Faculty Profiles - TOYOOKA Shinichi

Short hookwire placement under imaging guidance before thoracic surgery: A review Reviewed

T. Iguchi, T. Hiraki, Y. Matsui, H. Fujiwara, Y. Masaoka, M. Uka, H. Gobara, S. Toyooka, S. Kanazawa

Diagnostic and Interventional Imaging 99 ( 10 ) 591 - 597 2018

Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier Masson SAS

During video-assisted thoracic surgery (VATS), localization is sometimes needed to detect a target lesion that is too small and/or too far from the pleura. In 1995, Kanazawa et al. developed short hookwire and suture system. Since then, this system has been placed often for selected targets before VATS in Japan. This short hookwire and suture system is a representative preoperative localization method and the placement procedure is well-established. Its placement success rates are very high (range: 97.6%–99.6%), and dislodgement of this short hookwire rarely occurs with an incidence of 0.4%–2.5%. The most common complication of short hookwire placement is pneumothorax (incidence: 32.1%–68.1%), followed by pulmonary hemorrhage (incidence: 8.9%–41.6%). Complications are frequent
however, most complications are minor and asymptomatic.

DOI： 10.1016/j.diii.2018.04.001

Sumardika, I. W., Youyi, C., Kondo, E., Inoue, Y., Ruma, I. M. W., Murata, H., Kinoshita, R., Yamamoto, K. I., Tomida, S., Shien, K., Sato, H., Yamauchi, A., Futami, J., Putranto, E. W., Hibino, T., Toyooka, S., Nishibori, M., Sakaguchi, M.

Oncol Res 26 ( 3 ) 2018

Model of lung cancer surgery risk derived from a Japanese nationwide web-based database of 78 594 patients during 2014-2015 Reviewed

Shunsuke Endo, Norihiko Ikeda, Takashi Kondo, Jun Nakajima, Haruhiko Kondo, Kohei Yokoi, Masayuki Chida, Masami Sato, Shinichi Toyooka, Koichi Yoshida, Yoshinori Okada, Yukio Sato, Morihito Okada, Meinoshin Okumura, Koji Chihara, Eriko Fukuchi, Hiroaki Miyata

EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 52 ( 6 ) 1182 - 1189 2017.12

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

OBJECTIVES: Using data obtained from a Japanese nationwide annual database with web-based data entry, we developed a risk model of mortality and morbidity after lung cancer surgery.
METHODS: The characteristics and operative and postoperative data from 80 095 patients who underwent lung cancer surgery were entered into the annual National Clinical Database of Japan data sets for 2014 and 2015. After excluding 1501 patients, the development data set for risk models included 38 277 patients entering in 2014 and the validation data set included 40 317 patients entering in 2015. Receiver-operating characteristic curves were generated for the outcomes of mortality and composite mortality/major morbidity. The concordance index was used to assess the discriminatory ability and validity of the model.
RESULTS: The 30-day mortality and overall mortality rates, including in-hospital deaths, were 0.4% and 0.8%, respectively, in 2014, and 0.4% and 0.8%, respectively, in 2015. The rate of major morbidity was 5.6% in 2014 and 5.6% in 2015. Several risk factors were significantly associated with mortality, namely, male sex, performance status, comorbidities of interstitial pneumonia and liver cirrhosis, haemodialysis and the surgical procedure pneumonectomy. The concordance index for mortality and composite mortality/major morbidity was 0.854 (P < 0.001) and 0.718 (P < 0.001), respectively, for the development data set and 0.849 (P < 0.001) and 0.723 (P < 0.001), respectively, for the validation data set.
CONCLUSIONS: This model was satisfactory for predicting surgical outcomes after pulmonary resection for lung cancer in Japan and will aid preoperative assessment and improve clinical outcomes for lung cancer surgery.

