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

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

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

Background: The indication for endoscopic resection for submucosally invasive colorectal cancer (T1-CRC) depends on the preoperative diagnosis of invasion depth. The aim of this investigation was to evaluate the association between barium enema examination (BE) profile views and depth of submucosal (SM) invasion in CRCs.

Methods: We reviewed the radiographic and endoscopic findings of 145 T1-CRCs diagnosed from 2008 to 2019. We measured the widths of horizontal and vertical rigidity under a BE profile view corresponding to CRC and compared the values with SM invasion depth. Horizontal rigidity was defined as the horizontal length and vertical rigidity as the vertical width of the barium defect corresponding to each target lesion. The most appropriate cut-off values for predicting SM invasion ≥1.8 mm were calculated by receiver operating characteristic curve analysis.

Results: Values of horizontal rigidity (r = 0.626, P < 0.05) and vertical rigidity (r = 0.482, P < 0.05) correlated significantly with SM invasion depth. The most appropriate cut-off values for the prediction of SM invasion depth ≥ 1.8 mm were 4.5 mm for horizontal rigidity, with an accuracy of 80.7%; and 0.7 mm for vertical rigidity, with an accuracy of 77.9%. The prevalence of lympho-vascular invasion was significantly different when those cut-off values were applied (43.2% vs. 17.5% for horizontal rigidity, P < 0.005).

Conclusions: In T1-CRC, values of horizontal and vertical rigidities under a BE profile view were correlated with SM invasion depth. While the accuracy of the rigidities for the prediction of SM invasion depth ≥ 1.8 mm was not high, horizontal rigidity may be predictive of lympho-vascular invasion, thus aiding in therapeutic decision-making.

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

Background: Ustekinumab (UST), an antibody targeting the p40 subunit of interleukin (IL)-12 and IL-23, is effective in treating Crohn's disease (CD). To clarify the mechanism of UST, we investigated T-cell differentiation in CD patients treated with UST.

Methods: Twenty-seven patients with active CD were enrolled in this study. Seventeen patients were treated with UST, and 10 patients were treated with anti-tumor necrosis factor (TNF)-alpha therapy. The changes in the proportions of T-cell subsets after these therapies were analyzed by flow cytometry. Comprehensive gene expression changes in the colonic mucosa were also evaluated.

Results: The frequency of T helper (Th) 17 cells was significantly decreased in the peripheral blood of patients with active CD after UST therapy. Anti-TNF therapy had a minimal effect on Th17 cells but increased the proportion of regulatory T cells. Enrichment analysis showed the expression of genes involved in the Th17 differentiation pathway was downregulated in the colonic mucosa after UST but not anti-TNF therapy. There were no common differentially expressed genes between CD patients treated with UST and anti-TNF therapy, suggesting a clear difference in their mechanism of action.

Conclusion: In patients with active CD, UST therapy suppressed Th17 cell differentiation both in the peripheral blood and colonic tissues.

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

To investigate the mucosal microbiota in the stomach of patients with Helicobacter pylori-negative mucosa-associated lymphoid tissue (MALT) lymphoma by means of metagenomic analysis.Although some gastric MALT lymphomas are associated with the presence of H. pylori, other gastric MALT lymphomas occur independently of H. pylori infection. The pathogenesis of H. pylori-negative MALT lymphoma remains unclear.Mucosal biopsy specimens were collected from the gastric body from 33 MALT lymphoma patients with gastric lesions, including both H. pylori-infection naïve patients and posteradication patients, as well as 27 control participants without H. pylori infection or cancer. Subsequently, the samples were subjected to 16S rRNA gene sequencing. Quantitative insights into microbial ecology, linear discriminant analysis effect size, and phylogenetic investigation of communities by reconstruction of unobserved states softwares were used to analyze the participants' microbiota.H. pylori-negative MALT lymphoma patients had significantly lower alpha diversity (P = .04), compared with control participants. Significant differences were evident in the microbial composition (P = .04), as determined by comparison of beta diversity between the 2 groups. Taxonomic composition analysis indicated that the genera Burkholderia and Sphingomonas were significantly more abundant in MALT lymphoma patients, while the genera Prevotella and Veillonella were less abundant. Functional microbiota prediction showed that the predicted gene pathways "replication and repair," "translation," and "nucleotide metabolism" were downregulated in MALT lymphoma patients.H. pylori-negative MALT lymphoma patients exhibited altered gastric mucosal microbial compositions, suggesting that altered microbiota might be involved in the pathogenesis of H. pylori-negative MALT lymphoma.

