Faculty Profiles - Otsuka Motoyuki

Papers - Otsuka Motoyuki

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UnderwaterとUnder-gelでの大腸腫瘍性病変に対する境界診断能の検討

豊澤惇希, 山崎泰史, 青山祐樹, 井川翔子, 井口俊博, 衣笠秀明, 高原政宏, 平岡佐規子, 大塚基之

Gastroenterological Endoscopy 66 ( Suppl.1 ) 969 - 969 2024.4

結節を有するIPMNの良悪性診断における新規TIC解析プログラムを用いた造影EUSの有用性

宮本和也, 内田大輔, 服部直, 小幡泰介, 佐藤亮介, 織田崇志, 菊池達也, 松三明宏, 森本光作, 寺澤裕之, 藤井佑樹, 松本和幸, 堀口繁, 堤康一郎, 加藤博也, 大塚基之

Gastroenterological Endoscopy 66 ( Suppl.1 ) 977 - 977 2024.4

肝細胞癌の病態解明のためのトランスレーショナルリサーチ血清抗PD1自己抗体高値はアテゾリズマブ/ベバシズマブ治療予後不良の予測因子となる

高木章乃夫, 松本和幸, 佐々木裕貴, 須江真彦, 足立卓哉, 和田望, 竹内康人, 大西秀樹, 白羽英則, 大塚基之

日本消化器病学会雑誌 121 ( 臨増総会 ) A236 - A236 2024.3

経口胆道鏡検査におけるAIを用いた色素内視鏡画像への疑似変換

佐藤亮介, 松本和幸, 冨谷昌弘, 谷本太郁由, 大戸彰三, 原田圭, 服部直, 小幡泰介, 松三明宏, 宮本和也, 森本光作, 寺澤裕之, 藤井佑樹, 内田大輔, 衣笠秀明, 堤康一郎, 堀口繁, 加藤博也, 河原祥朗, 大塚基之

日本消化器病学会雑誌 121 ( 臨増総会 ) A356 - A356 2024.3

膵癌の分子異常と個別化治療切除不能進行膵癌治療において生殖細胞BRCA病的変異は体細胞CGP結果によらず白金製剤治療効果予測因子となる

堀口繁, 加藤博也, 寺澤裕之, 藤井佑樹, 山崎辰洋, 松本和幸, 堤康一郎, 大塚基之

日本消化器病学会雑誌 121 ( 臨増総会 ) A87 - A87 2024.3

神経内分泌腫瘍の新しい治療戦略膵消化管神経内分泌腫瘍肝転移に対するPRRTの治療効果予測因子についての検討

堀口繁, 加藤博也, 寺澤裕之, 藤井佑樹, 山崎辰洋, 松本和幸, 堤康一郎, 大塚基之

日本消化器病学会雑誌 121 ( 臨増総会 ) A108 - A108 2024.3

神経線維腫症の消化管合併症に関する検討

本田真奈美, 岩室雅也, 山崎泰史, 田中健大, 川野誠司, 平岡佐規子, 河原祥朗, 大塚基之

日本消化器病学会雑誌 121 ( 臨増総会 ) A349 - A349 2024.3

Satellite double-stranded RNA induces mesenchymal transition in pancreatic cancer by regulating alternative splicing. Reviewed International journal

Takuma Iwata, Takahiro Kishikawa, Takahiro Seimiya, Genso Notoya, Tatsunori Suzuki, Chikako Shibata, Yu Miyakawa, Nariaki Odawara, Kazuyoshi Funato, Eri Tanaka, Mari Yamagami, Kazuma Sekiba, Motoyuki Otsuka, Kazuhiko Koike, Mitsuhiro Fujishiro

