Papers - NAKASE Hiroshi

Associations between serum insulin-like growth factor-related molecules and colorectal cancer risk by tumor location: a nested case-control study.

Yasushi Adachi, Masanori Nojima, Yingsong Lin, Yasushi Sasaki, Hiro-O Yamano, Hiroshi Nakase, Kenji Wakai, Mitsuru Mori, Akiko Tamakoshi

Digestion     1 - 19  2025.03  [International journal]

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Introduction, The activity of the mitogen insulin-like growth factor (IGF) is controlled by IGF-binding protein (IGFBP). Colorectal cancers (CRCs) are heterogeneous, with left- and right-sided CRC showing different clinical and molecular characteristics. This case-control study, nested in the Japan Collaborative Cohort study, assessed associations between serum levels of IGF-related molecules and incidences of CRC by location. Methods, A baseline survey obtained serum samples from 39,242 participants. Subjects diagnosed with CRC during follow-up were regarded as cases. Conditional logistic regression modeling was used to calculate odds ratios (ORs) for cancer incidence associated with IGF-related molecules. Results, This analysis included 176 cases and 524 controls. No IGF-related molecules appeared associated with risks of overall or left-sided CRC. Both total IGFBP3 and free IGFBP3 (estimated as IGFBP3-(IGF1+IGF2)) were associated with incidence of right-sided CRC (P-for-trends=0.027 and 0.003, respectively), with the third tertile of total and free IGFBP3 showing the highest risk (OR=6.25 and 7.96, respectively). Free IGF, estimated as (IGF1+IGF2)/IGFBP3, was inversely associated with incidence of right-sided CRC (P-for-trends=0.014), with the third tertile showing the lowest risk (OR=0.18). Among subjects followed for over 3 years, association of IGF-related molecules with overall CRC was similar. Free IGFBP3 was associated with incidence of right-sided CRC (P-for-trends=0.004). Free IGF was inversely associated with incidence of right-sided CRC (P-for-trends=0.002). However, free IGFs were associated with risk of left-sided CRC (P-for-trends=0.041), with the third tertile showing the highest risk (OR=3.10). Conclusions, Serum IGF-related molecules are associated with risk of CRC. These associations might differ by tumor location.

DOI PubMed

Ulcerative Colitis Preceding Asymptomatic Wilson’s Disease: A Case Report and Literature Review

Jun Kunizaki, Yuko Yoto, Yoshinobu Nagaoka, Akira Ishii, Tomoe Kazama, Kohei Wagatsuma, Noriyuki Akutsu, Aki Ishikawa, Toju Tanaka, Shintaro Sugita, Takeshi Tsugawa, Hiroshi Nakase

Gastro Hep Advances ( Elsevier BV )  4 ( 1 ) 100548 - 100548  2025

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Involvement of Mediterranean fever gene mutations in colchicine-responsive enterocolitis: a retrospective cohort study

Hiroshi Nakase, Kohei Wagatsuma, Taku Kobayashi, Takayuki Matsumoto, Motohiro Esaki, Kenji Watanabe, Reiko Kunisaki, Teruyuki Takeda, Katsuhiro Arai, Takashi Ibuka, Dai Ishikawa, Yuichi Matsuno, Hirotake Sakuraba, Nobuhiro Ueno, Kaoru Yokoyama, Masayuki Saruta, Ryota Hokari, Junji Yokoyama, Shu Tamano, Masanori Nojima, Tadakazu Hisamatsu, Shusaku Yoshikawa, Sohachi Nanjo, Akira Andoh, Takeshi Kimura, Makoto Ooi, Ryosuke Kiyomori, Nobuo Aoyama, Fumihito Hirai, Atsushi Yamaushi, Masanao Nakamura, Fumikazu Koyama, Shuhei Hosomi, Kazuki Kakimoto, Satoshi Motoya, Ryosuke Sakemi, Hideo Suzuki, Tadashi Hosoya, Ken Takeuchi, Manabu Shiraki, Hideyuki Koide, Ichiro Takeuchi, Yosuke Furui, Kento Yoshida, Ayaka Minemura, Asami Matsumoto, Kentaro Oka

eBioMedicine ( Elsevier BV )  110   105454 - 105454  2024.12

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A rare case of delayed duodenal perforation due to an over-the-scope clip.

