詳細

津谷　康大 （ツタニ　ヤスヒロ）

  • 医学科　教授/主任
Last Updated :2024/04/29

コミュニケーション情報 byコメンテータガイド

  • コメント

    肺がんに対する胸腔鏡を用いた低侵襲手術、肺区域切除などの機能温存手術、術前・術後の薬物療法を専門としています。臨床試験や治験に関わり、常により良い治療を目指しています。

研究者情報

学位

  • 博士（医学）（2009年03月 広島大学）

ホームページURL

科研費研究者番号

  • 10534985

ORCID ID

J-Global ID

研究キーワード

  • 肺癌   悪性胸膜中皮腫   

現在の研究分野（キーワード）

    肺がんに対する胸腔鏡を用いた低侵襲手術、肺区域切除などの機能温存手術、術前・術後の薬物療法を専門としています。臨床試験や治験に関わり、常により良い治療を目指しています。

研究分野

  • ライフサイエンス / 呼吸器外科学

経歴

  • 2022年04月 - 現在  近畿大学医学部外科学教室呼吸器外科部門主任教授

学歴

  • 2005年04月 - 2009年03月   広島大学   大学院医歯薬学総合研究科   博士課程創生医科学専攻
  • 1994年04月 - 2000年03月   広島大学   医学部   医学科

研究活動情報

論文

  • Yu Izaki; Takahiro Mimae; Atsushi Kagimoto; Yoshinori Handa; Yasuhiro Tsutani; Yoshihiro Miyata; Morihito Okada; Yukio Takeshima
    Japanese Journal of Clinical Oncology 2024年04月
  • Aritoshi Hattori; Kenji Suzuki; Kazuya Takamochi; Masashi Wakabayashi; Yuta Sekino; Yasuhiro Tsutani; Ryu Nakajima; Keiju Aokage; Hisashi Saji; Masahiro Tsuboi; Morihito Okada; Hisao Asamura; Kenichi Nakamura; Haruhiko Fukuda; Shun-Ichi Watanabe
    The Lancet. Respiratory medicine 2024年01月 
    BACKGROUND: Although segmentectomy was better than lobectomy in terms of overall survival for patients with non-small-cell lung cancer (NSCLC) with a pure-solid tumour appearance on thin-section CT in the open-label, multicentre, randomised, controlled, phase 3 JCOG0802/WJOG4607L trial, the reasons why segmentectomy was associated with better overall survival were unclear. We aimed to compare the survival, cause of death, and recurrence patterns after segmentectomy versus lobectomy in trial participants with NSCLC with a pure-solid appearance METHODS: We conducted a post-hoc supplemental analysis of the JCO0802/WJOG4607L randomised, controlled, non-inferiority trial for the patients (aged 20-85 years) with small-sized NSCLC with radiologically pure-solid appearance on thin-section CT (≤2 cm, consolidation tumour ratio 1·0). The primary aim was to compare the overall and relapse-free survival, cause of death, and recurrence patterns associated with segmentectomy and lobectomy for patients with radiologically pure-solid NSCLC to determine why the overall survival of segmentectomy was superior to that of lobectomy, even for oncologically invasive lung cancers. JCO0802/WJOG4607L is registered with the UMIN Clinical Trials Registry, UMIN000002317, and is complete. FINDINGS: Between Aug 10, 2009, and Oct 21, 2014, 1106 patients were randomly assigned to undergo either lobectomy or segmentectomy. Of these participants, 553 (50%) had radiologically pure-solid NSCLC and were eligible for this post-hoc supplemental analysis. Of these 553 participants, 274 (50%) patients underwent lobectomy and 279 (50%) underwent segmentectomy. Median patient age was 67 years (IQR 61-73), 347 (63%) of 553 patients were male and 206 (37%) were female, and data on race and ethnicity were not collected. As of data cutoff (June 13, 2020), after a median follow-up of 7·3 years (IQR 6·0-8·5), the 5-year overall survival rate was significantly higher after segmentectomy than after lobectomy (86·1% [95% CI 81·4-89·7] in the lobectomy group, with 55 deaths vs 92·4% [88·6-95·0] in the segmentectomy group, with 38 deaths; hazard ratio (HR) 0·64 [95% CI 0·41-0·97]; log-rank test p=0·033), whereas the 5-year relapse-free survival was similar between the groups (81·7% [95% CI 76·5-85·8], with 34 events vs 82·0% [76·9-86·0], with 52 events; HR 1·01 [95% CI 0·72-1·42]; p=0·94). Deaths after a median follow-up of 7·3 years due to lung cancer occurred in 20 (7%) of 274 patients after lobectomy and 19 (7%) of 279 after segmentectomy, and deaths due to other causes occurred in 35 (13%) patients after lobectomy compared with 19 (7%) after segmentectomy (lung cancer death vs other cause of death, p=0·19). The locoregional recurrence was higher after segmentectomy (21 [8%] vs 45 [16%]; p=0·0021). In subgroup analyses, better 5-year overall survival after segmentectomy than after lobectomy was observed in the subgroup of patients aged 70 years or older (77·1% [95% CI 68·2-83·8] with lobectomy vs 85·6% [77·5-90·9] with segmentectomy; p=0·013) and in male patients (80·5% [73·7-85·7] vs 92·1% [87·0-95·2]; p=0·0085). By contrast, better 5-year relapse-free survival after lobectomy than after segmentectomy was observed in the subgroup younger than 70 years (87·4% [95% CI 81·2-91·7] with lobectomy vs 84·4% [77·9-89·1] with segmentectomy; p=0·049) and in female patients (94·2% [87·6-97·4] vs 82·2% [73·2-88·4]; p=0·047). INTERPRETATION: This post-hoc analysis showed improved overall survival after segmentectomy in patients with pure-solid NSCLC compared with lobectomy. However, survival outcomes of segmentectomy depend on the patient's age and sex. Given the results of this exploratory analysis, further research is necessary to determine clinically relevant indications for segmentectomy in radiologically pure-solid NSCLC. FUNDING: Japanese National Cancer Center Research and Development Fund and Practical Research for Innovative Cancer Control Fund, and a Grant-in-Aid for Scientific Research from the Ministry of Health, Labor, and Welfare of Japan.
  • Atsushi Kamigaichi; Akira Hamada; Masahiro Tsuboi; Kenichi Yoshimura; Isamu Okamoto; Nobuyuki Yamamoto; Yasuhiro Tsutani
    Clinical Lung Cancer 2024年01月
  • Yoshinori Handa; Yasuhiro Tsutani; Takahiro Mimae; Yoshihiro Miyata; Hiroyuki Ito; Yoshihisa Shimada; Haruhiko Nakayama; Norihiko Ikeda; Morihito Okada
    Japanese Journal of Clinical Oncology 2023年12月
  • Tomohiro Miyoshi; Hiroyuki Ito; Masashi Wakabayashi; Tadayoshi Hashimoto; Yuta Sekino; Kenji Suzuki; Masahiro Tsuboi; Yasumitsu Moriya; Ichiro Yoshino; Tetsuya Isaka; Aritoshi Hattori; Takahiro Mimae; Mitsuhiro Isaka; Tomohiro Maniwa; Makoto Endo; Hiroshige Yoshioka; Kazuo Nakagawa; Ryu Nakajima; Yasuhiro Tsutani; Hisashi Saji; Morihito Okada; Keiju Aokage; Haruhiko Fukuda; Shun-Ichi Watanabe
    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 2023年10月 
    OBJECTIVES: This study aimed to identify the risk factors for pulmonary functional deterioration after wedge resection for early-stage lung cancer with ground-glass opacity, which remain unclear, particularly in low-risk patients. METHODS: We analyzed 237 patients who underwent wedge resection for peripheral early-stage lung cancer in JCOG0804/WJOG4507L, a Phase III, single-arm confirmatory trial. The changes in forced expiratory volume in 1 second were calculated pre- and postoperatively, and a cutoff value of - 10%, the previously reported reduction rete after lobectomy, was used to divide the patients into two groups: the severely-reduced group ( ≤ -10%) and normal group ( > -10%). These groups were compared to identify predictors for severe reduction. RESULTS: Thirty-seven (16%) patients experienced severe reduction. Lesions with a total tumour size ≥ 1 cm were significantly more frequent in the severely-reduced group than in the normal group (89.2% vs 71.5%; P = 0.024). A total tumour size ≥ 1 cm [odds ratio (OR), 3.287; 95% confidence interval (CI), 1.114-9.699: P = 0.031] and pleural indentation (OR, 2.474; 95% CI, 1.039-5.890: P = 0.041) were significant predictive factors in the univariable analysis. In the multivariable analysis, pleural indentation (OR, 2.667; 95% CI, 1.082-6.574; P = 0.033) was an independent predictive factor, whereas smoking status, and total tumour size were marginally significant. CONCLUSIONS: Of the low-risk patients who underwent pulmonary wedge resection for early-stage lung cancer, 16% experienced severe reduction in pulmonary function. Pleural indentation may be a risk factor for severely-reduced pulmonary function in pulmonary wedge resection. CLINICAL REGISTRATION NUMBER: UMIN000002008.
  • Shota Fukuda; Kenichi Suda; Akira Hamada; Yasuhiro Tsutani
    Biomolecules 13 9 2023年09月 
    Several clinical trials have been revolutionizing the perioperative treatment of early-stage non-small cell lung cancer (NSCLC). Many of these clinical trials involve cancer immunotherapies with antibody drugs that block the inhibitory immune checkpoints programmed death 1 (PD-1) and its ligand PD-L1. While these new treatments are expected to improve the treatment outcome of NSCLC patients after pulmonary resection, several major clinical questions remain, including the appropriate timing of immunotherapy (neoadjuvant, adjuvant, or both) and the identification of patients who should be treated with neoadjuvant and/or adjuvant immunotherapies, because some early-stage NSCLC patients are cured by surgical resection alone. In addition, immunotherapy may induce immune-related adverse events that will require permanent treatment in some patients. Based on this fact as well, it is desirable to select appropriate patients for neoadjuvant/adjuvant immunotherapies. So far, data from several important trials have been published, with findings demonstrating the efficacy of adjuvant atezolizumab (IMpower010 trial), neoadjuvant nivolumab plus platinum-doublet chemotherapy (CheckMate816 trial), and several perioperative (neoadjuvant plus adjuvant) immunotherapies (AEGEAN, KEYNOTE-671, NADIM II, and Neotorch trials). In addition to these key trials, numerous clinical trials have reported a wealth of data, although most of the above clinical questions have not been completely answered yet. Because there are so many ongoing clinical trials in this field, a comprehensive understanding of the results and/or contents of these trials is necessary to explore answers to the clinical questions above as well as to plan a new clinical trial. In this review, we comprehensively summarize the recent data obtained from clinical trials addressing such questions.
  • Akira Hamada; Kenichi Suda; Masaya Nishino; Keiko Obata; Hana Oiki; Tomoyo Fukami; Shota Fukuda; Toshio Fujino; Shuta Ohara; Takamasa Koga; Masato Chiba; Masaki Shimoji; Masaoki Ito; Toshiki Takemoto; Junichi Soh; Yasuhiro Tsutani; Tetsuya Mitsudomi
    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 2023年09月 
    INTRODUCTION: Approximately 10% of mutations in the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer (NSCLC) are in-frame insertions in exon 20 (X20ins). These tumors usually do not respond to conventional EGFR-tyrosine kinase inhibitors (TKIs). Several novel EGFR-TKIs active for X20ins are in clinical development, including mobocertinib, which was recently approved by the US FDA. However, acquired resistance during treatment with these TKIs still occurs as in the case of EGFR-TKIs of earlier generations. METHODS: We chronically exposed Ba/F3 cells transduced with five most common X20ins (A763_Y764insFQEA, V769_D770insASV, D770_N771insSVD, H773_V774insNPH and H773_V774insH) to mobocertinib in the presence of N-ethyl-N-nitrosourea and searched for secondary EGFR mutations. We evaluated the efficacies of several EGFR X20ins inhibitors, including zipalertinib and sunvozertinib, against cells with acquired resistant mutations. RESULTS: All secondary mutations resulting in acquired resistance to mobocertinib were exclusively C797S in insFQEA and insSVD. However, in the case of other X20ins (insASV, insNPH and insH), T790M or C797S secondary mutations contributed to acquired resistance to mobocertinib. The emergence of T790M was more frequent in cells treated with lower drug concentrations. Sunvozertinib showed good activity against resistant cells with T790M. Cells with C797S were refractory to all EGFR-TKIs, except for erlotinib, which was active for insFQEA with C797S. CONCLUSIONS: T790M or C797S, depending on the original X20ins mutations, conferred acquired resistance to mobocertinib. Sunvozertinib may be the treatment of choice for patients with tumors resistant to mobocertinib because of T790M.
  • Nobutaka Kawamoto; Takahiro Mimae; Yasuhiro Tsutani; Atsushi Kamigaichi; Norifumi Tsubokawa; Yoshihiro Miyata; Morihito Okada
    The Journal of thoracic and cardiovascular surgery 2023年06月 
    OBJECTIVE: Pulmonary lymphatic drainage of the lower lobe into the mediastinal lymph nodes includes not only the pathway via the hilar lymph nodes but also the pathway directly into the mediastinum via the pulmonary ligament. This study aimed to determine the association between the distance from the mediastinum to the tumor and the frequency of occult mediastinal nodal metastasis (OMNM) in patients with clinical stage I lower-lobe non-small cell lung cancer (NSCLC). METHODS: Between April 2007 and March 2022, data of patients who underwent anatomical pulmonary resection and mediastinal lymph node dissection for clinical stage I radiological pure-solid lower-lobe NSCLC were retrospectively reviewed. In computed tomography axial sections, the ratio of the distance from the inner edge of the lung to the inner margin of the tumor within the lung width of the affected lung was defined as the inner margin ratio (IMR). Patients were divided into two groups based on whether the IMR was ≤0.50 (inner-type) or >0.50 (outer-type), and the association between IMR status and clinicopathological findings was assessed. RESULTS: In total, 200 patients were enrolled in the study. OMNM frequency was 8.5%. More inner- than outer-type patients had OMNM (13.2% vs. 3.2%; P=0.012) and skip N2 metastasis (7.5% vs. 1.1%; P=0.038). Multivariable analysis revealed that the IMR was the only independent preoperative predictor of OMNM (odds ratio, 4.72; 95% confidence interval, 1.31-17.07; P=0.018). CONCLUSIONS: Tumor distance from the mediastinum was the most important preoperative predictor of OMNM in patients with lower-lobe NSCLC.
  • Daisuke Ueda; Yasuhiro Tsutani; Morihito Okada
    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 2023年05月
  • Kenichi Suda; Kazuko Sakai; Tatsuo Ohira; Takaaki Chikugo; Takao Satou; Jun Matsubayashi; Toshitaka Nagao; Norihiko Ikeda; Yasuhiro Tsutani; Tetsuya Mitsudomi; Kazuto Nishio
    Cancers 15 9 2023年05月 
    BACKGROUND: The Idylla™ EGFR Mutation Test is an ultra-rapid single-gene test that detects epidermal growth factor receptor (EGFR) mutations using formalin-fixed paraffin-embedded specimens. Here, we compared the performance of the Idylla EGFR Mutation Test with the Cobas® EGFR Mutation Test v2. METHODS: Surgically resected NSCLC specimens obtained at two Japanese institutions (N = 170) were examined. The Idylla EGFR Mutation Test and the Cobas EGFR Mutation Test v2 were performed independently and the results were compared. For discordant cases, the Ion AmpliSeq Colon and Lung Cancer Research Panel V2 was performed. RESULTS: After the exclusion of five inadequate/invalid samples, 165 cases were evaluated. EGFR mutation analysis revealed 52 were positive and 107 were negative for EGFR mutation in both assays (overall concordance rate: 96.4%). Analyses of the six discordant cases revealed that the Idylla EGFR Mutation Test was correct in four and the Cobas EGFR Mutation Test v2 was correct in two. In a trial calculation, the combination of the Idylla EGFR Mutation Test followed by a multi-gene panel test will reduce molecular screening expenses if applied to a cohort with EGFR mutation frequency >17.9%. CONCLUSIONS: We demonstrated the accuracy and potential clinical utility of the Idylla EGFR Mutation Test as a molecular screening platform in terms of turnaround time and molecular testing cost if applied to a cohort with a high EGFR mutation incidence (>17.9%).
  • Nobutaka Kawamoto; Yasuhiro Tsutani; Morihito Okada
    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 2023年03月
  • Keiju Aokage; Kenji Suzuki; Hisashi Saji; Masashi Wakabayashi; Tomoko Kataoka; Yuta Sekino; Haruhiko Fukuda; Makoto Endo; Aritoshi Hattori; Takahiro Mimae; Tomohiro Miyoshi; Mitsuhiro Isaka; Hiroshige Yoshioka; Ryu Nakajima; Kazuo Nakagawa; Jiro Okami; Hiroyuki Ito; Hiroaki Kuroda; Masahiro Tsuboi; Norihito Okumura; Makoto Takahama; Yasuhisa Ohde; Tadashi Aoki; Yasuhiro Tsutani; Morihito Okada; Shun-Ichi Watanabe
    The Lancet. Respiratory medicine 2023年03月 
    BACKGROUND: Although segmentectomy is a widely used surgical procedure, lobectomy is the standard procedure for resectable non-small-cell lung cancer (NSCLC). This study aimed to evaluate the efficacy and safety of segmentectomy for NSCLC up to 3 cm in size, including ground-glass opacity (GGO) and predominant GGO. METHODS: A multicentre, single-arm, confirmatory phase 3 trial was conducted across 42 institutions (hospitals, university hospitals, and cancer centres) in Japan. Segmentectomy with hilar, interlobar, and intrapulmonary lymph node dissection was performed as protocol surgery for patients with a tumour diameter of up to 3 cm, including GGO and dominant GGO. Eligible patients were those aged 20-79 years with an Eastern Cooperative Oncology Group performance score of 0 or 1 and clinical stage IA tumour confirmed by thin-sliced CT. The primary endpoint was 5-year relapse-free survival (RFS). This study is registered with the University Hospital Medical Information Network Clinical Trials (UMIN000011819), and is ongoing. FINDINGS: A total of 396 patients were registered from Sept 20, 2013, to Nov 13, 2015, of whom 357 underwent segmentectomy. At a median follow-up of 5·4 years (IQR 5·0-6·0), the 5-year RFS was 98·0% (95% CI 95·9-99·1). This finding exceeded the 87% of the pre-set threshold 5-year RFS and the primary endpoint was met. Grade 3 or 4 early postoperative complications occurred in seven patients (2%), but no grade 5 treatment-related deaths occurred. INTERPRETATION: Segmentectomy should be considered as part of standard treatment for patients with predominantly GGO NSCLC with a tumour size of 3 cm or less in diameter, including GGO even if it exceeds 2 cm. FUNDING: National Cancer Centre Research and Development Fund and Japan Agency for Medical Research and Development.
  • Yasuhiro Tsutani; Jonathan W. Goldman; Sanja Dacic; Yasushi Yatabe; Margarita Majem; Xiangning Huang; Allen Chen; Toon van der Gronde; Jie He
    Clinical Lung Cancer 2023年02月 
    INTRODUCTION: Osimertinib is a third-generation, irreversible, oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR-TKI sensitizing and EGFR T790M resistance mutations, with demonstrated efficacy in EGFR mutation-positive (EGFRm) non-small cell lung cancer (NSCLC), including central nervous system (CNS) metastases. Here we present the rationale and study design for ADAURA2 (NCT05120349), which will evaluate adjuvant osimertinib vs. placebo in patients with stage IA2-IA3 EGFRm NSCLC, following complete tumor resection. PATIENTS AND METHODS: ADAURA2 is a phase III, global, randomized, double-blind, placebo-controlled study. Patients will be adults aged ≥18 years with resected primary nonsquamous NSCLC stage IA2 or IA3 and central confirmation of an EGFR exon 19 deletion or L858R mutation. Patients will be stratified by pathologic risk of disease recurrence (high vs. low), EGFR mutation type (exon 19 deletion vs. L858R) and race (Chinese Asian vs. non-Chinese Asian vs. non-Asian), and randomized 1:1 to receive osimertinib 80 mg once daily (QD) or placebo QD until disease recurrence, treatment discontinuation, or a maximum treatment duration of 3 years. The primary endpoint of this study is disease-free survival (DFS) in the high-risk stratum. Secondary endpoints include DFS in the overall population, overall survival, CNS DFS, and safety. Health-related quality of life and pharmacokinetics will also be evaluated. RESULTS: Study enrolment began in February 2022 and interim results of the primary endpoint are expected in August 2027.
  • Atsushi Kamigaichi; Akira Hamada; Yasuhiro Tsutani
    Frontiers in oncology 13 1287088 - 1287088 2023年 
    For decades, lobectomy has been the recommended surgical procedure for non-small cell lung cancer (NSCLC), including for small-sized lesions. However, two recent pivotal clinical trials conducted by the Japanese Clinical Oncology Group/West Japan Oncology Group (JCOG0802/WJOG4607L) and the Cancer and Leukemia Group B (CALGB140503), which compared the survival outcomes between lobectomy and sublobar resection (the JCOG0802/WJOG4607L included only segmentectomy, not wedge resection), demonstrated the efficacy of sublobar resection in patients with early-stage peripheral lung cancer measuring ≤ 2 cm. The JCOG0802/WJOG4607L demonstrated the superiority of segmentectomy over lobectomy with respect to overall survival, implying the survival benefit conferred by preservation of the lung parenchyma. Subsequently, the JCOG1211 also demonstrated the efficacy of segmentectomy, even for NSCLC, measuring up to 3 cm with the predominant ground-glass opacity phenotype. Segmentectomy has become the standard of care for early-stage NSCLC and its indications are expected to be further expanded to include solid lung cancers > 2 cm. However, local control is still a major concern for segmentectomy for higher-grade malignant tumors. Thus, the indications of segmentectomy, especially for patients with radiologically pure-solid NSCLC, remain controversial due to the aggressive nature of the malignancy. In this study, we reviewed previous studies and discussed the efficacy of segmentectomy for patients with such tumors.
  • Nobutaka Kawamoto; Yasuhiro Tsutani; Atsushi Kamigaichi; Manato Ohsawa; Takahiro Mimae; Yoshihiro Miyata; Morihito Okada
    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 2022年12月 
    OBJECTIVES: Pathological lymph node metastases are often observed in patients with clinical N0 lung cancer. Identifying preoperative predictors of occult hilar nodal metastasis is important in determining the surgical procedure in patients with clinical stage I non-small cell lung cancer. This study aimed to determine the frequency and predictors of occult hilar nodal metastasis by tumour location in these patients. METHODS: Between April 2007 and May 2019, data of patients who underwent lobectomy or segmentectomy for clinical stage I pure-solid non-small cell lung cancer were retrospectively reviewed. The ratio of the distance from the pulmonary hilum to the proximal side of the tumour to the distance from the pulmonary hilum to the visceral pleural surface through the centre of the tumour, named "distance ratio," was calculated. The relationship of the distance ratio with clinicopathological findings and prognosis was discussed. RESULTS: A total of 357 patients were enrolled. Occult hilar nodal metastasis frequency was 14.6%. Patients were divided into two groups based on whether the distance ratio was ≤0.67 (central-type) or > 0.67 (peripheral-type). The frequency of occult hilar nodal metastasis was significantly higher in the distance ratio ≤0.67 group (21.5% vs 7.4%; P < 0.001). Multivariable analysis revealed that distance ratio was the only independent preoperative predictor of occult hilar nodal metastasis (odds ratio, 3.63; 95% confidence interval, 1.83-7.18; P < 0.001). CONCLUSIONS: The frequency of occult hilar nodal metastasis was significantly higher in peripheral-type lung cancer; therefore, tumour location was the most important preoperative predictor of occult hilar nodal metastasis.
  • Atsushi Kagimoto; Yasuhiro Tsutani; Kei Kushitani; Takahiro Kambara; Takahiro Mimae; Yoshihiro Miyata; Yukio Takeshima; Morihito Okada
    Thoracic cancer 2022年12月 
    BACKGROUND: The S100 calcium-binding protein A4 (S100A4) and the accumulation of [18F]-fluoro-2-deoxy-D-glucose (FDG) in noncancerous interstitial pneumonia (IP) area are predictors of postoperative acute exacerbation (AE) of IP after pulmonary resection for lung cancer with IP. However, the significance of combining these markers for predicting short-term outcome and long-term prognosis is not known. METHODS: Patients diagnosed with IP on preoperative high-resolution computed tomography and who had undergone pulmonary resection for primary lung cancer between April 2010 and March 2019 at Hiroshima University were included in this study. Predictive factors for the cumulative incidence of death from other than lung cancer (CIDOL) were investigated using the Fine and Gray model. CIDOL, perioperative outcome, and cumulative incidence of all death (CIAD) were retrospectively compared based on serum S100A4 and FDG accumulation. RESULTS: A total of 121 patients were included in this study. High S100A4 (hazard ratio [HR], 2.541; p = 0.006) and FDG accumulation (HR, 3.199; p = 0.038) were significant predictors of CIDOL. AE of IP occurred only in patients with high S100A4/FDG (+). CIDOL of patients with high S100A4/FDG (+) was higher than those with high S100A4/FDG (-) or low S100A4/FDG (+) (p < 0.001), and CIAD of patients with high S100A4/FDG (+) was also higher than those with high S100A4/FDG (-) or low S100A4/FDG (+) patients (p = 0.021). CONCLUSIONS: Serum S100A4 and FDG accumulation in the noncancerous IP area were significant predictors of CIDOL after lung resection for lung cancer with IP and may help decide the treatment strategy.
  • Atsushi Kamigaichi; Yasuhiro Tsutani; Takahiro Mimae; Yoshihiro Miyata; Hiroyuki Adachi; Yoshihisa Shimada; Yukio Takeshima; Hiroyuki Ito; Norihiko Ikeda; Morihito Okada
    Seminars in thoracic and cardiovascular surgery 2022年12月 
    Discrepancies between radiological whole tumor size (RTS) and pathological whole tumor size (PTS) are sometimes observed. Unexpected pathological upsize may lead to insufficient margins during procedures like sublobar resections. Therefore, this study aimed to investigate the current status of these discrepancies and identify factors resulting in pathological upsize in patients with early-stage non-small cell lung cancer (NSCLC). Data from a multicenter database of 3,092 patients with clinical stage 0-IA NSCLC who underwent pulmonary resection were retrospectively analyzed. Differences between the RTS and PTS were evaluated using Pearson's correlation analysis and Bland-Altman plots. Unexpected pathological upsize was defined as an upsize of ≥ 1 cm when compared to the RTS, and the predictive factors of this upsize were identified based on multivariable analyses. The RTS and PTS showed a positive linear relationship (r = 0.659), and the RTS slightly overestimated the PTS. The Bland-Altman plot showed 131 of 3092 (5.2%) cases were over the upper 95% limits of agreement. In multivariable analyses, a maximum standardized uptake value (SUVmax) of the primary tumor on 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography (odds ratio [OR], 1.070; 95% confidence interval [CI], 1.035-1.107; P <0.001) and the adenocarcinoma histology (OR, 1.899; 95% CI, 1.071-3.369; P =0.049) were independent predictors of unexpected pathological upsize. More of the adenocarcinomas with pathological upsize were moderately or poorly differentiated, when compared to those without. The RTS tends to overestimate the PTS; however, care needs to be taken regarding unexpected pathological upsize, especially in adenocarcinomas with a high SUVmax.
  • Takahiro Mimae; Yoshihiro Miyata; Takashi Kumada; Yasuhiro Tsutani; Morihito Okada
    JTCVS techniques 16 132 - 138 2022年12月 
    OBJECTIVE: To clarify whether intersegmental pulmonary veins are always located on the intersegmental plane and determine the division from which blood flows into them. METHODS: We analyzed representative intersegmental veins located between the upper/lingular and superior/basal division of the lungs using preoperative chest computed tomography (CT) DICOM data from 22 patients who underwent lobectomy or segmentectomy during 2020. The location and blood flow of V3a+b and V6b+c were assessed using REVORAS (Ziosoft), a novel volume-rendering 3-dimensional (3D) image reconstruction software dedicated to lung segmentectomy. RESULTS: The V3a+b was in the upper division and on the intersegmental plane between the upper and lingular divisions of the left lung in 11 patients (50%) each. A main root of V3a+b was not found in the lingular division, but some peripheral flow in the V3a+b was derived from it in 14 patients (64%). The V6b+c was found in the superior division of the right lower lobe in 13 patients (59%) and the left lower lobe in 10 patients (45%), and on the intersegmental plane between the superior and basal division of the right lower lobe in 6 patients (27%) and the left lower lobe in 10 patients (45%). A main root of V6b+c was imperceptible in the basal division. Some peripheral blood flow was derived from the basal division in 6 patients (27%) with V6b+c veins located in the right lower lobe and in 8 patients (36%) with V6b+c veins located in the left lower lobe. CONCLUSIONS: Precise evaluation of intersegmental veins using preoperative volume-rendering 3D reconstructed CT images provides useful anatomic information for separating intersegmental pulmonary parenchyma.
  • Atsushi Kagimoto; Yasuhiro Tsutani; Yoshihisa Shimada; Takahiro Mimae; Yoshihiro Miyata; Hiroyuki Ito; Haruhiko Nakayama; Norihiko Ikeda; Morihito Okada
    Thoracic cancer 13 24 3477 - 3485 2022年11月 
    BACKGROUND: Squamous cell carcinoma of the lung-the second most common subtype of lung cancer-has a poorer prognosis than lung adenocarcinoma. However, in contrast to lobectomy, the oncological outcomes after segmentectomy for primary squamous cell carcinomas remain unknown; hence, this study investigated these outcomes. METHODS: Patients who underwent lobectomy or segmentectomy for clinically node-negative primary lung squamous cell carcinoma with a whole tumor size of ≤ 30 mm on preoperative computed tomography scan during April 2010 to December 2020 were included in this study. The cumulative incidence of recurrence (CIR) among all included patients and propensity score-matched patients were compared using the Gray method. Multivariate analysis using propensity scores and surgical procedures was performed using the Fine and Gray method. RESULTS: Overall, 230 patients were included in this study; of these, 172 (74.8%) underwent lobectomy and 58 (25.2%) underwent segmentectomy. No significant differences were observed in the CIR between patients who underwent lobectomy and those who underwent segmentectomy (5-year rate 18.1% vs. 14.2%; p  =  0.787). Moreover, no significant differences in CIR were observed between the propensity score-matched patients who underwent lobectomy (n = 43) and those who underwent segmentectomy (n   =  43) (8.6% vs. 8.0%; p = 0.571). Multivariable analysis was performed for CIR using the propensity score; it revealed that segmentectomy was not a significant predictor of worse CIR (hazard ratio, 0.987; p =   0.980). CONCLUSIONS: Segmentectomy may be feasible for treating clinically early-stage lung squamous cell carcinoma; its oncological outcomes are similar to those of lobectomy.
  • Yasuhiro Tsutani; Masaoki Ito; Yoshihisa Shimada; Hiroyuki Ito; Norihiko Ikeda; Haruhiko Nakayama; Morihito Okada
    The Journal of thoracic and cardiovascular surgery 164 5 1306 - 1315 2022年11月 
    OBJECTIVE: The aim of this study was to evaluate the role and effect of adjuvant chemotherapy based on epidermal growth factor receptor mutation status in patients with stage I lung adenocarcinoma. METHODS: Between 2010 and 2016, of 1901 patients with pathologic stage I (8th edition) non-small cell lung cancer, we identified 475 with high-risk (pT1c/T2a or positive for lymphovascular invasion) stage I lung adenocarcinoma who underwent lobectomy. We estimated propensity scores to adjust for confounding variables, including age, sex, Brinkman index, pulmonary functions, comorbidities, surgical approach, invasive component tumor size, visceral pleural, lymphatic, and vascular invasion, adenocarcinoma subtype, epidermal growth factor receptor mutation status, postoperative complications, and institution associated with the administration of adjuvant chemotherapy. The primary end point was recurrence-free survival. RESULTS: Of 292 patients without/unknown epidermal growth factor receptor mutation, 105 (36.0%) received adjuvant chemotherapy and 187 (64.0%) did not. In 69 pairs of patients who were propensity score matched, the 5-year recurrence-free survival was significantly better in those who underwent adjuvant chemotherapy (88.4%) than in those who did not (63.6%; P = .001). Of 183 patients with epidermal growth factor receptor mutation, 78 (42.6%) received adjuvant chemotherapy and 105 (57.4%) did not. In 49 pairs of propensity score-matched patients, there was no significant difference in the 5-year recurrence-free survival between those who underwent adjuvant chemotherapy (74.3%) and those who did not (80.5%; P = .573). CONCLUSIONS: The effect of adjuvant chemotherapy for high-risk stage I lung adenocarcinoma varied by epidermal growth factor receptor mutation status. Epidermal growth factor receptor mutation status may help to identify patients with high-risk stage I lung adenocarcinoma who may benefit from adjuvant chemotherapy.
  • Daisuke Ueda; Yasuhiro Tsutani; Atsushi Kamigaichi; Nobutaka Kawamoto; Norifumi Tsubokawa; Masaoki Ito; Takahiro Mimae; Yoshihiro Miyata; Morihito Okada
    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 63 1 2022年10月 
    OBJECTIVES: Erector spinae muscle is an antigravity muscle group that can be evaluated as an index of muscle loss on chest computed tomography. The amount of erector spinae muscle has been reported to be related to the prognosis of several respiratory diseases. However, few studies clarify the impact on postoperative non-small cell lung cancer. We investigated the relationship between erector spinae muscle and postoperative prognosis in early-stage non-small cell lung cancer. METHODS: We reviewed the medical records of 534 patients with stage I non-small cell lung cancer who underwent lobectomy or segmentectomy. The erector spinae muscle was identified by preoperative computed tomography, and the amount was normalized according to height and sex. Overall survival, lung cancer-related death, and non-lung cancer-related death were analyzed using log-rank and Gray's tests. Multivariable analyses were conducted to identify factors that influenced overall survival and non-lung cancer-related death. RESULTS: The amount of erector spinae muscle normalized according to height and sex was significantly associated with age and body mass index, and when the amount was low, overall survival (five-year overall survival, 79.6 vs 89.5%; P < 0.001) and non-lung cancer-related death (five-year cumulative mortality rate, 14.7 vs 6.8%; P < 0.001) were significantly worse, although no difference was found in lung cancer-related death. CONCLUSIONS: The amount of preoperative erector spinae muscle was strongly related to non-lung cancer-related death and was a significant prognostic factor for stage I non-small cell lung cancer. Patients with low amount of the muscle should be treated based on proper risk assessment.
  • Atsushi Kamigaichi; Yasuhiro Tsutani; Yoshinori Handa; Takahiro Mimae; Yoshihiro Miyata; Morihito Okada
    Surgery today 2022年10月 
    PURPOSE: This study aimed to elucidate the feasibility of repeated ipsilateral anatomical pulmonary resection. METHODS: The subjects of this retrospective analysis were 50 patients who underwent ipsilateral anatomical pulmonary resection after major lung surgery. The patients were divided into two groups according to the type of primary operation performed: a repeated anatomical pulmonary resection group (RA group; n = 24) and an anatomical pulmonary resection after wedge resection group (AW group; n = 26). We compared the perioperative outcomes of the two groups. RESULTS: Completion lobectomy was performed in 9 of the 24 patients (38%) from the RA group and adhesion of the pulmonary hilum was more severe in this group (P = 0.004). Although the operative time was significantly longer in the RA group (P = 0.030), there was no significant difference in the amount of blood loss (P = 0.217) between the groups. A significantly higher rate of severe postoperative complications was observed in the RA group (42%) than in the AW group (12%) (P = 0.024). None of the patients who underwent repeated surgery died within 90 days postoperatively. CONCLUSION: Although repeated anatomical pulmonary resection is a more challenging procedure than anatomical resection after wedge resection, it does not increase short-term mortality; therefore, it is a feasible treatment option.
  • 肺癌術後の経時的ctDNA測定が病勢予測に有用であった1例
    櫻井 真倫; 小原 秀太; 須田 健一; 福田 祥大; 濱田 顕; 千葉 眞人; 下治 正樹; 武本 智樹; 宗 淳一; 津谷 康大; 光冨 徹哉
    肺癌 62 5 439 - 439 (NPO)日本肺癌学会 2022年10月
  • Atsushi Kagimoto; Yasuhiro Tsutani; Morihito Okada
    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 62 4 2022年09月
  • Takahiro Mimae; Yoshihiro Miyata; Yasuhiro Tsutani; Yoshihisa Shimada; Hiroyuki Ito; Haruhiko Nakayama; Norihiko Ikeda; Morihito Okada
    JTCVS open 11 300 - 316 2022年09月 
    Objective: Lung adenocarcinoma often includes noninvasive components with postoperative lepidic morphology on pathologic specimens that appear on preoperative high-resolution computed tomography (HRCT) images as ground-glass opacity (GGO). We aimed to disclose the role of GGO on the aggressiveness of pathologically confirmed pure invasive tumors in patients with early-stage lung adenocarcinoma. Methods: The prognosis of 932 patients with clinical stage 0-IA and pathologic node-negative lung adenocarcinoma who underwent lobectomy at 3 institutions between 2010 and 2016 was investigated according to the status of GGO and lepidic components. Results: The recurrence-free survival (RFS) of patients with pathologically confirmed pure invasive tumors was worse without (n = 81) than with (n = 43) GGO (69.7%; 95% confidence interval [CI], 57.3%-79.2% vs 90.5%; 95% CI, 76.6%-96.3%, P = .028). The RFS of patients with radiologically confirmed pure solid tumors was worse without (n = 81), than with (n = 173) a lepidic component (69.7%; 95% CI, 57.3%-79.2% vs 85.3%; 95% CI, 77.2%-90.7%, P = .0012). Multivariable Cox regression analysis of overall survival and RFS revealed that pure solid and pure invasive tumors, respectively, determined by HRCT and pathologic assessment together comprised an independent prognostic factor like vascular or pleural invasion for patients with early-stage lung adenocarcinoma. Conclusions: Tumors of non–small cell lung cancer with pure solid and pure invasive components were more aggressive than those with some GGO and lepidic components. Complementary HRCT and pathologic findings can predict the malignant aggressiveness of adenocarcinoma.
  • Atsushi Kamigaichi; Yasuhiro Tsutani; Takahiro Mimae; Yoshihiro Miyata; Yoshihisa Shimada; Hiroyuki Ito; Haruhiko Nakayama; Norihiko Ikeda; Morihito Okada
    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 62 3 2022年08月 
    OBJECTIVES: The aim of this study was to assess the clinical effects of a small ground-glass opacity (GGO) component of a radiologically nearly pure-solid tumour on tumour aggressiveness in patients with clinical stage IA non-small-cell lung cancer (NSCLC). METHODS: Data of 988 patients with clinical stage IA NSCLC who had a consolidation-to-tumour ratio of ≥0.75 on high-resolution computed tomography were retrospectively analysed. The cumulative incidence of recurrence (CIR) was compared between patients with GGO (nearly pure-solid, n = 297) and those without GGO (pure-solid, n = 691). RESULTS: In patients with clinical T1mi + T1a and T1b, the CIR was significantly higher in the pure-solid group than in the nearly pure-solid group (5-year CIR, 15.2% and 19.3% vs 0% and 6.4%; P < 0.001); however, this was not the case for patients with clinical T1c (5-year CIR, 23.1% vs 26.5%; P = 0.580). In the multivariable analysis, pure-solid tumours were independently associated with a higher CIR than nearly pure-solid tumours in patients with clinical T1mi + T1a + T1b (solid tumour size ≤2 cm; subdistribution hazard ratio, 3.25; 95% confidence interval, 1.59-6.63; P = 0.001) but not in those with clinical T1c tumours (2-3 cm; subdistribution hazard ratio, 0.67; 95% confidence interval, 0.39-1.13; P = 0.130). CONCLUSIONS: Nearly pure-solid tumours with a small GGO component influence tumour aggressiveness based on solid tumour size, with a threshold of 2 cm in patients with clinical stage IA NSCLC. For tumours sized 2-3 cm, nearly pure-solid tumours had a similar tumour aggressiveness as pure-solid tumours.
  • Makoto Fujiwara; Takahiro Mimae; Yasuhiro Tsutani; Yoshihiro Miyata; Morihito Okada
    The Annals of thoracic surgery 2022年07月 
    BACKGROUND: Idiopathic pulmonary fibrosis guidelines changed the high-resolution computed tomography (HRCT) pattern from 3 to 4 categories in 2018. We assessed the relationship between surgical outcomes and HRCT patterns according to the 2018 guidelines. METHODS: Among 1503 patients who underwent pulmonary resection for clinical stage Ⅰ to stage Ⅲ lung cancer at our institution between April 2007 and June 2019, we retrospectively investigated 218 with interstitial lung abnormalities based on preoperative HRCT. We reclassified all interstitial lung abnormality cases with preoperative HRCT from 3 patterns-usual interstitial pneumonia (UIP), possible, and inconsistent with UIP-of the previous (2011) guidelines to 4 patterns-UIP, probable UIP, indeterminate, and alternative diagnosis-according to the new consensus guideline of idiopathic pulmonary fibrosis (2018). The occurrence of acute exacerbations and survival were analyzed, and the association with HRCT pattern was investigated. RESULTS: Interstitial lung abnormality cases were reclassified as UIP (n = 55 [25.2%]), probable UIP (n = 36 [16.5%]), indeterminate UIP (n = 56 [25.7%]), and alternative diagnosis (n = 71 [32.6%]). Acute exacerbations developed in 21 patients (UIP pattern, n = 9 [16.4%]; probable UIP, n = 5 [13.9%]; indeterminate, n = 3 [5.4%]; and alternative diagnosis, n = 4 [5.6%]). Multivariable Cox regression revealed that UIP pattern or probable UIP pattern of the 2018 guideline was an independent risk factor for severe acute exacerbations (grade III-Ⅴ; odds ratio, 6.81; 95% CI, 1.42-32.60) and postoperative overall survival (hazard ratio, 3.12; 95% CI, 1.70-5.73). CONCLUSIONS: UIP and probable UIP patterns were risk factors for postoperative severe acute exacerbations and death. The HRCT patterns of the 2018 guidelines can stratify outcomes of lung resection.
  • Atsushi Kagimoto; Yasuhiro Tsutani; Yoshihisa Shimada; Takahiro Mimae; Yoshihiro Miyata; Hiroyuki Ito; Haruhiko Nakayama; Norihiko Ikeda; Morihito Okada
    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 62 2 2022年07月 
    OBJECTIVES: Segmentectomy can provide oncologically acceptable results for small-sized non-small-cell lung cancer (NSCLC). However, in cases of NSCLC with pathological invasive characteristics such as lymphatic invasion (LY), vascular invasion (V), pleural invasion (PL) and/or lymph node metastasis, the feasibility of segmentectomy is not known. METHODS: The patients included in the study (i) underwent lobectomy or segmentectomy for NSCLC with invasive characteristics such as LY, V, PL or pathological lymph node metastasis; (ii) presented with a node-negative, solid component-predominant tumour (consolidation tumour ratio >50%) on preoperative computed tomography; (iii) had a whole-tumour size of 2 cm or less; and (iv) presented between January 2010 and December 2019 to one of the 3 institutions. Cumulative incidences of recurrence (CIRs) after segmentectomy and lobectomy were compared. RESULTS: A total of 321 patients were included. Segmentectomy and lobectomy were performed in 80 (24.9%) and 241 (75.1%) patients, respectively. There was no significant difference in CIR between segmentectomy (5-year CIR rate, 17.2%) and lobectomy patients (5-year CIR rate, 27.8%, P = 0.135). In the propensity score-matched cohort, there was no significant difference in CIR between segmentectomy (5-year CIR rate, 19.1%) and lobectomy patients (5-year CIR rate, 19.2%; P = 0.650). In the multivariable analysis using inverse probability of treatment weighting and surgical method, segmentectomy was not a significant predictor of worse CIR (P = 0.920). CONCLUSIONS: Segmentectomy is feasible for clinically early-stage NSCLC irrespective of the presence of LY, V, PL or lymph node metastasis.
  • Yoshinori Handa; Yasuhiro Tsutani; Takahiro Mimae; Yoshihiro Miyata; Yoshihisa Shimada; Hiroyuki Ito; Haruhiko Nakayama; Norihiko Ikeda; Morihito Okada
    Clinical lung cancer 23 5 393 - 401 2022年07月 
    BACKGROUND: Although sublobar resection is widely used for lung cancer treatment, very limited data are available comparing outcomes after complex segmentectomy and wedge resection. We compared the oncological outcomes of complex segmentectomy and wedge resection for clinical stage 0-IA lung cancer via a large cohort, multicenter database using propensity score-matched analysis. PATIENTS AND METHODS: We retrospectively analyzed data from 506 clinical stage 0-IA, solid component size ≤ 2.0 cm lung cancer patients who underwent surgical resection at three institutions between 2010 and 2018. Surgical results after complex segmentectomy (n = 222) and "location-adjusted" wedge resection (n = 284) were analyzed for all patients and their propensity score-matched pairs. RESULTS: In all cohort, the complex segmentectomy group tended to have a better prognosis than the wedge resection group (5 year cancer-specific survival rate, 97.4% vs. 93.7%; P = .065 and 5 year recurrence-free interval [RFI] rates, 96.9% vs. 86.1%; P = .0005). This trend was also identified in subanalyses for pure solid tumors. In 179 propensity score-matched pairs, the prognosis of patients with complex segmentectomy tended to be better than that of patients with wedge resection (5 year cancer-specific survival rates, 96.8% vs. 92.9%; 5 year RFI rates, 96.3% vs. 87.5%). Multivariable Cox regression analysis for RFI revealed that complex segmentectomy significantly reduced lung cancer recurrence compared with wedge resection (hazard ratio, 0.32; 95% confidence interval, 0.12-0.73; P = .0061). CONCLUSIONS: Complex segmentectomy can provide better oncological outcomes compared with wedge resection.
  • Atsushi Kagimoto; Yasuhiro Tsutani; Takahiro Mimae; Yoshihiro Miyata; Morihito Okada
    Interactive cardiovascular and thoracic surgery 34 5 814 - 821 2022年05月 
    OBJECTIVES: The prognosis of segmentectomy and wedge resection for solid predominant early-stage non-small cell lung cancer with low metabolic activity is unclear. METHODS: This study aimed to assess patients who underwent segmentectomy or wedge resection with curative intent for clinically node-negative non-small cell lung cancer presenting as a solid predominant tumour (consolidation tumour ratio >50%) with a whole size ≤3 cm and [18F]-fluoro-2-deoxy-D-glucose accumulation weaker than that of the mediastinum tissue (Deauville score, 1 or 2) on positron emission tomography/computed tomography. The cumulative incidence of recurrence (CIR) was compared using the Gray method, and the predictive factor of CIR was analysed using the Fine and Gray method. RESULTS: Of 140 patients included in this study, 93 (66.4%) underwent segmentectomy and 47 (33.6%) underwent wedge resection. No significant difference in the clinical stage was found between the 2 groups. The CIR was higher with wedge resection than with segmentectomy (P = 0.004). Recurrence after wedge resection was noted in 4 (8.5%) patients, 2 of whom had a recurrent site containing lung parenchyma of the preserved lobe and hilum lymph node, which would have been resected if segmentectomy had been performed. In the multivariable analysis for CIR using inverse probability of treatment weighting and the procedure, wedge resection was a significantly worse predictive factor (hazard ratio, 12.280; P = 0.025). CONCLUSIONS: Segmentectomy rather than wedge resection should be considered for solid predominant, small-size non-small cell lung cancer even if [18F]-fluoro-2-deoxy-D-glucose accumulation is low.
  • Takahiro Mimae; Yoshihiro Miyata; Takashi Kumada; Yoshinori Handa; Yasuhiro Tsutani; Morihito Okada
    Interactive cardiovascular and thoracic surgery 34 5 753 - 759 2022年05月 
    OBJECTIVES: Changes in postoperative pulmonary function vary among patients after lobectomy. We aimed to define preoperative factors that negatively influence postoperative % vital capacity (%VC) in patients treated by lobectomy. METHODS: We included 276 patients who had been treated by lobectomy at our institution between 2007 and 2018 and their preoperative and postoperative pulmonary function data were complete. We assigned them to groups based on postoperative pulmonary function defined as better (good) or worse (poor) than predicted %VC, then compared clinicopathological findings between them. Poor postoperative pulmonary function was also assessed using logistic regression analysis. RESULTS: Interstitial pneumonia (IP) was diagnosed in 37 (13.4%) patients. The preoperative and postoperative %VC values were, respectively, 101.1% (interquartile range, 90.5-110%) and 87.6% (interquartile range, 73.8-99.1%). Logistic regression analysis revealed that IP, advanced age (≥75 years), and induction therapy were independent risk factors for reduced postoperative pulmonary function [odds ratios 3.01 (1.41-6.41), 2.49 (1.35-4.60), and 9.03 (2.43-33.5), P = 0.0044, 0.0035, and 0.001, respectively]. Postoperative %VC worsened with increasing IP severity and advanced age. Six (75%) of 8 patients aged ≥80 years with usual IP or suspected usual IP on preoperative computed tomography images had poor postoperative %VC. CONCLUSIONS: Surgical indications for lobectomy based on predicted postoperative %VC require careful consideration for elderly patients with IP, particularly those aged ≥80 years.
  • Yasuhiro Tsutani; Kentaro Imai; Hiroyuki Ito; Yoshihiro Miyata; Norihiko Ikeda; Haruhiko Nakayama; Morihito Okada
    The Annals of thoracic surgery 113 5 1608 - 1616 2022年05月 
    BACKGROUND: This study aimed to investigate the efficacy of adjuvant chemotherapy for pathologic stage I non-small cell lung cancer (NSCLC) with high risk for recurrence. METHODS: Prospectively collected data from 1278 patients with pathologic stage I NSCLC according to eighth edition staging guidelines who were undergoing lobectomy were retrospectively analyzed. Factors associated with high risk for recurrence were determined using the multivariable Cox proportional hazards model for recurrence-free survival (RFS). Survival was compared between patients who received adjuvant chemotherapy and those who did not. RESULTS: In multivariable analysis, age (>70 years), invasive component size (>2 cm), visceral pleural invasion, lymphatic invasion, and vascular invasion were identified as independent factors for RFS. In patients with high-risk factors for recurrence such as pathologic T1c or T2a or lymphovascular invasion (high-risk group; n = 641), adjuvant chemotherapy resulted in significantly longer RFS and overall survival (n = 222; 5-year RFS, 81.4%; 5-year overall survival, 92.7%) than in patients who did not receive adjuvant chemotherapy (n = 418; 5-year RFS, 73.8%; P = .023; 5-year overall survival, 81.7%; P < .0001). In patients without any high-risk factors for recurrence (low-risk group; n = 637), RFS was not significantly different between those who received adjuvant chemotherapy (n = 83; 5-yeat RFS, 98.1%) and those who did not (n = 554; 5-year RFS, 95.7%; P = .30). CONCLUSIONS: Adjuvant chemotherapy may improve survival in patients with pathologic stage I NSCLC who have factors associated with high risk for recurrence, such as pathologic T1c or T2a or lymphovascular invasion.
  • Yoshinori Handa; Yasuhiro Tsutani; Takahiro Mimae; Yoshihiro Miyata; Hiroyuki Ito; Yoshihisa Shimada; Haruhiko Nakayama; Norihiko Ikeda; Morihito Okada
    Annals of Thoracic Surgery 113 4 1317 - 1324 2022年04月 
    Background: Due to its invasiveness, the indications for “complex segmentectomy” for radiologically hypermetabolic (high maximum standard uptake value) non-small cell lung cancer (NSCLC) remain controversial. This study compared the outcomes after complex segmentectomy and lobectomy in these patients. Methods: We retrospectively reviewed 717 patients with radiologically hypermetabolic (maximum standardized uptake value ≥2.5), clinical stage IA NSCLC who underwent complex segmentectomy (n = 61) or location-adjusted lobectomy (n = 656) at three institutions from 2010 to 2019. Postoperative outcomes were analyzed for all patients and their propensity score matched pairs. Factors affecting oncologic outcomes were assessed by Kaplan-Meier estimates and Cox proportional hazards regression analyses. Results: The prognosis of patients undergoing complex segmentectomy was not significantly different from that of patients undergoing lobectomy (5-year cancer-specific survival rate, 89.9% vs 91.1%, P = .98; and 5-year recurrence-free interval rate, 83% vs 77.5%, P = .62) in the nonadjusted cohort. In 55 propensity score matched pairs, oncologic outcomes were not significantly different between patients undergoing complex segmentectomy (5-year cancer-specific survival, 89.9%; 5-year recurrence-free interval, 83%) and lobectomy (5-year cancer-specific survival, 83.6%; 5-year recurrence-free interval, 82.5%). Multivariable Cox regression analysis for recurrence-free interval revealed no significant differences between oncologic outcomes associated with complex segmentectomy and lobectomy (hazard ratio, 0.84; 95% confidence interval, 0.25 to 2.14; P = .74). Conclusions: Oncologic outcomes of complex segmentectomy and lobectomy were not significantly different for patients with radiologically hypermetabolic, clinical stage IA NSCLC patients. Complex segmentectomy can treat high maximum standardized uptake value, clinical stage IA lung cancers without compromising oncologic results.
  • 原田敏之; 大泉聡史; 高村圭; 立原素子; 森川直人; 本田亮一; 渡部聡; 朝尾哲彦; 國崎守; 福原達朗; 野呂林太郎; 菊地英毅; 津谷康大; 天満紀之; 原田敏之; 大泉聡史; 高村圭; 立原素子; 森川直人; 本田亮一; 渡部聡; 朝尾哲彦; 國崎守; 福原達朗; 野呂林太郎; 菊地英毅; 津谷康大; 天満紀之; 小林国彦; 秋田弘俊
    日本呼吸器学会誌(Web) 27 4 676 - 683 2022年04月 
    OBJECTIVES: Only a few prospective studies have been conducted to examine the efficacy and safety of systemic chemotherapy for patients with pulmonary sarcomatoid carcinomas (PSCs). There is, thus, a crucial need to develop novel treatment strategies for this rare tumor. PATIENTS AND METHODS: Chemotherapy-naïve patients with histologically confirmed PSCs were assigned to receive either carboplatin/paclitaxel alone (CP) or with bevacizumab (CPB) followed by bevacizumab maintenance. The primary endpoint was overall response rate (ORR). Secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety. RESULTS: This study was closed before accumulating the expected number of cases due to slow patient accrual. Eventually, 16 patients were enrolled. The ORR was 25.0% and disease control rate was 56.3%. CPB was administered in all four patients with an objective response [partial response (PR)]; among the four PR cases, two patients had pleomorphic carcinoma, and two had carcinosarcoma. Median PFS and median survival time (MST) in all the enrolled patients were 2.6 months and 8.8 months, respectively. Median PFS was 1.2 months in the CP group and 4.2 months in the CPB group. In addition, MST was 7.9 months in the CP group and 11.2 months in the CPB group. Hematological and non-hematological adverse events were common and reversible, although ileus (grade 4) and nasal bleeding (grade 3) occurred in one case each in the CPB group. CONCLUSIONS: CPB might be effective as first-line treatment for PSCs. Further study is warranted to clarify the role of cytotoxic chemotherapy for this rare and aggressive tumor. CLINICAL TRIALS REGISTRATION: University Hospital Medical Information Network (UMIN) Clinical Trial Registry (UMIN000008707).
  • Yasuhiro Tsutani; Morihito Okada
    Operative Techniques in Thoracic and Cardiovascular Surgery 27 3 329 - 339 2022年02月 
    Now, the standard treatment for clinical stage I non-small cell lung cancer (NSCLC) is lobectomy with systematic nodal dissection. Sublobar resections, such as segmentectomy and wedge resection are often performed in compromised patients with peripheral small-sized NSCLC who are unfit or at high risk for standard lobectomy or even in those with indolent NSCLC who are fit for lobectomy. Anatomical segmentectomy rather than non-anatomical wedge resection as sublobar resection is usually recommended. Segmentectomy could be subdivided according to the number and shape of intersegmental plane. Segmentectomy that creates one, linear intersegmental plane, with a relatively easier procedure, could be considered simple segmentectomy, that is, resection of the superior segmentectomy of the lower lobe, the upper division, or lingula segment of the left upper lobe. Segmentectomy that creates several, or intricate intersegmental planes, with more a complex procedure, could be considered complex segmentectomy, that is, one other than simple segmentectomy, such as non-superior segmentectomy of the basilar segment of the lower lobe. Because of procedural complexity and risk of increased complications and incurability, compared with simple segmentectomy, some general thoracic surgeons may have concerns to perform complex segmentectomies. In this article, we show the technique of posterior basal segmentectomies, which is one of the most challenging procedures in complex segmentectomy, through a hybrid video-assisted thoracic surgery approach.
  • Atsushi Kagimoto; Yasuhiro Tsutani; Takahiro Mimae; Yoshihiro Miyata; Morihito Okada
    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 61 2 279 - 286 2022年01月 
    OBJECTIVES: Prognosis after segmentectomy for early-stage non-small cell lung cancer (NSCLC) with a high consolidation tumour ratio (CTR) and [18F]-fluoro-2-deoxy-d-glucose (FDG) accumulation on positron emission tomography/computed tomography is unclear. METHODS: Participants of this study were 465 patients who underwent lobectomy or segmentectomy for clinical N0 NSCLC presenting solid component predominant tumour (CTR >50%) with a whole size ≤3 cm. Accumulations of FDG on positron emission tomography/computed tomography scans were scored according to the Deauville criteria, a 5-point visual evaluating method (Deauville score). The correlations between Deauville score, prognosis, and procedures were analysed. RESULTS: Characteristics of pathological invasiveness, such as lymphatic invasion (P < 0.001), vascular invasion (P < 0.001) and pleural invasion (P < 0.001), and non-adenocarcinoma histologies (P < 0.001) were more common in patients with Deauville scores of 3-5. The cumulative incidence of recurrence (CIR) was higher in patients with Deauville scores of 3-5 (P < 0.001). The CIR after lobectomy and segmentectomy did not differ significantly among patients with Deauville scores of 1 or 2 (P = 0.598) or those with Deauville scores of 3-5 (P = 0.322). In the analysis of propensity score matched cohort, the CIR after lobectomy and segmentectomy did not differ significantly between patients with Deauville scores of 1 or 2 and Deauville scores of 3-5. CONCLUSIONS: Segmentectomy may be feasible for NSCLC with high CTR (>50%) and accumulation of FDG. This finding should be confirmed in larger prospective studies.
  • Yoshinori Handa; Yasuhiro Tsutani; Masaoki Ito; Yoshihiro Miyata; Hidenori Mukaida; Mayumi Kaneko; Yukio Takeshima; Morihito Okada
    Clinical lung cancer 23 1 e9-e16.e1  2022年01月 
    BACKGROUND: The aim of this study was to investigate and compare the clinical behaviors of combined and pure high-grade neuroendocrine carcinoma (large-cell neuroendocrine carcinoma [LCNEC] and small-cell lung carcinoma [SCLC]). PATIENTS AND METHODS: Data of 132 patients who underwent complete resection for combined or pure high-grade neuroendocrine carcinoma (combined group, 67; pure group, 65) between January 2001 and December 2015 were retrospectively reviewed. The clinicopathological features were analyzed and compared, and the prognoses were assessed by performing the Kaplan-Meier method and Cox regression analysis. RESULTS: The combined and pure groups had nearly equivalent clinicopathological characteristics, specifically, older males with smoking history, almost the same percentage of pleural/lymphatic/vascular invasion, and nearly the same recurrence rates and relapse patterns. The combined group had prognosis equivalent to that of the pure group (5-year overall survival [OS] rates: 61.8% vs. 52.2%, respectively; P = .82 and 5-year recurrence-free survival [RFS] rates: 42.4% vs. 43.9%, respectively; P = .96), and this trend was identified in sub-analyses only for patients with LCNEC, SCLC, and the same pathological stage. Multivariable Cox regression analysis in patients with high-grade neuroendocrine carcinoma revealed that vascular invasion and pathological stage were independent prognostic factors for OS; more importantly, combined and pure histologies were proven to have nearly equivalent associations with prognosis (hazard ratio, 0.96; 95% confidence interval, 0.22to 1.66; P = .96). RESULTS: Combined high-grade neuroendocrine carcinoma had clinical behavior equivalent to those of pure high-grade neuroendocrine carcinoma, with similar clinicopathological characteristics.
  • Atsushi Kagimoto; Yasuhiro Tsutani; Morihito Okada
    The Annals of thoracic surgery 114 5 1989 - 1990 2021年12月
  • Daisuke Ueda; Masaoki Ito; Yasuhiro Tsutani; Ana Gimenez-Capitan; Ruth Roman-Llado; Ana Perez-Rosado; Cristina Aguado; Kei Kushitani; Yoshihiro Miyata; Koji Arihiro; Miguel Angel Molina-Vila; Rafael Rosell; Yukio Takeshima; Morihito Okada
    JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 147 12 3709 - 3718 2021年12月 
    Purpose The clinicopathological or genetic features related to the prognosis of mucinous adenocarcinoma are unknown because of its rarity. The clinicopathological or targetable features were investigated for better management of patients with mucinous adenocarcinoma of the lung. Methods We comprehensively evaluated the clinicopathological and genetic features of 60 completely resected mucinous lung adenocarcinomas. Targetable genetic variants were explored using nCounter and polymerase chain reaction, PD-L1 and TTF-1 expression were evaluated using immunohistochemistry. We analyzed the prognostic impact using the Kaplan-Meier method and log-rank test. Results Of the 60 enrolled patients, 13 (21.7%) had adenocarcinoma in situ/minimally invasive adenocarcinoma, and 47 (78.3%) had invasive mucinous adenocarcinoma (IMA). Fifteen patients (25%) showed a pneumonic appearance on computed tomography (CT). CD74-NRG1 fusion, EGFR mutations, and BRAF mutation were detected in three (5%), four (6.7%), and one (1.7%) patient(s), respectively. KRAS mutations were detected in 31 patients (51.7%). Two patients (3.5%) showed immunoreactivity for PD-L1. No in situ or minimally invasive cases recurred. IMA patients with pneumonic appearance had significantly worse recurrence-free survival (RFS) and overall survival (OS) (p < 0.001). Furthermore, IMA patients harboring KRAS mutations had worse RFS (p = 0.211). Multivariate analysis revealed that radiological pneumonic appearance was significantly associated with lower RFS (p < 0.003) and OS (p = 0.012). KRAS mutations served as an unfavorable status for RFS (p = 0.043). Conclusion Mucinous adenocarcinoma had a low frequency of targetable genetic variants and PD-L1 immunoreactivity; however, KRAS mutations were frequent. Pneumonic appearance on CT imaging and KRAS mutations were clinicopathological features associated with a worse prognosis.
  • Yoshinori Handa; Yasuhiro Tsutani; Takahiro Mimae; Yoshihiro Miyata; Morihito Okada
    Annals of surgical oncology 28 13 8347 - 8355 2021年12月 
    BACKGROUND: Segmentectomy has been increasingly used for lung cancer treatment, however there are very limited data evaluating the postoperative pulmonary function of patients treated with complex segmentectomy. We evaluated the postoperative pulmonary function of patients who underwent complex segmentectomy compared with simple segmentectomy, wedge resection, and lobectomy. METHODS: We retrospectively analyzed data from 580 patients who underwent surgical resection. The patients were divided into four groups: complex segmentectomy (n = 135), simple segmentectomy (n = 83), wedge resection (n = 89), and lobectomy (n = 273). Functional testing included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and predicted diffusing capacity of the lung for carbon monoxide (%DLCO) measured preoperatively and at 12 months after surgery. RESULTS: During the postoperative course, the complex segmentectomy and simple segmentectomy groups showed a comparable course of pulmonary function. The complex segmentectomy group significantly preserved pulmonary function compared with the lobectomy group (FVC, p = 0.017; FEV1, p = 0.010; %DLCO, p = 0.0043). A similar trend was observed even when restricted to lung diseases in the right upper lobe. On the other hand, when comparing complex segmentectomy with wedge resection, complex segmentectomy showed a trend that was more disadvantageous than wedge resection, but this difference was not significant (FVC, p = 0.19; FEV1, p = 0.40; %DLCO, p = 0.96). CONCLUSIONS: Complex segmentectomy showed comparable postoperative pulmonary functions as simple segmentectomy. Complex segmentectomy could preserve pulmonary function significantly compared with lobectomy and did not result in significant loss compared with wedge resection.
  • Yoshinori Handa; Yasuhiro Tsutani; Morihito Okada
    Annals of surgical oncology 28 13 8356 - 8357 2021年12月
  • Yoshinori Handa; Yasuhiro Tsutani; Morihito Okada
    Annals of surgical oncology 28 Suppl 3 848 - 849 2021年12月
  • Masaoki Ito; Yoshihiro Miyata; Kei Kushitani; Atsushi Kagimoto; Daisuke Ueda; Yasuhiro Tsutani; Yukio Takeshima; Morihito Okada
    Thoracic cancer 12 23 3141 - 3149 2021年12月 
    INTRODUCTION: Tumor size is an absolute recurrence risk in lung cancer. Although morphological features also reflect recurrence risk, its significance among lower-risk cases characterized by small size is unknown. We aimed to evaluate the relationship between pathological invasive tumor size and morphological features, and their prognostic impact by considering them simultaneously in lung adenocarcinoma. PATIENTS AND METHODS: We retrospectively reviewed 563 pN0M0 patients with pathological invasive size of ≤40 mm. The patients were classified by pathological invasive size and pathological malignant grading using the proportion of subhistological components. The prognostic impact was evaluated using recurrence-free survival (RFS) and overall survival (OS). The impact on prognosis was evaluated using uni- and multivariate analyses. RESULTS: The proportion of histological grade changed according to invasive tumor size. Patients with high malignant grade (G3) showed worse RFS than those with low and intermediate malignant grade (G1+2) with invasive size ≤20 mm. The 5-year RFS (G1+2 vs. G3) in 5-10 mm was 96.0% vs. 83.3% (HR = 5.505, 95% CI = 7.156-1850, p < 0.001) and in 10-20 mm was 87.8% vs. 67.1% (HR = 2.829, 95% CI = 4.160-43.14, p < 0.001). G3 patients were significantly bigger in invasive size and included more pleural/lymphatic/vascular invasion and recurrence. Multivariate analysis indicated pathological G3 status was significantly associated with worse RFS (HR = 2.097, 95% CI = 1.320-3.333, p = 0.002). CONCLUSIONS: Invasive tumor size and pathological malignant grade overlap in invasive adenocarcinoma. G3 patients are more likely to have pleural/lymphatic/vascular invasion and significantly worse RFS compared to G1/G2 cases, even with a small invasive size of ≤20 mm.
  • Yoshinori Handa; Yasuhiro Tsutani; Takahiro Mimae; Yoshihiro Miyata; Hiroyuki Ito; Yoshihisa Shimada; Haruhiko Nakayama; Norihiko Ikeda; Morihito Okada
    Annals of surgical oncology 28 12 7162 - 7171 2021年11月 
    BACKGROUND: The optimal extent of lymph node dissection (LND) for hypermetabolic tumors that are associated with high rates of nodal disease, recurrence, or mortality has not been elucidated. METHODS: We reviewed 375 patients who underwent lobectomy with lymphadenectomy for clinical T2-3 N0-1 M0 hypermetabolic non-small cell lung cancer (NSCLC) [maximum standard uptake value (SUVmax) ≥ 6.60] via a multicenter database. Extent of LND was classified into systematic mediastinal LND (systematic LND) and lobe-specific mediastinal LND (lobe-specific LND). Postoperative outcomes after lobectomy with systematic LND (n = 128) and lobe-specific LND (n = 247) were analyzed for all patients and their propensity-score-matched pairs. RESULTS: Cancer-specific survival (CSS) and recurrence-free interval (RFI) of the systematic LND group were not significantly different from those of the lobe-specific LND group in the nonadjusted whole cohort. In the propensity-score-matched cohort (101 pairs), systematic LND dissected significantly more lymph nodes (20.0 versus 16.0 nodes, P = 0.0057) and detected lymph node metastasis more frequently (53.5% vs. 33.7%, P = 0.0069). Six (5.9%) patients in the systematic LND group had a metastatic N2 lymph node "in the systematic LND field" that lobe-specific LND could not dissect. The systematic LND group tended to have better prognosis than the lobe-specific LND group (5-year CSS rates, 82.6% versus 69.6%; 5-year RFI rates, 56.6% vs. 47.3%). CONCLUSIONS: Systematic LND was found to harvest more metastatic lymph nodes and provide better oncological outcome than lobe-specific LND in a cohort of hypermetabolic NSCLC patients.
  • Yoshinori Handa; Yasuhiro Tsutani; Morihito Okada
    Annals of surgical oncology 28 12 7172 - 7172 2021年11月
  • Takahiro Mimae; Yoshihiro Miyata; Kenichi Yoshimura; Yasuhiro Tsutani; Kentaro Imai; Hiroyuki Ito; Haruhiko Nakayama; Norihiko Ikeda; Morihito Okada
    Japanese journal of clinical oncology 51 10 1561 - 1569 2021年10月 
    OBJECTIVE: We aimed to determine the influences of surgical procedures on the postoperative death of octogenarians with clinical Stage IA non-small cell lung cancer excluding cT1mi. METHODS: We compared overall survival and the cumulative incidence of death due to all and other causes among 1 130 279, and 191 consecutive patients aged ≤79 and ≥80 years after lobectomy, segmentectomy and wedge resection at three institutions. Death due to other causes was defined as death due to any cause except non-small cell lung cancer. RESULTS: The median followup was 53 months. The 5-year overall survival rates for patients aged ≥ 80 and ≤ 79 years after lobectomy, segmentectomy and wedge resection were respectively, 78.0% (95% confidence interval, 63.8%-87.2%) versus 91.2% (95% confidence interval, 89.0%-92.9%), 68.1% (95% confidence interval, 45.2%-83.1%) versus 90.0% (95% confidence interval, 84.6%-93.5%), and 62.7% (95% confidence interval, 44.0-76.7%) versus 84.4% (95% confidence interval, 76.3%-89.9%) (P < 0.01 for all). The cumulative incidence of death due to other causes after wedge resection was similar between patients aged ≥ 80 and ≤ 79 years (P = 0.45), but significantly higher in those aged ≥ 80, than ≤ 79 years after lobectomy or segmentectomy (P = 0.00015 and 0.00091, respectively). CONCLUSIONS: The influence of wedge resection on death due to other causes was lower than that of lobectomy or segmentectomy in patients with non-small cell lung cancer aged ≥ 80 years. Wedge resection might be a useful option for octogenarians even if they can tolerate lobectomy/segmentectomy to avoid postoperative death due to causes other than non-small cell lung cancer.
  • Yasuhiro Tsutani; Yoshinori Handa; Yoshihisa Shimada; Hiroyuki Ito; Norihiko Ikeda; Haruhiko Nakayama; Kenichi Yoshimura; Morihito Okada
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 162 4 1244 - + 2021年10月 
    Objective: The study objective was to compare cancer control between segmentectomy and wedge resection in patients with clinical stage IA non-small cell lung cancer.Methods: Between 2010 and 2015, 457 patients with clinical stage IA (8th edition) non-small cell lung cancer undergoing wedge resection or segmentectomy were identified at 3 institutions. Propensity scores were calculated on the basis of the extent of resection (wedge resection or segmentectomy) and included adjustment for confounding variables, such as age, sex, smoking status, pulmonary functions, laterality, tumor size, maximum standardized uptake value on F-18-fluorodeoxyglucose positron emission tomography, presence of ground-glass opacity on high-resolution computed tomography, histology, and visceral pleural invasion for multivariable analysis and matching. The primary end point was cumulative incidence of recurrence.Results: In all cohorts, postoperative recurrence occurred in 36 of 195 patients (18.5%) undergoing wedge resection and 14 of 262 patients (5.3%) undergoing segmentectomy. Cumulative incidence of recurrence was significantly lower in patients undergoing segmentectomy (5-year cumulative incidence of recurrence, 5.3%) than in those undergoing wedge resection (5-year cumulative incidence of recurrence, 19.1%; P<.001). In propensity score-adjusted multivariable analysis, segmentectomy was identified as an independent favorable prognostic factor for cumulative incidence of recurrence (hazard ratio, 0.47; 95% confidence interval, 0.24-0.90; P < .022). In propensity score matching of 163 pairs, cumulative incidence of recurrence was significantly lower in patients undergoing segmentectomy (5-year cumulative incidence of recurrence, 6.6%) than in those undergoing wedge resection (5-year cumulative incidence of recurrence, 13.2%; P = .041).Conclusions: Cancer control was better in segmentectomy than in wedge resection. Segmentectomy is the preferred oncologic procedure as sublobar resection to treat clinical stage IA non-small cell lung cancer.
  • Tomo Sato; Yoshihisa Shimada; Takahiro Mimae; Yasuhiro Tsutani; Yoshihiro Miyata; Hiroyuki Ito; Haruhiko Nakayama; Morihito Okada; Norihiko Ikeda
    Lung cancer (Amsterdam, Netherlands) 158 9 - 14 2021年08月 [査読有り]
     