DOI： 10.1093/ejcts/ezx190

胸膜外肺全摘術と放射線療法で、術後13年無再発生存中の悪性胸膜中皮腫の1例

岡部和倫, 山本寛斉, 宗淳一, 豊岡伸一

肺癌 57 ( 7 ) 895 - 895 2017.12

Restrictive ventilatory impairment is associated with poor outcome in patients with cT1aN0M0 peripheral squamous cell carcinoma of the lung Reviewed

Hiroyuki Tao, Junichi Soh, Hiromasa Yamamoto, Toshiya Fujiwara, Tsuyoshi Ueno, Makio Hayama, Mikio Okazaki, Ryujiro Sugimoto, Motohiro Yamashita, Yoshifumi Sano, Kazunori Okabe, Motoki Matsuura, Kazuhiko Kataoka, Shigeharu Moriyama, Shinichi Toyooka, Shinichiro Miyoshi

JOURNAL OF THORACIC DISEASE 9 ( 11 ) 4325 - 4335 2017.11

Language：English Publishing type：Research paper (scientific journal) Publisher：AME PUBL CO

Background: Patients with squamous cell carcinoma (SqCC) of the lung sometimes have a comorbid pulmonary disease such as pulmonary emphysema or an interstitial lung disease (ILD), both of which negatively affect patient outcome. The aim of this study was to determine the outcome of patients in a multicenter database who underwent surgery for cT1aN0M0 peripheral SqCC lung cancer.
Methods: The medical records of a total of 228 eligible patients from seven institutions were reviewed to evaluate the impact of concomitant impaired pulmonary function and other clinicopathological factors on overall survival (OS) and relapse-free survival (RFS).
Results: Six patients with positive or unclear tumor margins were excluded. Of the 222 remaining study patients, 42 (18.9%) and 97 (43.7%) patients were found to have coexisting restrictive or obstructive ventilatory impairment, respectively. Over a median follow-up period of 30.6 months, the 5-year OS and RFS were 69.0% and 62.6%, respectively. By multivariate analysis, ILDs identified on high-resolution computed tomography (HRCT), pulmonary function test results indicating a restrictive ventilatory impairment, and wedge resection were found to be independent risk factors for poor OS. An increased level of serum squamous cell carcinoma antigen (SCC-Ag) (> 1.5 ng/mL) and the same risk factors for poor OS were independent risk factors for recurrence. Among patients who underwent anatomical lung resection (lobectomy and segmentectomy, n=173), a restrictive ventilatory impairment was an independent risk factor for poor OS, and increased serum SCC-Ag level, ILDs on HRCT, and restrictive ventilatory impairment were independent risk factors for poor RFS by multivariate analysis. Factors such as visceral pleural invasion, and lymphatic or vascular invasion were not significantly associated with outcome.
Conclusions: A restrictive ventilatory impairment negatively affects the outcome of patients with cT1aN0M0 peripheral SqCC lung cancer.

DOI： 10.21037/jtd.2017.10.70

Elacridar, a third-generation ABCB1 inhibitor, overcomes resistance to docetaxel in non-small cell lung cancer Reviewed

Haiyang Chen, Kazuhiko Shien, Ken Suzawa, Kazunori Tsukuda, Shuta Tomida, Hiroki Sato, Hidejiro Torigoe, Mototsugu Watanabe, Kei Namba, Hiromasa Yamamoto, Junichi Soh, Hiroaki Asano, Shinichiro Miyoshi, Shinichi Toyooka

