| 1. |
Kondo M, Torisu T, Nagasue T, Shibata H, Umeno J, Kawasaki K, Fujioka S, Matsuno Y, Moriyama T, Kitazono T, Duodenal microbiome in chronic kidney disease, Clin Exp Nephrol, 2024.04. |
| 2. |
Imazu N, Torisu T, Ihara Y, Umeno J, Kawasaki K, Fujioka S, Fuyuno Y, Matsuno Y, Moriyama T, Kitazono T, Ustekinumab Decreases Circulating Th17 Cells in Ulcerative Colitis, Intern Med, 2024.01. |
| 3. |
Kondo M, Torisu T, Ihara Y, Kawasaki K, Umeno J, Kawatoko S, Tsuchimoto A, Nakano T, Okabe Y, Kitazono T, Clinical Features of Gastroduodenal Ulcers in Kidney Transplant Patients, Intern Med, 2023.12. |
| 4. |
Yoshida Y, Fujioka S, Moriyama T, Umeno J, Kawasaki K, Fuyuno Y, Matsuno Y, Ihara Y, Torisu T, Kitazono T, Disease Flares Following COVID-19 Vaccination in Patients with Inflammatory Bowel Disease, Intern Med, 2023.12. |
| 5. |
Yuichi Matsuno, Takehiro Torisu, Junji Umeno, Hiroki Shibata, Atsushi Hirano, Yuta Fuyuno, Yasuharu Okamoto, Shin Fujioka, Keisuke Kawasaki, Tomohiko Moriyama, Tomohiro Nagasue, Keizo Zeze, Yoichiro Hirakawa, Shinichiro Kawatoko, Yutaka Koga, Yoshinao Oda, Motohiro Esaki, Takanari Kitazono, One-year clinical efficacy and safety of indigo naturalis for active ulcerative colitis: a real-world prospective study., Intestinal research, 10.5217/ir.2021.00124, 20, 2, 260-268, 2022.04, 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.. |
| 6. |
Keisuke Kawasaki, Takehiro Torisu, Takahisa Nagahata, Motohiro Esaki, Koichi Kurahara, Makoto Eizuka, Yoshihito Tanaka, Minako Fujiwara, Shinichiro Kawatoko, Yumi Oshiro, Shun Yamada, Koji Ikegami, Shin Fujioka, Yuta Fuyuno, Yuichi Matsuno, Junji Umeno, Tomohiko Moriyama, Takanari Kitazono, Tamotsu Sugai, Takayuki Matsumoto , Role of barium enema examination for the diagnosis of submucosal invasion depth in T1 colorectal cancers, Cancer Imaging, 2021.12. |
| 7. |
Keizo Zeze, Atsushi Hirano, Takehiro Torisu, Motohiro Esaki, Tomohiko Moriyama, Junji Umeno, Keisuke Kawasaki, Shin Fujioka, Yuta Fuyuno, Yuichi Matsuno, Takanari Kitazono, Adding Thiopurine After Loss of Response to Infliximab Versus Early Combination in Treating Crohn's Disease: A Retrospective Study., Digestive diseases and sciences, 10.1007/s10620-020-06600-z, 66, 9, 3124-3131, 2021.09, BACKGROUND: Although combining thiopurine with infliximab (IFX) is considered to improve the clinical efficacy of IFX when treating Crohn's disease (CD), it also increases the risk of adverse events (AEs). We compared the efficacy and safety of delayed thiopurine addition after loss of response (LOR) to IFX with the efficacy and safety of an earlier combination of thiopurine and IFX. METHODS: This retrospective study analyzed patients with CD who started IFX as a first-line biologic at Kyushu University Hospital between June 2002 and July 2018. Patients were assigned to either the early-combination (EC) group, who started IFX and thiopurine simultaneously, or the late-combination (LC) group, who were treated with IFX alone until they developed LOR. We compared the cumulative IFX continuation rates and AE incidence between the two groups. RESULTS: One hundred seventy-six patients were enrolled in this study; 49 were enrolled in the EC group, and 127 were enrolled in the LC group. Disease activity at baseline did not significantly differ between the groups, nor did the cumulative IFX continuation rates differ between the groups (P = 0.30); however, the AE rate was significantly higher in the EC group than in the LC group (38.7% vs. 21.2%; P = 0.02). The severe AE rate was also higher in the EC group than in the LC group (18.3% vs 3.1%; P = 0.001). CONCLUSION: Considering the risk-benefit balance, delayed addition of thiopurine after LOR to IFX might be an alternative strategy when using IFX to treat CD.. |