    Objectives: Lymphatic vessel invasion (Ly) plays a crucial role in pathological lymph node metastasis (pN), and we consider pN + Ly + disease to indicate a high affinity for the lymphatic system. This study evaluated the outcomes of patients with clinically node-negative (N0) non-small cell lung cancer (NSCLC) who presented with pN + with Ly+. Materials and Methods: This retrospective study evaluated 1775 patients with clinically N0 stage I & ndash;III NSCLC who underwent R0 anatomical resection and systematic lymph node dissection at three institutions between January 2010 and December 2017. Patients were classified into four groups according to their pN and Ly statuses. Univariable and multivariable analyses were performed to identify factors associated with poor recurrence-free survival (RFS) and pN + Ly+. Results: Kaplan-Meier curves revealed that the 5-year RFS rates were 90.8 % for pN & ndash;Ly & ndash; patients, 55.6 % for pN & ndash;Ly + patients, 63.4 % for pN + Ly & ndash; patients, and 41.3 % for pN + Ly + patients. Distant and lymph node recurrences were more common in the pN + Ly + group, relative to in the pN & ndash;Ly & ndash; and pN & ndash;Ly + groups (both p < 0.001). Multivariable analyses revealed that pN and Ly statuses were independently associated with RFS, while the solid tumor size and maximum standardized uptake value were independently associated with pN + Ly + status. The proportion of pN + Ly + disease was 17.2 % in patients with a solid-part size of > 1.80 cm and a SUVmax of > 3.55. Conclusion: pN and Ly statuses were independent prognostic factors in patients with clinically N0 stage I & ndash;III NSCLC. Diseases presenting with pN + with Ly + were associated with increased rates of distant and lymph node recurrence.
  • Masaoki Ito; Yoshihiro Miyata; Shoko Hirano; Fumiko Irisuna; Kei Kushitani; Yuichiro Kai; Naoto Kishi; Yasuhiro Tsutani; Yukio Takeshima; Morihito Okada
    Journal of cancer research and clinical oncology 148 6 1419 - 1428 2021年07月 
    PURPOSE: Liquid biopsy for early-stage lung cancer diagnosis is challenging, and optimal candidates' clinicopathological features are unknown. We investigated utility and clinicopathological features of optimal candidates in somatic mutation-targeted liquid biopsy using droplet digital polymerase chain reaction (ddPCR) in pN0M0 EGFR mutation-positive lung adenocarcinoma patients. METHODS: We performed EGFR mutation-targeted ddPCR liquid biopsy in 100 patients with resected pN0M0 invasive lung adenocarcinoma, whose tumor diameter in high-resolution computed tomography (HRCT) was ≤ 5 cm. Peripheral blood-derived serum was collected preoperatively. Two representative EGFR somatic variants (exon 19 [E746-A750 del (2235_2249 del)]; exon 21 (L858R)) were utilized as liquid biopsy targets. Clinicopathological features including radiological appearance, subhistology, and invasive status were compared between ddPCR-positive and ddPCR-negative patients. RESULTS: Among the 100 patients, 98 showed part-solid or pure-solid appearance in HRCT and 2 showed non-solid appearance; 98 were pathological stage IA1-IB. Of the 66 patients with EGFR mutation detection in ddPCR, 12 were significantly positive and 10 (83.3%, 10/12) exhibited pure-solid appearance in HRCT. Clinical invasive tumor ratio was significantly higher in ddPCR-positive than in ddPCR-negative patients (median: 100% vs. 85.4%, P = 0.0212), whereas other clinicopathological features were not significantly different. CONCLUSION: Mutation-targeted liquid biopsy using ddPCR detected lung cancer in 12.0% (12/100) of pN0M0 EGFR-mutant lung adenocarcinoma patients. In 83.3% of the ddPCR-positive patients, tumors showed pure-solid appearance in HRCT. The detection ratio increased to 21.3% (10/47) among patients with pure-solid appearance tumors. Tumor appearance might be useful for better selection of liquid biopsy candidates.
  • Kagimoto, Atsushi; Tsutani, Yasuhiro; Handa, Yoshinori; Mimae, Takahiro; Miyata, Yoshihiro; Okada, Morihito
    ANNALS OF THORACIC SURGERY 112 1 264 - 270 ELSEVIER SCIENCE INC 2021年07月 [査読有り]
     
    Background. Acute exacerbation (AE) of interstitial pneumonia (IP) is a fatal complication after lung resection. We aimed to investigate whether the visual accumulation of [18F]-fluoro-2-deoxy-D-glucose (FDG) in the field of IP on preoperative FDG-positron emission tomography & ndash;computed tomography is useful for predicting AE of IP. Methods. This study included 193 patients with IP findings on preoperative computed tomography who underwent curative intent lung resection for primary lung cancer at Hiroshima University Hospital between April 2007 and March 2019. If the uptake of IP area was higher than the background normal lung, the patients were considered to have positive FDG accumulation. The relationship of the accumulation of FDG in the IP area and the incidence of AE of IP and short-term mortality was analyzed. Results. Among the included patients, accumulation of FDG in the IP area was detected in 130 (67.4%) patients. The incidence of AE of IP was significantly different between patients with (10.0%) and without (0%) FDG accumulation in the IP area (P = .001). The 90-day mortality rate was also significantly different between patients with (6.9%) and without (0%) accumulation of FDG in the IP area (P = .007). In the multivariable analysis, the accumulation of FDG in the IP area was a significant risk factor of AE of IP (P = .005). Conclusions. The visual evaluation of accumulation of FDG in the IP area was useful to predict the AE of IP and short-term mortality after lung resection. (Ann Thorac Surg 2021;112:264-70) (c) 2021 by The Society of Thoracic Surgeons Superscript/Subscript Available
  • Tsutani, Yasuhiro; Kagimoto, Atsushi; Handa, Yoshinori; Mimae, Takahiro; Miyata, Yoshihiro; Okada, Morihito
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 51 7 1123 - 1131 OXFORD UNIV PRESS 2021年07月 [査読有り]
     
    Objectives: The prognostic role of interstitial pneumonia with emphysema in lung cancer is not fully understood. This study aimed to examine the prognostic role of the presence of emphysema in patients with clinical stage I lung cancer and interstitial pneumonia. Methods: The presence of interstitial pneumonia and emphysema was evaluated on preoperative high-resolution computed tomography. In total, 836 consecutive patients with clinical stage I lung cancer who underwent complete resection between April 2007 and March 2016 were retrospectively analyzed using the log-rank test and Cox proportional hazard model to examine survival differences. Results: There was a significant difference in 5-year overall survival between patients with interstitial pneumonia and emphysema (n = 65) and those without (n = 771) (62.6% vs. 86.5%; P < 0.001). However, in patients with interstitial pneumonia on high-resolution computed tomography, there was no significant difference in 5-year overall survival between patients with emphysema (n = 65) and those without emphysema (n = 50) (62.6% vs. 59.4%, P = 0.84). Multivariable backward stepwise Cox proportional hazard analysis in patients with interstitial pneumonia showed that histology, %diffusing capacity of the lungs for carbon monoxide, radiologic interstitial pneumonia pattern and surgical procedure were independent prognostic factors for overall survival, but the presence of emphysema was not. Conclusions: The presence of emphysema was not an independent prognostic factor for overall survival in patients with clinical stage I lung cancer with interstitial pneumonia. Poor survival of patients with IP and emphysema may be due to the presence of interstitial pneumonia.
  • Satoshi Nakao; Kakuhiro Yamaguchi; Hiroshi Iwamoto; Atsushi Kagimoto; Takahiro Mimae; Yasuhiro Tsutani; Yoshihiro Miyata; Hironobu Hamada; Morihito Okada; Noboru Hattori
    The Annals of thoracic surgery 2021年06月 
    BACKGROUND: In lung cancer patients with interstitial lung disease (ILD) postoperative acute exacerbation can be fatal. However the predictive biomarkers for postoperative exacerbation of ILD have not been fully elucidated. The soluble receptor for advanced glycation end products is a lung-derived antiinflammatory protein that can prevent acute lung injury. This study aimed to elucidate its role in this fatal complication, especially focusing on the predictive potential of serum levels of soluble receptor for advanced glycation end products. METHODS: We retrospectively enrolled 152 patients with lung cancer and ILD who underwent lung resection and had blood samples collected before surgery. Independent predictors of postoperative acute exacerbation were evaluated in all patients and in subgroups based on the surgical procedure. Additionally serial changes in soluble receptor levels in these subgroups were evaluated. RESULTS: Seventeen patients (11.2%) developed postoperative acute exacerbation. Receiver operating characteristic curve analysis revealed 547.4 pg/mL as the optimal soluble receptor level cutoff value. Univariate and multivariate logistic regression analyses revealed a significant association between soluble receptor serum levels (≤547.4 pg/mL) and postoperative acute exacerbation. In the subgroup analysis this independent association was observed only in the lobectomy group. Additionally lobectomy caused a significant reduction in postoperative soluble receptor levels. CONCLUSIONS: Decreased baseline levels of circulatory soluble receptor might be a potential risk factor for postoperative acute exacerbation in patients with lung cancer and ILD. Moreover additional reduction in the levels of this antiinflammatory protein occurs because of lung resection.
  • Atsushi Kagimoto; Yasuhiro Tsutani; Kei Kushitani; Takahiro Kambara; Takahiro Mimae; Yoshihiro Miyata; Yukio Takeshima; Morihito Okada
    BMC pulmonary medicine 21 1 186 - 186 2021年06月 [査読有り]
     