ONCOLOGY LETTERS 14 ( 4 ) 4349 - 4354 2017.10

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

Docetaxel is a third-generation chemotherapeutic drug that is widely used in the treatment of patients with non-small cell lung cancer (NSCLC). However, the majority of patients with NSCLC eventually acquire resistance to the treatment. In the present study, the mechanism of acquired resistance to docetaxel treatment in lung cancer cells was investigated. The three NSCLC cell lines, H1299 with wild-type epidermal growth factor receptor (EGFR), EGFR-mutant HCC4006 and HCC827, and experimentally established docetaxel-resistant (DR) cells, H1299-DR, HCC827-DR, and HCC4006-DR were used with stepwise increases in concentrations of docetaxel. It was demonstrated that the established cell lines showed resistance to docetaxel and EGFR-tyrosine kinase inhibitors (TKIs). Molecular analysis revealed that all of the resistant cell lines highly expressed ATP binding cassette subfamily B member 1 (ABCB1), which is also known as P-glycoprotein or MDR1. Furthermore, HCC827-DR and HCC4006-DR cells exhibited a cancer stem cell-like marker and epithelial-to-mesenchymal transition features, respectively. Elacridar (GF120918), a third-generation inhibitor of ABCB1, was able to overcome resistance to docetaxel. Additionally, knockdown of ABCB1 using small interfering RNA (si)-ABCB1 recovered sensitivity to docetaxel. However, elacridar and si-ABCB1 could not recover sensitivity to EGFR-TKIs in established resistant cells. The results of the present study revealed that docetaxelresis-tant NSCLC cells also acquired cross-resistance to EGFR-TKI therapy through mechanisms other than ABCB1, that ABCB1 serves an important role in acquired resistance to docetaxel in lung cancer, and that combination therapy with elacridar can overcome ABCB1-mediated docetaxel resistance.

DOI： 10.3892/ol.2017.6678

Postoperative pyoderma gangrenosum exacerbated by granulocyte-colony stimulating factor after lung cancer surgery Reviewed

Haruchika Yamamoto, Seiichiro Sugimoto, Shinji Otani, Shinichi Toyooka

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 47 ( 10 ) 991 - 992 2017.10

JAK1/STAT3 Activation through a Proinflammatory Cytokine Pathway Leads to Resistance to Molecularly Targeted Therapy in Non-Small Cell Lung Cancer Reviewed

Kazuhiko Shien, Vassiliki A. Papadimitrakopoulou, Dennis Ruder, Carmen Behrens, Li Shen, Neda Kalhor, Juhee Song, J. Jack Lee, Jing Wang, Ximing Tang, Roy S. Herbst, Shinichi Toyooka, Luc Girard, John D. Minna, Jonathan M. Kurie, Ignacio I. Wistuba, Julie G. Izzo

MOLECULAR CANCER THERAPEUTICS 16 ( 10 ) 2234 - 2245 2017.10

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

Molecularly targeted drugs have yielded significant therapeutic advances in oncogene-driven non-small cell lung cancer (NSCLC), but a majority of patients eventually develop acquired resistance. Recently, the relation between proinflammatory cytokine IL6 and resistance to targeted drugs has been reported. We investigated the functional contribution of IL6 and the other members of IL6 family proinflammatory cytokine pathway to resistance to targeted drugs in NSCLC cells. In addition, we examined the production of these cytokines by cancer cells and cancer-associated fibroblasts (CAF). We also analyzed the prognostic significance of these molecule expressions in clinical NSCLC samples. In NSCLC cells with acquired resistance to targeted drugs, we observed activation of the IL6-cytokine pathway and STAT3 along with epithelial-to-mesenchymal transition (EMT) features. In particular, IL6 family cytokine oncostatin-M (OSM) induced a switch to the EMT phenotype and protected cells from targeted drug-induced apoptosis in OSM receptors (OSMRs)/JAK1/STAT3-dependent manner. The crosstalk between NSCLC cells and CAFs also preferentially activated the OSM/STAT3 pathway via a paracrine mechanism and decreased sensitivity to targeted drugs. The selective JAK1 inhibitor filgotinib effectively suppressed STAT3 activation and OSMR expression, and cotargeting inhibition of the oncogenic pathway and JAK1 reversed resistance to targeted drugs. In the analysis of clinical samples, OSMR gene expression appeared to be associated with worse prognosis in patients with surgically resected lung adenocarcinoma. Our data suggest that the OSMRs/JAK1/STAT3 axis contributes to resistance to targeted drugs in oncogene-driven NSCLC cells, implying that this pathway could be a therapeutic target. (C) 2017 AACR.