| 8. |
Takahide Tanaka, Yuichi Matsuno, Takehiro Torisu, Hiroki Shibata, Atsushi Hirano, Junji Umeno, Keisuke Kawasaki, Shin Fujioka, Yuta Fuyuno, Tomohiko Moriyama, Motohiro Esaki, Takanari Kitazono, Gastric microbiota in patients with Helicobacter pylori-negative gastric MALT lymphoma., Medicine, 10.1097/MD.0000000000027287, 100, 38, e27287, 2021.09, ABSTRACT: 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.. |
| 9. |
Yoshihiro Endo, Motoki Yonekawa, Kazutaka Kukita, Masaki Katagiri, Takayuki Matsumoto, Keisuke Kawasaki, Shunichi Yanai, Shingo Kato, Kazuhito Kani, Tomonari Ogawa, Kazuya Kitamura, Izumi Hasegawa, Yusuke Inoue, Takuya Doi, Kazuhide Higuchi, Ken Kawakami, Kazuki Kakimoto, Hiroki Nakamura, Novel adsorptive type apheresis device Immunopure for ulcerative colitis from clinical perspectives based on clinical trials: Japan and Europe., Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy, 10.1111/1744-9987.13661, 25, 4, 432-436, 2021.08, Several adsorptive type devices for ulcerative colitis are used for the induction of remission in patients with active severe disease worldwide. In 2020, the novel apheresis device Immunopure for ulcerative colitis was launched in Japan. Immunopure, like the polyethylene terephthalate column, uses polyarylate, a type of polyester resin, as the adsorbent. Similar to the cellulose acetate column, Immunopure is filled with adsorbent beads and expected to provide ease of use, with minimal risk of column clogging. Immunopure adsorbs leukocytes and platelets, especially activated platelets and platelet-leukocyte aggregates. In this article, the capability of Immunopure is evaluated from clinical perspective based on a clinical trial in Japan/Europe. As a result, Immunopure is comparable to other products in clinical effectiveness and indicated for the treatment of patients with refractory moderate ulcerative colitis, making it highly useful in clinical practice.. |
| 10. |
Masanao Nakamura, Tomonori Yano, Motohiro Esaki, Shiro Oka, Keigo Mitsui, Fumihito Hirai, Keisuke Kawasaki, Mitsuhiro Fujishiro, Takehiro Torisu, Shinji Tanaka, Katsuhiko Iwakiri, Masahiro Kishi, Takayuki Matsumoto, Hironori Yamamoto, Novel ultrathin double-balloon endoscopy for the diagnosis of small-bowel diseases: a multicenter nonrandomized study., Endoscopy, 10.1055/a-1243-0226, 53, 8, 802-814, 2021.08, BACKGROUND: This study aimed to compare the markers of potential pancreatic injury during antegrade double-balloon endoscopy (DBE) using the newly developed ultrathin EN-580XP system and the conventional EN-580T system. METHODS: Patients who were scheduled for antegrade DBE during daily clinical practice were enrolled. Clinical background, adverse events, and laboratory data of patients were compared between those who underwent endoscopy using the EN-580XP system and those in whom the EN-580T system was used. The primary end points were pancreatic hyperamylasemia and hyperlipasemia after DBE. RESULTS: A total of 295 cases were registered. Pancreatic hyperamylasemia occurred in 2 of 92 patients (2.2 %) in the EN-580XP group and in 28 of 147 patients (19.1 %) in the EN-580 T diagnosis group (P |
| 11. |
Takahiro Gonai, Yosuke Toya, Keisuke Kawasaki, Shunichi Yanai, Risaburo Akasaka, Shotaro Nakamura, Takayuki Matsumoto , Risk factors of re-bleeding within a year in colonic diverticular bleeding patients., DEN open, 2021.08. |
| 12. |
Yutaro Ihara, Takehiro Torisu, Kohta Miyawaki, Junji Umeno, Keisuke Kawasaki, Atsushi Hirano, Shin Fujioka, Yuta Fuyuno, Yuichi Matsuno, Takeshi Sugio, Kensuke Sasaki, Tomohiko Moriyama, Koichi Akashi, Takanari Kitazono, Ustekinumab Improves Active Crohn's Disease by Suppressing the T Helper 17 Pathway., Digestion, 10.1159/000518103, 1-10, 2021.07, 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.. |
