount of blood loss during the operation for VATET (median 60mL; range nearly 0 to 940mL) was significantly lower as compared with that of TSET. The median weight of removed thymic tissue (37.0g; 18.3 to 100.0g) and remission rates (1 y: 12.5%; 3y: 30.8%; 4y: 44.4%) of VATET were comparable with those of TSET. The VATET group had a similar amount of thymofatty tissue removed and feasible clinical outcomes as compared with the TSET group, indicating that VATET provides a proper balance between less invasiveness and radical capability.
  • Atsuo Inoue; Noriyuki Tomiyama; Mitsuaki Tatsumi; Naoki Ikeda; Meinoshin Okumura; Hiroyuki Shiono; Masayoshi Inoue; Ichiro Higuchi; Katsuyuki Aozasa; Takeshi Johkoh; Hironobu Nakamura; Jun Hatazawa
    EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING SPRINGER 36 (8) 1219 - 1225 1619-7070 2009/08 [Refereed]
     
    Our aim was to determine dual-phase F-18-FDG PET imaging features for various subtypes of thymic epithelial tumors based on the World Health Organization classification. Forty-six patients with histologically verified thymic epithelial tumors [23 with low-risk tumors (4 with type A, 16 with AB, and 3 with B1) and 23 with high-risk tumors (7 with B2, 5 with B3, and 11 with thymic carcinoma] were enrolled in this study. All patients were injected with F-18-FDG.; after 1 h, they underwent scanning; after 3 h, 23 patients underwent an additional scanning. The maximum standard uptake value (SUVmax) and the retention index (RI%) of the lesions were determined. The early and delayed SUVmax values in the patients with high-risk tumors [early SUVmax (mean: 6.0) and delayed SUVmax (mean: 7.4)] were both significantly larger than those in patients with low-risk tumors [early SUVmax (mean: 3.2) and delayed SUVmax (mean: 3.4)] (P < 0.05). Early SUVmax values of greater than 7.1 differentiated thymic carcinomas from other types of tumors. For the histological differentiation between high-risk tumors and low-risk tumors, an early SUVmax value of 4.5 was used as the cutoff. The sensitivity, specificity, and accuracy were 78.3, 91.3, and 84.8%, respectively. High SUV values (early SUV > 4.5) suggest the presence of high-risk tumors. A very high SUV value (early SUV > 7.1) is useful for the differentiation of thymic carcinomas from other types of tumors. The delayed SUV values were higher than the early SUV values in all types of tumors.
  • Hiroyuki Shiono; Meinoshin Okumura; Kosei Yasumoto
    General Thoracic and Cardiovascular Surgery 1 57 (1) 22 - 27 1863-6705 2009/01 [Refereed]
     
    Currently, no specific item regarding endoscopic thymectomy for nonthymomatous myasthenia gravis is listed in the standards of deciding medical service fees. To understand the present situation regarding the medical fee-for-service for endoscopic thymectomy, a questionnaire survey was conducted involving the institutions and members participating in the Japanese Association for Research on the Thymus. Of 101 responding institutions, 18 (18%) reported basically performing endoscopic thymectomy in all qualifying patients, and 32% of the institutions reported mainly performing median sternotomy but sometimes performing endoscopic thymectomy. The methods of approaching endoscopic thymectomy varied among the institutions, but most included endoscopic clips or ultrasound-driven scalpels as well as anterior chest wall lifting devices. A total of 214 patients underwent thymectomy in 2004 in the responding institutions, of whom 77 patients (32%) underwent endoscopic thymectomy. In total, 71% of the responding institutions answered that a specific item regarding endoscopic thymectomy should be listed in the standards for deciding medical service fees. © 2009 The Japanese Association for Thoracic Surgery.
  • Toshiteru Tokunaga; Akio Hayashi; Yoshihisa Kadota; Hiroyuki Shiono; Masayoshi Inoue; Noriyoshi Sawabata; Meinoshin Okumura
    AUTOIMMUNITY TAYLOR & FRANCIS LTD 42 (8) 653 - 660 0891-6934 2009 [Refereed]
     
    Thymoma is a thymic epithelial neoplasm which induces T cell development. However, the frequency of mature CD4(+) T cells in thymomas is lower than in normal thymi. Recently, CD4/CD8 lineage commitment has been elucidated in animal model. The zinc finger transcription factor Th-POK is a critical factor to CD4(+) T cell development in CD4/CD8 lineage commitment, whereas CD8(+) T cell development requires the transcription factor Runx3. These factors antagonize in CD4/CD8 lineage commitment. In this study, we examined Th-POK and Runx3 mRNA expression in the T cell subsets of human normal thymus and thymoma. A quantitative reverse transcriptase-polymerase chain reaction examination revealed that Th-POK expression in normal thymi was higher in the CD4(+)CD8(-) subset than in the CD4(+)CD8(+) and CD4(-)CD8(+) subsets. In thymomas, Th-POK expression in the CD4(+)CD8(-) subset was significantly lower than that in normal thymi, and was significantly correlated with the proportion of CD3(+) cells in the CD4(+)CD8(-) subset. However, Th-POK expressions of the CD3(+)CD4(+)CD8(+) and CD3(+)CD4(+)CD8(-) subsets were not impaired in thymomas compared to normal thymi. These results suggest that thymoma neoplastic epithelial cells can induce Th-POK expression similarly to the normal thymic epithelial cells. In addition, there was no significant difference in Runx3 expression between normal thymi and thymomas. Therefore, CD4/CD8 lineage commitment dependent on Th-POK and Runx3 system seems to be working even in the neoplastic environment formed by human thymomas.
  • Tomoki Utsumi; Hiroyuki Shiono; Akihide Matsumura; Hajime Maeda; Mitsunori Ohta; Hirohito Tada; Akinori Akashi; Meinoshin Okumura
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY MOSBY-ELSEVIER 136 (6) 1481 - 1485 0022-5223 2008/12 [Refereed]
     
    Objectives: We investigated the relationships of recurrence site with the involved organ and cell type in patients with Masaoka stage III thymomas. Methods: Records of 84 patients who underwent a complete resection of stage III thymomas between 1957 and 2005 were reviewed and then divided according to involved organ. The number of patients with cell types determined according to World Health Organization criteria were 2, 5, 7, 37, and 7 for types A, AB, B1, B2, and B3, respectively, whereas type was not determined in 25 patients. Results: Lung invasion occurred in 58 patients, followed by invasion of the pericardium in 47 and invasion of the great vessels in 23. Recurrence occurred in 23 patients, which included 12 with pleural dissemination and 8 with distant metastasis, mostly in the lung. Lung invasion was seen in 8 of the 12 patients with pleural recurrence, whereas vascular invasion was seen in 6 of the 8 patients with distant metastasis. Local recurrence was less common. Disease-free survival after 10 years for all subjects was 74.2%, whereas it was lower for those with vascular invasion (46.1%) compared with those without invasion (87.1%, P <. 05). Of the 23 patients with recurrence, World Health Organization cell types B1, B2, and B3 were seen in 2, 11, and 3 cases, respectively, whereas type was not determined in 7 patients. Conclusions: The pleural cavity and lung are common sites of recurrence of Masaoka stage III thymomas. It is important to establish an inclusive therapeutic strategy that considers the relationships of involved organs and sites of recurrence in these patients.
  • TAMURA Mitsunobu; SHIONO Hiroyuki; NAKANISHI Masayoshi; ODA Tomofumi; OKUMURA Meinoshin
    The Journal of the Japanese Association for Chest Surgery The Japanese Association for Chest Surgery 22 (6) 967 - 973 0919-0945 2008/09 
    Liposarcomas are generally thought resistant to both radiotherapy and chemotherapy. Surgical treatment is, therefore, indicated even for a locally recurrent tumor, where resectable. Herein, we report a case of recurrent mediastinal liposarcoma undergoing surgical resection. A 69-year-old woman was referred to our department with a complaint of compression of the anterior chest. Two years ago, she had undergone radical surgery for a primary mediastinal liposarcoma (well-differentiated type), and had been doing well thereafter in the follow-up period. Computed tomography showed a low-attenuation area located extensively in the anterior and middle mediastinum, which was suggestive of a mass lesion. We suspected the lesion to be a local recurrence of the mediastinal liposarcoma. Although complete removal of the tumor was considered difficult, a second surgery was performed for debulking of the tumor, so as to avoid worsening of the symptoms due to compression caused by the recurrence. Surgical resection was performed via a sternotomy. The tumor was located in the anterior/middle mediastinum and compressed the surrounding intrathoracic structures, but fortunately did not show tumor infiltration. Although the tumor was extirpated, a small piece of adipose tissue remained on the left brachiocephalic vein because of strong adhesion to the vessel. Adjuvant radiotherapy was performed for the local control of possible tumor cells in the residual tissue. Pathological examination confirmed the tumor to be a well-differentiated liposarcoma with dedifferentiation. No signs of recurrence have been detected postoperatively and there have been no symptoms during the 1-year period after resection.
  • Marguerite E. Hill; Hiroyuki Shiono; John Newsom-Davis; Nick Willcox
    JOURNAL OF NEUROIMMUNOLOGY ELSEVIER SCIENCE BV 201 50 - 56 0165-5728 2008/09 [Refereed]
     
    In early-onset myasthenia gravis(EOMG), the thymus is colonized by lymph node-like infiltrates including T cell areas and germinal centers. Our Group(1) showed (1978) spontaneous anti-acetylcholine receptor (AChR) autoantibody production by EOMG thymic cells. Especially after enzymic dispersal, these are enriched in plasma cells that are evidently autonomous, long-lived, terminally differentiated and radio-resistant. Radiolabeled AChR is highly sensitive both for localizing them in situ and detecting their ongoing antibody production in culture at limiting cell numbers. Thus EOMG thymi are a readily available Source of specific autoimmune human plasma Cells Suitable for studying their biology and testing new therapies. (C) 2008 Elsevier B.V. All rights reserved.
  • Akio Hayashi; Hiroyuki Shiono; Meinoshin Okumura
    Interactive Cardiovascular and Thoracic Surgery 2 7 (2) 347 - 348 1569-9293 2008/04 [Refereed]
     
    Thymomas are associated at a high frequency with paraneoplastic autoimmune diseases. We treated a 64-year-old male with a thymoma, who also had lichen planus. The tumor was resected and diagnosed as thymoma, however, the symptoms associated with lichen planus did not subside and persisted. A preoperative examination showed an elevated serum level of squamous cell carcinoma antigen, which gradually decreased to normal after surgery. The findings of this case are interesting for understanding the correlation between a thymoma and autoimmune abnormalities. © 2008 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.
  • Hiroyuki Shiono; N. Shigemura; M. Okumura
    SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES SPRINGER 22 (4) 1135 - 1136 0930-2794 2008/04 [Refereed]
  • Masayoshi Inoue; Tetsuya Takakuwa; Masato Minami; Hiroyuki Shiono; Tomoki Utsumi; Yoshihisa Kadota; Takuma Nasu; Katsuyuki Aozasa; Meinoshin Okumura
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY MOSBY-ELSEVIER 135 (4) 830 - 836 0022-5223 2008/04 [Refereed]
     
    Objective: Recent technologic developments in computed tomography have increased the incidence of surgical intervention for small-sized lung cancer. Although indications of a sublobar resection for early disease have been discussed, we occasionally encounter locally advanced small-sized lung cancer with node metastasis. The present study aimed to clarify the histopathologic factors influencing nodal involvement and prognosis of such patients. Methods: We studied 97 patients who underwent complete resection for an adenocarcinoma of 2 cm or less in diameter. Lymph node metastasis and necrosis were microscopically evaluated, whereas immunohistochemical studies were also performed with Ki-67 and D2-40 for proliferation activity and lymphatic invasion, respectively. In addition, carcinoembryonic antigen expression in the tumor and its level in serum were investigated. Survival analysis was then conducted by using these clinicopathologic factors. Results: The 5-year disease-free survival rate was 90%. Nodal involvement was significantly frequent in patients with tumors showing microscopic necrosis, a Ki-67 labeling index of greater than 5%, and an increased serum carcinoembryonic antigen level. Furthermore, 5-year disease-free survival was worse in patients with lesions showing microscopic necrosis (68%), a Ki-67 labeling index of greater than 5% (76%), and lymphatic invasion detected with D2-40 staining (77%). Multivariate analysis identified lymphatic invasion detected with D2-40 to be an independent predictor for postoperative recurrence. Conclusions: These results indicate that microscopic necrosis, Ki-67 labeling index, and serum carcinoembryonic antigen level are predictors of nodal involvement. Careful postoperative follow-up examinations for recurrence are required for patients with tumors that show microscopic necrosis, high Ki-67 labeling index, and lymphatic invasion, even in those with stage IA disease.
  • Meinoshin Okumura; Yoshitaka Fujii; Hiroyuki Shiono; Masayoshi Inoue; Masato Minami; Tomoki Utsumi; Yoshihisa Kadota; Yoshiki Sawa
    General Thoracic and Cardiovascular Surgery 4 56 (4) 143 - 150 1863-6705 2008/04 [Refereed]
     
