Faculty Profiles - HIGO Hisao

Papers - HIGO Hisao

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Characteristics and prognosis of interstitial pneumonias complicated with pneumomediastinum. International journal

Shojiro Minomo, Toru Arai, Hisao Higo, Taisuke Tsuji, Kazunobu Tachibana, Masanori Akira, Yoshikazu Inoue

Respiratory investigation 58 ( 4 ) 262 - 268 2020.7

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The clinical characteristics and prognostic impact of complication with pneumomediastinum in patients with interstitial pneumonias (IPs) are not well studied due to the relatively limited nature of available reports. The purpose of this study was to clarify the characteristics and prognostic factors of IPs complicated with pneumomediastinum. METHODS: Consecutive patients with IPs complicated with pneumomediastinum detected by computed tomography (CT) between July 1, 2011, and April 30, 2014 were retrospectively reviewed. Clinical data including symptoms associated with pneumomediastinum, laboratory data, lung function tests, treatments, and mortality were collected from medical records. RESULTS: Forty-five patients (25 males, 20 females), including 32 with idiopathic IP (IIPs) and 13 connective tissue disease-associated interstitial lung diseases (CTD-ILDs) were identified. The median age of onset of pneumomediastinum was 72 years (interquartile range [IQR] 68-79 years). The most common symptom associated with occurrence of pneumomediastinum was appearance or worsening of dyspnoea. No specific treatment was performed for most (84%) of the cases. The median period between occurrence and improvement of pneumomediastinum was 29 days (IQR 5-69 days). Multivariate analysis revealed that IIPs and no improvement of pneumomediastinum were associated with poor prognosis. CONCLUSIONS: Patients with IIPs complicated with pneumomediastinum and those without improvement of pneumomediastinum had poor prognosis.

DOI： 10.1016/j.resinv.2020.02.007

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Deterioration of high-resolution computed tomography findings predicts disease progression after initial decline in forced vital capacity in idiopathic pulmonary fibrosis patients treated with pirfenidone. International journal

Hisao Higo, Nobuaki Miyahara, Akihiko Taniguchi, Satoru Senoo, Junko Itano, Hiromi Watanabe, Naohiro Oda, Hiroe Kayatani, Hirohisa Ichikawa, Takuo Shibayama, Kazuhiro Kajimoto, Yasushi Tanimoto, Arihiko Kanehiro, Yoshinobu Maeda, Katsuyuki Kiura

Respiratory investigation 58 ( 3 ) 185 - 189 2020.5

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Pirfenidone suppresses the decline of forced vital capacity (FVC) in patients with idiopathic pulmonary fibrosis (IPF). However, IPF progresses in some patients despite treatment. We analyzed patients with meaningful FVC declines during pirfenidone treatment and explored the factors predictive of disease progression after FVC decline. METHODS: This study was a retrospective, multicenter, observational study conducted by the Okayama Respiratory Disease Study Group. We defined initial decline in %FVC as 5% or greater per 6-month period during pirfenidone treatment. IPF patients who were treated with pirfenidone and experienced an initial decline from December 2008 to September 2017 were enrolled. RESULTS: We analyzed 21 patients with IPF. After the initial decline, 4 (19.0%) patients showed improvement in disease, 11 (52.4%) showed stable disease, and 6 (28.6%) showed progressive disease. There was no significant correlation between %FVC reduction on initial decline and subsequent %FVC change (p = 0.475). Deterioration of high-resolution computed tomography (HRCT) findings on initial decline was observed significantly more often in the progressive versus improved/stable disease groups (100% vs 20.0%, p = 0.009). CONCLUSIONS: We revealed that deterioration of HRCT findings may predict disease progression after the initial decline in %FVC in IPF patients treated with pirfenidone.

