Faculty Profiles - TOYOOKA Shinichi

【胸壁・横隔膜の手術-その1】診断胸壁原発脂肪肉腫におけるFDG PET/CTの有用性

山本治慎, 杉本誠一郎, 三好健太郎, 山本寛斉, 宗淳一, 山根正修, 豊岡伸一, 大藤剛宏, 三好新一郎

胸部外科 67 ( 1 ) 4 - 8 2014.1

Language：Japanese Publisher：(株)南江堂

76歳男性。増大する右胸壁腫瘤と右上肢のしびれ、脱力感を主訴に近医を受診、精査にて右大小胸筋や鎖骨下動静脈を背側から圧排する10cm大の腫瘤を指摘された。今回、穿刺吸引細胞診にて多形性細胞肉腫の診断にて精査加療目的で著者らの施設へ紹介となった。胸部造影CTでは右胸壁の胸郭出口に10cm大の腫瘍が存在しており、内部は不均一で脂肪成分を含み、右鎖骨下動静脈を背側から圧排するも、右腕神経叢や骨性胸郭への明らかな浸潤は認められなかった。PET/CTでは腫瘍内部にはFDGの高集積がみられたが辺縁部は低集積であり、遠隔臓器転移は認められなかった。以上、これらの所見より、本症例は右胸壁原発脂肪肉腫が疑われ、治療は腫瘍辺縁部が低悪性度のため浸潤や癒着は軽度と予測して腫瘍摘出術が施行された。その結果、摘出標本は11.4×6.3×8.8cm大で、被膜に覆われ黄白色調であり、内部は充実性で一部に出血が認められた。また、病理組織学的所見では腫瘍の辺縁部には高分化型脂肪肉腫の増殖がみられ、腫瘍内部では多形性を示す異型性の強い細胞が出血・壊死を伴って増殖し、脱分化型脂肪肉腫と診断された。尚、術後1年でPETにて右腕神経叢腹側にFDGの高集積を認め腫瘍の局所再発と診断され、広範囲切除術が計画されたが、患者の意思により目下は近医にて放射線治療の施行中である。

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J00349&link_issn=&doc_id=20131225140001&doc_link_id=40019920853&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F40019920853&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

[The role of 18F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) in liposarcoma of the chest wall]. Reviewed

Yamamoto H, Sugimoto S, Miyoshi K, Yamamoto H, Soh J, Yamane M, Toyooka S, Oto T, Miyoshi S

Kyobu geka. The Japanese journal of thoracic surgery 67 ( 1 ) 4 - 8 2014.1

Surgical Resection of a Massive Primary Mediastinal Liposarcoma Using Clamshell Incision Combined with Lower Median Sternotomy: Report of a Case Reviewed

Yutaka Hirano, Hiromasa Yamamoto, Koichi Ichimura, Shinichi Toyooka, Shinichiro Miyoshi

ANNALS OF THORACIC AND CARDIOVASCULAR SURGERY 20 606 - 608 2014

Language：English Publishing type：Research paper (scientific journal) Publisher：MEDICAL TRIBUNE INC

We experienced a case of massive mediastinal liposarcoma expanding to the bilateral pleural cavities. Preoperative positron emission tomography-computed tomography scan showed that the uptake of F-18-fluorodeoxyglucose (FDG) into the tumor was slight for its size. Clamshell incision together with lower median sternotomy provided the excellent visualization and the complete resection of the tumor. The surgical resection should be performed even for a massive liposarcoma, especially if the uptake of F-FDG into the tumor is low, as complete surgical resection is the only definitive treatment for liposarcoma.

DOI： 10.5761/atcs.cr.13.02263

Density of Tumor-Infiltrating FOXP3+T Cells as a Response Marker for Induction Chemoradiotherapy and a Potential Prognostic Factor in Patients Treated with Trimodality Therapy for Locally Advanced Non-Small Cell Lung Cancer Reviewed

Hiroyuki Tao, Kazuhiko Shien, Junichi Soh, Eisuke Matsuda, Shinichi Toyooka, Kazunori Okabe, Shinichiro Miyoshi

ANNALS OF THORACIC AND CARDIOVASCULAR SURGERY 20 ( 6 ) 980 - 986 2014

Language：English Publishing type：Research paper (scientific journal) Publisher：MEDICAL TRIBUNE INC