    Thymoma and thymic carcinoma are the representative tumors arising from the thymic epithelium. Thymoma is well known for association with autoimmune diseases including myasthenia gravis, suggesting its biological activity. Herein, recent progress in research of thymoma is reviewed with reference to its immunological function. Myasthenia gravis is frequently associated with WHO type B1 and B2 thymomas. These types of thymomas hold a significant number of CD4+CD8+ double-positive T cells, and at the same time, the neoplastic epithelial cells express HLA-DR molecules at a slightly reduced level compared with the normal thymus. The impaired expression of HLA-DR molecules in neoplastic epithelial cells of thymomas possibly affects positive selection of CD4+CD8- single-positive T cells and may result in alteration of its repertoire. The function of thymoma neoplastic cells as the cortical epithelium of the thymus and the morphological resemblance of thymomas to the cortex suggest that thymoma is of cortical epithelial origin this might imply that thymoma lacks the functional medulla where professional antigenpresenting cells are engaged in negative selection. These findings suggest that thymoma generates autoreactive T cells causing autoimmunity. Further investigation on immunological function of thymoma is supposed to elucidate the pathogenesis of thymoma-related autoimmunity and the high affinity of thymoma with myasthenia gravis. In addition, studying the biology of thymoma is also expected to contribute to further understanding of T-cell development and immunological tolerance in the human, because thymoma can be considered an acquired thymus. © 2008 The Japanese Association for Thoracic Surgery.
  • Shigenori Hoshino; Mitsugi Furukawa; Kazumi Aragane; Masayoshi Horimoto; Kunio Suzuki; Hiroyuki Shiono; Masato Minami; Meinoshin Okumura; Takashi Kijima; Khiro Kawase
    JOURNAL OF THORACIC ONCOLOGY LIPPINCOTT WILLIAMS & WILKINS 3 (1) 98 - 100 1556-0864 2008/01 [Refereed]
     
    Despite a benign histologic appearance, thymomas have metastatic potential. Here we report a case of a patient with a Masaoka stage IVb thymoma who was successfully treated using a multimodal strategy including systemic chemotherapy, radiofrequency ablatlon, and thoracic surgery. Despite complete remission after treatment, the patient developed myasthenia gravis with ptosis and neck drop symptoms. Hepatic meastasis of thymoma is a relatively rare occurrence and, to the best of our knowledge, this is the first report about the application of radiofrequency ablation to thymoma.
  • Meinoshin Okumura; Hiroyuki Shiono; Masato Minami; Masayoshi Inoue; Tomoki Utsumi; Yoshihisa Kadota; Yoshiki Sawa
    General Thoracic and Cardiovascular Surgery 1 56 (1) 10 - 16 1863-6705 2008/01 [Refereed]
     
    A histological classification of thymic epithelial tumors was presented by the World Health Organization (WHO) in 1999 and again in 2004 following slight modifications, in which thymic epithelial tumors were categorized as thymomas and thymic carcinomas. Whereas thymoma is defined as an organotypic (thymuslike) tumor, thymic carcinoma is a malignant epithelial neoplasm with a morphology similar to that of malignant neoplasms arising from other organs. Herein, the recent progress in research of thymic epithelial tumors is reviewed with reference to the WHO histological classification system, with the focus on thymomas. Thymomas are classified into five types-A, AB, B1, B2, B3-according to the shape and atypia of their epithelial cells as well as the abundance of lymphocytes. The invasiveness, prognosis, and genetic imbalance of thymomas have been shown to be related to this classification system. Myasthenia gravis is frequently associated with types B1 and B2. The WHO histological classification of thymomas is not only useful for treatment but reflects their biological characteristics, including genetic alterations. Advances are expected in future studies of thymomas from the standpoint of their clinical, pathological, and biological aspects. © 2008 The Japanese Association for Thoracic Surgery.
  • 門田 嘉久; 塩野 裕之; 内海 朝喜; 井上 匡美; 南 正人; 林 明男; 徳永 俊照; 奥村 明之進
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 22 (3) 438 - 438 2008
  • 塩野 裕之; 逆巻 靖; 奥田 倫久; 内海 朝喜; 井上 匡美; 奥村 明之進; 中本 将彦; 佐藤 嘉信
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 22 (3) 375 - 375 2008
  • 岡 大三; 向井 雅俊; 永原 啓; 芝 政宏; 中井 康友; 中山 雅志; 高山 仁志; 井上 均; 西村 和郎; 野々村 祝夫; 奥山 明彦; 塩野 裕之; 奥村 明之進
    日本泌尿器科学会雑誌 一般社団法人 日本泌尿器科学会 99 (2) 490 - 490 2008
  • Hiroyuki Shiono; Mitsunori Ohta; Meinoshin Okumura
    Thymus Gland Pathology: Clinical, Diagnostic, and Therapeutic Features Springer Milan 187 - 191 2008 [Refereed]
     
    A thymectomy is now generally accepted as a major option of treatment for myasthenia gravis (MG) patients, both with and without thymomas. In recent years, developments in endoscopic surgical procedures have achieved the benefit of less invasiveness, though that has led to discussion regarding the most suitable surgical approach. The rationale for choosing a thymectomy for nonthymomatous MG is based on its function to remove the germinal centers (GCs) in the thymi, where acetylcholine receptor (AChR)-specific B cells clonally proliferate, and differentiate into antibody producing cells with a high affinity, as demonstrated by the author when working with Willcox [1, 2]. In addition, we found that a decrease in antibody titer 1 year after a thymectomy had a significant inverted correlation with the number of GC B cells in thymic lymphocytes in those patients [3]. Further, the author and Willcox reported that lymphocytes in remnant thymi adjacent to tumors spontaneously produce anti-AChR an tibodies in MG patients with a thymoma [4]. © 2008 Springer Milan.
  • Akio Hayashi; Hiroyuki Shiono; Mitsuhiro Ohta; Kiyoe Ohta; Meinoshin Okumura; Yoshiki Sawa
    JOURNAL OF NEUROIMMUNOLOGY ELSEVIER SCIENCE BV 189 (1-2) 163 - 168 0165-5728 2007/09 [Refereed]
     
    We compared B cells and germinal centers in thymus from myasthenia gravis (MG) patients either with anti-acetylcholine receptor (AChR) autoantibodies or with neither anti-muscle-specific tyrosine kinase (MuSK) nor anti-AChR (seronegative MG: SN-MG). The numbers and frequencies of total and germinal center B cells varied in the SN-MG thymi, some of which were normal/atrophic. Others were clearly hyperplastic, their B cell parameters overlapping with those in AChR-positive MG, which implicates the thymus in pathogenesis. Indeed, some SN-MG patients apparently benefited from thymectomy, which should be considered a management option. (C) 2007 Elsevier B.V. All rights reserved.
  • Hiroyuki Shiono; Meinoshin Okumura; Noriyoshi Sawabata; Tomoki Utsumi; Masayoshi Inoue; Masato Minami; Noriyuki Tomiyama; Hikaru Matsuda; Yoshiki Sawa
    ANNALS OF THORACIC SURGERY ELSEVIER SCIENCE INC 84 (3) 995 - 1000 0003-4975 2007/09 [Refereed]
     
    Purpose. Virtual endoscopy can theoretically produce images of hollow organs from computed tomographic scanning by discriminating walls with the air space. We produced virtual images of the mediastinum (ie, virtual mediastinoscopy based on positron emission tomography and computed tomography scanning data to visualize lymph nodes and great vessels similar to cervical mediastinoscopy). Description. Virtual images from 5 patients with positive mediastinal positron emission tomography findings were produced using computer software designed for virtual endoscopy. Visualization of lymph nodes and vessels was done based on positron emission tomography-computed tomography and enhanced computed tomographic scanning data, respectively. Evaluation. Virtual mediastinoscopy clearly showed three-dimensional relationships between active nodes and surrounding structures. Great vessels, such as the innominate artery and azygos vein, which require assessment during a mediastinoscopy, were visualized in virtual movies. Further, perspective views in the craniocaudal direction based on surgeon-orientation, simulated actual views were obtained during cervical video mediastinoscopy. Conclusions. Virtual mediastinoscopy provided realistic images of the mediastinal anatomy, and has the potential to make cervical mediastinoscopy and other mediastinal explorations safer, as well as more accurate.
  • Ping He; Tetsuji Naka; Satoshi Serada; Minoru Fujimoto; Toshio Tanaka; Shoji Hashimoto; Yoshihito Shima; Tomoki Yamadori; Hidekazu Suzuki; Tomonori Hirashima; Kaoru Matsui; Hiroyuki Shiono; Meinoshin Okumura; Toshiro Nishida; Isao Tachibana; Naoko Norioka; Shigemi Norioka; Ichiro Kawase
    CANCER SCIENCE BLACKWELL PUBLISHING 98 (8) 1234 - 1240 1347-9032 2007/08 [Refereed]
     
    Autoantibodies against tumor antigens represent one type of biomarker that may be assayed in serum for detection of cancer and monitoring of disease progression. In the present study, we used a proteomics-based approach to identify novel tumor antigens in non-small cell lung cancer (NSCLC). By combining two-dimensional electrophoresis, western blotting, mass spectrometry and enzyme-linked immunosorbent assay technology, we detected autoantibodies against alpha-enolase in a subset of NSCLC patients' sera. When 'Mean ODhealthy control sera + 3 SDhealthy control sera' was used as the cut-off point, the prevalence of this autoantibody was 27.7% in patients with NSCLC (26 of 94), 1.7% in healthy control subjects (1 of 60), and not detectable in sera from 15 patients with small cell lung cancer, 18 patients with gastrointestinal cancer and nine patients with Mycobacterium avium complex infection of lung. Immunohistochemical staining showed that expression of alpha-enolase was increased in cancer tissues of NSCLC patients, and flow cytometric analysis confirmed the expression of alpha-enolase at the surface of cancer cells. The combined detection of autoantibodies against alpha-enolase, carcinoembryonic antigen and cytokeratin 19 fragment (CYFRA21-1) enhanced sensitivity for the diagnosis of NSCLC. Therefore, autoantibodies against alpha-enolase may constitute a promising biomarker for NSCLC.
  • Masayoshi Inoue; Meinoshin Okumura; Masato Minami; Hiroyuki Shiono; Noriyoshi Sawabata; Tomoki Utsumi; Yuko Ohno; Yoshiki Sawa
    General Thoracic and Cardiovascular Surgery 8 55 (8) 315 - 321 1863-6705 2007/08 [Refereed]
     
    Objective. Preoperative therapy is an optional strategy for locally advanced lung cancer, although the indication for pulmonary resection is often marginal, when considering the survival benefit and perioperative risks. The aim of the present study was to identify prognostic predictors by assessing clinical factors including prethoracotomy co-morbidity. Methods. This was a retrospective analysis of 54 patients who underwent complete resection after preoperative therapy was performed. Results. The overall 5-year survival rate was 38%. In patients without cardiopulmonary co-morbidity the 5-year survival rate was 49%, whereas it was 0% for those who had associated cardiopulmonary co-morbidity (P = 0.004). When analyzing only those who died from lung cancer, the group without cardiopulmonary co-morbidity showed a tendency for longer survival than those in the co-morbidity group (P = 0.092). The 5-year survival rate for patients-evaluated with a Charlson Co-morbidity Index (CCI)-with a CCI score of 0, was 45%, which tended to be better than that for those with a CCI score of 1-2 (P = 0.066). Furthermore, patients with a normal prethoracotomy level of carcinoembryonic antigen (CEA) had a 5-year survival rate of 44%, which was better than the 22% for patients with elevated CEA (P = 0.013). The 5-year survival rate for patients without lymph node metastasis was 52%, whereas it was 14% for those with residual node involvement (P = 0.002). Lymph node metastasis and cardiopulmonary co-morbidity were shown to be independent poor prognostic predictors by multivariate analysis. Conclusion. In addition to nodal status, preoperative cardiopulmonary co-morbidity should be noted when considering the operative indications following preoperative therapy for lung cancer patients. © 2007 The Japanese Association for Thoracic Surgery.
  • Masayoshi Inoue; Masato Minami; Hajime Ichikawa; Norihide Fukushima; Hiroyuki Shiono; Tomoki Utsumi; Meinoshin Okumura; Yoshiki Sawa
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY MOSBY-ELSEVIER 133 (6) 1680 - 1681 0022-5223 2007/06 [Refereed]
  • Javzandulam Natsag; Noriyuki Tomiyama; Atsuo Inoue; Naoki Mihara; Takeshi Johkoh; Hiromitsu Sumikawa; Osamu Honda; Hiroyuki Shiono; Meinoshin Okumura; Hironobu Nakamura
    Radiation Medicine - Medical Imaging and Radiation Oncology 5 25 (5) 202 - 210 0288-2043 2007/06 [Refereed]
     
