Language：English   Publisher：Gastric Cancer  

Background: Hepatoid adenocarcinoma of the stomach (HAS), a subtype of gastric cancer (GC), includes multiple tumor components, such as enteroblastic and tubular adenocarcinoma components. However, which component mostly contributes to the aggressive behavior of HAS remains unclear. Moreover, the role of tumor-associated macrophages (TAMs) has not been explored in HAS. This study evaluated the clinical significance of the proportion of the hepatoid component within the tumor, CD163 + macrophages, and macrophage colony-stimulating factor-1 (CSF-1) in HAS. Methods: In total, 56 cases of primary HAS were analyzed. In each case, hepatoid (HC), enteroblastic (EC), and tubular (TC) components were identified, and the ratio of HC to the entire tumor (hepatoid component ratio, HCR) was assessed to examine the correlation between HCR and clinicopathological features. Immunohistochemical staining for CD163 and CSF-1 was performed, and differences in immunohistochemical results among the three tumor components were analyzed. In each tumor component, the prognostic impact of CD163 and CSF-1 was examined. Results: A high HCR was associated with worse overall survival (OS). CD163 + TAMs and CSF-1 immunoreactivity score in HC were significantly higher than those in the other components. High infiltration of CD163 + TAMs and a high CSF-1 immunoreactivity score in HC were associated with an aggressive course and worse OS. Multivariate analysis revealed the proportion of HC in HAS as an independent prognostic factor (HR = 3.176, p = 0.006). Conclusions: The HCR and CD163 + TAMs may be useful prognostic predictors, and TAMs may be novel therapeutic targets of HAS.

DOI： 10.1007/s10120-024-01562-x

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

DOI： 10.1016/j.dld.2024.07.003

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

DOI： 10.1016/j.dld.2024.07.003

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Language：English  

DOI： 10.14309/ajg.0000000000003094

PubMed

Language：English  

DOI： 10.14309/ajg.0000000000003094

PubMed

Language：English   Publisher：シュプリンガー・ジャパン(株)  

Language：English   Publisher：シュプリンガー・ジャパン(株)  

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403203667

CiNii Research

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403203674

CiNii Research

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403203673

CiNii Research

Publisher：金原出版  

DOI： 10.18888/rp.0000002708

CiNii Research

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞患者は60歳代,男性.20XX-2年に気管支喘息を発症.20XX-1年に近医呼吸器内科で好酸球性肺炎と診断され,ステロイド内服加療中であった.20XX年に心窩部痛と血便が出現し当科を受診した.大腸内視鏡検査で遠位S状結腸～直腸に周囲を縁取るような発赤を伴う地図状潰瘍の多発を認めた.カプセル小腸内視鏡検査では上部～下部小腸にわたり大腸病変に相似する潰瘍性病変の散在を認めた.皮膚病変を検索したところ体幹と四肢に網状紫斑の多発を認め,臀部の網状紫斑より採取した皮膚生検組織で壊死性血管炎の所見を認め,好酸球性多発血管炎性肉芽腫症と確定診断した.心病変,神経炎の合併を認めシクロホスファミド大量静注療法を施行した.特徴的な小腸病変と大腸病変の内視鏡所見から本症を疑って皮膚病変を検索し,紫斑を皮膚生検した結果,本症の確定診断に至った症例であった.

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞消化管に虚血による病変を生じるまれな疾患として,クリオグロブリン血症性血管炎を提示する.患者は40歳代,男性.HCV陽性患者で直接作用型抗ウイルス薬による治療中に腹痛を生じ,消化管検査を行った.十二指腸に不整形の潰瘍を複数認め,大腸にはびらんが散見された.小腸には潰瘍や潰瘍瘢痕が観察された.クリオグロブリン弱陽性であり,クリオフィルトレーションと直接作用型抗ウイルス薬による治療を行った.経過中,横行結腸の瘢痕部から血管炎の所見が得られ,クリオグロブリン血症性血管炎と診断した.報告が少ないため消化管病変の特徴は明らかではないが,治療に結び付けるため鑑別診断として考えることは重要である.

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞消化管に虚血による病変を生じるまれな疾患として,クリオグロブリン血症性血管炎を提示する.患者は40歳代,男性.HCV陽性患者で直接作用型抗ウイルス薬による治療中に腹痛を生じ,消化管検査を行った.十二指腸に不整形の潰瘍を複数認め,大腸にはびらんが散見された.小腸には潰瘍や潰瘍瘢痕が観察された.クリオグロブリン弱陽性であり,クリオフィルトレーションと直接作用型抗ウイルス薬による治療を行った.経過中,横行結腸の瘢痕部から血管炎の所見が得られ,クリオグロブリン血症性血管炎と診断した.報告が少ないため消化管病変の特徴は明らかではないが,治療に結び付けるため鑑別診断として考えることは重要である.

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞患者は60歳代,男性.20XX-2年に気管支喘息を発症.20XX-1年に近医呼吸器内科で好酸球性肺炎と診断され,ステロイド内服加療中であった.20XX年に心窩部痛と血便が出現し当科を受診した.大腸内視鏡検査で遠位S状結腸～直腸に周囲を縁取るような発赤を伴う地図状潰瘍の多発を認めた.カプセル小腸内視鏡検査では上部～下部小腸にわたり大腸病変に相似する潰瘍性病変の散在を認めた.皮膚病変を検索したところ体幹と四肢に網状紫斑の多発を認め,臀部の網状紫斑より採取した皮膚生検組織で壊死性血管炎の所見を認め,好酸球性多発血管炎性肉芽腫症と確定診断した.心病変,神経炎の合併を認めシクロホスファミド大量静注療法を施行した.特徴的な小腸病変と大腸病変の内視鏡所見から本症を疑って皮膚病変を検索し,紫斑を皮膚生検した結果,本症の確定診断に至った症例であった.

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society of Gastroenterology  

<p>A 66-year-old male patient with a thyroid and nasopharyngeal cancer history visited our hospital because of a positive fecal occult blood test. Total colonoscopy detected sessile or subpedunculated polyps in the ascending colon, sigmoid colon, and rectum. These polyps were endoscopically resected, and the rectal polyp was pathologically diagnosed as adenocarcinoma in adenoma and the others as adenomas. Additionally, multiple sessile lesions were revealed in the sigmoid colon and rectum. A complete gastrointestinal tract examination revealed multiple foci of glycogenic acanthosis in the esophagus, multiple sessile lesions in the stomach, multiple sessile lesions, clubbings (rod-shaped lesions), and venous malformations in the small bowel. Mucocutaneous examination indicated hemangiomas on the body trunk, patchy pigmentation on the glans penis, and keratotic papules in the inguinal region. The National Comprehensive Cancer Network diagnostic criteria for Cowden syndrome were used in this case. The patient met four major and two minor criteria;thus, Cowden syndrome was diagnosed. Moreover, the patient was had phosphatase and tensin homolog deleted on chromosome 10 gene mutation. This is the first reported case of metachronal triple cancers in a male patient with Cowden syndrome, and our results indicate the importance of cancer surveillance.</p>

DOI： 10.11405/nisshoshi.121.489

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society of Gastroenterology  

<p>A 66-year-old male patient with a thyroid and nasopharyngeal cancer history visited our hospital because of a positive fecal occult blood test. Total colonoscopy detected sessile or subpedunculated polyps in the ascending colon, sigmoid colon, and rectum. These polyps were endoscopically resected, and the rectal polyp was pathologically diagnosed as adenocarcinoma in adenoma and the others as adenomas. Additionally, multiple sessile lesions were revealed in the sigmoid colon and rectum. A complete gastrointestinal tract examination revealed multiple foci of glycogenic acanthosis in the esophagus, multiple sessile lesions in the stomach, multiple sessile lesions, clubbings (rod-shaped lesions), and venous malformations in the small bowel. Mucocutaneous examination indicated hemangiomas on the body trunk, patchy pigmentation on the glans penis, and keratotic papules in the inguinal region. The National Comprehensive Cancer Network diagnostic criteria for Cowden syndrome were used in this case. The patient met four major and two minor criteria;thus, Cowden syndrome was diagnosed. Moreover, the patient was had phosphatase and tensin homolog deleted on chromosome 10 gene mutation. This is the first reported case of metachronal triple cancers in a male patient with Cowden syndrome, and our results indicate the importance of cancer surveillance.</p>

DOI： 10.11405/nisshoshi.121.489

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Language：Japanese   Publisher：(一財)日本消化器病学会  

66歳男性.検診異常のため下部消化管内視鏡検査を施行し,S状結腸・直腸に過形成性ポリープの多発を認めた.また直腸の隆起病変を内視鏡的に切除し,腺腫内癌と診断した.他に,食道の白色扁平隆起,胃・小腸の無茎性隆起,小腸の静脈奇形,特徴的な皮膚所見もあり,Cowden症候群と診断しPTEN遺伝子変異も確認した.甲状腺癌,上咽頭癌の既往があり,本症候群の男性に直腸腺腫内癌を含めた3重複癌はまれであり報告する.(著者抄録)

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Language：Japanese   Publisher：(一財)日本消化器病学会  

66歳男性.検診異常のため下部消化管内視鏡検査を施行し,S状結腸・直腸に過形成性ポリープの多発を認めた.また直腸の隆起病変を内視鏡的に切除し,腺腫内癌と診断した.他に,食道の白色扁平隆起,胃・小腸の無茎性隆起,小腸の静脈奇形,特徴的な皮膚所見もあり,Cowden症候群と診断しPTEN遺伝子変異も確認した.甲状腺癌,上咽頭癌の既往があり,本症候群の男性に直腸腺腫内癌を含めた3重複癌はまれであり報告する.(著者抄録)

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Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403203624

CiNii Research

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403203629

CiNii Research

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403203631

CiNii Research

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞患者は80歳代,男性.検診目的に施行されたEGDで十二指腸病変を指摘され,生検で腺癌と診断されたことから,精査目的に当科へ紹介され受診となった.低緊張性十二指腸X線造影検査で病変は下行部の乳頭対側に径15mm弱のIIa+IIc様病変として描出され,側面像では弧状変形相当の変形を認めた.EGDで病変部は厚みを伴っており,送気で伸展不良所見を認めた.周囲隆起の立ち上がりは粘膜下腫瘍様を呈しており,上皮性の変化は認めなかった.陥凹底には白苔が付着していたが,NBI拡大観察で周囲隆起の陥凹辺縁部では絨毛構造が消失し,走行異常を伴う微小血管構築像を認め,腫瘍の露出が疑われた.SM massiveに浸潤した癌を疑い,亜全胃温存膵頭十二指腸切除術を施行した.切除標本では周囲隆起部に腺癌成分を伴う内分泌細胞癌で,病変全体で粘膜下層に浸潤しており,陥凹内中央の一部でわずかに筋層へ浸潤している所見を認め,neuroendocrine carcinoma(NEC),large cell type(NEC 80%,adenocarcinoma 20%),pT2N1M0と診断された(WHO分類第5版).本邦の胃癌取扱い規約/大腸癌取扱い規約では内分泌細胞癌に該当した.併存する腺癌領域の免疫組織化学的検討の結果,Brunner腺分化を示す腺癌(MUC6陽性)を起源とする内分泌細胞癌の症例と考えられた.

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞非乳頭部十二指腸神経内分泌腫瘍(NEN)のX線造影所見・内視鏡所見を明らかにすることを目的として,当科において病理組織学的に非乳頭部十二指腸NENと診断した症例を対象に抽出し,遡及的にその臨床所見とX線造影所見・内視鏡所見を検討した.その結果,最近10年間に計14例15病変がNENと確定診断されており,NET 13例14病変(全病変G1)とNEC1例1病変に分類された.NET 14病変は全病変が十二指腸球部に位置し,内視鏡所見としては頂部にdelleを伴う黄白色調のSMT様隆起の形態が特徴的で,表面には白色観察およびNBI拡大観察で高率に血管拡張像と窩間部の開大を認めた.X線造影検査は7例に施行し,6例が透亮像として描出され,半数例でバリウム斑を伴っていた.切除標本を検討すると,13病変中2病変で病変表面に胃腺窩上皮化生を認めた.NECは下行部に位置し,IIa+IIc様の形態を呈していた.

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞患者は50歳代,女性.上部消化管内視鏡検査で胃底腺領域内に10個前後の発赤調の粘膜下腫瘍(SMT)様隆起があり,背景粘膜は肥厚様であった.SMT様隆起の生検病理検査は神経内分泌腫瘍(NET)の所見であった.血清ガストリンは著増していたが,抗胃壁細胞抗体および抗内因子抗体は陰性,胃以外に内分泌腫瘍を認めなかった.1cm大の2病変に対し,内視鏡的粘膜切除術を施行し,腫瘍部はNET G1であり,病理組織学的に背景粘膜の胃底腺に過形成性変化を認めた.後日,プロトンポンプのαサブユニットをコードするATP4A遺伝子に病的バリアントを認めることが判明し,胃壁細胞機能不全を原因とするIV型胃NETと診断した.

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞患者は80歳代,男性.検診目的に施行されたEGDで十二指腸病変を指摘され,生検で腺癌と診断されたことから,精査目的に当科へ紹介され受診となった.低緊張性十二指腸X線造影検査で病変は下行部の乳頭対側に径15mm弱のIIa+IIc様病変として描出され,側面像では弧状変形相当の変形を認めた.EGDで病変部は厚みを伴っており,送気で伸展不良所見を認めた.周囲隆起の立ち上がりは粘膜下腫瘍様を呈しており,上皮性の変化は認めなかった.陥凹底には白苔が付着していたが,NBI拡大観察で周囲隆起の陥凹辺縁部では絨毛構造が消失し,走行異常を伴う微小血管構築像を認め,腫瘍の露出が疑われた.SM massiveに浸潤した癌を疑い,亜全胃温存膵頭十二指腸切除術を施行した.切除標本では周囲隆起部に腺癌成分を伴う内分泌細胞癌で,病変全体で粘膜下層に浸潤しており,陥凹内中央の一部でわずかに筋層へ浸潤している所見を認め,neuroendocrine carcinoma(NEC),large cell type(NEC 80%,adenocarcinoma 20%),pT2N1M0と診断された(WHO分類第5版).本邦の胃癌取扱い規約/大腸癌取扱い規約では内分泌細胞癌に該当した.併存する腺癌領域の免疫組織化学的検討の結果,Brunner腺分化を示す腺癌(MUC6陽性)を起源とする内分泌細胞癌の症例と考えられた.

