研究者詳細 - 多田　周

論文 - 多田　周

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膵液瘻に伴う膿気胸に対する外科治療

大川美穂, 新井航, 高橋有毅, 槇龍之輔, 多田周, 三品泰二郎, 宮島正博, 渡辺敦

胸部外科 72 ( 3 ) 209 - 212 2019年03月 [国内誌]

A 46-year-old woman with cervical cancer with multiorgan metastasis visited our hospital. She underwent a total gastrectomy, splenectomy, distal pancreatectomy, left adrenalectomy, and left partial diaphragmatic resection. Postoperatively, she developed pleural effusion with high level of amylase secondary to a pancreatic ﬁstula, consequently causing left-sided empyema. She developed acute respiratory distress syndrome. Urgent surgical treatment was scheduled, and left lower lobectomy, with diaphragmatic partial resection were performed under the venovenous extracorporeal membrane oxygenation. After surgery, intensive care for 45 days was necessary and she was discharged home 6 months post operatively.

PubMed J-GLOBAL

Thoracoscopic Right Basilar Segmentectomy After Right Upper Lobectomy.

Makoto Tada, Masahiro Miyajima, Taijiro Mishina, Yuki Takahashi, Ryunosuke Maki, Atsushi Watanabe

The Annals of thoracic surgery 107 ( 2 ) e123-e125 2019年02月 [国際誌]

This report describes a case of thoracoscopic right basilar segmentectomy after upper lobectomy. A 76-year-old man who underwent right upper lobectomy for lung tuberculosis 50 years earlier had a diagnosis of squamous cell carcinoma, stage IB (T2a N0 M0), in the right lower lobe and underwent right basilar segmentectomy for limited resection. The postoperative course was uneventful. The patient showed no recurrence clinically, and the 1-year postoperative chest computed tomographic scan showed adequate volume of the middle and residual right lower lobe without emphysematous changes.

DOI PubMed

Characterization of distal airway stem-like cells expressing N-terminally truncated p63 and thyroid transcription factor-1 in the human lung.

Yusuke Tanaka, Miki Yamaguchi, Sachie Hirai, Toshiyuki Sumi, Makoto Tada, Atsushi Saito, Hirofumi Chiba, Takashi Kojima, Atsushi Watanabe, Hiroki Takahashi, Yuji Sakuma

Experimental cell research 372 ( 2 ) 141 - 149 2018年11月 [国際誌]

Distal airway stem cells (DASCs) in the mouse lung can differentiate into bronchioles and alveoli. However, it remains unclear whether the same stem cells exist in the human lung. Here, we found that human lung epithelial (HuL) cells, derived from normal, peripheral lung tissue, in monolayer, mostly express both the N-terminally truncated isoform of p63 (∆Np63), a marker for airway basal cells, and thyroid transcription factor-1 (TTF-1), a marker for alveolar epithelial cells, even though these two molecules are usually expressed in a mutually exclusive way. Three-dimensionally cultured HuL cells differentiated to form bronchiole-like and alveolus-like organoids. We also uncovered a few bronchiolar epithelial cells expressing both ∆Np63 and TTF-1 in the human lung, suggesting that these cells are the cells of origin for HuL cells. Taken together, ΔNp63+ TTF-1+ peripheral airway epithelial cells are possibly the human counterpart of mouse DASCs and may offer potential for future regenerative medicine.

