Faculty Profiles - Otsuka Motoyuki

Papers - Otsuka Motoyuki

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【膵・胆道癌の発生・進展メカニズムを探る】膵癌の薬剤耐性メカニズム

寺澤裕之, 堤康一郎, 原田圭, 服部直, 菊池達也, 小幡泰介, 佐藤亮介, 織田崇志, 松三明宏, 宮本和也, 藤井佑樹, 赤穂宗一郎, 内田大輔, 松本和幸, 堀口繁, 大塚基之

胆と膵 45 ( 8 ) 801 - 806 2024.8

【膵・胆道癌の発生・進展メカニズムを探る】胆道癌の薬剤耐性メカニズム

堤康一郎, 小幡泰介, 織田崇志, 松三明宏, 宮本和也, 寺澤裕之, 藤井佑樹, 内田大輔, 松本和幸, 堀口繁, 大塚基之

胆と膵 45 ( 8 ) 857 - 862 2024.8

【膵・胆道癌の発生・進展メカニズムを探る】膵癌の薬剤耐性メカニズム

胆と膵 45 ( 8 ) 801 - 806 2024.8

【今推しの肝胆膵研究手法と疾患モデル】新規モデルによる肝胆膵研究胆嚢オルガノイドを用いた新規治療の開発

織田崇志, 堤康一郎, 大塚基之

肝胆膵 89 ( 2 ) 249 - 254 2024.8

Recent updates on treatment options for primary follicular lymphoma of the gastrointestinal tract. Reviewed International journal

Masaya Iwamuro, Takehiro Tanaka, Daisuke Ennishi, Motoyuki Otsuka

Expert review of gastroenterology & hepatology 18 ( 7 ) 1 - 9 2024.7

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

BACKGROUND: Primary gastrointestinal follicular lymphoma is a subtype of follicular lymphoma that originates directly from the gastrointestinal tract. Pathologically, it exhibits substantial similarities with the secondary gastrointestinal involvement observed in nodal follicular lymphoma. However, primary gastrointestinal follicular lymphoma presents clinically distinct features, necessitating divergent considerations in treatment selection compared with nodal follicular lymphoma. AREAS COVERED: This narrative review focused on recent articles (2018-2023) regarding the long-term prognosis and treatment options for gastrointestinal follicular lymphoma. In addition, a brief overview of gastrointestinal follicular lymphomas is provided. EXPERT OPINION: Patients with primary gastrointestinal follicular lymphoma often present with a low tumor burden. Lymphoma lesions typically remain asymptomatic for several years or may undergo spontaneous regression without immediate treatment. Therefore, a 'watch and wait' approach is justified. Conversely, when large tumor masses are identified in the gastrointestinal tract, the potential for tumor bleeding or intestinal obstruction requires timely therapeutic interventions.

DOI： 10.1080/17474124.2024.2380337

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Characteristics of Early Gastric Cancer in a Patient with a History of Helicobacter pylori Infection and No History of Eradication Therapy. Reviewed

Sakiko Kuraoka, Seiji Kawano, Shoko Ino, Takuya Satomi, Kenta Hamada, Yoshiyasu Kono, Masaya Iwamuro, Yoshiro Kawahara, Takehiro Tanaka, Hiroyuki Okada, Motoyuki Otsuka

Internal medicine (Tokyo, Japan) 64 ( 3 ) 343 - 350 2024.7

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

Objective The characteristics of gastric cancer in patients with atrophic mucosa and no apparent history of Helicobacter pylori eradication have not been thoroughly investigated. Therefore, this study examined the clinicopathological characteristics of gastric cancer in these patients. Methods We retrospectively examined the endoscopic and pathological characteristics of gastric cancer in patients who underwent endoscopic submucosal dissection. Patients or Materials We divided the patients into 2 groups: those with gastric atrophy and no history of eradication (group A; n =102) and those with a history of eradication (group B; n =161). In group A, patients were further divided into mild atrophy (group C) and severe atrophy (group D) groups, while group B was further divided into those who underwent eradication treatment >5 years ago (group E) and those who underwent eradication 1-5 years ago (group F). Results Group A comprised significantly older individuals (75±8.0 vs. 71±7.5 years old, p <0.001) with a higher frequency of elevated gastric cancer than group B (32.4% vs. 17.4%, p =0.006). Compared with group E, group A was older and had a greater incidence of elevated gastric cancer. The incidence of gastric cancer in the U or M region was lower in group C than in group D. Conclusion Gastric cancer in patients with gastric atrophy and no history of eradication was associated with an older age and higher frequency of elevated-type morphology than in those with a history of eradication.