DOI： 10.1016/j.resinv.2019.12.007

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Pulmonary lymphangitic carcinomatosis from gallbladder cancer mimicking diffuse alveolar haemorrhage. International journal

Hisao Higo, Noriyuki Suzaki, Takuya Nagata, Taro Togami, Nobuya Ohara, Masaomi Marukawa

Respirology case reports 8 ( 3 ) e00540 2020.4

Language：English

Diagnosis in cases with pulmonary lymphangitic carcinomatosis as a primary manifestation is difficult due to unawareness of the cancer. An 81-year-old man was admitted due to a one-week history of dyspnoea and haemoptysis. Chest computed tomography showed diffuse bilateral ground-grass opacity and partial consolidation. We suspected diffuse alveolar haemorrhage. High-dose methylprednisolone and cyclophosphamide did not improve his condition and he died from respiratory failure. Autopsy revealed pulmonary lymphangitic carcinomatosis of whole lungs and primary gallbladder cancer. We should consider pulmonary lymphangitic carcinomatosis in the differential diagnosis of patients with haemoptysis and diffuse lung opacity of unknown origin.

DOI： 10.1002/rcr2.540

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Successful Re-administration of Osimertinib in Osimertinib-induced Interstitial Lung Disease with an Organizing Pneumonia Pattern: A Case Report and Literature Review.

Junko Itano, Hisao Higo, Kadoaki Ohashi, Go Makimoto, Kazuya Nishii, Katsuyuki Hotta, Nobuaki Miyahara, Yoshinobu Maeda, Katsuyuki Kiura

Internal medicine (Tokyo, Japan) 59 ( 6 ) 823 - 828 2020.3

Language：English Publishing type：Research paper (scientific journal)

Osimertinib is the standard therapy for epidermal-growth-factor-receptor (EGFR)-mutant lung cancers. We herein report a case of osimertinib-induced interstitial lung disease (OsiILD) with an organizing pneumonia (OP) pattern and provide a literature-based review. Six months after osimertinib administration, a 75-year-old woman with right pleural carcinomatosis developed ILD with an OP pattern. After salvage chemotherapy, osimertinib with corticosteroid was successfully re-administered. A literature review suggested that 1) OsiILD with an OP pattern was rare but should be recognized, and 2) re-administration of osimertinib in OsiILD was successful in select patients. A criterion that determines whether a patient would benefit from re-administration is warranted.

DOI： 10.2169/internalmedicine.3689-19

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Nintedanib can be used safely and effectively for idiopathic pulmonary fibrosis with predicted forced vital capacity ≤ 50%: A multi-center retrospective analysis. International journal

Satoru Senoo, Nobuaki Miyahara, Akihiko Taniguchi, Naohiro Oda, Junko Itano, Hisao Higo, Naofumi Hara, Hiromi Watanabe, Hirohisa Kano, Toshimitsu Suwaki, Yasuko Fuchimoto, Kazuhiro Kajimoto, Hirohisa Ichikawa, Kenichiro Kudo, Takuo Shibayama, Yasushi Tanimoto, Shoichi Kuyama, Arihiko Kanehiro, Yoshinobu Maeda, Katsuyuki Kiura

PloS one 15 ( 8 ) e0236935 2020

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Nintedanib is a multi-kinase inhibitor approved for idiopathic pulmonary fibrosis (IPF); however, its efficacy and safety for patients with IPF and restricted pulmonary function remain unclear. Therefore, the objective of this study was to determine the efficacy and safety of nintedanib for patients with IPF and forced vital capacity (FVC) ≤ 50%. METHODS: This was a multi-center retrospective study performed by the Okayama Respiratory Disease Study Group. Patients were allocated into FVC ≤ 50% and FVC > 50% groups based on their predicted FVC. The primary endpoints were FVC changes from baseline after 6 and 12 months. RESULTS: 45 patients were eligible for the study. 18 patients had FVC ≤ 50%, and 27 patients had FVC > 50%. Overall, 31 and 19 patients underwent pulmonary function tests at 6 and 12 months after initiating nintedanib, respectively. FVC changes from baseline at 6 and 12 months after initiating nintedanib were comparable between the two groups. Adverse events were seen in all patients, and the rates of patients who discontinued nintedanib were also comparable (38.9% vs. 37.0%, p = 1.000). Multiple regression analysis showed that age and forced expiratory volume in 1 second (FEV1)/FVC were negatively correlated with changes in FVC at 6 months after initiating nintedanib. CONCLUSIONS: Our data suggest that nintedanib can be a useful agent for IPF patients, including those with a low FVC, and that age and FEV1/FVC are predictive markers for changes in FVC following nintedanib treatment.

