Details of a Researcher - NAKASE Hiroshi

Papers - NAKASE Hiroshi

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Endoscopic full-thickness resection using an over-the-scope clip for colon cancer within a diverticulum.

Takakazu Miyake, Shinji Yoshii, Hiroshi Nakase

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 35 ( 1 ) e30-e32 2023.01 [International journal]

DOI PubMed

Final Analysis of COVID-19 Patients With Inflammatory Bowel Disease in Japan (J-COSMOS): A Multicenter Registry Cohort Study.

Hiroshi Nakase, Yuki Hayashi, Yoshihiro Yokoyama, Takayuki Matsumoto, Minoru Matsuura, Hideki Iijima, Katsuyoshi Matsuoka, Naoki Ohmiya, Shunji Ishihara, Fumihito Hirai, Daiki Abukawa, Tadakazu Hisamatsu

Gastro hep advances 2 ( 8 ) 1056 - 1065 2023 [International journal]

BACKGROUND AND AIMS: Japan has experienced 8 waves of the coronavirus disease 2019 (COVID-19) outbreak over the past 3 years, resulting in an increasing number of deaths and incidence of severe infections. This study aimed to analyze the data from the Japanese inflammatory bowel disease (IBD) patients with COVID-19 registry (J-COSMOS) up to the eighth wave to investigate the clinical course of IBD patients with COVID-19 and factors contributing to disease severity. METHODS: In this multicenter, observational, cohort study, we analyzed a cohort of 1308 IBD patients diagnosed with COVID-19, enrolled across 77 participating facilities in the J-COSMOS registry from June 2020 to December 2022. Data on age, sex, IBD (classification, treatment, and activity), and COVID-19 (symptoms, severity, and treatment) were analyzed. RESULTS: The majority of patients (76%) were in clinical remission. According to the World Health Organization classification of COVID-19 severity, 98.4% of IBD patients had nonsevere disease, while 1.6% of patients had severe or critical disease. COVID-19 did not affect disease activity in most IBD patients. Stepwise logistic regression analysis revealed that high body mass index, and cerebrovascular disease were risk factors for severe COVID-19. Corticosteroids could affect COVID-19 severity, whereas anti-tumor necrosis factor α antibodies and thiopurines were associated with a reduced risk of severe COVID-19. No deaths were observed among IBD patients with COVID-19 registered in this cohort. CONCLUSION: The impact of COVID-19 on IBD disease activity and factors associated with COVID-19 severity were consistent with findings of previous reports. No deaths in Japanese patients with IBD were observed.

DOI PubMed

Long-term effectiveness and safety of infliximab-biosimilar: A multicenter Phoenix retrospective cohort study.

Tomoe Kazama, Katsuyoshi Ando, Nobuhiro Ueno, Mikihiro Fujiya, Takahiro Ito, Atsuo Maemoto, Keisuke Ishigami, Masanori Nojima, Hiroshi Nakase

PloS one 18 ( 9 ) e0288393 2023 [International journal]

BACKGROUND: Infliximab (IFX) effectively treats patients with inflammatory bowel disease (IBD). IFX-biosimilar (IFX-BS) has the same amino acid sequence as that of the IFX originator, and its increasing use is expected to reduce national healthcare costs. Long-term efficacy and safety of IFX-BS in patients with Crohn's disease (CD) and ulcerative colitis (UC) have not been completely investigated. METHODS: We conducted a retrospective, multicenter observational study of patients with IBD who received IFX-BS treatment at three hospitals between October 2016 and April 2022. Clinical data were collected from electronic medical records and evaluated for achieving clinical remission (CR) using Crohn's disease activity index (CDAI) and partial Mayo (pMayo) score, persistency of long-term IFX-BS administration, and clinical response rate in the bio-naïve and bio-failure groups. RESULTS: A total of 117 patients with IBD (90 CD and 27 UC) were included. The study findings indicated that both bio-naïve and bio-failure groups of patients with UC showed similar effectiveness of IFX-BS. The treatment persistence rate in patients with CD was significantly higher in the bio-naïve (P = 0.042) and switch (P = 0.010) groups than in the bio-failure group. In the former two groups, the treatment persistence rate was high at two years after administration (more than 80%). In patients with UC, the findings indicated higher treatment persistence rate in the switch group than in the bio-naïve group. Univariable and multivariable analyses for treatment persistence rate showed that the albumin level at the initial IFX-BS administration and groups (bio-naïve, bio-failure and switch) were effective factors for patients with CD. Adverse events were reported in 18 patients (15.4%). CONCLUSION: The present study demonstrates the long-term effectiveness and safety of IFX-BS. In addition to the favorable remission induction in the bio-naïve and bio-failure groups, we demonstrated remission maintenance and treatment persistence rates beyond two years. Albumin level and groups were associated with better treatment persistence in patients with CD.