Language：Japanese  

Event date： 2019.5

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：福岡   Country：Japan  

【背景】近年、生薬である青黛が潰瘍性大腸炎(Ulcerative colitis; UC)の寛解導入療法において高い有効性を示すことが報告されている。しかし寛解維持療法における有効性や安全性は不明である。また、これまでクローン病(Crohn’s disease; CD)における青黛の有効性を検討した報告はない。今回UCとCDの両疾患を対象に、寛解導入および寛解維持療法における青黛の有効性、安全性を遡及的に検討した。
【方法】2015年3月から2017年4月の期間に当科において、青黛による加療を開始した活動期のUCおよびCD患者を対象とした。疾患活動性はUCではclinical activity index (CAI)、CDではCrohn’s disease activity index (CDAI)を用いて評価し、CAI≦4、CDAI≦150を寛解、それぞれのスコアの青黛投与前より30%以上の低下を有効と定義し、4週、8週における有効率、寛解率を検討した。また、52週、104週における青黛の継続率をKaplan-Meier 法で算出し、継続中の患者での寛解維持率を検討した。さらに全観察期間における有害事象を検討した。
【結果】UC 17例、CD 8例が対象となった。青黛開始時のCAIおよびCDAIの中央値はそれぞれ8（四分位: 6-10）、227（四分位: 193-254）であった。青黛の初期投与量と最終投与量の平均値はUCで2.47g、1.59g、CDで2.13ｇ、1.81gであった。4週、8週における有効率、寛解率はUCでは94.1%および88.2%、CDでは37.5%および25.0%であった。52週、104週における青黛の継続率はUCでは76%および71%、CDではいずれも38%であった。52週、104週の時点で青黛継続中の患者における寛解維持率はUCではいずれも100%、CDではいずれも66.7%であった。全体で10例において有害事象が生じ、そのうち入院を要する重篤な有害事象は3例に認められ、そのすべてが急性腸炎であった。そのうち1例では腸重積を合併し、外科的手術を要した。
【結論】青黛はUCの寛解導入、維持療法において高い有効性を示したが、CDにおける有効性は限定的であった。また、重篤な急性腸炎は、青黛の特徴的な有害事象であることが示唆された。

Event date： 2018.11

Language：English  

Venue：京都   Country：Japan  

【背景】Chronic enteropathy associated with SLCO2A1 gene（CEAS）は多発する小腸潰瘍による慢性的な貧血と低蛋白血症を特徴とするまれな難治性疾患である。近年、我々は本症の原因遺伝子としてプロスタグランジン輸送体をコードするSLCO2A1 遺伝子を同定した。CEASとCrohn病（CD）はともに小腸に多発潰瘍や狭窄を認めるため、実臨床において鑑別が困難な場合がある。我々の過去の検討では、CEAS患者における尿中プロスタグランジンE主要代謝産物（PGE-MUM）濃度は健常人と比較して有意に高値であった。今回、CEASとCDとの鑑別におけるPGE-MUM濃度測定の有用性を検討した。【方法】2012- 2017年の期間中に研究協力施設に通院中でSLCO2A1遺伝子変異陽性であることが確認されたCEAS 17例と九州大学病院消化管内科に通院中のCD 97例より文書による同意を得た上で尿検体を採取した。PGE-MUM濃度は放射性免疫測定法で測定した。交絡因子の同定のため単回帰分析を行い、オッズ比の算出のため、ロジスティック回帰分析を行った。ROC解析により、適切なカットオフ値を求めた。【結果】CEAS群におけるPGE-MUM濃度はCD群と比較して有意に高値であった（中央値 121 vs 28 μg/g×Cre, p < 0.0001）。対数変換を行った上での単位オッズ比は7.5（95%信頼区間 3.1-17.7）であった。この関係は肺疾患の既往や手術歴、罹病期間、CRP値による調整後でも有意であった。適切なカットオフ値は50.9 μg/g×Creと算出され、感度94%、特異度 80%、AUCは0.91であった。【結論】PGE-MUM検査はCEASとCDの鑑別において簡便で有用なスクリーニング検査となりうると考えられた。

Event date： 2024.1

Language：English   Presentation type：Oral presentation (general)  

Venue：Las vegas   Country：United States  

Event date： 2023.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：沖縄   Country：Japan  

Event date： 2023.5

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)