| 13. |
Keisuke Kawasaki, Shotaro Nakamura, Makoto Eizuka, Yoshihito Tanaka, Tomo Kumei, Shunichi Yanai, Yosuke Toya, Jun Urushikubo, Takehiro Torisu, Tomohiko Moriyama, Junji Umeno, Tamotsu Sugai, Takayuki Matsumoto, Is barium enema examination negligible for the management of colorectal cancer? Comparison with conventional colonoscopy and magnifying colonoscopy., Japanese journal of radiology, 10.1007/s11604-021-01157-x, 2021.06, PURPOSE: The aim of this investigation was to evaluate the clinical value of barium enema (BE) examination for the management of colorectal epithelial neoplasms. METHODS: We reviewed the colonoscopy records at our institution from 2014 to 2019 and identified cases of endoscopically or surgically resected colorectal epithelial neoplasms evaluated by BE, conventional colonoscopy, magnifying narrow-band imaging colonoscopy (M-NBI), and magnifying chromoendoscopy (MCE). The yield of each modality for the diagnosis of massively submucosal invasive (mSM) colorectal cancer was evaluated by a receiver-operating characteristic analysis including the area under the curve (AUC). RESULTS: We analyzed the records of 105 patients (17 adenomas, 53 high-grade dysplasias (HGDs), and 35 cancers). Smooth surface, irregularity in depression, and eccentric deformity on the profile view with BE were observed more frequently in mSM cancers than adenomas/HGDs/slightly submucosal invasive cancers (p |
| 14. |
Toya Y, Endo M, Oizumi T, Akasaka R, Yanai S, Kawasaki K, Nakamura S, Eizuka M, Fujita Y, Uesugi N, Ishida K, Sugai T, Matsumoto T, Diagnostic algorithm of magnifying endoscopy with crystal violet staining for non-ampullary duodenal epithelial tumors., Dig Endosc, 2020.11. |
| 15. |
Tanaka Y, Eizuka M, Uesugi N, Kawasaki K, Yamano H, Suzuki H, Matsumoto T, Sugai T, Traditional serrated adenoma has two distinct genetic pathways for molecular tumorigenesis with potential neoplastic progression., J Gastroenterol, 2020.09. |
| 16. |
Toya Y, Endo M, Oizumi T, Akasaka R, Yanai S, Kawasaki K, Nakamura S, Eizuka M, Fujita Y, Uesugi N, Sugai T, Matsumoto T, Risk Factors for Post-gastric Endoscopic Submucosal Dissection Bleeding with a Special Emphasis on Anticoagulant Therapy, Dig Dis Sci, 2020.02. |
| 17. |
Gonai T, Kawasaki K, Nakamura S, Yanai S, Akasaka R, Sato K, Toya Y, Asakura K, Urushikubo J, Fujita Y, Eizuka M, Uesugi N, Sugai T, Matsumoto T, Microvascular density under magnifying narrow-band imaging endoscopy in colorectal epithelial neoplasms, Intest Res, 2020.01. |
| 18. |
Akira Harada, Koichi Kurahara, Tomohiko Moriyama, Takahide Tanaka, Yutaka Nagata, Keisuke Kawasaki, Hiroki Yaita, Yuji Maehata, Junji Umeno, Yumi Oshiro, Tadahiko Fuchigami, Takanari Kitazono, Motohiro Esaki, Takayuki Matsumoto, Risk factors for reflux esophagitis after eradication of Helicobacter pylori., Scandinavian journal of gastroenterology, 10.1080/00365521.2019.1671487, 54, 10, 1183-1188, 2019.10, Objective: While there is an association between successful eradication of Helicobacter pylori (HP) and reflux esophagitis (RE), risk factors associated with RE remain obscure. The aim of this study is to determine risk factors associated with the development of RE after HP eradication.Materials and methods: Among all patients treated with successful HP eradication from 2008 to 2016, we retrospectively analyzed those who were free from RE at initial esophagogastroduodenoscopy (EGD) and who were followed up with EGD after eradication. Patients were classified according to the presence or absence of RE at the follow-up EGD. RE was defined as mucosal