DOI： 10.2169/internalmedicine.3617-24

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Colorectal Ganglioneuromas Associated with Cowden Syndrome. Reviewed

Toshiki Ozato, Yasushi Yamasaki, Toshihiro Inokuchi, Motoyuki Otsuka

Internal medicine (Tokyo, Japan) 63 ( 13 ) 1959 - 1960 2024.7

Response to the letter: "Predictive factors for transition to conversion therapy in HCC using atezolizumab plus bevacizumab". Reviewed International journal

Tatsuya Kikuchi, Yasuto Takeuchi, Kazuhiro Nouso, Kazuya Kariyama, Kenji Kuwaki, Junichi Toshimori, Shota Iwado, Akio Moriya, Hiroaki Hagihara, Hiroyuki Takabatake, Toshifumi Tada, Tetsuya Yasunaka, Masahiro Sakata, Masahiko Sue, Nozomi Miyake, Takuya Adachi, Nozomu Wada, Hideki Onishi, Hidenori Shiraha, Akinobu Takaki, Motoyuki Otsuka

Liver international : official journal of the International Association for the Study of the Liver 44 ( 7 ) 1736 - 1737 2024.7

Small Intestinal Complications of Intestinal Transplant-Associated Microangiopathy Post-stem Cell Transplantation. Reviewed International journal

Daisuke Kametaka, Masaya Iwamuro, Takehiro Tanaka, Ken-Ichi Matsuoka, Motoyuki Otsuka

Cureus 16 ( 7 ) e64111 2024.7

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

We present the case of a patient who underwent human leukocyte antigen-haploidentical transplantation for T-cell acute lymphoblastic leukemia. Seven weeks after transplantation, the patient developed intestinal transplant-associated microangiopathy (iTAM). Although the iTAM was resolved temporarily, it recurred. Video capsule enteroscopy revealed multiple erosions and shallow ulcers in the jejunum and ileum. To the best of our knowledge, this is the first report to present images of possible small intestinal lesions in iTAM. The small intestinal mucosal images presented herein may potentially aid in the management of similar patients.

DOI： 10.7759/cureus.64111

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Risk factors and treatment strategies for cholecystitis after metallic stent placement for malignant biliary obstruction: a multicenter retrospective study. Reviewed International journal

Akihiro Matsumi, Hironari Kato, Taiji Ogawa, Toru Ueki, Masaki Wato, Masakuni Fujii, Tatsuya Toyokawa, Ryo Harada, Yuki Ishihara, Masahiro Takatani, Hirofumi Tsugeno, Naoko Yunoki, Takeshi Tomoda, Toshiharu Mitsuhashi, Motoyuki Otsuka

Gastrointestinal endoscopy 100 ( 1 ) 76 - 84 2024.7

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

BACKGROUND AND AIMS: Cholecystitis can occur after self-expandable metallic stent (SEMS) placement for malignant biliary obstruction (MBO), but the best treatment option for cholecystitis has not been determined. Here, we aimed to identify the risk factors of cholecystitis after SEMS placement and determine the best treatment option. METHODS: Incidence, treatments, and predictive factors of cholecystitis were retrospectively evaluated in 1084 patients with distal MBO (DMBO) and 353 patients with hilar MBO (HMBO) who underwent SEMS placement at 12 institutions from January 2012 to March 2021. RESULTS: Cholecystitis occurred in 7.5% of patients with DMBO and 5.9% of patients with HMBO. The recurrence rate was significantly lower (P = .043) and the recurrence-free period significantly longer (P = .039) in endoscopic procedures than in percutaneous procedures for cholecystitis treatment. EUS-guided gallbladder drainage (EUS-GBD) was better in terms of technical success, procedure time, and recurrence-free period than endoscopic transpapillary gallbladder drainage. Obstruction across the cystic duct orifice by tumor (P = .015) and by stent (P = .037) were independent risk factors for cholecystitis in DMBO. Cases with multiple SEMS placements (odds ratio [OR], 11; 95% confidence interval [CI], 0.68-190; P = .091) and with gallbladder stones (OR, 2.3; 95% CI ,0.92-5.6; P = .075) had a higher risk for cholecystitis in HMBO. CONCLUSIONS: The incidences of cholecystitis after SEMS placement for DMBO and HMBO were similar. EUS-GBD is the optimal treatment option for patients with cholecystitis after SEMS placement for MBO.

