Papers - NAKASE Hiroshi

当科における免疫関連大腸炎の検討

大和田 紗恵, 三宅 高和, 風間 友江, 平山 大輔, 菅野 伸一, 吉井 新二, 山野 泰穂, 仲瀬 裕志

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  119 ( 臨増総会 ) A390 - A390  2022.03

高齢者に対する内視鏡的胃粘膜下層剥離術の偶発症における予後予測因子の検討

三宅 高和, 吉井 新二, 谷口 正浩, 大和田 紗恵, 風間 友江, 平山 大輔, 菅野 伸一, 山野 泰穂, 仲瀬 裕志

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  119 ( 臨増総会 ) A336 - A336  2022.03

胆道鏡下生検検体で遺伝パネル検査を施行しえた切除不能胆嚢管癌の1例

越前 栄次朗, 川上 裕次郎, 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, 本谷 雅代, 佐々木 茂, 杉田 真太郎, 櫻井 晃洋, 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 )  130回・124回   58 - 58  2022.03

治療困難肝内結石に対するSpyGlass DSを用いた胆道鏡下治療の検討

越前 栄次朗, 川上 裕次郎, 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, 本谷 雅代, 佐々木 茂, 仲瀬 裕志

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  119 ( 臨増総会 ) A372 - A372  2022.03

転移性肺腫瘍に対するEUS-FNAにて診断した後腹膜原発の絨毛癌の1例

廣部 洋輔, 川上 裕次郎, 越前 栄次朗, 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, 本谷 雅代, 佐々木 茂, 辻脇 光洋, 舛森 直哉, 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 )  130回・124回   45 - 45  2022.03

消化器疾患診療に必要なバイオマーカー開発のための研究 HSP47は胆道癌の予後を規定するBiomarkerになりえるか?

本谷 雅代, 柾木 喜晴, 仲瀬 裕志

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  119 ( 臨増総会 ) A172 - A172  2022.03

Gel immersion endoscopic mucosal resection for early gastric cancer near the pyloric ring.

Katsuyoshi Miura, Gota Sudo, Mitsunobu Saito, Kazunori Onuma, Yumemi Takada, Atsushi Yawata, Hiroshi Nakase

Endoscopy    2022.02  [International journal]

DOI PubMed

高齢者切除不能膵癌患者に対するGEM+nabPTX療法の有効性と安全性

大和田 紗恵, 室田 文子, 本谷 雅代, 我妻 康平, 沼田 泰尚, 川上 裕次郎, 石上 敬介, 柾木 喜晴, 阿久津 典之, 佐々木 茂, 仲瀬 裕志

日本高齢消化器病学会誌 ( (NPO)日本高齢消化器病学会 )  24 ( 2 ) 81 - 88  2022.02

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GEM+nabPTX(GnP)を施行した切除不能膵癌をO群(≧75歳)28例とY群(<75歳)52例の2群に分け、有効性・安全性を比較検討した。無増悪生存期間はO群8.9ヵ月、Y群7.8ヵ月(P=0.59)、生存期間はO群17.2ヵ月、Y群22.1ヵ月(P=0.22)であり、多変量解析の結果、年齢はいずれにおいても独立した予後因子とはならなかった。4ヵ月目までのRelative dose intensityはO群で有意に低かった(O群64%、Y群84%、P=0.025)。有害事象の頻度は両群で同等であったが、O群の有害事象中止症例は全例二次治療に移行できなかった。高齢者でもGnPを実施可能だが、より緻密な忍容性評価を要する。(著者抄録)

Impaired tryptophan metabolism in the gastrointestinal tract of patients with critical coronavirus disease 2019.