Yujiro Kawakami, Shinji Yoshii, Masahiro Taniguchi, Yoshiharu Masaki, Taro Sugawara, Yasutoshi Kimura, Hiroshi Nakase

Endoscopy   56 ( S 01 ) E331-E333  2024.12  [International journal]

DOI PubMed

自己免疫性膵炎診療の現状と課題 自己免疫性膵炎診療における消化管精査の意義

川上 裕次郎, 柾木 喜晴, 仲瀬 裕志

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 )  66 ( Suppl.2 ) 2158 - 2158  2024.10

新規デバイスデリバリーシステムEndoSheatherを用いた経乳頭的胆嚢生検

川上 裕次郎, 柾木 喜晴, 大沼 法永, 中村 友哉, 石上 敬介, 室田 文子, 仲瀬 裕志

胆道 ( (一社)日本胆道学会 )  38 ( 3 ) 476 - 476  2024.09

Predictors of occult metastases in potentially Resectable pancreatic ductal adenocarcinoma.

Takeshi Murakami, Yasutoshi Kimura, Masafumi Imamura, Minoru Nagayama, Toru Kato, Kazuharu Kukita, Makoto Yoshida, Yoshiharu Masaki, Hiroshi Nakase, Ichiro Takemasa

Surgery open science   20   222 - 229  2024.08  [International journal]

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BACKGROUND: Patients with resectable (R) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) sometimes show unexpected liver, peritoneal, and para-aortic lymph node metastases intraoperatively. Despite radical pancreatectomy, a nonnegligible number of patients relapse within 6 months after surgery. The aim of this study was to identify the preoperative predictors of occult metastases (OM), defined as intraoperative distant metastases or within 6 months after pancreatectomy. MATERIALS AND METHODS: This study included patients with R and BR PDAC who underwent curative-intent pancreatectomy or staging laparoscopy between 2006 and 2021. Multivariate logistic regression and Cox hazard analyses were performed to identify the preoperative predictors of OM and to assess the impact of these factors on prognosis after pancreatectomy. RESULTS: Of the 279 patients, OM was observed intraoperatively in 47 and postoperatively in 34. In the OM group, there were no differences in prognosis between patients who had intraoperative metastases and recurrence within 6 months (median survival time [MST], 18.1 vs. 12.9 months), and between patients who underwent pancreatectomy and those who did not (MST, 13.9 vs. 18.1 months). Preoperative tumor size ≥22 mm (odds ratio [OR], 2.03; 95 % confidence interval [CI], 1.16-3.53; p = 0.013) and preoperative CA19-9 level ≥ 118.8 U/mL (OR, 2.64; 95 % CI, 1.22-5.73; p = 0.014) were significant predictors of OM. Additionally, positive OM predictors were strong independent prognostic factors for overall survival after pancreatectomy (hazard ratio, 2.47; 95 % CI, 1.54-3.98; p < 0.001). CONCLUSION: Multidisciplinary treatment strategies should be considered for patients with predictors of OM to avoid inappropriate surgical interventions.

DOI PubMed

若年発症自己免疫性肝炎に対する部分的脾動脈塞栓術後に肝機能改善を認めた1例

沼田 泰尚, 阿久津 典之, 我妻 康平, 川上 裕次郎, 石上 敬介, 柾木 喜晴, 室田 文子, 齊藤 正人, 仲瀬 裕志

日本臨床免疫学会総会プログラム・抄録集 ( (一社)日本臨床免疫学会 )  52回   113 - 113  2024.08

Unique endoscopic features of primary biliary diffuse large B‐cell lymphoma: A case report with literature review (with video)

Tomoya Nakamura, Yoshiharu Masaki, Naohiro Kameyama, Yujiro Kawakami, Keisuke Ishigami, Yumemi Takada, Shuji Satoh, Taro Sugawara, Shintaro Sugita, Hiroshi Nakase

DEN Open ( Wiley )  5 ( 1 )  2024.07

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Abstract A 67‐year‐old man visited our hospital complaining of dark‐colored urine and upper abdominal pain. Magnetic resonance cholangiopancreatography showed stricture of the distal bile duct, and contrast‐enhanced computed tomography showed irregular thickening of the distal bile duct wall. However, no enlarged lymph nodes, pancreatic tumors, or other neoplastic lesions were apparent around the bile duct. Endoscopic ultrasonography and intraductal ultrasonography showed irregular thickening of the inner hypoechoic layer without the disappearance of the innermost thin hyperechoic layer. On the basis of these findings, we considered that the bile duct lesion was of non‐epithelial origin. Thus, we repeatedly performed bile duct biopsies from the same site under fluoroscopy to obtain a sample of the submucosal tissue. The pathological diagnosis was diffuse large B‐cell lymphoma, and the patient received systemic chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). After six courses of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, positron emission tomography‐computed tomography showed the disappearance of 18‐fluorodeoxyglucose uptake in the bile duct and endoscopic retrograde cholangiography showed improvement of the bile duct stricture. Endoscopic findings and repeated biopsies were useful in making the diagnosis of primary biliary diffuse large B‐cell lymphoma.