DOI PubMed

Mesenchymal stem cellを知る

永石歓和, 仲瀬裕志

消化器病サイエンス 7 33 - 38 2023

Hybrid Endoscopic Resection With Endo-knife and Snare for Colorectal Lesions: A Systematic Review and Meta-analysis

Shinji Yoshii, Takefumi Kikuchi, Yuki Hayashi, Masahiro Nojima, Hiro-o Yamano, Hiroshi Nakase

Techniques and Innovations in Gastrointestinal Endoscopy ( Elsevier BV ) 25 ( 2 ) 135 - 145 2023 [Refereed]

DOI

Serum soluble Fas levels and incidence of liver cancer in nested case-control study.

Yasushi Adachi, Masanori Nojima, Mitsuru Mori, Toshiyuki Kubo, Noriyuki Akutsu, Yasushi Sasaki, Hiroshi Nakase, Yingsong Lin, Youichi Kurozawa, Kenji Wakai, Akiko Tamakoshi

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2022.12 [International journal]

BACKGROUND: Soluble Fas (sFas) plays various roles in carcinogenesis and tumor dissemination by preventing apoptosis via binding to Fas ligand. We analyzed associations of serum sFas levels with the incidence of liver cancer in a prospective case-control study nested in the JACC Study. METHODS: A baseline survey was conducted from 1988, with blood samples obtained from 39,242 subjects. Patients diagnosed with liver cancer were regarded as cases. Two or three controls were selected and matched for sex, age, and geographical area. Conditional logistic regression was used to estimate odds ratios (ORs) for cancer incidence associated with sFas. RESULTS: This study contained 86 cases and 249 controls. After controlling for alcohol intake, body mass index, smoking, and hepatitis viral infection, participants with high sFas showed elevated risk of cancer (P-trend = 0.003) and the third tertile of sFas showed a higher risk compared to the first tertile (OR = 3.53, 95% confidence interval (CI) = 1.28-9.69). In hepatocellular carcinoma, high sFas was associated with elevated risk (P-trend < 0.001). In men and the elderly, subjects in the highest tertiles showed higher cancer risk. Limiting subjects to those followed for 3 years, high sFas was related to liver cancer risk (P-trend = 0.033) and the third tertile showed a higher risk compared to the first (OR = 2.94, 95%CI = 0.94-9.14). CONCLUSIONS: High serum sFas may be related to future risk of liver cancer. IMPACT: Our findings highlight this biomarker for further analysis in pooled investigations with different/larger prospective cohorts.

DOI PubMed

Serum amyloid A1 recruits neutrophils to the invasive front of T1 colorectal cancers.

Ayano Yoshido, Gota Sudo, Akira Takasawa, Hironori Aoki, Hiroshi Kitajima, Eiichiro Yamamoto, Takeshi Niinuma, Taku Harada, Toshiyuki Kubo, Hajime Sasaki, Kazuya Ishiguro, Akira Yorozu, Masahiro Kai, Akio Katanuma, Hiro-O Yamano, Makoto Osanai, Hiroshi Nakase, Hiromu Suzuki

Journal of gastroenterology and hepatology 38 ( 2 ) 301 - 310 2022.11 [International journal]

BACKGROUND AND AIM: The tumor microenvironment plays an essential role in the development and progression of colorectal cancer (CRC). We recently reported that crosstalk between CRC cells and tumor-associated macrophages (TAMs) via serum amyloid A1 (SAA1) promotes invasion by T1 CRCs. In the present study, we aimed to clarify the role of neutrophils in early CRCs. METHODS: Immunohistochemical analysis of CD66b, chemokine CXC motif ligand 8 (CXCL8 or interleukin-8, IL-8) and matrix metalloproteinase-9 (MMP-9) was performed using primary T1 CRCs (n = 49). The HL-60 human promyelocytic leukemia cell line and THP-1 human monocytic leukemia cell line were used to obtain neutrophil-like and macrophage-like cells, respectively. Boyden chamber assays were used to analyze cell migration and invasion, and quantitative RT-PCR was used to analyze gene expression. RESULTS: Immunohistochemical analysis revealed accumulation of neutrophils at the SAA1-positive invasive front of T1 CRCs. Experiments using HL-60 cells suggested that treatment with SAA1 induced neutrophil migration and expression of CXCL8 and MMP-9 in neutrophils and that neutrophils promote CRC cell migration and invasion. Immunohistochemistry confirmed accumulation of CXCL8- or MMP-9-positive neutrophils at the SAA1-positive invasive front of T1 CRCs. Moreover, co-culture experiments using CRC, THP-1 and HL-60 cells suggested that CRC cells activated by macrophages upregulate CXCL8 and MMP-9 in neutrophils. CONCLUSIONS: Our results suggest that interplay between macrophages and CRC cells leads to recruitment of neutrophils to the invasive front of T1 CRCs and that SAA1 secreted by CRC cells activate neutrophils to promote invasion.