    BackgroundAcute exacerbation (AE) of interstitial pneumonia (IP) is the most fatal complication after lung resection for lung cancer. To improve the prognosis of lung cancer with IP, the risk factors of AE of IP after lung resection should be assessed. S100 calcium-binding protein A4 (S100A4) is a member of the S100 family of proteins and is a known marker of tissue fibrosis. We examined the usefulness of S100A4 in predicting AE of IP after lung resection for lung cancer.MethodsThis study included 162 patients with IP findings on preoperative high-resolution computed tomography scan who underwent curative-intent lung resection for primary lung cancer between April 2007 and March 2019. Serum samples were collected preoperatively. Resected lung tissue from 76 patients exhibited usual IP (UIP) pattern in resected lung were performed immunohistochemistry (IHC). Relationship between S100A4 and the incidence of AE of IP and short-term mortality was analyzed.ResultsThe receiver operating characteristic area under the curve for serum S100A4 to predict postoperative AE of IP was 0.871 (95% confidence interval [CI], 0.799-0.943; P<0.001), with a sensitivity of 93.8% and a specificity of 75.3% at the cutoff value of 17.13 ng/mL. Multivariable analysis revealed that a high serum S100A4 level (>17.13 ng/mL) was a significant risk factor for AE of IP (odds ratio, 42.28; 95% CI, 3.98-449.29; P=0.002). A 1-year overall survival (OS) was significantly shorter in patients with high serum levels of S100A4 (75.3%) than in those with low serum levels (92.3%; P=0.003). IHC staining revealed that fibroblasts, lymphocytes, and macrophages expressed S100A4 in the UIP area, and the stroma and fibrosis in the primary tumor expressed S100A4, whereas tumor cells did not.ConclusionsSerum S100A4 had a high predictive value for postoperative AE of IP and short-term mortality after lung resection.
  • Yamaguchi, Kakuhiro; Nakao, Satoshi; Iwamoto, Hiroshi; Kagimoto, Atsushi; Handa, Yoshinori; Sakamoto, Shinjiro; Horimasu, Yasushi; Masuda, Takeshi; Mimae, Takahiro; Miyamoto, Shintaro; Nakashima, Taku; Tsutani, Yasuhiro; Fujitaka, Kazunori; Miyata, Yoshihiro; Hamada, Hironobu; Okada, Morihito; Hattori, Noboru
    SCIENTIFIC REPORTS 11 1 NATURE RESEARCH 2021年05月 [査読有り]
     
    Postoperative acute exacerbation of interstitial lung disease (AE-ILD) can be fatal in patients with lung cancer concomitant with ILD. We aimed to elucidate the predictive potential of high-mobility group box 1 (HMGB1), which is associated with the development and severity of lung injury, for evaluating the risk of this complication. We included 152 patients with lung cancer and ILD who underwent radical surgery between January 2011 and August 2019. We evaluated the preoperative levels of serum HMGB1 and its predictive potential for postoperative AE-ILD. Postoperative AE-ILD developed in 17 patients. Serum levels of HMGB1 were significantly higher in patients with postoperative AE-ILD than in those without (median [interquartile range]: 5.39 [3.29-11.70] ng/mL vs. 3.55 [2.07-5.62] ng/mL). Univariate and multivariate logistic regression analyses revealed that higher HMGB1 levels were significantly associated with the development of postoperative AE-ILD in entire studied patients (n = 152). In the subgroup analysis, higher HMGB1 levels were associated with a significantly increased risk of this complication in patients who underwent lobectomy (n = 77) than in those who underwent sublobar resection (n = 75). Serum HMGB1 could be a promising marker for evaluating the risk of postoperative AE-ILD, specifically in patients who underwent lobectomy.
  • Handa, Yoshinori; Tsutani, Yasuhiro; Okada, Morihito
    FRONTIERS IN ONCOLOGY 11 FRONTIERS MEDIA SA 2021年04月 [査読有り]
     
    Lobectomy has been the standard surgical treatment for non-small cell lung cancer (NSCLC). Over the decades, with the dramatic development of radiographic tools, such as high-resolution computed tomography (HRCT), and the widespread practice of low-dose helical CT for screening, the number of cases diagnosed with small-cell lung cancers with ground glass opacity (GGO) at early stages has been increasing. Accordingly, mainly after 2000, many retrospective studies and prospective trials have shown that patients with lung adenocarcinoma with GGO have a good prognosis and may be candidates for sublobar resection. Previous studies indicated that HRCT findings including the maximum diameter of the tumor, GGO ratio, and a consolidation/tumor ratio (CTR) are simple and useful tools to predict tumor invasiveness and prognosis in patients with NSCLC with GGO. Thus, sublobar resection may be considered a "standard therapy" for peripheral GGO-dominant small-cell lung adenocarcinomas. Ultimately, some of such tumors might not require surgical resection. A multicenter, prospective study has just begun in Japan to evaluate the validity of follow-up for small-sized GGO-dominant small-cell lung cancer. Lung cancers that do not require surgery should be identified. This study reviewed retrospective and prospective studies on GGO tumors and discussed the treatment strategies for such tumors.
  • 原田 敏之; 大泉 聡史; 高村 圭; 立原 素子; 森川 直人; 本田 亮一; 渡部 聡; 朝尾 哲彦; 國崎 守; 福原 達朗; 野呂 林太郎; 菊地 英毅; 津谷 康大; 天満 紀之; 小林 国彦; 秋田 弘俊; 北海道肺癌臨床研究会
    日本呼吸器学会誌 10 増刊 146 - 146 (一社)日本呼吸器学会 2021年04月
  • Kagimoto, Atsushi; Tsutani, Yasuhiro; Handa, Yoshinori; Mimae, Takahiro; Miyata, Yoshihiro; Okada, Morihito
    ANNALS OF SURGICAL ONCOLOGY 28 4 2068 - 2075 SPRINGER 2021年04月 [査読有り]
     
    Background This study aimed to investigate the efficacy of the Deauville criteria (a 5-point visual scale criteria) in assessing the accumulation of [18F]-fluoro-2-deoxy-d-glucose (FDG) on positron-emission tomography (PET)/computed tomography (CT) for predicting prognosis of early-stage lung adenocarcinoma and selecting candidates for sublobar resection. Methods This retrospective study included 648 patients undergoing curative resection for clinical N0 lung adenocarcinoma with a whole tumor size of 3 cm or smaller between April 2007 and March 2019. Accumulations of the FDG on PET/CT scans were scored using the Deauville criteria (Deauville score), and correlations between the Deauville score and prognosis were analyzed. Results The recurrence-free survival (RFS) was significantly better for the patients with a Deauville score of 1 or 2 (n = 415, 5-year RFS, 92.6%) than for those with a score of 3 (n = 82, 5-year RFS, 72.7%;P < 0.001) or a score of 4 or 5 (n = 151, RFS, 70.8%;P < 0.001). The RFS did not differ significantly among the patients with Deauville scores of 1 and 2 who underwent wedge resection (n = 102, 5-year RFS, 90.5%), segmentectomy (n = 188, RFS, 95.1%;P = 0.355), and lobectomy (n = 125, RFS, 91.1%;P = 0.462). Conclusion The 5-point-scale evaluation of FDG accumulation on PET/CT was useful in predicting the prognosis for patients with early-stage lung adenocarcinoma. Lung adenocarcinoma patients with a whole tumor size of 3 cm or smaller and a Deauville score of 1 or 2 can be candidates for sublobar resection.
  • Atsushi Kagimoto; Yasuhiro Tsutani; Yuya Hirai; Yoshinori Handa; Takahiro Mimae; Yoshihiro Miyata; Morihito Okada
    JTCVS open 5 110 - 118 2021年03月 
    Objective: Pleurodesis is among several treatment strategies for postoperative alveolo-pleural fistula (APF) after lung resection. Accordingly, the present study aimed to determine the influence of pleurodesis on postoperative pulmonary function. Methods: Patients who underwent anatomical segmentectomy between January 2009 and March 2020 and pulmonary function tests 6 and 12 months after initial surgery were included in this study. Differences in pulmonary function decline between patients who did and did not undergo pleurodesis were compared. Results: Among the 319 patients included, 39 (12.2%) underwent pleurodesis. Among patients who did not receive pleurodesis, there were no difference in decline of vital capacity at 6 months (-13.7% ± 1.1% vs -11.2% ± 0.7%; P = .063) and 12 months (-10.7% ± 1.3% vs -9.5% ± 0.7%; P = .391) after surgery between patients who had APF on postoperative day 2 and those who did not. Patients who received pleurodesis had a significantly larger decline in vital capacity at 6 months (-19.4% ± 2.4% vs -13.7% ± 1.1%; P = .015) and 12 months (-16.2% ± 1.6% vs -10.7% ± 1.3%; P = .010) after surgery compared with those who had APF on postoperative day 2 and did not receive pleurodesis. There were no significant differences in decline of forced expiratory volume in 1 second. Conclusions: Pleurodesis negatively influenced postoperative vital capacity after lung segmentectomy. Although the clinical influence of this is unknown, careful consideration is needed before performing pleurodesis given its potential influence on postoperative pulmonary function.
  • Atsushi Kagimoto; Yasuhiro Tsutani; Takahiro Mimae; Yoshihiro Miyata; Norihiko Ikeda; Hiroyuki Ito; Yoshimasa Maniwa; Kenji Suzuki; Masahiro Tsuboi; Kenichi Yoshimura; Seiji Umemoto; Morihito Okada
    BMJ Open 11 3 2021年03月 [査読有り]
     
    Introduction Recently, inhibition of programmed cell death 1 or its ligand has shown therapeutic effects on non-small cell lung cancer (NSCLC). However, the effectiveness of preoperative nivolumab monotherapy for stage I NSCLC remains unknown. The present study aimed to investigate the pathological response of preoperative treatment with nivolumab for clinically node negative but having a high risk of NSCLC recurrence. Methods and analysis The Preoperative Nivolumab (Opdivo) to evaluate pathologic response in patients with stage I non-small cell lung cancer: a phase 2 trial (POTENTIAL) study is a multicentre phase II trial investigating efficacy of preoperative nivolumab for clinical stage I patients at high risk of recurrence. This study includes histologically or cytologically confirmed NSCLC patients with clinical N0 who were found on preoperative high-resolution CT to have a pure solid tumour without a ground-glass opacity component (clinical T1b, T1c or T2a) or a solid component measuring 2-4 cm in size (clinical T1c or T2a). Patients with epidermal growth factor receptor (EGFR) mutation (deletion of exon 19 or point mutation on exon21, L858R), anaplastic lymphoma kinase (ALK) translocation or c-ros oncogene 1 (ROS-1) translocation are excluded from this study. Nivolumab (240 mg/body) is administrated intravenously as preoperative therapy every 2 weeks for three cycles. Afterward, lobectomy and mediastinal lymph node dissection (ND 2a-1 or ND 2a-2) are performed. The primary endpoint is a pathological complete response in the resected specimens. The secondary endpoints are safety, response rates and major pathological response. The planed sample size is 50 patients. Patients have been enrolled since April 2019. Ethics and dissemination This trial was approved by the Institutional Review Board of Hiroshima University Hospital and other participating institutions. This trial will help examine the efficacy of preoperative nivolumab therapy for clinical stage I NSCLC.
  • Handa, Yoshinori; Tsutani, Yasuhiro; Mimae, Takahiro; Miyata, Yoshihiro; Ito, Hiroyuki; Nakayama, Haruhiko; Ikeda, Norihiko; Okada, Morihito
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 51 3 451 - 458 OXFORD UNIV PRESS 2021年03月 [査読有り]
     
    Background: The significance of lymphadenectomy is yet to be fully examined in segmentectomy. We compared the oncological outcomes of mediastinal lymph node dissection (LND) and hilar LND for lung cancer treated with segmentectomy via a multicenter database using propensity score-matched analysis. Methods: We reviewed 357 clinical stage IA radiologically solid-dominant lung cancer patients who underwent segmentectomy with lymphadenectomy. The extent of LND was classified into systematic/lobe-specific mediastinal LND and hilar LND only groups. Postoperative results after segmentectomy with mediastinal LND (n = 179) and hilar LND (n = 178) were analyzed for all patients and their propensity score-matched pairs. Results: Cancer-specific survival (CSS) and recurrence-free interval (RFI) rates for the mediastinal LND group were determined to be not significantly different compared with the hilar LND group in all non-adjusted cohorts. In the propensity score-matched cohort (129 pairs), mediastinal LND harvested more lymph nodes compared with hilar LND, and both groups had significantly different pathological stages (P = 0.015). Adjuvant chemotherapy was performed in 10 (7.8%) patients in the mediastinal LND group and 4 (3.1%) in the hilar LND group. The mediastinal LND group tended to have better prognosis than the hilar LND group (5-year CSS rates, 97.4% vs 93.2%; 5-year RFI rates, 93.5% vs 88.5%). Conclusions: Mediastinal LND was found to provide more appropriate pathological staging compared with hilar LND in patients with segmentectomy by harvesting more lymph nodes. In addition, mediastinal LND might lead to better oncological outcome than hilar LND in segmentectomy.
  • Yamaguchi, Masafumi; Nakagawa, Kazuo; Suzuki, Kenji; Takamochi, Kazuya; Ito, Hiroyuki; Okami, Jiro; Aokage, Keiju; Shiono, Satoshi; Yoshioka, Hiroshige; Aoki, Tadashi; Tsutani, Yasuhiro; Okada, Morihito; Watanabe, Shun-ichi
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 51 3 333 - 344 OXFORD UNIV PRESS 2021年03月 [査読有り]
     
    Locally advanced non-small cell lung cancer, especially mediastinal lymph node metastasis-positive stage IIIA-N2 cancer, is a heterogeneous disease state characterized by anatomically locally advanced disease with latent micrometastases. Thus, surgical resection or radiotherapy alone has historically failed to cure this disease. During the last three decades, persistent efforts have been made to develop a suitable treatment modality to overcome these problems using chemotherapy and/or radiotherapy with surgical resection. However, the role of surgical resection remains unclear, and the standard treatment for stage IIIA-N2 disease is concurrent chemoradiotherapy. In general, adjuvant chemotherapy is indicated for completely resected pathological stage IB disease or lymph node metastasis-positive pathological stage II or IIIA disease. Platinum-based doublet cytotoxic chemotherapy is currently the standard regimen. Additionally, post-operative radiotherapy might be indicated for post-operatively proven mediastinal lymph node metastasis; i.e. clinical N0-1 and pathological N2 disease. With the remarkable progression that has recently been made in the field of chemotherapy, such as advances in molecular targeting agents and immune checkpoint inhibitors, the basic policy of chemotherapy has been shifting to personalized treatment based on the individual patient's oncogene driver mutation status, immune status and other parameters. The same trend is being seen in the treatment of stage IIIA-N2 disease. We should consider the past and upcoming results of several clinical trials to optimize the coming era of personalized treatment.
  • Yoshinori Handa; Yasuhiro Tsutani; Takahiro Mimae; Yoshihiro Miyata; Morihito Okada
    Clinical Lung Cancer 22 2 e224 - e233 2021年03月 [査読有り]
     
    This study aimed to compare operative and postoperative outcomes of complex segmentectomy and wedge resection, and evaluated the utility of complex segmentectomy in the treatment of non-small-cell lung cancer. Complex segmentectomy provided better overall survival/recurrence-free survival rates without compromising outcomes, such as mortality, major complications. Hence, our study suggests that complex segmentectomy can provide better oncological and survival outcomes with acceptable perioperative safety compared with wedge resection. Background: Although sublobar resection has become widely used for lung cancer treatment, very limited data comparing outcomes following complex segmentectomy or wedge resection have been available. Questions remain regarding mortality, morbidity, surgical margin, lymph node dissection, and long-term survival outcomes. This study compares operative and postoperative outcomes of complex segmentectomy and wedge resection. Patients and Methods: A total of 216 patients with clinical stage I lung cancer who underwent complex segmentectomy (n = 110) or wedge resection (n = 106) between April 2007 and March 2017 were retrospectively reviewed, and 61 propensity scoreematched pairs were analyzed. Operative and postoperative results were compared. Factors affecting survival were assessed using the Kaplan-Meier method. Results: Although the complex segmentectomy group tended to have higher overall complications (26.2% vs. 16.4%; P = .27) and prolonged air leakage (11.5% vs. 6.6%; P = .53) rates than the wedge resection group, major complications (>= grade IIIa) (0% vs. 3.3%; P = .50) and 30-day mortality (0% vs. 0%; P = 1.00) rates were comparable between both groups. Complex segmentectomy provided better median surgical margin distance (15.0 vs. 10.0 mm; P = .052) and number of dissected lymph nodes (6.0 vs. 0.0 nodes; P = .0002) than wedge resection. The complex segmentectomy group tended to have better prognosis than the wedge resection group (5-year overall survival rates, 94.7% vs. 79.4% and 5-year recurrence-free survival rates, 94.0% vs. 76.5%, respectively). Conclusions: Complex segmentectomy could provide better oncological and survival outcomes with acceptable perioperative safety compared with wedge resection. (C) 2020 Elsevier Inc. All rights reserved.
  • Atsushi Kamigaichi; Yasuhiro Tsutani; Takahiro Mimae; Yoshihiro Miyata; Yoshihisa Shimada; Hiroyuki Ito; Haruhiko Nakayama; Norihiko Ikeda; Morihito Okada
    Clinical Lung Cancer 22 2 120 - 126.e3 2021年03月 [査読有り]
     
    We aimed to identify the predictive criteria of unexpected N2 disease, defined as pathologic N2 disease with clinical N0 or N1, in clinical T1-2N0-1M0 non-small-cell lung cancer. The predictive criteria were defined as tumors with a standardized maximum uptake value of >= 3.1 and clinical N1, and showed high diagnostic accuracy in both derivation and validation cohorts. Background: Despite the recent development of radiologic mediastinal staging modality, unexpected mediastinal lymph node metastasis still occurs. Preoperative accurate nodal staging is important to determine the optimal treatment. Therefore, this study aimed to identify predictors of unexpected N2 disease in non-small-cell lung cancer (NSCLC). Patients and Methods: Data from a multicenter database of 2802 patients with clinical T1-2N0-1M0 NSCLC who underwent anatomical segmentectomy or lobectomy were retrospectively analyzed. Unexpected N2 disease was defined as pathologic N2 disease with clinical N0 or N1. The predictive criteria of unexpected N2 disease were established on the basis of the multivariable analysis results of a derivation cohort of 2019 patients, and the criteria were further tested in a validation cohort of 783 patients. Results: In multivariable analyses, maximum standardized uptake value (SUVmax) of the primary tumor on 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography (odds ratio, 1.072; 95% confidence interval, 1.018-1.129; P = .008) and clinical N1 (vs. clinical N0) disease (odds ratio, 5.40; 95% confidence interval, 1.829-15.94; P = .002) were independent predictors of unexpected N2 disease. The predictive criteria of unexpected N2 disease was defined as tumors with SUVmax of > 3.1, determined by receiver operating characteristic curves, and clinical N1 disease. This criterion showed diagnostic accuracy of 90.6% (sensitivity 32.0%, specificity 94.5%) in the derivation cohort and 91.3% (sensitivity 32.6%, specificity 94.7%) in the validation cohort. Conclusion: The predictive criteria of unexpected N2 disease (tumors with SUVmax of > 3.1 and clinical N1) can be used to select candidates for preoperative invasive mediastinal staging in patients with clinical T1-2N0-1M0 NSCLC. (C) 2020 Elsevier Inc. All rights reserved.
  • Handa, Yoshinori; Tsutani, Yasuhiro; Mimae, Takahiro; Miyata, Yoshihiro; Imai, Kentaro; Ito, Hiroyuki; Nakayama, Haruhiko; Ikeda, Norihiko; Yoshimura, Kenichi; Okada, Morihito
    ANNALS OF THORACIC SURGERY 111 3 1044 - 1051 ELSEVIER SCIENCE INC 2021年03月 [査読有り]
     
    Background. Complex segmentectomy creates several intricate intersegmental planes; however, it has not been fully established in lung cancer treatment. We compared the oncologic outcomes of complex segmentectomy and lobectomy through a large cohort, multicenter database using propensity score-matched analysis. Methods. We retrospectively analyzed data from 1517 patients with clinical stage I lung cancer with a solid component size 2.0 cm or less, who underwent surgical resection at 3 institutions between 2010 and 2018. Complex segmentectomy (n = 240) and location-adjusted lobectomy (n = 851) as well as surgical results were analyzed for all patients and their propensity scorematched pairs. Results. The prognosis of patients undergoing complex segmentectomy was not significantly different from that of patients undergoing lobectomy (5-year cancer-specific survival [CSS] rate, 96.4% versus 97.2%, P = .69; and 5-year recurrence-free interval [RFI] rate, 95.8% versus 93.4%, P = .19). This trend was also identified in subanalyses for pure solid tumors. However, there were major differences in clinicopathologic features between the 2 groups. After propensity score-matched analysis, proper matching of patients was ascertained. In 219 propensity score-matched pairs, long-term outcomes were similar between patients undergoing complex segmentectomy (5-year CSS, 96.0%; 5-year RFI, 95.5%) and lobectomy (5-year CSS, 97.8%; 5-year RFI, 95.9%). Propensity score-adjusted multivariable analysis for RFI revealed that prognosis associated with complex segmentectomy was comparable to the prognosis obtained with lobectomy (hazard ratio = 0.98; 95% confidence interval, 0.33-2.40; P = .98). Conclusions. Complex segmentectomy provides acceptable oncologic outcomes in clinical stage I lung cancer treatment. (C) 2021 by The Society of Thoracic Surgeons
  • Atsushi Kagimoto; Yasuhiro Tsutani; Takahiro Kambara; Yoshinori Handa; Takashi Kumada; Takahiro Mimae; Kei Kushitani; Yoshihiro Miyata; Yukio Takeshima; Morihito Okada
    JTO clinical and research reports 2 2 100126 - 100126 2021年02月 
    Introduction: The International Association for the Study of Lung Cancer proposed a new grading criteria for invasive adenocarcinoma. However, its utility has not been validated. Methods: Patients who underwent complete resection of lung adenocarcinoma were included in this study. Then, they were divided into the following three groups on the basis of the criteria recently proposed by the International Association for the Study of Lung Cancer: grade 1, lepidic predominant tumor, with less than 20% of high-grade patterns; grade 2, acinar or papillary predominant tumor, with less than 20% of high-grade patterns; and grade 3, any tumor with greater than or equal to 20% of high-grade patterns. Results: Recurrence-free survival (RFS) was significantly different among the proposed grades (p < 0.001). The RFS of patients upgrading from current grade 2 (papillary or acinar predominant tumor) to proposed grade 3 (5-y RFS, 65.2%) was significantly worse than that of patients with proposed grade 2 (77.1%, hazard ratio = 1.882, 95% confidence interval: 1.236-2.866) but not significantly different from that of patients with grade 3 in both the current (micropapillary or solid predominant tumor) and proposed criteria (53.2%, hazard ratio = 0.761, 95% confidence interval: 0.456-1.269). Among patients with pathologic stage 0 or I, RFS was well stratified by the new grading system (p < 0.001) but not among patients with stage II or III (p = 0.334). In the multivariable analysis, the new grading was not a predictive factor of RFS. Conclusions: Although the proposed grading system well stratified RFS in patients with pathologic stage 0 or I lung adenocarcinoma, there is room for improvement.
  • Kai, Yuichiro; Amatya, Vishwa Jeet; Kushitani, Kei; Kambara, Takahiro; Suzuki, Rui; Fujii, Yutaro; Tsutani, Yasuhiro; Miyata, Yoshihiro; Okada, Morihito; Takeshima, Yukio
    TRANSLATIONAL LUNG CANCER RESEARCH 10 2 766 - + AME PUBL CO 2021年02月 [査読有り]
     
    Background: The histological classification of non-small cell lung cancer (NSCLC) is essential in determining new cancer-specific targeted therapies. However, the accurate typing of poorly differentiated is difficult, particularly for poorly differentiated squamous cell carcinoma and adenocarcinoma of the lung with limited immunohistochemical markers. Thus, novel immunohistochemical markers are required. We assumed the possibility of the immunohistochemical expression of glypican-1 in lung squamous cell carcinoma. Methods: The microarray dataset GSE43580 from Gene Expression Omnibus database were analyzed for confirming the gene expression of glypican-1 in lung squamous cell carcinoma. We immunohistochemically investigated the use of glypican-1 as a novel positive diagnostic marker for lung squamous cell carcinoma. Glypican-1 expression in 63 cases of poorly differentiated lung squamous cell carcinoma and 60 cases of solid predominant lung adenocarcinoma was investigated by immunohistochemistry. Additionally, we compared glypican-1 expression with the expressions of p40, cytokeratin 5/6, thyroid transcription factor-1 (TTF-1), and napsin A. Results: All 63 cases of lung squamous cell carcinoma showed glypican-1 expression. In contrast, only 2 cases of lung adenocarcinoma showed glypican-1 expression. The sensitivity, specificity, and diagnostic accuracy of glypican-1 expression for differentiating lung squamous cell carcinoma from lung adenocarcinoma were 100%, 96.7%, and 98.4%, respectively. These were similar to those of p40 and significantly better than those of CK 5/6. Conclusions: We recommend the use of glypican-1 as an additional positive marker of lung squamous cell carcinoma.
  • Yotsukura, Masaya; Nakagawa, Kazuo; Suzuki, Kenji; Takamochi, Kazuya; Ito, Hiroyuki; Okami, Jiro; Aokage, Keiju; Shiono, Satoshi; Yoshioka, Hiroshige; Aoki, Tadashi; Tsutani, Yasuhiro; Okada, Morihito; Watanabe, Shun-ichi
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 51 1 28 - 36 OXFORD UNIV PRESS 2021年01月 [査読有り]
     
    The superior efficacy of immune checkpoint inhibitors for the treatment of advanced non-small cell lung cancer has inspired many clinical trials to use immune checkpoint inhibitors in earlier stages of lung cancer worldwide. Based on the theoretical feasibility that neoantigens derived from a tumor tissue are present in vivo, some clinical trials have recently evaluated the neoadjuvant, rather than the adjuvant, use of immune checkpoint inhibitors. Some of these trials have already produced evidence on the safety and efficacy of immune checkpoint inhibitors in a neoadjuvant setting, with a favorable major pathologic response and few adverse events. In the most impactful report from Johns Hopkins University and the Memorial Sloan Kettering Cancer Center, the programed death-1 inhibitor nivolumab was administered to 21 patients in a neoadjuvant setting. The authors reported a major pathologic response rate of 45%, with no unexpected delay of surgery related to the adverse effects of nivolumab. The adjuvant as well as the neoadjuvant administration of immune checkpoint inhibitors has also been considered in various clinical trials, with or without the combined use of chemotherapy or radiotherapy. The development of appropriate biomarkers to predict the efficacy of immune checkpoint inhibitors is also underway. The expression of programed death ligand-1 and the tumor mutation burden are promising biomarkers that have been evaluated in many settings. To establish an appropriate method for using immune checkpoint inhibitors in combination with surgery, the Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group will manage clinical trials using a multimodality treatment, including immune checkpoint inhibitors and surgery.
  • Yasuhiro Tsutani; Yoshihisa Shimada; Hiroyuki Ito; Yoshihiro Miyata; Norihiko Ikeda; Haruhiko Nakayama; Morihito Okada
    Frontiers in oncology 11 622742 - 622742 2021年06月 [査読有り]
     
    Objective This study aimed to identify patients at a high risk of recurrence using preoperative high-resolution computed tomography (HRCT) in clinical stage I non-small cell lung cancer (NSCLC). Methods A total of 567 patients who underwent screening and 1,216 who underwent external validation for clinical stage I NSCLC underwent lobectomy or segmentectomy. Staging was used on the basis of the 8(th) edition of the tumor-node-metastasis classification. Recurrence-free survival (RFS) was estimated using the Kaplan-Meier method, and the multivariable Cox proportional hazards model was used to identify independent prognostic factors for RFS. Results A multivariable Cox analysis identified solid component size (hazard ratio [HR], 1.66; 95% confidence interval [CI] 1.30-2.12; P < 0.001) and pure solid type (HR, 1.82; 95% CI 1.11-2.96; P = 0.017) on HRCT findings as independent prognostic factors for RFS. When patients were divided into high-risk (n = 331; solid component size of >2 cm or pure solid type) and low-risk (n = 236; solid component size of <= 2 cm and part solid type) groups, there was a significant difference in RFS (HR, 5.33; 95% CI 3.09-9.19; 5-year RFS, 69.8% vs. 92.9%, respectively; P < 0.001). This was confirmed in the validation set (HR, 5.32; 95% CI 3.61-7.85; 5-year RFS, 72.0% vs. 94.8%, respectively; P < 0.001). Conclusions In clinical stage I NSCLC, patients with a solid component size of >2 cm or pure solid type on HRCT were at a high risk of recurrence.
  • Kamigaichi, Atsushi; Tsutani, Yasuhiro; Mimae, Takahiro; Miyata, Yoshihiro; Ito, Hiroyuki; Nakayama, Haruhiko; Ikeda, Norihiko; Okada, Morihito
    EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 58 6 1245 - 1253 OXFORD UNIV PRESS INC 2020年12月 [査読有り]
     
    OBJECTIVES: The purpose of this study was to determine the radiological characteristics of aggressive small-sized lung cancer and to compare the outcomes between segmentectomy and lobectomy in patients with these lung cancers. METHODS: A series of 1046 patients with clinical stage IA1-IA2 lung cancer who underwent lobectomy or segmentectomy at 3 institutions was retrospectively evaluated to identify radiologically aggressive small-sized (solid tumour size <= 2 cm) lung cancers. Prognosis of segmentectomy was compared with that of lobectomy in 522 patients with radiologically aggressive small-sized lung cancer using propensity score matching. RESULTS: Multivariable analysis showed that increasing consolidation-to-tumour ratio on preoperative high-resolution computed tomography (CT) (P = 0.037) and maximum standardized uptake on 18 fluoro-2-deoxyglucose positron emission tomography/CT (P = 0.029) was independently associated with worse recurrence-free survival. Based on analysis of the receiver operating characteristic curve, radiologically aggressive lung cancer was defined as a radiologically solid (consolidation-to-tumour ratio >= 0.8) or highly metabolic (maximum standardized uptake >= 2.5) tumour. Among patients with radiologically aggressive lung cancer, no significant statistical differences in 5-year recurrence-free (81% vs 90%; P = 0.33) and overall (88% vs 93%; P = 0.76) survival comparing lobectomy (n = 392) to segmentectomy (n = 130) were observed. Among 115 propensity-matched pairs, 5-year recurrence-free survival and overall survival were similar between patients who underwent lobectomy and those who underwent segmentectomy (83.3% and 88.3% vs 90.9% and 94.5%, respectively). CONCLUSIONS: Difference in survival was not identified with segmentectomy and lobectomy in patients with radiologically aggressive small-sized lung cancer with high risk of recurrence.
  • Kagimoto, Atsushi; Tsutani, Yasuhiro; Handa, Yoshinori; Mimae, Takahiro; Miyata, Yoshihiro; Okada, Morihito
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 50 11 1306 - 1312 OXFORD UNIV PRESS 2020年11月 [査読有り]
     
    Objectives: This study aimed to determine the characteristics, ground glass opacity ratio and prognosis of patients with clinical N0 non-small cell lung cancer tumours exceeding 30 mm in size. Methods: Patients with clinical N0 non-small cell lung cancer and total tumour size >30 mm on preoperative computed tomography who underwent complete resection with lobectomy between January 2007 and December 2017 were included. The patients were divided into three groups: pure solid tumour, low ground glass opacity ratio (1-39%) tumour and high ground glass opacity ratio (=40%) tumour. The cut-off line was determined based on the recurrence rate for every 10% ground glass opacity ratio. Results: Among the 227 study patients, 129 (56.8%) had a pure solid tumour, 54 (23.8%) had a low ground glass opacity ratio tumour and 44 (19.4%) had a high ground glass opacity ratio tumour. Three-year recurrence-free survival was significantly shorter in patients with a pure solid tumour (57.4%) than in patients with a low ground glass opacity ratio (74.5%; P = 0.009) or a high ground glass opacity ratio tumour (92.1%; P < 0.001). Multivariable analysis showed that ground glass opacity ratio was a significant independent prognostic factor for recurrence-free survival (hazard ratio, 0.175; P = 0.037). Conclusion: Pure solid tumours comprised a large proportion of non-small cell lung cancer tumours >30 mm in size and their prognosis was poor. The presence of ground glass opacity and their relative proportion affect prognosis in patients with clinical N0 non-small cell lung cancer tumours >30 mm in size, similar to those with small-sized tumours.
  • Shimoyama, Ryo; Tsutani, Yasuhiro; Wakabayashi, Masashi; Katayama, Hiroshi; Fukuda, Haruhiko; Suzuki, Kenji; Watanabe, Shun-ichi
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 50 10 1209 - 1213 OXFORD UNIV PRESS 2020年10月 [査読有り]
     
    Anatomical segmentectomy or wedge resection is recommended for high-risk operable patients with clinical stage IA non-small cell lung cancer in guidelines of the National Comprehensive Cancer Network and the Japanese Lung Cancer Society. However, there is no clear evidence comparing the sublobar resections. The less invasive and more generally performed is wedge resection but anatomical segmentectomy may have better survival benefits than wedge resection owing to its superiority in locoregional control. In April 2020, we have initiated a randomized phase III trial in Japan to confirm the superiority of anatomical segmentectomy over wedge resection in high-risk operable patients with clinical stage IA non-small cell lung cancer. We plan to enroll a total of 370 patients from 47 institutions over a period of 5 years. The primary endpoint is overall survival; the secondary endpoints are adverse events, postoperative respiratory function, relapse-free survival, proportion of local recurrence, operative time and blood loss.
  • Yoshinori Handa; Yasuhiro Tsutani; Noriyuki Shiroma; Yuichiro Kai; Takahiro Mimae; Yoshihiro Miyata; Yukio Takeshima; Koji Arihiro; Morihito Okada
    Clinical lung cancer 21 4 e302-e314  2020年07月 [査読有り]
     
    BACKGROUND: The programmed death 1/programmed death-ligand 1 (PD-L1) pathway reportedly is as an important factor determining effects of immunotherapy; however, its prognostic impact is controversial, and its association with the surrounding immune microenvironment has not yet been elucidated. PATIENTS AND METHODS: We retrospectively analyzed 126 patients with pathologic stage I non-small-cell lung cancer. Patients with lepidic-dominant adenocarcinoma were excluded. PD-L1 expression was evaluated with immunohistochemistry correlated with clinicopathologic features and surrounding immune microenvironment status, including CD4, CD8, regulatory T cells, and human leukocyte antigen class I. Factors affecting prognosis were assessed by Kaplan-Meier and Cox regression analyses. RESULTS: Twenty-three (18.3%) patients were positive for PD-L1 expression. No significant correlation was observed between PD-L1 expression and the surrounding immune microenvironment status. The PD-L1-positive group had a worse prognosis than the PD-L1-negative group (5-year recurrence-free survival rates, 63.4% vs. 81.0%; P = .061). Among surrounding immune cells, intratumoral CD8 status had the strongest impact on prognosis (P = .12). In the intratumoral CD8-high group, PD-L1 expression demonstrated no significant prognostic impact, whereas in the intratumoral CD8-low group, patients positive for PD-L1 demonstrated a significantly worse prognosis than those negative for PD-L1 (5-year recurrence-free survival rates, 41.7% vs. 78.6%; P = .034). Multivariable Cox regression analysis revealed that 'PD-L1-positive and intratumoral CD8-low' status was an independent prognostic factor (hazard ratio, 3.80; 95% confidence interval, 1.22-10.5; P = .023). CONCLUSIONS: The prognostic impact of the PD-1/PD-L1 pathway may be distinct according to concurrent intratumoral CD8 status.
  • Takahiro Mimae; Yoshihiro Miyata; Yasuhiro Tsutani; Kentaro Imai; Hiroyuki Ito; Haruhiko Nakayama; Norihiko Ikeda; Morihito Okada
    Japanese journal of clinical oncology 2020年06月 [査読有り]
     
    OBJECTIVE: Anatomical resection with lymph node dissection is the standard treatment for early non-small cell lung cancer, whereas wedge resection is considered as a compromise. We aimed to determine whether wedge resection without lymph node dissection could be a treatment option for patients aged ≥80 years. METHODS: We assessed 669 patients with clinical stage IA non-small cell lung cancer, whole tumour sizes ≤2 cm and a consolidation to tumour ratio of >0.5 who underwent R0 resection at three institutions between 2010 and 2016. We selected 58 of them who were aged ≥80 years and analysed their clinicopathological findings and prognosis after surgical procedures over a median follow-up of 38 months. Propensity scores for surgical procedures were calculated using age, gender, smoking status and solid tumour size on computed tomography. RESULTS: Three-year overall and recurrence-free survival rates after wedge resection and after segmentectomy + lobectomy for patients aged ≥80 years did not significantly differ (overall survival: 88.9% [95% confidence interval, 69.4-96.3%] vs. 75.5% [95% confidence interval, 51.5-88.8%], P = 0.95; recurrence-free survival: 85.2% [95% confidence interval: 65.2-94.2%] vs. 68.0% [95% confidence interval, 44.4-83.2], P = 0.57). Multivariable Cox regression analysis of overall survival with propensity scores revealed that surgical procedure was not an independent predictor of a poor prognosis (hazard ratio: 0.86 (0.28-2.6), P = 0.78) in patients aged ≥80 years. CONCLUSIONS: Wedge resection might be an alternative to lobectomy or segmentectomy with lymph node dissection for patients aged ≥80 years with early non-small cell lung cancer.
  • Yasuhiro Tsutani; Haruhiko Nakayama; Hiroyuki Ito; Yoshinori Handa; Takahiro Mimae; Yoshihiro Miyata; Morihito Okada
    Clinical lung cancer 22 3 E431 - E437 2020年06月 [査読有り]
     
    PURPOSE: To evaluate long-term outcomes after sublobar resection for patients with clinical stage IA lung adenocarcinoma who met our proposed node-negative (N0) criteria, namely solid component size < 0.8 cm on high-resolution computed tomography (HRCT) or a maximum standardized uptake value (SUVmax) of < 1.5 on [18F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT). PATIENTS AND METHODS: Between April 2006 and December 2010, a total of 347 patients with clinical stage IA lung adenocarcinoma underwent complete resection in two medical centers. Long-term outcomes of patients with disease that met the N0 criteria after sublobar resection were evaluated. RESULTS: The disease of 201 patients (57.9%) met the N0 criteria. Meeting N0 criteria was significantly associated with low-grade adenocarcinoma subtype (P < .001) and absence of lymphatic invasion (P < .001), vascular invasion (P < .001), and pleural invasion (P < .001). One patient (0.5%) had lymph node metastasis. The median follow-up period was 86.1 months. There was a significant difference in the overall survival (OS) rates between patients with disease that met the N0 criteria (5-year OS, 93.9%; 10-year OS, 90.3%) and disease that did not (5-year OS, 81.5%; 10-year OS, 64.3%; P < .001). Among patients with disease that met the N0 criteria, there was no significant difference in the OS between those who underwent lobectomy (5-year OS, 94.3%; 10-year OS, 92.6%) and those who underwent sublobar resection (5-year OS, 93.8%; 10-year OS, 89.3%; P = .64). CONCLUSIONS: Sublobar resection of clinical stage IA lung adenocarcinoma is feasible in selected patients with disease that meets the N0 criteria, with excellent long-term survival.
  • Kiyo Tanaka; Yasuhiro Tsutani; Masashi Wakabayashi; Tomonori Mizutani; Keiju Aokage; Yoshihiro Miyata; Hiroaki Kuroda; Hisashi Saji; Shun-Ichi Watanabe; Morihito Okada
    Japanese journal of clinical oncology 50 9 1076 - 1079 2020年06月 [査読有り]
     
    The standard treatment for the patients with surgically resectable early non-small cell lung cancer (NSCLC) is lung lobectomy. However, if patients have idiopathic pulmonary fibrosis combined with early stage lung cancer, there is no standard treatment for this population. Patients with idiopathic pulmonary fibrosis have chronic progressive decline in respiratory function; thus, the preservation of respiratory function is essential. The aim of this trial is to confirm the clinical effectiveness of sublobar resection such as wedge resection or segmentectomy for early NSCLC with idiopathic pulmonary fibrosis compared with lobectomy in a randomized phase III trial. The primary endpoint is overall survival. If the non-inferiority of overall survival and minimal invasiveness are proven, it can be a new standard treatment for early NSCLC with idiopathic pulmonary fibrosis. A planned total 430 patients will be enrolled from 50 institutions over 5 years. This trial has been registered in the UMIN Clinical Trials Registry with code UMIN000032696 [http://www.umin.ac.jp/ctr/index.htm].
  • Zheng, Yu-Zhen; Zhai, Wen-Yu; Zhao, Jian; Luo, Rui-Xing; Gu, Wan-Jie; Fu, Shen-Shen; Wu, Da; Yuan, Lian-Xiong; Jiang, Wei; Tsutani, Yasuhiro; Liao, Hong-Ying; Li, Xiao-Qiang
    JOURNAL OF THORACIC DISEASE 12 6 3178 - + AME PUBL CO 2020年06月 [査読有り]
     
    Background: Lobectomy has long been regarded as the standard treatment for operable non-small cell lung cancer (NSCLC). Recent studies suggested that segmentectomy could achieve a gtxxl prognosis for early-stage NSCLC and might be an alternative to lobectomy in this cohort. Until now, on the issue of comparison between lobectomy and segmentectomy, there remains no published randomized controlled trial (RCT), and all existing evidence is low. Recently, a categorization of lower-level evidence has been proposed, namely, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The aim of this meta-analysis is to compare the oncologic outcome between lobectomy and segmentectomy in NSCLC with the clinical TINOMO stage according to the GRADE system. Methods: PubMed, the PMC database, EMBASE, Web of Science, and the Cochrane library were searched prior to May 2019 to identify studies that compared the prognosis between lobectomy and segmentectomy for clinical T1N0M0 NSCLC. The evidence level of the included studies was assessed according to the GRADE system, including level Mk, probably not confounded nonrandomized comparison; level IIB, possibly confounded nonrandomized comparison; and level IIC, probably confounded nonrandomized comparison. The predefined outcomes included overall survival (OS) and disease-free survival (DFS). Univariable and multivariable hazard ratios (HRs) with 95% confidence intervals (95% CI) were pooled using a random-effects model. Results: Twelve nonrandomized studies involving 8,072 participants were included. Of these studies, two were classified as IIA level (16.7%), six as IIB level (50.0%), and four as IIC level (33.3%). When crude HRs were included, compared with lobectomy, segmentectomy was associated with shorter OS but comparable DFS in the entire cohort (OS, pooled HR =1.45, 95% CI, 1.23 to 1.67; DFS, pooled HR =1.03, 95% CI, 0.65 to 1.82) and in patients with nodules <= 2 cm (OS, pooled HR =1.55, 95% CI, 1.33 to 1.80; DFS, pooled HR =0.98, 95% CI, 0.55 to 1.77). When adjusted HRs were included, the impact of segmentectomy on OS and DES was comparable to that of lobectomy in the entire cohort (OS, pooled ER =1.39, 95% CI, 0.92 to 2.10; DFS, pooled HR =0.83, 95% CI, 0.66 to 1.03) and in patients with nodules <= 2 cm (OS, pooled HR =1.61, 95% CI, 0.87 to 3.00; DFS, pooled ER =0.90, 95% CI, 0.63 to 1.27). Conclusions: Based on our results, although shorter OS is observed in patients received segmentectomy, it is necessary to wait for more results from RCT to draw a valid conclusion.
  • Kimitaka Makidono; Yoshihiro Miyata; Takuhiro Ikeda; Yasuhiro Tsutani; Kei Kushitani; Yukio Takeshima; Morihito Okada
    General thoracic and cardiovascular surgery 68 6 609 - 614 2020年06月 [査読有り]
     