DOI： 10.1371/journal.pone.0236935

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Rapid Acquisition of Alectinib Resistance in ALK-Positive Lung Cancer With High Tumor Mutation Burden. International journal

Go Makimoto, Kadoaki Ohashi, Shuta Tomida, Kazuya Nishii, Takehiro Matsubara, Hiroe Kayatani, Hisao Higo, Kiichiro Ninomiya, Akiko Sato, Hiromi Watanabe, Hirohisa Kano, Takashi Ninomiya, Toshio Kubo, Kammei Rai, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Shinichi Toyooka, Minoru Takata, Yoshinobu Maeda, Katsuyuki Kiura

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 14 ( 11 ) 2009 - 2018 2019.11

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: The highly selective ALK receptor tyrosine kinase (ALK) inhibitor alectinib is standard therapy for ALK-positive lung cancers; however, some tumors quickly develop resistance. Here, we investigated the mechanism associated with rapid acquisition of resistance using clinical samples. METHODS: Autopsied samples were obtained from lung, liver, and renal tumors from a 51-year-old male patient with advanced ALK-positive lung cancer who had acquired resistance to alectinib in only 3 months. We established an alectinib-resistant cell line (ABC-14) from pleural effusion and an alectinib/crizotinib-resistant cell line (ABC-17) and patient-derived xenograft (PDX) model from liver tumors. Additionally, we performed next-generation sequencing, direct DNA sequencing, and quantitative real-time reverse transcription polymerase chain reaction. RESULTS: ABC-14 cells harbored no ALK mutations and were sensitive to crizotinib while also exhibiting MNNG HOS transforming gene (MET) gene amplification and amphiregulin overexpression. Additionally, combined treatment with crizotinib/erlotinib inhibited cell growth. ABC-17 and PDX tumors harbored ALK G1202R, and PDX tumors metastasized to multiple organs in vivo, whereas the third-generation ALK-inhibitor, lorlatinib, diminished tumor growth in vitro and in vivo. Next-generation sequencing indicated high tumor mutation burden and heterogeneous tumor evolution. The autopsied lung tumors harbored ALK G1202R (c. 3604 G>A) and the right renal metastasis harbored ALK G1202R (c. 3604 G>C); the mutation thus comprised different codon changes. CONCLUSIONS: High tumor mutation burden and heterogeneous tumor evolution might be responsible for rapid acquisition of alectinib resistance. Timely lorlatinib administration or combined therapy with an ALK inhibitor and other receptor tyrosine-kinase inhibitors might constitute a potent strategy.

DOI： 10.1016/j.jtho.2019.07.017

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EGFR-TKI acquired resistance in lung cancers harboring EGFR mutations in immunocompetent C57BL/6J mice. International journal

Hisao Higo, Kadoaki Ohashi, Go Makimoto, Kazuya Nishii, Kenichiro Kudo, Hiroe Kayatani, Hiromi Watanabe, Hirohisa Kano, Kiichiro Ninomiya, Katsuyuki Hotta, Yoshinobu Maeda, Katsuyuki Kiura