Purpose: To examine the relationship between the density of tumor-infiltrating T cell sub-populations and the pathological response to induction chemoradiotherapy (CRT) in patients with locally advanced NSCLC, and to assess the impact of T cell density on patient prognosis.
Methods: A total of 64 patients with c-stages IIA-IIIB NSCLC who underwent induction CRT followed by R0 surgery were enrolled. Tumor-infiltrating T cells expressing either FOXP3 or CD8 were detected by immunohistochemical staining.
Results: Mean numbers of tumor-infiltrating FOXP3+ T cells were 39.9 for patients with minor pathological responses (n = 9), 18.4 for those with major pathological responses (n = 25), and 12.9 for those with complete pathological responses (n = 30; P < 0.001). The number of CD8+ T cells was not associated with pathological responses. Patients with lower FOXP3+ T cell densities showed better survival, although the difference was not statistically significant.
Conclusion: Our study demonstrated that the density of tumor-infiltrating FOXP3+ T cells indicated the degree of response for induction CRT and prognosis in patients treated with trimodality therapy for locally advanced NSCLC, suggesting that FOXP3+ T cells may be target for adjunct immunotherapy.

DOI： 10.5761/atcs.oa.13-00237

Thoracoscopic Lobectomy as Salvage Surgery for Local Recurrence of Non-Small Cell Lung Cancer after Carbon Ion Radiotherapy in an Initially Operable Patient Reviewed

Seiichiro Sugimoto, Shinichi Toyooka, Ken Suzawa, Kouichi Ichimura, Osamu Fujii, Shinichiro Miyoshi

ANNALS OF THORACIC AND CARDIOVASCULAR SURGERY 20 501 - 504 2014

Language：English Publishing type：Research paper (scientific journal) Publisher：MEDICAL TRIBUNE INC

Carbon ion radiotherapy (CIRT) for patients with early-stage non-small cell lung cancer (NSCLC) has recently provided favorable local control with very few toxic reactions. Because CIRT for NSCLC has been mostly performed for elderly or inoperable patients, salvage surgery for NSCLC after CIRT has rarely been reported. We describe a case of complete thoracoscopic right upper lobectomy with mediastinal lymphadenectomy performed as salvage surgery for local recurrence of stage IA NSCLC after CIRT in an initially operable patient who had refused surgery 27 months previously. Pleural adhesions caused by CIRT were localized to the pulmonary apex and the central pulmonary structures were intact at the time of the salvage surgery, which allowed us to successfully perform thoracoscopic lobectomy without any complications. Thus, salvage surgery for NSCLC after CIRT may be feasible in an initially operable patient, as CIRT appears to be unlikely to cause any difficulties in the salvage surgery.

DOI： 10.5761/atcs.cr.13-00223

Adult Mesenchymal Hamartoma of the Chest Wall: Report of a Case Reviewed

Hiromasa Yamamoto, Junichi Soh, Koichi Ichimura, Yusuke Konishi, Shinichi Toyooka, Takayuki Nojima, Shinichiro Miyoshi

ANNALS OF THORACIC AND CARDIOVASCULAR SURGERY 20 663 - 665 2014

Language：English Publishing type：Research paper (scientific journal) Publisher：MEDICAL TRIBUNE INC

We present an adult case of the chest wall tumor, which was accidentally pointed out by a medical checkup. Surgical resection was performed for the tumor, as preoperative biopsy of the tumor suggested the possibility of malignancy. Postoperative pathological examination revealed the diagnosis of mesenchymal hamartoma of the chest wall, which usually occurs in early infancy and childhood. Immunohistochemical staining for Sox9 was positive for chondrocytes and partially positive for spindle tumor cells. It is considered that the present case was not pointed out until the patient became an adult, because the tumor was relatively small and thus asymptomatic.