DOI PubMed

Guidelines for endoscopic balloon dilation in treating Crohn's disease-associated small intestinal strictures (supplement to the Clinical Practice Guidelines for Enteroscopy)

Hironori Yamamoto, Tomonori Yano, Akihiro Araki, Motohiro Esaki, Kazuo Ohtsuka, Naoki Ohmiya, Shiro Oka, Hiroshi Nakase, Shigeki Bamba, Fumihito Hirai, Naoki Hosoe, Tomoki Matsuda, Keigo Mitsui, Kenji Watanabe, Haruhiko Ogata, Shinichi Katsuki, Takayuki Matsumoto, Mitsuhiro Fujishiro, Kazuma Fujimoto, Haruhiro Inoue

DIGESTIVE ENDOSCOPY ( WILEY ) 34 ( 7 ) 1278 - 1296 2022.11

Balloon-assisted enteroscopy allows endoscopic treatments in the deeper segments of the small bowel. Endoscopic balloon dilation has become a popular minimally invasive alternative for the treatment of Crohn's disease-associated small intestinal strictures. As a supplement to the Clinical Practice Guidelines for Enteroscopy, the Japan Gastroenterological Endoscopy Society's Working Committee has developed the present "Guidelines for endoscopic balloon dilation in treating Crohn's disease-associated small intestinal strictures," based on new scientific techniques and evidence. The guidelines cover standard procedures for the insertion route of the balloon endoscope, bowel preparation, indications, procedure-related complications, efficacy, target diameter and duration, management of multiple strictures, and the current state of combined and alternative treatments. Unresolved future research questions are also listed in this guideline.

DOI

Guidelines for endoscopic balloon dilation in treating Crohn's disease-associated small intestinal strictures (supplement to the Clinical Practice Guidelines for Enteroscopy).

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 34 ( 7 ) 1278 - 1296 2022.11 [International journal]

DOI PubMed

A case of hepatocellular carcinoma with long-term survival by multidisciplinary treatment for cranial and skeletal muscle metastases.

Noriyuki Akutsu, Yujiro Kawakami, Yasunao Numata, Takehiro Hirano, Kohei Wagatsuma, Keisuke Ishigami, Shigeru Sasaki, Hiroshi Nakase

Clinical journal of gastroenterology 15 ( 5 ) 960 - 967 2022.10 [Domestic journal]

We report a case in which multidisciplinary treatment was effective for hepatocellular carcinoma (HCC) with cranial and skeletal muscle metastases. A 55-year-old male with HCC received sorafenib for lung metastases. He was admitted to our hospital due to the skull metastasis detected by fluorodeoxyglucose positron emission tomography (FDG-PET). The patient underwent resection for skull metastasis. After the surgical treatment, he was treated with sorafenib again. Eight months after craniectomy, FDG-PET showed FDG uptake in the semimembranosus and semitendinosus muscles. Histopathological examination of the muscle biopsy revealed HCC muscle metastasis. Sorafenib treatment was discontinued. The investigational new drug (tegafur-gimeracil-oteracil) and tegafur-uracil were used for the treatment. These treatments proved to be ineffective as the lung metastases enlarged and new metastases appeared on the mediastinal lymph nodes and dura cava. The patient was unable to walk due to the enlarged thigh muscle metastases. Sorafenib was re-administered, which reduced the enlargement of the lung and mediastinal lymph nodes. Dural metastases were treated with resection and radiotherapy. Additional radiation therapy to the thigh muscles relieved the patient from pain experienced during walking. Sorafenib treatment was continued for the next 3 years. The patient survived for 4 years after the skull resection.