Language：English   Publisher：シュプリンガー・ジャパン(株)  

日本において、その希少性から十二指腸癌以外の原発性小腸腺癌(PSBA)の臨床病理学的特徴と予後は明らかでない。日本大腸肛門病学会に登録された44施設における、2008年1月から2017年12月までのPSBA358症例を解析した。年齢の中央値は67歳(男性218例、61.6%)であった。平均腫瘍径は49.9(7～100)mmであった。PSBAの部位は空腸が66.2%、回腸が30.4%であった。219例(61.9%)で診断目的の小腸内視鏡検査(シングルバルーン内視鏡、ダブルバルーン内視鏡、カプセル内視鏡)が施行された。19例(5.4%)がリンチ症候群で、272例(76.8%)が初回診断時に有症状であった。病期0、I、II、III、IVの症例はそれぞれ5.4%、2.5%、27.1%、26.0%、35.6%であった。それぞれの病期の5年生存率は92.3%、60.0%、75.9%、61.4%、25.5%、疾患特異的5年生存率(DSS)は100%、75.0%、84.1%、59.3%、25.6%であった。空腸原発、初回診断時有症状、および進行臨床病期の症例の予後は不良であった。Coxハザードモデルを用いた多変量解析の結果、臨床病期のみがPSBA症例のDSSの有意な予知因子であった。PSBA症例のうち76.8%が初回診断時に有症状であり、その多くは進行した病期で診断されていた。以上より、良好な予後のためにはPSBAを早期病期の段階で発見することが重要である。

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞非乳頭部十二指腸神経内分泌腫瘍(NEN)のX線造影所見・内視鏡所見を明らかにすることを目的として,当科において病理組織学的に非乳頭部十二指腸NENと診断した症例を対象に抽出し,遡及的にその臨床所見とX線造影所見・内視鏡所見を検討した.その結果,最近10年間に計14例15病変がNENと確定診断されており,NET 13例14病変(全病変G1)とNEC1例1病変に分類された.NET 14病変は全病変が十二指腸球部に位置し,内視鏡所見としては頂部にdelleを伴う黄白色調のSMT様隆起の形態が特徴的で,表面には白色観察およびNBI拡大観察で高率に血管拡張像と窩間部の開大を認めた.X線造影検査は7例に施行し,6例が透亮像として描出され,半数例でバリウム斑を伴っていた.切除標本を検討すると,13病変中2病変で病変表面に胃腺窩上皮化生を認めた.NECは下行部に位置し,IIa+IIc様の形態を呈していた.

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞患者は50歳代,女性.上部消化管内視鏡検査で胃底腺領域内に10個前後の発赤調の粘膜下腫瘍(SMT)様隆起があり,背景粘膜は肥厚様であった.SMT様隆起の生検病理検査は神経内分泌腫瘍(NET)の所見であった.血清ガストリンは著増していたが,抗胃壁細胞抗体および抗内因子抗体は陰性,胃以外に内分泌腫瘍を認めなかった.1cm大の2病変に対し,内視鏡的粘膜切除術を施行し,腫瘍部はNET G1であり,病理組織学的に背景粘膜の胃底腺に過形成性変化を認めた.後日,プロトンポンプのαサブユニットをコードするATP4A遺伝子に病的バリアントを認めることが判明し,胃壁細胞機能不全を原因とするIV型胃NETと診断した.

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403203560

CiNii Research

Publisher：東京医学社  

DOI： 10.24479/endo.0000001383

CiNii Research

Publisher：東京医学社  

DOI： 10.24479/endo.0000001352

CiNii Research

Publisher：東京医学社  

DOI： 10.24479/endo.0000001354

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Language：English  

We herein describe a 49-year-old man with severe heart failure due to fulminant myocarditis who underwent left ventricular assist device implantation and received clopidogrel and warfarin as antithrombotic agents. The patient developed anemia secondary to chronic bleeding gastric hyperplastic polyps, necessitating endoscopic mucosal resection. Despite attempts to manage post-endoscopic mucosal resection bleeding from a gastric ulcer by endoscopic hemostasis using hemostatic forceps, local hemostatic agents, and polyglycolic acid sheets, the bleeding persisted. Hemostasis of the refractory bleeding was finally achieved by endoscopic hand-suturing of the ulcer. One month later, the ulcer was almost completely scarred. This case has important clinical value in that it demonstrates the efficacy of endoscopic hand-suturing even in challenging cases such as refractory bleeding gastric ulcers in patients with left ventricular assist devices.

DOI： 10.1002/deo2.369

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BACKGROUND: The intestinal microbiome is involved in the pathogenesis of chronic kidney disease (CKD). Despite its importance, the microbiome of the small intestinal mucosa has been little studied due to sampling difficulties, and previous studies have mainly focused on fecal sources for microbiome studies. We aimed to characterize the small intestinal microbiome of CKD patients by studying the microbiome collected from duodenal and fecal samples of CKD patients and healthy controls. METHODS: Overall, 28 stage 5 CKD patients and 21 healthy participants were enrolled. Mucosal samples were collected from the deep duodenum during esophagogastroduodenoscopy and fecal samples were also collected. The 16S ribosomal RNA gene sequencing using Qiime2 was used to investigate and compare the microbial structure and metagenomic function of the duodenal and fecal microbiomes. RESULTS: The duodenal flora of CKD patients had decreased alpha diversity compared with the control group. On the basis of taxonomic composition, Veillonella and Prevotella were significantly reduced in the duodenal flora of CKD patients. The tyrosine and tryptophan metabolic pathways were enhanced in the urea toxin-related metabolic pathways based on the Kyoto Encyclopedia of Genes and Genomes database. CONCLUSION: The small intestinal microbiome in CKD patients is significantly altered, indicating that increased intestinal permeability and production of uremic toxin may occur in the upper small intestine of CKD patients.

DOI： 10.1007/s10157-023-02434-x

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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

Language：English   Publisher：(一社)日本腎臓学会  

Language：English   Publisher：(一社)日本腎臓学会  

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

小腸カプセル内視鏡(CE)画像読影を補助するためのモデリング問題について検討するデータセットおよび対象検出CE人工知能(AI)モデルの作成を試みた。2014年9月から2021年6月までの間に施行した523回の小腸CEから18481枚の画像を抽出した。23033病変の12320枚の画像に対して注解を行い、6161枚の正常画像と組み合わせてデータセットとして、その特徴を解析した。このデータセットに基づいてYOLO v5を用いた対象検出AIモデルを作成し、その検証を行った。データセットで用いた注解項目は12種類で、同一画像に対して複数の注解項目を適用した。1396枚の画像を用いてAIモデルを検証し、全12種類の注解項目の感度は91%で、1375画像が真陽性、659画像が偽陽性、120画像が偽陰性であった。各注解項目のうち、最も感度が高かったのは97%で、受信者動作特性曲線下面積は0.98であったが、注解項目により診断能は異なっていた。以上より、YOLO v5を用いた小腸CEにおける対象検出AIモデルは効果的かつ理解が容易な読影補助となる可能性があることが示唆された。

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

Publisher：診断と治療社  

DOI： 10.34433/dt.0000000620

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Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403203469

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Publisher：東京医学社  

DOI： 10.24479/endo.0000001234

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Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403203479

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

PURPOSE: Limited information is available regarding the characteristics and outcomes of stage IV small bowel adenocarcinoma (SBA) in Japan. This study examined the clinical and pathological characteristics and outcomes according to the treatment strategies in patients with stage IV SBA. METHODS: This retrospective observational study used the data of patients with jejunal or ileal adenocarcinoma collected by the Small Bowel Malignant Tumor Project of the Japanese Society for Cancer of the Colon and Rectum. Descriptive statistics were expressed as the mean (standard deviation) or median (range). Survival analysis was performed using Kaplan-Meier curves and pairwise log-rank tests. RESULTS: Data from 128 patients were analyzed. The treatment strategies were chemotherapy alone (26 of 128, 20.3%), surgery alone (including palliative surgery; 21 of 128, 16.4%), surgery + chemotherapy (74 of 128, 57.8%), and best supportive care (7 of 128, 5.5%). The median (range) overall survival was 16 (0-125) months overall, and 11 (1-38) months, 8 (0-80) months, 18 (0-125) months, and 0 (0-1) months for the chemotherapy, surgery, surgery + chemotherapy, and best supportive care groups, respectively. Three main categories of chemotherapeutic regimen were used: a combination of fluoropyrimidine and oxaliplatin (F + Ox), fluoropyrimidine and irinotecan (F + Iri), and single-agent fluoropyrimidine. Among patients treated with chemotherapy, the median (range) OS was 16 (1-106) months overall, and 17 (1-87) months, 29 (7-39) months, and 16 (1-106) months in patients treated with fluoropyrimidine, F + Iri, and F + Ox, respectively. CONCLUSION: Patients treated with surgery, chemotherapy, or both had a better prognosis than those who received best supportive care. Among patients who received chemotherapy, survival did not differ according to the chemotherapeutic regimen.

DOI： 10.1200/GO.23.00392

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BACKGROUND: The clinicopathological features and prognosis of primary small bowel adenocarcinoma (PSBA), excluding duodenal cancer, remain undetermined due to its rarity in Japan. METHODS: We analyzed 354 patients with 358 PSBAs, between January 2008 and December 2017, at 44 institutions affiliated with the Japanese Society for Cancer of the Colon and Rectum. RESULTS: The median age was 67 years (218 males, 61.6%). The average tumor size was 49.9 (7-100) mm. PSBA sites consisted of jejunum (66.2%) and ileum (30.4%). A total of 219 patients (61.9%) underwent diagnostic small bowel endoscopy, including single-balloon endoscopy, double-balloon endoscopy, and capsule endoscopy before treatment. Nineteen patients (5.4%) had Lynch syndrome, and 272 patients (76.8%) had symptoms at the initial diagnosis. The rates for stages 0, I, II, III, and IV were 5.4%, 2.5%, 27.1%, 26.0%, and 35.6%, respectively. The 5-year overall survival rates at each stage were 92.3%, 60.0%, 75.9%, 61.4%, and 25.5%, respectively, and the 5-year disease-specific survival (DSS) rates were 100%, 75.0%, 84.1%, 59.3%, and 25.6%, respectively. Patients with the PSBA located in the jejunum, with symptoms at the initial diagnosis or advanced clinical stage had a worse prognosis. However, multivariate analysis using Cox-hazard model revealed that clinical stage was the only significant predictor of DSS for patients with PSBA. CONCLUSIONS: Of the patients with PSBA, 76.8% had symptoms at the initial diagnosis, which were often detected at an advanced stage. Detection during the early stages of PSBA is important to ensure a good prognosis.

DOI： 10.1007/s00535-024-02081-3

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞過去23年間に当科および関連施設にて診断された大腸の孤立性若年性ポリープ(JP)101例,孤立性PJP(Peutz-Jeghers type polyp)29例,IMGP(inflammatory myoglandular polyp)18例を対象とし,その臨床像,内視鏡像,病理組織像を遡及的に検討した.その結果,JPは平均年齢が低かった.内視鏡所見では,JPはびらん,白苔,白斑,NBI拡大観察下の開大した腺管開口部や疎に分布した腺窩辺縁上皮,細かい血管の増生,色素拡大観察下の星芒状,疎に分布したpitの,PJPは分葉状,NBIや色素拡大観察下の樹枝状構造の,IMGPは白斑,NBI拡大観察下の開大した腺管開口部,細かい血管の増生,色素拡大観察下の星芒状pitの頻度がそれぞれ高かった.以上よりJP,IMGPとPJPは異なる内視鏡像を呈していたが,JPとIMGPの内視鏡像は比較的類似していた.しかしながら,JPはIMGPに比べ,白苔,NBIや色素拡大観察下の疎に分布する腺窩辺縁上皮やpitの頻度が高いことを加味すると鑑別できる可能性があるものと推察する.

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞過去23年間に当科および関連施設にて診断された大腸の孤立性若年性ポリープ(JP)101例,孤立性PJP(Peutz-Jeghers type polyp)29例,IMGP(inflammatory myoglandular polyp)18例を対象とし,その臨床像,内視鏡像,病理組織像を遡及的に検討した.その結果,JPは平均年齢が低かった.内視鏡所見では,JPはびらん,白苔,白斑,NBI拡大観察下の開大した腺管開口部や疎に分布した腺窩辺縁上皮,細かい血管の増生,色素拡大観察下の星芒状,疎に分布したpitの,PJPは分葉状,NBIや色素拡大観察下の樹枝状構造の,IMGPは白斑,NBI拡大観察下の開大した腺管開口部,細かい血管の増生,色素拡大観察下の星芒状pitの頻度がそれぞれ高かった.以上よりJP,IMGPとPJPは異なる内視鏡像を呈していたが,JPとIMGPの内視鏡像は比較的類似していた.しかしながら,JPはIMGPに比べ,白苔,NBIや色素拡大観察下の疎に分布する腺窩辺縁上皮やpitの頻度が高いことを加味すると鑑別できる可能性があるものと推察する.

Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society of Internal Medicine  

<p><b>Objective </b>T helper (Th) cells play a central role in the pathogenesis of ulcerative colitis (UC). The present study analyzed the changes in circulating T cells by administration of ustekinumab (UST), an interleukin-12/23p40 antibody. </p><p><b>Methods </b>CD4 T cells were isolated from peripheral blood at 0 and 8 weeks after UST treatment, and we analyzed the proportion of CD4 T cells by flow cytometry. Clinical information and laboratory data were obtained at 0, 8, and 16 weeks. </p><p><b>Patients </b>We evaluated 13 patients with UC who received UST for the induction of remission between July 2020 and August 2021. </p><p><b>Results </b>The median partial Mayo score improved from 4 (1-7) to 0 (0-6) (p<0.001) with UST. Among serological parameters, albumin concentrations, C-reactive protein concentrations, the sedimentation rate, and leucine-rich alpha 2 glycoprotein concentrations showed significant improvement with UST. A flow cytometric analysis of circulating CD4 T cells showed that the percentage of Th17 cells was significantly decreased by UST treatment in all patients (1.85% to 0.98%, p<0.0001). Th1 cells were significantly increased by UST treatment (9.52% to 10.4%, p<0.05), but Th2 and regulatory T cells were not significantly different. The high-Th17 subgroup had a significantly better partial Mayo score than the low-Th17 subgroup at 16 weeks after UST treatment (0 vs. 1, p=0.028). </p><p><b>Conclusion </b>Treatment with UST decreases circulating Th17 cells, suggesting that this change may be related to the anti-inflammatory effect of UC. </p>

DOI： 10.2169/internalmedicine.1724-23

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society of Internal Medicine  

<p><b>Objective </b>T helper (Th) cells play a central role in the pathogenesis of ulcerative colitis (UC). The present study analyzed the changes in circulating T cells by administration of ustekinumab (UST), an interleukin-12/23p40 antibody. </p><p><b>Methods </b>CD4 T cells were isolated from peripheral blood at 0 and 8 weeks after UST treatment, and we analyzed the proportion of CD4 T cells by flow cytometry. Clinical information and laboratory data were obtained at 0, 8, and 16 weeks. </p><p><b>Patients </b>We evaluated 13 patients with UC who received UST for the induction of remission between July 2020 and August 2021. </p><p><b>Results </b>The median partial Mayo score improved from 4 (1-7) to 0 (0-6) (p<0.001) with UST. Among serological parameters, albumin concentrations, C-reactive protein concentrations, the sedimentation rate, and leucine-rich alpha 2 glycoprotein concentrations showed significant improvement with UST. A flow cytometric analysis of circulating CD4 T cells showed that the percentage of Th17 cells was significantly decreased by UST treatment in all patients (1.85% to 0.98%, p<0.0001). Th1 cells were significantly increased by UST treatment (9.52% to 10.4%, p<0.05), but Th2 and regulatory T cells were not significantly different. The high-Th17 subgroup had a significantly better partial Mayo score than the low-Th17 subgroup at 16 weeks after UST treatment (0 vs. 1, p=0.028). </p><p><b>Conclusion </b>Treatment with UST decreases circulating Th17 cells, suggesting that this change may be related to the anti-inflammatory effect of UC. </p>

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Language：English   Publisher：Journal of Gastroenterology and Hepatology (Australia)  

DOI： 10.1111/jgh.16347

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Language：English   Publisher：(一社)日本内科学会  

2020年7月～2021年8月に寛解導入目的でウステキヌマブ(UST)が投与された潰瘍性大腸炎(UC)患者13例(男性3例、女性10例、中央値42歳)を対象に、循環T細胞分画の変化を評価した。UST治療の0週目と8週目に末梢血からCD4 T細胞を分離し、フローサイトメトリーによりCD4 T細胞率を解析した。UST治療により、部分的Mayoスコア中央値が有意に改善し(4→0)、血清パラメータのうちアルブミン値、C反応性タンパク質値、沈降速度、ロイシンリッチα2グリコプロテイン値が有意に改善した。循環CD4 T細胞のフローサイトメトリー解析では、全患者でUST治療によりヘルパーT(Th)17細胞率が有意に低下し、Th1細胞率が有意に上昇したが、Th2細胞率と制御性T細胞率には有意な変化を認めなかった。治療開始前のTh17細胞率が2%超の患者は2%未満の患者に比べて16週時の部分的Mayoスコアが有意に良好であった(0 vs 1)。UC患者において、UST治療により循環Th17細胞が減少することが示された。

Language：English   Publisher：Journal of Gastroenterology and Hepatology (Australia)  

DOI： 10.1111/jgh.16347

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Society for Clinical Epidemiology  

<p><b>BACKGROUND</b></p><p>This registry aims to allow for a prospective non-interventional observational study of ulcerative colitis. This will facilitate monitoring of the current state of ulcerative colitis in Japan and improving the long-term disease course and adverse events associated with current treatment options.</p><p><b>METHODS</b></p><p>Inclusion of patients from five centres in Japan is planned. The study is expected to take place from July 15, 2020, to November 30, 2024. Background, demographics, and medical history/information will be collected from electronic medical records at enrolment. Medical information including medications, laboratory data, and disease activity will be collected automatically from electronic medical records throughout the study. Patient-reported quality of life data will be collected directly from patients via smartphone. Efficacy endpoints (clinical remission rate, clinical improvement rate, and endoscopic healing rate) and safety endpoints (incidence of adverse events and specific ulcerative colitis-related events) will be collected according to treatment administered. Treatment categories include no treatment, 5-aminosalicylic acids, corticosteroids, immunomodulators, immunosuppressants, anti-tumour necrosis alpha agents, cytapheresis, Janus kinase inhibitors, anti-integrin antibodies, and anti-interleukin-12/23 antibodies.</p><p><b>CONCLUSIONS</b></p><p>The dataset will include cross-sectional and longitudinal data and is expected to capture the state of ulcerative colitis in Japan. Patients will be included on a large scale, and the registry will be established automatically from electronic medical records and direct patient input, facilitating the accurate recording of medical information for patients with ulcerative colitis in Japan and minimizing limitations intrinsic to databases that require manual data entry, such as the burden on participating investigators and entry of data with errors/typos.</p>

DOI： 10.37737/ace.24010

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<p><b>BACKGROUND</b></p><p>This registry aims to allow for a prospective non-interventional observational study of ulcerative colitis. This will facilitate monitoring of the current state of ulcerative colitis in Japan and improving the long-term disease course and adverse events associated with current treatment options.</p><p><b>METHODS</b></p><p>Inclusion of patients from five centres in Japan is planned. The study is expected to take place from July 15, 2020, to November 30, 2024. Background, demographics, and medical history/information will be collected from electronic medical records at enrolment. Medical information including medications, laboratory data, and disease activity will be collected automatically from electronic medical records throughout the study. Patient-reported quality of life data will be collected directly from patients via smartphone. Efficacy endpoints (clinical remission rate, clinical improvement rate, and endoscopic healing rate) and safety endpoints (incidence of adverse events and specific ulcerative colitis-related events) will be collected according to treatment administered. Treatment categories include no treatment, 5-aminosalicylic acids, corticosteroids, immunomodulators, immunosuppressants, anti-tumour necrosis alpha agents, cytapheresis, Janus kinase inhibitors, anti-integrin antibodies, and anti-interleukin-12/23 antibodies.</p><p><b>CONCLUSIONS</b></p><p>The dataset will include cross-sectional and longitudinal data and is expected to capture the state of ulcerative colitis in Japan. Patients will be included on a large scale, and the registry will be established automatically from electronic medical records and direct patient input, facilitating the accurate recording of medical information for patients with ulcerative colitis in Japan and minimizing limitations intrinsic to databases that require manual data entry, such as the burden on participating investigators and entry of data with errors/typos.</p>

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Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403203432

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DOI： 10.14309/ajg.0000000000002366

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞●胃神経内分泌腫瘍(NET)は発生環境の違いによりI～III型の3つの亜型に分類される.近年,いずれの亜型とも異なる胃壁細胞の機能不全によるIV型胃NETの症例が報告されている.今回,その臨床的特徴を明らかにすることを目的とした.当科でIV型胃NETと診断した1例とI型胃NETと診断した13例を対象とし,臨床背景,画像所見,採血データおよび内視鏡治療後標本の病理組織学的所見を比較した.IV型胃NET症例では,プロトンポンプのαサブユニットをコードするATP4A遺伝子に複合ヘテロ接合体の病的変異が確認された.IV型胃NET症例では胃底腺領域内に10個程度の発赤調の粘膜下腫瘍様隆起を認めていた.背景粘膜は肥厚様であり,I型胃NETでみられるA型胃炎とは明らかに異なっていた.I型胃NETとの臨床徴候の比較では,発症時年齢やガストリン値はほぼ同等であったが,抗胃壁細胞抗体と抗内因子抗体は陰性であることと,MCVと血清ビタミンB12は正常であることが異なっていた.IV型胃NETは,プロトンポンプの機能不全に起因する遺伝性疾患と考えられ,新規の疾患概念である.

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DOI： 10.14309/ajg.0000000000002366

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＜文献概要＞●胃神経内分泌腫瘍(NET)は発生環境の違いによりI～III型の3つの亜型に分類される.近年,いずれの亜型とも異なる胃壁細胞の機能不全によるIV型胃NETの症例が報告されている.今回,その臨床的特徴を明らかにすることを目的とした.当科でIV型胃NETと診断した1例とI型胃NETと診断した13例を対象とし,臨床背景,画像所見,採血データおよび内視鏡治療後標本の病理組織学的所見を比較した.IV型胃NET症例では,プロトンポンプのαサブユニットをコードするATP4A遺伝子に複合ヘテロ接合体の病的変異が確認された.IV型胃NET症例では胃底腺領域内に10個程度の発赤調の粘膜下腫瘍様隆起を認めていた.背景粘膜は肥厚様であり,I型胃NETでみられるA型胃炎とは明らかに異なっていた.I型胃NETとの臨床徴候の比較では,発症時年齢やガストリン値はほぼ同等であったが,抗胃壁細胞抗体と抗内因子抗体は陰性であることと,MCVと血清ビタミンB12は正常であることが異なっていた.IV型胃NETは,プロトンポンプの機能不全に起因する遺伝性疾患と考えられ,新規の疾患概念である.

Language：English   Publisher：(一社)日本内科学会  

2021年10月～2022年2月、単一施設の炎症性腸疾患(IBD)患者411例を対象に、COVID-19ワクチン接種状況を調査し、臨床的寛解期に1回以上のワクチン接種を行った潰瘍性大腸炎(UC)患者188例とクローン病(CD)患者119例のワクチン接種後の経過を評価した。30日の追跡期間中、UC患者8例(4.3%)とCD患者1例(0.8%)でワクチン接種後の再燃を認めた。再燃を認めた計9例(男性3例、女性6例、中央値62歳)のうち、6例(UC患者5例、CD患者1例)は初回ワクチン接種後の再燃、3例(すべてUC患者)は2回目のワクチン接種後の再燃であった。8例(88.9%)ではワクチン接種後1週以内に再燃が認められ、2例(22.2%)は入院を要した。CD患者1例は、腹腔内膿瘍のために手術を要した。UC患者のうち、再燃を認めた患者と再燃を認めなかった患者で、ベースライン特性に有意差はなかった。COVID-19ワクチン接種後のIBD再燃は稀であることが示された。

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403203400

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DOI： 10.11477/mf.1403203397

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society of Internal Medicine  

DOI： 10.2169/internalmedicine.1830-23

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DOI： 10.2169/internalmedicine.1830-23

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DOI： 10.1111/den.14664

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DOI： 10.1111/den.14664

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DOI： 10.11477/mf.1403203358

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INTRODUCTION: Although the importance of mucosal healing has been suggested in Crohn's disease, it is difficult to repeat endoscopy, especially for the entire small bowel. Recently, serum leucine-rich alpha-2 glycoprotein (LRG) has been used as a surrogate marker of endoscopy. However, few studies have investigated a correlation between LRG and mucosal injury of the entire small bowel. METHODS: We retrospectively analyzed the clinical data of 30 patients with Crohn's disease from June 2020 to August 2022 at Yamaguchi Red Cross Hospital. All the patients were surveyed through the gastrointestinal tract by esophagogastroduodenoscopy, total colonoscopy, and capsule endoscopy (CE). Subjects with mucosal injury only in the small bowel were selected. Then, we assessed the relationship between serum biomarkers (LRG, C-reactive protein [CRP], hemoglobin, albumin) and small bowel mucosal injury scores (Lewis score [LS], Capsule Endoscopy Crohn's Disease Activity Index [CECDAI], and Crohn's Disease Activity in Capsule Endoscopy [CDACE]) calculated by CE. RESULTS: LRG and CRP were significantly correlated with small bowel mucosal injury scores (LS, CECDAI, CDACE) (p < 0.05, Spearman's rank correlation coefficient). The degree of correlation was greater for LRG than for CRP. CONCLUSIONS: LRG is a useful surrogate marker that closely reflects small bowel mucosal injury in the entire small bowel.

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Publisher：Journal of Gastroenterology  

Background: Evidence of small-bowel capsule endoscopy (SBCE) for evaluating lesions in Crohn’s disease (CD) is lacking. We aimed to clarify the effectiveness and safety of SBCE in a large sample of patients with CD. Methods: This multicenter prospective registration study recorded the clinical information and SBCE results of patients with definitive CD (d-CD) or suspected CD (s-CD). The primary outcomes were the rates of successful assessment of disease activity using SBCE, definitive diagnosis of CD, and adverse events. Secondary outcomes were the assessment of SBCE findings in patients with d-CD and s-CD and factors affecting SBCE incompletion and retention; and tertiary outcomes included the association between clinical disease activity or blood examination, endoscopic disease activity, ileal CD, and the questionnaire assessment of patient acceptance of SBCE. Results: Of 544 patients analyzed, 541 underwent SBCE with 7 (1.3%) retention cases. Of 468 patients with d-CD, 97.6% could be evaluated for endoscopic activity. Of 76 patients with s-CD, 15.8% were diagnosed with ‘confirmed CD’. CD lesions were more frequently observed in the ileum and were only seen in the jejunum in 3.4% of the patients. Male sex and stenosis were risk factors for incomplete SBCE, and high C-reactive protein levels and stenosis were risk factors for capsule retention. In L1 (Montreal classification) patients, clinical remission was associated with endoscopic remission but showed low specificity and accuracy. The answers to the acceptability questionnaire showed the minimal invasiveness and tolerability of SBCE. Conclusion: SBCE is practical and safe in patients with CD.