DOI： 10.5761/atcs.cr.13-00225

The degree of microRNA-34b/c methylation in serum-circulating DNA is associated with malignant pleural mesothelioma Reviewed

Takayuki Muraoka, Junichi Soh, Shinichi Toyooka, Keisuke Aoe, Nobukazu Fujimoto, Shinsuke Hashida, Yuho Maki, Norimitsu Tanaka, Kazuhiko Shien, Masashi Furukawa, Hiromasa Yamamoto, Hiroaki Asano, Kazunori Tsukuda, Takumi Kishimoto, Takemi Otsuki, Shinichiro Miyoshi

LUNG CANCER 82 ( 3 ) 485 - 490 2013.12

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

Objectives: Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. microRNA-34b/c (miR-34b/c), which plays an important role in the pathogenesis of MPM, is frequently downregulated by DNA methylation in approximately 90% of MPM cases. In this study, we estimated the degree of miR-34b/c methylation in serum-circulating DNA using a digital methylation specific PCR assay (MSP).
Materials and methods: A real-time MSP assay was performed using the SYBR Green method. The melting temperature (Tm) of each PCR product was examined using a melting curve analysis. For a digital MSP assay, 40 wells were analyzed per sample. A total of 110 serum samples from 48 MPM cases, 21 benign asbestos pleurisy (BAP) cases, and 41 healthy volunteers (HVs) were examined.
Results: Positive range of Tm value for miR-34b/c methylation was defined as 77.71-78.79 degrees C which was the mean 3 standard deviations of 40 wells of a positive control. The number of miR-34b/c methylated wells was counted per sample according to this criterion. The number of miR-34b/c methylated wells in MPM cases was significantly higher than that in BAP cases (P = 0.03) or HVs (P < 0.001). Advanced MPM cases tended to have higher number of miR-34b/c methylated wells than early MPM cases. Receiver-operating characteristic (ROC) curve analysis revealed that three number of miR-34b/c methylated wells per sample was the best cut-off of positivity of MPM with a 67% of sensitivity and a 77% specificity for prediction. The area under the ROC curve was 0.77.
Conclusions: Our digital MSP assay can quantify miR-34b/c methylation in serum-circulating DNA. The degree of miR-34b/c methylation in serum-circulating DNA is associated with MPM, suggesting that this approach might be useful for the establishment of a new detection system for MPM. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.lungcan.2013.09.017

山本寛斉, 宗淳一, 三好新一郎, 豊岡伸一

日本臨床 71 ( 増刊6 最新肺癌学 ) 109 - 113 2013.11

キュアサルコーマボード共同治療連携病院間"水平"連携による肉腫、GISTの集学的治療

高橋克仁, 山村倫子, 冨田裕彦, 上浦祥司, 矢嶋淳, 寺岡慧, 波多江亮, 大野烈士, 宗淳一, 豊岡伸一, 小池幸宏, 烏野隆博, 楢原啓之, 小山隆文, 大山優

日本癌治療学会誌 48 ( 3 ) 1214 - 1214 2013.9

新規高感度検出法によるEGFR T790M変異陽性肺腺癌の臨床的特徴の同定

橋田真輔, 宋淳一, 豊岡伸一, 大塚智昭, 諏澤健, 古川公之, 枝園和彦, 山本寛斉, 浅野博昭, 佃和憲, 三好新一郎

日本癌治療学会誌 48 ( 3 ) 1153 - 1153 2013.9

Bleeding into a pulmonary cyst caused by pulmonary radiofrequency ablation Reviewed

Ryotaro Kishi, Hidefumi Mimura, Takao Hiraki, Hideo Gobara, Mayu Uka, Shinichi Toyooka, Susumu Kanazawa

Journal of Vascular and Interventional Radiology 24 ( 7 ) 1069 - 1071 2013.7

Different sizes of centrilobular ground-glass opacities in chest high-resolution computed tomography of patients with pulmonary veno-occlusive disease and patients with pulmonary capillary hemangiomatosis Reviewed

Aya Miura, Satoshi Akagi, Kazufumi Nakamura, Keiko Ohta-Ogo, Katsushi Hashimoto, Satoshi Nagase, Kunihisa Kohno, Kengo Kusano, Aiko Ogawa, Hiromi Matsubara, Shinichi Toyooka, Takahiro Oto, Aiji Ohtsuka, Tohru Ohe, Hiroshi Ito