DOI PubMed

左肺全摘後，体外式肺補助下に胸腔鏡下右肺区域切除を行った1例

多田周, 高橋有毅, 槙龍之輔, 三品泰二郎, 宮島正博, 渡辺敦

肺癌 ( 特定非営利活動法人日本肺癌学会 ) 58 ( 4 ) 298 - 302 2018年08月

背景．異時性多発肺癌に対する3回以上の解剖学的肺切除や，片肺全摘後の残肺解剖学的切除例の報告はいまだ少ない．症例．66歳男性．50歳時に左上葉肺癌（肺癌取扱い規約第8版：微小浸潤性腺癌，stage IA1）に対して左上葉切除術，61歳時に左下葉異時性多発肺癌（微小浸潤性腺癌，stage IA1）に対して左下葉切除術の既往があった．定期検診で胸部異常陰影を指摘された．術前残存肺呼吸機能は肺活量2.32 l，1秒量1.59 lであった．組織学的な確定診断は得られなかったが，CT所見から原発性肺癌が強く疑われたため，体外式肺補助（ECLA）下に胸腔鏡下右S⁶区域切除を施行した．術後合併症はなく，術後14日目に退院した．組織学的診断は上皮内腺癌であった．結論．ECLAの使用により，左肺全摘後，右肺に出現した異時性肺癌（3重癌）に対し，安全に胸腔鏡下区域切除を施行することが可能であった．

DOI DOI2 CiNii

Thoracoscopic one-stage lobectomy and diaphragmatic plication for T3 lung cancer.

Yuki Takahashi, Masahiro Miyajima, Taijiro Mishina, Ryunosuke Maki, Makoto Tada, Kodai Tsuruta, Atsushi Watanabe

Journal of cardiothoracic surgery 13 ( 1 ) 86 - 86 2018年07月 [国際誌]

BACKGROUND: Combined resection of a phrenic nerve is occasionally required in T3 primary lung carcinomas invading the phrenic nerve to completely remove a malignant tumour, resulting in diaphragmatic paralysis. We describe the first case of thoracoscopic lobectomy and diaphragmatic plication as a one-stage surgery for lung cancer invading the phrenic nerve. CASE PRESENTATION: A 56-year-old woman with a T3N0M0 primary adenosquamous carcinoma in the left upper lobe presented with suspicious invasion to the anterior mediastinal fat tissue and left phrenic nerve and underwent left upper lobectomy, node dissection, and partial resection of the anterior mediastinal fat tissue with the left phrenic nerve. Furthermore, thoracoscopic diaphragmatic plication was performed as a concomitant procedure. The patient's postoperative course was favourable, without any complications, and respiratory function was preserved for 1 year postoperatively. CONCLUSIONS: Thoracoscopic one-stage lobectomy and diaphragmatic plication for T3 lung cancer invading the phrenic nerve is effective for preservation of postoperative pulmonary function.

DOI PubMed

Survivin knockdown induces senescence in TTF‑1-expressing, KRAS-mutant lung adenocarcinomas.

Toshiyuki Sumi, Sachie Hirai, Miki Yamaguchi, Yusuke Tanaka, Makoto Tada, Gen Yamada, Tadashi Hasegawa, Yohei Miyagi, Toshiro Niki, Atsushi Watanabe, Hiroki Takahashi, Yuji Sakuma

International journal of oncology 53 ( 1 ) 33 - 46 2018年07月 [国際誌]

Survivin plays a key role in regulating the cell cycle and apoptosis, and is highly expressed in the majority of malignant tumors. However, little is known about the roles of survivin in KRAS-mutant lung adenocarcinomas. In the present study, we examined 28 KRAS-mutant lung adenocarcinoma tissues and two KRAS-mutant lung adenocarcinoma cell lines, H358 and H441, in order to elucidate the potential of survivin as a therapeutic target. We found that 19 (68%) of the 28 KRAS-mutant lung adenocarcinomas were differentiated tumors expressing thyroid transcription factor‑1 (TTF‑1) and E-cadherin. Patients with tumors immunohistochemically positive for survivin (n=18) had poorer outcomes than those with survivin-negative tumors (n=10). In the H358 and H441 cells, which expressed TTF‑1 and E-cadherin, survivin knockdown alone induced senescence, not apoptosis. However, in monolayer culture, the H358 cells and H441 cells in which survivin was silenced, underwent significant apoptosis following combined treatment with ABT-263, a Bcl‑2 inhibitor, and trametinib, a MEK inhibitor. Importantly, the triple combination of survivin knockdown with ABT-263 and trametinib treatment, clearly induced cell death in a three-dimensional cell culture model and in an in vivo tumor xenograft model. We also observed that the growth of the H358 and H441 cells was slightly, yet significantly suppressed in vitro when TTF‑1 was silenced. These findings collectively suggest that the triple combination of survivin knockdown with ABT-263 and trametinib treatment, may be a potential strategy for the treatment of KRAS-mutant lung adenocarcinoma. Furthermore, our findings indicate that the well‑differentiated type of KRAS-mutant lung tumors depends, at least in part, on TTF‑1 for growth.