    OBJECTIVE: Bronchial fistulae following lung surgery are associated with high mortality. We examined the histological effects of mucosal ablation as a technique for closing bronchial stumps to prevent bronchial fistulae in an animal model. METHODS: Left lower lobectomy was performed in beagles under general anesthesia. The bronchial stumps were closed using one of the following four methods: (A) manual suturing using 3-0 absorbable sutures, (B) ablation of bronchial mucosa with electric cautery and manual sutures, (C) stapling and reinforcement with manual sutures, or (D) ablation and stapling followed by reinforcement with manual sutures. Bronchial stumps were histologically evaluated on postoperative day 14. RESULTS: No bronchial fistulae were noted in the animals during the observation period. Histologically, there were no adhesions between the bronchial mucosae at the suture and staple lesions in groups A and C. The bronchial mucosae were adherent at the ablation sites in groups B and D. Inflammatory cells, myofibroblasts, and neovascular vessels were abundant around the ablated lesions. CONCLUSIONS: Bronchial mucosal ablation may play a key role in mucosal adhesion and tight union of the bronchial stump.
  • Yumiko Koi; Yasuhiro Tsutani; Yukie Nishiyama; Daisuke Ueda; Yuta Ibuki; Shinsuke Sasada; Tomoyuki Akita; Norio Masumoto; Takayuki Kadoya; Yuki Yamamoto; Ryou-u Takahashi; Junko Tanaka; Morihito Okada; Hidetoshi Tahara
    CANCER SCIENCE 111 6 2104 - 2115 2020年06月 [査読有り]
     
    Emerging evidence indicates that small RNAs, including microRNAs (miRNAs) and their isoforms (isomiRs), and transfer RNA fragments (tRFs), are differently expressed in breast cancer (BC) and can be detected in blood circulation. Circulating small RNAs and small RNAs in extracellular vesicles (EVs) have emerged as ideal markers in small RNA-based applications for cancer detection. In this study, we first undertook small RNA sequencing to assess the expression of circulating small RNAs in the serum of BC patients and cancer-free individuals (controls). Expression of 3 small RNAs, namely isomiR of miR-21-5p (3 ' addition C), miR-23a-3p and tRF-Lys (TTT), was significantly higher in BC samples and was validated by small RNA sequencing in an independent cohort. Our constructed model using 3 small RNAs showed high diagnostic accuracy with an area under the receiver operating characteristic curve of 0.92 and discriminated early-stage BCs at stage 0 from control. To test the possibility that these small RNAs are released from cancer cells, we next examined EVs from the serum of BC patients and controls. Two of the 3 candidate small RNAs were identified, and shown to be abundant in EVs of BC patients. Interestingly, these 2 small RNAs are also more abundantly detected in culture media of breast cancer cell lines (MCF-7 and MDA-MB-231). The same tendency in selective elevation seen in total serum, serum EV, and EV derived from cell culture media could indicate the efficiency of this model using total serum of patients. These findings indicate that small RNAs serve as significant biomarkers for BC detection.
  • Atsushi Kamigaichi; Yasuhiro Tsutani; Atsushi Kagimoto; Makoto Fujiwara; Takahiro Mimae; Yoshihiro Miyata; Morihito Okada
    Clinical lung cancer 2020年05月 [査読有り]
     
    INTRODUCTION: We aimed to determine the feasibility of segmentectomy for radiologically solid-dominant clinical stage IA lung cancer measuring 2.1 to 3 cm (whole tumor size). PATIENTS AND METHODS: Data from 197 patients with radiologically solid-dominant clinical stage IA lung cancer measuring 2.1 to 3 cm who underwent lobectomy (n = 154) or segmentectomy (n = 43) were retrospectively analyzed. Recurrence-free survival (RFS) and overall survival (OS) at 5 years were assessed. Finally, propensity score matching was performed by age, gender, radiologic whole tumor size, consolidation to maximum tumor ratio, tumor location, maximum standardized uptake value, and preoperative forced expiratory volume in 1 second (FEV1) and vital capacity (VC). RESULTS: Only 2 (4.7%) patients in the segmentectomy group were converted to lobectomy because of lymph node metastasis or inadequate surgical margins. Postoperative reductions in VC and FEV1 at 12 months were significantly less in the segmentectomy group (VC, 7.4%; FEV1, 6.9%) than in the lobectomy group (VC, 17.6%; FEV1, 14.4%). RFS was comparable between patients who underwent lobectomy and segmentectomy in both the unmatched (73.4% and 82.7%, respectively; P = .30) and the 37 propensity-matched (79.5% and 80.1%, respectively) patients. Similarly, OS was comparable between patients who underwent lobectomy and segmentectomy in the unmatched (80.0% and 90.6%, respectively; P = .42) and matched (82.9% and 89.3%, respectively) patients. CONCLUSIONS: Segmentectomy can be feasible in patients with radiologically solid-dominant clinical stage IA lung cancers measuring 2.1 to 3 cm when patients are appropriately selected.
  • Takahiro Mimae; Yasuhiro Tsutani; Yoshihiro Miyata; Kentaro Imai; Hiroyuki Ito; Haruhiko Nakayama; Norihiko Ikeda; Morihito Okada
    The Annals of thoracic surgery 109 5 1530 - 1536 2020年05月 [査読有り]
     
    BACKGROUND: The prognosis of patients with cT1N0 lung adenocarcinoma is better when tumors include mixed ground glass opacity (GGO), compared with pure solid tumors. However, whether the prognosis of patients with mixed GGO tumors is favorable regardless of the solid component size remains unknown. Therefore, we aimed to determine the prognostic role of the solid component size in mixed GGO. METHODS: We retrospectively analyzed the clinicopathological findings and prognoses of 856 patients with mixed GGO tumors based on solid component size during a median follow-up of 45 months, among 1215 patients with cT1N0 lung adenocarcinoma according to the TNM Classification of Malignant Tumors, Eighth Edition, who underwent R0 resection at 3 institutions between 2010 and 2015. RESULTS: Four-year recurrence-free survival rates were significantly worse for patients with mixed GGO cT1c tumors (solid component size: 2-3 cm; 81.5%; 95% confidence interval [CI], 72.8%-87.7%) than for those with cT1mi+1a tumors (0-1 cm; 96.8%; 95% CI, 94.2%-98.2%) and cT1b (1-2 cm; 95.3%; 95% CI, 92.1%-97.2%) (both P < .001), although that for cT1b tumors was comparably favorable to those of T1mi+1a tumors. Multivariable Cox regression analysis of recurrence-free survival revealed that a solid component size of 2 cm to 3 cm (cT1c) vs less than or equal to 2 cm (cT1mi+1a+1b) was an independent prognostic factor (hazard ratio, 4.16; 95% CI, 2.24-7.72; P < .001). CONCLUSIONS: The prognostic impact of a solid component size less than or equal to 2 cm and greater than 2 cm significantly differs after complete resection of GGO-mixed T1N0 lung adenocarcinoma. The prognosis of patients with solid components less than or equal to 2 cm is favorable, whereas the behavior of those solid components greater than 2 cm is more aggressive.
  • Yumiko Koi; Yasuhiro Tsutani; Yukie Nishiyama; Miyuki Kanda; Yoshitomo Shiroma; Yuki Yamamoto; Shinsuke Sasada; Tomoyuki Akita; Norio Masumoto; Takayuki Kadoya; Ryou-u Takahashi; Junko Tanaka; Morihito Okada; Hidetoshi Tahara
    CANCER SCIENCE 111 5 1856 - 1861 2020年05月 [査読有り]
     
    The telomere G-tail (G-tail) plays an essential role in maintaining chromosome stability. In this study, we assessed the leukocyte G-tail length of breast cancer (BC) patients and cancer-free individuals and evaluated the association between the G-tail length and the presence of BC. A significant shortening of the median G-tail length was observed in BC patients compared with cancer-free individuals and was found in the early phase of BC. Our study indicated that the leukocyte G-tail length might be a potential biomarker for BC detection.
  • Atsushi Kagimoto; Yasuhiro Tsutani; Yu Izaki; Yoshinori Handa; Takahiro Mimae; Yoshihiro Miyata; Morihito Okada
    The Annals of thoracic surgery 2020年04月 [査読有り]
     
    BACKGROUND: This study aimed to investigate the efficacy of the Deauville criteria, a 5-point semiquantitative scale criteria to assess the maximum standardized uptake value (SUVmax) of [18F]-fluoro-2-deoxy-D-glucose (FDG) on positron emission tomography (PET)/computed tomography (CT), in predicting lymph node metastasis and other pathological invasive characteristics of early-stage lung adenocarcinoma. METHODS: In this retrospective study including 453 patients undergoing lobectomy or segmentectomy with lymph node dissection for clinical T1 or Tis N0 adenocarcinoma between April 2011 and March 2019, the FDG-PET/CT scans were evaluated using the Deauville criteria to analyze the relationship of Deauville score with the clinicopathological characteristics and prognosis. RESULTS: The lymph node metastases were present in 0 (0%), 2 (1.1%), 6 (9.5%), 6 (15.8%), and 13 (15.7%) patients with Deauville scores of 1, 2, 3, 4 and 5, respectively. The pathological invasive characteristics (lymphatic, vascular, or visceral pleural invasion) were detected in 2 (2.4%), 17 (9.9%), 18 (28.6%), 23 (60.5%), and 54 (65.1%) patients with Deauville score 1, 2, 3, 4, and 5, respectively. The 3-year recurrence-free survival was longer in the patients with a Deauville score of 1-2 (97.2%) than those with a Deauville score of 3 (86.2%, p < 0.001) or 4-5 (80.7%, p < 0.001). CONCLUSIONS: The 5-point-scale evaluation of the SUVmax on FDG-PET/CT using the Deauville score was useful in predicting not only lymph node metastasis but also other malignant features of early-stage lung adenocarcinoma.
  • Atsushi Kagimoto; Yasuhiro Tsutani; Yu Izaki; Yoshinori Handa; Takahiro Mimae; Yoshihiro Miyata; Morihito Okada
    Japanese journal of clinical oncology 50 4 440 - 445 2020年04月 [査読有り]
     
    OBJECTIVE: Anatomical segmentectomy has the potential to replace lobectomy as the standard procedure for early stage non-small cell lung cancer. We investigated the safety and feasibility of robotic anatomical segmentectomy for non-small cell lung cancer. METHODS: Overall 20 patients underwent robotic anatomical segmentectomy at Hiroshima University Hospital between January 2014 and January 2018. The clinicopathological characteristics, surgical outcomes, complications and prognosis were analyzed. RESULTS: The median age was 68 (range 42-86) years, and 15 patients were female. Six patients were non-smokers. The most common clinical stage was IA1 (nine patients). Complex segmentectomies were performed in four patients (one right S3 segmentectomy, two right S8 segmentectomies and one left S8 + S9 segmentectomy). The median operation time was 163.5 (range, 114-314) minutes, and the median console time was 104 (range, 60-246) minutes. The median blood loss was 26.5 (range, 5-247) ml. The median resection margin and number of dissected lymph node were 15 (range, 2-60) mm and 5 (range, 1-15), respectively. Although five (25.0%) patients had grade IIIa complications (pleurodesis for prolonged air leakage) and one (5.0%) had a grade IIIb complication (reoperation for prolonged air leakage), no post-operative deaths occurred. The surgical outcomes were comparable with those of anatomical segmentectomy performed under hybrid video-assisted thoracoscopic surgery during the same period. CONCLUSION: In our initial experience of robotic anatomical segmentectomy for early stage non-small cell lung cancer, the procedure seems to be safe and feasible.
  • Tomoharu Yoshiya; Takahiro Mimae; Masaoki Ito; Shinsuke Sasada; Yasuhiro Tsutani; Kenichi Satoh; Takeshi Masuda; Yoshihiro Miyata; Noboru Hattori; Morihito Okada
    Investigational new drugs 38 2 485 - 492 2020年04月 [査読有り]
     
    Purpose Anorexia induced by cytotoxic chemotherapy on delayed phase is a highly frequent adverse event. We aimed to determine the effects of rikkunshito (RKT) on chemotherapy-induced anorexia (CIA) in patients with lung cancer. Methods This prospective, randomized, cross-over pilot trial included 40 lung cancer patients scheduled to undergo cisplatin-based chemotherapy and randomized to either a group given RKT 7.5 g/day for 14 days (Group A, N = 20) or not (Group B, N = 20), then the treatments were switched. All patients received dexamethasone, palonosetron hydrochloride and aprepitant regardless of group assignment. Rescue drugs were allowed as required. The primary and key secondary endpoints were changes in caloric intake and in plasma acylated ghrelin (AG) levels, respectively. Average daily caloric intake during days 3 to 5 was compared with that on day 1 of each course. Results The primary and key secondary endpoints were analyzed in 31 patients (per protocol population) completing the study. Reduction rate of caloric intake was lower in RKT, than in control courses (18% vs. 25%, P = 0.025). Plasma AG levels significantly declined between days 1 and 3 in RKT (12.3 vs. 7.5 fmol/mL, P < 0.001) and control (10.8 vs. 8.6 fmol/mL, P < 0.001) courses. However, those obviously increased to 8.5 fmol/mL (P = 0.025) by day 5 in RKT course but not in control course (7.7 fmol/mL, P = 0.28). Conclusions Rikkunshito could mitigate CIA and ameliorate plasma AG levels during the delayed phase of CDDP-based chemotherapy in lung cancer patients. Clinical trial registration numbers: UMIN000010748.
  • Manato Ohsawa; Yasuhiro Tsutani; Makoto Fujiwara; Takahiro Mimae; Yoshihiro Miyata; Morihito Okada
    The Annals of thoracic surgery 109 4 1054 - 1060 2020年04月 [査読有り]
     
    BACKGROUND: Interstitial pneumonia is linked to lung cancer, and treatment can cause acute exacerbation. We aimed to identify predictors of severe postoperative complications in patients with lung cancer and interstitial pneumonia. METHODS: Between April 2007 and April 2017, 199 patients were diagnosed with primary lung cancer and interstitial pneumonia using high-resolution computed tomography. Multivariable logistic regression analyses were performed to identify independent predictors of severe complications (Clavien-Dindo grade IIIa or higher). RESULTS: Multivariable analyses revealed that severe complications were independently predicted by the percent diffusing capacity of the lungs for carbon monoxide (%Dlco [odds ratio 0.88; 95% confidence interval, 0.82 to 0.95; P < .001]) and surgical procedures (lobectomy, odds ratio 4.49; 95% confidence interval, 1.86 to 23.32; P = .045). Severe complications occurred in 39.2% of patients with low %Dlco (less than 40%) and in 4.2% of patients with high %Dlco (greater than 40%). The rates of severe complications were 11.5% for patients who underwent lobectomy and 9.7% for patients who underwent sublobar resection. For patients with low %Dlco, the rates of severe complications were 85.7% for those undergoing lobectomy and 23.8% for those undergoing sublobar resection (P = .009). Overall survival (OS) was significantly different between patients with low %Dlco (5-year OS 33.5%) and patients with high %Dlco (5-year OS 65.3%; P = .001). Among patients with low %Dlco, there was a significant difference in OS between patients who underwent lobectomy (5-year OS 0%) and those who underwent sublobar resection (5-year OS 49.6%; P = .029). CONCLUSIONS: Severe postoperative complications were predicted by %Dlco and surgery type. Sublobar resection might be a better option for patients with low %Dlco values (less than 40%).
  • Yuta Ibuki; Yukie Nishiyama; Yasuhiro Tsutani; Manabu Emi; Yoichi Hamai; Morihito Okada; Hidetoshi Tahara
    PLOS ONE 15 4 2020年04月 [査読有り]
     
    BackgroundMicroRNA (miR)s are promising diagnostic biomarkers of cancer. Recent next generation sequencer (NGS) studies have found that isoforms of micro RNA (isomiR) circulate in the bloodstream similarly to mature micro RNA (miR). We hypothesized that combination of circulating miR and isomiRs detected by NGS are potentially powerful cancer biomarker. The present study aimed to investigate their application in esophageal cancer.MethodsSerum samples from patients with esophageal squamous cell carcinoma (ESCC) and age and sex matched healthy control (HC) individuals were investigated for the expression of miR/isomiRs using NGS. Candidate miR/isomiRs which met the criteria in the 1st group (ESCC = 18 and HC = 12) were validated in the 2nd group (ESCC = 30 and HC = 30). A diagnostic panel was generated using miR/isomiRs that were consistently confirmed in the 1st and 2nd groups. Accuracy of the panel was tested then in the 3rd group (ESCC = 18 and HC = 18). Their use was also investigated in 22 paired samples obtained pre- and post-treatment, and in patients with esophageal adenocarcinoma (EAD) and high-grade dysplasia (HGD).ResultsTwenty-four miR/isomiRs met the criteria for diagnostic biomarker in the 1st and 2nd group. A multiple regression model selected one mature miR (miR-30a-5p) and two isomiRs (isoform of miR-574-3p and miR-205-5p). The index calculated from the diagnostic panel was significantly higher in ESCC patients than in the HCs (13.3 +/- 8.9 vs. 3.1 +/- 1.3, p<0.001). The area under the receiver operating characteristics (ROC) curves of the panel index was 0.95. Sensitivity and specificity were 93.8%, and 81% in the 1st and 2nd groups, and 88.9% and 72.3% in the 3rd group, respectively. The panel index was significantly lower in patients with EAD (6.2 +/- 4.5) and HGD (4.2 +/- 1.7) than in those with ESCC and was significantly decreased at post-treatment compared with pre-treatment (6.2 +/- 5.6 vs 11.6 +/- 11.5, p = 0.03).ConclusionOur diagnostic panel had high accuracy in the diagnosis of ESCC. MiR/isomiRs detected by NGS could serve as novel biomarkers of ESCC.
  • Yoshinori Handa; Yasuhiro Tsutani; Morihito Okada
    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 57 3 614 - 615 2020年03月 [査読有り]
  • Naoto Kishi; Masaoki Ito; Yoshihiro Miyata; Akinori Kanai; Yoshinori Handa; Yasuhiro Tsutani; Kei Kushitani; Yukio Takeshima; Morihito Okada
    Annals of surgical oncology 27 3 945 - 955 2020年03月 [査読有り]
     
    BACKGROUND: Lung adenocarcinoma with the micropapillary (MP) component poses a higher risk of recurrence even when the MP component is not predominant. This study explored genetic features associated with highly malignant behavior of lung adenocarcinoma with the MP component. METHODS: The MP and papillary (PaP) components were captured separately in three patients. Comprehensive mRNA expressions of somatic variants were compared between the MP and PaP components of each patient using next-generation sequencing (NGS). The protein expression of the NGS-detected variant was validated by immunohistochemistry. The prognostic impact of the detected variant was evaluated in 288 adenocarcinoma patients with resection of pN0M0. RESULTS: In two cases, NGS suggested higher RNA expression of EGFR L858R in the MP component than in the PaP component (allele frequency, 0.485 vs. 0.155 and 1.000 vs. 0.526, respectively; P < 0.001 for both). Immunohistochemistry validated intense expression of L858R in the MP component of 27 MP-positive (MP+) patients. Among 288 pN0M0 patients, L858R was more frequently harbored in the MP+ patients than in the MP-negative (MP-) patients. The MP+ patients harboring L858R showed significantly worse recurrence-free survival (RFS) than the MP+ patients without L858R (median RFS 38.7 and 55.0 months, respectively; hazard ratio [HR] 3.004; 95% confidence interval [CI] 1.306-9.132; P = 0.012). Multivariate analysis of the MP+ patients showed that positive L858R status was associated with poorer RFS (HR 2.976; 95% CI 1.190-7.442; P = 0.020). CONCLUSIONS: EGFR L858R was more frequently harbored in the MP+ adenocarcinoma patients than in the MP- adenocarcinoma patients. Intense expression of L858R in the MP component was suggested, and the MP+ patients harboring L858R were at comparatively higher risk of recurrence in the group with pN0M0 lung adenocarcinoma.
  • Masaoki Ito; Yoshihiro Miyata; Yasuhiro Tsutani; Hiroyuki Ito; Haruhiko Nakayama; Kentaro Imai; Norihiko Ikeda; Morihito Okada
    Lung cancer (Amsterdam, Netherlands) 141 107 - 113 2020年03月 [査読有り]
     
    OBJECTIVES: Recurrence risk of resected lung adenocarcinoma is represented by pathological stage (pStage), histological subtype, and potentially by EGFR mutation. However, the relationship among these factors and their combined impact on prognosis are unclear. MATERIALS AND METHODS: Using a multicenter database, we retrospectively investigated the prognostic impact of EGFR mutation status in relation to pStage and histological subtype in resected pN0-1M0 lung adenocarcinoma. RESULTS: Among 1155 pN0-1M0 adenocarcinoma cases, pStage 0 and IA1-IB were confirmed predominantly in EGFR-positive cases. AIS, MIA, and lepidic predominant adenocarcinoma were also more frequently found in EGFR-positive cases and showed no/little recurrence regardless of EGFR mutation status. The 5-year recurrence-free survival (RFS) of papillary, acinar, solid, and micropapillary predominant adenocarcinoma was stratified by pStage (IA1-IB, IIA-IIIA) or histological malignant subtype (intermediate or high malignant subtype), and more finely subdivided by EGFR mutation status. Positive EGFR mutation cases showed worse RFS in both classifications. Low malignant subtype and pStage IA1-IB intermediate malignant subtype showed low frequency of recurrence. Whereas, in pStage IA1-IB high malignant subtype and pStage IIA-IIIA cases, EGFR-positive cases showed poorer 5-year RFS than EGFR-negative (49.6% and 75.6%, respectively, hazard ratio [HR] = 1.84, 95% CI = 1.38-7.42, p <  0.01) and multivariate analysis indicated positive EGFR mutation status was significantly related to poorer PRF (HR = 2.005, 95% CI = 1.029-3.906, p =  0.041). CONCLUSION: EGFR mutation harbored primarily in early-stage or low-malignant histological subtypes with no/little recurrence. In pN0-1M0 adenocarcinoma with higher risk of recurrence, positive EGFR mutation cases showed worse RFS. EGFR mutation status enables better stratification of recurrence risk when considering pStage and histological malignant subtype.
  • Hiroyuki Ito; Kenji Suzuki; Tomonori Mizutani; Keiju Aokage; Masashi Wakabayashi; Haruhiko Fukuda; Shun ichi Watanabe; Teruaki Koike; Yasuhiro Tsutani; Hisashi Saji; Kazuo Nakagawa; Yoshitaka Zenke; Kazuya Takamochi; Tadashi Aoki; Jiro Okami; Hiroshige Yoshioka; Satoshi Shiono; Morihito Okada
    Journal of Thoracic and Cardiovascular Surgery 2020年 [査読有り]
     
    © 2020 Objective: The aim of this study was to assess long-term outcomes after lobectomy in patients with clinical T1 N0 lung cancer based on thin-section computed tomography. Methods: We collected the data of patients with pathological adenocarcinoma who had undergone lobectomy. The patients were categorized into 4 groups according to a consolidation tumor ratio and tumor size. Groups A and B included tumors with consolidation tumor ratio ≤0.5 and size ≤3 cm. Group A consisted of tumors ≤2 cm. Group B consisted of the remaining tumors. Groups C and D consisted of tumors with consolidation tumor ratio >0.5. Group C consisted of those with tumors ≤2 cm and Group D consisted of tumors of size 2 to 3 cm. The 10-year overall survival and recurrence-free survival rates were examined. Results: Among the 543 patients, the 10-year overall survival was 80.4% and the 10-year recurrence-free survival rate was 77.1%. The 10-year overall survival for group A was 94.0%, 92.7% for group B, 84.1% for group C, and 68.8% for group D, and the 10-year recurrence-free survival rate for each group was 94.0%, 89.0%, 79.7%, and 66.1%, respectively. Group A + B showed better overall survival than group C + D (hazard ratio, 2.78; 95% confidence interval, 1.45-5.06) and better 10-year recurrence-free survival (hazard ratio, 2.74; 95% confidence interval, 1.55-4.88). No patient in group A had recurrence. Conclusions: Those patients with total tumor size ≤3 cm and consolidation tumor ratio ≤0.5 showed excellent prognosis and might be suitable candidates for sublobar resection. If noninferior survival of segmentectomy compared with lobectomy is confirmed in an ongoing Japan Clinical Oncology Group trial, segmentectomy will be included in the standard of care.
  • Aritoshi Hattori; Kenji Suzuki; Kazuya Takamochi; Masashi Wakabayashi; Keiju Aokage; Hisashi Saji; Shun ichi Watanabe; Yasuhiro Tsutani; Hiroshige Yoshioka; Shiono Satoshi; Hiroyuki Ito; Tadashi Aoki; Kazuo Nakagawa; Jiro Okami; Morihito Okada; Tomonori Mizutani; Ryo Shimoyama; Haruhiko Fukuda
    Journal of Thoracic and Cardiovascular Surgery 2020年 [査読有り]
     
    © 2020 The American Association for Thoracic Surgery Objective: We performed a validation study to confirm the prognostic importance of the presence of a ground-glass opacity component based on data of the Japan Clinical Oncology Group study, JCOG0201, which was a prospective observational study to predict the pathological noninvasiveness of clinical stage IA lung cancer in Japan. Methods: Among the 811 patients registered in JCOG0201, 671 were confirmed eligible by study monitoring and a central review of computed tomography. Registered c-stage IA lung cancer was less than 30 mm in maximum tumor size, which was classified into a with ground-glass opacity group (pure ground-glass opacity and part-solid tumor) or solid group based on the status of a ground-glass opacity component. T staging was reassigned in accordance with the 8th edition of the TNM staging system. To validate the prognostic impact, overall survival was estimated. Results: Of the cases, 432 (64%) were in the with ground-glass opacity group and 239 (36%) were in the solid group with a median follow-up time of 10.1 years. The 5-year overall survival was significantly different between the with ground-glass opacity group and solid group (95.1% vs 81.1%). The 5-year overall survival was excellent regardless of the solid component size in the with ground-glass opacity group (c-T1a or less: 97.2%, c-T1b: 93.4%, c-T1c: 91.7%). In contrast, prognostic impact of the tumor size was definitive in the solid group (c-T1a: 87.5%, c-T1b: 85.9%, c-T1c: 73.7%). Conclusions: Favorable prognostic impact of the presence of a ground-glass opacity component was demonstrated in JCOG0201. The presence or absence of a ground-glass opacity should be considered as an important parameter in the next clinical T classification.
  • Yoshinori Handa; Yasuhiro Tsutani; Takahiro Mimae; Yoshihiro Miyata; Morihito Okada
    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 57 1 114 - 121 2020年01月 [査読有り]
     
    OBJECTIVES: Although segmentectomy for lung cancer has been widely accepted, complex segmentectomy, which creates several, intricate intersegmental planes, remains controversial. Potential arguments include risk of incurability and 'failure of cancer control'. We compared the outcomes of complex segmentectomy versus lobectomy and evaluated its use in lung cancer treatment. METHODS: We retrospectively reviewed clinical stage IA lung cancer patients who underwent complex segmentectomy (n = 99) or location-adjusted lobectomy (n = 94) between April 2009 and December 2017. Clinicopathological and postoperative results were compared. Factors affecting survival were assessed by the Kaplan-Meier method and the Cox regression analysis. RESULTS: No significant differences were detected in 30-day mortality (0% vs 0%), overall complications (26.3% vs 21.3%) and prolonged air leakage (11.1% vs 9.6%) rates between the 2 groups, respectively. Comparable results were obtained for 5-year overall (93.5% vs 96.4%, respectively; P = 0.21) or recurrence-free (92.3% vs 88.5%, respectively; P = 0.82) survivals after complex segmentectomy or lobectomy. There were 2 (2.0%) recurrences after complex segmentectomy and 7 (7.5%) after lobectomy (P = 0.094), with 0 (0%) margin relapses in each group. Multivariable Cox regression analysis revealed that complex segmentectomy and lobectomy had a numerically similar impact on recurrence-free survival (hazard ratio 0.93, 95% confidence interval 0.32-2.69; P = 0.90). CONCLUSIONS: Complex segmentectomy can provide acceptable short- and long-term outcomes in lung cancer treatment.
  • Yasuhiro Tsutani; Atsushi Kagimoto; Yoshinori Handa; Takahiro Mimae; Yoshihiro Miyata; Morihito Okada
    Japanese journal of clinical oncology 49 12 1134 - 1142 2019年12月 [査読有り]
     
    OBJECTIVE: The present study aimed to compare the outcomes of wedge resection and segmentectomy in patients with clinical stage I non-small-cell lung cancer (NSCLC) who were unfit for lobectomy. METHODS: Between April 2007 and December 2015, 99 patients with stage I NSCLC who were considered unfit for lobectomy and had undergone sublobar resection were identified. Propensity scores were estimated for multivariable analyses, and surgical outcomes were compared between patients who underwent wedge resection and those who underwent segmentectomy. RESULTS: Sixty patients underwent wedge resection and 39 underwent segmentectomy. Severe postoperative complications (>Grade IIIa) were more frequent in segmentectomy (15.4%) than in wedge resection (3.3%, P = 0.054). Propensity score-adjusted multivariable analysis revealed that operative procedure was an independent predictive factor for severe postoperative complication (segmentectomy, odds ratio = 8.18; P = 0.021). Overall survival (OS) and recurrence-free survival (RFS) were not significantly different between wedge resection (5-year OS, 61.3%, 5-year RFS, 49.4%) and segmentectomy (5-year OS, 68.2%, 5-year RFS, 56.8 %, P = 0.95, P = 0.93, respectively). Propensity score-adjusted multivariable Cox analysis revealed that operative procedure was not an independent factor for OS (segmentectomy, hazard ratio = 1.21, P = 0.62) or RFS (segmentectomy, hazard ratio = 1.07, P = 0.84). CONCLUSION: Segmentectomy was more toxic but failed to show the superiority of survival compared with wedge resection. Wedge resection may be the optimal procedure for patients with clinical stage I NSCLC who are considered to be unfit for lobectomy.
  • Yasuhiro Tsutani; Kenji Suzuki; Teruaki Koike; Masashi Wakabayashi; Tomonori Mizutani; Keiju Aokage; Hisashi Saji; Kazuo Nakagawa; Yoshitaka Zenke; Kazuya Takamochi; Hiroyuki Ito; Tadashi Aoki; Jiro Okami; Hiroshige Yoshioka; Morihito Okada; Shun-Ichi Watanabe
    The Annals of thoracic surgery 108 5 1484 - 1490 2019年11月 [査読有り]
     
    BACKGROUND: The aim of this study was to identify patients with pathological stage I lung adenocarcinoma at high risk of recurrence. METHODS: We retrieved data from 536 patients with pathological stage I lung adenocarcinoma who underwent lobectomy and were enrolled in a prospective multiinstitutional study (the JCOG0201 study). Invasive component size, excluding lepidic component, was used as the tumor size. Recurrence-free survival (RFS) was estimated by the Kaplan-Meier method, and a multivariable Cox proportional hazards model identified independent prognostic factors associated with worse RFS. RESULTS: The all-patient 10-year RFS was 83.9% (median follow-up 10.2 years). Multivariable Cox analysis revealed that age greater than 65 years (hazard ratio [HR], 2.60; 95% confidence interval (CI), 1.66-4.07), invasive component size greater than 2 cm (HR, 2.70; 95% CI, 1.40-5.23), visceral pleural invasion (HR, 2.17; 95% CI, 1.23-3.81), and vascular invasion (HR, 2.59; 95% CI, 1.47-4.55) were potential independent prognostic factors for RFS. When patients were divided into a high-risk group for recurrence (invasive component size >2 cm or positive for visceral pleural invasion or for vascular invasion; n = 124) and a low-risk group (invasive component size ≤2 cm and negative for visceral pleural invasion and vascular invasion; n = 408), there was a significant difference in RFS between the high-risk and low-risk groups (high-risk group: HR, 3.61; 95% CI, 2.35-5.55). CONCLUSIONS: Pathological stage I lung adenocarcinoma patients with an invasive component size greater than 2 cm, visceral pleural invasion, or vascular invasion were at high risk for recurrence.
  • 伊藤 宏之; 鈴木 健司; 水谷 友紀; 青景 圭樹; 佐治 久; 津谷 康大; 青木 正; 岡見 次郎; 中川 加寿夫; 高持 一矢; 中山 治彦; 塩野 知志; 吉岡 弘鎮; 岡田 守人; 福田 治彦; 渡辺 俊一
    肺癌 59 6 584 - 584 (NPO)日本肺癌学会 2019年11月 [査読有り]
  • Yamakita I; Mimae T; Tsutani Y; Miyata Y; Ito A; Okada M
    Biochemical and biophysical research communications 518 2 266 - 272 2019年10月 [査読有り]
     
    Previously, we identified molecules involved in human invasive lung adenocarcinoma, and guanylatebinding protein 1 (GBP-1) was selected for further analysis. RT-PCR of normal lung and invasive lung adenocarcinoma tissue samples showed that the relative GBP-1 expression levels normalized to GAPDH for invasive lung adenocarcinoma were three-fold higher than those for normal lung samples (P < 0.05). GBP-1 gene and protein expression levels were also higher in mesenchymal-like than in epithelial-like lung adenocarcinoma cell lines. To determine whether GBP-1 participates in lung adenocarcinoma invasion, we performed migration and wound healing assays using RERF-LC-OK cells transfected with various siRNAs. The relative migration of transfected GBP1-siRNA1 and GBP1-siRNA2 cells was significantly lower than that of transfected control-siRNA cells. The relative wound healing capacities 6 and 12 h after cells transfected with GBP1-siRNA1 and GBP1-siRNA2 were scratched were significantly lower than those of the control-siRNA cells. Immunohistochemistry of 80 patients with Stage I lung adenocarcinoma revealed that non-invasive cells were GBP-1 negative in all cases. Invasive cells were GBP-1 positive in 10 cases (12.5%) and GBP-1 negative in 70 cases (87.5%). Lymphatic-vascular invasion was positive in 20 patients (25%) and positively correlated with GBP-1 expression (P < 0.05). In conclusion, GBP-1 may enhance lung adenocarcinoma invasiveness by promoting cell motility, and control of GBP-1 expression has the potential to contribute to the development of new therapeutic strategies for lung adenocarcinoma. (C) 2019 Elsevier Inc. All rights reserved.
  • Atsushi Kamigaichi; Yasuhiro Tsutani; Makoto Fujiwara; Takahiro Mimae; Yoshihiro Miyata; Morihito Okada
    Clinical lung cancer 20 5 397 - 403 2019年09月 [査読有り]
     
    BACKGROUND: Although radical segmentectomy is an accepted treatment option for small-sized lung cancer, the outcomes remain unclear. The present study aimed to elucidate recurrence patterns and to identify predictors of time to recurrence after intentional segmentectomy for early lung cancer. PATIENTS AND METHODS: Prospectively collected data of 166 patients who could tolerate lobectomy and underwent intentional segmentectomy for clinical stage 0 or IA non-small-cell lung cancer between 2007 and 2016 were retrospectively analyzed. Surgical indication for intentional segmentectomy was clinical stage 0 or IA ground glass opacity-dominant tumor ≤ 3 cm or solid-dominant tumor ≤ 2 cm on high-resolution computed tomography. RESULTS: The median follow-up duration was 48.8 months, during which 6 (3.6%) patients developed recurrences. The 5-year recurrence-free survival and 5-year overall survival rates were 93.1% (95% confidence interval [CI], 87.9%-96.1%) and 93.5% (95% CI, 87.7%-96.4%), respectively. Two (1.2%) patients who developed local-only recurrences subsequently underwent completion lobectomy; no cancer-related deaths were seen for these patients. In multivariable analysis, consolidation to maximum tumor diameter (C/T) ratio (hazard ratio, 1.07; 95% CI, 1.01-1.22; P = .02) was an independent predictive factor for time to recurrence. All 6 patients with recurrence had a tumor with a C/T ratio of 86% or higher. CONCLUSIONS: Based on these findings, favorable survival is expected after intentional segmentectomy for selected patients with clinical stage 0 or IA non-small-cell lung cancer. Patients with a higher C/T ratio tumor appear to be at higher risk of recurrence after intentional segmentectomy.
  • Masaoki Ito; Yoshihiro Miyata; Shoko Hirano; Shingo Kimura; Fumiko Irisuna; Kyoko Ikeda; Kei Kushitani; Naoto Kishi; Yasuhiro Tsutani; Yukio Takeshima; Morihito Okada
    Journal of cancer research and clinical oncology 145 9 2325 - 2333 2019年09月 [査読有り]
     
    PURPOSE: Nodal positive lung adenocarcinoma includes wide range of survival. Several methods for the classification of nodal-positive lung cancer have been proposed. However, classification considering the impact of targetable genetic variants are lacking. The possibility of genetic variants for the better stratification of nodal positive lung adenocarcinoma was estimated. METHODS: Mutations of 36 genes between primary sites and metastatic lymph nodes (LNs) were compared using next-generation sequencing. Subsequently, mutations in EGFR and BRAF, rearrangements in ALK and ROS1 were evaluated in 69 resected pN1-2M0 adenocarcinoma cases. Recurrence-free survival (RFS), post-recurrence survival (PRS), and overall survival (OS) were evaluated with respect to targetable variants and tyrosine kinase inhibitor (TKI) therapy after recurrence. RESULTS: About 90% of variants were shared and allele frequencies were similar between primary and metastatic sites. In 69 pN1-2M0 cases, EGFR/ALK were positive in primary sites of 39 cases and same EGFR/ALK variants were confirmed in metastatic LNs of 96.7% tissue-available cases. Multivariate analyses indicated positive EGFR/ALK status was associated with worse RFS (HR 2.366; 95% CI 1.244-4.500; P = 0.009), and PRS was prolonged in cases receiving TKI therapy (no post-recurrence TKI therapies, HR 3.740; 95% CI 1.449-9.650; P = 0.006). OS did not differ with respect to targetable variants or TKI therapy. CONCLUSIONS: Cases harbouring targetable genetic variants had a higher risk of recurrence, but PRS was prolonged by TKI therapy. Classification according to the targetable genetic status provides a basis for predicting recurrence and determining treatment strategies after recurrence.
  • Nakanishi Y; Masuda T; Yamaguchi K; Sakamoto S; Horimasu Y; Mimae T; Nakashima T; Miyamoto S; Tsutani Y; Iwamoto H; Fujitaka K; Miyata Y; Hamada H; Hattori N
    International journal of clinical oncology 2019年09月 [査読有り]
  • Nakanishi Y; Masuda T; Yamaguchi K; Sakamoto S; Horimasu Y; Nakashima T; Miyamoto S; Tsutani Y; Iwamoto H; Fujitaka K; Miyata Y; Hamada H; Okada M; Hattori N
    Respiratory investigation 2019年06月 [査読有り]
  • Yoshinori Handa; Yasuhiro Tsutani; Takahiro Mimae; Takuro Tasaki; Yoshihiro Miyata; Morihito Okada
    The Annals of thoracic surgery 107 4 1032 - 1039 2019年04月 [査読有り]
     
    BACKGROUND: As segmentectomy becomes widely used for lung cancer treatment, complex segmentectomy, which makes several, intricate intersegmental planes, remains controversial because of procedural complexity and risk of increased complications and incurability. Questions remain about mortality, morbidity, surgical margin, lymph nodes dissection, and postoperative pulmonary function. We evaluated operative and postoperative outcomes of complex compared with simple segmentectomy. METHODS: We retrospectively reviewed patients with clinical stage I lung cancer who could tolerate lobectomy and underwent complex or simple segmentectomy between April 2007 and March 2017. Clinicopathologic, operative, and postoperative results of the complex (n = 117) and simple (n = 92) segmentectomy groups were compared. RESULTS: No statistically significant differences were detected in age, sex, comorbidities, preoperative pulmonary function, tumor histology, and size. Although only median operative time (180 versus 143.5 minutes, p < 0.0001) was significantly longer in the complex group, 30-day mortality (0% versus 0%), overall complications (24.8% versus 22.8%), and prolonged air leakage (11.9% versus 10.9%) were nearly equivalent between the two groups, respectively. The complex group showed comparable results in median surgical margin distance (16.0 versus 17.5 mm) and number of dissected lymph nodes (6.0 versus 7.0 nodes). Margin relapse occurred in 2 patients in the simple group but none occurred in the complex group. Both groups also showed similar postoperative pulmonary functions. CONCLUSIONS: Complex segmentectomy is a safe option in the treatment of lung cancers with adequate operative outcomes.
  • Yuichiro Kai; Yasuhiro Tsutani; Norifumi Tsubokawa; Masaoki Ito; Takeshi Mimura; Yoshihiro Miyata; Morihito Okada
    Oncology letters 17 3 3607 - 3614 2019年03月 [査読有り]
     