breaks proximal to the squamous-columnar junction. Demographic data, underlying diseases, medications and endoscopic findings at the initial EGD were compared between patients with and without RE.Results: Among 1575 patients, 142 (9.0%) had RE at the follow-up EGD. The time interval from HP eradication until EGD ranged from 4 to 24 months. The endoscopic grade of RE was higher in males than in females. Multivariate analysis revealed that male sex (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.24), body mass index ≥25 kg/m2 (OR, 2.91; 95% CI, 2.00-4.22), use of calcium channel blockers (OR, 1.70; 95% CI, 1.12-2.55), and hiatal hernia (OR, 3.46; 95% CI, 2.41-5.00) were associated with the development of RE.Conclusions: Calcium channel blocker use was found to be a risk factor for the development of RE after eradication of HP.. |
| 19. |
Kawasaki K, Nakamura S, Esaki M, Kurahara K, Eizuka M, Okamoto Y, Hirata T, Hirahashi M, Oshiro Y, Yanai S, Sato K, Toya Y, Maemondo M, Terayama Y, Sugai T, Matsumoto T, Gastrointestinal involvement in patients with vasculitis: IgA vasculitis and eosinophilic granulomatosis with polyangiitis., Endoscopy International Open, 2019.07. |
| 20. |
Yosuke Toya, Masaki Endo, Shotaro Nakamura, Risaburo Akasaka, Shunichi Yanai, Keisuke Kawasaki, Keisuke Koeda, Makoto Eizuka, Yasuko Fujita, Noriyuki Uesugi, Kazuyuki Ishida, Tamotsu Sugai, Takayuki Matsumoto, Long-term outcomes and prognostic factors with non-curative endoscopic submucosal dissection for gastric cancer in elderly patients aged ≥ 75 years., Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 10.1007/s10120-018-00913-9, 22, 4, 838-844, 2019.07, BACKGROUND: Little is known about the long-term outcomes and prognostic factors with non-curative endoscopic submucosal dissection (ESD) in elderly patients with early gastric cancer. METHODS: Clinicopathological findings and long-term outcomes were evaluated in 87 patients with early gastric cancer (EGC) aged ≥ 75 years who were treated with non-curative ESD. Prognostic factors for overall survival (OS) were analyzed with the Kaplan-Meier method and a Cox proportional hazards model. RESULTS: During the follow-up period, among 27 patients who died of any cause, only one patient died of gastric cancer. OS probabilities after 3 and 5 years were 89.7% and 79.3%, respectively. Univariate analyses revealed that Eastern Cooperative Oncology Group performance status 2-3, Charlson comorbidity index (CCI) ≥ 3, neutrophil/lymphocyte ratio ≥ 3.3, prognostic nutritional index |
| 21. |
Kawasaki K, Nakamura S, Esaki M, Kurahara K, Eizuka M, Nuki Y, Kochi S, Fujiwara M, Oshiro Y, Sugai T, Matsumoto T, Clinical usefulness of magnifying colonoscopy for the diagnosis of ulcerative colitis-associated neoplasia. , Dig Endosc, 2019.04. |
| 22. |
Shunichi Yanai, Satoko Yamaguchi, Shotaro Nakamura, Keisuke Kawasaki, Yosuke Toya, Noriyuki Yamada, Makoto Eizuka, Noriyuki Uesugi, Junji Umeno, Motohiro Esaki, Eiko Okimoto, Shunji Ishihara, Tamotsu Sugai, Takayuki Matsumoto, Distinction between Chronic Enteropathy Associated with the SLCO2A1 Gene and Crohn's Disease., Gut and liver, 10.5009/gnl18261, 13, 1, 62-66, 2019.01, Background/Aims: We recently identified recessive mutations in the solute carrier organic anion transporter family member 2A1 gene (SLCO2A1) as causative variants of chronic nonspecific multiple ulcers of the small intestine (chronic enteropathy associated with SLCO2A1, CEAS). The aim of this study was to investigate the gastroduodenal expression of the SLCO2A1 protein in patients with CEAS and Crohn's disease (CD). Methods: Immunohistochemical staining for SLCO2A1 was performed with a polyclonal antibody, HPA013742, on gastroduodenal tissues obtained by endoscopic biopsy from four patients with CEAS and 29 patients with CD. Results: The expression of SLCO2A1 was observed in one of four patients (25%) with CEAS and in all 29 patients (100%) with CD (pC (exon 7) or c.940+1G>A (exon 10). The remaining one CEAS patient with positive expression of SLCO2A1 had compound heterozygous c.664G>A and c.1807C>T mutations. Conclusions: Immunohistochemical staining for SLCO2A1 in gastroduodenal tissues obtained by endoscopic biopsy is considered useful for the distinction of CEAS from CD.. |