The Journal of biological chemistry 300 ( 3 ) 105742 - 105742 2024.3

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

Human satellite II (HSATII), composed of tandem repeats in pericentromeric regions, is aberrantly transcribed in epithelial cancers, particularly pancreatic cancer. Dysregulation of repetitive elements in cancer tissues can facilitate incidental dsRNA formation; however, it remains controversial whether dsRNAs play tumor-promoting or tumor-suppressing roles during cancer progression. Therefore, we focused on the double-stranded formation of HSATII RNA and explored its molecular function. The overexpression of double-stranded HSATII (dsHSATII) RNA promoted mesenchymal-like morphological changes and enhanced the invasiveness of pancreatic cancer cells. We identified an RNA-binding protein, spermatid perinuclear RNA-binding protein (STRBP), which preferentially binds to dsHSATII RNA rather than single-stranded HSATII RNA. The mesenchymal transition of dsHSATII-expressing cells was rescued by STRBP overexpression. Mechanistically, STRBP is involved in the alternative splicing of genes associated with epithelial-mesenchymal transition (EMT). We also confirmed that isoform switching of CLSTN1, driven by dsHSATII overexpression or STRBP depletion, induced EMT-like morphological changes. These findings reveal a novel tumor-promoting function of dsHSATII RNA, inducing EMT-like changes and cell invasiveness, thus enhancing our understanding of the biological significance of aberrant expression of satellite arrays in malignant tumors.

DOI： 10.1016/j.jbc.2024.105742

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大腸鋸歯状病変の病態解明と診療戦略 Serrated polyposis syndromeの臨床病理学的特徴とその発癌ポテンシャルの検討

平井亮佑, 衣笠秀明, 平岡佐規子, 田中健大, 大塚基之

日本消化器病学会雑誌 121 ( 臨増総会 ) A215 - A215 2024.3

AIを用いた消化器疾患の診断・治療への応用内視鏡画像を用いた早期胃癌の深達度診断支援プログラムの性能

平田翔一郎, 濱田健太, 河原祥朗, 倉岡紗樹子, 内田大輔, 河野吉泰, 岩室雅也, 川野誠司, 大塚基之

日本消化器病学会雑誌 121 ( 臨増総会 ) A36 - A36 2024.3

免疫関連有害事象による胃炎の5例

岩室雅也, 田中健大, 平田翔一郎, 河野吉泰, 川野誠司, 河原祥朗, 大塚基之

Gastroenterological Endoscopy 66 ( 3 ) 266 - 272 2024.3

経口胆道鏡検査におけるAIを用いた色素内視鏡画像への疑似変換

日本消化器病学会雑誌 121 ( 臨増総会 ) A356 - A356 2024.3

大腸鋸歯状病変の病態解明と診療戦略 Serrated polyposis syndromeの臨床病理学的特徴とその発癌ポテンシャルの検討

平井亮佑, 衣笠秀明, 平岡佐規子, 田中健大, 大塚基之

日本消化器病学会雑誌 121 ( 臨増総会 ) A215 - A215 2024.3

Long-term monitoring of gastric mucosa-associated lymphoid tissue lymphoma in patients with extra copies of the MALT1 gene. Reviewed International journal

Masaya Iwamuro, Ryuta Takenaka, Koji Miyahara, Shotaro Okanoue, Masao Yoshioka, Chihiro Sakaguchi, Kumiko Yamamoto, Yoshinari Kawai, Tatsuya Toyokawa, Takehiro Tanaka, Motoyuki Otsuka

Scientific reports 14 ( 1 ) 4953 - 4953 2024.2

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

The objective of this study was to clarify the long-term prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma with additional copies of MALT1. In this multicenter retrospective study, we enrolled 145 patients with gastric MALT lymphoma who underwent fluorescence in situ hybridization (FISH) analysis to detect t(11;18) translocation. The patient cohort was divided into three groups: Group A (n = 87), comprising individuals devoid of the t(11;18) translocation or extra MALT1 copies; Group B (n = 27), encompassing patients characterized by the presence of the t(11;18) translocation; and Group C (n = 31), including patients with extra MALT1 copies. The clinical outcomes in each cohort were collected. Over the course of a mean follow-up of 8.5 ± 4.2 years, one patient died of progressive MALT lymphoma, while 15 patients died due to etiologies unrelated to lymphoma. The progression or relapse of MALT lymphoma was observed in 11 patients: three in Group A, two in Group B, and six in Group C. In Groups A, B, and C, the 10-year overall survival rates were 82.5%, 93.8%, and 86.4%, respectively, and the 10-year event-free survival rates were 96.1%, 96.0%, and 82.9%, respectively. The event-free survival rate in Group C was significantly lower than that in Group A. However, no differences were observed in the 10-year event-free survival rates among individuals limited to stage I or II1 disease (equivalent to excluding patients with stage IV disease in this study, as there were no patients with stage II2), with rates of 98.6%, 95.8%, and 92.3% for Groups A, B, and C, respectively. In conclusion, the presence of extra copies of MALT1 was identified as an inferior prognostic determinant of event-free survival. Consequently, trisomy/tetrasomy 18 may serve as an indicator of progression and refractoriness to therapeutic intervention in patients with gastric MALT lymphoma, particularly stage IV gastric MALT lymphoma.