Lung cancer (Amsterdam, Netherlands) 136 86 - 93 2019.10

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: Lung cancers harboring epidermal growth factor receptor (EGFR) mutations inevitably develop resistance to EGFR tyrosine-kinase inhibitors (EGFR-TKIs). Therefore, we sought to establish clinically relevant lung-cancer mouse models to achieve deep remission of cancers. MATERIALS AND METHODS: We previously established two transgenic lung-cancer mouse models harboring human EGFR exon 21 L858R substitution (hLR) and mouse Egfr exon 19 deletion (mDEL) in the C57BL/6 J background. Lung tumors from these two transgenic mouse strains were transplanted subcutaneously into BALB/c-nunu mice or C57BL/6 J mice. RESULTS: The transplanted tumors developed the ability to grow on the subcutaneous tissue, peritoneum, or lung of C57BL/6 J mice. While hLR tumors could grow only in C57BL/6 J mice carrying the transgene, mDEL tumors could grow in wild-type C57BL/6 J mice. The tumors maintained EGFR-dependency, and, thus, the EGFR-TKI gefitinib inhibited tumor growth; however, similar to human lung cancers, hLR and mDEL tumors acquired resistance in 60 and 200 days, respectively, following gefitinib administration. Secondary EGFR T790 M mutation in hLR tumors and secondary Egfr T792I mutation in mDEL tumors developed; however, no MET activation was detected. Accordingly, the third-generation EGFR-TKI osimertinib effectively inhibited gefitinib-resistant tumors in vivo. Furthermore, gefitinib-resistant tumors developed resistance to osimertinib in 100 days. CONCLUSION: These syngeneic lung-cancer mouse models harboring EGFR mutations are suitable for studying the drug-resistance mechanisms and the role of the tumor microenvironment. Further investigation with these mouse models is warranted for developing next-generation treatment strategies for lung cancer.

DOI： 10.1016/j.lungcan.2019.08.019

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Cause of pleuroparenchymal fibroelastosis following allogeneic hematopoietic stem cell transplantation. International journal

Hisao Higo, Nobuaki Miyahara, Akihiko Taniguchi, Yoshinobu Maeda, Katsuyuki Kiura

Respiratory investigation 57 ( 4 ) 321 - 324 2019.7

Language：English Publishing type：Research paper (scientific journal)

Late-onset noninfectious pulmonary complications (LONIPCs) are life-threatening complications after hematopoietic stem cell transplantation (HSCT). Pleuroparenchymal fibroelastosis (PPFE) is a LONIPC, but its etiology remains elusive. Chronic graft-versus-host disease (cGVHD) and alkylating agents used for conditioning have been considered possible causes of PPFE. Therefore, to investigate the primary cause of PPFE in allogeneic HSCT, we compared three secondary PPFE groups, namely, the post-lung-transplantation, post-autologous-HSCT or chemotherapy-alone, and post-allogeneic-HSCT groups, and focused on the coexistence of bronchiolitis obliterans (BO), a typical phenotype of cGVHD. We found a trend towards higher rates of PPFE with BO in the post-allogeneic-HSCT and post-lung-transplantation groups (71% and 90%, respectively) than in the post-autologous-HSCT or chemotherapy-alone group (25%). The incidence of BO following allogeneic HSCT is reportedly <10%. If PPFE in the post-allogeneic-HSCT group has no association with BO and is induced by alkylating agents rather than cGVHD, the incidence of BO in PPFE in this group is estimated to be <10%, which is inconsistent with our data (71%). Thus, this study suggests that PPFE following allogeneic HSCT could be mainly induced by cGVHD because the majority of cases are associated with BO, a typical phenotype of cGVHD.

DOI： 10.1016/j.resinv.2019.04.003

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Chemoradiotherapy for locally advanced lung cancer patients with interstitial lung abnormalities. International journal

Hisao Higo, Toshio Kubo, Satoko Makimoto, Go Makimoto, Hiroki Ihara, Yoshihisa Masaoka, Takashi Ninomiya, Eiki Ichihara, Kadoaki Ohashi, Akiko Sato, Katsuyuki Hotta, Masahiro Tabata, Nagio Takigawa, Yoshinobu Maeda, Katsuyuki Kiura