Yoshihiro Yokoyama, Tomoko Ichiki, Tsukasa Yamakawa, Yoshihisa Tsuji, Koji Kuronuma, Satoshi Takahashi, Eichi Narimatsu, Hiroshi Nakase

Frontiers in medicine   9   941422 - 941422  2022  [International journal]

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INTRODUCTION: Coronavirus disease 2019 (COVID-19) is still causing a global pandemic. But the mechanism of COVID-19 severity is not well elucidated. MATERIALS AND METHODS: We conducted two single-center observational studies of patients with COVID-19. In the first study, the enrolled patients were distinguished based on critical vs. non-critical COVID-19. We collected blood samples from the patients at admission to measure markers related to inflammation and thrombosis and stool samples to analyze the fecal microbiome, metabolome, and calprotectin level. In the second study, we collected ileum and colon tissue samples from patients with critical COVID-19 who required colonoscopy due to severe gastrointestinal symptoms and analyzed mucosal gene expression. RESULTS: A total of 19 blood samples and 10 stool samples were collected. Interleukin (IL)-6 was the only serum inflammatory marker with significantly higher levels in the critical group than in the non-critical group. The fecal calprotectin level in the critical group was significantly higher than that in the non-critical group (P = 0.03), regardless of the presence of gastrointestinal symptoms. Stool metabolomic analysis showed that the level of indole-3-propionic acid, a ligand for aryl hydrocarbon receptor (AhR), was markedly decreased in the critical group compared to that in the non-critical group (P = 0.01). The expression of genes involved in tryptophan metabolism, including ACE2, AHR, CARD9, and IL22, was downregulated in the ileum of critical COVID-19 patients who required a colonoscopy. DISCUSSION: Critical COVID-19 patients have gastrointestinal inflammation potentially caused by impaired tryptophan metabolism in the small intestine due to decreased expression of genes involved in tryptophan metabolism.

DOI PubMed

間葉系幹細胞を用いた炎症性疾患の 細胞治療

永石 歓和, 仲瀬 裕志

BIO Clinica   37   87 - 90  2022

Snapshots of lymphatic pathways in colorectal cancer surgery using near-infrared fluorescence, in vivo and ex vivo.

Yu Sato, Tetsuta Satoyoshi, Kenji Okita, Daisuke Kyuno, Atsushi Hamabe, Koichi Okuya, Toshihiko Nishidate, Emi Akizuki, Masayuki Ishii, Hiro-O Yamano, Shintaro Sugita, Hiroshi Nakase, Tadashi Hasegawa, Ichiro Takemasa

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology   47 ( 12 ) 3130 - 3136  2021.12  [International journal]

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INTRODUCTION: Indocyanine green (ICG) fluorescence imaging has been used for blood flow assessment in anastomoses in the field of colorectal cancer surgery. However, whether ICG fluorescence is related to the presence of cancer cells in the lymph nodes is unclear. We explored the utilization of ICG fluorescence in colorectal cancer surgery. MATERIALS AND METHODS: ICG was injected into the submucosa around the tumor before radical resection in colorectal cancer patients. Intraoperatively, near-infrared (NIR) fluorescence was used for lymphatic flow visualization. After specimen removal, harvested lymph nodes were classified as positive or negative based on the detection of fluorescence, followed by pathological examination. ICG distribution on a section of each lymph node was examined by fluorescence microscopy. RESULTS: Overall, 155 patients underwent real-time NIR fluorescence imaging-guided surgery. Altogether, 1,017 lymph nodes were retrieved from these patients. Metastatic lymph nodes were present in 36 (5.8%) of 622 fluorescence-negative lymph nodes, which was significantly higher than 11 (2.8%) of 395 fluorescence-positive lymph nodes (odds ratio: 2.15, P = 0.03). Fluorescence microscopy of metastatic lymph nodes showed that ICG fluorescence was present in the normal structural region but not in the cancerous region of the lymph nodes. Furthermore, ICG fluorescence was observed in all metastatic lymph nodes, except those with cancer cells occupying >90% of the total area. CONCLUSIONS: ICG fluorescence detected only the normal parts of the lymph node draining from the peritumoral area and not the cancer tissues. This finding is important for developing appropriate strategies for navigation surgery using NIR fluorescence.

DOI PubMed

Mediterranean fever gene-associated enterocolitis in an elderly Japanese woman.