| 23. |
Tamotsu Sugai, Makoto Eizuka, Yasuko Fujita, Keisuke Kawasaki, Eiichiro Yamamoto, Kazuyuki Ishida, Hiroo Yamano, Hiromu Suzuki, Takayuki Matsumoto, Molecular Profiling Based on KRAS/BRAF Mutation, Methylation, and Microsatellite Statuses in Serrated Lesions., Digestive diseases and sciences, 10.1007/s10620-018-5167-4, 63, 10, 2626-2638, 2018.10, AIM: The aim of your study is to characterize serrated lesions according to their molecular patterns, specifically BRAF/KRAS mutation, methylation, and microsatellite statuses. We evaluated the molecular patterns of 163 serrated lesions, including 37 microvesicular hyperplastic polyps, 73 sessile serrated adenomas/polyps (SSA/Ps), 31 traditional serrated adenomas, and 22 SSA/Ps with cytological dysplasia/adenocarcinoma. METHODS: Mutations in BRAF (V600E)/KRAS (exon 2) and microsatellite status [microsatellite stability (MSS) vs. MSI] were examined using a pyrosequencer and the PCR-based microsatellite method, respectively. DNA methylation status was classified as low (LME), intermediate (IME), or high methylation epigenotype (HME) according to a PCR-based two-step method. In addition, mucin and annexin A10 expression was examined. Finally, we performed a hierarchical clustering analysis of the BRAF/KRAS mutation, DNA methylation, and microsatellite statuses. RESULTS: The molecular patterns observed in the serrated lesions could be divided into five subgroups: lesions characterized by (1) BRAF mutation, HME, and MSI; (2) BRAF mutation, HME, and MSS; (3) BRAF mutation, LME/IME, and MSS; (4) no BRAF/KRAS mutations, LME/IME, and MSS; and (5) KRAS mutation, LME/IME, and MSS. In addition, we demonstrated that these observed molecular patterns help identify the associations of the molecular patterns and markers (i.e., mucin and annexin A10) with the clinicopathological findings, including histological features and histological diagnosis. CONCLUSIONS: We suggest that the identified molecular patterns play an important role in the pathway of serrated lesion development.. |
| 24. |
Jun Urushikubo, Shunichi Yanai, Shotaro Nakamura, Keisuke Kawasaki, Risaburo Akasaka, Kunihiko Sato, Yosuke Toya, Kensuke Asakura, Takahiro Gonai, Tamotsu Sugai, Takayuki Matsumoto, Practical fecal calprotectin cut-off value for Japanese patients with ulcerative colitis., World journal of gastroenterology, 10.3748/wjg.v24.i38.4384, 24, 38, 4384-4392, 2018.10, AIM: To determine appropriate fecal calprotectin cut-off values for the prediction of endoscopic and histologic remission in Japanese patients with ulcerative colitis (UC). METHODS: We performed a cross-sectional observational study of 131 Japanese patients with UC and measured fecal calprotectin levels by fluorescence enzyme immunoassay. The clinical activity of UC was assessed with the partial Mayo score (PMS). Relapse was defined as increase of PMS by 2 points or more in stool frequency or rectal bleeding subscore. The endoscopic and histologic activities of UC were evaluated in 50 patients within a 2-mo period from fecal sampling. Endoscopic activity was determined by Mayo endoscopic subscore, Rachmilewitz endoscopic index, and ulcerative colitis endoscopic index of severity. The histologic grade of inflammation was evaluated with biopsy specimens obtained from the endoscopically most severely inflamed site, according to the scheme by Matts grade and Riley's score. RESULTS: Fecal calprotectin levels varied from 1-20783 μg/g. There was a significant correlation between the partial Mayo score and fecal calprotectin levels (r = 0.548, P |