Japanese journal of clinical oncology 49 ( 5 ) 458 - 464 2019.5

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Although chemoradiotherapy for locally advanced lung cancer has the potential for cure, treatment is avoided in patients with interstitial lung disease because of the risk for severe radiation pneumonitis. Interstitial lung abnormalities (ILA) can be evaluated using high-resolution computed tomography (HRCT) to assess interstitial changes. In this study, we retrospectively examined the feasibility and efficacy of chemoradiotherapy for locally advanced lung cancer patients with ILA. METHODS: Patients who underwent chemoradiotherapy for locally advanced lung cancer at Okayama University Hospital between 2012 and 2015 were reviewed retrospectively. HRCT prior to treatment was evaluated by one pulmonologist and two radiologists using a sequential reading method. RESULTS: Of the 77 patients enrolled in this study, ILA was present in 25 (32.5%) and indeterminate ILA in 24 patients; 28 patients did not have ILA. Desaturation at rest (SpO2 < 95%) and honeycombing on HRCT were not observed in ILA patients. Only one patient with ILA had a low vital capacity (%VC < 80%). Severe radiation pneumonitis (≥Grade 2) occurred in 36.0% of the patients with ILA, but it was controllable; Grade 4 or 5 was not observed. Multivariate analysis showed that >25% of the lung volume receiving >20 Gy was risk factors of severe radiation pneumonitis, but ILA was not. The 2-year survival rates of patients with and without ILA were 56.8% and 74.1%, respectively, but the difference was not significant (P = 0.33). CONCLUSIONS: Chemoradiotherapy was feasible and effective in some patient population with ILA without desaturation, low VC and honeycombing on HRCT.

DOI： 10.1093/jjco/hyz016

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Lung transplant candidates with idiopathic pulmonary fibrosis and long-term pirfenidone therapy: Treatment feasibility influences waitlist survival. International journal

Shin Tanaka, Kentaroh Miyoshi, Hisao Higo, Takeshi Kurosaki, Shinji Otani, Seiichiro Sugimoto, Masaomi Yamane, Katsuyuki Kiura, Shinichi Toyooka, Takahiro Oto

Respiratory investigation 57 ( 2 ) 165 - 171 2019.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronically progressive lung disease with exceptionally poor prognosis. While lung transplantation (LTx) is considered the last-resort therapeutic option, dismal waitlist mortality still hampers the salvage of patients with IPF. Pirfenidone, originally designed for IPF treatment, has increasingly been utilized. This study aimed to evaluate whether Pirfenidone could influence outcomes of patients with IPF on the Japanese LTx waitlist. METHODS: This retrospective single-center cohort study included 25 consecutive patients with IPF who were registered as LTx candidates at our institution between July 1999 and August 2016. Patients with a history of pretransplant Pirfenidone therapy (Pirfenidone group) were compared with those with no history (non-Pirfenidone group). RESULTS: In total, 6 (24%) patients received Pirfenidone as pretransplant therapy for 45.2 (range, 18.6-66.8) months. During the treatment period, the Pirfenidone group achieved a significant reduction in the decline rate of the forced vital capacity (-6.2% vs. -0.3%, p = 0.04) and a lower lung allocation score (31 vs. 41, p = 0.013) compared with the non-Pirfenidone group. The Pirfenidone group exhibited 100% waitlist survival three years after registration that was comparable to other indications, and 66% of the patients were still alive at the time of organ availability. No patient in the Pirfenidone group developed Pirfenidone-related surgical complications postoperatively. CONCLUSIONS: Patients with IPF successfully managed with long-term Pirfenidone therapy achieved favorable outcomes after LTx registration, comparable to other patients with LTx indications. The tolerability to antifibrotic therapy can be a predictor of waitlist survival.

DOI： 10.1016/j.resinv.2018.12.002

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MET or NRAS amplification is an acquired resistance mechanism to the third-generation EGFR inhibitor naquotinib. International journal

Kiichiro Ninomiya, Kadoaki Ohashi, Go Makimoto, Shuta Tomida, Hisao Higo, Hiroe Kayatani, Takashi Ninomiya, Toshio Kubo, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura

Scientific reports 8 ( 1 ) 1955 - 1955 2018.1

Language：English Publishing type：Research paper (scientific journal)

As a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), osimeritnib is the standard treatment for patients with non-small cell lung cancer harboring the EGFR T790M mutation; however, acquired resistance inevitably develops. Therefore, a next-generation treatment strategy is warranted in the osimertinib era. We investigated the mechanism of resistance to a novel EGFR-TKI, naquotinib, with the goal of developing a novel treatment strategy. We established multiple naquotinib-resistant cell lines or osimertinib-resistant cells, two of which were derived from EGFR-TKI-naïve cells; the others were derived from gefitinib- or afatinib-resistant cells harboring EGFR T790M. We comprehensively analyzed the RNA kinome sequence, but no universal gene alterations were detected in naquotinib-resistant cells. Neuroblastoma RAS viral oncogene homolog (NRAS) amplification was detected in naquotinib-resistant cells derived from gefitinib-resistant cells. The combination therapy of MEK inhibitors and naquotinib exhibited a highly beneficial effect in resistant cells with NRAS amplification, but the combination of MEK inhibitors and osimertinib had limited effects on naquotinib-resistant cells. Moreover, the combination of MEK inhibitors and naquotinib inhibited the growth of osimertinib-resistant cells, while the combination of MEK inhibitors and osimertinib had little effect on osimertinib-resistant cells. Clinical assessment of this novel combination (MEK inhibitors and naquotinib) is worth considering in osimertinib-resistant lung tumors.