    Purpose. Preoperative localization of the thymic veins is considered important to prevent intraoperative severe bleeding prior to video-assisted thoracoscopic thymectomy. The purpose of this study was to determine the optimal dose of contrast material for preoperative CT imaging for the detection of thymic veins on the basis of patient weight. Materials and methods. The records of 31 patients who underwent thymectomy were examined retrospectively. All patients were scanned using an eight-channel multidetector-row computed tomography (CT) scanner at 1.25 mm collimation and a 0.625-mm reconstruction interval. CT scans were obtained after injection of 300 mg I/ml nonionic contrast material at a rate of 2 ml/s. A 90-ml contrast bolus was used for the first 16 consecutive patients (group I), and a 150-ml bolus was used for the following 15 patients (group II). The scan delay was 60 s and 90 s in groups I and II respectively. Two independent radiologists who were blinded to the surgical results evaluated the number of thymic veins observed on preoperative CT, which was later correlated with the actual number of thymic veins clipped during surgery. The responses were analyzed with respect to contrast amount by single bolus and per kilogram of body weight. Results. Thymic veins were correctly detected in 9 of 16 (56%) patients in group I and 14 of 15 (93%) patients in group II. Thymic vein detection was significantly better in patients who received the ≥2.0 ml/kg contrast medim compared to those who received the 1.00-1.99 ml/kg medium (P < 0.05). Conclusion. An intravenous contrast material volume of 2 ml/kg (300 mg I/ml) is appropriate for the identification of thymic veins on prethymectomy CT. © 2007 Japan Radiological Society.
  • Tomoki Utsumi; Hiroyuki Shiono; Ichiro Fukai; Akinori Akashi
    Interactive Cardiovascular and Thoracic Surgery 3 6 (3) 411 - 412 1569-9293 2007/06 [Refereed]
     
    A 67-year-old woman underwent a thoracoscopic resection of a large anterior mediastinal cyst. Before surgery, artificial pneumomediastinum was performed with a retrosternal technique. Injection of 400 ml of air from the sternal notch caused emphysema throughout the mediastinum. In those areas, dissection of loose connective tissue was mostly accomplished by the injected air, which formed an air layer around the cyst. On the other hand, emphysema was not apparent in the areas around the left innominate and thymic veins. Artificial pneumomediastinum may be useful as a supplementary technique in a thoracoscopic surgery setting.
  • Noriyoshi Sawabata; Meinoshin Okumura; Tomoki Utsumi; Masayoshi Inoue; Hiroyuki Shiono; Masahito Minami; Toshirou Nishida; Yoshiki Sawa
    General Thoracic and Cardiovascular Surgery 5 55 (5) 189 - 192 1863-6705 2007/05 [Refereed]
     
    Objective. Reverse transcriptase-polymerase chain reaction assay results have indicated that tumor cells sometimes appear during surgery for primary non-small-cell lung cancer. In this study, we attempted to determine whether cancer cells can be detected during and after surgery using an immunocytology method. Methods. Nine patients undergoing a lobectomy for non-small-cell lung cancer were studied. The presence of circulating tumor cells was determined by the detection of magnified EpCAM antibodies. The criteria used to identify circulating tumor cells were a round-to-oval morphology with a visible nucleus (4′-6′-diamidino-2-phenylindole (DAPI)-positive), which were positive for cytokeratin and negative for CD45. Results. One patient showed evidence of circulating tumor cells at thoracotomy, and 3 patients did so after surgery. Ten days after the operation, the circulating tumor cells had disappeared in all these cases. The median follow-up period was 14 months, and there was no cancer recurrence in any of the patients. Conclusion. Using this technique, tumor cells were detected in the peripheral blood of patients before and after lobectomy procedures. It could be argued that this method can provide useful information about patients undergoing lung cancer treatment. © 2007 The Japanese Association for Thoracic Surgery.
  • Jun Maeda; Mitsunori Ohta; Masayoshi Inoue; Meinoshin Okumura; Masato Minami; Hiroyuki Shiono; Hikaru Matsuda
    SURGERY TODAY SPRINGER 37 (4) 316 - 319 0941-1291 2007/04 [Refereed]
     
    Malignant fibrous histiocytoma (MFH) of the lung is rare, accounting for less than 0.2% of all pulmonary neoplasms, and an optimal treatment strategy has not yet been elucidated. We encountered a 62-year-old male patient with MFH of the lung who underwent a resection of the lymph node of recurrence 7 months after a lobectomy. We herein review 93 cases of pulmonary MFH in the literature, and discuss the surgical treatment for this disorder with special reference to lymph node involvement. Lymphogenic metastasis was observed in 14 of 72 cases (19%) who underwent surgical treatment. The 5-year survival rates for these reported patients with and without surgical treatment were 43% and 0% (P = 0.01) and the 5-year survival rates for "resected" patients with and without lymph node metastasis were 27% and 49%, respectively (P = 0.03). A complete resection with the systematic dissection of regional lymph nodes is therefore considered to positively contribute to the survival of patients with primary pulmonary MFH.
  • TOKUNAGA Toshiteru; UTSUMI Tomoki; INOUE Masayoshi; SHIONO Hiroyuki; MINAMI Masato; OKUMURA Meinoshin
    The Journal of the Japanese Association for Chest Surgery The Japanese Association for Chest Surgery 21 (2) 174 - 177 0919-0945 2007/03 
    A 53-year-old woman with a mass in the anterior mediastinum was admitted to our hospital. Video assisted thoracic surgery was performed for extirpation and the postoperative diagnosis was bronchogenic cyst of the thymus. Such cysts are commonly located in the middle mediastinum. Herein, we report a rare case of a bronchogenic cyst of the thymus in the anterior mediastinum.
  • SHIONO Hiroyuki; OKUMURA Meinoshin; YASUMOTO Kosei
    The Journal of the Japanese Association for Chest Surgery The Japanese Association for Chest Surgery 21 (1) 17 - 22 0919-0945 2007/01 
    Currently, no specific item regarding endoscopic thymectomy for myasthenia gravis is listed in the standards of deciding medical service fees. To understand the present situation regarding the medical fee-for-service of endoscopic thymectomy, a questionnaire survey was conducted involving the institutions and members participating in the Japanese Association for the Research on the Thymus, Of 101 responding institutions, 18 institutions (18%) reported basically performing endoscopic thymectomy in all qualifying patients, while 32% of theinstitutions reported mainly performing median sternotomy, but sometimes performing endoscopic thymectomy. The methods of approaching endoscopic thymectomy varied among the institutions, but most of them included endoscopic clips or ultrasound-driven scalpels, as well as anterior chest wall lifting devices. A total of 214 patients underwent thymectomy in 2004 in the responding institutions, of which 77 patients (32%) underwent endoscopic thymectomy. Seventy-one percent of the responding institutions answered that a specific item regarding endoscopic thymectomy should be listed in the standards for deciding medical service fees.
  • Meinoshin Okumura; Hiroyuki Shiono; Masayoshi Inoue; Hisaichi Tanaka; Hyun-Eng Yoon; Katsuhiro Nakagawa; Akihide Matsumura; Mitsunori Ohta; Keiji Iuchi; Hikaru Matsuda
    JOURNAL OF SURGICAL ONCOLOGY WILEY-LISS 95 (1) 40 - 44 0022-4790 2007/01 [Refereed]
     
    Background and Objectives: The aim of this study was to clarify the significance of surgical treatment for recurrent thymic epithelial tumors with reference to the World Health Organization (WHO) histological classification system. Patients: Among 67 patients with tumor recurrence, 22 underwent a re-resection. There were 1 patient with a type AB tumor, 5 with type B1 tumors, 10 with type B2 tumors, 5 with type B3 tumors, and 1 with a carcinoma. Results: The 10-year survival rate following the initial resection was 70% in patients who underwent a re-resection and 35% in those who did not. The average intervals from the initial resection to re-resection were 10.3, 7.8, 6.0, 2.4, and 2.6 years for patients with type AB, 131, 132, 133 tumors, and carcinoma, respectively. The patient with a type AB tumor was alive at 2.4 years after re-resection, 12.7 years after the initial resection. The 5-year survival rates following re-resection in the patients with type 131, 132, and 133 tumors were 100, 56, and 60, respectively. The patient with a carcinoma died as a result of the tumor 2 years after re-resection. Conclusion: WHO histological classification indicates the outcome of surgical treatment for recurrent thymic epithelial tumors.
  • 塩野 裕之; 奥村 明之進; 内海 朝喜; 富山 憲幸; 澤 芳樹
    日本VR医学会学術大会プログラム・抄録集 日本VR医学会 2007 15 - 15 2188-3491 2007
  • 塩野 裕之; 奥村 明之進; 内海 朝喜; 小田 知文; 田村 光信; 井上 匡美; 南 正人; 林 明男; 徳永 俊照; 出口 寛; 澤 芳樹
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 21 (3) 324 - 324 2007
  • 徳永 俊照; 塩野 裕之; 林 明男; 小田 知文; 出口 寛; 田村 光信; 内海 朝喜; 井上 匡美; 南 正人; 奥村 明之進; 澤 芳樹
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 21 (3) 474 - 474 2007
  • 林 明男; 塩野 裕之; 小田 知文; 徳永 俊照; 出口 寛; 田村 光信; 内海 朝喜; 井上 匡美; 南 正人; 奥村 明之進; 澤 芳樹
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 21 (3) 476 - 476 2007
  • 内海 朝喜; 奥村 明之進; 塩野 裕之; 井上 匡美; 南 正人; 澤 芳樹
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 21 (3) 473 - 473 2007
  • 小田 知文; 徳永 俊照; 出口 寛; 林 明男; 田村 光信; 内海 朝喜; 井上 匡美; 塩野 裕之; 南 正人; 奥村 明之進; 澤 芳樹
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 21 (3) 381 - 381 2007
  • 南 正人; 田村 光信; 小田 知文; 徳永 俊照; 出口 寛; 林 明男; 内海 朝喜; 井上 匡美; 塩野 裕之; 奥村 明之進; 澤 芳樹
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 21 (3) 417 - 417 2007
  • 出口 寛; 奥村 明之進; 内海 朝喜; 井上 匡美; 塩野 裕之; 南 正人; 澤 芳樹
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 21 (3) 375 - 375 2007
  • 井上 匡美; 奥村 明之進; 南 正人; 塩野 裕之; 内海 朝喜; 田村 光信; 林 明男; 出口 寛; 徳永 俊照; 小田 知文; 澤 芳樹
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 21 (3) 364 - 364 2007
  • 太田 三徳; 井上 匡美; 塩野 裕之; 南 正人; 奥村 明之進; 松村 晃秀; 井内 敬二
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 21 (3) 378 - 378 2007
  • 南 正人; 田村 光信; 小田 知文; 徳永 俊照; 出口 寛; 林 明男; 内海 朝喜; 井上 匡美; 塩野 裕之; 奥村 明之進; 澤 芳樹
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 21 (3) 505 - 505 2007
  • 田村 光信; 塩野 裕之; 南 正人; 井上 匡美; 内海 朝喜; 小田 知史; 奥村 明之進; 中西 正芳
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 21 (3) 486 - 486 2007
  • Norihisa Shigemura; Meinoshin Okumura; Shinya Mizuno; Yukiko Imanishi; Akifumi Matsuyama; Hiroyuki Shiono; Toshikazu Nakamura; Yoshiki Sawa
    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE AMER THORACIC SOC 174 (11) 1199 - 1205 1073-449X 2006/12 [Refereed]
     
    Rationale and Objectives: Hepatocyte growth factor (HGF) is a potent regenerative factor generated after a lung injury, and HGF supplementation after surgical reduction has been shown to enhance compensatory growth in remnant lungs and improve pathophysiologic conditions in a rat model of emphysema. Adipose tissue-derived stromal cells (ASCs) produce a large amount of angiogenic factors, including HGF. After lung volume reduction surgery (LVRS), we treated rats by implanting HGF-secreting ASCs with a scaffold onto the remnant lung tissue to determine the usefulness of this technique for treating respiratory dysfunction. Methods and Main Results: Cells were isolated from rat inguinal adipose tissue and characterized by flow cytometry. ASCs were cultured on a polyglycolic acid felt sheet as a sealant material, and were shown to secrete significantly greater amounts of HGF than other angiogenic factors. Next, ASCs on polyglycolic acid felt sheets were used to cover the cut edge of the remaining lungs after LVRS for emphysema in rats. One week after implantation of the ASCs, both alveolar and vascular regeneration were significantly accelerated as compared with the rats that underwent LVRS alone. Consequently, gas exchange and exercise tolerance were also significantly restored, with these good results persisting for more than 1 mo. Conclusions: The present findings demonstrate the therapeutic potential of cell therapy using ASCs with a scaffold for selective delivery of HGF to remnant lungs, which resulted in enhancement of compensatory growth, after surgical resection. This approach may provide a new strategy for lung tissue engineering to improve LVRS outcome.
  • Okumura M; Shiono H; Inoue M; Sawa Y
    Nihon Geka Gakkai zasshi 6 107 257 - 261 0301-4894 2006/11 [Refereed]
  • N. Shigemura; H. Shiono; M. Inoue; M. Minami; M. Ohta; M. Okumura; H. Matsuda
    SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES SPRINGER 20 (10) 1614 - 1618 0930-2794 2006/10 [Refereed]
     