DOI： 10.1007/s00535-023-02017-3

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Publisher：Journal of Gastroenterology  

Background: Evidence of small-bowel capsule endoscopy (SBCE) for evaluating lesions in Crohn’s disease (CD) is lacking. We aimed to clarify the effectiveness and safety of SBCE in a large sample of patients with CD. Methods: This multicenter prospective registration study recorded the clinical information and SBCE results of patients with definitive CD (d-CD) or suspected CD (s-CD). The primary outcomes were the rates of successful assessment of disease activity using SBCE, definitive diagnosis of CD, and adverse events. Secondary outcomes were the assessment of SBCE findings in patients with d-CD and s-CD and factors affecting SBCE incompletion and retention; and tertiary outcomes included the association between clinical disease activity or blood examination, endoscopic disease activity, ileal CD, and the questionnaire assessment of patient acceptance of SBCE. Results: Of 544 patients analyzed, 541 underwent SBCE with 7 (1.3%) retention cases. Of 468 patients with d-CD, 97.6% could be evaluated for endoscopic activity. Of 76 patients with s-CD, 15.8% were diagnosed with ‘confirmed CD’. CD lesions were more frequently observed in the ileum and were only seen in the jejunum in 3.4% of the patients. Male sex and stenosis were risk factors for incomplete SBCE, and high C-reactive protein levels and stenosis were risk factors for capsule retention. In L1 (Montreal classification) patients, clinical remission was associated with endoscopic remission but showed low specificity and accuracy. The answers to the acceptability questionnaire showed the minimal invasiveness and tolerability of SBCE. Conclusion: SBCE is practical and safe in patients with CD.

DOI： 10.1007/s00535-023-02017-3

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society of Internal Medicine  

DOI： 10.2169/internalmedicine.1177-22

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society of Internal Medicine  

DOI： 10.2169/internalmedicine.1177-22

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society of Internal Medicine  

<p><b>Objective </b>Flares of inflammatory bowel disease (IBD) can occur infrequently after vaccination for coronavirus disease 2019 (COVID-19), although the details of this phenomenon are poorly understood. To clarify the possibility of an unfavorable response in patients with IBD, we investigated IBD-related symptoms during the COVID-19 vaccination. </p><p><b>Methods </b>Between October 2021 and February 2022, we obtained the COVID-19 vaccination status of 411 IBD patients who were being treated at our institution. The disease course of IBD after vaccination was investigated in 188 patients with ulcerative colitis (UC) and 119 patients with Crohn's disease (CD) who had received at least one dose of the vaccine during the clinical remission phase. The baseline characteristics before vaccination were compared between the patients with UC with or without disease flares. </p><p><b>Results </b>During the 30-day follow-up period, eight patients with UC (4.3%) and one patient with CD (0.8%) experienced disease flares following vaccination. Disease flares occurred after the first vaccination in six patients and after the second vaccination in three patients. As for the timing of onset of disease flares, eight events (88.9%) occurred within one week of vaccination. Two patients required hospitalization, and one patient with CD required surgery for an intra-abdominal abscess. The baseline characteristics did not significantly differ between patients with UC who experienced flares and those who did not. </p><p><b>Conclusion </b>IBD flares following COVID-19 vaccination are rare and vaccination should therefore be recommended for patients with IBD. However, the possibility of disease flares should be considered for approximately one week after each vaccination, especially in patients with UC. </p>

DOI： 10.2169/internalmedicine.2335-23

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Language：English   Publisher：シュプリンガー・ジャパン(株)  

青黛の潰瘍性大腸炎への効果から、フェロトーシスと潰瘍性大腸炎発症との関連について解析した。遺伝子解析では、青黛治療により潰瘍性大腸炎患者の粘膜における抗酸化遺伝子の上昇が観察された。in vitro分析では、NRF2関連遺伝子発現が青黛によって上方制御された。青黛処理によって細胞のフェロトーシスに対する耐性が得られた。メタボロミクス分析では、青黛によって還元型グルタチオンの上昇が示唆された。青黛による治療により、直腸でCYP1A1とGPX4の蛋白質発現が上昇した。青黛の主成分のインジルビンとインディゴはフェロトーシスを阻害した。青黛で治療している潰瘍性大腸炎患者の直腸粘膜で、インジルビンが検出された。青黛による腸管上皮でのフェロトーシス抑制が潰瘍性大腸炎の治療の標的であり、青黛の主要な活性成分はインジルビンと考えられた。

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403203293

CiNii Research

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞非乳頭部十二指腸腫瘍様病変の内視鏡所見/拡大内視鏡所見を明らかにすることを目的として,当科において内視鏡的切除標本の検討により病理組織学的に腫瘍様病変(異所性胃粘膜,Brunner腺過形成,胃腺窩上皮型過形成性ポリープ,Peutz-Jeghers型ポリープ)と診断した症例を対象として抽出し,遡及的にその臨床所見と内視鏡所見/拡大内視鏡所見を検討した.内視鏡的切除により異所性胃粘膜5例,Brunner腺過形成・過誤腫13例,胃腺窩上皮型過形成性ポリープ12例,Peutz-Jeghers型ポリープ6例が診断されていた.拡大観察所見はdemarcation lineを胃腺窩上皮型過形成性ポリープで全例に認めたが,異所性胃粘膜60.0%,Brunner腺過形成では22.2%にとどまった.dense patternは異所性胃粘膜40.0%,胃腺窩上皮型過形成性ポリープ50.0%にみられたが,Brunner腺過形成では22.2%であった.腫瘍様病変の中で,胃腺窩上皮型過形成性ポリープ,異所性胃粘膜とBrunner腺過形成は表面全体ないし一部が胃腺窩型上皮に被覆されるため,NBI観察では背景粘膜に比してbrownishに見える.特に胃腺窩上皮型過形成性ポリープ,異所性胃粘膜は拡大観察でdense patternを呈する頻度が高く,NBI拡大観察が腫瘍様病変の診断に有用と考えられた.

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞非乳頭部十二指腸腫瘍様病変の内視鏡所見/拡大内視鏡所見を明らかにすることを目的として,当科において内視鏡的切除標本の検討により病理組織学的に腫瘍様病変(異所性胃粘膜,Brunner腺過形成,胃腺窩上皮型過形成性ポリープ,Peutz-Jeghers型ポリープ)と診断した症例を対象として抽出し,遡及的にその臨床所見と内視鏡所見/拡大内視鏡所見を検討した.内視鏡的切除により異所性胃粘膜5例,Brunner腺過形成・過誤腫13例,胃腺窩上皮型過形成性ポリープ12例,Peutz-Jeghers型ポリープ6例が診断されていた.拡大観察所見はdemarcation lineを胃腺窩上皮型過形成性ポリープで全例に認めたが,異所性胃粘膜60.0%,Brunner腺過形成では22.2%にとどまった.dense patternは異所性胃粘膜40.0%,胃腺窩上皮型過形成性ポリープ50.0%にみられたが,Brunner腺過形成では22.2%であった.腫瘍様病変の中で,胃腺窩上皮型過形成性ポリープ,異所性胃粘膜とBrunner腺過形成は表面全体ないし一部が胃腺窩型上皮に被覆されるため,NBI観察では背景粘膜に比してbrownishに見える.特に胃腺窩上皮型過形成性ポリープ,異所性胃粘膜は拡大観察でdense patternを呈する頻度が高く,NBI拡大観察が腫瘍様病変の診断に有用と考えられた.

Language：Others   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s00535-023-02016-4

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Other Link： https://link.springer.com/article/10.1007/s00535-023-02016-4/fulltext.html

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403203252

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Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403203249

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DOI： 10.1007/s00535-023-01998-5

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Language：Others   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Abstract

Objectives

Artificial intelligence (AI) may be practical for image classification of small bowel capsule endoscopy (CE). However, creating a functional AI model is challenging. We attempted to create a dataset and an object detection CE AI model to explore modeling problems to assist in reading small bowel CE.

Methods

We extracted 18,481 images from 523 small bowel CE procedures performed at Kyushu University Hospital from September 2014 to June 2021. We annotated 12,320 images with 23,033 disease lesions, combined them with 6161 normal images as the dataset, and examined the characteristics. Based on the dataset, we created an object detection AI model using YOLO v5 and we tested validation.

Results

We annotated the dataset with 12 types of annotations, and multiple annotation types were observed in the same image. We test validated our AI model with 1396 images, and sensitivity for all 12 types of annotations was about 91%, with 1375 true positives, 659 false positives, and 120 false negatives detected. The highest sensitivity for individual annotations was 97%, and the highest area under the receiver operating characteristic curve was 0.98, but the quality of detection varied depending on the specific annotation.

Conclusions

Object detection AI model in small bowel CE using YOLO v5 may provide effective and easy‐to‐understand reading assistance. In this SEE‐AI project, we open our dataset, the weights of the AI model, and a demonstration to experience our AI. We look forward to further improving the AI model in the future.

DOI： 10.1002/deo2.258

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞非特異性多発性小腸潰瘍症(CEAS)は持続的な出血に起因する慢性の貧血と低蛋白血症を特徴とする比較的まれな遺伝性疾患である.小腸に多発潰瘍を来すためCrohn病(CD)との鑑別が必要であるが,全例で遺伝学的検査を行うことは現実的でないため,簡便かつ非侵襲的なスクリーニング検査法が必要とされている.今回筆者らは,CEASとCDの鑑別における尿中プロスタグランジンE主要代謝産物(PGE-MUM)濃度の有用性について検討した.CEAS 20例とCD 98例を対象とした.PGE-MUM濃度はCD患者と比較しCEAS患者において有意に高値であった(中央値102.7 vs 27.9μg/g×Cre,p<0.0001).ROC解析では至適カットオフ値は48.9μg/g×Creと算出され,その際の感度は95.0%,特異度は79.6%であった.PGE-MUMは,CEASとCDの鑑別において有用な検査であると考えられた.

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞患者は10歳代,男性.主訴は腹痛,下痢.大腸内視鏡検査で上行結腸から下行結腸にかけて粘膜浮腫と縦走潰瘍を,S状結腸には小潰瘍から不整形潰瘍を認めた.Crohn病と診断しインフリキシマブを導入し,アザチオプリンの投与を行うものの寛解維持が困難であり,経過観察の大腸内視鏡検査では終末回腸はやや粗そうで,また直腸から連続性に全大腸に粗そう粘膜,びらん,血管透見像の消失を認めた.回腸からの生検では非乾酪性類上皮細胞肉芽腫を,大腸からの生検では炎症細胞浸潤,陰窩炎,陰窩膿瘍および杯細胞の減少を認めた.異時性にCrohn病,潰瘍性大腸炎両者の内視鏡所見を,同時性に両者の病理組織像を認めたことから,IBDUと診断した.青黛の内服投与で寛解導入され,3年後の大腸内視鏡検査では粘膜治癒が確認された.

Language：English   Publisher：Journal of Gastroenterology and Hepatology (Australia)  

DOI： 10.1111/jgh.16027

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Language：English   Publisher：Journal of Gastroenterology and Hepatology (Australia)  

DOI： 10.1111/jgh.16027

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞非特異性多発性小腸潰瘍症(CEAS)は持続的な出血に起因する慢性の貧血と低蛋白血症を特徴とする比較的まれな遺伝性疾患である.小腸に多発潰瘍を来すためCrohn病(CD)との鑑別が必要であるが,全例で遺伝学的検査を行うことは現実的でないため,簡便かつ非侵襲的なスクリーニング検査法が必要とされている.今回筆者らは,CEASとCDの鑑別における尿中プロスタグランジンE主要代謝産物(PGE-MUM)濃度の有用性について検討した.CEAS 20例とCD 98例を対象とした.PGE-MUM濃度はCD患者と比較しCEAS患者において有意に高値であった(中央値102.7 vs 27.9μg/g×Cre,p<0.0001).ROC解析では至適カットオフ値は48.9μg/g×Creと算出され,その際の感度は95.0%,特異度は79.6%であった.PGE-MUMは,CEASとCDの鑑別において有用な検査であると考えられた.

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞患者は10歳代,男性.主訴は腹痛,下痢.大腸内視鏡検査で上行結腸から下行結腸にかけて粘膜浮腫と縦走潰瘍を,S状結腸には小潰瘍から不整形潰瘍を認めた.Crohn病と診断しインフリキシマブを導入し,アザチオプリンの投与を行うものの寛解維持が困難であり,経過観察の大腸内視鏡検査では終末回腸はやや粗そうで,また直腸から連続性に全大腸に粗そう粘膜,びらん,血管透見像の消失を認めた.回腸からの生検では非乾酪性類上皮細胞肉芽腫を,大腸からの生検では炎症細胞浸潤,陰窩炎,陰窩膿瘍および杯細胞の減少を認めた.異時性にCrohn病,潰瘍性大腸炎両者の内視鏡所見を,同時性に両者の病理組織像を認めたことから,IBDUと診断した.青黛の内服投与で寛解導入され,3年後の大腸内視鏡検査では粘膜治癒が確認された.