DOI： 10.1016/j.gie.2024.02.019

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後期高齢者におけるIPMNの治療移行割合及び長期経過についての検討

宮本和也, 松本和幸, 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, 内田大輔, 堀口繁, 堤康一郎, 加藤博也, 大塚基之

膵臓 39 ( 3 ) A425 - A425 2024.7

膵EUS-FNA診断の功罪嚢胞・壊死を伴う膵管癌に対するFNA/B合併症リスクの検討

寺澤裕之, 松本和幸, 田中健大, 友田健, 小川泰司, 石原裕基, 菊池達也, 小幡泰介, 織田崇志, 松三明宏, 宮本和也, 森本光作, 藤井佑樹, 山崎辰洋, 内田大輔, 堀口繁, 堤康一郎, 加藤博也, 大塚基之

膵臓 39 ( 3 ) A234 - A234 2024.7

Predictive factors for transition to conversion therapy in hepatocellular carcinoma using atezolizumab plus bevacizumab. Reviewed International journal

Liver international : official journal of the International Association for the Study of the Liver 44 ( 6 ) 1456 - 1463 2024.6

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

BACKGROUND: To identify predictive factors associated with successful transition to conversion therapy following combination therapy with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC). METHODS: In total, 188 patients with HCC, who received atezolizumab plus bevacizumab combination therapy as the first-line chemotherapy, were studied. Patients who achieved complete response (CR) with systemic chemotherapy alone were excluded. Clinical factors possibly linked to successful transition to conversion therapy and the achievement of cancer-free status were identified. RESULTS: Fifteen (8.0%) patients underwent conversion therapy. In the conversion group, there was a significantly higher proportion of patients with Barcelona Clinic Liver Cancer (BCLC) stage A or B (73.3% versus [vs.] 45.1%; p = .03) and tended to have lower Child-Pugh scores and alpha-fetoprotein levels. Multivariate analysis revealed that BCLC stage was a predictive factor for the implementation of conversion therapy (A or B; odds ratio 3.7 [95% CI: 1.1-13]; p = .04). Furthermore, 10 (66.7%) patients achieved cancer-free status and exhibited a smaller number of intrahepatic lesions at the start of treatment (3.5 vs. 7; p < .01), and a shorter interval between systemic chemotherapy induction and conversion therapy (131 vs. 404 days; p < .01). In addition, the rate of achieving cancer-free status by undergoing surgical resection or ablation therapy was significantly higher (p = .03). CONCLUSION: BCLC stage was the sole predictive factor for successful transition to conversion therapy when using combination therapy with atezolizumab and bevacizumab to treat HCC. Furthermore, a small number of intrahepatic lesions and early transition to conversion therapy were associated with the achievement of cancer-free status.

DOI： 10.1111/liv.15907

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A Duodenal Ulcer and Biliopancreatic Lesions: What is the Culprit? Reviewed International journal

Ryosuke Sato, Kazuyuki Matsumoto, Motoyuki Otsuka

Gastroenterology 167 ( 7 ) 1266 - 1269 2024.5

Current status of endoscopic ultrasound-guided antitumor treatment for pancreatic cancer. Reviewed International journal

Kazuyuki Matsumoto, Hironari Kato, Koichiro Tsutsumi, Motoyuki Otsuka

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 37 ( 1 ) 18 - 28 2024.5

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

Endoscopic ultrasound (EUS) was developed in the 1990s and has significantly transformed pancreatic tumor diagnosis. Subsequently, EUS has rapidly shifted from being a purely diagnostic procedure to being used in a wide range of interventional procedures. Recently, new therapeutic techniques, such as EUS-guided fine needle injection (EUS-FNI) or radiofrequency ablation (RFA), have been developed to deliver various antitumor agents. Despite technological advancements, pancreatic cancer (PC) has a poor prognosis and improvements in treatment outcomes are urgently required. One of the reasons for the limited response to antitumor agents in PC is the abundant desmoplasia and hypovascular nature of the tumor, complicating drug delivery into the tumor. Thus, changing the tumor microenvironment may be important to enhance the effectiveness of chemotherapy, and direct injection of antitumor agents into the tumor under EUS guidance can help overcome treatment challenges in PC. Treatment approaches using the EUS-FNI or RFA technique are expected to further improve the prognosis of PC. Therefore, this study reviewed the existing literature on EUS-guided antitumor therapy, specifically highlighting its application in PC to address the current challenges and to identify potential advancements in the field.