    The present study analyzed surgical results in patients with malignant pleural mesothelioma (MPM) who underwent extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D). Data for 44 patients who achieved macroscopic complete resection following neoadjuvant chemotherapy followed by EPP (n=29) or P/D (n=15) were reviewed. Patient demographics and oncological outcomes were compared between the EPP and P/D groups. The median overall (OS) and progression-free survival (PFS) times were 22 and 14 months, respectively. OS was significantly different between the EPP and P/D groups (median OS, 17 vs. 34 months; 5-year OS, 11 vs. 44%; P=0.019); no difference was noted in PFS (median PFS, 13 vs. 21 months; 5-year PFS, 11 vs. 17%; P=0.373). Univariate analysis demonstrated that epithelial histology (P=0.0003) and P/D (P=0.018) were significant favorable prognostic factors for OS. Using multivariate analysis, epithelial histology (P=0.001) remained the only significant factor. Post-recurrence survival (PRS) among all patients was significantly longer in the P/D group (median PRS, 3 vs. 20 months; 1.5-year PRS, 5 vs. 54%; P=0.003), even among patients with epithelial-type MPM (median PRS, 6 s vs. 20 months; 1.5-year PRS, 8 vs. 61%; P=0.012). Chemotherapy following recurrence (P=0.033) was significantly associated with superior PRS in multivariate analysis. Postoperative pulmonary function was significantly improved in the P/D group. In summary, P/D may be an alternative procedure to EPP for resectable MPM providing similar PFS and improved PRS.
  • Yuichiro Kai; Vishwa J. Amatya; Kei Kushitani; Takahiro Kambara; Rui Suzuki; Yasuhiro Tsutani; Yoshihiro Miyata; Morihito Okada; Yukio Takeshima
    Histopathology 74 4 545 - 554 2019年03月 [査読有り]
     
    © 2018 John Wiley & Sons Ltd Aims: The process of differential diagnosis between epithelioid mesothelioma and lung adenocarcinoma has been progressing; however, there are no absolute immunohistochemical markers with which to definitively diagnose epithelioid mesothelioma. The aim of this study was to search for a novel negative marker of epithelioid mesothelioma. Methods and results: We immunohistochemically studied the applicability of mucin 21 (MUC21), which was identified in our previous study, as a novel, negative diagnostic marker for epithelioid mesothelioma. Seventy epithelioid mesotheliomas and 70 lung adenocarcinomas were investigated for the expression of MUC21, along with other previously reported markers, by the use of immunohistochemistry. MUC21 was expressed in only two of the 70 (3%) epithelioid mesotheliomas, as compared with 67 of the 70 (96%) lung adenocarcinomas. The sensitivity, specificity and accuracy of negative MUC21 expression for differentiating epithelioid mesothelioma from lung adenocarcinoma were 97%, 96%, and 96%, respectively; these are similar to those of carcinoembryonic antigen and claudin-4, and better than those of thyroid transcription factor-1, napsin-A, and mucin 4. Conclusion: MUC21 could be used as an additional, novel, negative immunohistochemical marker to differentiate mesothelioma from lung adenocarcinoma.
  • Morihito Okada; Yoshihiro Miyata; Kazuya Takamochi; Yasuhiro Tsutani; Shiaki Oh; Kenji Suzuki
    The Journal of thoracic and cardiovascular surgery 157 1 388 - 395 2019年01月 [査読有り]
     
    OBJECTIVE: Vascular sealing with an energy vessel sealing system during lung resection may allow surgeons to treat small vessels with minimal dissection, possibly decreasing likelihood of injury. Few large prospective trials have examined the proximal sides of vessels not ligated in addition to sealing during surgery. We therefore assessed feasibility of an energy device to seal pulmonary artery and vein branches without further ligation. METHODS: This prospective, preoperative registration study at 2 institutions evaluated safety of energy sealing with the LigaSure (Medtronic, Minneapolis, Minn), with no additional reinforcing material such as suture ligation, for pulmonary vessels as large as 7 mm during anatomic lung resection (cohort 1 study). A postoperative hemorrhage occurred in the 128th case, so a cohort 2 study proceeded after we changed inclusion criterion for pulmonary arteries from a maximum of 7 mm to a maximum of 5 mm. RESULTS: In cohort 1 (n = 128) and cohort 2 (n = 200), 216 and 250 pulmonary arteries and 189 and 213 pulmonary veins, respectively, were treated with energy sealing. Overall postoperative hemorrhage rate was 0.3% (1/328 patients); however, no serious postoperative complications were associated with energy sealing among the 200 patients in cohort 2. Subsequent inspection of the torn artery stump confirmed that the bleeding in the 128th case was in an area adjacent to the sealing zone. CONCLUSIONS: Energy sealing without reinforcement allows secure treatment during lung resection of pulmonary arteries as large as 5 mm in diameter and pulmonary veins as large as 7 mm.
  • Yuichiro Kai; Yasuhiro Tsutani; Masaoki Ito; Takeshi Mimura; Yoshihiro Miyata; Morihito Okada
    The Annals of thoracic surgery 107 1 e1-e3 - E3 2019年01月 [査読有り]
     
    Pleurectomy/decortication is a surgical procedure for malignant pleural mesothelioma (MPM) and has been proposed as an alternative to extrapleural pneumonectomy. We report a second primary lung cancer developing after pleurectomy/decortication for MPM. A 59-year-old man was diagnosed with MPM on the right side and underwent pleurectomy/decortication. Follow-up computed tomography detected a nodule in the right upper lobe that was diagnosed as adenocarcinoma by wedge resection. Lung cancer and MPM are associated with asbestos exposure. However, predicting lung cancer after treatment for MPM is difficult. Careful follow-up of the spared lung is necessary for detecting second primary lung cancer or MPM recurrence.
  • Yasuhiro Tsutani; Yoshihiro Miyata; Takeshi Masuda; Kazunori Fujitaka; Mihoko Doi; Yoshikazu Awaya; Shoichi Kuyama; Soichi Kitaguchi; Kazuhiro Ueda; Noboru Hattori; Morihito Okada
    BMC cancer 18 1 1231 - 1231 2018年12月 [査読有り]
     
    BACKGROUND: We evaluated the safety and efficacy of induction chemotherapy with bevacizumab followed by maintenance chemotherapy with bevacizumab for advanced non-small cell lung cancer (NSCLC) in this multicenter phase II study. METHODS: Chemotherapy-naïve patient with stage IIIB-IV or recurrent nonsquamous NSCLC were eligible. We planned approximately four cycles of induction cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and bevacizumab (15 mg/kg) followed by maintenance with pemetrexed (500 mg/m2) and bevacizumab (15 mg/kg) until disease progression. Progression-free survival (PFS) was the primary endpoint. RESULTS: Forty patients received a median of four induction chemotherapy cycles. Of them, 35 (87.5%) patients received a median of nine maintenance chemotherapy cycles. The objective response was 70.6%, and the disease control rate was 97.1%. The median PFS was 10.8 (95% CI, 9.0-12.6), and overall survival was 48.0 (95% CI, 32.9-63.1) months. Median PFS of 23 patients with epidermal growth factor receptor (EGFR) mutations and of 16 patients without EGFR mutations were 12.9 (95% CI, 9.4-16.3) and 7.9 (95% CI, 1.1-14.7) months, respectively. Toxicities graded ≥3 included neutropenia (15%), anemia (15%), hypertension (7.5%), anorexia (7.5%), fatigue (7.5%), thromboembolic events (5%), jaw osteonecrosis (5%), nausea (2.5%), oral mucositis (2.5%), tumor pain (2.5%), hyponatremia (2.5%), and gastrointestinal perforation (2.5%). Treatment-related deaths were not found. CONCLUSIONS: In patients with advanced or recurrent nonsquamous NSCLC, induction chemotherapy with cisplatin, pemetrexed, and bevacizumab followed by maintenance chemotherapy with pemetrexed and bevacizumab is safe and effective regardless of their EGFR mutation status. TRIAL REGISTRATION: UMIN Clinical Trial Registry: UMIN000005569 . Registered date: May 8, 2011.
  • Masaoki Ito; Yoshihiro Miyata; Kei Kushitani; Tomoharu Yoshiya; Yuichiro Kai; Yasuhiro Tsutani; Takeshi Mimura; Kazuo Konishi; Yukio Takeshima; Morihito Okada
    Thoracic cancer 9 12 1594 - 1602 2018年12月 [査読有り]
     
    BACKGROUND: This study was conducted to evaluate the prognostic and recurrent impact of EGFR mutation status in resected pN0M0 lung adenocarcinoma with consideration of the histological subtype. METHODS: Following retrospective analysis of whole 474 consecutive pathological N0M0 lung adenocarcinoma patients, the prognostic significance of EGFR mutation status was evaluated in limited 394 subjects. Overall survival and recurrence-free interval (RFI) were estimated using the Kaplan-Meier method and compared using a log-rank test. Univariate and multivariate analyses were performed using Cox proportional hazard models. RESULTS: The five-year RFI was 85.7% and 93.3% for EGFR positive (n = 176) and negative (n = 218) cases, respectively (hazard ratio [HR] 1.992, 95% confidence interval [CI] 1.005-3.982; P = 0.048). Following the exclusion of specific subtypes free from recurrence or EGFR mutation (adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive mucinous adenocarcinoma), the five-year RFI was obviously poorer in EGFR positive compared to negative cases (80.7% and 92.1%, respectively; HR 2.163, 95% CI 1.055-4.341; P = 0.035). Multivariate analysis excluding the specific subtypes confirmed that male sex, age, current or Ex-smoking status, pleural invasion, and EGFR-positive status were independently associated with shorter RFI. No significant differences in five-year overall survival were found between the EGFR mutation positive and negative groups (88.7% and 93.7%, respectively; HR 1.630, 95% CI 0.787-3.432; P = 0.2). CONCLUSION: EGFR mutations are associated with recurrence in pN0M0 lung adenocarcinoma. EGFR mutation status and histological subtype should be considered when evaluating the risk of recurrence in resected lung adenocarcinoma patients.
  • Tomoharu Yoshiya; Takahiro Mimae; Norifumi Tsubokawa; Shinsuke Sasada; Yasuhiro Tsutani; Kei Kushitani; Yukio Takeshima; Yoshihiro Miyata; Morihito Okada
    Interactive cardiovascular and thoracic surgery 27 3 372 - 378 2018年09月 [査読有り]
     
    OBJECTIVES: Histological changes after division of the pulmonary artery (PA) and the pulmonary vein (PV) using a vessel-sealing device are not fully understood. The goal of the present study was to clarify histologically and immunohistochemically how division with the device affects the wall layers of the pulmonary vasculature. METHODS: This prospective cohort study analysed outcomes of 20 patients who underwent anatomical lung resection. After a single proximal ligation, the PA and the PV (diameter 2-7 mm) were divided using a LigaSure Blunt Tip (LSB). Histological findings and thermal damage were evaluated in vascular specimens from resected lungs. RESULTS: The PA has a well-developed media with rich elastic fibres and a thin adventitia, whereas the PV has a thinner media and a thicker adventitia with abundant collagen fibres. Vascular division of the PAs and PVs appeared complete to the naked eye. However, in all divided PAs, the area adjacent to the sealed zone comprised only adventitia and thin disrupted media. Additionally, thermal energy generated by the LSB resulted in a wide area of thermal necrosis over the histologically fragile region in all cases. Conversely, the wall layers of all divided PVs were completely fused without disruption. Thermal spread and disruption did not significantly differ between small (2-4 mm) and large (5-7 mm) PAs [187 (150-253) vs 236 (190-275) μm, P = 0.22; 180 (138-200) vs 210 (161-305) μm, P = 0.22]. Histological changes differed significantly between the pulmonary vessels after division using the LSB. CONCLUSIONS: Surgeons should consider that dividing the pulmonary vessels with a vessel-sealing device might have more histological impact on the layers of the wall of the PA than on those of the PV, although it remains unclear whether these findings constitute a clinical risk.
  • Yoshinori Handa; Yasuhiro Tsutani; Morihito Okada
    VIDEO-ASSISTED THORACIC SURGERY 3 2018年08月
  • Yasuhiro Tsutani; Morihito Okada
    Thoracic surgery clinics 28 3 299 - 304 2018年08月 [査読有り]
     
    Although there is insufficient information in the literature on atypical bronchoplasties, these procedures can be performed on centrally located benign or low-grade malignant tumors or advanced lung cancer at the hilum. In particular, sleeve segmentectomy is performed for low-grade malignant tumors and early lung cancer at the hilum; extended sleeve lobectomy is performed for advanced lung cancer at the hilum; and segmental bronchial sleeve resection is performed for benign or low-grade malignancies. These procedures should be performed after strict evaluation of the lymph node status and bronchial margins using intraoperative frozen section analysis.
  • Norifumi Tsubokawa; Yasuhiro Tsutani; Yoshihiro Miyata; Yoshinori Handa; Keizo Misumi; Hideaki Hanaki; Eisuke Hida; Morihito Okada
    World journal of surgery 42 8 2493 - 2501 2018年08月 [査読有り]
     
    BACKGROUND: Segmentectomy for radiologically pure solid tumors is still controversial because these tumors are more aggressive in malignancy than those with ground-glass opacity. This study aimed to determine the feasibility of intentional segmentectomy for pure solid small-sized lung cancer. METHODS: We retrospectively analyzed 96 radiologically pure solid tumors in clinical T1a-bN0M0 lung cancer. Patients whose tumor was located at a central region or right middle lobe were excluded. Forty-four patients who underwent lobectomy were compared with 52 those who underwent segmentectomy. Segmentectomy got converted to lobectomy if lymph node metastases or inadequate surgical margin was confirmed. Factors affecting survival were assessed using Cox regression. Propensity score stratification analysis was also performed. RESULTS: Eight patients (8%) were identified as a histological type other than adenocarcinoma or squamous cell carcinoma. Moreover, 14 patients (14%) displayed lymph node metastasis. Among those who underwent segmentectomy, nine patients (16%) were converted to lobectomy due to lymph node metastasis or inadequate surgical margin. The 3-year recurrence-free survival rates were 84.1 and 82.2% in patients who underwent segmentectomy and lobectomy, respectively (P = 0.745). In addition, the recurrence-free survival was not statistically significant between segmentectomy and lobectomy, as determined via multivariable Cox regression analysis (hazard ratio 1.11; 95% confidence interval 0.40-3.06), even after propensity score stratification (hazard ratio 1.17; 95% confidence interval 0.38-3.65). CONCLUSIONS: Segmentectomy with intraoperative assessment of lymph node metastasis and adequate surgical margin may be a feasible surgical procedure for pure solid tumors in clinical T1a-bN0M0 lung cancer.
  • Yoshinori Handa; Yasuhiro Tsutani; Takuhiro Ikeda; Hideaki Hanaki; Yoshihiro Miyata; Hidenori Mukaida; Morihito Okada
    The Annals of thoracic surgery 105 5 1543 - 1550 2018年05月 [査読有り]
     
    BACKGROUND: The purpose of this study was to elucidate the clinical behavior of right middle lobe lung cancer, with focus on the tumor location. METHODS: We reviewed retrospectively 711 patients who underwent lobectomy or bilobectomy for clinical stage I non-small cell lung cancer (upper lobe, 346; middle lobe, 82; lower lobe, 283). Factors affecting survival were assessed by log rank tests and Cox regression analyses. RESULTS: The prognosis of patients with segment 5 tumors (n = 39) was significantly worse than that of patients with segment 4 tumors (n = 43; 5-year overall survival rates, 69.8% versus 87.6%, p = 0.040; and 5-year recurrence-free survival rates, 58.4% versus 73.0%, p = 0.029). Segment 5 tumors were an independent factor for poor prognosis in multivariable Cox regression analysis, and tended to cause more pathologic mediastinal lymph node metastases than segment 4 tumors (12.8% versus 2.3%, p = 0.097). Compared with tumors in the other lobes, patients with segment 4 tumors demonstrated no significant difference in prognosis; however, patients with segment 5 tumors demonstrated a significantly and outstandingly worse prognosis than patients with other lobe tumors (5-year overall survival rates, 69.8% versus 82.2%, p = 0.020; and 5-year recurrence-free survival rates, 58.4% versus 71.4%, p = 0.0071). CONCLUSIONS: Patients with segment 5 tumors had a worse prognosis than patients with segment 4 and other lobe tumors. We speculate that is because segment 5 tumors cause more metastases to the mediastinal lymph nodes. Tumor location was an important prognostic factor for patients with right middle lobe lung cancer.
  • Yasuhiro Tsutani; Norifumi Tsubokawa; Masaoki Ito; Keizo Misumi; Hideaki Hanaki; Yoshihiro Miyata; Morihito Okada
    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 53 2 366 - 371 2018年02月 [査読有り]
     
    OBJECTIVES: The study aimed to investigate the outcomes of sublobar resection in elderly patients with non-small-cell lung cancer. METHODS: A total of 205 patients aged ≥75 years were identified from 794 consecutive patients who underwent complete surgical resection for clinical Stage I non-small-cell lung cancer. The outcomes of lobectomy and sublobar resection were compared. Propensity scores were estimated for multivariable analyses and matching. RESULTS: Sublobar resection (n = 99) was more frequently performed than lobectomy (n = 106) in older patients (P = 0.027) and those with lower maximum standardized uptake on positron emission tomography (P < 0.001), lower T stage (P < 0.001), lower %vital capacity (P = 0.007) and lower %diffusing capacity of the lungs for carbon monoxide (P = 0.025). Severe (≥Grade IIIa) postoperative complications occurred more frequently with lobectomy (11 of 106 procedures, 10.4%) than with sublobar resection (5 of 99, 5.1%; P = 0.16). In propensity score-adjusted multivariable analysis, lobectomy was an independent predictive factor for severe postoperative complications (odds ratio 3.49, 95% confidence interval 1.01-12.05; P = 0.048). Overall survival (OS) was not significantly different following lobectomy (5-year OS 67.2%) or sublobar resection (5-year OS 73.9%; P = 0.93). In multivariable analysis, the surgical procedure was not an independent predictive factor for OS (lobectomy: hazard ratio 1.03, 95% confidence interval 0.49-2.16; P = 0.94). CONCLUSIONS: Sublobar resection may be the optimal procedure in elderly patients with clinical Stage I non-small-cell lung cancer and is associated with less severe postoperative complications than lobectomy and similar OS.
  • 中川加寿夫; 鈴木健司; 若林将史; 津谷康大; 高持一矢; 伊藤宏之; 岡見次郎; 青木正; 青景圭樹; 佐治久; 岡田守人; 坪井正博; 守屋康充; 吉野一郎; 光冨徹哉; 淺村尚生; 渡辺俊一
    日本呼吸器外科学会総会(Web) 35th 3 PS - 1 (NPO)日本呼吸器外科学会 2018年04月 [査読有り]
  • Masaoki Ito; Yoshihiro Miyata; Shoko Hirano; Shingo Kimura; Fumiko Irisuna; Kyoko Ikeda; Kei Kushitani; Yasuhiro Tsutani; Daisuke Ueda; Norifumi Tsubokawa; Yukio Takeshima; Morihito Okada
    Oncotarget 8 65 108936 - 108945 2017年12月 [査読有り]
     
    Small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung are classified as variants of endocrine carcinoma and subdivided into pure or combined type. Clinical benefit of target therapy has not been established in these tumors. This study aimed to compare genetic and clinicopathological features between SCLC and LCNEC or pure and combined types, and explore the possibility of target therapy using next-generation sequencing. In 13 SCLC and 22 LCNEC cases, 72 point mutations, 19 deletions, and 3 insertions were detected. As therapeutically targetable variants, mutations in EGFR (L858R), KRAS (G12D, G12A, G12V), and PIK3CA (E545K) were detected in 5 cases. The case harboring EGFR mutation showed response to EGFR-tyrosine kinase inhibitor. However, there are no clinicopathological features associated with therapeutically targetable cases. And there was no significant genetic feature between SCLC and LCNEC or pure and combined types. In conclusion, although patients with SCLC and LCNEC may benefit from target therapy, they were not identifiable by clinicopathologic background. And there was not significant genetic difference between SCLC and LCNEC, including between pure and combined types. Classifying SCLC and LCNEC in same category is reasonable. However, distinguishing the pure type from combined type was not validated. Comprehensive genetic analysis should be performed to detect targetable variants in any type of SCLC and LCNEC.
  • Shun-Ichi Watanabe; Kazuo Nakagawa; Kenji Suzuki; Kazuya Takamochi; Hiroyuki Ito; Jiro Okami; Keiju Aokage; Hisashi Saji; Hiroshige Yoshioka; Yoshitaka Zenke; Tadashi Aoki; Yasuhiro Tsutani; Morihito Okada
    Japanese journal of clinical oncology 47 12 1112 - 1118 2017年12月 [査読有り]
     
    The treatments for advanced non-small cell lung cancer (NSCLC) should control both local and microscopic systemic disease, because the 5-year survival of patients with Stage III NSCLC who underwent surgical resection alone has been dismal. One way to improve surgical outcome is the administration of chemotherapy before or after the surgical procedure. During the last two decades, many clinical studies have focused on developing optimal adjuvant or neoadjuvant chemotherapy regimens that can be combined with surgical treatment and/or radiotherapy. Based on the results of those clinical studies, multimodality therapy is considered to be an appropriate treatment approach for Stage IIIA NSCLC patients; although, optimal treatment strategies are still evolving. When N2 nodal involvement is discovered postoperatively, adjuvant cisplatin-based chemotherapy confers an overall survival benefit. The addition of postoperative radiotherapy might be considered for patients with nodal metastases. Although definitive chemoradiation remains a standard of care for cN2 NSCLC, alternative approaches such as induction chemotherapy or chemoradiotherapy and surgery can be considered for a selective group of patients. When surgical resection can be performed after induction therapy with low risk and a good chance of complete resection, the outcome may be optimal. The decision to proceed with resection after induction therapy must include a detailed preoperative pulmonary function evaluation as well as a critical intraoperative assessment of the feasibility of complete resection.
  • Yoshinori Handa; Yasuhiro Tsutani; Norifumi Tsubokawa; Keizo Misumi; Hideaki Hanaki; Yoshihiro Miyata; Morihito Okada
    ANNALS OF THORACIC SURGERY 104 6 1896 - 1901 2017年12月 [査読有り]
     
    Background. Despite its extensive size, variations in the clinicopathologic features of tumors in the lower lobe have been little studied. The present study investigated the prognostic differences in tumors originating from the superior and basal segments of the lower lobe in patients with non-small cell lung cancer. Methods. Data of 134 patients who underwent lobectomy or segmentectomy with systematic nodal dissection for clinical stage I, radiologically solid-dominant, non-small cell lung cancer in the superior segment (n = 60) or basal segment (n = 74) between April 2007 and December 2015 were retrospectively reviewed. Factors affecting survival were assessed by the Kaplan-Meier method and Cox regression analyses. Results. Prognosis in the superior segment group was worse than that in the basal segment group (5-year overall survival rates 62.6% versus 89.9%, p = 0.0072; and 5-year recurrence-free survival rates 54.4% versus 75.7%, p = 0.032). In multivariable Cox regression analysis, a superior segment tumor was an independent factor for poor overall survival (hazard ratio 3.33, 95% confidence interval: 1.22 to 13.5, p = 0.010) and recurrence-free survival (hazard ratio 2.90, 95% confidence interval: 1.20 to 7.00, p = 0.008). The superior segment group tended to have more pathologic mediastinal lymph node metastases than the basal segment group (15.0% versus 5.4%, p = 0.080). Conclusions. Tumor location was a prognostic factor for clinical stage I non-small cell lung cancer in the lower lobe. Patients with superior segment tumors had worse prognosis than patients with basal segment tumors, with more metastases in mediastinal lymph nodes. (C) 2017 by The Society of Thoracic Surgeons
  • Yasuhiro Tsutani; Takeshi Mimura; Yuichiro Kai; Masaoki Ito; Keizo Misumi; Yoshihiro Miyata; Morihito Okada
    The Journal of thoracic and cardiovascular surgery 154 3 1089 - 1096 2017年09月 [査読有り]
     
    OBJECTIVE: Since the prognosis after standard lobectomy for non-small cell lung cancer (NSCLC) in patients with interstitial lung disease (ILD) is poor, we investigated the possibility of sublobar resection for the improvement of the surgical results in such patients. METHODS: Of 796 consecutive patients with clinical stage I NSCLC who underwent pulmonary resection, 107 were diagnosed with ILD using high-resolution computed tomography (HRCT). Overall survivals (OS) were compared between patients with non-ILD and those with ILD or between patients with ILD who underwent lobectomy and those who underwent sublobar resection. ILD patterns consisted of usual interstitial pneumonia (UIP), possible UIP, and inconsistent with UIP. The log-rank statistics and Cox proportional hazard models were used to test for survival differences. RESULTS: OS was significantly lower in patients with "ILD inconsistent with UIP" pattern (hazard ratio [HR], 2.66; 95% confidence interval [CI], 1.19-5.97; P = .014), or "ILD with possible UIP or UIP" patterns (HR, 2.38; 95% CI, 1.76-3.21; P < .001) compared with patients with non-ILD. No significant difference in OS was observed between patients with ILD who underwent either lobectomy or sublobar resection (HR, 1.82; 95% CI, 0.81-4.06; P = .19). Multivariable Cox analysis demonstrated diffusing capacity of the lung for carbon monoxide (HR, 0.95; 95% CI, 0.91-0.99; P = .009) and not surgical procedure (HR, 2.76; 95% CI, 0.83-9.16; P = .099), as an independent prognostic factor for OS. CONCLUSIONS: Sublobar resection may be a potential alternative choice for clinical stage I NSCLC with ILD on HRCT.
  • Keizo Misumi; Hiroaki Harada; Norifumi Tsubokawa; Yasuhiro Tsutani; Kotaro Matsumoto; Yoshihiro Miyata; Yoshinori Yamashita; Morihito Okada
    General thoracic and cardiovascular surgery 65 7 392 - 399 2017年07月 [査読有り]
     
    BACKGROUND: Considering that pneumonectomy itself is a disease, avoidance of pneumonectomy needs to be deliberated. Herein, we evaluated the role of neoadjuvant chemoradiotherapy for avoidance of pneumonectomy in patients with centrally located locally advanced non-small cell lung cancer. METHODS: Patients who underwent neoadjuvant chemoradiotherapy after being judged to require pneumonectomy by cancer board between 1997 and 2011 were retrospectively evaluated. RESULTS: Twelve patients, including 10 males and 2 females with median age 63.5 years, were referred. Clinical stage was IB (1 patient), IIB (2 patients), IIIA (8 patients), and IIIB (1 patient). There were no disease progression after neoadjuvant chemoradiotherapy, and all patients underwent curative resection. For 8 patients, pneumonectomy was avoided, with 3 bronchoplasties and 3 pulmonary arterial angioplasties. We had 4 pneumonectomies: three cases of metastatic enlarged lymph nodes invading either the carina or a more central portion of the pulmonary artery than the left A3 branch or vein which needs incision of the inner pericardium and 1 case with a tumor involving the upper lobe bronchus to the inferior lobe bronchus. There were no postoperative deaths and 1 case of bronchopleural fistula. The 5-year disease-free and overall survival rates were 55.6 and 72.7% without stump or anastomotic recurrence. CONCLUSIONS: Neoadjuvant chemoradiotherapy for centrally located NSCLC appeared to be a useful treatment option for avoiding pneumonectomy without impairing curability and safety, especially in highly selected cases without invasion to carina or right-or-left main trunk of pulmonary artery or vein at pretreatment.
  • 津谷 康大; 坪川 典史; 伊藤 正興; 三隅 啓三; 花木 英明; 宮田 義浩; 岡田 守人
    日本外科学会定期学術集会抄録集 117回 SF - 4 (一社)日本外科学会 2017年04月
  • 吉川 徹; 三隅 啓三; 半田 良憲; 坪川 典史; 花木 英明; 津谷 康大; 宮田 義浩; 岡田 守人
    日本外科学会定期学術集会抄録集 117回 PS - 3 (一社)日本外科学会 2017年04月
  • 坪川 典史; 宮田 義浩; 津谷 康大; 半田 良憲; 三隅 啓三; 花木 英明; 岡田 守人
    日本呼吸器外科学会雑誌 31 3 O26 - 2 (NPO)日本呼吸器外科学会 2017年04月
  • Yuta Ibuki; Yasuhiro Tsutani; Yoshihiro Miyata; Haruhiko Nakayama; Sakae Okumura; Masahiro Yoshimura; Morihito Okada
    Japanese Journal of Clinical Oncology 47 2 157 - 163 2017年02月 [査読有り]
     
    © The Author 2016. Published by Oxford University Press. All rights reserved. Objective: We aimed to identify patients with clinical Stage IA lung adenocarcinoma who are at high risk for distant recurrence to preoperatively organize treatment strategies. Methods: We analyzed correlations between preoperative clinical factors and the incidence of distant recurrence in 609 patients with clinical Stage IA lung adenocarcinoma that had been completely resected at four institutions. We excluded 24 patients with only locoregional recurrence and analyzed data from 585 patients. Results: Distant recurrence after complete resection was identified in 34 patients during a median follow-up period of 41.4 months. Multivariate Cox analysis identified solid tumor size on high-resolution computed tomography and the maximum standardized uptake value on F-18- fluorodeoxyglucose positron emission tomography/computed tomography as independent predictors for distant recurrence-free survival. Receiver operating characteristic analyses showed that solid tumor size ≥1.7 cm and the maximum standardized uptake value ≥3.3 were optimal criteria with which to detect patients at high risk for distant recurrence. In fact, 3-year distant recurrence rates were higher in patients who met the criteria for high risk (n = 85) than those who did not (n = 500) (28.1% vs. 3.7%; P < 0.001). A similar trend was also found in patients with pathological node negative. Conclusions: Solid tumor size on high-resolution computed tomography and the maximum standardized uptake value on F-18-fluorodeoxyglucose positron emission tomography/computed tomography were clinical predictors of distant recurrence among patients with clinical Stage IA lung adenocarcinoma. Our findings might be useful to determine personalized therapeutic strategies including systemic therapy.
  • Masaoki Ito; Yoshihiro Miyata; Tomoharu Yoshiya; Yasuhiro Tsutani; Takeshi Mimura; Shuji Murakami; Hiroyuki Ito; Haruhiko Nakayama; Morihito Okada
    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 51 2 218 - 222 2017年02月 [査読有り]
     
    OBJECTIVES: Acinar predominant and papillary predominant invasive adenocarcinomas are likely to be classified as intermediate-malignant types. Although these two types of adenocarcinoma are distinguished morphologically, the differences between their malignant behaviours and prognoses are not clear. The aim of this study is to provide a prognostically relevant stratification of these similar subtypes based on pathological features. METHODS: We retrospectively reviewed 347 consecutive clinically N0M0 lung adenocarcinomas of ≤3 cm in diameter that were resected between April 2006 and December 2010 at two institutes. Acinar and papillary predominant adenocarcinomas were classified into acinar/papillary-lepidic type and acinar/papillary-non-lepidic type according to whether the second predominant component was a lepidic or invasive component. RESULTS: Fifty-four acinar and 59 papillary predominant adenocarcinoma cases were classified as acinar/papillary-lepidic type (n = 65) or acinar/papillary-non-lepidic type (n = 48) cases. Acinar/papillary-non-lepidic type cases were accompanied by more vascular invasion (13.8% vs 31.3%, P = 0.0451) and pleural invasion (9.2% vs 25.0%, P = 0.0450) than were acinar/papillary-lepidic type cases. Five-year overall survival (OS) and recurrence-free survival (RFS) also differed significantly between these types (5-year OS: acinar/papillary-lepidic type, 96.3% vs acinar/papillary-non-lepidic type, 61.8%, hazard ratio = 6.315, P = 0.00650; 5-year RFS: acinar/papillary-lepidic type, 91.4% vs acinar/papillary-non-lepidic type, 68.8%, hazard ratio = 2.967, P = 0.0210). Multivariate analysis revealed that a second predominant component was an independent prognostic factor for RFS (acinar/papillary-non-lepidic type: hazard ratio = 3.784, 95% confidence interval 1.091–13.128, P = 0.036). CONCLUSIONS: The pathological second predominant component allows intermediate-malignant adenocarcinomas to be subclassified with prognostic significance. It can be utilized when assessing postoperative risks for recurrence and when considering therapeutic strategies.
  • 肺原発髄外性形質細胞腫の1例
    大澤 真那人; 津谷 康大; 吉川 徹; 半田 良憲; 坪川 典史; 伊藤 正興; 三隅 啓三; 花木 英明; 宮田 義浩; 岡田 守人
    肺癌 56 7 1086 - 1086 (NPO)日本肺癌学会 2016年12月
  • 宮田 義浩; 津谷 康大; 花木 英明; 三隅 啓三; 坪川 典史; 半田 良憲; 吉川 徹; 伊藤 正興; 岡田 守人
    肺癌 56 6 495 - 495 (NPO)日本肺癌学会 2016年11月
  • 三隅 啓三; 津谷 康大; 吉川 徹; 半田 良憲; 坪川 典史; 花木 英明; 三村 剛史; 原田 洋明; 宮田 義浩; 山下 芳典; 岡田 守人
    肺癌 56 6 527 - 527 (NPO)日本肺癌学会 2016年11月
  • 津谷 康大; 三村 剛史; 甲斐 佑一郎; 伊藤 正興; 吉川 徹; 半田 良憲; 坪川 典史; 三隅 啓三; 花木 英明; 宮田 義浩; 岡田 守人
    肺癌 56 6 536 - 536 (NPO)日本肺癌学会 2016年11月
  • 坪川 典史; 宮田 義浩; 半田 良憲; 三隅 啓三; 花木 英明; 津谷 康大; 村上 修司; 伊藤 宏之; 中山 治彦; 岡田 守人
    肺癌 56 6 557 - 557 (NPO)日本肺癌学会 2016年11月
  • 上田 大介; 津谷 康大; 吉川 徹; 半田 良憲; 坪川 典史; 伊藤 正興; 三隅 啓三; 花木 英明; 宮田 義浩; 岡田 守人
    肺癌 56 6 767 - 767 (NPO)日本肺癌学会 2016年11月
  • Yoshiya, Tomoharu; Mimae, Takahiro; Tsutani, Yasuhiro; Tsubokawa, Norifumi; Sasada, Shinsuke; Miyata, Yoshihiro; Kushitani, Kei; Takeshima, Yukio; Murakami, Shuji; Ito, Hiroyuki; Nakayama, Haruhiko; Okada, Morihito
    Annals of Thoracic Surgery 102 5 1668 - 1673 2016年11月 
    © 2016 The Society of Thoracic SurgeonsBackground The prognosis of patients with small, node-negative lung cancers, which the current indication for adjuvant chemotherapy never includes, is sometimes poor despite complete tumor resection. The present study aimed to identify independent prognostic factors and to clarify possible candidates for adjuvant chemotherapy among patients with small, node-negative invasive adenocarcinoma. Methods This study involved 153 patients with completely resected small (≤20 mm) pathologic N0 invasive adenocarcinomas. Invasive adenocarcinoma was classified as lepidic predominant (LPA), papillary or acinar predominant (PA), or solid or micropapillary predominant (SM), according to the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society classification. Overall survival and recurrence-free survival were estimated from Kaplan-Meier curves. Prognostic factors for recurrence-free survival were determined using univariate and multivariate Cox proportional hazards models. Results Three-year overall survival and recurrence-free survival rates were 98% and 98%, 97% and 88%, and 85% and 64% for LP
  • Shinsuke Sasada; Yoshihiro Miyata; Takahiro Mimae; Yasuhiro Tsutani; Takeshi Mimura; Morihito Okada
    Clinical lung cancer 17 5 433 - 440 2016年09月 [査読有り]
     
    BACKGROUND: In the present study we aimed to investigate whether the predominance of the lepidic component in tumors was associated with the outcome of postoperative adjuvant chemotherapy for stage I lung adenocarcinoma. PATIENTS AND METHODS: Charts for patients with pathological stage I lung adenocarcinoma were retrospectively reviewed and then outcomes of adjuvant chemotherapy were assessed according to the lepidic component predominance in tumors. Prognostic factors were evaluated using a Cox proportional hazard model. Propensity scores were determined using the optimal matching method on the basis of Cox modeling and matched (1:1) analysis was applied after classification into lepidic and nonlepidic predominant tumors. RESULTS: Among 798 patients with stage I lung adenocarcinoma, 168 received adjuvant chemotherapy. Although adjuvant chemotherapy conferred no disease-free survival (DFS) advantage upon patients with lepidic predominant tumors, it improved DFS in T1b and T2a nonlepidic predominant tumors (P = .045 and P = .029, respectively). Propensity score matched analysis revealed no survival benefits of adjuvant oral fluoropyrimidines in lepidic predominant tumors (DFS, P = .461 and overall survival, P = .983) and the positive survival advantages in nonlepidic predominant tumors (DFS, P = .015 and overall survival, P = .027). CONCLUSION: Adjuvant oral fluoropyrimidines conferred a better survival advantage upon patients with nonlepidic predominant tumors than patients with lepidic predominant tumors. The predominance of a lepidic component could serve as an indicator of adjuvant chemotherapy with oral fluoropyrimidines in stage I lung adenocarcinoma.
  • Takeshi Mimura; Yoshihiro Miyata; Yasuhiro Tsutani; Shigeru Takamizawa; Eiji Nishijima; Morihito Okada
    General thoracic and cardiovascular surgery 64 2 113 - 5 2016年02月 [査読有り]
     
    Blunt bronchial injuries can be difficult to diagnose and can present months or years after an initial incident. The present case report describes complete transection of a major airway after a potentially fatal delayed diagnosis with a successful outcome after bronchoplasty without the removal of lung parenchyma.
  • Ibuki Yuta; Tsutani Yasuhiro; Miyata Yoshihiro; Nakayama Haruhiko; Okumura Sakae; Yoshimura Masahiro; Okada Morihito
    Japanese journal of clinical oncology 2016年 
    OBJECTIVE:We aimed to identify patients with clinical Stage IA lung adenocarcinoma who are at high risk for distant recurrence to preoperatively organize treatment strategies.;METHODS:We analyzed correlations between preoperative clinical factors and the incidence of distant recurrence in 609 patients with clinical Stage IA lung adenocarcinoma that had been completely resected at four institutions. We excluded 24 patients with only locoregional recurrence and analyzed data from 585 patients.;RESULTS:Distant recurrence after complete resection was identified in 34 patients during a median follow-up period of 41.4 months. Multivariate Cox analysis identified solid tumor size on high-resolution computed tomography and the maximum standardized uptake value on F-18-fluorodeoxyglucose positron emission tomography/computed tomography as independent predictors for distant recurrence-free survival. Receiver operating characteristic analyses showed that solid tumor size ≥1.7 cm and the maximum standardized uptake value ≥3.3 were optimal criteria with which to detect patients at high risk for distant recurrence. In fact, 3-year distant recurrence rates were higher in patients who met the criteria for high risk (n = 85) than those who did not (n = 500) (28.1% vs. 3.7%; P < 0.001). A similar trend was also found in patients with pathological node negative.;CONCLUSIONS:Solid tumor size on high-resolution computed tomography and the maximum standardized uptake value on F-18-fluorodeoxyglucose positron emission tomography/computed tomography were clinical predictors of distant recurrence among patients with clinical Stage IA lung adenocarcinoma. Our findings might be useful to determine personalized therapeutic strategies including systemic therapy.
  • Takaoki Furukawa; Yoshihiro Miyata; Kei Kushitani; Takahiro Mimae; Yasuhiro Tsutani; Yukio Takeshima; Morihito Okada
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 45 12 1154 - 1161 2015年12月 [査読有り]
     
    Objective: High maximum standardized uptake values on [F-18]-fluoro-2-deoxyglucose positron emission tomography are associated with inferior survival in non-small cell lung cancer. Here, we investigated the biological mechanisms underlying [F-18]-fluoro-2-deoxyglucose uptake in non-small cell lung cancer. Methods: This study included 133 patients with non-small cell lung cancer (109 with adenocarcinoma and 24 with squamous cell carcinoma). The patients underwent tumour resection, at the latest, 4 weeks after [F-18]-fluoro-2-deoxyglucose positron emission tomography. The maximum standardized uptake values for primary lesions were calculated based on [F-18]-fluoro-2-deoxyglucose uptake. The expression of hypoxia-inducible factor 1 alpha and glucose transporter 1 was evaluated on immunostained tumour sections using six-point grading scales. Results: Maximum standardized uptake values and the expression of hypoxia-inducible factor 1 alpha and glucose transporter 1 were significantly higher in squamous cell carcinoma than in adenocarcinoma (P < 0.001, P = 0.034 and P < 0.001, respectively). In adenocarcinoma, but not squamous cell carcinoma, maximum standardized uptake values, hypoxia-inducible factor 1 alpha and glucose transporter 1 correlated with various clinicopathological factors relating to malignancy, and maximum standardized uptake values and glucose transporter 1 were associated with disease-free survival (P < 0.001 and P = 0.029) and overall survival (P < 0.001 and P = 0.033, respectively). Patients with high expression of hypoxia-inducible factor 1 alpha tended to exhibit shorter disease-free survival and overall survival than those with low expression, but the differences were not significant (P = 0.32 and P = 0.15, respectively). And then in adenocarcinoma, hypoxia-inducible factor 1 alpha and glucose transporter 1, glucose transporter 1 and maximum standardized uptake values, and hypoxia-inducible factor 1 alpha and maximum standardized uptake values were significantly correlated (P < 0.001 for all), suggesting that hypoxia-inducible factor 1 alpha-induced glucose transporter 1 might influence maximum standardized uptake values on [F-18]-fluoro-2-deoxyglucose positron emission tomography. Conclusions: In lung adenocarcinoma, but not squamous cell carcinoma, hypoxia-inducible factor 1 alpha and glucose transporter 1 expressions indicate tumour aggressiveness pathologically and might explain high [F-18]-fluoro-2-deoxyglucose uptake on positron emission tomography and correlate with poor prognosis.
  • Y. Tsutani; Y. Miyata; T. Mimura; M. Ito; Y. Kai; A. Kagimoto; H. Nakayama; S. Okumura; M. Yoshimura; M. Okada
    EUROPEAN JOURNAL OF CANCER 51 S596 - S596 2015年09月
  • Masaoki Ito; Yoshihiro Miyata; Yasuhiro Tsutani; Takeshi Mimura; Shuji Murakami; Hiroyuki Ito; Haruhiko Nakayama; Morihito Okada
    JOURNAL OF THORACIC ONCOLOGY 10 9 S263 - S263 2015年09月
  • Yasuhiro Tsutani; Shuji Murakami; Yoshihiro Miyata; Haruhiko Nakayama; Masahiro Yoshimura; Morihito Okada
    EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 47 6 1022 - 1026 2015年06月 [査読有り]
     