DOI PubMed

血清SOD活性と大腸癌罹患リスク(Association of serum superoxide dismutase activity and the incidence of colorectal cancer in a nested case-control study)

足立靖, 野島正寛, 森満, 久保俊之, 山野泰穂, 佐々木泰史, 仲瀬裕志, 遠藤高夫, 林櫻松, 若井建志, 玉腰暁子

日本癌学会総会記事 ( (一社)日本癌学会 ) 81回 E - 3034 2022.09

血清SOD活性と大腸癌罹患リスク(Association of serum superoxide dismutase activity and the incidence of colorectal cancer in a nested case-control study)

足立靖, 野島正寛, 森満, 久保俊之, 山野泰穂, 佐々木泰史, 仲瀬裕志, 遠藤高夫, 林櫻松, 若井建志, 玉腰暁子

日本癌学会総会記事 ( (一社)日本癌学会 ) 81回 E - 3034 2022.09

内視鏡診療を想定した体外バキューム装置によるエアロゾル減少効果の報告

山野泰穂, 足立靖, 吉井新二, 仲瀬裕志

日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 ( 日本消化器病学会-北海道支部 ) 131回・125回 32 - 32 2022.09

小腸原発Gastrointestinal stromal tumor(GIST)に対するイマチニブ投与中に肝転移破裂、腹腔内出血をきたした1例

山本智香, 室田文子, 沼田泰尚, 川上裕次郎, 石上敬介, 柾木喜晴, 阿久津典之, 本谷雅代, 佐々木茂, 仲瀬裕志

日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 ( 日本消化器病学会-北海道支部 ) 131回・125回 46 - 46 2022.09

当院における悪性肝門部胆管狭窄に対するドレナージの成績

室田文子, 我妻康平, 川上裕次郎, 沼田泰尚, 石上敬介, 柾木喜晴, 阿久津典之, 本谷雅代, 佐々木茂, 仲瀬裕志

胆道 ( (一社)日本胆道学会 ) 36 ( 3 ) 445 - 445 2022.09

十二指腸乳頭部に神経線維腫を合併したvon-Reckling hausen病の1例

三浦克予志, 柾木喜晴, 浪岡万由子, 川上裕次郎, 石上敬介, 室田文子, 本谷雅代, 杉田真太郎, 仲瀬裕志

日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 ( 日本消化器病学会-北海道支部 ) 131回・125回 53 - 53 2022.09

Sustained Eosinophilic Cholangitis Due to a Mite Allergy Mimicking Sclerosing Cholangitis.

Masayo Motoya, Shun Takai, Hiroshi Moriya, Takehiro Hirano, Kohei Wagatsuma, Yasunao Numata, Yujiro Kawakami, Yoshiharu Masaki, Keisuke Ishigami, Ayako Murota, Hiroshi Nakase

Internal medicine (Tokyo, Japan) 61 ( 16 ) 2477 - 2482 2022.08 [Domestic journal]

Eosinophilic cholangiopathy (EC) presents with thickening and stenosis of the bile duct wall that is histologically characterized by eosinophil infiltration. The diagnosis is often difficult. We herein report a patient who had been followed up with a diagnosis of primary sclerosing cholangitis but had a final diagnosis of EC based on eosinophilia, histological findings of bile duct and liver biopsy specimens, and a review of a previous surgical specimen of the gallbladder. Antigen tests, isolation from her house, and accidental re-exposure to the antigen revealed that the causative antigen was the mite Dermatophagoides pteronyssinus.

DOI PubMed

Genomic analysis of an aggressive case with metastatic intrahepatic mucinous cholangiocarcinoma.

Yoshiharu Masaki, Noriyuki Akutsu, Yasushi Adachi, Keisuike Ishigami, Norikazu Iwata, Takao Endo, Yoshifumi Ishii, Yasushi Sasaki, Minoru Nagayama, Yasutoshi Kimura, Hiroshi Nakase

Clinical journal of gastroenterology 15 ( 4 ) 809 - 817 2022.08 [Domestic journal]