    Background: Because evidence-based data regarding the quality of video-assisted thoracoscopic thymectomy for the treatment of myasthenia gravis are lacking, a prospective trial comparing three different operative approaches was conducted to evaluate their efficacy. Methods: This prospective study enrolled 20 consecutive patients with nonthymomatous myasthenia gravis. A series of three approaches for bilateral video-assisted thoracoscopic extended thymectomy (VATET) using the anterior chest wall-lifting method (original), the original method with a flexed-neck position (modified), and the original method with a transcervical approach (final) were prospectively performed in each patient for quantitative and pathologic evaluation of the residual thymus after each approach. Results: Complete VATET required 242 +/- 48 min, with the transcervical procedure requiring 23 +/- 12 min. After the modified method, the residual thymus in the cervical region was 1.5 cm in size and weighed 0.8 g (0.8% of the entire thymus), as compared with a size of 2.2 cm and a weight of 1.3 g (3.2%) after the original method. Each value is the result of comparison with the final method. Histopathologic studies showed residual tissue in the germinal center as well as Hassall's corpuscles in more than 70% of cases. Conclusion: The findings show that VATET without the transcervical approach could be an immunologically incomplete treatment for myasthenia gravis. Therefore, the transcervical approach should be included in VATET procedures to ensure radicality.
  • Norihisa Shigemura; Akinori Akashi; Soichiro Funaki; Tomoyuki Nakagiri; Masayoshi Inoue; Noriyoshi Sawabata; Hiroyuki Shiono; Masato Minami; Yukiyasu Takeuchi; Meinoshin Okumura; Yoshiki Sawa
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY MOSBY, INC 132 (3) 507 - 512 0022-5223 2006/09 [Refereed]
     
    Background: Although video-assisted thoracic surgery (VATS) has been in use for more than a decade, its application to major lung resection for lung cancer is still not widely practiced. The success of a cancer operation is judged by the long-term survival of the treated patients. Therefore, the goal of the present study was to evaluate long-term outcomes associated with various video-assisted lobectomy techniques and conventional surgery in patients with peripheral non-small cell lung cancer less than or equal to 2 cm in diameter (stage IA). Methods: A multi-institutional, retrospective review was performed in 145 consecutive patients. Patients with clinical stage IA disease, with tumor size less than or equal to 2 cm in diameter, from three institutions underwent a complete VATS (c-VATS, n = 56), an assisted VATS (a-VATS, n = 34), or a conventional open (open, n = 55) approach for pulmonary lobectomy and lymph node dissection. Results: Patients undergoing lobectomy and lymph node dissection with c-VATS had less blood loss, faster recovery, shorter hospitalization, and longer operating times than did patients undergoing the lobectomy with the a-VATS and open approaches. At a mean follow-up of 38.8 months, Kaplan-Meier probabilities of survival at 5 years were as follows: c-VATS, 96.7%; a-VATS, 95.2%; open, 97.2%. There was no significant difference in the rate of recurrence among the 3 different procedures. Conclusion: VATS lobectomy, a safe procedure with earlier return to normal activities, can be regarded as an acceptable cancer operation for the patients with peripheral non-small cell lung cancer less than or equal to 2 cm in diameter (clinical stage IA) with the same long-term survivals as open surgery.
  • H. Shiono; A. Inoue; N. Tomiyama; N. Shigemura; K. Ideguchi; M. Inoue; M. Minami; M. Okumura
    SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES SPRINGER 20 (9) 1419 - 1422 0930-2794 2006/09 [Refereed]
     
    Background: Video-assisted thoracoscopic (VATS) thymectomy has been applied as a surgical option for autoimmune myasthema gravis. Prior identification and fine division of the thymic veins are critical to the prevention of unexpected severe bleeding that may require conversion to open surgery. Until recently, such bleeding could be avoided only by meticulous dissection of thymic fat tissue away from the left brachiocephalic vein (LBV). With recent advances in computed tomography (CT), multidetector-row computed tomography (MDCT) can readily be obtained and provides three-dimensional (3D) images. This study explored its value for preoperative identification of the thymic veins drainina into the LBV, and thus for prevention of injury to these veins during endoscopic thymectomy. Methods: Five patients with myasthenia gravis, thymoma, or both underwent enhanced MDCT preoperatively. The thymic veins draining into the LBV were visualized using both horizontal and sagittal/coronal CT images. Then 3D images were reconstructed to enable operators to simulate endoscopic views. During each VATS extended thymectomy, the numbers and branching patterns of the thymic veins were compared with the preoperative MDCT images. Results: The thymic veins draining into the LBV were clearly identified with MDCT in all five patients examined. Reconstructed 3D images clearly located their courses in the thymic/fat tissue and their entry routes into the LBV. thus simulating the actual intraoperative endoscopic views. All tributaries divided during surgery were identified preoperatively with MDCT. Conclusions: Location of thymic veins with MDCT can provide precise preoperative information about thymic venous anatomy. This easy and less invasive examination has the potential to make VATS thymectomy easier and safer.
  • J Maeda; M Inoue; M Okumura; M Ohta; M Minami; H Shiono; Y Shintani; H Matsuda; N Matsuura
    LUNG CANCER ELSEVIER IRELAND LTD 52 (2) 235 - 240 0169-5002 2006/05 [Refereed]
     
    We evaluated the usefulness of a real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) method for detecting occult tumor cells in histologically malignant-negative lymph nodes resected from patients with non-small cell tung cancer. First, we examined the relationship between tumor cell number and carcinoembryonic antigen (CEA) mRNA copy number using a PCR method with a cancer cell tine (A549) in a serial dilution study. Next, we evaluated the relationship between nodal metastatic area size and CEA mRNA copy number using lymph nodes with histologically proven metastasis in a serial slice study. On the basis of those results, we performed RT-PCR analyses with 28 primary tumors and 211 lymph nodes from 28 patients who underwent a lobectomy with systematic node dissection. Our results in the serial dilution study showed that the detectable [imitation by quantitative RT-PCR was 25-100 neoplastic cells and 20-100 CEA mRNA copy numbers. In the serial slice study, we found a correlation between CEA mRNA copy number and nodal metastatic area. In the clinical samples, amplification of CEA mRNA was obtained with all 28 primary tumors and 13 of the lymph nodes with metastasis shown by hematoxylin-eosin staining. Furthermore, 52 (25%) of 211 histologically negative lymph nodes and the specimens from 14 (64%) of the 22 pN0 patients revealed a significant level. of CEA mRNA. These results indicate that micrometastases, which are not detectable with conventional examinations, can be detected by the present method of RT-PCR for CEA mRNA in a proportion of patients with resected pN0 non-small cell lung cancer. (C) 2006 Elsevier Ireland Ltd. All rights reserved.
  • M Inoue; M Minami; H Shiono; N Sawabata; K Ideguchi; M Okumura
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY MOSBY, INC 131 (5) 988 - 993 0022-5223 2006/05 [Refereed]
     
    Objective: The number of surgical interventions for small-sized lung cancer has increased with the development of computed tomography. We attempted to identify clinicopathologic characteristics of peripheral, small-sized, non-small cell lung cancer to show the limitation of partial resection or segmentectomy. Methods: A retrospective analysis of 143 patients who underwent a complete resection for a peripheral non-small cell lung cancer of 2 cm or less in diameter was performed. The relationships between nodal involvement and other clinical factors were also assessed in patients who underwent a lobectomy plus node dissection. Results: The overall 5-year survival rate was 88.1%. The 5-year survival rate was 100% for patients with a tumor of 1.5 cm or less. Survival for patients with adenocarcinoma histology was significantly better than for those with nonadenocarcinoma histology (P=.03). The 5-year survival rate for patients without lymph node metastases was 91.6%, whereas it was 62.5% for those with nodal involvement (P<.01). Increase of prethoracotomy serum carcinoembryonic antigen level was an independent predictor of a poor prognosis. Lymph node metastasis was significantly increased in those with pleural invasion by the primary lesion and increased serum carcinoembryonic antigen level. Fourteen (16.9%) of 83 patients with a tumor diameter of larger than 1.5 cm had nodal metastasis. Conclusions: Nodal involvement should be considered in patients with non-small cell lung cancer of 2 cm or less in diameter who show pleural invasion or an increased carcinoembryonic antigen level. A lobectomy with node dissection is recommended for patients with a tumor larger than 1.5 cm, suspected pleural invasion, or prethoracotomy carcinoembryonic antigen level increase.
  • M Inoue; M Minami; H Shiono; S Miyoshi; S Takeda; M Ohta; M Goto; H Takano; Y Sawa; M Okumura
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY MOSBY, INC 131 (3) 755 - 756 0022-5223 2006/03 [Refereed]
  • Teruo Iwasaki; Katsuhiro Nakagawa; Motoaki Yasukawa; Hiroyuki Shiono; Teruaki Nagano; Kunimitsu Kawahara
    Japanese Journal of Thoracic and Cardiovascular Surgery 1 54 (1) 35 - 39 1344-4964 2006/01 [Refereed]
     
    Ectopic cervical or cervico-mediastinal thymomas are very rare and most of them are asymptomatic, except for the presence of a cervical mass. We present the case of a 71-year-old man with an ectopic cervico-mediastinal thymoma threatening superior vena cava syndrome. He had a slight headache and presented with venous dilatation on the chest wall. A computed tomographic scan and magnetic resonance imaging of the chest demonstrated a mass extending from the right neck to the hilum, that indented the trachea and compressed and displaced the brachiocephalic veins anteriorly. Under a right hemicollar incision and median sternotomy, the mass was resected en bloc together with the thymus. The resected specimen was an encapsulated mass measuring 11×7×4 cm. The pathological diagnosis was type AB, non-invasive thymoma, confirmed by 3-color flow cytometry of tumor-derived lymphocytes. Flow cytometry using biopsy material may contribute to the preoperative diagnosis of ectopic thymoma.
  • 出口寛; 塩野 裕之; 富山 憲幸; 濱田 星紀; 岩本 康男; 工藤 正幸; 内海 朝喜; 井上 匡美; 南 正人; 奥村 明之進; 澤 芳樹
    日本VR医学会学術大会プログラム・抄録集 日本VR医学会 2006 24 - 24 2188-3491 2006
  • 内海 朝喜; 明石 章則; 舟木 壮一郎; 深井 一郎; 塩野 裕之
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 20 (3) 780 - 780 2006
  • 太田 三徳; 奥田 倫久; 北原 直人; 池田 直樹; 田中 寿一; 松村 晃秀; 井内 敬二; 前田 元; 井上 匡美; 塩野 裕之; 南 正人; 奥村 明之進; 澤 芳樹
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 20 (3) 799 - 799 2006
  • 前田 純; 奥村 明之進; 南 正人; 塩野 裕之; 井上 匡美; 内海 朝喜; 大倉 英司; 林 明男; 出口 寛; 後藤 正志; 澤 芳樹
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 20 (3) 814 - 814 2006
  • N Sawabata; M Inoue; H Shiono; M Monami; M Okumura
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY MOSBY, INC 130 (5) 1479 - 1480 0022-5223 2005/11 [Refereed]
  • K Inada; M Okumura; H Shiono; M Inoue; Y Kadota; M Ohta; H Matsuda
    JOURNAL OF SURGICAL RESEARCH ACADEMIC PRESS INC ELSEVIER SCIENCE 126 (1) 34 - 40 0022-4804 2005/06 [Refereed]
     
    Background. A human thymoma is a thymic epithelial neoplasm and is characterized by its frequent association with myasthenia gravis. The histological characteristic of thymoma is coexistence of a large number of lymphocytes, including CD4(+)CD8(+) double positive T cells, phenotypes of the cortical thymocytes. To elucidate the role of these T lymphocytes in the pathogenesis of thymoma-associated myasthenia gravis, we examined the usage of alpha beta gamma delta T cell receptor of the T lymphocytes in thymoma in conjunction with the positive selection event. Materials and Methods. Thymomas were obtained from 28 patients. Nine patients were associated with myasthenia gravis. Lymphocytes were freshly isolated from the tumor tissue and were subjected to four-color flow cytometric analysis. Results. The average proportion of TCR alpha beta(+) cells in thymomas associated with myasthenia gravis was 47.0% and was significantly higher (P = 0.0008) than that without myasthenia gravis (23.4%). Positive selection event was then examined in terms of CD69, a positive selection marker. The mean proportion of TCR alpha beta(+)CD69(+)CD4(+)CD8(-) cells in the myasthenic thymomas (8.22%) was significantly greater (P = 0.015) than the nonmyasthenic thymomas (2.99%). On the other hand, there was not a significant difference in the mean proportion of TCR alpha beta(+)CD69(+)CD4(-)CD8(+) cells between the myasthenic and the nonmyasthenic thymomas. Conclusions. The possible role of development of TCR alpha beta(+) T cells, especially the role of positive selection of TCR alpha beta(+)CD4(+)CD8(-) T cells in thymoma, was suggested in the pathogenesis of thymoma-associated myasthenia gravis. (C) 2005 Elsevier Inc. All rights reserved.
  • Y Okumura; S Takeda; H Asada; M Inoue; N Sawabata; H Shiono; H Maeda
    ANNALS OF THORACIC SURGERY ELSEVIER SCIENCE INC 79 (6) 1857 - 1861 0003-4975 2005/06 [Refereed]
     