    This multicentre study aimed to investigate the predictors of pathological lymph node status in patients with clinical stage IA squamous cell carcinoma of the lung, to select candidates for sublobar resection. In total, we analysed 100 patients with clinical stage IA squamous cell carcinoma of the lung who underwent lobectomy or segmentectomy with systematic lymph node dissection. The relationship between lymph node status and tumour size on computed tomography, maximum standardized uptake value (SUV) on [18F]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) and serum tumour markers were examined. Lymph node metastases were present in 12% of the study subjects, and 54% had evidence of pathological tumour invasiveness such as lymph node metastasis and/or lymphatic, vascular or pleural invasion. The areas under the receiver operating characteristic (ROC) curves for tumour size, maximum SUV, serum carcinoembryonic antigen and serum cytokeratin-19 fragments used to predict lymph node metastasis were 0.54 (P = 0.69), 0.46 (P = 0.67), 0.47 (P = 0.74) and 0.42 (P = 0.37), respectively. After multivariate analysis, no independent predictive factors for lymph node metastasis remained among those preoperative parameters. Likewise, we could find no preoperative predictors from either the ROC curves or multivariate analysis for pathological tumour invasiveness. All examined factors in this dataset were not predictive for lymph node metastasis or pathological invasiveness in patients with clinical stage IA squamous cell carcinoma of the lung. Systematic lymphadenectomy is advisable for this type of tumour.
  • Yoshihiro Miyata; Yasuhiro Tsutani; Kenji Suzuki; Kazuya Takamochi; Fumihiro Tanaka; Haruhiko Nakayama; Yoshinori Yamashita; Masahiro Tsuboi; Makoto Oda; Morihito Okada
    JOURNAL OF CLINICAL ONCOLOGY 33 15 2015年05月
  • Takahiro Mimae; Yoshihiro Miyata; Yasuhiro Tsutani; Takeshi Mimura; Haruhiko Nakayama; Sakae Okumura; Masahiro Yoshimura; Morihito Okada
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 45 4 367 - 372 2015年04月 [査読有り]
     
    Objective: Small pulmonary nodules are often followed up. This study aimed to establish radiographic criteria with which to accurately and reproducibly predict indolent cancers including adenocarcinoma in situ. Methods: We examined correlations between pre-operative factors and surgical outcomes, including pathological findings and prognosis among 609 patients with clinical Stage IA lung adenocarcinoma that had been completely resected at multiple institutions. Indolent cancers were defined as tumors without lymphatic, blood vessel, pleural invasion or lymph node involvement (LY0V0PL0N0) regardless of stromal invasion. Results: Pathological assessments of specimens of 35 of 85 (41%) pure ground glass opacity tumors including 3 (23%) of 13 pure ground glass opacity tumors <= 1 cm, revealed partially invasive components. Receiver operating characteristic curves for LY0V0PL0N0 revealed solid tumor size <= 6 mmon high-resolution computed tomography or maximum standardized uptake values <= 0.6 on 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography as radiographic indolent tumor criteria for predicting indolent tumors. Among 216 (35.5%) of 609 patients who met these criteria, none developed recurrence over a median follow-up of 41.6 months. Conclusions: Pure ground glass opacity lesions on high-resolution computed tomography could pathologically include invasive components and would not correspond to adenocarcinoma in situ. Solid tumor size on high-resolution computed tomography and maximum standardized uptake values on positron emission tomography/computed tomography can predict indolent LY0V0PL0N0 lung tumors that can be followed up.
  • Yasuhiro Tsutani; Yoshihiro Miyata; Takeshi Mimura; Kei Kushitani; Yukio Takeshima; Masahiro Yoshimura; Morihito Okada
    General thoracic and cardiovascular surgery 63 3 153 - 8 2015年03月 
    OBJECTIVE: The purpose of this study was to investigate the prognostic factors for pathological stage I squamous cell carcinoma of the lung to aid decisions regarding adjuvant chemotherapy. METHODS: We retrospectively analyzed data from 114 consecutive patients with completely resected pathological stage I squamous cell carcinoma of the lung by lobectomy or segmentectomy with systematic lymphadenectomy. RESULTS: The median tumor size was 2.9 cm. Lymphatic, vascular, and pleural invasions were present in 39 (34.2%), 50 (43.9%), and 25 (21.9%) patients, respectively. There were significant differences in recurrence-free and overall survival between patients with and without lymphatic invasion (P = 0.044 and P = 0.040, respectively). Multivariate Cox proportional hazards models demonstrated that postoperative complications (hazard ratio 3.37, 95% confidence interval 1.53-7.42, P = 0.003) and lymphatic invasion (hazards ratio 2.76, 95% confidence interval 1.26-6.04, P = 0.011) were independent prognostic factors influencing recurrence-free survival. Furthermore, age (hazard ratio 1.10, 95% confidence interval 1.02-1.18, P = 0.013) and lymphatic invasion (hazard ratio 3.54, 95% confidence interval 1.33-9.42, P = 0.011) were independent prognostic factors influencing overall survival. CONCLUSIONS: Lymphatic invasion is an independent prognostic factor influencing both recurrence-free and overall survival in patients with pathological stage I squamous cell carcinoma of the lung. Patients with lymphatic invasion may be candidates for adjuvant chemotherapy.
  • Tomoharu Yoshiya; Yoshihiro Miyata; Yuta Ibuki; Takahiro Mimae; Yasuhiro Tsutani; Haruhiko Nakayama; Sakae Okumura; Masahiro Yoshimura; Morihito Okada
    RESPIRATION 90 4 293 - 298 2015年 [査読有り]
     