DOI： 10.1158/1535-7163.MCT-17-0148

Effects of Cold Ischemia on RNA Stability and Quality of Lung Tissues Based on Standard PREanalytical Code Categorization Reviewed

Takehiro Matsubara, Shuta Tomida, Junichi Soh, Takahiro Uwabo, Yoshiko Mori, Mizuki Morita, Yasutomo Nasu, Susumu Kanazawa, Shinichi Toyooka

BIOPRESERVATION AND BIOBANKING 15 ( 5 ) 484 - 486 2017.10

臨床試験から視た肺癌手術瀬戸内肺癌研究会13年の活動

宗淳一, 奥村典仁, 山下芳典, 片岡和彦, 佐野由文, 片岡正文, 岡部和倫, 山下素弘, 青江基, 中田昌男, 根津賢司, 中村廣繁, 三好新一郎, 豊岡伸一, 伊達洋至

日本臨床外科学会雑誌 78 ( 増刊 ) 333 - 333 2017.10

Estimation of age-related DNA degradation from formalin-fixed and paraffin-embedded tissue according to the extraction methods Reviewed

Mototsugu Watanabe, Shinsuke Hashida, Hiromasa Yamamoto, Takehiro Matsubara, Tomoaki Ohtsuka, Ken Suzawa, Yuho Maki, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Shinichi Toyooka, Shinichiro Miyoshi

EXPERIMENTAL AND THERAPEUTIC MEDICINE 14 ( 3 ) 2683 - 2688 2017.9

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

Techniques for the extraction and use of nucleic acids from formalin-fixed and paraffin-embedded (FFPE) tissues, preserved over long time periods in libraries, have been developed. However, DNA extracted from FFPE tissues is generally damaged, and long-term storage may affect DNA quality. Therefore, it is important to elucidate the effect of long-term storage on FFPE tissues and evaluate the techniques used to extract DNA from them. In the present study, the yield, purity, and integrity of DNA in FFPE tissue samples was evaluated. Two DNA extraction techniques were used: A silica-binding DNA collection method using QIAamp DNA FFPE Tissue kit (QIA) and a total tissue DNA collection method using a WaxFree DNA extraction kit (WAX). A total of 25 FFPE tissues from lung adenocarcinomas were studied, which had been surgically resected and fixed at Okayama University Hospital prior to examination and subsequent storage at room temperature for 0.5, 3, 6, 9 and 12 years. Extracted DNA was quantified using ultraviolet absorbance, fluorescent dye, and quantitative polymerase chain reaction (qPCR). The quality of the DNA was defined by the absorbance ratio of 260 to 280 nm (A260/280) and Q-score, which is the quantitative value of qPCR product size ratio. The results demonstrated that the yield of total DNA extracted using WAX was significantly greater than when QIA was used (P<0.01); however, DNA extracted using WAX included more contaminants and was significantly more fragmented compared with DNA extracted using QIA (P<0.01). Aging had no significant effect on absolute DNA yield or DNA purity, although it did significantly contribute to increased DNA degradation for both QIA and WAX extraction (QIA P=0.02, WAX P=0.03; 0.5 years vs. 3 years, QIA P<0.01, WAX P=0.03; 9 years vs. 12 years). Both extraction methods are viable depending on whether high yield or high quality of extracted DNA is required. However, due to the increased degradation with age, storage time limits the available DNA in FFPE tissues regardless of the extraction method.