DOI PubMed

p40陰性肺類基底細胞型扁平上皮癌の1例

槙龍之輔, 杉田真太朗, 小野祐輔, 宮島正博, 多田周, 高橋有毅, 三品泰二郎, 渡辺敦

胸部外科 71 ( 7 ) 547 - 550 2018年07月 [国内誌]

Immunohistochemical staining is important for the differential diagnosis of basaloid squamous cell carcinoma(BSC)and other similar carcinomas, such as small-cell carcinomas and large-cell neuroendocrine carcinomas. p40 is a useful marker of squamous cell carcinoma that can be used for the diagnosis of BSC. We present the case of a 64-year-old man who was referred to our hospital for investigation of an abnormal shadow revealed on chest radiography. Computed tomography(CT) revealed a 16×11 mm nodule in the left lung(S1+2), and a thoracoscopic left upper lobectomy was performed. Histologically, lobular pattern with peripheral palisading was observed and the immunohistochemical staining revealed the tumor cells to be positive for p63 and negative for both p40 and neuroendocrine markers, leading to the diagnosis of BSC.

PubMed J-GLOBAL

Trametinib downregulates survivin expression in RB1-positive KRAS-mutant lung adenocarcinoma cells.

Toshiyuki Sumi, Sachie Hirai, Miki Yamaguchi, Yusuke Tanaka, Makoto Tada, Toshiro Niki, Hiroki Takahashi, Yuji Sakuma

Biochemical and biophysical research communications 501 ( 1 ) 253 - 258 2018年06月 [国際誌]

High expression levels of survivin in KRAS-mutant lung adenocarcinomas are linked with unfavorable patient outcomes, suggesting that survivin is a promising target for tumor treatment. We found that trametinib, a MEK inhibitor, downregulates survivin expression in the RB1-positive KRAS-mutant lung adenocarcinoma cell lines H358 and H441. In these cell lines, trametinib treatment induced p21 expression and dephosphorylated RB1, leading to sustained suppression of survivin. Knockdown of p21 or RB1 restored survivin expression in trametinib-treated cells, at least partially, which supports the contribution of these molecules to trametinib-mediated survivin suppression. In RB1-negative KRAS-mutant lung adenocarcinoma H2009 cells, survivin downregulation by trametinib was only slight and transient, and trametinib-resistant (TR) cells developed within 1 month of treatment. H2009 TR cells depended much more on survivin for survival than its parental cells, as evidenced by apoptosis induction when survivin was depleted. These findings collectively suggest that trametinib is effective for the treatment of RB1-positive KRAS-mutant lung adenocarcinomas through sustained survivin suppression, but not for RB1-negative lung adenocarcinomas. Thus, the RB1 status could be a biomarker for trametinib application in KRAS-mutant lung adenocarcinomas.

DOI PubMed

左肺全摘後,体外式肺補助下に胸腔鏡下右肺区域切除を行った1例

多田周, 高橋有毅, 槙龍之輔, 三品泰二郎, 宮島正博, 渡辺敦

肺癌(Web) 58 ( 4 ) 2018年

J-GLOBAL

Video-assisted thoracoscopic surgery node dissection for lung cancer treatment.