    Background: Findings on F-18-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) are surrogate markers of malignancy in lung adenocarcinoma. Breathing during PET/CT can substantially reduce the maximum standardized uptake value (maxSUV) of lung tumors when they are located at the lower zone (LZ). Objectives: We assessed whether lung cancer location influences the malignancy predicted by maxSUV. Methods: 608 patients with clinical stage IA lung adenocarcinoma had been preoperatively examined by PET/CT and high-resolution computed tomography (HRCT). We evaluated the clinicopathological characteristics of these patients and the accuracy of precognition obtained by maxSUV between the upper zone (UZ, n = 395) and the LZ (n = 213). maxSUV was also analyzed for matched pairs between the two groups. Results: The mean maxSUV in the LZ group was significantly lower than that in the UZ group (1.98 +/- 1.73 vs. 2.44 +/- 2.43, respectively; p = 0.0145). The receiver operating characteristics curve of maxSUV for predicting high-grade malignancy (lymphatic, vascular, pleural invasion, or lymph node metastasis) was larger for the UZ group than for the LZ group [0.89, 95% confidence interval (CI) 0.86-0.93, vs. 0.82, 95% CI 0.76-0.88]. Analysis for maxSUV of 213 pairs matched for the solid component size on HRCT, pathological characteristics, and gender revealed that maxSUV in the LZ group was significantly lower than that in the UZ group (1.98 +/- 1.73 vs. 2.47 +/- 2.39, respectively; p < 0.001). Conclusions: maxSUV of a tumor in the LZ group is apparently lower than the value which reflects the potential malignancy of a tumor. We have to carefully consider these facts when selecting the appropriate surgical procedure for lung cancer with PET/CT and HRCT. (C) 2015 S. Karger AG, Basel
  • Yasuhiro Tsutani; Yoshihiro Miyata; Haruhiko Nakayama; Sakae Okumura; Shuji Adachi; Masahiro Yoshimura; Morihito Okada
    EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 46 4 637 - 642 2014年10月 
    OBJECTIVES: This study aimed to compare prognosis after segmentectomy and after lobectomy for radiologically determined solid-dominant clinical stage IA lung adenocarcinoma. METHODS: From a multicentre database of 610 consecutive patients with clinical stage IA lung adenocarcinoma who underwent complete resection after preoperative high-resolution computed tomography (HRCT) and F-18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), 327 patients with a radiologically determined solid-dominant tumour (solid component on HRCT >= 50%) who underwent lobectomy (n = 286) or segmentectomy (n = 41) were included. RESULTS: No significant difference existed in recurrence-free survival (RFS) between the lobectomy and segmentectomy groups (3-year RFS, 84.4 vs 84.8%, respectively; P = 0.69). There was no significant difference in recurrence pattern between these two groups (local, 5.6 vs 7.3%, P = 0.72; distant, 9.1 vs 4.9%, P = 0.55, respectively). Even in patients with pure solid tumours, no significant difference was observed in RFS between lobectomy and segmentectomy groups (3-year RFS, 76.8 vs 84.7%, respectively; P = 0.48), as well as in those with a mixed ground-glass opacity tumour (3-year RFS, 91.0 vs 85.0%, respectively; P = 0.60). Multivariate Cox analysis demonstrated that solid tumour size on HRCT (P = 0.048) and maximum standardized uptake value (SUVmax) on FDG-PET/CT (P < 0.001), not the surgical procedure (P = 0.40), were independent prognostic factors for RFS. CONCLUSIONS: RFS depends on solid tumour size on HRCT and SUVmax on FDG-PET/CT, rather than on the surgical procedure, in patients with radiologically detected solid-dominant clinical stage IA lung adenocarcinoma. Patient prognosis is similar after lobectomy and after segmentectomy for solid-dominant tumour.
  • Yasuhiro Tsutani; Yoshihiro Miyata; Kei Kushitani; Yukio Takeshima; Masahiro Yoshimura; Morihito Okada
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 148 4 1179 - 1185 2014年10月 
    Objective: The aim of this study was to reevaluate the role of adjuvant chemotherapy for patients with stage I non-small cell lung cancer (NSCLC). Methods: Data from 800 patients with completely resected pathologic stage I NSCLC who received adjuvant chemotherapy (n = 191) and those who did not (n = 609) were analyzed retrospectively and propensity score-matched pairs were determined. Results: Although recurrence-free survival (RFS) and overall survival (OS) were not significantly different between patients who received adjuvant chemotherapy and those who did not in the univariate analyses, multivariate Cox analyses demonstrated that adjuvant chemotherapy was an independent prognostic factor for RFS and OS (P = .008 and P = .009, respectively). In 159 propensity score-matched pairs, including variables such as age, gender, smoking history, comorbidity, postoperative complication, histology, size of the invasive component of the tumor, and status of lymphatic, vascular, and pleural invasion, RFS and OS were considerably better in patients who received adjuvant chemotherapy (5-year RFS rate, 79.8%; 5-year OS rate, 89.3%) than in those who did not (5-year RFS rate, 60.2%; 5-year OS rate, 75.2%). Patients who received adjuvant chemotherapy showed significantly better RFS than those who did not in the group with an invasive component larger than 2 cm (5-year RFS rate, 74.4% vs 55.2%; P = .015) or in those with positive lymphatic invasion (5-year RFS rate, 63.3% vs 44.8%; P = .05). Conclusions: Adjuvant chemotherapy is effective for patients with stage I NSCLC, particularly those with an invasive component larger than 2 cm or those with lymphatic invasion.
  • T. Mimae; Y. Miyata; Y. Tsutani; T. Yoshiya; N. Tsubokawa; H. Nakayama; S. Okumura; M. Yoshimura; M. Okada
    ANNALS OF ONCOLOGY 25 2014年09月
  • Yasuhiro Tsutani; Morihito Okada
    LUNG CANCER MANAGEMENT 3 3 241 - 244 2014年06月
  • Takahiro Mimae; Yasuhiro Tsutani; Yoshihiro Miyata; Tomoharu Yoshiya; Yuta Ibuki; Kei Kushitani; Yukio Takeshima; Haruhiko Nakayama; Sakae Okumura; Masahiro Yoshimura; Morihito Okada
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 147 6 1820 - 1826 2014年06月 
    Objective: Some patients with clinical T1 N0 M0 lung adenocarcinoma have pathologic lymph node metastasis. However, neither the precise prognosis nor the factors predictive of the prognosis of such patients have yet been identified. Methods: Our study included 609 patients with clinical T1 N0 M0 lung adenocarcinoma; 568 (93.3%) pathologic node negative [pN(-)] and 41 (6.7%) pathologic node positive [pN(+)] patients, diagnosed after complete surgical resection. The association between prognosis and pathologic findings was analyzed retrospectively. Results: pN(+) patients had a significantly lower lepidic growth component ratio (10% vs 50%), a higher lymphatic invasion (LI) rate (68% vs 11%), vessel invasion rate (59% vs 14%), and visceral pleural invasion rate (29% vs 9%), compared with pN(-) patients (all Ps < .001). Surprisingly, 13 of 41 (32%) pN(+) patients showed no LI. In pN(-) patients, a multivariate analysis of recurrence-free survival revealed that lower lepidic growth component ratio, and lymphatic, vessel, and pleural invasion were significantly correlated with a poor prognosis (P = .008, .045, .031, and .024). However, in pN(+) patients, the multivariate analysis of recurrence-free survival showed that only LI was a significant independent prognostic factor (P = .037). The 5-year recurrence-free survival rates were as follows: 91.2% for pN(-)/LI(-) patients, 68.2% for pN(-)/LI(+) patients, 63.5% for pN(+)/LI(-) patients, and 41.9% for pN(+)/LI(+) patients. LI status stratified the prognosis not only in patients with no nodal metastasis but also in those with metastasis. Conclusions: LI, which is not always present in node-positive adenocarcinoma, is an important prognostic variable in patients with node involvement.
  • Yasuhiro Tsutani; Yoshihiro Miyata; Haruhiko Nakayama; Sakae Okumura; Shuji Adachi; Masahiro Yoshimura; Morihito Okada
    ANNALS OF THORACIC SURGERY 97 5 1701 - 1707 2014年05月 
    Background. This study evaluated the usefulness of sublobar resection for patients with clinical stage IA lung adenocarcinoma that met our proposed node-negative criteria: solid tumor size of less than 0.8 cm on high-resolution computed tomography or maximum standardized uptake value of less than 1.5 on [18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography. Methods. A multicenter database of 618 patients with completely resected clinical stage IA lung adenocarcinoma who underwent preoperative high-resolution computed tomography and [18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography was used to evaluate the surgical results of sublobar resection for patients who met our node-negative criteria. Results. No patient who met the node-negative criteria had any pathological lymph node metastasis. Recurrence-free survival (RFS) and overall survival (OS) rates at 5 years were significantly higher for patients who met the node-negative criteria (RFS: 96.6%; OS: 95.9%) than for patients who did not (RFS: 75.5%, p < 0.0001; OS: 83.1%, p < 0.0001). Among patients who met the node-negative criteria, RFS and OS rates at 5 years were not significantly different between those who underwent lobectomy (RFS: 96.0%; OS: 95.9%) and those who underwent sublobar resection (RFS: 97.2%, p =0.94; OS: 95.9%, p =.98). Of 264 patients with T1b (2-cm to 3-cm) tumors, 106 (40.2%) met the node-negative criteria. Conclusions. Sublobar resection without systematic nodal dissection is feasible for clinical stage IA lung adenocarcinoma that meets the above-mentioned nodenegative criteria. Even a T1b tumor, which is generally unsuitable for intentional sublobar resection, can be a candidate for sublobar resection if it meets these node-negative criteria. (C) 2014 by The Society of Thoracic Surgeons
  • Morihito Okada; Takahiro Mimae; Yasuhiro Tsutani; Haruhiko Nakayama; Sakae Okumura; Masahiro Yoshimura; Yoshihiro Miyata
    Annals of cardiothoracic surgery 3 2 153 - 9 2014年03月 
    BACKGROUND: Despite the increasing prevalence of the early discovery of small-sized non-small cell lung cancers (NSCLCs), particularly adenocarcinoma, sublobar resection has not yet gained acceptance for patients who can tolerate lobectomy. METHODS: We compared the outcomes of segmentectomy (n=155) and lobectomy (n=479) in 634 consecutive patients with clinical stage IA lung adenocarcinoma and in propensity score-matched pairs. Those who had undergone wedge resection were excluded. RESULTS: The 30-day postoperative mortality rate in this population was zero. Patients with large or right-sided tumors, high maximum standardized uptake value (SUVmax), pathologically invasive tumors (with lymphatic, vascular, or pleural invasion), and lymph node metastasis underwent lobectomy significantly more often. Three-year recurrence-free survival (RFS) was significantly higher after segmentectomy compared to lobectomy (92.7% vs. 86.9%, P=0.0394), whereas three-year overall survival (OS) did not significantly differ (95.7% vs. 94.1%, P=0.162). Multivariate analyses of RFS and OS revealed age and SUVmax as significant independent prognostic factors, whereas gender, tumor size and procedure (segmentectomy vs. lobectomy) were not. In 100 propensity score-matched pairs with variables adjusted for age, gender, tumor size, SUVmax, tumor location, the three-year RFS (90.2% vs. 91.5%) and OS (94.8% vs. 93.3%) after segmentectomy and lobectomy respectively were comparable. CONCLUSIONS: Segmentectomy with reference to SUVmax should be considered as an alternative for clinical stage IA adenocarcinoma, even for low-risk patients.
  • Yasuhiro Tsutani; Yoshihiro Miyata; Haruhiko Nakayama; Sakae Okumura; Shuji Adachi; Masahiro Yoshimura; Morihito Okada
    CHEST 145 1 66 - 71 2014年01月 
    Background: The purpose of this multicenter study was to characterize ground glass opacity (GGO)-dominant clinical stage IA lung adenocarcinomas and evaluate prognosis of these tumors after sublobar resection, such as segmentectomy and wedge resection. Methods: We evaluated 610 consecutive patients with clinical stage IA lung adenocarcinoma who underwent complete resection after preoperative high-resolution CT scanning and F-18-fluorodeoxyglucose PET/CT scanning and revealed 239 (39.2%) that had a >50% GGO component. Results: GGO-dominant tumors rarely exhibited pathologic invasiveness, including lymphatic, vascular, or pleural invasion and lymph node metastasis. There was no significant difference in 3-year recurrence-free survival (RFS) among patients who underwent lobectomy (96.4%), segmentectomy (96.1%), and wedge resection (98.7%) of GGO-dominant tumors (P = .44). Furthermore, for GGO-dominant T1b tumors, 3-year RFS was similar in patients who underwent lobectomy (93.7%), segmentectomy (92.9%), and wedge resection (100%, P = .66). Two of 84 patients (2.4%) with GGO-dominant T1b tumors had lymph node metastasis. Multivariate Cox analysis showed that tumor size, maximum standardized uptake value on F-18-fluorodeoxyglucose PET/CT scan, and surgical procedure did not affect RFS in GGO-dominant tumors. Conclusions: GGO-dominant clinical stage IA lung adenocarcinomas are a uniform group of tumors that exhibit low-grade malignancy and have an extremely favorable prognosis. Patients with GGO-dominant clinical stage IA adenocarcinomas can be successfully treated with wedge resection of a T1a tumor and segmentectomy of a T1b tumor.
  • Hirofumi Uehara; Yasuhiro Tsutani; Sakae Okumura; Haruhiko Nakayama; Shuji Adachi; Masahiro Yoshimura; Yoshihiro Miyata; Morihito Okada
    ANNALS OF THORACIC SURGERY 96 6 1958 - 1965 2013年12月 
    Background. This multicenter study aimed to validate the ability of F-18-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) plus high-resolution computed tomography (HR-CT) to predict the malignant behavior and prognosis of early adenocarcinomas of the lung. Methods. We calculated maximum standardized uptake values (maxSUV) from PET/CT images and ground-glass opacity (GGO) ratios on HR-CT images before complete surgical intervention in 610 patients with clinical stage IA lung adenocarcinoma. Pathologic invasiveness and survival were compared with clinical factors and radiographic findings including the maxSUV, which was revised to correct for interinstitutional discrepancies that confer limitations upon multicenter PET studies. Results. Analyses of receiver-operating characteristic curves revealed optimal maxSUV and GGO ratio cutoffs to predict recurrence of 2.9 and 25%, respectively. Both the maxSUV and GGO ratio reflected tumor invasiveness, nodal metastasis, recurrence, and patient survivals, and were significant prognostic factors for recurrence-free and cancer-specific survivals on multivariate Cox analysis (all, p < 0.001). The combination of maxSUV and GGO ratio is a better predictor of malignant tumor grade than either alone. Conclusions. The combination of maxSUV and GGO ratio as well as each alone are important predictors of prognosis in patients with clinical stage IA adenocarcinoma of the lung and should be considered before selecting therapeutic strategies. (C) 2013 by The Society of Thoracic Surgeons
  • Kazuya Takamochi; Yoshihiro Miyata; Yasuhiro Tsutani; Kenji Suzuki; Fumihiro Tanaka; Haruhiko Nakayama; Yoshinori Yamashita; Makoto Oda; Masahiro Tsuboi; Morihito Okada
    JOURNAL OF THORACIC ONCOLOGY 8 S856 - S857 2013年11月
  • Masaoki Ito; Yoshinori Yamashita; Yasuhiro Tsutani; Keizo Misumi; Hiroaki Harada; Yoshihiro Miyata; Morihito Okada
    CLINICAL LUNG CANCER 14 6 651 - 657 2013年11月 
    We evaluated the classification of patients with N2 nonesmall-cell lung cancer by the metastatic status of mediastinal lymph nodes in 187 patients with pN1-N2 and 136 patients with pN2. The potential usefulness in determining the risk for patients with N2 by assessment of mediastinal lymph nodes alone was indicated. Background: Subdivisions of N2 nonesmall-cell lung cancer (NSCLC) cases based on metastatic status of mediastinal and non-mediastinal lymph nodes have been proposed. This study aimed to evaluate N2 disease classification by mediastinal lymph nodes alone. Patients and Methods: We reviewed 187 patients with NSCLC pN1-N2 who were surgically treated to evaluate the proposed classifications: number, rate, nodal zone of metastatic lymph nodes. We evaluated N2 disease classification based on mediastinal lymph nodes alone in 136 pN2 cases. Results: The number (1-2, 3-5, and 6 <=) or rate (15% <=, 15%< to 40%>, and 40% <=) classification based on all metastatic lymph nodes was validated by the log-rank test and Cox proportional hazards model. After reclassification by number or rate of metastatic mediastinal lymph nodes alone, a significant difference was maintained among all groups except between the 3-5 and 6 groups. The 5-year survival rates of the 1-2, 3-5, and 6 <= groups were 63.4%, 32.4%, and 18.2%, respectively (1-2 vs. 3-5, P.015; 3-5 vs. 6, P<.134). With rate classification, the 5-year survival rates of the 15% >=, 15%-40% (15%< to 40%>), and 40% >= groups were 56.0%, 27.3%, and 5.04%, respectively (15% <= vs. 15%-40%, P<.011; 15-40% vs. 40% <=, P.011). The Spearman's rank correlation coefficient showed a highly significant correlation of metastatic status between mediastinal lymph nodes and all lymph nodes (both P <.001). Conclusion: Classification by number and rate of mediastinal lymph nodes alone enabled subdivision of N2 NSCLC cases. Metastatic status of mediastinal lymph nodes reflects that of all lymph nodes and is prognostic indicators.
  • 見前 隆洋; 津谷 康大; 坪川 典史; 笹田 伸介; 吉屋 智晴; 宮田 義浩; 中山 治彦; 奥村 栄; 吉村 雅裕; 岡田 守人
    肺癌 53 5 477 - 477 (NPO)日本肺癌学会 2013年10月
  • 浅野 早苗; 二井谷 真由美; 青山 菜緒; 上野 和美; 上村 健一郎; 村上 義昭; 首藤 毅; 鈴木 崇久; 平田 英司; 津谷 康大; 片岡 健
    広島大学保健学ジャーナル 11 2 63 - 70 広島大学保健学出版会 2013年10月 
    化学療法の有害事象のうち味覚障害は発生頻度の高い有害事象である.味覚と血清亜鉛値との関連については以前から指摘されているが,抗がん剤投与後の味覚変化に血清亜鉛値が影響していることを示した報告は少ない.本研究の目的は,抗がん剤投与後のがん患者の味覚閾値と血清亜鉛値を測定し,両者の関連性を検証することである.60名のがん患者の抗がん剤投与前,抗がん剤投与後3日と投与後6日に味覚と血清亜鉛値,血清銅値を測定した.抗がん剤投与後の味覚の変化は,塩味で時間経過による有意差を認めた(p<0.01).血清亜鉛値でも時間経過による有意差を認めた(p<0.01).味覚と血清亜鉛値との関係では,抗がん剤投与後3日において,血清亜鉛値と塩味の感度に負の相関を認め(r =- 0.402,p<0.01),血清亜鉛値が低い時,塩味の感度が鈍麻したことが示された.一方,血清銅値と味覚感度には相関を認めなかった.抗がん剤投与後の味覚感度,特に塩味の鈍麻については血清亜鉛値との関連が示された.
  • Masahiro Ohara; Hideo Shigematsu; Yasuhiro Tsutani; Akiko Emi; Norio Masumoto; Shinji Ozaki; Takayuki Kadoya; Morihito Okada
    BREAST 22 5 958 - 963 2013年10月 
    Background: The aim of this study was to evaluate the significance of F-18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for speculating the malignant level and prognostic value of operable breast cancers. Methods: Of 578 consecutive patients with primary invasive breast cancer who underwent curative surgery between 2005 and 2010, 311 patients (53.8%) who received FDG-PET/CT before initial therapy were examined. Results: Receiver operating characteristics (ROC) curve analysis showed the cutoff value of the maximum standardized uptake value (SUVmax) to predict cancer recurrence was 3.8 in all patients and 8.6 in patients with the triple-negative subtype, respectively. In all patients, 3-year DFS rates were 98.8% for patients with a tumor of SUVmax <= 3.8 and 91.6% for patients with a tumor of SUVmax > 3.8 (p < 0.001). High value of SUVmax was significantly associated with large tumor size (p < 0.001), lymph node metastasis (p = 0.040), high nuclear grade (p < 0.001), lymphovascular invasion (p = 0.032), negative hormone receptor status (p < 0.001), and positive HER2 status (p = 0.014). Based on the results of multivariate Cox analysis in all patients, high SUVmax (p = 0.001) and negative hormone receptor status (p = 0.005) were significantly associated with poor prognosis. In patients with triple-negative subtype, 3-year DFS rates were 90.9% for patients with a tumor of SUVmax <= 8.6 and 42.9% for patients with a tumor of SUVmax > 8.6 (p = 0.002), and high SUVmax was the only significant independent prognostic factor (p = 0.047). Conclusion: FDG-PET/CT is useful for predicting malignant behavior and prognosis in patients with operable breast cancer, especially the triple-negative subtype. (C) 2013 Elsevier Ltd. All rights reserved.
  • Yasuhiro Tsutani; Yoshihiro Miyata; Takahiro Mimae; Kei Kushitani; Yukio Takeshima; Masahiro Yoshimura; Morihito Okada
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 146 3 580 - 585 2013年09月 
    Objectives: We performed an investigation of the prognostic significance of the invasive component size, excluding lepidic growth, in lung adenocarcinoma patients. Methods: The data from 603 patients with completely resected pathologic stage I lung adenocarcinomas were analyzed retrospectively to determine the relationship between pathologic tumor size and surgical results. Results: The median tumor size of the total growth and the invasive component were 2.2 cm and 1.3 cm, respectively. There were significant differences in recurrence-free survival between patients classified on the basis of invasive component sizes (<= 0.5 cm vs 0.5-2.0 cm, P < .001; and 0.5-2.0 cm vs > 2.0 cm; P = .026). A multivariate Cox regression analysis showed that invasive component size (P = .002), age, sex, and lymphatic invasion were independent prognostic factors for recurrence-free survival, whereas total tumor size was not (P = .068). There were no significant differences in recurrence-free survival between patients who received adjuvant chemotherapy and those who did not in the group with invasive component size of 0.5 cm or less (P = .29) and in the group with invasive component size of 0.5 to 2.0 cm (P = .50). However, the recurrence-free survival of patients who received adjuvant chemotherapy was significantly better than that of those who did not in the group with invasive component size greater than 2.0 cm (P = .009). Conclusions: Pathologic invasive component size, as opposed to total tumor size, is associated more significantly with malignant behavior and prognosis and specifically should be considered before choosing candidates for adjuvant chemotherapy in pathologic stage I lung adenocarcinoma.
  • Yasuhiro Tsutani; Yoshihiro Miyata; Morihito Okada
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 146 3 729 - 729 2013年09月
  • S. Murakami; H. Nakayama; Y. Tsutani; Y. Miyata; S. Okumura; M. Yoshimura; S. Adachi; M. Okada
    EUROPEAN JOURNAL OF CANCER 49 S815 - S815 2013年09月
  • T. Mimae; Y. Tsutani; Y. Miyata; T. Yoshiya; Y. Ibuki; H. Nakayama; S. Okumura; M. Yoshimura; M. Okada
    EUROPEAN JOURNAL OF CANCER 49 S810 - S810 2013年09月
  • Y. Tsutani; Y. Miyata; H. Nakayama; S. Okumura; S. Adachi; M. Yoshimura; M. Okada
    ANNALS OF ONCOLOGY 24 9 2376 - 2381 2013年09月 
    To better describe clinical T descriptors using solid tumor size (the maximum dimension of the solid component of the tumor) on high-resolution computed tomography (HRCT) and maximum standardized uptake value (SUVmax) on F-18-fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT). We examined 610 consecutive patients with clinical stage IA lung adenocarcinoma who underwent complete resection. Recurrence-free survival (RFS) was assessed on the basis of whole tumor size (maximum dimension of the tumor), solid tumor size, or a combination of solid tumor size and SUVmax. RFS based on whole tumor size was not significantly different between patients with tumors measuring < 2 cm and 2-3 cm (P = 0.089), whereas RFS based on solid tumor size was significantly different (P < 0.0001). We divided patients into four groups on the basis of solid tumor size and SUVmax: group 1: solid tumor size < 2 cm, SUVmax < 1.8; group 2: solid tumor size < 2 cm, SUVmax > 1.8; group 3: solid tumor size 2-3 cm, SUVmax < 3.6; and group 4: solid tumor size 2-3 cm, SUVmax > 3.6. Groups 2 and 3 were combined because they showed similar RFS each other. RFS was significantly different among these groups: group 1 versus groups 2 + 3, P < 0.0001; groups 2 + 3 versus group 4, P = 0.019. Both solid tumor size on HRCT and SUVmax on FDG-PET/CT reflect prognosis well in patients with clinical stage IA lung adenocarcinoma and may support new clinical T descriptors.
  • Masaoki Ito; Riki Okita; Yasuhiro Tsutani; Takeshi Mimura; Yukari Kawasaki; Yoshihiro Miyata; Morihito Okada
    THORACIC CANCER 4 3 327 - 329 2013年08月 
    We report a case of adenoid cystic carcinoma of the submandibular gland where pulmonary metastasis occurred twice 16 years after resection, and each metastasis mimicked primary lung adenocarcinoma in imaging findings. The first pulmonary relapse was clinically diagnosed as primary lung adenocarcinoma and intraoperative pathological examination showed that the tumor was an adenocarcinoma; lobectomy with mediastinal lymph node dissection was performed. However, postoperative immunohistochemical analysis showed that the tumor was a metastatic adenoid cystic carcinoma. During the secondary pulmonary relapse, although the tumor was correctly diagnosed as a metastatic adenoid cystic carcinoma by intraoperative examination, it again mimicked primary lung adenocarcinoma.
  • Yasuhiro Tsutani; Yoshihiro Miyata; Haruhiko Nakayama; Sakae Okumura; Shuji Adachi; Masahiro Yoshimura; Morihito Okada
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 146 2 358 - 364 2013年08月 
    Objective: Our objective was to compare the oncologic outcomes of lobectomy and segmentectomy for clinical stage IA lung adenocarcinoma. Methods: We examined 481 of 618 consecutive patients with clinical stage IA lung adenocarcinoma who underwent lobectomy or segmentectomy after preoperative high-resolution computed tomography and F-18-fluorodeoxyglucose positron emission tomography/computed tomography. Patients (n = 137) who underwent wedge resection were excluded. Lobectomy (n 383) and segmentectomy (n 98) as well as surgical results were analyzed for all patients and their propensity score-matched pairs. Results: Recurrence-free survival (RFS) and overall survival (OS) were not significantly different between patients undergoing lobectomy (3-year RFS, 87.3%; 3-year OS, 94.1%) and segmentectomy (3-year RFS, 91.4%; hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.27-1.20; P = .14; 3-year OS, 96.9%; HR, 0.49; 95% CI, 0.17-1.38; P = .18). Significant differences in clinical factors such as solid tumor size (P < .001), maximum standardized uptake value (SUVmax) (P < .001), and tumor location (side, P = .005; lobe, P = .001) were observed between both treatment groups. In 81 propensity score-matched pairs including variables such as age, gender, solid tumor size, SUVmax, side, and lobe, RFS and OS were similar between patients undergoing lobectomy (3-year RFS, 92.9%, 3-year OS, 93.2%) and segmentectomy (3-year RFS, 90.9%; 3-year OS, 95.7%). Conclusions: Segmentectomy is suitable for clinical stage IA lung adenocarcinoma, with survivals equivalent to those of standard lobectomy.
  • Ryutaro Mori; Kazuhiro Yoshida; Toshiyuki Tanahashi; Kazunori Yawata; Junko Kato; Naoki Okumura; Yasuhiro Tsutani; Morihito Okada; Naohide Oue; Wataru Yasui
    GASTRIC CANCER 16 3 345 - 354 2013年07月 
    Oxaliplatin is effective against many types of cancer, and the combination of 5-fluorouracil (5FU) and oxaliplatin is synergistically effective against gastric cancer, as well as colon cancer. The FANCJ protein is one of the Fanconi anemia (FA) gene products, and its interaction with the tumor suppressor BRCA1 is required for DNA double-strand break (DSB) repair. FANCJ also functions in interstrand crosslinks (ICLs) repair by linking to mismatch repair protein complex MLH1-PMS2 (MutL alpha). While oxaliplatin causes ICLs, 5FU is considered to cause DSBs. Therefore, we investigated the importance of FANCJ in the synergistic effects of oxaliplatin and 5FU in MKN45 gastric cancer cells and the derived 5FU-resistant cell line, MKN45/F2R. MKN1, TMK1, MKN45, and MKN45/F2R (5FU-resistant) gastric cancer cells were treated with 5FU and/or oxaliplatin. The signaling pathway was evaluated by a western blotting analysis and reverse transcription polymerase chain reaction (RT-PCR). Drug resistance was evaluated by the 3-(4,5-dimethyl-2-tetrazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay. In MKN45 cells, the combination of 5FU and oxaliplatin had synergistic effects. DSBs appeared when the cells were treated with 5FU. FANCJ was down-regulated, and BRCA1 was induced in a dose- and time-dependent manner. MKN45 cells showed increased sensitivity to oxaliplatin when FANCJ was knocked down by short interfering (si) RNA. However, these findings were not observed in MKN45/F2R 5FU-resistant cells. These results strongly suggest that the decrease in FANCJ caused by 5FU treatment leads to an increase in sensitivity to oxaliplatin, thus indicating that the FANCJ protein plays an important role in the synergism of the combination of 5FU and oxaliplatin.
  • Yasuhiro Tsutani; Yoshihiro Miyata; Takeharu Yamanaka; Haruhiko Nakayama; Sakae Okumura; Shuji Adachi; Masahiro Yoshimura; Morihito Okada
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 146 1 17 - 23 2013年07月 
    Objective: This study aimed to compare malignant behavior and prognosis between solid tumors and mixed tumors with a ground-glass opacity component on high-resolution computed tomography. Methods: We examined 436 of 502 consecutive patients with clinical stage IA adenocarcinoma who had undergone preoperative high-resolution computed tomography and F-18-fluorodeoxyglucose positron emission tomography/computed tomography; 66 patients with tumors with pure ground-glass opacity components were excluded. Tumor type (solid, n = 137; mixed, n = 299) and surgical results were analyzed for all patients and their matched pairs. Results: In all patients, solid tumors showed a significantly greater association (P < .001) with lymphatic, vascular, and pleural invasion and lymph node metastasis compared with mixed tumors. The disease-free survival was also worse in patients with solid tumors (P = .0006). Analysis of 97 pairs matched for solid component size confirmed that solid tumors were significantly associated with lymphatic, vascular, and pleural invasion (P = .008, P = .029, P = .003, respectively) and poor prognosis. When maximum standardized uptake value and solid component size were matched (n = 79), the differences in pathologic prognostic parameters and disease-free survivals between patients with solid and mixed tumors disappeared. Conclusions: Solid tumors exhibit more malignant behavior and have a poorer prognosis compared with mixed tumors, even when the solid component size is the same in both tumor types. However, differences in malignant behavior can be identified using maximum standardized uptake values determined by F-18-fluorodeoxyglucose positron emission tomography/computed tomography.
  • Shinsuke Sasada; Yoshihiro Miyata; Yasuhiro Tsutani; Jun Hihara; Morihito Okada
    JOURNAL OF CLINICAL ONCOLOGY 31 15 2013年05月
  • Morihito Okada; Yasuhiro Tsutani; Yoshihiro Miyata
    The Journal of thoracic and cardiovascular surgery 145 4 1148 - 1149 2013年04月 [査読有り]
  • Morihito Okada; Yasuhiro Tsutani; Yoshihiro Miyata
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 145 4 1148 - 1149 2013年04月
  • Y. Tsutani; T. Takuwa; Y. Miyata; K. Fukuoka; S. Hasegawa; T. Nakano; M. Okada
    ANNALS OF ONCOLOGY 24 4 1005 - 1010 2013年04月 
    To select optimal candidates for extrapleural pneumonectomy (EPP), we retrospectively evaluated the usefulness of metabolic response by fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) after neoadjuvant chemotherapy to predict prognosis for patients with resectable malignant pleural mesothelioma (MPM) who underwent EPP in a multicenter study. We carried out high-resolution CT (HRCT) and FDG-PET/CT before and after neoadjuvant platinum-based chemotherapy on 50 patients with clinical T1-3 N0-2 M0 MPM who underwent EPP +/- postoperative hemithoracic radiotherapy. A decrease of >= 30% in the tumor maximum standardized uptake value (SUVmax) was defined as a metabolic responder. The radiologic response using the modified RECIST or metabolic response and surgical results were analyzed. The median overall survival (OS) from diagnosis was 20.5 months. Metabolic responders significantly correlated to OS with median OS for metabolic responders not reached versus 18.7 months for non-responders. No correlation was observed between OS and radiologic response with median OS for radiologic responders and non-responders. Based on the multivariate Cox analyses, decreased SUVmax and epithelioid subtype were significantly independent factors for OS. The metabolic response after neoadjuvant chemotherapy is an independent prognostic factor for patients with resectable MPM. Patients with metabolic responder or epithelioid subtype may be good candidates for EPP.
  • 三隅 啓三; 津谷 康大; 伊富貴 雄太; 見前 隆洋; 吉屋 智晴; 宮田 義浩; 中山 治彦; 奥村 栄; 吉村 雅裕; 岡田 守人
    日本外科学会雑誌 114 2 一般社団法人日本外科学会 2013年03月
  • 伊富貴 雄太; 津谷 康大; 見前 隆洋; 吉屋 智晴; 宮田 義浩; 中山 治彦; 奥村 栄; 吉村 雅裕; 岡田 守人
    日本外科学会雑誌 114 2 一般社団法人日本外科学会 2013年03月
  • 吉屋 智晴; 見前 隆洋; 津谷 康大; 伊富 貴雄太; 三隅 啓三; 宮田 義浩; 中山 治彦; 奥村 栄; 吉村 雅裕; 岡田 守人
    日本外科学会雑誌 114 2 一般社団法人日本外科学会 2013年03月
  • Shinsuke Sasada; Yoshihiro Miyata; Yasuhiro Tsutani; Naohiro Tsuyama; Tsutomu Masujima; Jun Hihara; Morihito Okada
    Oncology reports 29 3 925 - 31 2013年03月 
    Metabolomics has developed as an important new tool in cancer research. It is expected to lead to the discovery of biomarker candidates for cancer diagnosis and treatment. The current study aimed to perform a comprehensive metabolomic analysis of the intracellular dynamic responses of human gastric cancer cells to 5-fluorouracil (5-FU), referencing the mechanisms of drug action and drug resistance. Small metabolites in gastric cancer cells and 5-FU-resistant cells were measured by liquid chromatography-mass spectrometry. Candidates for drug targets were selected according to the presence or absence of resistance, before and after 5-FU treatment. In addition, the gene expression of each candidate was assessed by reverse transcription-polymerase chain reaction. The number of metabolites in cancer cells dramatically changed during short-term treatment with 5-FU. Particularly, proline was reduced to one-third of its original level and glutamate was increased by a factor of 3 after 3 h of treatment. The metabolic production of glutamate from proline proceeds by proline dehydrogenase (PRODH), producing superoxide. After 5-FU treatment, PRODH mRNA expression was upregulated 2-fold and production of superoxide was increased by a factor of 3. In 5-FU-resistant cells, proline and glutamate levels were less affected than in non-resistant cells, and PRODH mRNA expression and superoxide generation were not increased following treatment. In conclusion, the authors identified a candidate biomarker, PRODH, for drug effects using a meta-bolomic approach, a result that was confirmed by conventional methods. In the future, metabolomics will play an important role in the field of cancer research.
  • Ibuki, Yuta; Miyata, Yoshihiro; Yoshiya, Tomoharu; Mimae, Takahiro; Tsutani, Yasuhiro; Okada, Morihito
    JOURNAL OF CLINICAL ONCOLOGY 31 15 2013年
  • Miyata, Y.; Ibuki, Y.; Tsutani, Y.; Yoshiya, T.; Mimae, T.; Nakayama, H.; Okumura, S.; Yoshimura, M.; Okada, M.
    EUROPEAN JOURNAL OF CANCER 49 S810 - S811 2013年
  • Yasuhiro Tsutani; Yoshihiro Miyata; Haruhiko Nakayama; Sakae Okumura; Shuji Adachi; Masahiro Yoshimura; Morihito Okada
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 144 6 1365 - 1371 2012年12月 
    Objective: Patients with pathologic node-negative early lung cancer may be optimal candidates for sublobar resection. We aimed to identify predictors of pathologic lymph node involvement in clinical stage IA lung adenocarcinoma. Methods: The data from a multicenter database of 502 patients with completely resected clinical stage IA lung adenocarcinoma were retrospectively analyzed to determine the relationship between the lymph node metastasis status and tumor size on high-resolution computed tomography (HRCT) or maximum standardized uptake value (SUVmax) on [18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDGPET/CT). Revised SUVmax was used to correct interinstitutional discrepancies. Results: In multivariate analyses, either a solid tumor size on HRCT (P = .001) or an SUVmax on FDG-PET/CT (P = .049) was an independent predictor of lymph node metastasis. The predictive criteria of pathologic node-negative early lung cancer were a solid tumor size of less than 0.8 cm or an SUVmax of less than 1.5. Patients who met the predictive criteria of pathologic node-negative disease had less pathologic invasiveness, such as lymphatic, vascular, or pleural invasion (P < .001), and better disease-free survival (P < .0001) than those who did not, and 86 (40.4%) of the 213 patients with T1b (2-3 cm) tumors met the predictive criteria. Conclusions: Either a solid tumor size or an SUVmax was a significant independent predictor of nodal involvement in clinical stage IA lung adenocarcinoma. The pathologic node-negative status criteria of a solid tumor size of less than 0.8 cm on HRCT or an SUVmax of less than 1.5 on FDG-PET/CT may be helpful for avoiding systematic lymphadenectomy for clinical stage IA lung adenocarcinoma, even in cases of T1b (2-3 cm) tumor. (J Thorac Cardiovasc Surg 2012; 144:1365-71)
  • 津谷 康大; 宮田 義浩; 岡田 守人
    内科 110 5 709 - 712 南江堂 2012年11月
  • Yasuhiro Tsutani; Yoshinori Yamashita; Keizo Misumi; Takuhiro Ikeda; Yoshihiro Miyata; Morihito Okada
    EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 42 5 E96 - E101 2012年11月 
    The study aimed to evaluate the prognostic significance of carcinoembryonic antigen levels in pleural lavage fluid (p-CEA) in patients with completely resected non-small-cell lung cancer (NSCLC). We examined 72 patients who underwent curative surgical resections. Pleural lavage fluid was collected at thoracotomy before lung resection. Pleural lavage cytology and p-CEA were determined. The relationships between p-CEA and clinicopathological factors were analysed. Four patients (5.6%) had positive pleural lavage cytologies. The median p-CEA was 65.2 ng/g protein (range, 0-7331.7). p-CEA was significantly correlated with pleural invasion and CEA levels in serum (s-CEA). Receiver operating characteristic curve analysis identified an optimal cut-off of 38 ng/g protein for p-CEA for predicting recurrence [area under the curve (AUC) = 0.669; sensitivity = 91.7%; specificity = 43.7%; 95% confidence interval (CI) = 0.541-0.796; P = 0.020], whereas this could not be identified for s-CEA (AUC = 0.535; 95% CI = 0.392-0.678; P = 0.629). With a mean follow-up period of 57.5 months, 5-year disease-free survival (DFS) rates were 86.5% for p-CEA < 38 ng/g protein and 47.7% for p-CEA > 38 ng/g protein (P = 0.0013). Even for patients with Stage I lung cancer, 5-year DFS rates were 88.2 and 53.8%, respectively (P = 0.017). Multivariate Cox analysis revealed that p-CEA was a significant independent factor for DFS and overall survival. Intraoperative p-CEA may be a more powerful prognostic determinant than s-CEA for patients with NSCLC.
  • Y. Miyata; T. Furukawa; Y. Tsutani; T. Mimae; K. Misumi; T. Yoshiya; Y. Ibuki; M. Okada
    ANNALS OF ONCOLOGY 23 385 - 385 2012年09月
  • Yasuhiro Tsutani; Teruhisa Takuwa; Yoshihiro Miyata; Kazuya Fukuoka; Seiki Hasegawa; Takashi Nakano; Morihito Okada
    JOURNAL OF CLINICAL ONCOLOGY 30 15 2012年05月
  • 津谷 康大; 坪川 典史; 小林 美恵; 三隅 啓三; 松本 耕太郎; 宮田 義浩; 中山 治彦; 奥村 栄; 吉村 雅裕; 岡田 守人
    日本呼吸器外科学会雑誌 26 3 SY2 - 01 (NPO)日本呼吸器外科学会 2012年04月
  • 松本 耕太郎; 坪川 典史; 小林 美恵; 三隅 啓三; 津谷 康大; 宮田 義浩; 岡田 守人
    日本呼吸器外科学会雑誌 26 3 VSY - 03 (NPO)日本呼吸器外科学会 2012年04月
  • 宮田 義浩; 津谷 康大; 松本 耕太郎; 三隅 啓三; 坪川 典史; 小林 美恵; 中山 治彦; 奥村 栄; 吉村 雅裕; 岡田 守人
    日本呼吸器外科学会雑誌 26 3 O16 - 07 (NPO)日本呼吸器外科学会 2012年04月
  • 坪川 典史; 津谷 康大; 小林 美恵; 三隅 啓三; 松本 耕太郎; 宮田 義浩; 岡田 守人
    日本呼吸器外科学会雑誌 26 3 P37 - 02 (NPO)日本呼吸器外科学会 2012年04月
  • Masaoki Ito; Yoshinori Yamashita; Yoshihiro Miyata; Masahiro Ohara; Yasuhiro Tsutani; Takuhiro Ikeda; Keizo Misumi; Hiroaki Harada; Ken-ichi Omori
    LUNG CANCER 76 1 93 - 97 2012年04月 
    The status of mediastinal lymph node metastasis is one of the main factors determining the treatment strategy for non-small cell lung cancer (NSCLC), but the primary tumor location is not considered crucial in the tumor-node-metastasis (TMN) classification at present. The aim of this study was to estimate the prognostic value of the primary tumor location on the basis of the hilar structures in NSCLC with mediastinal lymph node metastasis. We retrospectively reviewed the cases of 337 consecutive patients who underwent surgical resection for NSCLC between 1995 and 2004, divided the pN2 NSCLC cases (n = 40) into central- and peripheral-type tumors according to the distance of the primary tumor from the first branch of the extrapulmonary bronchus, and compared the surgical outcomes between these tumor groups. Eighteen and twenty-two cases were classified as central- and peripheral-type tumors, respectively. The 5-year survival rate was significantly better for patients with central-type tumors than peripheral-type tumors (51.5% vs. 21.2%, P = 0.034). The location-specific prognostic tendency was noted irrespective of the presence (n = 13) or absence of skip metastasis. In a multivariate Cox analysis of the N2 NSCLC cases, the primary tumor location was a significant (P = 0.026) prognostic factor for overall survival. In conclusion, evaluation of the primary tumor location based on the hilar structures is useful to predict the prognosis in N2 NSCLC. (C) 2012 Published by Elsevier Ireland Ltd.
  • Takuhiro Ikeda; Yoshihiro Miyata; Yasuhiro Tsutani; Keizo Misumi; Koji Arihiro; Morihito Okada
    EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 41 4 926 - 932 2012年04月 
    To repair unexpected damage of the pulmonary artery (PA) during thoracic surgery, fibrinogen/thrombin-based collagen fleece (TachoComb((R)) [TC]) can be applied as a haemostatic material. The progression of vessel restoration with TC has not been elucidated. In this study, we investigate details of the healing process with TC after PA injury using a canine model. Left thoracotomy was performed on female beagles under general anaesthesia. PA injury was induced and repaired using TC. Repair sites were histologically evaluated 2, 4 and 8 weeks after surgery (n = 3 in each group). Haemostasis of PA injury was achieved promptly after TC application. After surgery, no bleeding was found in the thoracic cavity, and no repair sites revealed stenosis, thrombi or false aneurism formation. Two weeks after surgery, inflammatory cells had infiltrated around the vascular defect, and vascular endothelium had regenerated on the innermost surface of TC applied to the defect. At Week 4, elastic and smooth muscle fibres had begun to extend into the defect between the endothelial layer and collagen fleece. By Week 8, elastic fibres and smooth muscle had completely regenerated in the medial layer. The adventitial layer had also fully regenerated. Haemostasis of injured PA using TC was safe and reliable. TC provided a mechanical scaffold on which vascular regeneration occurred. Three layers reconstructed in the PA defect were identical to those in normal structures.
  • Takahiro Mimae; Morihito Okada; Man Hagiyama; Yoshihiro Miyata; Yasuhiro Tsutani; Takao Inoue; Kenjiro Aogi; Yoshinori Murakami; Akihiko Ito
    CANCER RESEARCH 72 2012年04月
  • 笹田 伸介; 津谷 康大; 宮田 義浩; 水野 初; 津山 尚宏; 升島 努; 岡田 守人
    日本外科学会雑誌 113 2 749  一般社団法人日本外科学会 2012年03月
  • 宮田 義浩; 津谷 康大; 三隅 啓三; 松本 耕太郎; 岡田 守人
    日本外科学会雑誌 113 2 345  一般社団法人日本外科学会 2012年03月
  • 津谷 康大; 小林 美恵; 三隅 啓三; 松本 耕太郎; 宮田 義浩; 中山 治彦; 奥村 栄; 吉村 雅裕; 岡田 守人
    日本外科学会雑誌 113 2 232  一般社団法人日本外科学会 2012年03月
  • Yasuhiro Tsutani; Yoshihiro Miyata; Haruhiko Nakayama; Sakae Okumura; Shuji Adachi; Masahiro Yoshimura; Morihito Okada
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 143 3 607 - 612 2012年03月 
    Objectives: The present multicenter study compared the usefulness of the solid tumor size with that of the whole tumor size on preoperative high-resolution computed tomography for predicting pathologic high-grade malignancy (positive lymphatic, vascular, or pleural invasion) and the prognosis of clinical stage IA lung adenocarcinoma. Methods: We performed high-resolution computed tomography and F-18 fluorodeoxyglucose-positron emission tomography/computed tomography before curative surgical resection in 502 patients with clinical stage IA lung adenocarcinoma. The revised maximum standardized uptake values on F-18 fluorodeoxyglucose-positron emission tomography/computed tomography were used to correct interinstitutional discrepancies. The whole and solid tumor sizes on high-resolution computed tomography were then analyzed in relation to surgical results. Results: The mean whole and solid tumor size was 1.97 +/- 0.59 cm and 1.20 +/- 0.88 cm, respectively. The receiver operating characteristics area under the curve for the whole and solid tumor sizes used to identify high-grade malignancy were 0.590 and 0.829, respectively. Multiple logistic regression analyses demonstrated solid tumor size (P < .001) and maximum standardized uptake values of the tumor (P < .001) as independent variables for the prediction of high-grade malignancy. Multivariate Cox analysis of disease-free survival demonstrated the former (hazard ratio, 2.30; 95% confidence interval, 1.46-3.63; P < .001) and latter (hazard ratio, 1.08; 95% confidence interval, 1.00-1.17; P = .05) as independent prognostic factors. Conclusions: The solid tumor size on high-resolution computed tomography and maximum standardized uptake values on positron emission tomography/computed tomography have greater predictive value for high-grade malignancy and prognosis in clinical stage IA lung adenocarcinoma than that of whole tumor size. (J Thorac Cardiovasc Surg 2012;143:607-12)
  • 津谷 康大; 坪川 典史; 小林 美恵
    広島医学 65 2 72 - 77 広島医学会 2012年02月
  • Takahiro Mimae; Morihito Okada; Man Hagiyama; Yoshihiro Miyata; Yasuhiro Tsutani; Takao Inoue; Yoshinori Murakami; Akihiko Ito
    CLINICAL CANCER RESEARCH 18 4 945 - 955 2012年02月 
    Purpose: Lung adenocarcinoma often manifests as tumors with mainly lepidic growth. The size of invasive foci determines a diagnosis of in situ, minimally invasive adenocarcinoma, or invasive types and suggests that some adenocarcinomas undergo malignant progression in that order. This study investigates how transcriptional aberrations in adenocarcinoma cells at the early stage define the clinical phenotypes of adenocarcinoma tumors at the advanced stage. Experimental Design: We comprehensively searched for differentially expressed genes between preinvasive and invasive cancer cells in one minimally invasive adenocarcinoma using laser capture micro-dissection and DNA microarrays. We screened expression of candidate genes in 11 minimally invasive adenocarcinomas by reverse transcriptase PCR and examined their involvement in preinvasive-to-invasive progression by transfection studies. We then immunohistochemically investigated the presence of candidate molecules in 64 samples of advanced adenocarcinoma and statistically analyzed the findings, together with clinicopathologic variables. Results: The transcription factors Notch2 and Six1 were upregulated in invasive cancer cells in all 11 minimally invasive adenocarcinomas. Exogenous Notch2 transactivated Six1 followed by Smad3, Smad4, and vimentin, and enlarged the nuclei of NCI-H441 lung epithelial cells. Immunochemical staining for the transcription factors was double positive in the invasive, but not in the lepidic growth component of a third of advanced Ads, and the disease-free survival rates were lower in such tumors. Conclusions: Paired upregulation of Notch2 and Six1 is a transcriptional aberration that contributes to preinvasive-to-invasive adenocarcinoma progression by inducing epithelial-mesenchymal transition and nuclear atypia. This aberration persisted in a considerable subset of advanced adenocarcinoma and conferred a more malignant phenotype on the subset. Clin Cancer Res; 18(4); 945-55. (C)2011 AACR.
  • 浅野早苗; 上野和美; 二井谷真由美; 上村健一郎; 村上義明; 首藤毅; 平田英司; 鈴木崇久; 津谷康大; 楢原啓之; 片岡健
    癌と化学療法 39 9 1389 - 1393 2012年 
    For cancer patients undergoing chemotherapy, there is an onset of a variety of adverse events related to treatment. Among the adverse events at the moment is taste disorder, for which there is no established effective supportive care. We report the measurement and study their relationship across the changes in serum zinc and changes in the taste of patients undergoing chemotherapy. For cancer patients undergoing chemotherapy, taste threshold and serum zinc levels were measured on the day before administration of the therapeutic anti-cancer agent, and after administration of anticancer drugs on day 4 and day 7. Of taste thresholds in the test results, the threshold was salty on day 4 and day 7 after administration of anticancer agents, and a significant difference was found on day 7 after treatment with anticancer drugs on a day prior to administration of anticancer agents on day 1 (p< 0.001, p=0.007), respectively. The serum zinc level was measured. There was no significant difference on day 7 after administration of anticancer agents and anti-cancer agent before administration on day 1 and day 7 after administration of anticancer drugs on day 4 (p< 0.001, p< 0.05), respectively. A negative correlation was shown between the "salt of the fourth day threshold" and "serum zinc levels" (r=-0.418, p< 0.05). From the results of this study, salty and low serum zinc values tended to be blunted. The higher the serum zinc level was, the more sensitivity there was to salty taste.
  • Yoshihiro Miyata; Yasuhiro Tsutani; Morihito Okada
    Seminars in thoracic and cardiovascular surgery 24 4 267 - 74 2012年 
    Preoperative determination of malignant behavior is critical in choosing suitable therapeutic strategies such as sublobar resection for patients with small lung cancers. The aim of present review was to evaluate high-resolution computed tomography and fluorodeoxyglucose-positron emission tomography/computed tomography as tools for management of clinical stage IA adenocarcinoma.
  • Morihito Okada; Yasuhiro Tsutani; Takuhiro Ikeda; Keizo Misumi; Kotaro Matsumoto; Masahiro Yoshimura; Yoshihiro Miyata
    INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY 14 1 5 - 11 2012年01月 
    We analysed the results of radical segmentectomy achieved through a hybrid video-assisted thoracic surgery (VATS) approach that used both direct vision and television monitor visualization at a median follow-up of over 5 years. Between April 2004 and October 2010, 102 consecutive patients able to tolerate lobectomy to treat clinical T1N0M0 non-small cell lung cancer (NSCLC) underwent hybrid VATS segmentectomy in which we used electrocautery without a stapler to divide the intersegmental plane detected by selective jet ventilation in addition to the path of the intersegmental veins. Curative resection was achieved in all patients. The median surgical duration and blood loss during the surgery were 129 min (range, 60-275 min) and 50 ml (range, 10-350 ml), respectively. The complication rate was 9.8% (10/102) with the most frequent being prolonged air leak, and there was no case of in-hospital death or 30-day mortality post procedure. Five and seven patients developed locoregional and distant recurrences, respectively. The overall and disease-free 5-year survival rates were 89.8% and 84.7%, respectively. Radical hybrid VATS segmentectomy including atypical resection of (sub)segments is a useful option for clinical staged NSCLC. The exact identification of anatomical intersegmental plane followed by dissection using electrocautery is critical from oncological and functional perspectives.
  • Yasuhiro Tsutani; Yoshihiro Miyata; Keizo Misumi; Takuhiro Ikeda; Takeshi Mimura; Jun Hihara; Morihito Okada
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 41 7 890 - 896 2011年07月 
    Objective: This study evaluates the prognostic significance of [18F]-fluoro-2-deoxyglucose positron emission tomography/computed tomography findings according to histological subtypes in patients with completely resected non-small cell lung cancer. Methods: We examined 176 consecutive patients who had undergone preoperative [18F]-fluoro-2-deoxyglucose-positron emission tomography/computed tomography imaging and curative surgical resection for adenocarcinoma (n = 132) or squamous cell carcinoma (n 44). Maximum standardized uptake values for the primary lesions in all patients were calculated as the [18F]-fluoro-2-deoxyglucose uptake and the surgical results were analyzed. Results: The median values of maximum standardized uptake value for the primary tumors were 2.60 in patients with adenocarcinoma and 6.95 in patients with squamous cell carcinoma (P < 0.001). Analyses of receiver operating characteristic curves identified an optimal maximum standardized uptake value cutoff value to predict recurrence of 3.7 for adenocarcinoma, whereas such an indicator could not be identified for squamous cell carcinoma. Although 2-year disease-free survival rates were 70.2% for maximum standardized uptake value <= 6.95 and 59.3% for maximum standardized uptake value >6.95 (P = 0.83) among patients with squamous cell carcinoma, 2-year disease-free survival rates were 93.9% for maximum standardized uptake value <= 3.7 and 52.4% for maximum standardized uptake value >3.7 (P, < 0.0001) among those with adenocarcinoma, and notably, 100 and 57.2%, respectively, in patients with Stage I adenocarcinoma (P < 0.0001). On the basis of the multivariate Cox analyses of patients with adenocarcinoma, maximum standardized uptake value (P = 0.008) was a significantly independent factor for disease-free survival as well as nodal metastasis (P = 0.001). Conclusions: Maximum standardized uptake value of the primary tumor was a powerful prognostic determinant for patients with adenocarcinoma, but not with squamous cell carcinoma of the lung.
  • Yasuhiro Tsutani; Yoshinori Yamashita; Keizo Misumi; Takuhiro Ikeda; Yoshihiro Miyata; Morihito Okada
    JOURNAL OF THORACIC ONCOLOGY 6 6 S501 - S501 2011年06月
  • 池田 拓広; 伊富貴 雄太; 津谷 康大; 宮田 義浩; 岡田 守人
    日本外科学会雑誌 112 1 831  一般社団法人日本外科学会 2011年05月
  • 古川 高意; 宮田 義浩; 津谷 康大; 池田 拓広; 櫛谷 桂; 武島 幸男; 井内 康輝; 岡田 守人
    日本外科学会雑誌 112 1 584  一般社団法人日本外科学会 2011年05月
  • 津谷 康大; 伊富貴 雄太; 池田 拓広; 宮田 義浩; 岡田 守人
    日本外科学会雑誌 112 1 363  一般社団法人日本外科学会 2011年05月
  • Y. Tsutani; Y. Ibuki; T. Ikeda; Y. Miyata; H. Nakayama; M. Okada
    JOURNAL OF CLINICAL ONCOLOGY 29 15 2011年05月
  • Y. Tsutani; Y. Miyata; K. Misumi; T. Ikeda; M. Okada
    ANNALS OF ONCOLOGY 21 132 - 132 2010年10月
  • 三村 剛史; 宮田 義浩; 津谷 康大; 沖田 理貴; 川崎 由香里; 櫛谷 桂; 武島 幸男; 井内 康輝; 有廣 光司; 岡田 守人
    肺癌 50 2 130 - 135 特定非営利活動法人 日本肺癌学会 2010年04月 
    目的．悪性胸膜中皮腫（MPM；malignant pleural mesothelioma）の予後不良の一因には早期症例に対する確定診断の難しさが挙げられる．胸腔鏡下胸膜生検が推奨されるが，これでも十分ではない．そこで今回，我々が行ってきた壁側胸膜全層切除を基本とした胸膜生検の有用性について検討した．対象と方法．2007年4月より2009年3月まで施行した胸膜生検症例12例を対象にした．MPMの確定診断後に胸膜肺全摘術を含む開胸手術を行う際，生検部位の合併切除が必須となるため，その皮膚切開予定ライン上に2～3 cmの皮切をおいた．直視下に壁側胸膜外側の胸内筋膜側を露出，2×1 cm大の短冊状に壁側胸膜全層を採取した．術中迅速診断にて十分なサンプルが採取されたか確認，もし十分であるとされなければ，さらに壁側胸膜欠損部から胸腔鏡にて胸腔内を検索，肉眼的に明らかな病変が存在すれば追加切除を考慮した．結果．胸膜生検12例を行い，MPM 8例（4例上皮型，1例二相型，3例肉腫型），胸膜炎4例を診断した．生検に伴う合併症は皆無であった．結論．MPMの確定診断には複数回の胸壁穿刺を回避し，胸膜生検による壁側胸膜の全層切除を基本にすることが重要である．
  • 三村 剛史; 宮田 義浩; 津谷 康大; 沖田 理貴; 川崎 由香里; 櫛谷 桂; 武島 幸男; 井内 康輝; 有廣 光司; 岡田 守人
    肺癌 50 2 130 - 135 The Japan Lung Cancer Society 2010年04月 
    目的．悪性胸膜中皮腫（MPM；malignant pleural mesothelioma）の予後不良の一因には早期症例に対する確定診断の難しさが挙げられる．胸腔鏡下胸膜生検が推奨されるが，これでも十分ではない．そこで今回，我々が行ってきた壁側胸膜全層切除を基本とした胸膜生検の有用性について検討した．対象と方法．2007年4月より2009年3月まで施行した胸膜生検症例12例を対象にした．MPMの確定診断後に胸膜肺全摘術を含む開胸手術を行う際，生検部位の合併切除が必須となるため，その皮膚切開予定ライン上に2～3 cmの皮切をおいた．直視下に壁側胸膜外側の胸内筋膜側を露出，2×1 cm大の短冊状に壁側胸膜全層を採取した．術中迅速診断にて十分なサンプルが採取されたか確認，もし十分であるとされなければ，さらに壁側胸膜欠損部から胸腔鏡にて胸腔内を検索，肉眼的に明らかな病変が存在すれば追加切除を考慮した．結果．胸膜生検12例を行い，MPM 8例（4例上皮型，1例二相型，3例肉腫型），胸膜炎4
  • 宮田 義浩; 津谷 康大; 池田 拓広; 三隅 啓三; 岡田 守人
    日本外科学会雑誌 111 2 211  一般社団法人日本外科学会 2010年03月
  • Y. Tsutani; H. Daisaki; H. Nakayama; S. Okumura; S. Adachi; M. Yoshimura; H. Sakai; K. Otsu; M. Okada
    EJC SUPPLEMENTS 7 2 515 - 515 2009年09月
  • Yasuhiro Tsutani; Masahiro Ohara; Takahisa Suzuki; Kazuhito Minami; Eiji Miyahara; Akira Kameda; Yoshihiro Noso
    ANTICANCER RESEARCH 29 7 2775 - 2779 2009年07月 
    Background: The safety and efficacy of docetaxel plus S-1 combination chemotherapy as a first-line treatment in patients with advanced or recurrent gastric cancer was verified retrospectively. Patients and Methods: Eighteen patients with advanced or recurrent gastric cancer were enrolled. The regimen used was intravenous docetaxel, 40 mg/m(2), on day 1 and oral S-1, 80 mg/m(2)/day, on days 1-14 every three weeks. Results: In total 101 cycles were administered. One and 11 patients achieved complete and partial responses, while six and zero patients showed stable and progressive disease, respectively. The median time to progression (TTP) and median overall survival were 7.0 and 14.3 months, respectively. Neutropenia was the most common grade 314 hematological toxicity. Nausea and stomatitis were the most common grade 3 nonhematological toxicities. No treatment-related death was observed. Conclusion: Docetaxel plus S-1 combination is an active and tolerable regimen as a first-line treatment in patients with advanced or recurrent gastric cancer.
  • Tsutani, Yasuhiro; Yoshida, Kazuhiro; Yoshida, Kazuhiro; Sanada, Yuichi; Oeda, Mamoru; Suzuki, Takahisa; Hihara, Jun; Morihito, Okada
    Molecular Medicine Reports 1 5 713 - 719 2008年12月 
    Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyltransferase (OPRT) are fluoropyrimidine metabolic enzymes which play important roles in the response of cancer patients to chemotherapy. In esophageal cancer, little is known about the relationship between the expression of these enzymes and corresponding clinicopathological features. In the present study, TS, DPD and OPRT expression levels were evaluated in 72 resected esophageal cancer specimens using immuno-histochemistry. The relationship between enzyme expression and clinicopathological features was assessed using Fisher's exact test or the χ2 test (categorical variables), or the Mann-Whitney rank-sum test (continuous variables). Survival curves were calculated using the Kaplan-Meier method, and differences evaluated using the log-rank test. The Cox proportional hazards model was also used. High DPD expression was associated with depth of invasion, nodal status, tumor stage, lymphatic invasion and venous invasion (P<0.001, P=0.004, P<0.001, P=0.006, P=0.038, respectively), as well as with decreased patient survival (P=0.007). In patients receiving adjuvant chemotherapy, low DPD expression did not significantly improve recurrence-free survival. OPRT was particularly expressed in esophageal cancer cells as compared to normal squamous cells. High OPRT expression was associated with depth of invasion and venous invasion (P=0.006, P=0.003, respectively). To conclude, in esophageal cancer DPD expression was associated with tumor progression and prognosis, and OPRT expression was correlated with carcinogenesis and tumor progression.
  • Yasuhiro Tsutani; Kazuhiro Yoshida; Yuichi Sanada; Yoshiyuki Wada; Kazuo Konishi; Masakazu Fukushima; Morthito Okada
    ONCOLOGY REPORTS 20 6 1545 - 1551 2008年12月 
    To elucidate the mechanism of resistance to Introduction 5-fluorouracil (5-FU) in human gastric cancer cells, we established a cell line MKN45/F2R, which acquired 5-FU resistance as a result of continuous exposure to increasing dosages of 5-FU over a year. The cell line showed 157-fold elevated 5-FU resistance compared to the MKN45 human gastric cancer parental cell line. Furthermore, the cells acquired crossresistance to paclitaxel and docetaxel. To identify the mechanism of 5-FU resistance, the expressions of 5-FU metabolic enzymes were examined. Although protein expression and activity of thymidylate synthase and dihydropyrimidine dehydrogenase did not change, orotate phosphoribosyltransferase (OPRT) protein expression and activity significantly decreased in the 5-FU resistant MKN45/F2R cells. Interestingly, expression of proteins related to taxane resistance including P-glycoprotein, class III beta-tubulin and Bc1-2 increased in MKN45/F2R cells. OPRT-knockout MKN45 parent cells using small interfering RNA demonstrated 15.8-fold increased resistance to 5-FU compared to the control cells. However, resistance to paclitaxel and docetaxel was not observed. These results strongly indicate that decreased activity of OPRT plays an important role in the acquired resistance of gastric cancer cells towards 5-FU; however, it does not play a direct role in paclitaxel and docetaxel resistance. Further Studies are now underway to identify genes related to crossresistance to these chemotherapeutic agents.
  • Yasuhiro Tsutani; Kazuhiro Yoshida; Yuichi Sanada; Mamoru Oeda; Takahisa Suzuki; Jun Hihara; Morihito Okada
    MOLECULAR MEDICINE REPORTS 1 5 713 - 719 2008年09月 
    Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyltransferase (OPRT) are fluoropyrimidine metabolic enzymes which play important roles in the response of cancer patients to chemotherapy. In esophageal cancer, little is known about the relationship between the expression of these enzymes and corresponding clinicopathological features. In the present study, TS, DPD and OPRT expression levels were evaluated in 72 resected esophageal cancer specimens using immunohistochemistry. The relationship between enzyme expression and clinicopathological features was assessed using Fisher's exact test or the chi(2) test (categorical variables), or the Mann-Whitney rank-sum test (continuous variables). Survival curves were calculated using the Kaplan-Meier method, and differences evaluated using the log-rank test. The Cox proportional hazards model was also used. High DPD expression was associated with depth of invasion, nodal status, tumor stage, lymphatic invasion and venous invasion (P < 0.001, P=0.004, P < 0.001, P=0.006, P=0.038, respectively), as well as with decreased patient survival (P=0.007). In patients receiving adjuvant chemotherapy, low DPD expression did not significantly improve recurrence-free survival. OPRT was particularly expressed in esophageal cancer cells as compared to normal squamous cells. High OPRT expression was associated with depth of invasion and venous invasion (P=0.006, P=0.003, respectively). To conclude, in esophageal cancer DPD expression was associated with tumor progression and prognosis, and OPRT expression was correlated with carcinogenesis and tumor progression.
  • 津谷 康大; 吉田 和弘; 大原 正裕; 大枝 守; 眞田 雄市; 重松 英郎; 和田 幸之; 鈴木 崇久; 小西 和男; 岡田 守人
    日本外科学会雑誌 109 2 218 - 218 一般社団法人日本外科学会 2008年04月
  • 大原 正裕; 津谷 康大; 南 一仁
    広島医学 61 6 509 - 511 広島医学会 2008年
  • Miyahara Eiji; Tsutani Yasuhiro; Suzuki Takahisa; Minami Kazuhito; Kameda Akira; Noso Yoshihiro
    Gan to kagaku ryoho. Cancer & chemotherapy 35 3 2008年 
    BACKGROUND:Recently, several randomized trials have shown that postoperative adjuvant treatment improves survival among patients with completely resected non-small cell lung cancer (NSCLC). Platinum-based chemotherapy has been reported to be effective for patients with postoperative stage II to IIIA.;PATIENTS AND METHODS:In the present study, 5 patients with completely resected stage IIB and IIIA received carboplatin AUC 4 on day 1 and gemcitabine 1,000 mg/m(2) on days 1 and 8 every 3 weeks for six cycles as adjuvant chemotherapy.;RESULTS:No early or toxic deaths were observed. All patients were administered 6 cycles completely and safely. Three patients had grade 3 neutropenia and three had grade 2 thrombocytopenia. One patient had grade 3 neutropenia on day 8 in the 2nd and 3rd cycle, and the medications were postponed for a week. Non-hematological toxicity including alopecia and neuropathy were not found.;CONCLUSION:In the present study, the combination of carboplatin and gemcitabine has been a safe and feasible regimen in adjuvant therapy for stage II and IIIA NSCLC.
  • Minami Kazuhito; Tsutani Yasuhiro; Suzuki Takahisa; Miyahara Eiji; Kameda Akira; Noso Yoshihiro
    Gan to kagaku ryoho. Cancer & chemotherapy 35 1 2008年 
    :In our hospital, beginning in April 2005, chemotherapy for non-curative advanced or recurrent gastric cancer was integrated, and 9 regimens including 6 combination therapies were prepared. First-line chemotherapy mainly focusing on TS-1 plus docetaxel combination therapy(S-1+DOC)was done. Second-line and subsequent chemotherapy treatments were chosen by the doctor in charge. 78.6% of second-line chemotherapy was monotherapy. Median survival time(MST)since first-line chemotherapy was 15.6 months, and 1-year survival rate since first-line chemotherapy was 65.0%. MST since the start of first-line S-1+DOC was over 16.4 months, and 1-year survival rate since this therapy start was 69.0%. The good results were ascribed to following: 1. good response rate(30.4%), prolonged time to progression(TTP)(6.1 months), and good control against adverse events at first-line chemotherapy; 2. good shift rate of second-line chemotherapy from the first-line one(82.4%); and 3. good disease control rate(78.6%), prolonged TTP(7.0 months), and good control against adverse events at second-line chemotherapy. In patients with peritoneal metastasis, however, despite the prolonged TTP of 8.7 months by first-line chemotherapy, MST since first-line chemotherapy was poor at 11.1 months. Thus, improvement of second-line or subsequent chemotherapy is warranted.
  • 鈴木 崇久; 津谷 康大; 南 一仁
    外科 69 7 855 - 857 南江堂 2007年07月
  • 南 一仁; 鈴木 崇久; 津谷 康大; 宮原 栄治; 亀田 彰; 野宗 義博
    日本消化器外科学会雑誌 40 7 一般社団法人日本消化器外科学会 2007年07月
  • 津谷 康大; 鈴木 崇久; 南 一仁; 宮原 栄治; 亀田 彰; 野宗 義博
    日本消化器外科学会雑誌 40 7 一般社団法人日本消化器外科学会 2007年07月
  • 津谷 康大; 吉田 和弘; 大枝 守; 眞田 雄市; 重松 英朗; 和田 幸之; 鈴木 崇久; 小西 和男
    日本外科学会雑誌 108 2 一般社団法人日本外科学会 2007年03月
  • 重松 英朗; 吉田 和弘; 和田 幸之; 小西 和男; 大枝 守; 津谷 康大; 田辺 和照
    日本外科学会雑誌 108 2 一般社団法人日本外科学会 2007年03月
  • 吉田 和弘; 和田 幸之; 津谷 康大; 大枝 守; 浜井 洋一; 田辺 和照; 檜原 淳
    日本外科学会雑誌 108 2 一般社団法人日本外科学会 2007年03月
  • 南 一仁; 津谷 康大; 鈴木 崇久; 宮原 栄治; 亀田 彰; 野宗 義博
    日本消化器外科学会雑誌 40 11 1775 - 1780 The Japanese Society of Gastroenterological Surgery 2007年 
    症例は58歳の女性, 2005年9月, 胃癌の診断にて胃全摘術およびD2郭清を施行した. 進行度はpT3, pN2, sH0, sP0, pCY0, cM0; fStage IIIBであり, 総合的根治度Bが得られた. 組織型は非充実型低分化腺癌 (por2) であった. 2005年11月より術後補助化学療法としてTS-1100mg/dayを開始した. この治療開始3日目に, 患者は咽頭違和感を自覚した. 患者の口腔内を観察し, 左口蓋扁桃が30mm径に腫大しているのを確認した. 生検にてgroup V (por2) の診断を得, 原発巣の組織型と類似していることより胃癌の左口蓋扁桃転移と診断した. この時点で, CT にて全身検索を施行したが, 他臓器に転移・再発を示唆する所見は認めなかった. TS-1投与開始14日目に完全奏効 (以下, CR) の腫瘍縮小効果が得られ, 2006年6月まで総合効果CRが維持された. 胃癌の口蓋扁桃転移は, 極めて予後が悪く, 患者のquality of life (以下, QOL) 低下が著しい, と報告されている. TS-1投与による胃癌口蓋扁桃転移巣の縮小効果が, 患者に予後の改善および良好なQOLをもたらす
  • 南 一仁; 津谷 康大; 鈴木 崇久; 宮原 栄治; 亀田 彰; 野宗 義博
    日本臨床外科学会雑誌 68 8 2067 - 2071 Japan Surgical Association 2007年 
    術前multi-detector computed tomography (MDCT) のみにて胆嚢十二指腸瘻および胆石イレウスが診断しえた1例を経験した. 症例は86歳, 女性, 認知症を合併. 右下腹痛を主訴として当科受診. 受診時MDCTにて25mm径の胆嚢結石を認めたが, 主訴の原因となる病変は指摘できなかった. 入院後, 症状は軽快していたが4日目に再度臍部痛および嘔吐が出現した. 緊急MDCTを施行したところ, 胆嚢十二指腸瘻および小腸へ落下した胆嚢結石がイレウスを引き起こしている像が得られた. 超高齢で認知症を合併していたためイレウス解除術のみ施行した. MDCTを用いた"胆石イレウス+内胆汁瘻"の診断は, 低侵襲で, 簡単・迅速に施行でき, 胆石イレウスのような急性腹症例を全身状態が良好なうちに一期的根治術 (イレウス解除術+胆嚢摘出術+瘻孔閉鎖術) に導ける可能性があると思われる.
  • Yuichi Sanada; Kazuhiro Yoshida; Masahiro Ohara; Yasuhiro Tsutani
    PATHOLOGY & ONCOLOGY RESEARCH 13 2 105 - 113 2007年 
    The purpose of this study was to clarify the role of orotate phosphoribosyltransferase (OPRT) in the progression of hepatobiliary and pancreatic carcinomas. Representative sections from 8 surgically resected pancreatic carcinomas, 5 gallbladder carcinomas and 19 hepatocellular carcinomas (HCCs) were examined microscopically. Sites of pancreatic intraepithelial neoplasia (PanIN) were counted, and histologic subtypes of invasive ductal carcinoma of the pancreas (IDC) were determined. Gallbladder carcinomas and HCCs were examined histologically, and the subtypes and spread patterns were assessed. Expression of OPRT was examined immunohistochemically. A total of 75 PanINs were identified. Expression of OPRT increased as lesions progressed from early to high-grade PanINs (PanIN-1A and -1B versus PanIN-2 and -3, P=0.0004). Three (37.5%) of the 8 pancreatic IDCs were positive for OPRT. In the remaining 5 cases, OPRT was expressed only in the neoplastic ducts adjacent to PanIN-3s. In gallbladder carcinomas, mucosal neoplastic epithelium showed dense cytoplasmic expression in 4 of the 5 cases, but expression was absent in the deeply invasive lesions. Among HCCs, 15 of the 19 cases were negative for OPRT in the central area of the tumor, but 8 of the 19 cases expressed OPRT in vascularly invasive lesions. Our data suggest that OPRT is involved in early events of pancreatic and gallbladder carcinogenesis and invasion of HCC.
  • Yoshiyuki Wada; Kazuhiro Yoshida; Yasuhiro Tsutani; Hideaki Shigematsu; Mamoru Oeda; Yuichi Sanada; Takahisa Suzuki; Hirozumi Mizuiri; Yoichi Hamai; Kazuaki Tanabe; Kei Ukon; Jun Hihara
    ONCOLOGY REPORTS 17 1 161 - 167 2007年01月 
    Rapid regrowth or recurrent growth of occult cancer cells are often observed after esophagectomy or postoperative complications. In order to clarify the mechanism of such oncological circumstances, we focused on neutrophil elastase (NE), which degrades a broad spectrum of extracellular matrix and cell surface proteins. In the present study, we demonstrated that NE stimulated the growth of all of the five esophageal cell lines (TE-1, -7, -8, -12 and -13) by MTT assay and promoted cell invasion by cell migration assay. Protransforming growth factor-alpha (pro-TGF-alpha) from the cell membrane was released to the culture medium as a mature form after treatment with 5 mu g/ml NE, and it reached the maximum level of 153% compared to the control values at 15 min of treatment in TE-13 cells. The phosphorylation of epidermal growth factor receptor (EGFR) rapidly occurs after treatment with NE and triggered the extracellular signal-regulated kinases 1 and 2 (ERK) signaling pathway. Moreover, NE induced release of platelet-derived growth factor-AA (PDGF-AA), PDGF-BB and vascular endothelial growth factor (VEGF) to 141.9, 227.7, and 171.6% of the control values, respectively. A specific NE inhibitor, sivelestat, significantly inhibited the NE-induced cell proliferation, cell invasion and subsequently inhibited the signal transduction pathway. Furthermore, sivelestat significantly inhibited NE-induced release of TGF-cc, PDGF-AA, PDGF-BB and VEGF in the medium in TE-13 esophageal carcinoma cells. These results strongly indicate that NE released from activated neutrophils stimulates the growth and progression of esophageal cancer cells by releasing the growth factors on the cell surface and that sivelestat, a specific NE inhibitor, blocks these processes. Furthermore, we postulate that postoperative administration of sivelestat might be useful as a new molecular-targeting cancer therapy as well as for the treatment of postoperative respiratory complications.
  • Minami Kazuhito; Kameda Akira; Tsutani Yasuhiro; Suzuki Takahisa; Miyahara Eiji; Noso Yoshihiro
    Gan to kagaku ryoho. Cancer & chemotherapy 34 4 2007年 
    :FOLFOX regimens were administered to 14 patients with unresectable advanced or recurrent colorectal cancer from 1 to 9 cycles (median 5 cycles). In our patient characteristics, 10 patients had previous chemotherapies, 3 patients showed performance status 3. The response rate was 21%, and median time to progression was 5.0 months. Frequency of grade 3/4 adverse effect was 57% in neutropenia, 36% in leucopenia, 36% in thrombocytopenia, and 7% in allergic reaction. Only 64% patients could complete the treatment, for these adverse events brought treatment failure at 3-6 cycles. Median relative dose-intensity was 80-90% during 1-4 cycles, but about 50% after 5 cycles for these adverse events. No patient had grade 3 neurologic toxicity,because no one was administered over 10 cycles. FOLFOX regimens showed good anti-tumor effects but poor tolerability after 5-6 cycles in our patients.
  • 南 一仁; 吉田 和弘; 津谷 康大; 鈴木 崇久; 宮原 栄治; 亀田 彰
    日本臨床外科学会雑誌 = The journal of the Japan Surgical Association 67 11 2599 - 2603 2006年11月
  • 鈴木 崇久; 宮原 栄治; 津谷 康大; 南 一仁; 亀田 彰; 野宗 義博
    日本消化器外科学会雑誌 39 7 一般社団法人日本消化器外科学会 2006年07月
  • 南 一仁; 津谷 康大; 鈴木 崇九; 宮原 栄治; 亀田 彰; 野宗 義博
    日本消化器外科学会雑誌 39 7 一般社団法人日本消化器外科学会 2006年07月
  • 眞田 雄市; 津谷 康大; 小西 和男; 大枝 守; 吉田 和弘
    日本消化器外科学会雑誌 39 7 一般社団法人日本消化器外科学会 2006年07月
  • 大枝 守; 吉田 和弘; 眞田 雄市; 和田 幸之; 津谷 康大; 田辺 和照; 右近 圭; 浜井 洋一
    日本消化器外科学会雑誌 39 7 一般社団法人日本消化器外科学会 2006年07月
  • 津谷 康大; 吉田 和弘; 大枝 守; 眞田 雄市; 重松 英朗; 和田 幸之; 鈴木 崇久; 小西 和男; 檜原 淳
    日本消化器外科学会雑誌 39 7 1039 - 1039 一般社団法人日本消化器外科学会 2006年07月
  • Y Sanada; K Yoshida; K Konishi; M Oeda; M Ohara; Y Tsutani
    ONCOLOGY REPORTS 15 5 1157 - 1161 2006年05月 
    The purpose of this study was to examine the expression pattern of MUC5AC and SOX2 in ampulla of vater adenocarcinoma and evaluate the association between expression of these gastric epithelial markers and the histologic phenotype of ampulla of vater carcinoma. Six surgically resected samples of ampulla of vater adenocarcinoma, including four intestinal type carcinomas and two pancreatobiliary type carcinomas, were studied. We performed immunohistochemistry with a monoclonal antibody against MUC5AC and a polyclonal anti-SOX2 antibody. In two of the four intestinal type carcinomas, MUC5AC and SOX2 were focally expressed in the superficial neoplastic mucosa. However, in the centre of the tumour and in other invasive lesions, including vascular invasive lesions and metastatic lymph nodes, neither MUC5AC nor SOX2 was expressed. In contrast, in both pancreatobiliary type carcinomas, of MUC5AC and SOX2 was maintained or increased in invasive lesions. Our immunohistochemistry data suer-est that MUC5AC and SOX2 are associated with the cc pancreatobiliary phenotype of ampulla of vater carcinoma and involved in later events in carcinogenesis, such as invasion metastasis.
  • 津谷 康大; 久保 義郎; 栗田 啓
    手術 60 5 671 - 675 金原出版 2006年05月
  • Y Sanada; K Yoshida; K Konishi; M Oeda; M Ohara; Y Tsutani
    ONCOLOGY REPORTS 15 5 1157 - 1161 2006年05月 
    The purpose of this study was to examine the expression pattern of MUC5AC and SOX2 in ampulla of vater adenocarcinoma and evaluate the association between expression of these gastric epithelial markers and the histologic phenotype of ampulla of vater carcinoma. Six surgically resected samples of ampulla of vater adenocarcinoma, including four intestinal type carcinomas and two pancreatobiliary type carcinomas, were studied. We performed immunohistochemistry with a monoclonal antibody against MUC5AC and a polyclonal anti-SOX2 antibody. In two of the four intestinal type carcinomas, MUC5AC and SOX2 were focally expressed in the superficial neoplastic mucosa. However, in the centre of the tumour and in other invasive lesions, including vascular invasive lesions and metastatic lymph nodes, neither MUC5AC nor SOX2 was expressed. In contrast, in both pancreatobiliary type carcinomas, of MUC5AC and SOX2 was maintained or increased in invasive lesions. Our immunohistochemistry data suer-est that MUC5AC and SOX2 are associated with the cc pancreatobiliary phenotype of ampulla of vater carcinoma and involved in later events in carcinogenesis, such as invasion metastasis.
  • 小西 和男; 吉田 和弘; 津谷 康大; 重松 英朗; 大枝 守; 眞田 雄市; 和田 幸之; 浜井 洋一; 田辺 和照; 田原 英俊; 安井 弥
    日本外科学会雑誌 107 2 一般社団法人日本外科学会 2006年03月
  • 眞田 雄市; 小西 和男; 大枝 守; 津谷 康大; 吉田 和弘
    日本外科学会雑誌 107 2 512 - 512 一般社団法人日本外科学会 2006年03月
  • Yuichi Sanada; Kazuhiro Yoshida; Masahiro Ohara; Mamoru Oeda; Kazuo Konishi; Yasuhiro Tsutani
    PANCREAS 32 2 164 - 170 2006年03月 
    Objectives: The purpose of this study was to perform histopathologic and immunohistochemical analyses of gastric transcription factor SOX2 and gastric mucin MUC5AC to better understand the stepwise progression of pancreatic carcinoma. Methods: Twenty-eight representative sections from 14 surgically resected pancreatic carcinomas were assessed microscopically. Sites of pancreatic intraepithelial neoplasia (PanIN) were counted, and histologic subtypes of invasive ductal carcinoma (IDC) were determined. The expression of SOX2 and MUC5AC in PanIN and IDC was examined immumohistochemically. Results: One hundred thirty-eight PanINs were identified. In 4 of the 14 cases, gradual transition from PanIN-1A to PanIN-3 was observed in a single duct, suggesting stepwise progression. The expression of MUC5AC increased with the progression of lesions from PanIN-1A to PanIN-3. SOX2 was expressed in only 6 of 107 early PanINs (5.8%). Out of 31 PanIN-3s, 7 were positive (22.6%), and SOX2 protein was localized in the nuclei of cells of the basal epithelium or in the vicinity of luminal necrosis. In addition, SOX2 was frequently and strongly expressed in poorly differentiated (57.1%) and neurally invasive (63.6%) components. Conclusions: The results of our histopathologic examinations suggest that PanIN progresses stepwise to IDC. Immunohistochemistry results suggest that SOX2 is involved in later events of carcinogenesis.
  • 亀田 彰; 津谷 康大; 鈴木 崇久
    広島医学 59 8 664 - 666 広島医学会 2006年
  • 津谷 康大; 久保 義郎; 棚田 稔; 柿下 大一; 沖田 充司; 野崎 功雄; 南 一仁; 青儀 健二郎; 栗田 啓; 高嶋 成光
    日本消化器外科学会雑誌 39 2 232 - 236 The Japanese Society of Gastroenterological Surgery 2006年 
    症例は27歳の男性で, 突然の吐血でショック状態となり搬送された. 初診時Hgb3.8g/dlと高度の貧血を認めた. 腹部CTでは膵頭部に約5cmの嚢胞性病変を認め, また膵体部から尾部にかけ石灰化が存在し, 慢性膵炎の像であった. 入院中突然の下血を認め, 緊急上部消化管内視鏡検査を施行した. 十二指腸下行脚は壁外性の圧排を受け, その中心部は壊死に陥り, 同部位より持続性の出血を認めた. 出血のコントロールは困難であり, 緊急で開腹手術を施行した. 術中所見では膵頭部に嚢胞性腫瘤を認め, 周囲は浮腫状であった. 膵仮性嚢胞の十二指腸穿破による出血と診断し, 膵頭十二指腸切除術を施行した. 病理組織学的検査では膵仮性嚢胞であり主膵管との交通も認めた. 術後経過は良好で, 第18病日に退院した. 膵仮性嚢胞の消化管への穿破はまれであり, 特に十二指腸への穿破の報告は少ないが, 嚢胞が原因となる出血により急激な経過をたどることもあり, 注意が必要と思われた.
  • 津谷 康大; 久保 義郎; 棚田 稔; 柿下 大一; 沖田 充司; 野崎 功雄; 南 一仁; 青儀 健二郎; 栗田 啓; 高嶋 成光
    日本消化器外科学会雑誌 39 2 232 - 236 一般社団法人日本消化器外科学会 2006年 
    症例は27歳の男性で, 突然の吐血でショック状態となり搬送された.初診時Hgb 3.8g/dlと高度の貧血を認めた.腹部CTでは膵頭部に約5cmの嚢胞性病変を認め, また膵体部から尾部にかけ石灰化が存在し, 慢性膵炎の像であった.入院中突然の下血を認め, 緊急上部消化管内視鏡検査を施行した.十二指腸下行脚は壁外性の圧排を受け, その中心部は壊死に陥り, 同部位より持続性の出血を認めた.出血のコントロールは困難であり, 緊急で開腹手術を施行した.術中所見では膵頭部に嚢胞性腫瘤を認め, 周囲は浮腫状であった.膵仮性嚢胞の十二指腸穿破による出血と診断し, 膵頭十二指腸切除術を施行した.病理組織学的検査では膵仮性嚢胞であり主膵管との交通も認めた.術後経過は良好で, 第18病日に退院した.膵仮性嚢胞の消化管への穿破はまれであり, 特に十二指腸への穿破の報告は少ないが, 嚢胞が原因となる出血により急激な経過をたどることもあり, 注意が必要と思われた.
  • Tsutani Yasuhiro; Ohsumi Shozo; Aogi Kenjiro; Taira Naruto; Kataoka Masaaki; Hamamoto Yasushi; Nishimura Rieko; Takashima Shigemitsu
    Breast cancer (Tokyo, Japan) 13 4 374 - 377 2006年 
    :An 80-year-old woman visited our hospital with a massive ulcerated tumor in the upper lateral quadrant of the right breast. Her performance status was 2. Histopathologically, a mass consisting of a huge primary tumor and metastatic axillary lymph nodes was seen and invasive ductal carcinoma was diagnosed. Both estrogen and progesterone receptors were negative. Herceptest (DakoCytomation, Glostrup, Denmark) showed 2 + staining and HER2 amplification was detected by fluorescent in situ hybridization. CT revealed multiple lung metastases. Her old age and performance status of 2 made aggressive chemotherapy difficult. After receiving 5'-DFUR 600 mg/day as the first line treatment for two months, the tumors progressed. As second-line treatment, single agent therapy with a loading dose, a trastuzumab 4 mg/kg followed by 2 mg/kg weekly was recommended. The patient also received 60 Gy radiotherapy. Six months after the second line treatment, the breast tumor disappeared and only a scar remained on the chest wall and axilla. CT showed no lung tumors. During the trastuzumab treatment, no adverse effect was observed. Her performance status improved to zero, and she is alive and free from the disease 24 months after the disappearance of the tumor.
  • 南 一仁; 山口 佳之; 津谷 康大; 鈴木 崇久; 宮原 栄治; 亀田 彰; 野宗 義博
    日本消化器外科学会雑誌 39 9 1523 - 1528 The Japanese Society of Gastroenterological Surgery 2006年 
    5-FU系抗癌剤をベースとした化学療法が奏功した非切除小腸腺癌の1例を経験した. 症例は74歳の女性で, 小腸悪性腫瘍の診断にて開腹手術を施行した. 病変占居部位は空腸, 長軸8cmに及ぶ全周性腫瘍であった. 横行結腸, 横行結腸間膜および胃に直接浸潤しており, 多数の腹膜播種を認めた. 播種結節の病理診断はtubular adenocarcinomaであった. 以上より, 根治性はないと判断しバイパス術のみ施行した. 術後化学療法としてlow dose FP療法, 続いてTS-1療法を施行した. 原発巣を標的病変とした治療効果は, 部分奏功(PR)が得られ, 無増悪生存期間は25か月であった. 有害事象は, low dose FP療法中にはgrade3の口内炎, 皮膚炎, 悪心・嘔吐, 食欲不振, grade2の白血球減少が見られた. 一方, TS-1療法中はgrade 1の白血球減少および皮膚色素沈着以外認めず, 22か月に及ぶ外来治療が継続され, 良好なquality of life (QOL) が維持できた.
  • 吉田和弘; 山口佳之; 檜原淳; 村上茂; 清水克彦; 田辺和照; 右近圭; 浜井洋一; 恵美学; 岡脇誠; 弘中克治; 大枝守; 大下純子; 真田雄一; 重松英朗; 和田幸之; 池田拓広; 大原正裕; 津谷康大; 長嶺一郎; 峠哲哉
    広島医学 58 9 511-519  2005年09月
  • 津谷 康大; 久保 義郎; 南 一仁; 青儀 健二郎; 棚田 稔; 栗田 啓; 高嶋 成光
    日本消化器外科学会雑誌 38 7 一般社団法人日本消化器外科学会 2005年07月
  • 津谷 康大; 栗田 啓; 青儀 健二郎; 久保 義郎; 棚田 稔; 高嶋 成光
    日本臨床外科学会雑誌 = The journal of the Japan Surgical Association 66 6 1328 - 1332 Japan Surgical Association 2005年06月 
    胃軸捻転を伴う食道裂孔ヘルニアに合併した胃癌は非常に稀で,本邦では過去に6例報告されているのみである.若干の文献的考察を加え報告する.症例は73歳,女性.心窩部不快感を主訴に近医受診し,胃癌の診断にて当科へ紹介入院した.上部消化管造影では胃の大部分は縦隔内に存在し,長軸性胃軸捻転を伴い,いわゆるupside down stomachを呈していた.また胃体部に不正形の隆起性病変を認めた.胃内視鏡検査では胃体上部小彎に隆起性病変を認めた.高度の食道裂孔ヘルニアを伴う0 I型早期胃癌の診断にて噴門側胃切除術, D1郭清,空腸間置再建,食道裂孔縫縮術を施行した.最終診断は, Type 0 I, T1 (M), N0, H0, P0, M0, tub2, ly0, v0, fStage I A, 根治度Aであった.術後食道空腸吻合部の縫合不全にて開腹ドレナージ術,裂孔縫縮解除を施行した.その後の経過は良好で,第27病日に軽快退院した.術後1年5カ月の現在愁訴なく外来通院中である.
  • 津谷 康大; 佐伯 俊昭; 青儀 健二郎; 大住 省三; 高嶋 成光
    日本外科学会雑誌 106 0 一般社団法人日本外科学会 2005年04月
  • 津谷 康大; 栗田 啓; 青儀 健二郎; 久保 義郎; 棚田 稔; 高嶋 成光
    日本臨床外科学会雑誌 66 6 1328 - 1332 Japan Surgical Association 2005年 
    胃軸捻転を伴う食道裂孔ヘルニアに合併した胃癌は非常に稀で,本邦では過去に6例報告されているのみである.若干の文献的考察を加え報告する.症例は73歳,女性.心窩部不快感を主訴に近医受診し,胃癌の診断にて当科へ紹介入院した.上部消化管造影では胃の大部分は縦隔内に存在し,長軸性胃軸捻転を伴い,いわゆるupside down stomachを呈していた.また胃体部に不正形の隆起性病変を認めた.胃内視鏡検査では胃体上部小彎に隆起性病変を認めた.高度の食道裂孔ヘルニアを伴う0 I型早期胃癌の診断にて噴門側胃切除術, D1郭清,空腸間置再建,食道裂孔縫縮術を施行した.最終診断は, Type 0 I, T1 (M), N0, H0, P0, M0, tub2, ly0, v0, fStage I A, 根治度Aであった.術後食道空腸吻合部の縫合不全にて開腹ドレナージ術,裂孔縫縮解除を施行した.その後の経過は良好で,第27病日に軽快退院した.術後1年5カ月の現在愁訴なく外来通院中である.
  • Tsutani Yasuhiro; Saeki Toshiaki; Aogi Kenjiro; Ohsumi Shozo; Takashima Shigemitsu
    Gan to kagaku ryoho. Cancer & chemotherapy 32 6 2005年 
    :We evaluated the toxicity of 4 cycles of doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks (AC 60/600) in adjuvant chemotherapy for breast cancer. Between 1994 and 2003, 62 patients received 6 cycles of doxorubicin (40 mg/m2) and cyclophosphamide (500 mg/m2) every 3 weeks (AC 40/500), and 106 patients received AC 60/600 as adjuvant chemotherapy for breast cancer. The performance status of all patients was 0 or 1. Toxicity was determined using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) ver. 2. Grade 3/4 neutropenia was frequent in AC 60/600 (6.5% vs 24.3%, p < 0.001). However, febrile neutropenia was not significant in either group (1.6% vs 3.8%, p = 0.39). There was also no statistical difference in the toxicity greater than grade 3 of anemia, nausea, vomiting, fatigue, diarrhea and cardiotoxicity. There was no treatment-related death in both groups. The number of patients who completed chemotherapy was higher in those receiving AC 60/600 than in those receiving AC 40/500 (91.9% vs 99.1%, p = 0.026). AC 60/600 is tolerated and feasible in adjuvant chemotherapy of breast cancer in Japanese patients from the viewpoint of toxicities.
  • 小森 栄作; 津谷 康大; 澤田 茂樹; 山下 泰弘; 栗田 啓; 藤原 義朗; 別所 昭宏; 新海 哲
    肺癌 44 4 日本肺癌学会 2004年08月
  • 津谷 康大; 青木 秀樹; 原野 雅生; 佐々木 寛; 小野田 正; 塩崎 滋弘; 大野 聡; 二宮 基樹; 高倉 範尚; 瀬口 智子
    日本消化器外科学会雑誌 37 8 1485 - 1490 The Japanese Society of Gastroenterological Surgery 2004年 
    術前化学療法が著効し根治切除しえた大腸内分泌細胞癌を経験したので報告する. 症例は38歳の男性で, 急性心筋梗塞を契機に貧血の精査で十二指腸浸潤を伴う横行結腸原発内分泌細胞癌が発見された. CT上, 右上腹部に認めた腫瘍は急速に増大し腸閉塞となり, 回腸瘻造設による減圧後, 術前化学療法としてCisplatin (CDDP) +CPT-11療法を施行した. CT上腫瘍は完全に消失し, 根治術として結腸右半切除, 胃十二指腸部分切除, 胆嚢摘出術を施行した, 病理組織学的検査では大腸粘膜面にわずかに癌細胞を認めるのみで組織学的効果Grade2であった. 術後もCDDP+CPT-11療法施行後退院し, 1年2か月後の現在無再発生存中である. 大腸内分泌細胞癌は非常に予後不良な疾患で, 外科的切除のみでは限界があると思われるが, 術前化学療法を含めた集学的治療により予後の改善が見込める可能性があると思われた.
  • 桧垣 健二; 津谷 康大; 畝 大; 元木 崇之; 原野 雅生; 佐々木 寛; 小野田 正; 塩崎 滋弘; 二宮 基樹; 高倉 範尚
    日本外科学会雑誌 104 0 574 - 575 一般社団法人日本外科学会 2003年04月
  • 術前診断が困難であった胃外発育型胃平滑筋肉腫の1例
    吉山 知幸; 二宮 基樹; 佐々木 寛; 池田 俊行; 黒田 新士; 窪田 康浩; 畝 大; 藤原 康宏; 津谷 康大; 元木 崇之; 原野 雅生; 青木 秀樹; 小野田 正; 塩崎 滋弘; 大野 聡; 桧垣 健二; 小林 直廣; 高倉 範尚; 河村 譲
    社会保険広島市民病院医誌 19 1 76 - 80 広島市立広島市民病院 2003年03月 
    54歳男.人間ドックの腹部超音波検査により上腹部腫瘤が指摘された.上部消化管造影,上部消化管内視鏡検査,腹部CTにより腹腔内悪性腫瘍が疑われた.血管造影検査を行い,大網あるいは結腸間膜由来の悪性腫瘍を疑い,開腹手術を施行した.腫瘍は横行結腸間膜を圧排するように発育しており,根部は胃角部大彎後壁にあった.胃壁との付着はごく小範囲であり,胃外発育型の比較的稀な胃平滑筋肉腫と考えられた.腫瘍,胃,大網と横行結腸間膜の一部を合併切除した.病理組織学的検査により,Gastrointestinal stromal tumor,smooth muscle type,malignantと診断された.術前診断が困難であったので,文献的考察を加えて報告した
  • 津谷康大; 青木秀樹; 小野田正; 塩崎滋弘; 大野聡; 小林直広; 二宮基樹; 高倉範尚
    日本消化器外科学会雑誌 36 7 一般社団法人日本消化器外科学会 2003年07月
  • 佐々木 寛; 二宮 基樹; 池田 俊行; 藤原 康宏; 津谷 康大; 鵜垣 伸也; 眞田 雄市; 藤本 善三; 元木 崇之; 原野 雅生; 青木 秀樹; 小野田 正; 塩崎 滋弘; 大野 聡; 桧垣 健二; 小林 直広; 高倉 範尚
    日本消化器外科学会雑誌 35 8 一般社団法人日本消化器外科学会 2002年08月