Yasuhiro Shibata, Keisuke Ishigami, Tomoe Kazama, Toshiyuki Kubo, Hiro-O Yamano, Shintaro Sugita, Masaki Murata, Hiroshi Nakase

Clinical journal of gastroenterology   14 ( 6 ) 1661 - 1666  2021.12  [Domestic journal]

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An 86-year-old woman was admitted to our hospital with anemia. She had never experienced symptoms of serositis. Colonoscopy revealed colitis with erosions and a friable mucosa. First, she was diagnosed with unclassified inflammatory bowel disease (IBD-U). We suspected familial Mediterranean fever as a differential diagnosis of IBD-U, and MEFV gene analysis showed heterozygosity for Exon2 R202Q. The patient was treated with colchicine 0.5 mg. After 4 months, a follow-up colonoscopy showed remarkable improvement of the mucosal inflammation throughout the entire colon. MEFV gene-associated enterocolitis responding to colchicine may be observed in patients with IBD-U and elucidating the role of MEFV gene mutations in intestinal inflammation is a future challenge.

DOI PubMed

Crohn's disease and early exposure to thiopurines are independent risk factors for mosaic chromosomal alterations in patients with inflammatory bowel diseases.

Yoichi Kakuta, Hideya Iwaki, Junji Umeno, Yosuke Kawai, Masahiro Kawahara, Tetsuya Takagawa, Yusuke Shimoyama, Takeo Naito, Rintaro Moroi, Masatake Kuroha, Hisashi Shiga, Kenji Watanabe, Shiro Nakamura, Hiroshi Nakase, Makoto Sasaki, Hiroyuki Hanai, Yuta Fuyuno, Atsushi Hirano, Takayuki Matsumoto, Hisaaki Kudo, Naoko Minegishi, Minoru Nakamura, Tadakazu Hisamatsu, Akira Andoh, Masao Nagasaki, Katsushi Tokunaga, Yoshitaka Kinouchi, Atsushi Masamune

Journal of Crohn's & colitis   16 ( 4 ) 643 - 655  2021.11  [International journal]

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BACKGROUND AND AIMS: Mosaic chromosomal alterations (mCAs) increase the risk for hematopoietic malignancies and may be risk factors for several other diseases. Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), are associated with mCAs, and patients may be at risk for hematopoietic malignancy development and/or modification of IBD phenotypes. In the present study, we screened patients with IBD for the presence of mCAs and explored the possible pathophysiological and genetic risk factors for mCAs. METHODS: We analyzed mCAs in peripheral blood from 3,339 patients with IBD and investigated the clinical and genetic risk factors for mCAs. RESULTS: CD and exposure to thiopurines before the age of 20 years were identified as novel independent risk factors for mCAs (odds ratio = 2.15 and 5.68, P = 1.17e-2 and 1.60e-3, respectively). In contrast, there were no significant associations of disease duration, anti-tumor necrosis factor alpha antibodies, or other clinical factors with mCAs. Gene ontology enrichment analysis revealed that genes specifically located in the mCAs in patients with CD were significantly associated with factors related to mucosal immune responses. A genome-wide association study revealed that ERBIN, CD96, and AC068672.2 were significantly associated with mCAs in patients with CD (P = 1.56e-8, 1.65e-8, and 4.92e-8, respectively). CONCLUSION: The difference in mCAs between patients with CD and UC supports the higher incidence of hematopoietic malignancies in CD. Caution should be exercised when using thiopurines in young patients with IBD, particularly CD, in light of possible chromosomal alterations.

DOI PubMed

Association of the Low-density Lipoprotein Cholesterol/High-density Lipoprotein Cholesterol Ratio with Glecaprevir-pibrentasvir Treatment.