DOI： 10.1038/s41598-024-55663-9

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Endoscopic and clinical features of gastric emphysema. Reviewed International journal

Masaya Iwamuro, Ryuta Takenaka, Tatsuya Toyokawa, Masahide Kita, Takao Tsuzuki, Masao Yoshioka, Tatsuhiro Gotoda, Shotaro Okanoue, Minoru Matsubara, Chihiro Sakaguchi, Motoyuki Otsuka

Scientific reports 14 ( 1 ) 2202 - 2202 2024.1

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

Gastric emphysema is characterized by the presence of intramural gas in the stomach without bacterial infection. Due to its rarity, most reports on gastric emphysema have been limited to single-case studies, and this condition's clinical and endoscopic features have not been thoroughly investigated. In this study, we analyzed 45 patients with gastric emphysema from 10 institutions and examined their characteristics, endoscopic features, and outcomes. The mean age at diagnosis of gastric emphysema in our study population (35 males and 10 females) was 68.6 years (range, 14-95 years). The top five underlying conditions associated with gastric emphysema were the placement of a nasogastric tube (26.7%), diabetes mellitus (20.0%), post-percutaneous endoscopic gastrostomy (17.8%), malignant neoplasms (17.8%), and renal failure (15.6%). Among the 45 patients, 42 were managed conservatively with fasting and administration of proton pump inhibitors. Unfortunately, seven patients died within 30 days of diagnosis, and 35 patients experienced favorable recoveries. The resolution of gastric emphysema was confirmed in 30 patients through computed tomography (CT) scans, with a mean duration of 17.1 ± 34.9 days (mean ± standard deviation [SD], range: 1-180 days) from the time of diagnosis to the disappearance of the gastric intramural gas. There were no instances of recurrence. Endoscopic evaluation was possible in 18 patients and revealed that gastric emphysema presented with features such as redness, erosion, coarse mucosa, and ulcers, with fewer mucosal injuries on the anterior wall (72.2%), a clear demarcation between areas of mucosal injury and intact mucosa (61.1%), and predominantly longitudinal mucosal injuries on the stomach folds (50.0%). This study is the first English-language report to analyze endoscopic findings in patients with gastric emphysema.

DOI： 10.1038/s41598-024-52633-z

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Anti-PD-1 Autoantibody Predicts Survival of Patients With Hepatocellular Carcinoma Receiving Atezolizumab/Bevacizumab Reviewed International journal

Yuki Sasaki, Kazuyuki Matsumoto, Akinobu Takaki, Takuya Adachi, Masahiro Takahara, Keita Ozato, Yasuto Takeuchi, Masahiko Sue, Nozomi Miyake, Nozomu Wada, Hideki Onishi, Hidenori Shiraha, Takashi Oda, Koichiro Tsutsumi, Kazuhiro Nouso, Kazuya Kariyama, Hiroaki Hagihara, Akio Moriya, Motoyuki Otsuka

Gastro Hep Advances 3 ( 8 ) 1138 - 1147 2024.1

Serum level of full-length connective tissue growth factor reflects liver fibrosis stage in patients with Fontan-associated liver disease. Reviewed International journal

Tomomi Kogiso, Kayo Takayanagi, Tsutomu Ishizuka, Motoyuki Otsuka, Kei Inai, Yuri Ogasawara, Kentaro Horiuchi, Makiko Taniai, Katsutoshi Tokushige