DOI： 10.1111/den.14815

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Impact of Nutritional Status on Neutrophil-to-Lymphocyte Ratio as a Predictor of Efficacy and Adverse Events of Immune Check-Point Inhibitors. Reviewed International journal

Masahiko Sue, Yasuto Takeuchi, Shoichiro Hirata, Akinobu Takaki, Motoyuki Otsuka

Cancers 16 ( 10 ) 2024.5

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

The neutrophil -to-lymphocyte ratio (NLR) is useful for predicting the effectiveness of treatment with immune checkpoint inhibitors (ICIs) and immune-related adverse events (irAEs). Because a growing body of evidence has recently shown that the number of lymphocytes that comprise NLR fluctuates according to nutritional status, this study examined whether the usefulness of NLR varies in ICI treatment due to changes in nutritional status. A retrospective analysis was performed on 1234 patients who received ICI treatment for malignant tumors at our hospital. Progression-free survival (PFS) was significantly prolonged in patients with NLR < 4. Multivariate analysis revealed that the factors associated with the occurrence of irAE were NLR < 4 and the use of ipilimumab. However, when limited to cases with serum albumin levels <3.8 g/dL, lymphocyte counts significantly decreased, and the associations between NLR and PFS and between NLR and irAE occurrence disappeared. In contrast, when limited to the cases with serum albumin levels ≥3.8 g/dL, the associations remained, with significantly prolonged PFS and significantly increased irAE occurrence at NLR < 4. NLR may be a good predictive tool for PFS and irAE occurrence during ICI treatment when a good nutritional status is maintained.

DOI： 10.3390/cancers16101811

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Association of screening tool scores with overall survival in older patients with unresectable gastrointestinal or biliary pancreatic cancer: A retrospective study. Reviewed International journal

Shoko Inoo, Yoshiyasu Kono, Hiromitsu Kanzaki, Shigeru Horiguchi, Hironari Kato, Yasushi Yamasaki, Shoichiro Hirata, Sakiko Kuraoka, Katsunori Matsueda, Shotaro Okanoue, Takuya Satomi, Kenta Hamada, Masaya Iwamuro, Seiji Kawano, Yoshiro Kawahara, Hiroyuki Okada, Motoyuki Otsuka

Journal of geriatric oncology 15 ( 4 ) 101714 - 101714 2024.5

Drug-induced mucosal alterations observed during esophagogastroduodenoscopy. Reviewed International journal

Masaya Iwamuro, Seiji Kawano, Motoyuki Otsuka

World journal of gastroenterology 30 ( 16 ) 2220 - 2232 2024.4

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

Several features of drug-induced mucosal alterations have been observed in the upper gastrointestinal tract, i.e., the esophagus, stomach, and duodenum. These include pill-induced esophagitis, desquamative esophagitis, worsening of gastroesophageal reflux, chemotherapy-induced esophagitis, proton pump inhibitor-induced gastric mucosal changes, medication-induced gastric erosions and ulcers, pseudomelanosis of the stomach, olmesartan-related gastric mucosal inflammation, lanthanum deposition in the stomach, zinc acetate hydrate tablet-induced gastric ulcer, immune-related adverse event gastritis, olmesartan-asso-ciated sprue-like enteropathy, pseudomelanosis of the duodenum, and lanthanum deposition in the duodenum. For endoscopists, acquiring accurate knowledge regarding these diverse drug-induced mucosal alterations is crucial not only for the correct diagnosis of these lesions but also for differential diag-nosis of other conditions. This minireview aims to provide essential information on drug-induced mucosal alterations observed on esophagogastroduodenoscopy, along with representative endoscopic images.

DOI： 10.3748/wjg.v30.i16.2220

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Endoscopic manifestation of intestinal transplant-associated microangiopathy after stem cell transplantation. Reviewed International journal

Masaya Iwamuro, Daisuke Ennishi, Nobuharu Fujii, Ken-Ichi Matsuoka, Takehiro Tanaka, Toshihiro Inokuchi, Sakiko Hiraoka, Motoyuki Otsuka