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DOI： 10.1016/j.gie.2023.04.2086

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DOI： 10.14309/ajg.0000000000002175

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DOI： 10.14309/ajg.0000000000002175

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Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403203197

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society of Internal Medicine  

<p><b>Objective </b>The risk of developing peptic ulcers and gastrointestinal bleeding is high in patients with chronic kidney disease (CKD). Whether or not kidney transplant patients, who are treated with multiple medications, including immunosuppressive drugs, are at an increased risk of developing peptic ulcers is unclear. </p><p><b>Methods </b>In this retrospective study, we compared the clinical and endoscopic features of gastroduodenal ulcers between kidney transplant patients and CKD patients. The subjects underwent upper gastrointestinal endoscopy between January 2015 and March 2021. </p><p><b>Results </b>Gastroduodenal ulcers were observed more frequently (6.5%) in kidney transplant patients than in CKD patients (2.1%) (p=0.026). Due in part to the lower median age in the kidney transplant ulcer group than in the CKD ulcer group (59 vs. 70 years old, p=0.016), the rates of atrophic gastritis and <i>Helicobacter pylori</i> infection were also lower in the kidney transplant ulcer group than in the CKD ulcer group. Significantly more kidney transplant patients were treated with acid secretion inhibitors than CKD ulcer patients (100% vs. 34.8%, p=0.0005). Peptic ulcers were observed frequently in kidney transplant patients, even though common risk factors for gastroduodenal ulcers other than immunosuppressive drugs were few. All kidney transplant patients were taking immunosuppressive medications, and tacrolimus, mycophenolate mofetil, and methylprednisolone were taken more frequently than others. </p><p><b>Conclusion </b>Kidney transplant patients have a high risk of developing gastroduodenal ulcers. All kidney transplant patients take immunosuppressive medications, so there may be an association between immunosuppressive medications and gastroduodenal ulcer development. </p>

DOI： 10.2169/internalmedicine.1508-22

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Introduction The proportion of gastroduodenal ulcers caused by drugs is increasing. However, the risk of gastroduodenal ulcer from drugs other than non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin (LDA) is unclear. An association between immunosuppressive drugs and gastroduodenal ulcers has been suggested. We aimed to identify the immunosuppressive drugs and clinical characteristics associated with gastroduodenal ulcers in post-liver transplant patients. Methods The study investigated 119 patients who underwent esophagogastroduodenoscopy after liver transplantation and two patients were excluded. Clinical characteristics, medications, and endoscopic images were retrospectively reviewed. Results Among 117 post-living donor liver transplant recipients, gastroduodenal ulcers were found in 10 (9.2%) patients. The ulcer group had endoscopically gastritis more frequently (40%) compared with the non-ulcer group (10%). Logistic regression analysis revealed gastritis, NSAIDs use and mycophenolate mofetil were risk factors in the post-liver transplant patients. Among 103 patients not on NSAIDs, eight (7.8%) had peptic ulcer. The most common ulcer site and ulcer shape were the gastric antrum and a circular shape, respectively. All patients in the ulcer group were taking mycophenolate mofetil, which was the only immunosuppressive drug that showed a significant difference between the two groups. Five out of eight ulcer patients (63%) were taking gastric acid suppressants, and gastroduodenal ulcers in post-liver transplant recipients were suggested to be refractory. Conclusion Patients treated with immunosuppressive drugs after liver transplantation can develop gastroduodenal ulcers, even with gastric acid suppressant medication. Mycophenolate mofetil may increase the risk of gastroduodenal ulcers compared with other immunosuppressive drugs.

DOI： 10.1159/000530472

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Although chemotherapy has been an essential treatment for cancer, the development of immune checkpoint blockade therapy was revolutionary, and a comprehensive understanding of the immunological tumor microenvironment (TME) has become crucial. Here, we investigated the impact of neoadjuvant chemotherapy (NAC) on immune cells in the TME of human esophageal squamous cell carcinoma using single cell RNA-sequencing. Analysis of 30 fresh samples revealed that CD8+/CD4+ T cells, dendritic cells (DCs), and macrophages in the TME of human esophageal squamous cell carcinoma showed higher levels of an anti-tumor immune response in the NAC(+) group than in the NAC(-) group. Furthermore, the immune cells of the NAC(+) group interacted with each other resulting in enhanced anti-tumor immune response via various cytokines, including IFNG in CD8+/CD4+ T cells, EBI3 in DCs, and NAMPT in macrophages. Our results suggest that NAC potentially enhances the anti-tumor immune response of immune cells in the TME.

DOI： 10.1016/j.isci.2023.106480

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Language：Japanese   Publisher：大道学館出版部  

72歳男性。前立腺癌の術後再発に対するホルモン療法中に肺、肝臓の多発腫瘤が認められ、当科へ紹介となった。上部消化管内視鏡では胃体下部前後壁に粘膜下腫瘍状隆起を伴う潰瘍性病変が認められた。経過中に高熱と全身倦怠感が著明となり、緊急入院となり、画像所見から悪性リンパ腫が疑われた。病歴を再確認した結果、関節リウマチに対するメトトレキサート(MTX)の内服歴が判明し、泌尿器科の精査結果を総合して、本症例は胃MTX関連リンパ増殖性疾患と診断された。治療としてMTXの休薬を行い、胃病変や多臓器の多発腫瘤は自然寛解した。2年経過現在、無再発生存中である。

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

PURPOSE: Therapeutic efficacy of ustekinumab in the real-world data is limited in patients with refractory Crohn's disease (CD). In addition, factors predictive of better therapeutic efficacy of ustekinumab remains unsolved in CD. We aimed to evaluate therapeutic efficacy of ustekinumab in patients with refractory CD and to identify the factors associated with the efficacy of ustekinumab. METHODS: We retrospectively analyzed the clinical data of 72 patients treated with ustekinumab for refractory CD. Therapeutic efficacy was assessed at weeks 8, 26, 52, and 104 on the basis of dual remission, defined as the combination of Crohn's Disease Activity Index < 150 and CRP < 0.3 mg/dL, and factors predictive of the induction and maintenance of dual remission were investigated. The cumulative continuation rates and safety of ustekinumab were assessed. RESULTS: The dual remission rates at weeks 8, 26, 52, and 104 were 31.9%, 37.9%, 47.5%, and 42.6%, respectively. A short disease duration (≤ 2 years) and higher baseline serum albumin levels (≥ 3.1 g/dL) were positively associated with dual remission at weeks 8 and 52. Meanwhile, higher serum CRP levels (≥ 1.19 mg/dL) were negatively associated with dual remission at week 8. The cumulative ustekinumab continuation rate was favorable, and no severe adverse events were found. CONCLUSION: A short disease duration and higher baseline serum albumin levels might be predictive of favorable therapeutic efficacy of ustekinumab in refractory CD. Induction efficacy appears to be lower in patients with higher serum CRP levels.

DOI： 10.1007/s00384-023-04359-z

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BACKGROUND AND AIMS: Perianal lesion is a refractory phenotype of Crohn's disease (CD) with significantly diminished quality of life. We evaluated the clinical characteristics of perianal lesions in newly diagnosed CD patients and the impact of perianal lesions on the quality of life in Japanese patients with CD. METHODS: Patients newly diagnosed with CD after June 2016 were included between December 2018 and June 2020 from the Inception Cohort Registry Study of Patients with CD (iCREST-CD). RESULTS: Perianal lesions were present in 324 (48.2%) of 672 patients with newly diagnosed CD. 71.9% (233/324) were male. The prevalence of perianal lesions was higher in patients aged <40 years versus ≥40 years, and it decreased with age. Perianal fistula (59.9%) and abscess (30.6%) were the most common perianal lesions. In multivariate analyses, male sex, age <40 years, and ileocolonic disease location were significantly associated with a high prevalence of perianal lesions, whereas stricturing behaviour and alcohol intake were associated with low prevalence. Fatigue was more frequent (33.3% vs 21.6%) and, work productivity and activity impairment-work time missed (36.3% vs 29.5%) and activity impairment (51.9% vs 41.1%) were numerically higher in patients with than those without perianal lesions. CONCLUSIONS: At the time of CD diagnosis, approximately half of the patients had perianal lesions; perianal abscesses and perianal fistulas were the most common. Young age, male sex, disease location, and behaviour are significantly associated with the presence of perianal lesions. The presence of perianal lesion was associated with fatigue and impairment of daily activities.

DOI： 10.1093/ecco-jcc/jjad038

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DOI： 10.1016/j.gie.2022.10.030

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DOI： 10.1016/j.gie.2022.10.030

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Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403203108

CiNii Research

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403203120

CiNii Research

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

BACKGROUND AND AIM: The aim of this study was to elucidate the continuous use of antithrombotic medications during the peri-colorectal endoscopic submucosal dissection (ESD) period. METHODS: This study included 468 patients with colorectal epithelial neoplasms treated by ESD, consisting of 82 under antithrombotic medications and 386 patients without the medications. Among patients taking antithrombotic medications, antithrombotic agents were continued during the peri-ESD period. Clinical characteristics and adverse events were compared after propensity score matching. RESULTS: Before and after propensity score matching, post-colorectal ESD bleeding rate was higher in patients continuing antithrombotic medications (19.5% and 21.6%, respectively) than in those not taking antithrombotic medications (2.9% and 5.4%, respectively). In the Cox regression analysis, continuation of antithrombotic medications was associated with post-ESD bleeding risk (hazard ratio, 3.73; 95% confidence interval, 1.2-11.6; P < 0.05) compared with patients without antithrombotic therapy. All patients who experienced post-ESD bleeding were successfully treated by endoscopic hemostasis procedure or conservative therapy. CONCLUSIONS: Continuation of antithrombotic medications during the peri-colorectal ESD period increases the risk of bleeding. However, the continuation may be acceptable under careful monitoring for post-ESD bleeding.

DOI： 10.1111/jgh.16149

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞過去13年間に当科および関連施設にて診断された癌併存大腸SSL 17例を対象とし,病理組織学的所見と対比可能であったSSLと癌の領域の内視鏡所見を遡及的に比較検討した.その結果,癌領域はSSL領域に比べ,発赤(癌領域64.7%/SSL領域0%,p<0.05),結節・顆粒状隆起(癌領域64.7%/SSL領域5.9%,p<0.05)が多くみられた.一方でSSL領域の色調は全例で同色調,ないし褪色調を呈した(癌領域35.3%/SSL領域100%,p<0.05).以上より発赤,結節・顆粒状隆起の存在が癌併存SSLにおける癌領域の特徴的な所見であり,癌併存大腸SSLは通常内視鏡で診断できる可能性が示唆された.

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞患者は50歳代,男性.20XX年8月より心窩部痛,嘔気,体重減少が出現し,当院へ紹介となった.上部消化管X線造影検査では前庭部から胃体部に辺縁の毛羽立ちと粗そうな粘膜像を認め,EGDでは前庭部から胃体部に不整形のびらんや潰瘍が多発していた.当初は胃MALTリンパ腫を疑ったが,風俗店の利用歴と梅毒血清反応陽性であったため胃生検組織の抗T. pallidum抗体染色を行い,胃梅毒と診断した.ペニシリン,アモキシシリンによる駆梅療法を行った結果,速やかに軽快した.近年,梅毒感染症の増加が報告されており,消化器領域の日常診療でも胃梅毒に注意すべきである.

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞過去13年間に当科および関連施設にて診断された癌併存大腸SSL 17例を対象とし,病理組織学的所見と対比可能であったSSLと癌の領域の内視鏡所見を遡及的に比較検討した.その結果,癌領域はSSL領域に比べ,発赤(癌領域64.7%/SSL領域0%,p<0.05),結節・顆粒状隆起(癌領域64.7%/SSL領域5.9%,p<0.05)が多くみられた.一方でSSL領域の色調は全例で同色調,ないし褪色調を呈した(癌領域35.3%/SSL領域100%,p<0.05).以上より発赤,結節・顆粒状隆起の存在が癌併存SSLにおける癌領域の特徴的な所見であり,癌併存大腸SSLは通常内視鏡で診断できる可能性が示唆された.

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DOI： 10.1016/j.gie.2023.01.032

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BACKGROUND: Tumour immune microenvironment is related with carcinogenesis and efficacy of immunotherapy. B cells play major roles in humoral immunity, but detailed functions of tumour-infiltrating B lymphocytes (TIL-Bs) are unknown. Therefore, our aim was to investigate the functional heterogeneity of TIL-Bs in oesophageal squamous cell carcinoma (ESCC) and lymph nodes (LNs) during chemotherapy. METHODS: Single-cell transcriptome analysis was performed on 23 specimens. We also performed immunohistochemical analysis of immunoglobulin κ C (IGKC), an antibody-secreting cell (ASC) marker, in 166 ESCC samples and evaluated the implication of IGKC in 2-year recurrence free survival (RFS) and 3-year overall survival (OS). RESULTS: A total of 81,246 cells were grouped into 24 clusters. We extracted B cell clusters based on canonical markers and identified 12 TIL-B subtypes in ESCC. We found that several functions, such as co-stimulation and CD40 signalling, were enhanced in TIL-Bs after chemotherapy. The proportion of naive B cells (NBCs) decreased and B cell activation genes were up-regulated in NBCs after chemotherapy. The proportion of ASCs in tumours increased with the loss of migratory abilities and antibody production in ASCs was promoted after chemotherapy. Differentially expressed genes up-regulated with chemotherapy in ASCs correlated with prolonged survival with oesophageal cancer (p = .028). In a metastatic LN, the ASC proportion increased and B cell differentiation was enhanced. In immunohistochemical analysis, RFS and OS of high IGKC expression cases were significantly better than those of low IGKC expression cases (RFS: p < .0001, OS: p < .0001). And in multivariable analysis, the expression of IGKC was an independent favourable prognostic factor for RFS (hazard ratio (HR): 0.23, 95% confidence interval (CI): 0.12-0.45, p < .0001) and OS (HR: 0.20, 95% CI: 0.086-0.47, p = .0002) in ESCC. CONCLUSIONS: Our findings provide novel insights for the heterogeneity of TIL-Bs during chemotherapy and will be useful to understand the clinical importance of TIL-Bs.

DOI： 10.1002/ctm2.1181

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DOI： 10.1016/j.dld.2022.08.024

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DOI： 10.1016/j.dld.2022.08.024

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Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403203050

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BACKGROUND: The Inception Cohort Registry Study of Patients with Crohn's Disease aimed to clarify clinical characteristics and disease course of newly diagnosed Crohn's disease patients in Japan throughout a 4-year period. Results from an interim analysis of the largest nation-wide registry study that covers approximately 1% of Crohn's disease patient population in Japan are reported. METHODS: This prospective, observational registry study was conducted at 19 tertiary centers in Japan. Patients newly diagnosed with Crohn's disease after June 2016 (age ≥ 16 years at informed consent) were enrolled between December 17, 2018 and June 30, 2020. Patient demographics, diagnostic procedures and categories, disease location and lesion behavior (Montreal classification) at the time of diagnosis were recorded. RESULTS: Of 673 patients enrolled, 672 (99.9%) were analyzed (458: men, 214: women), male-to-female ratio: 2.1, median age at diagnosis 25 (range 13-86) years; peak age of disease diagnosis: 20-24 years. Most common disease location was L3 (ileocolonic; 60.1%). Non-stricturing, non-penetrating (B1) disease was most common behavior (62.8%); 48.9% reported perianal lesions. Notably, age-wise analysis revealed disease phenotypes varied between patients aged < 40 and ≥ 40 years in terms of male-to-female ratio (2.5/1.3)/disease location (L3: 66.3%/37.0%)/disease behavior (B1: 66.4%/50.0%)/perianal lesion: (55.7%/20.5%) at Crohn's disease diagnosis, respectively. CONCLUSIONS: Interim analysis of this nation-wide Inception Cohort Registry Study of Patients with Crohn's Disease revealed the demographics and disease characteristics of newly diagnosed Crohn's disease patients in Japan and demonstrated that disease phenotype varied between patients aged < 40 and ≥ 40 years, serving as important information for management of individual patients.