    Background. Successful treatment of chronic empyema remains a challenge for thoracic surgeons. Herein, we report our 17 years of experience with the omental peclicled flap procedure for management of chronic empyema secondary to pulmonary tuberculosis. Methods. We retrospectively reviewed the surgical results of 23 patients who underwent surgical treatment for chronic empyema using an omental pedicled flap from 1987 to 2003. Results. The subjects were 20 men and 3 women (mean age, 58.1 years) with average % vital capacity (VC) and forced expiratory volume in 1 second (FEV1) values of 48.1% and 1.19 L, respectively. Sixteen patients (69.6%) had bronchopleural fistulas and 21 (91.3%) were associated with infection by causative organisms (6 Aspergillus organisms, 4 methicillin-resistant Staphylococcus aureus, 10 others). An open window thoracostomy preceded in 17 patients (72.9%). Eleven patients were treated using an omental peclicled flap with or without a muscle flap, and 12 were treated using an omental pedicled flap with a partial thoracoplasty. There was 1 operation-related death, and clinical success was achieved in 19 patients (82.6%), in whom pulmonary function did not decrease significantly. During long-term follow-up, 5 patients died of respiratory failure, and their mean postoperative %VC and FEV1 values were 30.1% and 0.76 L, respectively. Conclusions. We concluded that the use of an omental pedicled flap for chronic empyema was effective even in cases with active infection, and did not compromise pulmonary function. Further, an additional thoracoplasty may completely obliterate the dead space, although indications should be referenced to preoperative pulmonary function. (c) 2005 by The Society of Thoracic Surgeons.
  • Y Funakoshi; H Shiono; M Inoue; Y Kadota; M Ohta; H Matsuda; M Okumura; T Eimoto
    JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY SPRINGER 131 (5) 314 - 322 0171-5216 2005/05 [Refereed]
     
    Purpose: Glucocorticoids exert anti-proliferative effects in various cell types and have long been known to induce apoptosis in thymocytes. Although a few reports have described the regression of human thymoma with glucocorticoid therapy, its effects on neoplastic thymic epithelial cells (TECs) have not been reported. In the present study, we investigated glucocorticoid receptor (GR) expression on neoplastic TECs and the effects of glucocorticoids in vitro on the cell cycle progression of tumor cells. Patients and methods: Thymoma specimens were obtained during surgery from 21 patients. Three of the specimens with glucocorticoid therapy were examined using the TdT-mediated dUTP-biotin nick-end labeling method. Primary tumor specimens from ten untreated thymomas were examined for GR expression by immunohistochemistry. Isolated neoplastic TECs from the remaining eight untreated thymomas were examined using immunohistochemistry, flow cytometric and cell cycle analysis. Results: GR are expressed on neoplastic TECs as well as on non-neoplastic thymocytes in thymomas, regardless of WHO histological classification. Glucocorticoids caused an accumulation of TEC in G0/G1 phase in all cases examined (n = 6), and also induced apoptosis in the three with the lowest levels of Bcl-2 expression. Conclusions: Our results indicate that neoplastic TECs express GR and that glucocorticoids directly suppress their in vitro proliferation.
  • M Ohta; H Hirabayasi; H Shiono; M Minami; H Maeda; H Takano; S Miyoshi; H Matsuda
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY MOSBY, INC 129 (4) 804 - 808 0022-5223 2005/04 [Refereed]
     
    Objective: The purpose of this study was to evaluate the results of a combined resection of the thoracic aorta and primary lung cancer. Methods: Sixteen patients underwent thoracic aorta resection along with a left pneumonectomy (n = 6), left upper lobectomy (n = 9), or partial lung resection (n = 1), of whom 10 also received preoperative induction therapy. Cardiopulmonary bypass was used in 10 patients, and a passive shunt between the ascending aorta and the descending aorta was used in 4 patients. Results: Six postoperative major complications occurred in 5 patients, including postoperative bleeding (n = 3), intraoperative bleeding (n = 1), chylothorax (n = I), and respiratory failure (n = 1). The postoperative morbidity rate was 31%, and the mortality rate was 12.5% (2/16). Furthermore, 4 patients died of systemic tumor relapse, and 1 patient died of intrapleural recurrence. Nine patients were alive after a median follow-up of 54 months (range, 12-199 months). The median survival time of patients with postoperative pathologic NO disease was 31 months, whereas it was 10 months for those with pathologic N2 or N3 disease. Five-year survivals were 70% for patients with NO disease and 16.7% for patients with N2 or N3 disease (P = .0070). Conclusions: Although pulmonary resection with the involved aorta might cause high surgical morbidity and mortality rates, encouraging long-term survivals were obtained in patients without mediastinal nodal involvement.
  • Y Shintani; M Ohta; M Minami; H Shiono; H Hirabayashi; M Inoue; G Matsumiya; H Matsuda
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY MOSBY, INC 129 (4) 809 - 812 0022-5223 2005/04 [Refereed]
     
    Objective: We sought to investigate the correlation between type of vascular reconstruction and long-term graft patency after replacement of brachiocephalic veins combined with resection of mediastinal malignancies. Methods: Eighteen patients underwent surgical resection of tumors and the superior vena cava with concomitant vascular reconstruction using ringed polytetrafluoroethylene grafts. Graft patency was verified by means of venography or contrast-enhanced computed tomography at time points ranging from 3 to 77 months (median, 33 months) postoperatively. Results: Seven patients underwent sole reconstruction of the right brachiocephalic vein, with occlusion observed in only 1 patient. In 6 patients who underwent reconstruction of the bilateral brachiocephalic veins with 2 separate grafts, the grafts remained patent in 2, whereas 4 patients experienced occlusion of one of the two grafts yet remained asymptomatic. Both patients who underwent reconstruction with a Y graft experienced left brachiocephalic vein graft occlusion. In the 3 patients who underwent reconstruction of a left brachiocephalic vein, the graft became occluded, and superior versa cava syndrome developed in 2 of these patients. Conclusion: When replacing the superior vena cava, reconstruction of a left brachiocephalic vein alone results in a significant rate of occlusion and development of superior vena cava syndrome. Thus we advocate sole right brachiocephalic vein reconstruction or bilateral brachiocephalic vein reconstruction in this setting, and separate reconstruction of the veins is preferable to use of a Y graft.
  • 塩野 裕之; 奥村 明之進; 太田 三徳; 松村 晃秀; 多田 弘人; 前田 元; 中川 勝裕; 尹 亨彦; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 19 (3) 318 - 318 2005
  • 太田 三徳; 松村 晃秀; 井内 敬二; 前田 元; 塩野 裕之; 南 正人; 奥村 明之進; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 19 (3) 309 - 309 2005
  • 井上 匡美; 奥村 明之進; 南 正人; 塩野 裕之; 平林 弘久; 中根 茂; 狭間 研至; 大倉 英司; 船越 康信; 重村 周文; 前田 純; 麻田 博輝; 林 明男; 出口 寛; 後藤 正志; 太田 三徳; 武田 伸一; 三好 新一郎; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 19 (3) 407 - 407 2005
  • 出口 寛; 塩野 裕之; 中根 茂; 後藤 正志; 井上 匡美; 南 正人; 奥村 明之進; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 19 (3) 385 - 385 2005
  • 奥村 明之進; 林 明男; 麻田 博輝; 船越 康信; 井上 匡美; 塩野 裕之; 南 正人; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 19 (3) 374 - 374 2005
  • M Ohta; H Hirabayasi; H Shiono; M Minami; H Maeda; N Sawabata; G Matsumiya; S Miyoshi; H Matsuda
    THORACIC AND CARDIOVASCULAR SURGEON GEORG THIEME VERLAG KG 52 (4) 200 - 205 0171-6425 2004/08 [Refereed]
     
    Background: The hemi-clamshell approach provides a wide anterior view of the mediastinum, apical dome, and cervicothoracic area. However, only a few reports have been made regarding this technique. Methods: The hemi-clamshell approach was used in 24 patients, of whom 5 had a Pancoast tumor, 15 had mediastinal involvement, and 4 underwent mediastinal lymphadenopathy for left-sided lung cancer. Twenty-one of the patients received preoperative therapy. Results: Twenty-one operations were complete resections. In addition, 12 patients received cardio-vascular reconstruction and 5 a first rib resection. Postoperative major morbidity was 21% (6/24) and mortality was 4.2% (1/24). Nine patients died of systemic tumor relapse and 14 patients were alive after a median follow-up of 24 months (range 3 - 68 months) following the initial therapy. The 5-year survival rate of patients with mediastinal involvement was 37% and that of 13 patients with postoperative stage I or II was 35%. Conclusions: The hemi-clamshell approach provides a wide exposure allowing a safe and complete removal of lung cancer that involves the mediastinum and apical thoracic dome, leading to a better long-term survival rate for patients with this disease.
  • FUKUHARA Kenjiro; NAKAGAWA Katsuhiro; SHIONO Hiroyuki; KADOTA Yoshihisa; IDEGUCHI Kan; YASUMITSU Tsutomu
    The Journal of the Japanese Association for Chest Surgery The Japanese Association for Chest Surgery 18 (2) 88 - 92 0919-0945 2004/03 
    A retrospective study was performed to evaluate patterns of recurrence and prognosis in resected non-small cell lung cancer cases with ipsilateral intrapulmonary metastasis (pm (+) lung cancer (n=89; pml (metastasized in the same lobe with primary); 65, pm2 (metastasized in the different lobe from primary); 24)). The 3-year and 5-year survival rates of patients with pml and pm2 were 28.9%, 14.2% and 26.6%, 21.3%, respectively (N. S.).
    When we divide pm (+) lung cancer patients into two groups group (1); patients who survived more than 3 years (n=22); group (2); patients who survived less than 3 years (n=67), significant differences were recognized between the groups in CEA value (p=0.002) and p-n factor (p=0.007). Multivariate analyses also showed that both factors were significant prognostic factors. The 5-year survival rate of pm (+) lung cancer patients with normal CEA level and p-n0 disease was 50.7%, which was nearly equal to stage I B (53.3%) and II A (47.1%) patients and significantly higher than III B (9.4%) patients.
    No significant difference in survival rates according to operative method was observed in pm (+) lung cancer patients. Postoperative distant metastases were detected in 53 of 89 (59.6%) pm (+) lung cancer patients, and 56.6% of these were intrapulmonary metastases (only 13.3% of which were ipsilateral).
    These results suggest that pneumonectomy is not useful to prevent recurrence in pm (+) lung cancer patients and the staging system should be revised to consider CEA level and p-n factor because of good prognosis in pm (+) lung cancer patients with normal CEA level and p-n0 disease.
  • H Shiono; M Ohta; H Hirabayashi; M Minami; J Maeda; N Shigemura; G Matsumiya; H Matsuda
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY MOSBY, INC 127 (2) 586 - 587 0022-5223 2004/02 [Refereed]
  • 奥村 奥村明之進; 井上 匡美; 田中 壽一; 塩野 裕之; 太田 三徳; 松村 晃秀; 井内 敬二; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 18 (3) 287 - 287 2004
  • 塩野 裕之; Nick Willcox; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 18 (3) 289 - 289 2004
  • 重村 周文; 太田 三徳; 井上 匡美; 塩野 裕之; 南 正人; 澤 芳樹; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 18 (3) 289 - 289 2004
  • 大倉 英司; 太田 三徳; 南 正人; 塩野 裕之; 平林 弘久; 井上 匡美; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 18 (3) 488 - 488 2004
  • M Okumura; M Ohta; Y Takeuchi; H Shiono; M Inoue; K Fukuhara; Y Kadota; S Miyoshi; Y Fujii; H Matsuda
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY MOSBY, INC 126 (6) 1922 - 1928 0022-5223 2003/12 [Refereed]
     