DOI

膵EUS-FNA診断の功罪 切除不能膵臓癌のがんゲノムプロファイリング検査のための適正な検体採取方法の検討

室田 文子, 大沼 法永, 中村 友哉, 平野 雄大, 我妻 康平, 川上 裕次郎, 石上 敬介, 柾木 喜晴, 仲瀬 裕志

膵臓 ( (一社)日本膵臓学会 )  39 ( 3 ) A237 - A237  2024.07

Clinical performance of fecal calprotectin, lactoferrin, and hemoglobin for evaluating the disease activity of IBD and detecting colorectal tumors.

Tsukasa Yamakawa, Takakazu Miyake, Yoshihiro Yokoyama, Tomoe Kazama, Yuki Hayashi, Daisuke Hirayama, Shinji Yoshii, Hiro-O Yamano, Satoshi Takahashi, Hiroshi Nakase

JGH open : an open access journal of gastroenterology and hepatology   8 ( 6 ) e13077  2024.06  [International journal]

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BACKGROUND AND AIM: Recently, noninvasive fecal markers have been used as indicators of intestinal inflammation in patients with inflammatory bowel disease (IBD). We conducted a clinical validation study to measure fecal calprotectin (Cp), lactoferrin (Lf), and hemoglobin (Hb) levels using an all-in-one kit in patients with IBD and colorectal tumors and aimed to clarify the utility of these fecal markers. METHODS: In this study, 104 patients were analyzed, including 25 patients with ulcerative colitis (UC), 20 with Crohn's disease (CD), 48 with colorectal tumors, and 13 healthy controls (HC). Of the 48 patients with colorectal tumors, 14 had invasive cancer. We validated the utility of fecal Cp, Lf, and Hb levels by simultaneously measuring fecal markers in patients with IBD and colorectal tumors. RESULTS: Fecal Cp and Lf had almost equivalent abilities in detecting clinical remission in patients with UC; however, fecal Cp was slightly superior to Lf. Regarding colorectal tumors, fecal Cp and Lf levels tended to be higher in patients with adenomas and colorectal cancer than in HCs. Although fecal Hb alone had the best sensitivity and specificity for detecting colorectal cancer, it had relatively low sensitivity for detecting advanced neoplasms and colorectal cancer. CONCLUSION: Fecal Cp and Lf can be used as almost equivalent biomarkers to assess the clinical activity in patients with UC. Fecal Hb is the most useful marker for screening colorectal cancer; however, adding fecal Cp and Lf may compensate for the low sensitivity of detecting for advanced colorectal tumors based on Hb alone.

DOI PubMed

研究者の最新動向 難治性腸炎に対する間葉系幹細胞を用いた細胞療法

永石 歓和, 仲瀬 裕志

Precision Medicine ( (株)北隆館 )  7 ( 7 ) 593 - 597  2024.06

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間葉系幹細胞(Mesenchymal Stem Cells:MSC)は,多彩な生理活性物質を産生・分泌して免疫制御能や組織修復・再生能を発揮する体性幹細胞である。炎症組織では,MSCが局所の炎症性サイトカインによる刺激を受けて活性化する。MSCは,各種方法で3次元培養することで免疫制御能や血管新生能,抗アポトーシス効果などの細胞機能が向上する。MSCは,炎症性腸疾患領域における新しい治療選択肢として実用化とさらなる研究開発が進んでいる。(著者抄録)

Peroral cholangioscopy-guided biopsy with novel biopsy forceps in comprehensive cancer genomic profiling for cystic duct carcinoma

Yujiro Kawakami, Yoshiharu Masaki, Keisuke Ishigami, Takehiro Hirano, Ayako Murota, Shintaro Sugita, Hiroshi Nakase

Endoscopy ( Georg Thieme Verlag KG )  56 ( S 01 ) E414 - E415  2024.05

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Cytokine Profile in Predicting the Effectiveness of Advanced Therapy for Ulcerative Colitis: A Narrative Review.