| 25. |
Satoko Yamaguchi, Shunichi Yanai, Shotaro Nakamura, Keisuke Kawasaki, Makoto Eizuka, Noriyuki Uesugi, Tamotsu Sugai, Junji Umeno, Motohiro Esaki, Takayuki Matsumoto, Immunohistochemical differentiation between chronic enteropathy associated with SLCO2A1 gene and other inflammatory bowel diseases., Intestinal research, 10.5217/ir.2018.16.3.393, 16, 3, 393-399, 2018.07, Background/Aims: We recently identified recessive mutations in the solute carrier organic anion transporter family member 2A1 gene (SLCO2A1) as causative variants of chronic enteropathy associated with SLCO2A1 (CEAS). The aim of this study was to evaluate SLCO2A1 protein expression in the intestinal tissues of patients with CEAS, intestinal Behçet's disease (BD), simple ulcer (SU), and Crohn's disease (CD). Methods: Immunohistochemical staining using a polyclonal anti-SLCO2A1 antibody was performed on the resected intestinal specimens from 13 cases of CD, 9 cases of intestinal BD/SU, and 3 cases of CEAS. The extent of SLCO2A1 expression was determined by counting positively-staining vascular endothelial cells and scored as 0 (no cells), 1 (1%-30% cells), 2 (31%-60%), or 3 (>60%). The intensity of SLCO2A1 expression was scored either as 0 (negative), 1 (intermediate), or 2 (strong). The extent score and intensity score were summed for the final score of 0, 2, 3, 4, or 5. Results: SLCO2A1 protein expression was observed in 1 of 3 cases of CEAS (33%), all 13 cases of CD (100%), and all 9 cases of BD/SU (100%). The mean final expression scores of CEAS, CD, and BD/SU were 1.6 (range, 0-5), 4.8 (range, 4-5), and 4.3 (range, 4-5), respectively. The final expression score in CEAS was significantly lower than in CD (P=0.03). Conclusions: Immunohistochemical staining of the SLCO2A1 protein is considered useful to distinguish CEAS from other inflammatory bowel diseases.. |
| 26. |
Tamotsu Sugai, Noriyuki Uesugi, Yuriko Kitada, Noriyuki Yamada, Mitsumasa Osakabe, Makoto Eizuka, Ryo Sugimoto, Yasuko Fujita, Keisuke Kawasaki, Eiichiro Yamamoto, Hiroo Yamano, Hiromu Suzuki, Takayuki Matsumoto, Analysis of the expression of cancer-associated fibroblast- and EMT-related proteins in submucosal invasive colorectal cancer., Journal of Cancer, 10.7150/jca.25646, 9, 15, 2702-2712, 2018.06, Objective: Recent studies have shown that cancer-associated fibroblasts (CAFs) and the epithelial-mesenchymal transition (EMT) play important roles in the progression and metastasis of CRC. Although prediction of lymph node metastasis in submucosal invasive colorectal cancer (SiCRC) is important, the relationships of CAF and EMT with lymph node metastasis of SiCRC have not yet been examined. Here, we aimed to analyze the expression patterns of CAF- and EMT-related proteins in SiCRC. Materials and Methods: The expression of CAF-related markers, including α-smooth muscle actin, CD10, podoplanin, fibroblast specific protein 1, and adipocyte enhancer-binding protein 1, and EMT-related proteins [zinc finger protein SNAI2 (ZEB1) and twist-related protein 1 (TWIST1) in SiCRC with (n = 29) or without (n = 80) lymph node metastasis was examined by immunohistochemistry. We examined the expression patterns of biomarkers using hierarchical cluster analysis. Consequently, four subgroups were established based on the expression patterns of CAF- and EMT-related markers, and the associations of these subgroups with clinicopathological variables. Results: In multivariate analysis, subgroup 2, which was characterized by high expression of all markers, was correlated with lymph node metastasis (p |