    Background and Purpose: Thymectomy is generally accepted as the major option of treatment for myasthenia gravis. To elucidate the biological role of thymectomy in the treatment of myasthenia gravis, the immunologic characteristics of the thymus was studied in association with the postoperative kinetics of the anti-acetylcholine receptor antibody titer. Materials and Methods: Thirty-four patients with nonthymomatous myasthenia gravis who had positive anti-acetylcholine receptor antibody titer and undergoing extended thymectomy were subjected to the study. Reduction of anti-acetylcholine receptor antibody titer was evaluated in terms of the proportion of anti-acetylcholine receptor antibody titer at 1 year after thymectomy to that before the operation. The numbers of B lymphocytes (CD19(+) cells) and the germinal center B lymphocytes (CD19(+)CD38(high) cells) present in 1 g of the thymic tissue were calculated by flow cytometry. Results: The proportion of anti-acetylcholine receptor antibody titer at 1 year after thymectomy ranged from 27.5% to 150%. The numbers of B lymphocytes and the germinal center B lymphocytes in 1 g of the thymic tissue ranged from 0.19x10(6)/g to 162.8x10(6)/g and from 0.09x10(6)/g to 33.4x10(6)/g, respectively. The proportion of anti-acetylcholine receptor antibody titer at 1 year after thymectomy had a significant inverted correlation with the number of B lymphocytes (P=.002) as well as that of the germinal center B lymphocytes (P=.007). Conclusion: Effectiveness of thymectomy was dependent on predominance of B lymphocytes and the germinal center B lymphocytes in the thymus, suggesting that one of the biological roles of thymectomy in the treatment of myasthenia gravis is removing the thymus-associated germinal centers.
  • H Shiono; YL Wong; Matthews, I; JL Liu; W Zhang; G Sims; A Meager; D Beeson; A Vincent; N Willcox
    INTERNATIONAL IMMUNOLOGY OXFORD UNIV PRESS 15 (8) 903 - 913 0953-8178 2003/08 [Refereed]
     
    Myasthenia gravis (MG) is mediated by autoantibodies to the acetylcholine receptor (AChR), expressed in muscle and rare thymic myoid cells. Most early-onset cases show thymic lymph node-type infiltrates, including pre-activated plasma cells spontaneously producing anti-AChR antibodies. Since these are not evident in the associated thymomas found in another 10% of MG patients, AChR-specific B cells must be autosensitized elsewhere. Unexpectedly, at diagnosis, >70% of MG/thymoma patients also have high-titer neutralizing autoantibodies to IFN-alpha, and >50% to IL-12; moreover, titers increase strikingly if the thymomas recur, indicating a closer tumor relationship than for anti-AChR. To investigate this, we have measured autoantibody production by cells cultured from thymomas, any available thymic remnants and blood, with or without the B cell stimulant pokeweed mitogen (PWM). To check autoantibody specificity and clonal origins, we isolated Fabs from two combinatorial libraries from producer thymus/thymoma cells. Surprisingly, thymoma cells spontaneously produced antibodies to IFN-alpha and/or IL-12 in >40% of seropositive cases, showing typical plasma cell behavior, whereas they produced anti-AChR only after PWM stimulation. We isolated 15 combinatorial Fabs to IFN-alpha (versus only one to AChR). Their strong binding in radio-immunoprecipitation and Western blots implies high affinities. The four Fabs tested neutralized anti-viral actions of IFN-alpha. The diverse V genes clearly showed ongoing antigen-driven selection. These results imply pre-activation in situ by native IFN-alpha/IL-12 expressed within a 'dangerous' tumor microenvironment. With these molecules, it should be easier to identify provoking cell type(s) that may give novel additional clues to autoimmunization against T-cell epitopes from the more complex AChR.
  • K Nakagawa; T Yasumitu; K Fukuhara; H Shiono; M Kikui
    ANNALS OF THORACIC SURGERY ELSEVIER SCIENCE INC 75 (6) 1740 - 1744 0003-4975 2003/06 [Refereed]
     
    Background. We evaluated the prognosis of adenosquamous carcinoma of the lung after lung resection in comparison with other types of carcinoma. Methods. We retrospectively reviewed charts of patients who underwent lung resection for lung cancer. Results. Surgical outcomes for 30 patients with adenosquamous carcinoma of the lung, who were treated between 1976 and 1998, were compared with the surgical results for 1,219 patients similarly treated for adenocarcinoma or squamous cell carcinoma during the same period. Adenosquamous carcinoma comprised only 2.1% of 1,408 lung cancer cases treated by resection. The overall cumulative 5-year survival rate was only 6.2% for the patients with adenosquamous carcinoma, indicating a significantly poorer prognosis than for adenocarcinoma or squamous cell carcinoma. Conclusions. The cumulative survival rate for patients with adenosquamous carcinoma in pathologic stages IA to IIB was similar to that of patients with stage IIIA adenocarcinoma or squamous cell carcinoma. (Ann Thorac Surg 2003;75:1740-4) (C) 2003 by The Society of Thoracic Surgeons.
  • 重村 周文; 明石 章則; 太田 三徳; 前田 純; 平林 弘久; 塩野 裕之; 南 正人; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 17 (3) 366 - 366 2003
  • 武田 伸一; 太田 三徳; 南 正人; 塩野 裕之; 平林 弘久; 奥村 明之新; 前田 元; 三好 新一郎; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 17 (3) 256 - 256 2003
  • 塩野 裕之; 太田 三徳; 南 正人; 平林 弘久; 前田 純; 重村 周文; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 17 (3) 271 - 271 2003
  • 奥村 明之進; 関 哲男; 塩野 裕之; 大田 三徳; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 17 (3) 302 - 302 2003
  • 平林 弘久; 太田 三徳; 塩野 裕之; 南 正人; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 17 (3) 321 - 321 2003
  • FUKUHARA Kenjiro; NAKAGAWA Katsuhiro; FUJIWARA Kiyohiro; SHIONO Hiroyuki; IDEGUCHI Kan; YASUMITSU Tsutomu
    The Journal of the Japanese Association for Chest Surgery The Japanese Association for Chest Surgery 16 (5) 609 - 614 0919-0945 2002/07 
    A retrospective review was performed to evaluate the extent of mediastinal node metastasis and prognosis in resected non-small cell lung cancer patients showing metastasis only to ND2 region (n1 (-) n2 (+) patients) (n=80). Patients with single-station metastases had a significantly better survival rate than those with more than three station metastases. And there was no significant difference between cases with single-station metastases and n1 cases. This finding suggests that single mediastinal station metastases may be metastases to the sentinel lymph node. When we divided n1 (-) n2 (+) patients into two groups (group (1): cases whose primary tumor was located in the upper or middle lobe and LN metastases were seen at upper mediastinum only and cases whose primary tumor was located in the lower lobe and LN metastases were seen at lower mediastinum only; group (2): cases whose primary tumor was located in the upper or middle lobe and LN metastases were seen at lower mediastinum only and cases whose primary tumor was located in the lower lobe and LN metastases were seen at upper mediastinum only.), group (2) had a significantly worse survival rate. Group (2) cases are a high risk group for limited mediastinal lymphadenectomy.
  • K Fukuhara; M Okumura; H Shiono; M Inoue; Y Kadota; S Miyoshi; H Matsuda
    HUMAN IMMUNOLOGY ELSEVIER SCIENCE INC 63 (5) 394 - 404 0198-8859 2002/05 [Refereed]
     
    CD45 molecules arc known to appear as various isoforms generated by alternative splicing of variable exons 4, 5, and 6, but the detailed profile of CD45 isoform expression during thymocyte development has not been revealed. We examined the CD45 isoforms expressed in the various human thymocytes' subsets defined by CD3, CD4, and CD8 expressions using RT-PCR and 4-color flow cytometry. RT-PCR study revealed that RABC, RAB, RBC, RB, and RO isoforms were expressed in thymocytes while any of RAC, RA, or RC isoforms were not detected. RABC, RAB and RBC isoforms were expressed at CD3(-)CD4(-)CD8(-) and CD3(+)CD4(+)CD8(-) stages, but were barely detectable at CD(3-)CD4(+)CD8(+) stage. RB isoform was consistently expressed at a relatively high level at all stages. RO isoform was expressed at a low level at CD3(-)CD4(-)CD8(-) and CD3(-)CD4(+)CD3(+) stages but upregulated at CD3(+)CD4(+)CD8(+) and CD3(+) CD4(+)CD8(-) stages. In combination with the results obtained by 4-color flow cytometric study, CD45 isoform expression on human thymocytes were determined to be RABC(+) RAB(+/-)RBC(+)RB(+)RO(+/-) at CD3(-)CD4(-)CD8(-) stage, RABC(-)RAB(-)RBC(-)RB(+)RO(+) at CD3(-)CD4(+)CD8(-) and CD3(-)CD4(+)CD8(+) stages, RABC(+/-)RAB(+)RBC(+) RB++RO++ at CD3(+)CD4(+)CD8(+) stage, and RABC(+)RAB(+)RBC(+)RB(+) RO+ at CD3(+)CD4(+)CD8(-) stage. Bcl-2 expression was upregulated between CD3(-)CD4(+)CD8(+)CD45RO(+) and CD3(+)CD4(+)CD8(+)CD45RO(+) stages. Expression of CD45RO epitope was upregulated between CM_Cf)4+CD8+CD69_ and CD3 CD4+ CD8(+)CD69(+)- stages while CD45RA epirope expression was unchanged. Thus, when thymocytes are positively selected, CD45RO isoform expression seems to be upreguated while CD45RABC isoform expression stays at a very low level. In Summary, various isoforms of CD45 were shown to be rightly regulated during thymocyte development and through the selection process.
  • M Okumura; Y Fujii; S Miyoshi; H Shiono; M Inoue; Y Kadota; K Fukuhara; H Matsuda
    JOURNAL OF SURGICAL RESEARCH ACADEMIC PRESS INC ELSEVIER SCIENCE 101 (2) 130 - 137 0022-4804 2001/12 [Refereed]
     
    Background. Anterior mediastinal masses derive from a variety of diseases. Thymomas have been shown to commonly hold CD4(+)CD8(+) double-positive (DP) lymphocytes, and identification of this subset by two-color flow cytometric study was suggested to help diagnosis of thymoma. Several other thymic diseases, however, possibly hold CD4(+)CD8(+) DP lymphocytes. In this study, we utilized the three-color flow cytometric method for further examination of the phenotypes of lymphocytes in the thymic diseases. Materials and methods. One hundred eight specimens (77 primary and 10 metastatic thymomas, 10 thymic carcinomas, 2 thymic carcinoids, 4 malignant lymphomas, 2 seminomas, an inflammatory pseudotumor, and 2 nonneoplastic thymic hyperplasias) were subjected to the study. The expressions of CD3, CD4, and CD8 on tumor-associated lymphocytes were evaluated by three-color flow cytometric study. Results. The proportion of the CD4(+)CD8(+) DP subset was more than 30% in all 78 lymphocyte-rich thymomas, in 2 malignant lymphomas, and in both thymic hyperplasias. CD3 expression of the CD4(+)CD8(+) DP subset ranged from a negative to a high level in thymomas and thymic hyperplasias, while it was restricted to a particular level in CD4(+)CD8(+) DP-type malignant lymphomas. The proportion of CD3(+) cells in the CD4(+)CD8(-) single-positive subset was consistently less than 90% in the lymphocyte-rich thymomas, while it was more than 90%. in the thymic hyperplasias. Conclusion. Although identification of the CD4(+)CD8(+) DP subset in the tumor-associated lymphocytes does not necessarily indicate thymoma, a further characterization of thymic neoplasms possessing the CD4(+)CD8(+) DP subset was enabled by three-color flow cytometric study, suggesting the utility of this method as an ancillary tool for differential diagnosis of these diseases. (C) 2001 Elsevier Science.
  • M Okumura; S Miyoshi; Y Fujii; Y Takeuchi; H Shiono; M Inoue; K Fukuhara; Y Kadota; H Tateyama; T Eimoto; H Matsuda
    AMERICAN JOURNAL OF SURGICAL PATHOLOGY LIPPINCOTT WILLIAMS & WILKINS 25 (1) 103 - 110 0147-5185 2001/01 [Refereed]
     
    We examined the clinical and functional significance of histologic classification of thymic epithelial neoplasms proposed by the World Health Organization (WHO), based on an analysis of 146 consecutive tumors derived from 141 patients and 47 normal thymuses derived from children ranging in age from 1 to 9 years. Invasive tumors were seen in 12.5%, 38.6%, 40.0%, 69.4%, 80.0%, and 100% of type A, AB, B1, B2, B3, and C primary tumors, respectively. All of six recurrent or metastatic lesions were type B2 tumors. Myasthenia gravis was associated in 0%, 6.8%, 40.0%, 55.6%, 10.0%, and 0% in patients with type A, AB, B1, B2, B3, and C tumors, respectively. The average number (x10(6)) of tumor-associated CD4(+)CD8(+) cells present in 1 g of tumor tissue was 1.5, 391.1, 1041.7, 333.9, 24.5, and 0.2 in type A, AB, BI, B2, B3, and C, respectively, and it was 1168.2 in the normal thymuses. Thus, type B1 tumor retained the function to induce CD4+CD8+ double-positive cells at a level comparable to that of the normal thymic cortical epithelial cells, followed by type AB and type B2 tumors. Type A and B3 tumors had this function at a barely detectable level, and type C tumor was nonfunctional. WHO histologic classification was shown to reflect the clinical features and the T-cell-inducing function of thymic epithelial tumors.
  • Y Kadota; M Okumura; S Miyoshi; S Kitagawa-Sakakida; M Inoue; H Shiono; Y Maeda; T Kinoshita; R Shirakura; H Matsuda
    CLINICAL AND EXPERIMENTAL IMMUNOLOGY BLACKWELL SCIENCE LTD 121 (1) 59 - 68 0009-9104 2000/07 [Refereed]
     