CARDIOVASCULAR PATHOLOGY 22 ( 4 ) 287 - 293 2013.7

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Background: Centrilobular ground-glass opacity (GGO) is one of the characteristic findings in chest high-resolution computed tomography (HRCT) of patients with pulmonary veno-occlusive disease (PVOD) and patients with pulmonary capillary hemangiomatosis (PCH). However, clinical differential diagnosis of these two diseases is difficult and has not been established. In order to clarify their differences, we compared the sizes of GGOs in chest HRCT and the sizes of capillary assemblies in pulmonary vascular casts between patients diagnosed pathologically with PVOD and PCH.
Methods: We evaluated chest HRCT images for four patients with idiopathic pulmonary arterial hypertension (IPAH), three patients with PVOD and three patients with PCH, and we evaluated pulmonary vascular casts of lung tissues obtained from those patients at lung transplantation or autopsy.
Results: Centrilobular GGOs in chest HRCT were observed in patients with PVOD and patients with PCH but not in patients with IPAH. We measured the longest diameter of the GGOs. The size of centrilobular GGOs was significantly larger in patients with PCH than in patients with PVOD (5.60 +/- 1.43 mm versus 2.51 +/- 0.79 mm, P<.01). We succeeded in visualization of the 3-dimensional structures of pulmonary capillary vessels obtained from the same patients with PVOD and PCH undergoing lung transplantation or autopsy and measured the diameters of capillary assemblies. The longest diameter of capillary assemblies was also significantly larger in patients with PCH than in patients with PVOD (5.44 +/- 1.71 mm versus 3.07 +/- 1.07 mm, P<.01).
Conclusion: Measurement of the sizes of centrilobular GGOs in HRCT is a simple and useful method for clinical differential diagnosis of PVOD and PCH. (C) 2013 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.carpath.2012.12.002

多数の具体的達成・評価項目票使用による診療参加型臨床実習の導入

山根正修, 杉本誠一郎, 宗淳一, 万代康弘, 三好健太郎, 山本寛斉, 豊岡伸一, 大藤剛宏, 三好新一郎

医学教育 44 ( Suppl. ) 110 - 110 2013.7

Downregulation of microRNA-34 induces cell proliferation and invasion of human mesothelial cells Reviewed

Norimitsu Tanaka, Shinichi Toyooka, Junichi Soh, Kazunori Tsukuda, Kazuhiko Shien, Masashi Furukawa, Takayuki Muraoica, Yuho Maki, Tsuyoshi Ueno, Hiromasa Yamamoto, Hiroaki Asano, Takemi Otsuki, Shinichiro Miyoshi

ONCOLOGY REPORTS 29 ( 6 ) 2169 - 2174 2013.6

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Malignant mesothelioma (MM) is an aggressive tumor with a dismal prognosis, and the molecular alterations involved in this disease remain unknown. We previously reported that microRNA-34s (miR-34s) are methylated and downregulated in MM and may play an important role in the carcinogenesis of MM. In this study, we downregulated miR-34s in human mesothelial cells to investigate the cellular effect of miR-34 knockdown. For the cell study, we used LP-9, a human mesothelial cell line, and three human primary-cultured mesothelial cell lines. RNA-based miR-34a, -34b and -34c inhibitors were transfected into these cells, and their effects on proliferation and invasion were evaluated. A scramble RNA oligonucleotide was used as a control. The protein expression status was estimated using western blotting. After miR-34 inhibitor transfection, miR-34a, -34b and -34c were downregulated in all the examined mesothelial cell lines. miR-34 inhibitor transfection significantly increased cell proliferation in all of the mesothelial cell lines, compared with the scramble control. The invasive ability also increased in the miR-34 inhibitor transfectants, compared with the scramble control, in the LP-9 cell line. Western blotting confirmed the upregulation of c-MET, phospho-c-MET, and Bcl-2 proteins in LP-9 cells after miR-34 inhibitor transfection. In conclusion, our study showed that the downregulation of miR-34s induced an oncogenic phenotype in non-malignant mesothelial cells. The present study, together with the results of our previous report, strongly suggest that miR-34s play an important role in the early carcinogenic process involved in the transformation of human mesothelial cells to MM.