Hiroki Kurumi, Yoshihiro Yokoyama, Takehiro Hirano, Kotaro Akita, Yuki Hayashi, Tomoe Kazama, Hajime Isomoto, Hiroshi Nakase

Biomedicines   12 ( 5 )  2024.04  [International journal]

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Cytokine-targeted therapies have shown efficacy in treating patients with ulcerative colitis (UC), but responses to these advanced therapies can vary. This variability may be due to differences in cytokine profiles among patients with UC. While the etiology of UC is not fully understood, abnormalities of the cytokine profiles are deeply involved in its pathophysiology. Therefore, an approach focused on the cytokine profile of individual patients with UC is ideal. Recent studies have demonstrated that molecular analysis of cytokine profiles in UC can predict response to each advanced therapy. This narrative review summarizes the molecules involved in the efficacy of various advanced therapies for UC. Understanding these associations may be helpful in selecting optimal therapeutic agents.

DOI PubMed

Real-world NUDT15 genotyping and thiopurine treatment optimization in inflammatory bowel disease: a multicenter study.

Motoki Makuuchi, Yoichi Kakuta, Junji Umeno, Toshimitsu Fujii, Tetsuya Takagawa, Takashi Ibuka, Miki Miura, Yu Sasaki, Sakuma Takahashi, Hiroshi Nakase, Hiroki Kiyohara, Keiichi Tominaga, Yosuke Shimodaira, Sakiko Hiraoka, Nobuhiro Ueno, Shunichi Yanai, Takeo Yoshihara, Kazuki Kakimoto, Katsuyoshi Matsuoka, Ryohei Hayashi, Sohachi Nanjo, Itaru Iwama, Yoh Ishiguro, Hirofumi Chiba, Katsuya Endo, Takashi Kagaya, Tomohiro Fukuda, Yasuhisa Sakata, Takahiro Kudo, Tomohisa Takagi, Kenichi Takahashi, Makoto Naganuma, Masaru Shinozaki, Noriyuki Ogata, Hiroki Tanaka, Kazuyuki Narimatsu, Haruka Miyazaki, Takashi Ishige, Motoyuki Onodera, Yu Hashimoto, Hiroshi Nagai, Yusuke Shimoyama, Takeo Naito, Rintaro Moroi, Hisashi Shiga, Yoshitaka Kinouchi, Akira Andoh, Tadakazu Hisamatsu, Atsushi Masamune

Journal of gastroenterology    2024.04  [Domestic journal]

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BACKGROUND: This study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world data, and aimed to establish genotype-based treatment strategies. METHODS: A retrospective analysis of 4628 IBD patients who underwent NUDT15 codon 139 genotyping was conducted. This study assessed the purpose of the genotyping test and subsequent prescriptions following the obtained results. Outcomes were compared between the Genotyping group (thiopurine with genotyping test) and Non-genotyping group (thiopurine without genotyping test). Risk factors for adverse events (AEs) were analyzed by genotype and prior genotyping status. RESULTS: Genotyping test for medical purposes showed no significant difference in thiopurine induction rates between Arg/Arg and Arg/Cys genotypes, but nine Arg/Cys patients opted out of thiopurine treatment. In the Genotyping group, Arg/Arg patients received higher initial doses than the Non-genotyping group, while Arg/Cys patients received lower ones (median 25 mg/day). Fewer AEs occurred in the Genotyping group because of their lower incidence in Arg/Cys cases. Starting with < 25 mg/day of AZA reduced AEs in Arg/Cys patients, while Arg/Arg patients had better retention rates when maintaining ≥ 75 mg AZA. Nausea and liver injury correlated with thiopurine formulation but not dosage. pH-dependent mesalamine reduced leukopenia risk in mesalamine users. CONCLUSIONS: NUDT15 codon 139 genotyping effectively reduces thiopurine-induced AEs and improves treatment retention rates in IBD patients after genotype-based dose adjustments. This study provides data-driven treatment strategies based on genotype and identifies risk factors for specific AEs, contributing to a refined thiopurine treatment approach.