    Thymoma is known to contain CD4(+)CD8(+) T cells, indicating that neoplastic epithelial cells of thymoma have a function as thymic cortical epithelium. However, it has been shown that there is an impairment of CD4(+) T cell development in thymoma and that IFN-gamma-induced HLA-DR expression on cultured thymic epithelial cells (TEC) derived from thymoma is decreased when compared with the normal thymus. MHC class II transactivator (CIITA) is known to play a critical role in IFN-gamma-induced MHC II expression. In this study, we attempted to elucidate whether CIITA is responsible for the impaired up-regulation of MHC II molecules in response to IFN-gamma in thymoma TEC. A quantitative reverse transriptase-polymerase chain reaction examination revealed that the induced level of CIITA was significantly lower in thymoma TEC than in normal TEC. The induced levels of invariant chain (Ii) and HLA-DR in thymoma TEC were correlated with CIITA expression. The proportion of CD3(+) cells in the CD4(+)CD8(-) subset in thymoma was also correlated with CIITA expression. A gel mobility shift assay however, revealed translocation of STAT1 to the nucleus in thymoma as well as normal TEC. Intercellular adhesion molecule-1 was up-regulated in the thymoma TEC to a level similar to normal TEC in response to IFN-gamma. These results indicate that impaired up-regulation of HLA-DR in response to IFN-gamma results from insufficient induction of CIITA, but not from the signal from IFN-gamma receptor to the nucleus. The abnormal regulation of HLA-DR expression caused by impaired induction of CIITA may affect CD4(+) T cell development in thymoma.
  • S Takeda; S Miyoshi; Y Kadota; H Shiono; H Matsuda
    RESPIRATION KARGER 67 (2) 234 - 237 0025-7931 2000/03 [Refereed]
  • M Inoue; M Okumura; S Miyoshi; H Shiono; K Fukuhara; Y Kadota; R Shirakura; H Matsuda
    CLINICAL AND EXPERIMENTAL IMMUNOLOGY BLACKWELL SCIENCE LTD 117 (1) 1 - 7 0009-9104 1999/07 [Refereed]
     
    A human thymoma is a neoplasm derived from the thymic epithelial cell, and is well known for its association with autoimmune diseases, especially myasthenia gravis. The neoplastic epithelial cells of thymoma clearly retain thymic epithelial functions, but the development of T cells in thymoma is somewhat impaired. In this study, we quantified by flow cytometry the in vitro expression of MHC molecules on neoplastic epithelial cells precultured with IFN-gamma. While MHC class I expression was comparable with that on normal thymic epithelial cells, the level of MHC class II molecules on neoplastic epithelial cells was lower than in controls, and also varied greatly from case to case. Additionally, there was a significant positive correlation between the expression level of MHC class II and the proportion of mature CD3(+) cells in the CD4(+)CD8(-) subset. Thus, accumulation of CD3(-)CD4(+)CD8(-) cells in thymoma may result from impaired expression of the MHC class II molecules, suggesting that the function of the neoplastic epithelial cells might determine the maturation and the positively selected repertoire of T cells in thymomas.
  • T Utsumi; T Mizuta; Y Fujii; H Shiono; M Okumura; M Minami; S Takeda; S Miyoshi; H Matsuda
    TRANSPLANTATION LIPPINCOTT WILLIAMS & WILKINS 67 (12) 1622 - 1626 0041-1337 1999/06 [Refereed]
     
    Backgrounds. We reported the increased nitric oxide (NO) level in exhaled air of rat lung transplant recipients during acute rejection (AR). The aim of this study was to determine the site and level of NO production in the rejected graft. Methods. Rat lung transplantation was performed in isografts and allografts. Results. In isografts, no AR and no significant increase in NO production was identified. In allografts, grades I-II of AR was seen on postoperative day (POD) 3 and grade III on POD 5, NO produced by BAL cells increased on both POD 3 (11.8+/-2.0 parts per billion [ppb]) and POD 5 (115.3+/-66.9 ppb). There was a highly significant correlation between the level of NO and the severity of AR (p=0.862, P<0.005). BAL cells from, allografts expressed iNOS mRNA, Among them, macrophages, lymphocytes and neutrophils were immunostained for iNOS. Conclusion. NO produced by BAL cells was detected in the early stages of rejection. Therefore, it may serve as a sensitive indicator of AR in lung transplantation.
  • M Inoue; Y Fujii; M Okumura; S Miyoshi; H Shiono; K Fukuhara; Y Kadota; H Matsuda
    PATHOLOGY RESEARCH AND PRACTICE GUSTAV FISCHER VERLAG 195 (8) 541 - 547 0344-0338 1999 [Refereed]
     
    Human thymoma is derived from thymic epithelial cells and often associated with a large number of cortical thymocytes. Since thymic epithelial cells play key roles in T-cell development in the normal thymus, we hypothesized that the neoplastic epithelial cells of thymoma may support T-cell differentiation. We attempted to reconstitute the T-cell development in vitro by using neoplastic epithelial cells isolated from thymoma. CD34, a stem cell marker, was expressed on a proportion of CD4(-)CD8(-) cells in thymoma. These CD34(+)CD4(-)CD8(-) cells also expressed both IL-7R alpha-chain and common gamma-chain. Purified CD4(-)CD8(-) cells from thymomas were cultured with the neoplastic epithelial cells, and their differentiation into CD4(+)CD8(+) cells via CD4 single positive intermediates was observed within 9 days' coculture in the presence of recombinant IL-7. The CD34(+)CD4(-)CD8(-) cells purified from a normal thymus also differentiated to CD4(+)CD8(+) cells in an allogeneic co-culture with the neoplastic epithelial cells of thymoma. In addition, a pleural dissemination from thymoma contained a large amount of cortical thymocytes. These results suggest that the neoplastic epithelial cells retain the function of thymic epithelium and can support T-cell development in thymomas.
  • M Inoue; M Okumura; Y Fujii; S Miyoshi; H Shiono; K Fukuhara; Y Kadota; H Matsuda
    CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY ACADEMIC PRESS INC 88 (3) 249 - 255 0090-1229 1998/09 [Refereed]
     
    Thymoma is a thymic epithelial tumor which often contains a large number of immature T cells. Although the metastatic lesions are also associated with abundant lymphocytes, their characteristics have not been assessed in detail. In this study, the phenotype was analyzed and compared with those in their primary lesions. Nine metastatic thymomas were obtained from seven patients. In the metastatic lesions, CD1a(+) cells and CD4(+)CD8(+) cells accounted for 77.7 +/- 10.6 and 52.3 +/- 15.8% of all the lymphocytes, respectively. In five primary lesions and their metastatic lesions, CD3(-)CD4(+)CD8(-) cells accounted for 23.9 +/- 16.9 and 45.2 +/- 15.5% of the CD4(+)CD8(-) cells, respectively. CD69 was expressed on 70.9 +/- 9.5 and 53.1 +/- 11.8% of the CD4(+)CD8(-) cells, respectively. These results indicate that the metastatic lesions of thymoma are associated with abundant immature T cells which are phenotypically less mature than those in their primary lesions. (C) 1998 Academic Press.
  • M Inoue; Y Fujii; M Okumura; Y Takeuchi; H Shiono; S Miyoshi; H Matsuda; R Shirakura
    CLINICAL AND EXPERIMENTAL IMMUNOLOGY BLACKWELL SCIENCE LTD 112 (3) 419 - 426 0009-9104 1998/06 [Refereed]
     
    Human thymoma is a thymic epithelial cell tumour which often contains a large number of immature T cells and is frequently associated with autoimmune diseases. Since thymic epithelial cells play key roles in the development and selection of T cells in the normal thymus, we hypothesized that the neoplastic thymic epithelial cells of thymoma may support T cell differentiation in the tumour. We characterized CD4(-)CD8(-) cells in thymoma and applied an irt vitro reconstitution culture system using the CD4(-)CD8(-) cells and the neoplastic epithelial cells isolated from thymoma. CD34, a stem cell marker, was expressed on 29.9 +/- 12.2% of CD4(-)CD8(-) cells in thymoma. TCR gamma delta was expressed on 27.4+/-15.1% of CD4(-)CD8(-) cells and CD19, a B cell marker, was expressed on 14.1+/-23.1% of CD4(-)CD8(-) cells. CD4(-)CD8(-) cells expressed both IL-7R alpha-chain and common gamma-chain. Purified CD4(-)CD8(-) cells from thymomas were cultured with the neoplastic epithelial cells, and their differentiation into CD4(+)CD8(+) cells via CD4 single-positive intermediates was observed within 9 days' co-culture in the presence of recombinant IL-7. Furthermore, we examined the reconstitution culture using CD34(+)CD4(-)CD8(-) cells purified from normal infant thymus. The CD34(+)CD4(-)CD8(-) cells in normal thymus also differentiated to CD4(+)CD8(+) cells in the allogeneic co-culture with the neoplastic epithelial cells of thymoma. These results indicate that the tumour cells of thymoma retain the function of thymic epithelial cells and can induce differentiation of T cells in thymoma.
  • INOUE Masayoshi; FUJII Yoshitaka; OKUMURA Meinoshin; TAKEUCHI Yukiyasu; SHIONO Hiroyuki; FUKUHARA Kenjiro; KADOTA Yoshihisa; TAKEDA Shinichi; MINAMI Masato; YOON Hyung-Eun; MIYOSHI Shinichiro; MATSUDA Hikaru
    The Journal of the Japanese Association for Chest Surgery The Japanese Association for Chest Surgery 11 (6) 704 - 709 0919-0945 1997/09 
    Thymoma contains abundant immature T lymphocytes. Since thymic epithelial cells have an important key role in T cell development and selection, it may be possible that the immature T lymphocytes differentiate in thymoma. In this report, we analyzed the surface antigens on lymphocytes in a metastatic thymoma of lung to investigate the maturity. CD4-CD8- (DN) cells accounted for 3.6%, CD4+CD8+ (DP) cells for 75.2%, CD4+CD8+ (CD4SP) cells for 9.7 %, and CD4-CD8+ (CD8SP) cells for 11.5%. 85.9% of the lymphocytes expressed CD1. Although all CD8SP cells expressed CD3, TcRafl and CD69, a large proportion of CD4SP cells did not and were immature CD4SP cells which were differentiating to DP cells from DN cells. These results indicate that a metastatic thymoma contained abundant immature T cells, and also suggest that the tumor thymic epithelial cells may govern the developing T cells though incompletely.
  • M Inoue; Y Fujii; M Okumura; Y Takeuchi; H Shiono; S Miyoshi; H Matsuda; R Shirakura
    PATHOBIOLOGY KARGER 65 (4) 216 - 222 1015-2008 1997/07 [Refereed]
     
    Human thymoma, which is occasionally associated with autoimmune disease, is a thymic epithelial cell tumor and often contains a large number of lymphocytes, In a previous study, we have shown that a proportion of CD4 single positive T cells in human thymomas lack CD3, suggesting immaturity. In this study, we focused on the rest of the CD4 single positive T cells in thymomas that expressed CD3/TcR alpha beta and investigated the maturity of single positive a cells by analyzing lymphocyte surface antigens and the cells' proliferative response to a mitogen, CD4 single positive cells that expressed CT)3 or TcR alpha beta also expressed CD69 and had probably undergone positive selection in the tumor. Further, isolated CD4 or CD8 single positive cells from the thymomas responsed to a mitogen although at lower levels than the corresponding single positive cells in the peripheral blood, These results indicate that thymomas contain single positive T cells which have mature phenotype and proliferative ability, and suggest that T cells may differentiate in thymoma.
  • H Shiono; Y Fujii; M Okumura; Y Takeuchi; M Inoue; H Matsuda
    EUROPEAN JOURNAL OF IMMUNOLOGY VCH PUBLISHERS INC 27 (4) 805 - 809 0014-2980 1997/04 [Refereed]
     