BMC gastroenterology 24 ( 1 ) 140 - 140 2024.4

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

BACKGROUND: Endoscopic features of intestinal transplant-associated microangiopathy (iTAM) have not been comprehensively investigated. This study aimed to examine the endoscopic characteristics of patients diagnosed with iTAM. METHODS: This retrospective analysis included 14 patients pathologically diagnosed with iTAM after stem cell transplantation for hematolymphoid neoplasms (n = 13) or thalassemia (n = 1). The sex, age at diagnosis, endoscopic features, and prognosis of each patient were assessed. Serological markers for diagnosing transplant-associated thrombotic microangiopathy were also evaluated. RESULTS: The mean age at the time of iTAM diagnosis was 40.2 years. Patients diagnosed based on the pathognomonic pathological changes of iTAM presented with diverse symptoms at the times of endoscopic examinations, including diarrhea (n = 10), abdominal pain (n = 5), nausea (n = 4), appetite loss (n = 2), bloody stools (n = 2), abdominal discomfort (n = 1), and vomiting (n = 1). At the final follow-up, six patients survived, while eight patients succumbed, with a median time of 100.5 days (range: 52-247) post-diagnosis. Endoscopic manifestations included erythematous mucosa (n = 14), erosions (n = 13), ulcers (n = 9), mucosal edema (n = 9), granular mucosa (n = 9), and villous atrophy (n = 4). Erosions and/or ulcers were primarily observed in the colon (10/14, 71%), followed by the ileum (9/13, 69%), stomach (4/10, 40%), cecum (5/14, 36%), duodenum (3/10, 30%), rectum (4/14, 29%), and esophagus (1/10, 10%). Cytomegalovirus infection (n = 4) and graft-versus-host disease (n = 2) coexisted within the gastrointestinal tract. Patients had de novo prolonged or progressive thrombocytopenia (6/14, 43%), decreased hemoglobin concentration (4/14, 29%), reduced serum haptoglobin level (3/14, 21%), and a sudden and persistent increase in lactate dehydrogenase level (2/14, 14%). Peripheral blood samples from 12 patients were evaluated for schistocytes, with none exceeding 4%. CONCLUSIONS: This study provides a comprehensive exploration of the endoscopic characteristics of iTAM. Notably, all patients exhibited erythematous mucosa throughout the gastrointestinal tract, accompanied by prevalent manifestations, such as erosions (93%), ulcers (64%), mucosal edema (64%), granular mucosa (64%), and villous atrophy (29%). Because of the low positivity for serological markers of transplant-associated thrombotic microangiopathy in patients with iTAM, endoscopic evaluation and biopsy of these lesions are crucial, even in the absence of these serological features.

DOI： 10.1186/s12876-024-03221-y

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Detection of residual stones by peroral direct cholangioscopy in patients with intrahepatic stones after hepaticojejunostomy: A prospective study (with video). International journal

Kazuyuki Matsumoto, Hironari Kato, Akihiro Matsumi, Kazuya Miyamoto, Kosaku Morimoto, Yuki Fujii, Ryosuke Sato, Nao Hattori, Taisuke Obata, Hiroyuki Terasawa, Daisuke Uchida, Shigeru Horiguchi, Koichiro Tsutsumi, Motoyuki Otsuka

Gastrointestinal endoscopy 100 ( 3 ) 457 - 463 2024.4

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

BACKGROUND AND AIMS: The difficulty of radiographic confirmation of the presence of stones remains a challenge in the treatment of intrahepatic bile duct (IHBD) stones in patients after hepaticojejunostomy (HJ). Peroral direct cholangioscopy (PDCS) enables direct observation of the bile duct and is useful for detecting and removing residual stones; however, its effectiveness is not clearly established in this clinical context. METHODS: This single-center, single-arm, prospective study included 44 patients with IHBD who underwent bowel reconstruction with HJ during the study period. Stone removal was performed by short-type double-balloon enteroscopy (DBE). Following balloon-occluded cholangiography, the DBE was exchanged for an ultraslim endoscope through the balloon overtube for PDCS. The primary endpoint was the rate of residual stones detected by PDCS. Secondary endpoints were success rate of PDCS, residual stone removal with PDCS, procedure time for PDCS, procedure-related adverse events, and stone recurrence rate. RESULTS: PDCS was successful in 39/44 patients (89%), among whom residual stones were detected in 16 (41%) (95% CI: 28%-54%). Twelve patients (75%) had residual stones <5 mm. Stone removal was successful in 15 (94%) patients and median procedure time for PDCS was 16 (IQR: 10-26) min. The rate of procedure-related adverse events was 7% (3/44), all of which improved with conservative treatment. During median follow-up of 2.1 years (IQR: 1.4-3.3), the overall probability of recurrence-free status at 1, 2, and 3 years was 100%, 92%, and 86%, respectively. CONCLUSIONS: PDCS is a safe and effective procedure for complete stone removal in patients with IHBD stones after HJ.

DOI： 10.1016/j.gie.2024.04.014

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Papers - Otsuka Motoyuki