Intrahepatic mucinous cholangiocarcinoma (IHMC) is rare and behaves notoriously; however, the details of the clinicopathological characteristics of IHMC remain unknown. A 70-year-old man was admitted for examination of the hepatic mass in the S1 segment. He underwent extended left hepatic lobectomy. Histopathological evaluation demonstrated mixed papillary carcinoma that comprised well to moderately differentiated tubular adenocarcinoma and signet-ring cell carcinoma with large amounts of mucus lakes. Tumor was relapsed 9 months after surgery. Although he received chemotherapy with the combination of gemcitabine and cisplatin, he had renal failure and discontinued the chemotherapy. He received palliative radiotherapy for metastasis in the cervical spine. Then, the patient treated with S-1, however, he died 16 months after the initial diagnosis. The autopsy findings showed multiple nodules in the lungs, pleura, kidneys, adrenal glands, stomach, pancreas, and lymph nodes. Histological examination revealed that all nodules were IHMC. Next-generation sequencing revealed that somatic mutations in ADGRB3, TAF1L and EPHA3 may affect carcinogenesis, and those in TAF1, EPHA3, PIK3C2B, FN1, ERBB3, BRIP1, SYNE1 and TGFBR2 may affect metastasis. Molecular carcinogenesis of IHMC may be distinct from that of ordinary cholangiocarcinoma. Further studies are needed to elucidate the genetic mutations and their functions in IHMC.

DOI PubMed

Adrenomedullin for biologic-resistant Crohn's disease: A randomized, double-blind, placebo-controlled phase 2a clinical trial.

Toshihiro Kita, Shinya Ashizuka, Teruyuki Takeda, Takayuki Matsumoto, Naoki Ohmiya, Hiroshi Nakase, Satoshi Motoya, Hidehisa Ohi, Keiichi Mitsuyama, Tadakazu Hisamatsu, Shuji Kanmura, Naoya Kato, Shunji Ishihara, Masanao Nakamura, Tomohiko Moriyama, Masayuki Saruta, Ryoichi Nozaki, Shojiro Yamamoto, Haruhiko Inatsu, Koji Watanabe, Kazuo Kitamura

Journal of gastroenterology and hepatology 37 ( 11 ) 2051 - 2059 2022.07 [International journal]

BACKGROUND AND AIM: Adrenomedullin is a bioactive peptide with many pleiotropic effects, including mucosal healing and immunomodulation. Adrenomedullin has shown beneficial effects in rodent models of inflammatory bowel disease and, more importantly, in clinical trials including patients with ulcerative colitis. We performed a successive clinical trial to investigate the efficacy and safety of adrenomedullin in patients with Crohn's disease (CD). METHODS: This was a multicenter, double-blind, placebo-controlled phase 2a trial that evaluated 24 patients with biologic-resistant CD in Japan. Patients were randomly assigned to three groups and were given an infusion of 10 or 15 ng/kg/min of adrenomedullin or placebo for 8 h per day for 7 days. The primary endpoint was the change in the CD activity index (CDAI) at 8 weeks. The main secondary endpoints included changes in CDAI from week 4 to week 24. RESULTS: No differences in the primary or secondary endpoints were observed between the three groups by the 8th week. Changes in CDAI in the placebo group gradually decreased and disappeared at 24 weeks, but those in the adrenomedullin-treated groups (10 or 15 ng/kg/min group) remained at steady levels for 24 weeks. Therefore, a significant difference was observed between the placebo and adrenomedullin-treated groups at 24 weeks (P = 0.043) in the mixed-effects model. We noted mild adverse events caused by the vasodilatory effect of adrenomedullin. CONCLUSION: In this trial, we observed a long-lasting (24 weeks) decrease in CDAI in the adrenomedullin-treated groups. Adrenomedullin might be beneficial for biologic-resistant CD, but further research is needed.

DOI PubMed

Remitting Seronegative Symmetrical Synovitis with Pitting Edema (RS3PE) Syndrome Precedes the Development of Hepatocellular Carcinoma.

Sae Ohwada, Noriyuki Akutsu, Yoshiharu Masaki, Shigeru Sasaki, Minoru Nagayama, Yasutoshi Kimura, Ichiro Takemasa, Hiroki Takahashi, Hiroshi Nakase

JMA journal 5 ( 3 ) 393 - 397 2022.07 [Domestic journal]

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is characterized by bilateral synovitis and marked pitting edema of the hands and/or feet. Despite the unknown etiology of RS3PE, several reports have described the putative association of this disease with malignant tumors. We herein report the findings of a 76-year-old man with RS3PE syndrome who developed hepatocellular carcinoma 3 years after achieving clinical remission of RS3PE using corticosteroid treatment; high vascular endothelial growth factor and tumor necrosis factor-alpha levels were considered to have contributed to carcinogenesis in this patient. The sequence of clinical events in this case strongly suggests that careful follow-up, even after clinical remission, is necessary for patients with RS3PE syndrome whose malignancy is not confirmed at diagnosis.

DOI PubMed

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Papers - NAKASE Hiroshi