PloS one 19 ( 1 ) e0296375 2024

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

BACKGROUND: Chronic liver disease leads to liver fibrosis, and an accurate diagnosis of the fibrosis stage is crucial for medical management. Connective tissue growth factor (CTGF) is produced by endothelial cells and platelets and plays a central role in inducing fibrosis in various organs. In the present study, we tested the validity of measuring the serum levels of two types of CTGF to estimate the biopsy-confirmed liver fibrosis stage. METHODS: We used two detection antibodies targeting the N- and C-terminal of CTGF to measure the serum levels of two forms of CTGF consisting of its full length and its N-terminal fragment. We analyzed the level of CTGF (via enzyme-linked immunosorbent assay) and the liver fibrosis stage in 38 patients with Fontan-associated liver disease (FALD) (26 cases of which were diagnosed pathologically). Correlations were determined by multivariate analysis and the area under the receiver operating characteristic curve. The 65 patients with nonalcoholic fatty liver disease (NAFLD) were included as a disease control group for examination. RESULTS: Full-length CTGF was significantly inversely correlated with liver fibrosis in patients with FALD. Although the platelet count was also associated with the liver fibrosis stage, full-length CTGF was more closely correlated with the fibrosis stage. Furthermore, the level of full-length CTGF was inversely associated with high central venous pressure. Conversely, the serum level of CTGF was not correlated with the fibrosis stage in NAFLD. CONCLUSION: The serum level of full-length CTGF may be useful for estimating the liver fibrosis stage in patients with FALD.

DOI： 10.1371/journal.pone.0296375

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[Small intestinal perforation manifesting as post-transplant lymphoproliferative disorder occurring 23 years after living lung transplantation: a case report].

Daisuke Kametaka, Masaya Iwamuro, Shoko Inoo, Seiji Kawano, Takehiro Tanaka, Yoshiro Kawahara, Motoyuki Otsuka

Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology 121 ( 11 ) 896 - 903 2024

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

A Japanese female patient underwent a living lung transplant at age 29 and has been on immunomodulatory drug therapy since then. At age 52, she presented with sudden hematochezia. Despite abdominal computed tomography scan, esophagogastroduodenoscopy, and colonoscopy, no definitive source of bleeding was identified. Considering the possibility of small bowel bleeding, video capsule endoscopy was performed, which revealed a suspected ulcerative lesion in the jejunum. Subsequent per-oral double-balloon endoscopy confirmed the presence of an ulcerative lesion in the jejunum. A potential pathological diagnosis of post-transplant lymphoproliferative disorder (PTLD) was considered based on endoscopic biopsy specimens from the jejunal lesion. However, before the pathologic biopsy results were available, the patient experienced small intestinal perforation, necessitating emergency partial resection. Pathologic examination revealed a dense proliferation of medium-to-large atypical lymphocytes with neutrophilic infiltration in the perforated area of the small intestinal wall. Immunostaining showed lymphoid cells positive for CD20 but negative for CD3. Epstein-Barr virus (EBV) -encoded RNA was detected by in situ hybridization, and Ki-67 staining demonstrated a higher percentage of positive cells. Consequently, an EBV-positive diffuse large B-cell lymphoma, developed as PTLD, was diagnosed. Complete remission was achieved with a reduced immunomodulatory drug dosage and rituximab therapy. She has been alive for 8 months postoperatively without recurrence. This case suggests that PTLD should be considered in assessing patients presenting with abdominal symptoms following organ transplantation.

DOI： 10.11405/nisshoshi.121.896

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Alpha-fetoprotein and des-gamma-carboxy prothrombin can predict the objective response of patients with hepatocellular carcinoma receiving durvalumab plus tremelimumab therapy. Reviewed International journal

Issei Saeki, Shigeo Shimose, Tetsu Tomonari, Takanori Ito, Joji Tani, Yasuto Takeuchi, Naoki Yoshioka, Takehito Naito, Mamiko Takeuchi, Satoru Kakizaki, Takeshi Hatanaka, Kyo Sasaki, Tetsuya Yasunaka, Masahiro Sakata, Hideki Iwamoto, Satoshi Itano, Tomotake Shirono, Norikazu Tanabe, Takafumi Yamamoto, Yuki Kanayama, Atsushi Naganuma, Sohji Nishina, Motoyuki Otsuka, Hideki Kobara, Hiroki Kawashima, Tetsuji Takayama, Takumi Kawaguchi, Takahiro Yamasaki, Taro Takami