DOI： 10.1038/s41598-018-20326-z

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Clinical characteristics of Japanese candidates for lung transplant for interstitial lung disease and risk factors for early death while on the waiting list. International journal

Hisao Higo, Takeshi Kurosaki, Eiki Ichihara, Toshio Kubo, Kentaroh Miyoshi, Shinji Otani, Seiichiro Sugimoto, Masaomi Yamane, Nobuaki Miyahara, Katsuyuki Kiura, Shinichiro Miyoshi, Takahiro Oto

Respiratory investigation 55 ( 4 ) 264 - 269 2017.7

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Lung transplants have produced very favorable outcomes for patients with interstitial lung disease (ILD) in Japan. However, because of the severe donor lung shortage, patients must wait approximately 2.5 years before they can undergo transplantation and many candidates die before allocation. We reveal the clinical characteristics of Japanese patients with ILD who are candidates for lung transplants and the risk factors for early death while on the waiting list. METHODS: We retrospectively reviewed the clinical data of patients registered in the Japan Organ Transplant Network from Okayama University Hospital who are candidates for cadaveric lung transplants for ILD between 1999 and 2015. RESULTS: Fifty-three patients with ILD were included (24 patients with idiopathic pulmonary fibrosis and 29 others). They had severe pulmonary dysfunction and low exercise tolerability. The median waiting time for transplantation was 462 days, and 22 patients died before allocation. Patients who died before 462 days without undergoing transplantation had more severe dyspnea, shorter 6-minute walk distance (6MWD), and lower performance status than those who waited ≥462 days. CONCLUSIONS: Japanese candidates for cadaveric lung transplants for ILD have severe pulmonary dysfunction. Severe dyspnea, short 6MWD, and low performance status are risk factors for early death while on the waiting list.

DOI： 10.1016/j.resinv.2017.03.002

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Triplet therapy with afatinib, cetuximab, and bevacizumab induces deep remission in lung cancer cells harboring EGFR T790M in vivo. International journal

Kenichiro Kudo, Kadoaki Ohashi, Go Makimoto, Hisao Higo, Yuka Kato, Hiroe Kayatani, Yasuko Kurata, Yoichiro Takami, Daisuke Minami, Takashi Ninomiya, Toshio Kubo, Eiki Ichihara, Akiko Sato, Katsuyuki Hotta, Tadashi Yoshino, Mitsune Tanimoto, Katsuyuki Kiura

Molecular oncology 11 ( 6 ) 670 - 681 2017.6

Language：English Publishing type：Research paper (scientific journal)

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the treatment strategy for EGFR-mutant lung cancers; however, resistance usually occurs due to a secondary mutation, T790M, in EGFR. Combination therapy using afatinib and cetuximab has had good results in lung tumors harboring EGFRT790M mutations in clinical trials. The effect of bevacizumab, an antivascular endothelial growth factor (VEGF) antibody, combined with EGFR-TKIs has also been investigated. We hypothesized that the dose of afatinib and cetuximab could be reduced by combination with bevacizumab and that the triplet therapy may result in better tumor inhibition with tolerable toxicity. Using a xenograft mouse model with H1975-harboring EGFRL858R+T790M and RPC-9-harboring EGFR19DEL+T790M , we tested the efficacy of the triplet therapy with a modified dose of afatinib, cetuximab, and bevacizumab, and compared this therapy to single and double therapies. Triplet therapy with afatinib, cetuximab, and bevacizumab induced pathological complete remission in xenograft tumors with H1975 and RPC-9 cells versus tumors treated with single or double therapies. We saw no body weight loss in the mice. The triple therapy induced a significant reduction in CD31-positive vascular endothelial cells and increased cleaved caspase-3-positive cells in the tumors. This suggests that one mechanism underlying the deep remission could be suppression of neovascularization and induction of apoptosis by intensive inhibition of driver oncoproteins and VEGF. These results highlight the potential of afatinib, cetuximab, and bevacizumab to induce deep remission in tumors harboring EGFRT790M mutations. Therefore, clinical trials of this combination therapy are warranted.