| 27. |
Yosuke Toya, Masaki Endo, Risaburo Akasaka, Jun Urushikubo, Takahiro Gonai, Kensuke Asakura, Shunichi Yanai, Keisuke Kawasaki, Makoto Eizuka, Noriyuki Uesugi, Shotaro Nakamura, Tamotsu Sugai, Takayuki Matsumoto, Clinicopathological Features and Magnifying Chromoendoscopic Findings of Non-Ampullary Duodenal Epithelial Tumors., Digestion, 10.1159/000485505, 97, 3, 219-227, 2018.03, BACKGROUND AND AIMS: We aimed to investigate an association between clinicopathological features, including immunohistochemical mucin phenotypes, and magnifying chromoendoscopic findings with crystal violet staining (ME-CV) in non-ampullary duodenal epithelial tumors (NADETs). METHODS: A total of 55 patients with NADET were divided into 3 groups by mucin phenotype: intestinal, gastrointestinal, or gastric. ME-CV findings were classified into 4 patterns: convoluted, leaf-like, reticular/sulciolar, and pinecone. The clinicopathological features and ME-CV findings were compared among the mucin phenotypes. RESULTS: Tumors of the gastric type were located in the duodenal bulb (p |
| 28. |
Kawasaki K, Eizuka M, Nakamura S, Endo M, Yanai S, Akasaka R, Toya Y, Fujita Y, Uesugi N, Ishida K, Sugai T, Matsumoto T., Association between white opaque substance under magnifying colonoscopy and lipid droplets in colorectal epithelial neoplasms, World J Gastroenterol, 2017.12. |
| 29. |
Makoto Eizuka, Tamotsu Sugai, Wataru Habano, Noriyuki Uesugi, Yayoi Takahashi, Keisuke Kawasaki, Eiichiro Yamamoto, Hiromu Suzuki, Takayuki Matsumoto, Molecular alterations in colorectal adenomas and intramucosal adenocarcinomas defined by high-density single-nucleotide polymorphism arrays., Journal of gastroenterology, 10.1007/s00535-017-1317-2, 52, 11, 1158-1168, 2017.11, BACKGROUND: We examined colorectal adenomas and intramucosal adenocarcinomas (IMAs) to develop a genome-wide overview of copy number alterations (CNAs) during colorectal tumorigenesis. METHODS: We analysed CNAs using a high-resolution SNP array of isolated tumour glands obtained from 55 colorectal adenomas (35 low-grade adenomas and 20 high-grade adenomas) and 30 IMAs. Next, we examined whether frequent CNAs differed between low-grade and high-grade adenomas or high-grade adenomas and IMAs. Finally, we investigated the total lengths of the CNAs in low-grade adenomas, high-grade adenomas, and IMAs. RESULTS: Although no frequent CNAs were found in low-grade adenomas, the most frequent alterations of high-grade adenomas were gains of 7q11, 7q21 and 9p13 and loss of 5q14.3-35. High levels of gains were detected at 13q, 7q, 8p, 20q, 7p, 18p and 17p in IMAs. Although no frequent alteration differed between low-grade and high-grade adenomas, significant differences of gains at 13q, 17p and 18p were found between high-grade adenoma and IMAs. Although the total lengths of all CNAs (gains and losses), copy number gains, and losses of heterozygosity were significantly greater in high-grade adenomas than in low-grade adenomas, no significant differences in the lengths of CNAs were found between high-grade adenomas and IMAs. CONCLUSIONS: Genomic alterations play an essential role in early colorectal carcinogenesis. CNAs in colorectal tumours provide new insights for evaluation of colorectal tumorigenesis.. |
| 30. |