PloS one 19 ( 9 ) e0311084 2024

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

Durvalumab plus tremelimumab (Durva/Treme) combined immunotherapy is the first-line therapy recommended for unresectable hepatocellular carcinoma (HCC). Since sequential therapy is more effective in improving prognosis, tumor markers have been used as predictive biomarkers for response to systemic therapy. This study aimed to investigate the predictive ability of objective response (OR) by tumor markers for Durva/Treme therapy against HCC. In this multicenter study, 110 patients with HCC who received Durva/Treme therapy were retrospectively enrolled. The OR rate was 15.5%. To aid early decision-making regarding OR, we evaluated the predictors contributing to OR in two steps: before (first step) and 4 weeks after (second step) treatment induction. Changes in tumor markers (alpha-fetoprotein [AFP] and des-gamma-carboxy prothrombin [DCP]) from baseline to 4 weeks after treatment (ΔAFP/ΔDCP) were included as the input factors. In the first step, multivariable analysis identified only the baseline AFP level (odds ratio 3.497, p = 0.029) as a predictor of OR. Patients with AFP ≥ 400 ng/mL had a significantly higher OR rate than those with < 400 ng/mL (28.2 vs. 8.5%, p = 0.011), and there was no significant difference in progression-free survival (PFS) between the two groups. When AFP/DCP response was defined as a ≥10% reduction from baseline, multivariable analysis showed that AFP response (odds ratio 6.023, p = 0.042) and DCP response (odds ratio 11.657, p = 0.006) were both independent predictors of OR in the second step. The PFS of patients with AFP or DCP response was significantly longer than that of patients without AFP or DCP response. The study demonstrated that the use of AFP and DCP can predict the OR of patients with HCC receiving Durva/Treme therapy.

DOI： 10.1371/journal.pone.0311084

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Prospective observational study of zinc deficiency symptoms during first-line chemotherapy for gastric and colorectal cancer. Reviewed International journal

Chihiro Sakaguchi, Tomohiro Nishina, Yoshiyasu Kono, Kaori Hino, Akinori Asagi, Yoshinori Ohno, Takeshi Kajiwara, Seijin Nadano, Natsumi Yamashita, Mikiko Tohyama, Ichinosuke Hyodo, Hiroyuki Okada, Motoyuki Otsuka

Journal of gastrointestinal oncology 14 ( 6 ) 2384 - 2394 2023.12

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

BACKGROUND: Zinc deficiency during long-term chemotherapy and its related symptoms, including skin rash, taste disorders, and oral mucositis, have not been sufficiently investigated. METHODS: This prospective observational study enrolled patients with gastric and colorectal cancer who underwent standard first-line chemotherapy. According to the Practice Guidelines for Zinc Deficiency, zinc deficiency is defined as a serum level of <60 µg/dL. Serum zinc levels were measured before and after (1, 3, and 6 months) chemotherapy, and symptoms were assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events version 1.0. Repeated measures were analyzed using a generalized linear mixed model. RESULTS: Of the 61 enrolled patients, 48 who underwent standard first-line chemotherapy with fluoropyrimidine plus oxaliplatin were analyzed. Zinc deficiency was observed in 18 patients (38%) before chemotherapy. The least-squares means of serum zinc levels significantly decreased at 3 and 6 months of chemotherapy in 30 patients without zinc deficiency at the start of chemotherapy (both P<0.01) but not in 18 with zinc deficiency at the beginning. Changes in serum zinc levels during chemotherapy negatively correlated with changes in taste, rash, and itching (all P<0.04) in patients without zinc deficiency before treatment initiation. CONCLUSIONS: Serum zinc levels decreased during chemotherapy in zinc-non-deficient patients at the beginning of chemotherapy and correlated with taste changes, skin rash, and itching. Therefore, investigating whether zinc supplementation ameliorates these symptoms is necessary.

DOI： 10.21037/jgo-23-517

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Papers - Otsuka Motoyuki