DOI： 10.3892/etm.2017.4797

Induction chemoradiotherapy using docetaxel and cisplatin with definitive-dose radiation followed by surgery for locally advanced non-small cell lung cancer Reviewed

Hidejiro Torigoe, Junichi Soh, Shuta Tomida, Kei Namba, Hiroki Sato, Kuniaki Katsui, Katsuyuki Hotta, Kazuhiko Shien, Hiromasa Yamamoto, Masaomi Yamane, Susumu Kanazawa, Katsuyuki Kiura, Shinichiro Miyoshi, Shinichi Toyooka

JOURNAL OF THORACIC DISEASE 9 ( 9 ) 3076 - 3086 2017.9

Language：English Publishing type：Research paper (scientific journal) Publisher：AME PUBL CO

Background: Induction chemoradiotherapy (CRT) followed by surgery is a therapeutic option for locally advanced non-small cell lung cancer (LA-NSCLC). Typically, around 40-50 Gy of radiation is applied as the induction-dose; however, a definitive-dose (DD) of radiation (60 Gy or higher) is occasionally applied to increase local control. We investigated the impact of induction CRT with DD radiation in LA-NSCLC patients treated with a single regimen of docetaxel and cisplatin.
Methods: We reviewed 110 patients with LA-NSCLC who underwent induction CRT followed by surgery using a single regimen (docetaxel and cisplatin) between January 1999 and December 2014 at our hospital. The clinical outcomes of a DD group (60 Gy or higher, n= 11) and a non-DD group (less than 60 Gy, n= 99) were investigated using a propensity score (PS)-matched analysis.
Results: An advanced clinical stage was significantly more common in the DD group than in the nonDD group (P= 0.033). Before and after the PS-matching based on seven factors including clinical stage, there was no significant difference in the rates of postoperative (PO) complication, mortality, 5-year overall survival (OS), or 5-year recurrence-free survival (RFS) between the two groups. After the PS-matching, the pathological complete response (CR) rate was significantly higher in the DD group than in the non-DD group [50% (n= 5/10) vs. 0% (n= 0/10), P= 0.033].
Conclusions: Induction CRT followed by surgery using docetaxel and cisplatin with DD radiation can be performed safely and is associated with a higher pathological CR rate than that attained using non-DD radiation in LA-NSCLC patients.

DOI： 10.21037/jtd.2017.08.87

Advantage of Induction Chemoradiotherapy for Lung Cancer in Securing Cancer-Free Bronchial Margin Reviewed

Hiroki Sato, Shinichi Toyooka, Junichi Soh, Katsuyuki Hotta, Kuniaki Katsui, Kazuhiko Shien, Hiromasa Yamamoto, Takahiro Oto, Susumu Kanazawa, Katsuyuki Kiura, Shinichiro Miyoshi

ANNALS OF THORACIC SURGERY 104 ( 3 ) 971 - 978 2017.9

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

Background. Bronchoplasty is a useful procedure for preserving pulmonary function. For this procedure, it is critical to secure the negative surgical margin for avoiding local recurrence. In this study, we examined the status of the surgical bronchial margin as well as the clinical outcomes in bronchoplasty with or without induction chemoradiotherapy (CRT) for non-small cell lung cancer (NSCLC).
Methods. The medical records of NSCLC patients who underwent bronchoplasty at our institution between January 1999 and September 2014 were reviewed. We compared the clinical outcomes of bronchoplasty with or without induction CRT.
Results. A total of 58 NSCLC patients were included in this study. Among these, 38 patients underwent primary surgical procedure with bronchoplasty and 20 patients underwent bronchoplasty after induction CRT. Intraoperative pathologic diagnosis for the surgical margin of the bronchus revealed that the patients in the primary surgical procedure group had a significantly higher rate of positive surgical margin than the induction CRT group (p = 0.023), requiring an additional bronchial resection to secure the negative margin. After additional resection of positive bronchial stumps, no significant difference was found in the rate of positive margin with postoperative histologic diagnosis between the two groups. In addition, no significant differences in the postoperative complication rate and overall and recurrence-free survivals were observed between the two groups.
Conclusions. Our results suggest that induction CRT before surgical procedure may help ensure the intraoperative negative surgical margin of the bronchus. Our study also indicates that bronchoplasty after induction CRT is feasible in comparison with bronchoplasty in primary surgical procedure. (C) 2017 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2017.03.045