DOI PubMed

ESD後穿孔における縫縮困難例への対策

山川 司, 吉井 新二, 秋田 浩太朗, 三宅 高和, 川上 裕次郎, 柾木 喜晴, 山野 泰穂, 仲瀬 裕志

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 )  66 ( Suppl.1 ) 1019 - 1019  2024.04

膵腫瘤性病変に対するTrident針とFranseen針を用いたEUS-FNBの比較検討

中村 友哉, 川上 裕次郎, 大沼 法永, 平野 雄大, 我妻 康平, 沼田 泰尚, 石上 敬介, 柾木 喜晴, 室田 文子, 阿久津 典之, 仲瀬 裕志

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 )  66 ( Suppl.1 ) 995 - 995  2024.04

A rare case of resection of a mucinous cystic neoplasm originating from the extrahepatic bile duct with cholangioscopic imaging.

Yoshiharu Masaki, Yujiro Kawakami, Keisuke Ishigami, Ayako Murota, Masahiro Shitani, Kazuharu Kukita, Yasutoshi Kimura, Keiko Segawa, Tadashi Hasegawa, Hiroshi Nakase

DEN open   4 ( 1 ) e349  2024.04  [International journal]

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A 29-year-old woman was admitted to our hospital for examination of obstructive jaundice and an extrahepatic bile duct lesion. Contrast-enhanced computed tomography revealed a 20 mm cystic lesion with a thin external capsule in the common hepatic duct. Cholangioscopy revealed translucent oval masses with capillary vessels attached to the bile duct walls. The surface was mostly smooth yet partially irregular with redness, suggesting that the masses were epithelial neoplasms. Histological findings of cholangioscopy-guided targeted biopsies of the mass showed subepithelial spindle cell proliferation with no atypical epithelium. The patient underwent an extrahepatic bile duct resection to confirm the pathological diagnosis. Immunohistochemistry of surgical specimens revealed that the spindle cells were positive for estrogen and progesterone receptors. Finally, the cystic lesion with ovarian-like stroma was diagnosed as a mucinous cystic neoplasm with low-grade intraepithelial neoplasia. This is the first report of cholangioscopic imaging of a biliary mucinous cyctic neoplasm. Cholangioscopic imaging can be helpful in the differential diagnosis of biliary neoplasms and in the determination of treatment strategies.

DOI PubMed

Effectiveness and Persistency of Ustekinumab Treatment for Ulcerative Colitis: A Phoenix retrospective Cohort Study.

Katsuyoshi Ando, Mikihiro Fujiya, Nobuhiro Ueno, Takahiro Ito, Atsuo Maemoto, Masanao Nasuno, Hiroki Tanaka, Kensuke Sakurai, Takehiko Katsurada, Fumika Orii, Toshifumi Ashida, Satoshi Motoya, Tomoe Kazama, Yoshihiro Yokoyama, Daisuke Hirayama, Hiroshi Nakase

Crohn's & colitis 360   6 ( 2 ) otae024  2024.04  [International journal]

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BACKGROUND: Real-world data regarding ustekinumab (UST) for ulcerative colitis (UC) particularly in biologics-naïve patients is currently limited. This study aimed to elucidate the real-world effectiveness and safety of UST for UC. METHODS: Overall, 150 patients with UC treated with UST from March 2020 to January 2023 were enrolled across 7 referral hospitals. To assess the clinical efficacy and persistence of UST, retrospective analyses were conducted from weeks 8 to 56. Predictive factors concerning the response and persistence of UST were examined through univariate and multivariate analyses. RESULTS: Of the 150 patients, 125 received UST for remission induction, including 36% biologics-naïve. The response and remission rates were 72.8% and 56.0% at week 8 and 73.2% and 63.4% at week 56, respectively. Biologics-naïve patients represented higher response and remission rates at week 8 (84.4% and 73.3%) than those with biologics exposure (66.2% and 46.2%). Patients with prior antitumor necrosis factor (anti-TNF) and vedolizumab (VDZ) exposure had relatively lower response and remission rates (34.5% and 24.1%, respectively). The 1-year cumulative persistence rate was 84.0%. Multivariate analysis revealed that the chronic continuous type and prior anti-TNF and VDZ exposure were negative predictive factors for week 8 responsiveness. Clinical response at week 8 was a predictor of 1-year persistence. Adverse event incidence remained notably low at 6.4%. CONCLUSIONS: This study highlights the safety and effectiveness of UST as an induction and maintenance therapy for UC. Chronic continuous type and previous anti-TNF and VDZ exposure negatively contributed to short-term effectiveness, whereas short-term effectiveness provided good persistency.

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十二指腸乳頭部腫瘍に対するhybrid EPの有用性

川上 裕次郎, 柾木 喜晴, 仲瀬 裕志

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 )  66 ( Suppl.1 ) 982 - 982  2024.04