    The most unusual characteristic of myasthenia gravis (MG) is that the thymus has germinal centers (GC). Cultured thymic lymphocytes from MG patients spontaneously produce anti-acetylcholine receptor antibodies, indicating that autoreactive B cells have escaped negative selection. To investigate the underlying mechanism, we examined the expression of the apoptosis-related protein Bcl-2 in GC B cells (defined as CD19(+)CD38(+) cells) in the thymus in 14 MG patients using three-color flow cytometry. GC in MG patients did not show the normal down-regulation of Bcl-2 (the frequency of Bcl-2(+) GC B cells in the MG thymus and in control tonsils 54.3 +/- 16.2% versus 20.6 +/- 8.0%; mean +/- SD, p < 0.0001). In contrast, Bcl-2 in GC in the mediastinal lymph nodes from four patients was down-regulated to a relatively normal level. Using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method to detect DNA fragmentation in situ, the frequency of TUNEL+ cells in GC in the MG thymus was lower than in control tonsils. These results suggest that autoreactive B cells which normally undergo apoptosis in GC may survive because of Bcl-2 up-regulation in this unusual location.
  • 武田 伸一; 南 正人; 尹 亨彦; 奥村 明之進; 竹内 幸康; 塩野 裕之; 平林 弘久; 田中 壽一; 井上 匡美; 内海 朝喜; 福原 謙二郎; 小間 勝; 門田 嘉久; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 11 (3) 391 - 391 1997
  • 塩野 裕之; 奥村 明之進; 武田 伸一; 南 正人; 尹 亨彦; 竹内 幸康; 平林 弘久; 井上 匡美; 田中 壽一; 内海 朝喜; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 11 (3) 429 - 429 1997
  • 尹 亨彦; 武田 伸一; 南 正人; 奥村 明之進; 竹内 幸康; 塩野 裕之; 平林 弘久; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 11 (3) 341 - 341 1997
  • 田中 壽一; 武田 伸一; 南 正人; 尹 亨彦; 奥村 明之進; 竹内 幸康; 塩野 裕之; 平林 弘久; 井上 匡美; 内海 朝喜; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 11 (3) 340 - 340 1997
  • 南 正人; 門田 嘉久; 福原 謙二郎; 小間 勝; 内海 朝喜; 井上 匡美; 田中 寿一; 平林 弘久; 塩野 裕之; 竹内 幸康; 尹 亨彦; 奥村 明之進; 武田 伸一; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 11 (3) 476 - 476 1997
  • 奥村 明之進; 井上 匡美; 内海 朝喜; 平林 弘久; 塩野 裕之; 竹内 幸康; 田中 壽一; 尹 亨彦; 南 正人; 武田 伸一; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 11 (3) 377 - 377 1997
  • 福原 謙二郎; 武田 伸一; 南 正人; 尹 亨彦; 奥村 明之進; 竹内 幸康; 塩野 裕之; 平林 弘久; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 11 (3) 432 - 432 1997
  • 井上 匡美; 武田 伸一; 南 正人; 尹 亨彦; 奥村 明之進; 竹内 幸康; 塩野 裕之; 平林 弘久; 田中 寿一; 松田 暉; 安光 勉; 古武 彌宏; 森 隆; 井内 敬二; 桑原 修; 前田 元
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 11 (3) 309 - 309 1997
  • 竹内 幸康; 藤井 義敬; 水田 隆俊; 武田 伸一; 尹 亨彦; 塩野 裕之; 井上 匡美; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 10 (3) 289 - 289 1996
  • 南 正人; 藤井 義敬; 水田 隆俊; 稲田 啓次; 尹 亨彦; 貴島 弘樹; 竹内 幸康; 阪口 全宏; 岩崎 輝夫; 塩野 裕之; 平林 弘久; 井上 匡美; 松田 暉
    気管支学 特定非営利活動法人 日本呼吸器内視鏡学会 17 (3) 275 - 275 1995
  • 水田 隆俊; 中原 数也; 藤井 義敬; 松村 晃秀; 南 正人; 稲田 啓次; 尹 亨彦; 貴島 弘樹; 竹内 幸康; 阪口 全宏; 岩崎 輝夫; 塩野 裕之; 平林 弘久; 井上 匡美; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 9 (3) 333 - 333 1995
  • 小西 裕之; 桑原 修; 前田 元; 太田 三徳; 塩野 裕之; 宮崎 実; 内海 朝喜
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 9 (3) 440 - 440 1995
  • 南 正人; 井上 匡美; 平林 弘久; 塩野 裕之; 岩崎 輝夫; 阪口 全宏; 竹内 幸康; 貴島 弘樹; 尹 亨彦; 稲田 啓次; 水田 隆俊; 藤井 義敬; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 9 (3) 450 - 450 1995
  • 南 正人; 井上 匡美; 平林 弘久; 塩野 裕之; 岩崎 輝夫; 阪口 全宏; 竹内 幸康; 貴島 弘樹; 尹 亨彦; 稲田 啓次; 水田 隆俊; 藤井 義敬; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 9 (3) 426 - 426 1995
  • 藤井 義敬; 竹内 幸康; 尹 亨彦; 阪口 全宏; 塩野 裕之; 平林 弘久; 水田 隆俊; 南 正人; 稲田 啓次; 貴島 弘樹; 岩崎 輝夫; 井上 匡美; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 9 (3) 308 - 308 1995
  • 水田 隆俊; 中原 数也; 藤井 義敬; 松村 晃秀; 南 正人; 稲田 啓次; 末岐 博文; 尹 亨彦; 貴島 弘樹; 竹内 幸康; 坂口 全宏; 岩崎 輝夫; 塩野 裕之; 松田 暉
    日本呼吸器外科学会雑誌 特定非営利活動法人 日本呼吸器外科学会 8 (3) 325 - 325 1994
  • Shiono Hiroyuki; Kuwahara Osamu; Maeda Hajime; Ohta Mitsunori; Miyazaki Minoru
    The Journal of the Japanese Association for Chest Surgery The Japanese Association for Chest Surgery 8 (7) 773 - 778 0919-0945 1994 
    Among the 385 patients who had pulmonary resection with mediastinal dissection for lung cancer during the past 10 years (1982, 41992, 3) at Toneyama National Hospital, there have been 8 cases of post operative chylothorax. Four patients recovered with conservative therapy, but the other 4 patients required surgery. The sites of chyle leakage were easily identified by the feeding of milk before re-operation.
    We used our procedure to prevent post operative chylothorax in all patients undergoing pulmonary resections for lung cancer during the past year. After the induction of anesthesia a nasogastric tube is inserted, and 200 ml of milk is administered through the tube. Since fat has been absorbed and is travelling upward in the thoracic duct by the time of mediastinal dissection, the thoracic duct and chyle leakage can be easily identified and treated. Leakage can be checked again when the operative field is washed. No chylothorax occurred in the 55 patients undergoing this procedure, and there were no complications of milk administration. This method is recommended for the prevention of chylothorax following resection for lung cancer.
  • Shiono Hiroyuki; Kuwahara Osamu; Maeda Hajime; Ohta Mitsunori; Miyazaki Minoru
    The Journal of the Japan Society for Respiratory Endoscopy The Japan Society for Respiratory Endoscopy 15 (6) 560 - 565 1993 
    An unusual case is described of a woman who presented endobronchial chondroma, in addition, previous reports of Japanese cases of endobronchial chondroma are reviewed. A 63-year-old female who complained of hemoptysis was examined by bronchofiberscopy. A polypoid tumor was found at the orifice of right B^3. The biopsy specimens demonstrated a bronchial chondroma consisting of cartilaginous tissue. The polypoid tumor was almost completely removed in pieces with biopsy forceps and the residual tumor was resected with high frequency electrocautery. Bronchoscopic findings 27 months after removal revealed no recurrence of the tumor. This case is the 20th case reported in Japan. All 20 cases were examined bronchofiberscopically, but only 6 cases were diagnosed histologically with this method. Four of these 6 cases were treated bronchoscopically. Almost all cases with no histological diagnosis were resected surgically. Multiple and sufficient biopsies are necessary to confirm the diagnosis of chondroma and to treat bronchoscopically.

Books etc

MISC

Awards & Honors

  • 2008/06 大阪大学医学部第一外科同窓会 小澤賞
     
    受賞者: 塩野 裕之
  • 2007/12 JSES Karl Storz Award 2007
     Navigation system for mediastinoscopy with virtual images 
    受賞者: SHIONO Hiroyuki

Research Grants & Projects

  • より正確,安全な縦隔リンパ節生検をめざした,バーチャルナビゲーションシステムの開発
    科学技術振興機構:シーズ発掘試験
    Date (from‐to) : 2007 -2008 
    Author : 塩野裕之
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(基盤研究(C))
    Date (from‐to) : 2007 -2008 
    Author : 塩野 裕之; Masato MINAMI; Meinoshin OKUMURA; Yoshiki SAWA; Tomoki UTSUMI; Masayoshi INOUE; Hiroshi UYAMA
     
    肺気腫に対して、従来の肺容量減少手術(LVRS)に、再生医療を導入した新しい治療法、すなわち、気腫肺に効果的に成長因子を到達させる具体的な方法として、自己脂肪組織から分離した間葉系細胞を足場に培養付着させ貼布する細胞シート法、および細胞を用いず担体から直接成長因子を放出するDrug Delivery System (DDS)の臨床応用の可能性を動物実験において明らかにした。
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research
    Date (from‐to) : 2005 -2006 
    Author : MINAMI Masato; OKUMURA Meinoshin; SHIONO Hiroyuki; INOUE Masayoshi
     
    Accurate diagnosis of acute rejection, reperfusion injury, or pulmonary infection is difficult in the postoperative acute phase in the lung transplantation. We investigate the clinical utility of flow cytometry for surface antigen (CD3, CD4, CD8, CD25, CD69, CD45RA, CD45RO) on peripheral blood lymphocytes in order to diagnose the posttransplant status of patients. Also, the effect of anti-CD25 antibody administration was discussed. We found no evident change of CD4/CD8 ratio, CD25 expression, CD69 expression, and the proportion of CD45RA/RO in the patient with stable course. CD28 expression level decreased during the 1st month after transplant and this tendency was predominantly found in CD8 T cells as compared to CD4 subset. In a patient suffering interstitial pneumonia, increase of CD25 expression in CD4 T cells and increase of CD69 expression in CD8 T cells were shown. CD25 expression might be suppressed by CD25 antibody administration.
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(基盤研究(C))
    Date (from‐to) : 2005 -2006 
    Author : Hiroyuki SHIONO; Meinoshin OKUMURA; Masato MINAMI; Masayoshi INOUE; Hikaru MATSUDA
     
    Purpose: Glucocorticoids exert anti-proliferative effects in various cell types and have long been known to induce apoptosis in thymocytes. Although a few reports have described the regression of human thymoma with glucocorticoid therapy, its effects on neoplastic thymic epithelial cells (TECs) have not been reported. In the present study, we investigated glucocorticoid receptor (GR) expression on neoplastic TECs and the effects of glucocorticoids in vitro on the cell cycle progression of tumor cells.Patients and methods : Thymoma specimens were obtained during surgery from 21 patients. Three of the specimens with glucocorticoid therapy were examined using the TdT-mediated dUTP-biotin nick-end labeling method. Primary tumor specimens from ten untreated thymomas were examined for GR expression by immunohistochemistry. Isolated neoplastic TECs from the remaining eight untreated thymomas were examined using immunohistochemistry, flow cytometric and cell cycle analysis.Results: GR are expressed on neoplastic TECs as well as on non-neoplastic thymocytes in thymomas, regardless of WHO histological classification. Glucocorticoids caused an accumulation of TEC in GO/G1 phase in all cases examined (n=6), and also induced apoptosis in the three with the lowest levels of Bcl-2 expression.Conclusions : Our results indicate that neoplastic TECs express GR and that glucocorticoids directly suppress their in vitro proliferation.
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(基盤研究(C))
    Date (from‐to) : 2003 -2004 
    Author : Hiroyuki SHIONO; 太田 三徳; Masato MINAMI; Hikaru MATSUDA
     
    Inhibition of the graft rejection is essential for the successful organ transplantation. Although the improvement of immunosuppressants have been made the transplantation safer, more effective methods for the control of rejection are still needed.Our novel strategy for the control of the graft rejection is to down-regulate the expression of MHC class II molecules in the transplanted organs by interfering the function of MHC class II transactivator (CIITA), which is one of the transcription factor of MHC molecules.A deletion mutant protein which express only the biding domain is supposed to work as a dominant negative mutation and to suppress the expression of MHC class II molecules. Dominant mutant cDNA was introduced into Raji cells, the B cell line expressing HLA-DR. Expression of HLA-DR antigen was shown to be significantly suppressed in the stable transfectants.Hemagglutinating virus of Japan (HVJ virus) envelope vector with cDNA was amplified, and infused via a catheter which was inserted into the vein dorsalis penis superficiales of rats. The expression of the protein of inserted cDNA was clearly detected in the alveolar in the rat lungs.These achievement should enable us to develop the rat donor lungs in which HLA class II molecules are down-regulated for the inhibition of the rejection. This novel strategy for the control of the rejection could be useful against any sorts of organ transplants.

Committee Membership

  • 2020/03 - Today   Mediastinum   Editorial Board

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