DOI： 10.1002/1878-0261.12063

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ガイドシース併用気管支腔内超音波断層法の肺癌診断への導入効果

南大輔, 瀧川奈義夫, 二宮貴一朗, 小田尚廣, 豊田容輔, 槙本剛, 肥後寿夫, 久保寿夫, 大橋圭明, 佐藤晃子, 堀田勝幸, 宮原信明, 金廣有彦, 田端雅弘, 谷本光音, 木浦勝行

肺癌 54 ( 5 ) 534 - 534 2014.10

Diffuse parenchymal pulmonary amyloidosis showing an objective response to bortezomib-based chemotherapy.

Hisao Higo, Keiichi Fujiwara, Hiromi Watanabe, Go Makimoto, Nobuhisa Kameyama, Mizuho Matsushita, Kammei Rai, Ken Sato, Tomoko Inomata, Kazutaka Sunami, Takuo Shibayama

Internal medicine (Tokyo, Japan) 53 ( 16 ) 1809 - 12 2014

Language：English Publishing type：Research paper (scientific journal)

A 77-year-old woman was admitted because of bilateral hand numbness and dyspnea on exertion. Her serum IgG was increased, and a bone marrow aspiration analysis supported a diagnosis of multiple myeloma. Additionally, computed tomography scans of the chest showed bilateral ground glass attenuations, linear opacities, and consolidations. Transbronchial lung biopsy revealed Congo Red-positive amorphous eosinophilic deposits. She was therefore diagnosed with diffuse parenchymal pulmonary amyloidosis accompanied by multiple myeloma. Following combination chemotherapy including bortezomib, her serum monoclonal protein levels were normalized, and pulmonary function and oxygenation improved.

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脊髄横断症状にて発症した原発性肺癌症例の検討

時政雄平, 松尾潔, 槇本剛, 肥後寿夫, 亀山伸久, 松下瑞穂, 佐藤賢, 藤原慶一, 米井敏郎, 佐藤利雄

日本呼吸器学会誌 2 ( 4 ) 321 - 326 2013.7

高周波スネアにて切除した気管原発MALTリンパ腫の1例

太田徹, 松尾潔, 槇本剛, 肥後寿夫, 時政雄平, 亀山伸久, 萱谷紘枝, 松下瑞穂, 佐藤賢, 藤原慶一, 米井敏郎, 佐藤利雄

呼吸と循環 61 ( 4 ) 379 - 382 2013.4

A case of tracheal mucosa-associated lymphoid tissue lymphoma successfully treated using a high-frequency electrosurgical snare

Toru Ota, Kiyoshi Matsuo, Gou Makimoto, Hisao Higo, Yuhei Tokimasa, Nobuhisa Kameyama, Hiroe Kayatani, Mizuho Matsushita, Ken Sato, Keiichi Fujiwara, Toshiro Yonei, Toshio Sato

Respiration and Circulation 61 ( 4 ) 379 - 382 2013.4

胸腺カルチノイド5例の臨床的検討

肥後寿夫, 松尾潔, 槇本剛, 亀山伸久, 時政雄平, 佐藤賢, 藤原慶一, 米井敏郎, 佐藤利雄

肺癌 52 ( 5 ) 781 - 781 2012.10

当院における進行非小細胞肺癌に対するBevacizumabの使用経験

亀山伸久, 藤原慶一, 槇本剛, 時政雄平, 肥後寿夫, 松下瑞穂, 佐藤賢, 米井敏郎, 佐藤利雄

肺癌 52 ( 5 ) 553 - 553 2012.10

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Papers - HIGO Hisao