DOI： 10.3892/or.2013.2351

Acquired Resistance to EGFR Inhibitors Is Associated with a Manifestation of Stem Cell-like Properties in Cancer Cells Reviewed

Kazuhiko Shien, Shinichi Toyooka, Hiromasa Yamamoto, Junichi Soh, Masaru Jida, Kelsie L. Thu, Shinsuke Hashida, Yuho Maki, Eiki Ichihara, Hiroaki Asano, Kazunori Tsukuda, Nagio Takigawa, Katsuyuki Kiura, Adi F. Gazdar, Wan L. Lam, Shinichiro Miyoshi

CANCER RESEARCH 73 ( 10 ) 3051 - 3061 2013.5

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER ASSOC CANCER RESEARCH

Acquired resistance to EGF receptor (EGFR) tyrosine kinase inhibitor (TKI) is a critical problem in the treatment of lung cancer. Although several mechanisms have been shown to be responsible for acquired resistance, all mechanisms have not been uncovered. In this study, we investigated the molecular and cellular profiles of the acquired resistant cells to EGFR-TKI in EGFR-mutant lung cancers. Four EGFR-mutant cell lines were exposed to gefitinib by stepwise escalation and high-concentration exposure methods, and resistant sublines to gefitinib were established. The molecular profiles and cellular phenotypes of these resistant sublines were characterized. Although previously reported, alterations including secondary EGFR T790M mutation, MET amplification, and appearance of epithelial-to-mesenchymal transition (EMT) features were observed, these 2 drug-exposure methods revealed different resistance mechanisms. The resistant cells with EMT features exhibited downregulation of miRNA-200c by DNA methylation. Furthermore, the HCC827-derived subline characterized by the high-concentration exposure method exhibited not only EMT features but also stem cell-like properties, including aldehyde dehydrogenase isoform 1 (ALDH1A1) overexpression, increase of side-population, and self-renewal capability. Resistant sublines with stem cell-like properties were resistant to conventional chemotherapeutic agents but equally sensitive to histone deacetylase and proteasome inhibitors, compared with their parental cells. ALDH1A1 was upregulated in clinical samples with acquired resistance to gefitinib. In conclusion, our study indicates that the manner of EGFR-TKI exposure influences the mechanism of acquired resistance and the appearance of stem cell-like property with EGFR-TKI treatment. Cancer Res; 73(10); 3051-61. (C) 2013 AACR.

DOI： 10.1158/0008-5472.CAN-12-4136

非小細胞肺癌術後補助化学療法としてのS-1+CBDCA併用療法とS-1単剤継続維持療法の多施設共同認容性試験(SLCG1001)

松本博文, 福田実, 豊岡伸一, 佐野功, 長島聖二, 橋口浩二, 谷口英樹, 中村洋一, 永安武, 河野茂, 奥村典仁, 岡部和倫, 中村廣繁, 片岡正文, 山下素弘, 中田昌男, 片岡和彦, 吉岡弘鎮, 坂本純一, 伊達洋至

気管支学 35 ( 3 ) 330 - 330 2013.5

Sacrificing the pulmonary arterial branch to the spared lobe is a risk factor of bronchopleural fistula in sleeve lobectomy after chemoradiotherapy Reviewed

Shinichi Toyooka, Junichi Soh, Kazuhiko Shien, Seiichiro Sugimoto, Masaomi Yamane, Takahiro Oto, Hiroshi Date, Shinichiro Miyoshi

EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 43 ( 3 ) 568 - 572 2013.3

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS INC

A sleeve lobectomy is a widely accepted procedure for enabling the pulmonary parenchyma to be spared. Induction chemoradiotherapy (CRT) followed by surgery is one treatment option for locally advanced non-small cell lung cancer (NSCLC), but CRT is considered to have a negative effect on subsequent surgery, especially for anastomotic healing. In this study, we describe our experience performing sleeve lobectomies and the associated anastomotic complications after induction CRT.
The medical records of NSCLC patients who underwent surgery after receiving CRT were reviewed. The relationships between anastomotic complications and clinicopathological factors were examined.
Between December 1998 and October 2011, a total of 104 patients received CRT followed by surgery. Among them, 14 NSCLC patients underwent a bronchial sleeve resection: nine patients underwent a right upper lobe resection, two patients underwent a left lingular division and lower lobe resection and one patient each underwent a right lower lobe, a right upper and middle lobe and a right middle and lower lobe resection. A bronchopleural fistula at the anastomosis occurred in two patients. A pulmonary arterial (PA) branch to the spared lobe had been sacrificed in both of these patients because of tumour involvement. In contrast, the PA branches to the spared lobes were preserved in 11 of the 12 patients who did not exhibit anastomotic complications (P = 0.033).
Our experience strongly suggests that the sacrifice of the PA branch to the spared lobe is a possible risk factor for anastomotic complications for a sleeve lobectomy after induction CRT.

DOI： 10.1093/ejcts/ezs323