書籍

  • 肺癌 呼吸器疾患診断治療アプローチ
    (担当:共著範囲:)中山書店 2018年01月
  • (担当:共著範囲:)メディカ出版 2018年
  • 高齢者肺癌の実際
    (担当:共著範囲:)医薬ジャーナル社 2016年

講演・口頭発表等

  • 肺原発肉腫様癌における化学療法の有効性および安全性の検討（HOT1201/NEJ024）  [通常講演]
    第61回日本肺癌学会学術集会 2020年11月 日本肺癌学会
  • “リンパ行性転移親和型肺癌 (Ly+pN+)”の臨床病理学的特徴 - 多施設共同データベースを用いた後方視的検討 -  [通常講演]
    第61回日本肺癌学会学術集会 2020年11月 日本肺癌学会
  • 胸部悪性疾患におけるFDG-PET/CTの役割  [招待講演]
    第73回日本胸部外科学会定期学術集会 2020年10月 日本胸部外科学会
  • 解剖学的肺切除（区域切除/葉切除）後の同側再手術としての解剖学的肺切除  [通常講演]
    第37回日本呼吸器外科学会学術集会 2020年09月 日本呼吸器外科学会
  • PET-CTにおけるDeauville criteriaを用いた，原発性肺腺癌の リンパ節転移・悪性度予測  [通常講演]
    第37回日本呼吸器外科学会学術集会 2020年09月 回日本呼吸器外科学会
  • 第８版臨床病期I期非小細胞肺癌における再発高リスク・低リスク分類  [通常講演]
    津谷 康大
    第60回日本肺癌学会学術集会 2019年12月
  • Role of surgery for SCLC  [通常講演]
    Yasuhiro Tsutani
    第60回日本肺癌学会学術集会 2019年12月
  • 間質性肺炎合併肺がんに対する外科的治療  [招待講演]
    津谷 康大
    Kanagawa Lung Cancer Comprehensive Meeting 2019年11月
  • Role of surgery in LD-SCLC  [招待講演]
    Yasuhiro Tsutani
    Korean Association for Lung Cancer 2019 2019年11月
  • HRCTによる再発高リスク臨床病期I期非小細胞肺癌の同定  [通常講演]
    津谷 康大
    第72回日本胸部外科学会定期学術集会 2019年11月
  • Stage I 非小細胞肺癌における術後補助化学療法 〜エビデンスと現在の問題点〜  [招待講演]
    津谷 康大
    Taiho Web Lecture on Lung Cancer 2019年10月
  • Yasuhiro Tsutani
    2019 World Conference on Lung Cancer 2019年09月
  • 肺癌治療における免疫チェックポイント阻害剤の役割  [招待講演]
    津谷 康大
    第113回広島がん治療研究会 2019年08月
  • 悪性胸膜中皮腫に対するNivolumabの使用経験  [招待講演]
    津谷 康大
    オプジーボWEBセミナー 2019年08月
  • 令和時代のがん医療 NEXT#4 〜肺癌〜 呼吸器外科肺葉切除から縮小手術へ  [招待講演]
    津谷 康大
    JCRミッドサマーセミナー2019 2019年07月
  • 病理病期I期非小細胞肺癌 術後補助化学療法について  [招待講演]
    津谷 康大
    広島オンコロジーセミナー2019 2019年06月
  • Adjuvant chemotherapy for pathological stage I non-small cell lung cancer with high-risk factors for recurrence: a multicenter study  [通常講演]
    Yasuhiro Tsutani
    American Society of Clinical Oncology Annual Meeting 2019 2019年06月 CHICAGO
  • Neoadjuvant chemotherapy with bevacizumab for clinical stage II/IIIA non-Sq NSCLC (NAVAL): pathologic response and survival  [通常講演]
    津谷 康大
    第36回日本呼吸器外科学会学術集会 2019年05月
  • Yasuhiro Tsutani
    The Society of Thoracic Surgeons 55th Annual Meeting 2019年01月 San Diego
  • Recurrent pattern after segmentectomyfor peripheral small lung cancer  [通常講演]
    Atsushi Kamigaichi
    第59回日本肺癌学会学術集会 2018年11月
  • 区域切除術における局所再発防止の工夫  [通常講演]
    津谷康大
    第59回日本肺癌学会学術集会 2018年11月
  • Neoadjuvant chemotherapy with bevacizumab followed by surgery for clinical stage II/IIIA non-squamous non-small cell lung cancer: survival results from a phase II feasibility study (NAVAL)  [通常講演]
    Yasuhiro Tsutani
    European Society of Medical Oncology Meeting 2018 2018年10月 Munich European Society of Medical Oncology
  • PROGNOSTIC FACTORS IN RESECTED LUNG MUCINOUS ADENOCARCINOMA: CLINICAL AND PATHOLOGICAL FEATURES  [通常講演]
    Daisuke Ueda
    World Conference on Lung Cancer 2018 2018年09月
  • Prognostic Role of Combined Pulmonary Fibrosis and Emphysema (CPFE) in Patients with Clinical Stage I Lung Cancer  [通常講演]
    Yasuhiro Tsutani
    World Conference on Lung Cancer 2018 2018年09月 Toronto International Association for the Study of Lung Cancer
  • Long-term outcomes after sublobar resection for clinical stage IA lung adenocarcinoma meeting node-negative criteria defined by HRCT and FDG-PET/CT  [通常講演]
    Yasuhiro Tsutani
    American Society of Clinical Oncology 2018 2018年06月 CHICAGO American Society of Clinical Oncology
  • Lobar versus sublobar resection for patients with clinical stage I non-small cell lung cancer with idiopathic pulmonary fibrosis  [通常講演]
    Yasuhiro Tsutani
    第35回日本呼吸器外科学会学術集会 2018年05月
  • Multicenter phase II study of cisplatin, pemetrexed, plus bevacizumab followed by maintenance pemetrexed plus bevacizumab for patients with advanced or recurrent non-squamous non-small cell lung cancer: MAP study  [通常講演]
    2017年11月
  • Segmentectomy versus wedge resection in patients with clinical stage I non-small cell lung cancer who were unfit for lobectomy  [通常講演]
    2017年10月
  • 間質性肺炎合併肺癌の術後呼吸機能に与える術式の役割  [通常講演]
    2017年10月
  • 下葉肺癌における、S6原発と底区原発の予後比較  [通常講演]
    2017年09月
  • 間質性肺炎合併肺癌の長期的な術後呼吸機能変化における術式の影響  [通常講演]
    2017年09月
  • 臨床病期I期非小細胞肺癌に対する消極的縮小手術における区域切除術と楔状切除術の比較  [通常講演]
    2017年09月
  • c-N2 IIIA期非小細胞肺癌に対する治療方針  [通常講演]
    2017年05月
  • 臨床病期IA期非小細胞肺癌に対する治療戦略  [通常講演]
    2017年05月
  • 高齢者臨床病期I期非小細胞肺癌に対する縮小手術の意義  [通常講演]
    2017年04月
  • 肺原発髄外性形質細胞腫の1例  [通常講演]
    第181回広島外科会 2016年02月
  • 病理腫瘍径20mm以下肺腺癌の予後予測におけるLepidic componentの重要性  [通常講演]
    第56回日本肺癌学会定期学術集会 2015年11月
  • 胸膜中皮腫に対する胸膜切除／肺剥皮術後、同側肺内に発症した原発性肺癌の1例．  [通常講演]
    第56回日本肺癌学会学術集会 2015年11月
  • 切除可能臨床病期IIIA期非扁平上皮非小細胞肺癌に対する術前Cisplatin + Pemetrexed + Bevacizumab療法の治療成績  [通常講演]
    第56回日本肺癌学会学術集会 2015年11月
  • 術前肺拡散機能と術後合併症・予後との関連．  [通常講演]
    第56回日本肺癌学会学術集会 2015年11月
  • 悪性胸膜中皮腫に対する胸膜切除／肺剥皮術を用いた治療戦略．  [通常講演]
    第56回日本肺癌学会総会 2015年11月
  • EGFR MUTATION IS PREDICTIVE STATUS FOR RECCURRENCE IN EARLY LUNG ADENOCRCINOMA  [通常講演]
    Third International Joint Meeting on Thoracic Surgery 2015年11月
  • HRCT, FDG-PET/CT所見に基づく小型肺癌の治療戦略.  [通常講演]
    第68回日本胸部外科学会定期学術集会 2015年10月
  • ThopazTMを用いた胸腔内圧測定と手術術式の関係．  [通常講演]
    第68回日本胸部外科学会定期学術集会 2015年10月
  • 多発GGO病変に対する画像診断による治療方針決定．  [通常講演]
    第68回日本胸部外科学会定期学術集会 2015年10月
  • FDG uptake on PET correlates with IASLC/ATS/ERS histologic subtypes and prognosis of clinical stage IA lung adenocarcinoma.  [通常講演]
    The 29th Annual Meeting of the European Association for Cardio-Thoracic Surgery 2015年10月
  • Sublobar resection choice based on HRCT and FDG-PET/CT findings for clinical stage IA non-small cell lung cancer.  [通常講演]
    The 18th European Cancer Congress-40th European Society for Medical Oncology 2015年09月
  • The relationship between the malignancy grade of lung adenocarcinoma with micropapillary pattern and the findings of positron emission tomography.  [通常講演]
    the 25th Anniversary Congress of the World Society of Cardiothoracic Surgeons 2015年09月
  • Association between [18F]-fluoro-2-deoxyglucose uptake and expressions of hypoxia-induced factor 1α and glucose transporter 1 in non-small cell lung cancer.  [通常講演]
    25th WSCTS Annual Meeting and Exhibition 2015年09月
  • Different significance of HRCT and FDG-PET/CT to predict lymph node status between patients with clinical stage IA lung adenocarcinoma and squamous cell carcinoma.  [通常講演]
    The 25th World Society of Cardiothoracic Surgeons Annual Meeting and Exhibition 2015. 2015年09月
  • Completion lobectomy for unanticipated pN1 disease on postoperative pathology after segmentectomy for cT1N0 lung cancer: Prevention of pleural adhesion by using fibrin glue.  [通常講演]
    25th WSCTS anuuaal meeting and exhibition 2015 2015年09月
  • Pathological Second-Predominant Component Predicts Recurrence in Lung Adenocarcinoma.  [通常講演]
    16th WORLD CONFERENCE OF LUNG CANCER 2015年09月
  • Patients with pN0 small non-lepidic predominant invasive adenocarcinoma can be candidates for adjuvant chemotherapy.  [通常講演]
    The 13th Annual Meeting of Japanese Society of Medical Oncology 2015年07月
  • 左肺上葉切除後異時性多発GGO病変に対し２度根治的縮小術を施行した１例  [通常講演]
    第54回日本肺癌学会中国・四国支部会 2015年07月
  • A phase II feasibility study of preoperative chemotherapy with bevacizumab for resectable stage II/IIIA non-squamous non-small cell lung cancer.  [通常講演]
    The 2015 ASCO Annual Meeting 2015年05月

MISC

受賞

  • 2016年05月 日本呼吸器外科学会 日本呼吸器外科学会賞

共同研究・競争的資金等の研究課題

  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2023年09月 -2027年03月 
    代表者 : 宗 淳一; 津谷 康大; 小原 秀太; 須田 健一; 濱田 顕
  • 10,000症例マルチオミクス解析の経験にもとづく、全ゲノム解析の患者還元に関する研究
    国立研究開発法人日本医療研究開発機構：革新的がん医療実用化研究事業
    研究期間 : 2022年04月 -2027年03月
  • 悪性胸膜中皮腫を対象した核酸医薬の反復投与の医師主導治験
    国立研究開発法人日本医療研究開発機構：臨床研究・治験推進研究事業
    研究期間 : 2022年04月 -2026年03月
  • 特発性肺線維症（IPF）合併臨床病期I期非小細胞肺癌に対する肺縮小手術に関するランダム化比較第III相試験
    日本医療研究開発機構：日本医療研究開発機構 革新的がん医療実用化研究事業
    研究期間 : 2020年 -2025年 
    代表者 : 岡田守人
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2021年04月 -2024年03月 
    代表者 : 津谷 康大
     
    悪性胸膜中皮腫に特異的なsmall RNA発現パターンの特定：新規バイオマーカー開発のために2022年3月までに悪性胸膜中皮腫患者43名、健常人34名、肺癌患者53名の治療前血清を用いてsmall RNAを精製した。悪性胸膜中皮腫患者43名と健常人34名small RNAの次世代シークエンサーにより発現パターンを網羅的に解析した。解析した77サンプルのうち20サンプルはannotated read数が少ないことが確認された。このため、両群の比較は全サンプル77例での解析、annotated read数が保たれている57例の2グループでそれぞれ解析を行い、両グループで共通する両群で有意な差を認める26のsmall RNAを同定した。この解析では既知のmicro RNAのみならず、未知のマイクロRNAやtransfer RNAの断片、成熟マイクロRNA（miR）など以外に1塩基の付加や欠失を認めるisomiRも同定可能であリ、実際に解析結果に含まれている。 今後は健常人サンプル13例、肺癌患者53サンプルを追加解析し、悪性胸膜中皮腫に特異的に発現（低発現）するsmall RNAの同定を更に進める予定である。特異的発現パターンは特定のsmall RNAのみならず、複数のsmall RNAの組み合わせパターンであることも想定されるため、その解析には人工知能（AI）を用いる予定である。また次世代シークエンサーで同定されたsmall RNAの発現はRT-PCR法でも確認する予定である。
  • 肺葉切除高リスク臨床病期IA期非小細胞肺癌に対する区域切除と楔状切除のランダム化比較試験
    日本医療研究開発機構：日本医療研究開発機構 革新的がん医療実用化研究事業
    研究期間 : 2021年 -2023年 
    代表者 : 鈴木健司
  • 天然型マイクロRNA補充療法による悪性胸膜中皮腫を対象とした医師主導治験
    日本医療研究開発機構：日本医療研究開発機構 シーズC
    研究期間 : 2021年 -2023年 
    代表者 : 田原栄俊
  • COPD合併患者肺切除における安全な周術期管理の開発：低侵襲経皮血液ガスモニターの有効性に関する前向き観察研究
    ノバルティス ファーマ：2019年度 ノバルティス研究助成
    研究期間 : 2019年 -2019年 
    代表者 : 津谷 康大
  • 日本学術振興会：科学研究費助成事業 研究活動スタート支援
    研究期間 : 2015年08月 -2017年03月 
    代表者 : 津谷 康大
     
    これまでに肺癌細胞株においてはBNPの分泌は確認されていない。次段階として我々は癌細胞のエクソソーム分泌に注目した。エクソソーム中には様々なsmall RNAが含まれている。健常者と肺腺癌患者の血清中small RNAの網羅的解析を次世代シークエンサーを用いて行った。肺腺癌患者において特定のsmall RNAが高発現していることが判明した。また癌患者の血清中に特異的に発現しているこれらのsmall RNAのいくつかは癌患者の血清中エクソソーム、がん細胞株培養上清にも発現していることが明らかとなった。これらのsmall RNAは新たながん診断バイオマーカーとなる可能性がある。
  • 日本学術振興会：科学研究費助成事業 若手研究(B)
    研究期間 : 2015年04月 -2017年03月 
    代表者 : 伊藤 正興; 岡田 守人; 宮田 義浩; 津谷 康大; 三隅 啓三; 岸 直人; 上田 大介; 平野 尚子; 木村 真吾; 入砂 文子; 池田 今日子
     
    現行の肺癌stagingは腫瘍の大きさや転移の有無・場所で規定され、それを参考に治療方針が決まる。肺腺癌治療は分子標的薬剤が広く使われ、使用の可否は特定の遺伝子形態の有無によるが、現行のstagingは遺伝子形態の有無は考慮しない。 本研究では分子標的薬剤使用の指標となる遺伝子形態の発現が、肺癌切除後の再発因子と判明し、さらに次世代シークエンサーによる遺伝子の網羅的解析で原発巣と転移巣に同様に存在すると判明した。 この結果に基づき、遺伝子形態の有無で過去の肺腺癌症例を層別化すると遺伝子形態の有無が再発後の予後に関係しており、特定の遺伝子形態の有無による腺癌の新たな分類方法の提唱に至った。
  • 肺気腫発生メカニズムにおけるnatriuretic peptideの役割
    GSKジャパン：2015年度GSKジャパン研究助成
    研究期間 : 2015年 -2017年 
    代表者 : 津谷 康大
  • Natriuretic peptideを介するCancer autocrine pathwayの臨床応用
    公益財団法人 武田科学振興財団：公益財団法人 武田科学振興財団 2015年度 医学系研究奨励
    研究期間 : 2015年 -2017年 
    代表者 : 津谷 康大
  • 文部科学省：科学研究費助成事業(研究活動スタート支援)
    研究期間 : 2015年 -2016年 
    代表者 : 津谷 康大
  • 抗癌剤耐性獲得細胞株を用いた抗癌剤耐性メカニズムの解明とその臨床応用
    公益財団法人 武田科学振興財団：公益財団法人 武田科学振興財団 2011年度 医学系研究奨励
    研究期間 : 2011年 -2015年 
    代表者 : 津谷 康大
  • 脂肪肉腫に対する新規分子標的剤の開発
    公益財団法人 上原記念生命科学財団：公益財団法人 上原記念生命科学財団海外留学助成金
    研究期間 : 2012年 -2012年 
    代表者 : 津谷康大
  • 日本学術振興会：科学研究費助成事業 若手研究(B)
    研究期間 : 2012年 -2012年 
    代表者 : 津谷 康大
     
    【はじめに】がん治療成績向上には薬剤に対する細胞応答と耐性機序を解明することが重要である.ヒト胃癌細胞のメタボロームを網羅的に解析することにより,5-RIの作用と耐性因子を検討した.【方法と結果】5-FU感受性が異なる2種類のヒト胃癌細胞株に5-FUを曝露したのち経時的に細胞を回収し,メタノール抽出した液体クロマトグラフィー質量分析法(LC-MS)を用いて,細胞内の低分子動態を一斉解析した.ヒト胃癌細胞株の分析結果よりm/z50～1000の範囲で約700(個のピークを検出できたそのうち特定のアミノ酸代謝と脂質代謝は2種の細胞株間で特徴的な動態を示した.これらの代謝を媒介する酵素に対してRT-PCRを行い,発現量を解析した.【考察】メタボローム解析によりヒト胃癌細胞株の5-FU曝露による細胞内応答を追跡することが可能であった5-FUの作用には特定のアミノ酸代謝と脂質代謝が特徴的であり,薬剤耐性に関与していることが示唆された.また、5FU投与によるFANCJタンパクの減少がoxaliplatinの作用を増強させることを胃癌細胞床で確認したこれは5FU耐性株においては確認されなかった。この所見により5m感受性細胞株ではoxaliplatinとの併用効果の可能性があることが示唆された。また、5-FU耐性株においてその代謝酵素OPRTの発現低下が5-FU耐性機構に関与していると考えられたが現在Stage I非小細胞肺癌切除例においてOPRTを含めた5-FU代謝酵素の発現を免疫染色にて検討し、これらの酵素の発現と術後無再発生存斑間との関連を検討中である。OPRT発現と術後補助療法(5-FU系薬剤)の効果に関連性が認められれば今後OPRTの発現の有無により5-FU系薬剤の使用を考慮するというオーダーメード治療が実現する可能性が考えられる。
  • Prognostic value of carcinoembryonic antigen from pleural lavage fluid in non-small cell lung cancer
    内藤記念科学振興財団：内藤記念若手研究者海外派遣助成金 （夏季)
    研究期間 : 2011年 -2011年 
    代表者 : 津谷康大
  • 日本学術振興会：科学研究費助成事業 若手研究(B)
    研究期間 : 2010年 -2011年 
    代表者 : 津谷 康大
     
    ヒト胃癌細胞株、ヒト食道癌細胞株に対する抗癌剤耐性株4種に対しマイクロアレイにて網羅的解析を行い、5-FU, oxaliplatin, CPT-11に関する抗癌剤耐性関連遺伝子を同定した。特にoxalipatinにおいては耐性株にてup regulationしている遺伝子AGR2, MUC4, LGALS7, GJB6, KDM5D、down regulationしている遺伝子FLRT2, SLC25A27, ANKRD20A1, FRG1, SAMD4Aをそれぞれ同定した。
  • 抗癌剤細胞株を用いた薬剤耐性メカニズムの解明―マイクロアレイ、プロテオミクスによる抗癌剤効果予測因子の探索―
    財団法人土谷記念医学振興基金：財団法人土谷記念医学振興基金
    研究期間 : 2010年
  • 小型肺癌に対するリピオドールを用いた術前経気管支鏡的マーキングおよび胸腔鏡補助下肺縮小手術
    財団法人 内視鏡医学研究振興財団：財団法人内視鏡医学研究振興財団 研究助成（Ｂ）
    研究期間 : 2010年

メディア報道

  • ASCO2023 肺癌
    報道 : 2023年07月
    番組・新聞雑誌 : 日経メディカル
    　新聞・雑誌
  • 病院の実力＊大阪編174 肺がん
    報道 : 2022年11月
    番組・新聞雑誌 : 読売新聞
    　新聞・雑誌

その他のリンク

researchmap


Copyright © MEDIA FUSION Co.,Ltd. All rights reserved.