DOI： 10.1007/s00535-022-01907-2

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞当科で内視鏡的ないし外科的切除により病理組織学的に非乳頭部十二指腸腺腫・癌と確定診断された85例94病変のうち胃型形質と診断された32例35病変を対象とし,その臨床病理学的特徴を遡及的に検討した.32例35病変の平均年齢は72.2歳で,男性25例,女性7例であった.35病変は十二指腸球部25病変(71.4%),下行部乳頭口側6病変(17.1%)と乳頭より近位側の十二指腸に好発し.肉眼型はSMT様隆起が20病変(57.1%),0-I型が14病変(40.0%)と丈の高い病変がほとんどであった.白色化は35病変中6病変(17.1%)に認めるのみであった.術前に生検を施行した26病変のなかで評価可能であった25病変中22病変(88.0%)で病理組織学的に胃型腫瘍の可能性が示唆されていた.切除標本を検討すると病理組織学的に病変表面には胃腺窩上皮への分化を示す細胞から成る領域を35病変中34病変(97.1%)に認めた.35病変は病理組織学的に腺腫26病変,NUMP(neoplasms of uncertain malignant potential)3病変,腺癌6病変に分類された.NBI併用拡大観察では,NUMPと癌は,腺腫と比較してirregular MS pattern, irregular MV patternをそれぞれより高頻度に認めた.腺癌は全例,高分化管状腺癌で,M癌2例,SM癌4例であった.35病変は優位形質から分類すると,MUC5AC優位型(foveolar type)15病変(腺腫13病変,NUMP 2病変),MUC6優位型(pyloric gland type)18病変(腺腫13病変,NUMP 1病変,腺癌4病変)と分類不能型2病変(腺癌2病変)に分類された.MUC6優位型でより高頻度にSMT様の形態を呈していた.

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞当科で内視鏡的ないし外科的切除により病理組織学的に非乳頭部十二指腸腺腫・癌と確定診断された85例94病変のうち胃型形質と診断された32例35病変を対象とし,その臨床病理学的特徴を遡及的に検討した.32例35病変の平均年齢は72.2歳で,男性25例,女性7例であった.35病変は十二指腸球部25病変(71.4%),下行部乳頭口側6病変(17.1%)と乳頭より近位側の十二指腸に好発し.肉眼型はSMT様隆起が20病変(57.1%),0-I型が14病変(40.0%)と丈の高い病変がほとんどであった.白色化は35病変中6病変(17.1%)に認めるのみであった.術前に生検を施行した26病変のなかで評価可能であった25病変中22病変(88.0%)で病理組織学的に胃型腫瘍の可能性が示唆されていた.切除標本を検討すると病理組織学的に病変表面には胃腺窩上皮への分化を示す細胞から成る領域を35病変中34病変(97.1%)に認めた.35病変は病理組織学的に腺腫26病変,NUMP(neoplasms of uncertain malignant potential)3病変,腺癌6病変に分類された.NBI併用拡大観察では,NUMPと癌は,腺腫と比較してirregular MS pattern, irregular MV patternをそれぞれより高頻度に認めた.腺癌は全例,高分化管状腺癌で,M癌2例,SM癌4例であった.35病変は優位形質から分類すると,MUC5AC優位型(foveolar type)15病変(腺腫13病変,NUMP 2病変),MUC6優位型(pyloric gland type)18病変(腺腫13病変,NUMP 1病変,腺癌4病変)と分類不能型2病変(腺癌2病変)に分類された.MUC6優位型でより高頻度にSMT様の形態を呈していた.

Language：English   Publisher：シュプリンガー・ジャパン(株)  

全国クローン病患者診断時登録コホート研究の目的は、4年間に日本で新たに診断されたクローン病患者の臨床的特徴と疾患の経過を明らかにすることである。日本におけるクローン病患者の約1%を網羅する国内最大の登録研究の中間解析結果を報告した。日本の第三次医療機関19ヶ所で、前向き観察登録研究を施行した。2016年6月以降に新たに診断された症例(同意取得時の年齢≧16歳)を2018年12月17日から2020年6月30日までの間に登録した。診断時における人口統計学的データ、診断方法および分類、疾患部位と病巣の状態(モントリオール分類)を記録した。673例が登録され、672例(99.9%)を対象とした(男性458例、女性214例)。男女比は2.1で診断時の年齢の中央値は25歳(範囲13～86)であった。診断時の年齢で最も多かったのは20～24歳であった。罹患部位が最も多かったのはL3(回盲部、60.1%)であった。非狭窄性、非穿通性病変(B1)が最も多い病態であった(62.8%)。48.9%に肛門周囲病変が認められた。年齢別の解析の結果、40歳未満と40歳以上との間で、診断時疾患の表現型のうち、男女比(2.5/1.3)、病変部位(L3、66.3%/37.0%)、病態(B1、66.4%/50.0%)、肛門周囲病変の合併(55.7%/20.5%)が異なっていた。全国クローン病患者診断時登録コホート研究の中間解析により、クローン病診断時の人口統計学的データおよび疾患特性が明らかになった。疾患表現型が40歳未満と40歳以上で異なることが見出された。

Publisher：東京医学社  

DOI： 10.24479/endo.0000000381

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Publisher：東京医学社  

DOI： 10.24479/endo.0000000474

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Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403202993

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

Solid-type poorly differentiated adenocarcinoma (solid-type-PDA) of the stomach is a unique histological subtype of "tubular adenocarcinoma", but little is known about its clinicopathological features, molecular pathological characteristics and immunoregulatory tumor microenvironment. Herein, we examined the immunohistochemical expressions of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, MSH6) in 57 cases of solid-type-PDA and classified them as either MMR-deficient or -proficient (dMMR, N = 23; pMMR, N = 34), and additionally identified 18 dMMR-well-differentiated adenocarcinoma (WDA) and 34 pMMR-WDA as control groups. We analyzed and compared solid-type-PDA with WDA by evaluating the immunoexpressions of key immune pathway proteins (programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1)) and tumor-infiltrating lymphocytes (TILs) (CD8, Foxp3 and PD-1). The results reveled IDO1 was significantly more frequent in dMMR-solid-type-PDA than in dMMR-WDA (P = 0.0046). Moreover, dMMR-solid-type-PDA tended to have higher mean CD8+ and Foxp3+ TILs compared with dMMR-WDA [P = 0.0006 (CD8+) and P = 0.1061 (Foxp3+)], and IDO1-positive tended to be associated with a large number of CD8+, Foxp3+ or PD-1+ TILs in almost all tumor subtypes. PD-L1 was significantly observed in 44 % (15/34) of pMMR-solid-type-PDA compared with 18 % (6/34) of pMMR-WDA (P = 0.0344). Although they are molecularly and morphologically classified as the same chromosomal instability subtype, overall survival (OS) and disease-free-survival (DFS) in pMMR-solid-type-PDA were significantly worse than those in pMMR-WDA [P = 0.0216 (OS) and P = 0.0160 (DFS)]. Our study demonstrates that immunoexpressions of several immunoregulatory proteins and TILs are more prevalent in dMMR-solid-type-PDA, potentially a useful discovery for designing tumor treatments with immune checkpoint inhibitors or combination therapies with a PD-1/PD-L1-inhibitor and IDO1-inhibitor.

DOI： 10.1016/j.prp.2022.154124

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E-カドヘリン欠損胃印環細胞癌(SRCC)における新規治療標的を同定することを目的とした。E-カドヘリンをコードするCDH1遺伝子をノックアウト(KO)したヒト胃オルガノイド(hGO)を用いて、in vitroのE-カドヘリン欠損胃癌モデルを作製し、新規治療標的を探索した。CDH1 KO hGO細胞は、SRCCに類似した特徴的な形態変化と高い細胞運動性を示した。RNA配列解析の結果、CDH1 KO hGO細胞では、野生型と比較して、マトリックスメタロプロテアーゼ(MMP)遺伝子の発現が増加していた。MMP阻害剤は、in vitroでCDH1 KO hGO細胞およびSRCC細胞株の細胞運動を抑制した。95例の臨床胃癌組織を用いた免疫蛍光分析により、MMP-3はE-カドヘリン異常のSRCCに特異的に多く存在することが示された。また、CDH1 KO後、CXCR4分子が細胞膜上に移行した。CXCR4のリガンドであるCXCL12を培養液に添加すると、CDH1 KO hGO細胞の細胞生存率が延長し、CXCR4アンタゴニストであるAMD3100によってその効果が消失した。SRCCの臨床サンプルでは、CXCL12を分泌する線維芽細胞が癌領域に著しく浸潤していることを確認した。以上より、MMPとCXCL12/CXCR4軸は、E-カドヘリン欠損SRCCの新規治療標的として有望な候補であると考えられた。

Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

クエン酸マグネシウム(Mg)製剤による大腸内視鏡前処置後に著明な高Mg血症を生じた2例を経験した.両症例とも前処置前には腎障害を認めず,大腸癌による腸管切除歴を有していた.発症時,症例1は直腸吻合部付近の便塊貯留による糞便性腸閉塞を,症例2はS状結腸に吻合部狭窄による通過障害を認めていた.それぞれ全身管理のもとで用手摘便とバルーン拡張にて閉塞を解除することで病状の改善が得られた.潜在的に腸管通過障害を有する被験者では,腎機能に関わらずMg製剤を用いた前処置による高Mg血症の出現に十分注意する必要があると考えられた.(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00192&link_issn=&doc_id=20220926340005&doc_link_id=10.11280%2Fgee.64.1564&url=https%3A%2F%2Fdoi.org%2F10.11280%2Fgee.64.1564&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

クエン酸マグネシウム(Mg)製剤による大腸内視鏡前処置後に著明な高Mg血症を生じた2例を経験した.両症例とも前処置前には腎障害を認めず,大腸癌による腸管切除歴を有していた.発症時,症例1は直腸吻合部付近の便塊貯留による糞便性腸閉塞を,症例2はS状結腸に吻合部狭窄による通過障害を認めていた.それぞれ全身管理のもとで用手摘便とバルーン拡張にて閉塞を解除することで病状の改善が得られた.潜在的に腸管通過障害を有する被験者では,腎機能に関わらずMg製剤を用いた前処置による高Mg血症の出現に十分注意する必要があると考えられた.(著者抄録)

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

BACKGROUND: Loss of E-cadherin expression is frequently observed in signet ring carcinoma (SRCC). People with germline mutations in CDH1, which encodes E-cadherin, develop diffuse gastric cancer at a higher rate. Loss of E-cadherin expression is thus assumed to trigger oncogenic development. METHODS: To investigate novel therapeutic targets for gastric SRCC, we engineered an E-cadherin-deficient SRCC model in vitro using a human gastric organoid (hGO) with CDH1 knockout (KO). RESULTS: CDH1 KO hGO cells demonstrated distinctive morphological changes similar to SRCC and high cell motility. RNA-sequencing revealed up-regulation of matrix metalloproteinase (MMP) genes in CDH1 KO hGO cells compared to wild type. MMP inhibitors suppressed cell motility of CDH1 KO hGO cells and SRCC cell lines in vitro. Immunofluorescent analysis with 95 clinical gastric cancer tissues revealed that MMP-3 was specifically abundant in E-cadherin-aberrant SRCC. In addition, CXCR4 molecules translocated onto the cell membrane after CDH1 KO. Addition of CXCL12, a ligand of CXCR4, to the culture medium prolonged cell survival of CDH1 KO hGO cells and was abolished by the inhibitor, AMD3100. In clinical SRCC samples, CXCL12-secreting fibroblasts showed marked infiltration into the cancer area. CONCLUSIONS: E-cadherin deficient SRCCs might gain cell motility through upregulation of MMPs. CXCL12-positive cancer-associated fibroblasts could serve to maintain cancer-cell survival as a niche. MMPs and the CXCL12/CXCR4 axis represent promising candidates as novel therapeutic targets for E-cadherin-deficient SRCC.