Atsushi Watanabe, Masahiro Miyajima, Taijiro Mishina, Kodai Tsuruta, Yuki Takahashi, Ryunosuke Maki, Makoto Tada

Surgery today 47 ( 12 ) 1419 - 1428 2017年12月 [国内誌]

PURPOSE: Mediastinal node dissection (MND) is an integral component of the surgical treatment for non-small cell lung cancer (NSCLC). Although video-assisted thoracoscopic surgery (VATS) has been used increasingly for lung cancer treatment, the accuracy of by VATS MND still remains controversial. We reviewed the surgical results of VATS MND for NSCLC. METHODS: A systematic review of literature was performed, and articles that fully described the surgical procedure, devices, and results of VATS MND were selected to compare the efficacy of MND by VATS and thoracotomy. RESULTS: Various techniques and equipments have been shown to perform adequate MND, but there is an argument as to the method of estimation of the accuracy of MND. Most of the recent studies showed that the nodal upstaging and number of dissected nodes are significantly lower by VATS than after thoracotomy. Oppositely, some studies showed VATS noninferiority in these issues. Complications such as chylothorax, pleural effusion, bleeding, and nerve damage were similar in both groups. CONCLUSIONS: Although ND by VATS remains controversial, VATS MND is becoming easier and more feasible owing to the development of more advanced endoscopic cameras and equipments. We should learn further to become more adept at performing adequate ND by VATS.

DOI PubMed

Angiotensin-converting enzyme 2 is a potential therapeutic target for EGFR-mutant lung adenocarcinoma.

Miki Yamaguchi, Sachie Hirai, Toshiyuki Sumi, Yusuke Tanaka, Makoto Tada, Yukari Nishii, Tadashi Hasegawa, Hiroaki Uchida, Gen Yamada, Atsushi Watanabe, Hiroki Takahashi, Yuji Sakuma

Biochemical and biophysical research communications 487 ( 3 ) 613 - 618 2017年06月 [国際誌]

EGFR-mutant lung adenocarcinomas contain a subpopulation of cells that have undergone epithelial-to-mesenchymal transition and can grow independently of EGFR. To kill these cancer cells, we need a novel therapeutic approach other than EGFR inhibitors. If a molecule is specifically expressed on the cell surface of such EGFR-independent EGFR-mutant cancer cells, it can be a therapeutic target. We found that a mesenchymal EGFR-independent subline derived from HCC827 cells, an EGFR-mutant lung adenocarcinoma cell line, expressed angiotensin-converting enzyme 2 (ACE2) to a greater extent than its parental cells. ACE2 was also expressed at least partially in most of the primary EGFR-mutant lung adenocarcinomas examined, and the ACE2 expression level in the cancer cells was much higher than that in normal lung epithelial cells. In addition, we developed an anti-ACE2 mouse monoclonal antibody (mAb), termed H8R64, that was internalized by ACE2-expressing cells. If an antibody-drug conjugate consisting of a humanized mAb based on H8R64 and a potent anticancer drug were produced, it could be effective for the treatment of EGFR-mutant lung adenocarcinomas.

DOI PubMed

高齢者気管腺様嚢胞癌に対し気管管状切除・再建術を施行した1例

多田周, 高橋有毅, 槙龍之輔, 三品泰二郎, 宮島正博, 渡辺敦

肺癌 ( 特定非営利活動法人日本肺癌学会 ) 57 ( 7 ) 870 - 874 2017年

背景．高齢者に対する気管切除・再建術の報告はいまだ少ない．症例．84歳女性．検診で胸部異常陰影を指摘された．胸部CT検査で胸部中部気管前壁の結節性病変を認めた．前医で行われた経気管支鏡生検で腺様嚢胞癌の診断であった．胸骨正中切開で気管管状切除・再建術を施行した．術後合併症はなく，術後33日目に退院した．結論．80歳代女性患者の気管原発腺様嚢胞癌に対して気管切除・再建術を施行した．切除後12か月無再発生存中である．

DOI DOI2 CiNii

高齢者気管腺様嚢胞癌に対し気管管状切除・再建術を施行した1例

多田周, 高橋有毅, 槙龍之輔, 三品泰二郎, 宮島正博, 渡辺敦

肺癌(Web) 57 ( 7 ) 2017年

J-GLOBAL

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