Noriyuki Akutsu, Shigeru Sasaki, Takeshi Matsui, Hirofumi Akashi, Kazuhiko Yonezawa, Keisuke Ishigami, Masayuki Tsujisaki, Hiroyuki Isshiki, Atsushi Yawata, Satoshi Yamaoka, Toshihiro Ban, Takeya Adachi, Seiya Nakahara, Hideyasu Takagi, Kohei Nakachi, Katsunori Tanaka, Takehiro Hirano, Itaru Yamamoto, Hiroyuki Kaneto, Kohei Wagatsuma, Yasunao Numata, Hiroshi Nakase

Internal medicine (Tokyo, Japan)   60 ( 21 ) 3369 - 3376  2021.11  [Domestic journal]

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Objective The change in serum lipid levels by direct-acting antiviral (DAA) treatment for chronic hepatitis C varies depending on the type of DAA. How the lipid level changes induced by glecaprevir-pibrentasvir (G/P) treatment contribute to the clinical outcome remains unclear. We conducted a prospective observational study to evaluate the effectiveness of G/P treatment and the lipid level changes. Methods The primary endpoint was a sustained virologic response at 12 weeks (SVR12). The total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels and LDL-C/HDL-C (L/H) ratio were measured every two weeks. Patients This study included 101 patients. Seventeen cases of liver cirrhosis and nine cases of DAA retreatment were registered. The G/P treatment period was 8 weeks in 74 cases and 12 weeks in 27 cases. Results SVR12 was evaluated in 96 patients. The rate of achievement of SVR12 in the evaluable cases was 100%. We found significantly elevated TC and LDL-C levels over the observation period compared to baseline. The serum levels of HDL-C did not change during treatment but were significantly increased after treatment compared to baseline. The L/H ratio was significantly increased two weeks after the start of treatment but returned to the baseline after treatment. Conclusion The primary endpoint of the SVR12 achievement rate was 100%. G/P treatment changed the serum lipid levels. Specifically, the TC and LDL-C levels increased during and after treatment, and the HDL-C levels increased after treatment. G/P treatment may be associated with a reduced thrombotic risk. Therefore, validation in large trials is recommended.

DOI PubMed

Mixed neuroendocrine non-neuroendocrine neoplasm of the gallbladder complicated by a pancreaticobiliary maljunction of a non-dilated biliary duct: A case report.

Kohei Wagatsuma, Kotaro Akita, Masayo Motoya, Yasutoshi Kimura, Shintaro Sugita, Takehiro Hirano, Yujiro Kawakami, Yasunao Numata, Keisuke Ishigami, Yoshiharu Masaki, Ayako Murota, Masahiro Shitani, Noriyuki Akutsu, Shigeru Sasaki, Hiroshi Nakase

Medicine   100 ( 39 ) e27336  2021.10  [International journal]

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RATIONALE: Mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) is a rare tumor. MiNEN of the gallbladder (GB) with pancreaticobiliary maljunction (PMJ) is extremely rare. The origin of MiNEN of the GB remains unknown; the biliary tract normally lacks neuroendocrine cells. MiNEN of the GB has a poor prognosis; because of its rarity, no treatment or management guidelines have been established yet. PATIENT CONCERNS: A 47-year-old male presenting with right hypochondrial pain and malaise for 3 months was referred to our hospital for further management. DIAGNOSIS: The neuron-specific enolase level was increased. Contrast-enhanced computed tomography revealed a mass of 70 mm in size with unclear boundaries in the liver. The GB was surrounded by this mass, narrowing the lumen of the GB. Many swollen lymph nodes were observed in the hepatoduodenal ligament. Endoscopic retrograde cholangiopancreatography revealed a PMJ with a non-dilated biliary duct. A percutaneous biopsy was performed on the liver mass, and the pathological findings were neuroendocrine carcinoma (NEC) (small cell type). We diagnosed a NEC of the GB, T3N1M0, stage IIIB (Union for International Cancer Control, 7th edition). INTERVENTIONS: Because of advanced lymph node metastasis, we considered this tumor difficult to cure solely by surgical intervention. After initial chemotherapy consisting of cisplatin and irinotecan, a marked reduction in both tumor and lymph node sizes enabled conversion surgery. The pathological diagnosis of the resected tumor was MiNEN consisting of NEC and adenocarcinoma. The primary lesion was the adenocarcinoma occupying the luminal side of the GB. As a postsurgical treatment, the patient received additional irradiation therapy to the common hepatic duct and liver stump because of positive surgical margins. OUTCOMES: At 13 months postoperatively, computed tomography findings revealed the appearance of a hypervascular liver tumor, and laboratory data showed increased serum neuron-specific enolase levels. Chemotherapy was unsuccessful, leading to the death of the patient 36 months from the date of diagnosis. LESSONS: There are several reports on the development of MiNEN of the GB. In our case, a PMJ-related adenocarcinoma of the GB transdifferentiated into NEC. Further accumulation of cases is necessary to establish a treatment strategy for MiNEN of the GB.