DOI： 10.1007/s10120-022-01307-8

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Language：English   Publisher：シュプリンガー・ジャパン(株)  

E-カドヘリン欠損胃印環細胞癌(SRCC)における新規治療標的を同定することを目的とした。E-カドヘリンをコードするCDH1遺伝子をノックアウト(KO)したヒト胃オルガノイド(hGO)を用いて、in vitroのE-カドヘリン欠損胃癌モデルを作製し、新規治療標的を探索した。CDH1 KO hGO細胞は、SRCCに類似した特徴的な形態変化と高い細胞運動性を示した。RNA配列解析の結果、CDH1 KO hGO細胞では、野生型と比較して、マトリックスメタロプロテアーゼ(MMP)遺伝子の発現が増加していた。MMP阻害剤は、in vitroでCDH1 KO hGO細胞およびSRCC細胞株の細胞運動を抑制した。95例の臨床胃癌組織を用いた免疫蛍光分析により、MMP-3はE-カドヘリン異常のSRCCに特異的に多く存在することが示された。また、CDH1 KO後、CXCR4分子が細胞膜上に移行した。CXCR4のリガンドであるCXCL12を培養液に添加すると、CDH1 KO hGO細胞の細胞生存率が延長し、CXCR4アンタゴニストであるAMD3100によってその効果が消失した。SRCCの臨床サンプルでは、CXCL12を分泌する線維芽細胞が癌領域に著しく浸潤していることを確認した。以上より、MMPとCXCL12/CXCR4軸は、E-カドヘリン欠損SRCCの新規治療標的として有望な候補であると考えられた。

Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

クエン酸マグネシウム(Mg)製剤による大腸内視鏡前処置後に著明な高Mg血症を生じた2例を経験した.両症例とも前処置前には腎障害を認めず,大腸癌による腸管切除歴を有していた.発症時,症例1は直腸吻合部付近の便塊貯留による糞便性腸閉塞を,症例2はS状結腸に吻合部狭窄による通過障害を認めていた.それぞれ全身管理のもとで用手摘便とバルーン拡張にて閉塞を解除することで病状の改善が得られた.潜在的に腸管通過障害を有する被験者では,腎機能に関わらずMg製剤を用いた前処置による高Mg血症の出現に十分注意する必要があると考えられた.(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00192&link_issn=&doc_id=20220926340005&doc_link_id=10.11280%2Fgee.64.1564&url=https%3A%2F%2Fdoi.org%2F10.11280%2Fgee.64.1564&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

クエン酸マグネシウム(Mg)製剤による大腸内視鏡前処置後に著明な高Mg血症を生じた2例を経験した.両症例とも前処置前には腎障害を認めず,大腸癌による腸管切除歴を有していた.発症時,症例1は直腸吻合部付近の便塊貯留による糞便性腸閉塞を,症例2はS状結腸に吻合部狭窄による通過障害を認めていた.それぞれ全身管理のもとで用手摘便とバルーン拡張にて閉塞を解除することで病状の改善が得られた.潜在的に腸管通過障害を有する被験者では,腎機能に関わらずMg製剤を用いた前処置による高Mg血症の出現に十分注意する必要があると考えられた.(著者抄録)

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

BACKGROUND: Loss of E-cadherin expression is frequently observed in signet ring carcinoma (SRCC). People with germline mutations in CDH1, which encodes E-cadherin, develop diffuse gastric cancer at a higher rate. Loss of E-cadherin expression is thus assumed to trigger oncogenic development. METHODS: To investigate novel therapeutic targets for gastric SRCC, we engineered an E-cadherin-deficient SRCC model in vitro using a human gastric organoid (hGO) with CDH1 knockout (KO). RESULTS: CDH1 KO hGO cells demonstrated distinctive morphological changes similar to SRCC and high cell motility. RNA-sequencing revealed up-regulation of matrix metalloproteinase (MMP) genes in CDH1 KO hGO cells compared to wild type. MMP inhibitors suppressed cell motility of CDH1 KO hGO cells and SRCC cell lines in vitro. Immunofluorescent analysis with 95 clinical gastric cancer tissues revealed that MMP-3 was specifically abundant in E-cadherin-aberrant SRCC. In addition, CXCR4 molecules translocated onto the cell membrane after CDH1 KO. Addition of CXCL12, a ligand of CXCR4, to the culture medium prolonged cell survival of CDH1 KO hGO cells and was abolished by the inhibitor, AMD3100. In clinical SRCC samples, CXCL12-secreting fibroblasts showed marked infiltration into the cancer area. CONCLUSIONS: E-cadherin deficient SRCCs might gain cell motility through upregulation of MMPs. CXCL12-positive cancer-associated fibroblasts could serve to maintain cancer-cell survival as a niche. MMPs and the CXCL12/CXCR4 axis represent promising candidates as novel therapeutic targets for E-cadherin-deficient SRCC.

DOI： 10.1007/s10120-022-01307-8

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Publisher：東京医学社  

DOI： 10.24479/endo.0000000301

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Publisher：東京医学社  

DOI： 10.24479/endo.0000000300

CiNii Research

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

A 71-year-old man was admitted to our institution complaining of abdominal pain and constipation. Barium enema examination revealed narrowing, cobble stoning, and longitudinal ulcerations in the sigmoid colon and upper rectum. Conventional colonoscopy, magnifying narrow-band imaging endoscopy, and magnifying chromoendoscopy revealed edematous mucosa, longitudinal ulcerations with luminal narrowing, and multiple pseudopolyps. The histologic examination of the biopsy specimens showed thick-walled (arterialized) capillaries and subendothelial fibrin deposits in the mucosa and submucosa. Based on a preoperative diagnosis of idiopathic myointimal hyperplasia of mesenteric veins (IMHMV), he underwent a laparoscopic resection of the sigmoid colon and upper rectum. The histologic examination of the resected specimens showed marked proliferation of venous walls with marked myointimal thickening and luminal occlusion from the submucosa to the mesentery throughout the entire resected tissue section. The final diagnosis was IMHMV.

DOI： 10.1007/s12328-022-01647-z

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

A 71-year-old man was admitted to our institution complaining of abdominal pain and constipation. Barium enema examination revealed narrowing, cobble stoning, and longitudinal ulcerations in the sigmoid colon and upper rectum. Conventional colonoscopy, magnifying narrow-band imaging endoscopy, and magnifying chromoendoscopy revealed edematous mucosa, longitudinal ulcerations with luminal narrowing, and multiple pseudopolyps. The histologic examination of the biopsy specimens showed thick-walled (arterialized) capillaries and subendothelial fibrin deposits in the mucosa and submucosa. Based on a preoperative diagnosis of idiopathic myointimal hyperplasia of mesenteric veins (IMHMV), he underwent a laparoscopic resection of the sigmoid colon and upper rectum. The histologic examination of the resected specimens showed marked proliferation of venous walls with marked myointimal thickening and luminal occlusion from the submucosa to the mesentery throughout the entire resected tissue section. The final diagnosis was IMHMV.

DOI： 10.1007/s12328-022-01647-z

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Language：English   Publisher：シュプリンガー・ジャパン(株)  

症例は71歳男性で、4ヵ月前からの間欠性腹痛と便秘を訴えて入院した。バリウム注腸検査で、S状結腸と上部直腸の狭窄、cobble stoning、縦断的潰瘍形成が認められた。従来型結腸鏡検査と拡大狭帯域光観察、拡大色素内視鏡検査では、浮腫性粘膜、内腔狭窄と皺襞集中像を伴う縦断的潰瘍形成、多発性ポリープ様病変が認められた。生検標本の組織学的所見は、厚壁(動脈化)毛細管、粘膜および粘膜下層の内皮下フィブリン沈着であった。直腸S状結腸の特発性腸間膜静脈筋内膜過形成(IMHMV)と術前診断し、S状結腸と上部直腸の腹腔鏡下切除術を行った。切除標本の組織学的所見は、著明な筋内膜肥厚を伴う静脈壁の著明な増殖、粘膜下層から腸間膜への内腔閉塞であった。IMHMVと最終診断した。術後8ヵ月の時点で、再発の徴候は認めていない。

Language：English   Publisher：The Japanese Society of Internal Medicine  

DOI： 10.2169/internalmedicine.8475-21

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Language：English   Publisher：The Japanese Society of Internal Medicine  

DOI： 10.2169/internalmedicine.8475-21

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Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403202916

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Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403202910

CiNii Research

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403202757

CiNii Research

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403202793

CiNii Research

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403202850

CiNii Research

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403202844

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Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403202819

CiNii Research

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403202830

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Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403202762

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Language：English   Publisher：Digestive and Liver Disease  

DOI： 10.1016/j.dld.2020.11.014

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞過去15年間に当科および関連施設にて診断された原発性空・回腸癌19例を対象とし,臨床像,小腸X線造影所見を検討した.平均腫瘍径は43.4mmで,病変部位は空腸12例,回腸7例であった.肉眼型は潰瘍型が14例と最多で,すべて輪状狭窄型であった.TNM分類Stage IVの割合が高く(32%),5年後のOS(overall survival)は58%,TNM分類Stage IVはOS,EFS(event-free survival)の,空腸,潰瘍型はEFSの予後不良因子であった.小腸X線造影所見では輪状狭窄型の全例,および全周性の隆起型病変でnapkin-ring sign,口側腸管の拡張像を,輪状狭窄型はさらに全例でoverhanging edgeを認めた.以上より,原発性空・回腸癌の予後不良因子はTNM分類Stage IVであり,輪状狭窄型および全周性の隆起型病変は特徴的な小腸X線造影検査所見を有していた.

Language：English   Publisher：Digestive and Liver Disease  

DOI： 10.1016/j.dld.2020.11.014

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞過去15年間に当科および関連施設にて診断された原発性空・回腸癌19例を対象とし,臨床像,小腸X線造影所見を検討した.平均腫瘍径は43.4mmで,病変部位は空腸12例,回腸7例であった.肉眼型は潰瘍型が14例と最多で,すべて輪状狭窄型であった.TNM分類Stage IVの割合が高く(32%),5年後のOS(overall survival)は58%,TNM分類Stage IVはOS,EFS(event-free survival)の,空腸,潰瘍型はEFSの予後不良因子であった.小腸X線造影所見では輪状狭窄型の全例,および全周性の隆起型病変でnapkin-ring sign,口側腸管の拡張像を,輪状狭窄型はさらに全例でoverhanging edgeを認めた.以上より,原発性空・回腸癌の予後不良因子はTNM分類Stage IVであり,輪状狭窄型および全周性の隆起型病変は特徴的な小腸X線造影検査所見を有していた.

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

INTRODUCTION: An association has been found between human-gut microbiota and various diseases (e.g., metabolic disease) by analyzing fecal or colonic microbiota. Despite the importance of the small intestinal microbiota, sampling difficulties prevent its full analysis. We investigated the composition and metagenomic functions of microbiota along the small intestine and compared them with the microbiota from feces and from other gastrointestinal (GI) sites. METHODS: Mucosal samples from the six GI sites (stomach, duodenum, distal jejunum, proximal ileum, terminal ileum, and rectum) were collected under balloon-assisted enteroscopy. Fecal samples were collected from all participants. The microbial structures and metagenomic functions of the small intestinal mucosal microbiota were compared with those from feces and other GI sites using 16S ribosomal RNA gene sequencing. RESULTS: We analyzed 133 samples from 29 participants. Microbial beta diversity analysis showed that the jejunum and ileum differed significantly from the lower GI tract and the feces (p < 0.001). Jejunal and duodenal microbiotas formed similar clusters. Wide clusters spanning the upper and lower GI tracts were observed with the ileal microbiota, which differed significantly from the jejunal microbiota (p < 0.001). Veillonella and Streptococcus were abundant in the jejunum but less so in the lower GI tract and feces. The metagenomic functions associated with nutrient metabolism differed significantly between the small intestine and the feces. CONCLUSIONS: The fact that the compositional structures of small intestinal microbiota differed from those of fecal and other GI microbiotas reveals that analyzing the small intestinal microbiota is necessary for association studies on metabolic diseases and gut microbiota.

DOI： 10.1159/000524023

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BACKGROUND/AIMS: Recent studies suggested a favorable effect of indigo naturalis (IN) in inducing remission for refractory ulcerative colitis (UC), however, the maintenance effect of IN for patients with UC remains unknown. Therefore, we conducted a prospective uncontrolled open-label study to analyze the efficacy and safety of IN for patients with UC. METHODS: Patients with moderate to severe active UC (clinical activity index [CAI] ≥ 8) took 2 g/day of IN for 52 weeks. CAI at weeks 0, 4, 8, and 52 and Mayo endoscopic subscore (MES) and Geboes score (GS) at weeks 0, 4, and 52 were assessed. Clinical remission (CAI ≤ 4), mucosal healing (MES ≤ 1), and histological healing (GS ≤ 1) rates at each assessment were evaluated. Overall adverse events (AEs) during study period were also evaluated. The impact of IN on mucosal microbial composition was assessed using 16S ribosomal RNA gene sequences. RESULTS: Thirty-three patients were enrolled. The rates of clinical remission at weeks 4, 8, and 52 were 67%, 76%, and 73%, respectively. The rates of mucosal healing at weeks 4 and 52 were 48% and 70%, respectively. AEs occurred in 17 patients (51.5%) during follow-up. Four patients (12.1%) showed severe AEs, among whom 3 manifested acute colitis. No significant alteration in the mucosal microbial composition was observed with IN treatment. CONCLUSIONS: One-year treatment of moderate to severe UC with IN was effective. IN might be a promising therapeutic option for maintaining remission in UC, although the relatively high rate of AEs should be considered.

DOI： 10.5217/ir.2021.00124

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

BACKGROUND/AIMS: Recent studies suggested a favorable effect of indigo naturalis (IN) in inducing remission for refractory ulcerative colitis (UC), however, the maintenance effect of IN for patients with UC remains unknown. Therefore, we conducted a prospective uncontrolled open-label study to analyze the efficacy and safety of IN for patients with UC. METHODS: Patients with moderate to severe active UC (clinical activity index [CAI] ≥ 8) took 2 g/day of IN for 52 weeks. CAI at weeks 0, 4, 8, and 52 and Mayo endoscopic subscore (MES) and Geboes score (GS) at weeks 0, 4, and 52 were assessed. Clinical remission (CAI ≤ 4), mucosal healing (MES ≤ 1), and histological healing (GS ≤ 1) rates at each assessment were evaluated. Overall adverse events (AEs) during study period were also evaluated. The impact of IN on mucosal microbial composition was assessed using 16S ribosomal RNA gene sequences. RESULTS: Thirty-three patients were enrolled. The rates of clinical remission at weeks 4, 8, and 52 were 67%, 76%, and 73%, respectively. The rates of mucosal healing at weeks 4 and 52 were 48% and 70%, respectively. AEs occurred in 17 patients (51.5%) during follow-up. Four patients (12.1%) showed severe AEs, among whom 3 manifested acute colitis. No significant alteration in the mucosal microbial composition was observed with IN treatment. CONCLUSIONS: One-year treatment of moderate to severe UC with IN was effective. IN might be a promising therapeutic option for maintaining remission in UC, although the relatively high rate of AEs should be considered.

DOI： 10.5217/ir.2021.00124

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Language：English   Publisher：Gastrointestinal Endoscopy  

DOI： 10.1016/j.gie.2021.09.032

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Language：English   Publisher：Gastrointestinal Endoscopy  

DOI： 10.1016/j.gie.2021.09.032

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

Lymphoproliferative disorder (LPD) can occur in patients with inflammatory bowel disease (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD). On rare occasion, patients with IBD develop myeloid neoplasms; however, the frequency and clinicopathological features of IBD-associated lymphoid and myeloid proliferative disorder (LMPD) in Japanese patients is still unclear. In this study, we reviewed 2474 Japanese patients with IBD, and found that LMPD occurred in 12 (0.5%) patients with UC (n=7) or CD (n=5). Together with an additional 3 cases, we analyzed a total of 15 cases of LMPD for clinicopathological and histological features. Based on the status of using immunosuppressants such as biologics and immunomodulators, Epstein-Barr virus (EBV) infection, and histopathology, the 15 cases were classified into the Group I (high-grade LPD; n=7), Group II (low-grade LPD; n=5), and Group III (myeloid neoplasms; n=3). Most patients in Group I were undergoing strong immunosuppressive therapy, and the LPD lesions corresponded to high-grade B-cell or T/NK-cell lymphoma often with EBV infection. Discontinuation of immunosuppressive drugs alone did not resolve these LPDs; Group I patients required chemotherapy, and eventually 4 of them (57%) died of the tumor. Most cases in Group II were low-grade B-cell lymphoma without EBV infection and had an indolent clinical course with excellent prognosis. All patients in Group III developed acute myeloid leukemia (AML) during the course of CD. Two (67%) of these patients died of AML. Our study suggests that IBD-associated LMPD is very rare, but can follow an aggressive clinical course.

DOI： 10.1016/j.humpath.2021.12.010

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Language：Japanese   Publisher：Japan Gastroenterological Endoscopy Society  

<p>Two cases of extreme hypermagnesemia occurred after administration of bowel preparation with magnesium citrate for colonoscopy. Neither patient had renal dysfunction but both had a history of bowel resection for treatment of colorectal cancer. Each patient presented with bowel obstruction secondary to fecal impaction at the rectal anastomosis or severe anastomotic stricture at the sigmoid colon. The hypermagnesemia improved in each with the successful release of the bowel obstruction by digital disimpaction or balloon dilation under systemic management. In a patient with a possible intestinal obstruction, the risk of hypermagnesemia incidence with bowel preparation with magnesium products should be considered regardless of renal function.</p>

DOI： 10.11280/gee.64.1564

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Language：Japanese   Publisher：Japan Gastroenterological Endoscopy Society  

<p>Two cases of extreme hypermagnesemia occurred after administration of bowel preparation with magnesium citrate for colonoscopy. Neither patient had renal dysfunction but both had a history of bowel resection for treatment of colorectal cancer. Each patient presented with bowel obstruction secondary to fecal impaction at the rectal anastomosis or severe anastomotic stricture at the sigmoid colon. The hypermagnesemia improved in each with the successful release of the bowel obstruction by digital disimpaction or balloon dilation under systemic management. In a patient with a possible intestinal obstruction, the risk of hypermagnesemia incidence with bowel preparation with magnesium products should be considered regardless of renal function.</p>

DOI： 10.11280/gee.64.1564

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CiNii Research

Language：Japanese   Publisher：日本小腸学会  

<p>【背景】</p><p>　クローン病（CD）は小腸診療において多く遭遇する疾患の一つである。炎症性腸疾患において、1〜3%程度の頻度でCOVID-19ワクチン接種後に病勢が増悪することが報告されているが、潰瘍性大腸炎と統合された頻度であり、個々の病態の変化に関する詳細な報告は少ない。そこで我々は、CDにおけるCOVID-19ワクチン接種後の病勢変化を明らかにすることを目的とし、本研究を行なった。</p><p>【方法】</p><p>　2021年10月から2022年2月の期間に、当科通院中のCD患者を対象にワクチン接種状況および接種前後のCDに関連する症状について後方視的観察研究を行った。</p><p>　詳細な臨床情報が得られた179例中、ワクチン接種を受けていた患者は148例であった。非ストーマ患者では接種前後のHarvey-Bradshaw index（HBI）を、ストーマ患者ではInternational organization for the study of IBD score（IOIBD）を算出した。</p><p>　接種前のHBI≦３もしくはIOIBD≦1を寛解期、HBI≧4もしくはIOIBD≧2を活動期と定義し、⊿HBI≧2あるいは⊿IOIBD≧2を増悪と定義した。接種後の発熱や倦怠感は4日以上持続するものを全身状態の悪化と判定した。</p><p>【結果】</p><p>　ワクチンを接種したCD症例148例の平均年齢は44.3歳であり、男性104例、女性44例で、病型は小腸大腸型が87例、小腸型が43例、大腸型が18例であった。</p><p>　接種前のHBIおよびIOIBDの平均値はそれぞれ0.51および0.2であり、寛解期が119例、活動期が29例であった。病勢が増悪した症例を2例認めた。寛解期に増悪を認めた症例は1例（0.8%）で、初回接種の7日後から増悪し、腹腔内膿瘍のため手術を要した。活動期に増悪を認めた症例も１例（3.4%）であり、2回の接種期間を通じて徐々に増悪したため、ステロイドおよびアザチオプリン内服を追加した。</p><p>【結語】</p><p>　CDにおいて、ワクチン接種後に病勢が増悪した症例を２例（1.4％）認めたものの、頻度は極めて少なく、ウィズコロナ時代において、CD患者へのワクチン接種は推奨されるべきと考えられた。</p>

DOI： 10.32264/shocho.6.0_56

CiNii Research

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

DOI： 10.1007/s00535-021-01829-5

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DOI： 10.1097/MD.0000000000027287

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DOI： 10.1159/000518103

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DOI： 10.2169/internalmedicine.6341-20

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DOI： 10.1007/s00535-021-01793-0

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DOI： 10.1007/s11604-021-01157-x

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DOI： 10.1016/j.jot.2020.12.005

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DOI： 10.1002/hon.2816

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DOI： 10.1055/a-1243-0226

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DOI： 10.1007/s10620-020-06600-z

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DOI： 10.1007/s12328-020-01205-5

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DOI： 10.1093/ibd/izaa033

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DOI： 10.1111/den.13776

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DOI： 10.1038/s41598-020-66951-5

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DOI： 10.1002/hon.2717

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DOI： 10.1002/hon.2717

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DOI： 10.1111/jgh.14823

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DOI： 10.1111/jgh.14823

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DOI： 10.1111/jgh.14885

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DOI： 10.1007/s13730-019-00421-4

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DOI： 10.1016/j.humpath.2019.09.003

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DOI： 10.1016/j.humpath.2019.09.003

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DOI： 10.1053/j.gastro.2019.07.047

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DOI： 10.1053/j.gastro.2019.07.047

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DOI： 10.1111/jgh.14689

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DOI： 10.1111/jgh.14685

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DOI： 10.5217/ir.2018.00107

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DOI： 10.5217/ir.2018.00161

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DOI： 10.1007/s13730-018-0371-9

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DOI： 10.3748/wjg.v25.i14.1753

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DOI： 10.1007/s00535-018-1511-x

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DOI： 10.1007/s00535-018-1511-x

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

A 68-year-old man was referred to our hospital because of watery diarrhea lasting for three months. On colonoscopy, severe luminal stenosis with coarse granular mucosa was observed in the rectosigmoid colon. Based on the findings of imaging and histological examinations, ischemic colitis due to either inferior mesenteric venous occlusion or disordered venous perfusion associated with thrombosis or arteriovenous malformation was suspected. However, Hartmanns operation was performed considering the possibility of type 4 colorectal cancer. Histological examination of the resected specimen revealed a small superficial depressed rectal adenocarcinoma accompanied by marked venous invasion with a tumor embolus in the inferior mesenteric vein, that caused long-segmental ischemic change of the rectosigmoid colon. We herein report this unusual case of superficial rectal cancer that required differentiation from ischemic colitis caused by other morbidities.

DOI： 10.11280/gee.61.163

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DOI： 10.1159/000496826

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DOI： 10.3748/wjg.v25.i14.1753

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DOI： 10.1016/j.dld.2017.12.003

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DOI： 10.1016/j.dld.2017.12.003

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DOI： 10.1111/jgh.14129

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DOI： 10.1111/jgh.14129

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DOI： 10.1097/MD.0000000000008987

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DOI： 10.1097/MD.0000000000008987

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DOI： 10.1242/bio.027458

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DOI： 10.1242/bio.027458

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DOI： 153

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DOI： 10.1053/j.gastro.2017.01.020

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DOI： 10.1053/j.gastro.2017.01.020

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DOI： 10.1111/gtc.12402

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Genomewide association studies have shown that a nonsynonymous single nucleotide polymorphism in PRKCH is associated with cerebral infarction and atherosclerosis-related complications. We examined the role of PKCη in lipid metabolism and atherosclerosis using apolipoprotein E-deficient (Apoe-/- ) mice. PKCη expression was augmented in the aortas of mice with atherosclerosis and exclusively detected in MOMA2-positive macrophages within atherosclerotic lesions. Prkch+/+ Apoe-/- and Prkch-/- Apoe-/- mice were fed a high-fat diet (HFD), and the dyslipidemia observed in Prkch+/+ Apoe-/- mice was improved in Prkch-/- Apoe-/- mice, with a particular reduction in serum LDL cholesterol and phospholipids. Liver steatosis, which developed in Prkch+/+ Apoe-/- mice, was improved in Prkch-/- Apoe-/- mice, but glucose tolerance, adipose tissue and body weight, and blood pressure were unchanged. Consistent with improvements in LDL cholesterol, atherosclerotic lesions were decreased in HFD-fed Prkch-/- Apoe-/- mice. Immunoreactivity against 3-nitrotyrosine in atherosclerotic lesions was dramatically decreased in Prkch-/- Apoe-/- mice, accompanied by decreased necrosis and apoptosis in the lesions. ARG2 mRNA and protein levels were significantly increased in Prkch-/- Apoe-/- macrophages. These data show that PKCη deficiency improves dyslipidemia and reduces susceptibility to atherosclerosis in Apoe-/- mice, showing that PKCη plays a role in atherosclerosis development.

DOI： 10.1111/gtc.12402

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DOI： 10.1053/j.gastro.2016.06.018

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DOI： 10.1053/j.gastro.2016.06.018

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DOI： 10.1111/acel.12423

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DOI： 10.1111/acel.12423

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DOI： 10.1038/nm.3288

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DOI： 10.1016/j.crohns.2011.10.010

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DOI： 10.1016/j.crohns.2011.10.010

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DOI： 10.1186/1471-2458-10-386

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DOI： 10.1186/1471-2458-10-386

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DOI： 10.1016/j.archger.2009.04.005

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DOI： 10.1007/BF03324812

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DOI： 10.3109/10641960903407009

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DOI： 10.3109/10641960903407009

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DOI： 10.1159/000162260

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DOI： 10.5551/jat.943

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DOI： 10.1007/s00535-008-2219-0

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DOI： 10.1159/000129757

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DOI： 10.1111/j.1741-2358.2007.00203.x

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DOI： 10.1111/j.1741-2358.2007.00203.x

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DOI： 10.1002/hep.22214

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DOI： 10.1002/hep.22214

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Suppressor of cytokine signaling 1 (SOCS1) is an important negative regulator for cytokines; however, the role of SOCS1 in Th17 differentiation has not been clarified. We generated T cell-specific SOCS1-deficient mice and found that these mice were extremely resistant to a Th17-dependent autoimmune disease model, experimental autoimmune encephalomyelitis. SOCS1-deficient naive CD4 ⁺ T cells were predominantly differentiated into Th1 and poorly into Th17 in vitro. These phenotypes were canceled in IFN-γ^-/- background, suggesting that a large amount of IFN-γ in SOCS1-deficient T cells suppressed Th17 differentiation. IL-6 plus TGF-β enhanced retinoic acid receptor-related orphan receptor (ROR)-γt expression and suppressed IFN-γ production in wild-type T cells, whereas these effects were severely impaired in SOCS1-deficient T cells. These phenotypes can be partly explained by STAT3 suppression by enhanced SOCS3 induction through hyper-STAT1 activation in SOCS1-deficient T cells. In addition, SOCS1-deficient T cells were much less sensitive to TGF-β. Suppression of Th1 differentiation by TGF-β was impaired in SOCS1-deficient T cells. TGF-β-mediated Smad transcriptional activity was severely inhibited in SOCS1-deficient cells in the presence of IFN-γ. Such impairment of TGF-γ functions were not observed in SOCS3-overexpressed cells, indicating that suppression of Smads was independent of SOCS3. Therefore, SOCS1 is necessary for Th17 differentiation by suppressing antagonistic effect of IFN-γ on both STAT3 and Smads. Induction of SOCS3 can partly explain IFN-γ-mediated STAT3 suppression, while other mechanism(s) will be involved in IFN-β-mediated Smad suppression. SOCS1-deficient T cells will be very useful to investigate the molecular mechanism for the STAT1-mediated suppression of Th17 development.

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

Type 1 diabetes results from the selective destruction of insulin-producing pancreatic β-cells during islet inflammation, which involves inflammatory cytokines and free radicals. However, mechanisms for protecting β-cells from destruction have not been clarified. In this study, we define the role of SOCS3 on β-cell destruction using β-cell-specific SOCS3-conditional knockout (cKO) mice. The β-cell-specific SOCS3-deficient mice were resistant to the development of diabetes caused by streptozotocin (STZ), a genotoxic methylating agent, which has been used to trigger β-cell destruction. The islets from cKO mice demonstrated hyperactivation of STAT3 and higher induction of Bcl-xL than did islets from WT mice, and SOCS3-deficient β-cells were more resistant to apoptosis induced by STZ in vitro than were WT β-cells. These results suggest that enhanced STAT3 signaling protects β-cells from destruction induced by a genotoxic stress and that STAT3/SOCS3 can be a potential therapeutic target for the treatment of type 1 diabetes.

DOI： 10.1016/j.bbrc.2007.05.198

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DOI： 10.1210/me.2006-0413

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DOI： 10.1111/j.1365-2443.2007.01044.x

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DOI： 10.1111/j.1365-2443.2007.01044.x

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DOI： 10.1038/nm1071

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DOI： 10.1038/nm1071

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

DOI： 10.1097/00004836-200207000-00010

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