DOI PubMed

The clinical efficacy of azathioprine as maintenance treatment for autoimmune pancreatitis: a systematic review and meta-analysis.

Yoshiharu Masaki, Hiroshi Nakase, Yoshihisa Tsuji, Masanori Nojima, Kyoko Shimizu, Nobumasa Mizuno, Tsukasa Ikeura, Kazushige Uchida, Akio Ido, Yuzo Kodama, Hiroshi Seno, Kazuichi Okazaki, Seiji Nakamura, Atsushi Masamune

Journal of gastroenterology   56 ( 10 ) 869 - 880  2021.10  [Domestic journal]

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The effectiveness of azathioprine (AZA) in preventing relapse and maintaining autoimmune pancreatitis (AIP) remission has been reported; however, most of these studies are case series with no randomized control trials available in the literature. Therefore, this study performed a systematic review and meta-analysis of the existing literature on this subject to determine the clinical efficacy of AZA as maintenance therapy for AIP patients. A systematic search was performed to identify studies on the clinical efficacy of AZA as maintenance therapy in AIP patients. The crude multiple relapse rate was estimated to assess the ability of AZA to control relapses in AIP. Pooled estimates were obtained using a random-effects model with the DerSimonian-Laird method. We identified AIP patients who did not respond to initial steroid treatment, experienced steroid weaning failure, or those who relapsed during remission as refractory cases. After reviewing the studies, ten articles fulfilled the inclusion criteria and were selected for meta-analysis. Of all 4504 patients, 3534 patients were treated with steroids, and 346 patients were treated with AZA for relapsed AIP. In this meta-analysis, 14/73 (19.2%) patients receiving AZA for refractory AIP relapsed. Meanwhile, 14/47 (29.8%) patients without AZA experienced relapse. The integrated odds ratio for relapse risk in patients receiving AZA was estimated to be 0.52 (p = 0.15). This systematic review and meta-analysis demonstrated the efficacy of AZA in preventing relapse of AIP, which supports the use of AZA as a maintenance treatment in patients with AIP who relapse upon withdrawal of steroid therapy.

DOI PubMed

後腹膜線維症に対するEUS-FNAの可能性

川上 裕次郎, 本谷 雅代, 高田 夢実, 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, 佐々木 茂, 仲瀬 裕志

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 )  63 ( Suppl.2 ) 2047 - 2047  2021.10

当科における胆道癌に対する化学放射線療法の治療成績

平野 雄大, 本谷 雅代, 我妻 康平, 沼田 泰尚, 川上 裕次郎, 石上 敬介, 柾木 喜晴, 室田 文子, 阿久津 典之, 佐々木 茂, 仲瀬 裕志

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  118 ( 臨増大会 ) A468 - A468  2021.10

炎症性腸疾患のモニタリングと治療選択 潰瘍性大腸炎に対するウステキヌマブの実臨床での治療成績と短期有効性予測因子

安藤 勝祥, 藤谷 幹浩, 仲瀬 裕志

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  118 ( 臨増大会 ) A652 - A652  2021.10

当科における胆道癌に対する化学放射線療法の治療成績

平野 雄大, 本谷 雅代, 我妻 康平, 沼田 泰尚, 川上 裕次郎, 石上 敬介, 柾木 喜晴, 室田 文子, 阿久津 典之, 佐々木 茂, 仲瀬 裕志

日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  118 ( 臨増大会 ) A468 - A468  2021.10