Hiroyoshi Nakanishi, Hisashi Doyama, Hideki Ishikawa, Noriya Uedo, Takuji Gotoda, Mototsugu Kato, Shigeaki Nagao, Yasuaki Nagami, Hiroyuki Aoyagi, Atsushi Imagawa, Junichi Kodaira, Shinya Mitsui, Nozomu Kobayashi, Manabu Muto, Hajime Takatori, Takashi Abe, Masahiko Tsujii, Jiro Watari, Shuhei Ishiyama, Ichiro Oda, Hiroyuki Ono, Kazuhiro Kaneko, Chizu Yokoi, Tetsuya Ueo, Kunihisa Uchita, Kenshi Matsumoto, Takashi Kanesaka, Yoshinori Morita, Shinichi Katsuki, Jun Nishikawa, Katsuhisa Inamura, Tetsu Kinjo, Katsumi Yamamoto, Daisuke Yoshimura, Hiroshi Araki, Hiroshi Kashida, Ayumu Hosokawa, Hirohito Mori, Haruhiro Yamashita, Osamu Motohashi, Kazuhiko Kobayashi, Michiaki Hirayama, Hiroyuki Kobayashi, Masaki Endo, Hiroo Yamano, Kazunari Murakami, Tomoyuki Koike, Kingo Hirasawa, Youichi Miyaoka, Hidetaka Hamamoto, Takuto Hikichi, Norihiro Hanabata, Ryo Shimoda, Shinichiro Hori, Tadashi Sato, Shinya Kodashima, Hiroyuki Okada, Tomohiko Mannami, Shojiro Yamamoto, Yasumasa Niwa, Kazuo Yashima, Satoshi Tanabe, Hiro Satoh, Fumisato Sasaki, Tetsuro Yamazato, Yoshiou Ikeda, Hogara Nishisaki, Masahiro Nakagawa, Akio Matsuda, Fumio Tamura, Hitoshi Nishiyama, Keiko Arita, Keisuke Kawasaki, Kazushige Hoppo, Masashi Oka, Shinichi Ishihara, Michita Mukasa, Hiroaki Minamino, Kenshi Yao, Evaluation of an e-learning system for diagnosis of gastric lesions using magnifying narrow-band imaging: a multicenter randomized controlled study., Endoscopy, 10.1055/s-0043-111888, 49, 10, 957-967, 2017.10, Background and study aim Magnifying narrow-band imaging (M-NBI) is useful for the accurate diagnosis of early gastric cancer (EGC). However, acquiring skill at M-NBI diagnosis takes substantial effort. An Internet-based e-learning system to teach endoscopic diagnosis of EGC using M-NBI has been developed. This study evaluated its effectiveness. Participants and methods This study was designed as a multicenter randomized controlled trial. We recruited endoscopists as participants from all over Japan. After completing Test 1, which consisted of M-NBI images of 40 gastric lesions, participants were randomly assigned to the e-learning or non-e-learning groups. Only the e-learning group was allowed to access the e-learning system. After the e-learning period, both groups received Test 2. The analysis set was participants who scored |
| 31. |
Kawasaki K, Nakamura S, Kurahara K, Nagasue T, Yanai S, Harada A, Yaita H, Fuchigami T, Matsumoto T., Continuing use of antithrombotic medications for patients with bleeding gastroduodenal ulcer requiring endoscopic hemostasis: a case-control study, Scand J Gastroenterol, 2017.09. |
| 32. |
Tamotsu Sugai, Wataru Habano, Ryo Takagi, Hiroo Yamano, Makoto Eizuka, Noriyuki Arakawa, Yayoi Takahashi, Eiichiro Yamamoto, Keisuke Kawasaki, Syunichi Yanai, Kazuyuki Ishida, Hiromu Suzuki, Takayuki Matsumoto, Analysis of molecular alterations in laterally spreading tumors of the colorectum., Journal of gastroenterology, 10.1007/s00535-016-1269-y, 52, 6, 715-723, 2017.06, BACKGROUND: Colorectal laterally spreading tumors (LSTs) are classified into LST-Gs and LST-NGs, according to macroscopic findings. In the present study, we determined the genetic and epigenetic alterations within colorectal LSTs and protruding adenomas. METHODS: A crypt isolation method was used to isolate DNA from tumors and normal glands of 73 macroscopically verified colorectal LSTs (histologically defined adenomas; 38 LST-Gs and 35 LST-NGs) and 36 protruding adenomas. The DNA was processed using polymerase chain reaction (PCR) microsatellite assays, single-strand conformation polymorphism (SSCP) assays, and pyrosequencing to detect chromosomal allelic imbalance (AI), mutations in APC, KRAS, and TP53, and the methylation of MLH1, MGMT, CDKN2A, HPP1, RASSF2A, SFRP1, DKK1, ZFP64, and SALL4 genes. In addition, methylation status was examined using the following set of markers: MIN1, MINT2, MINT31, MLH1, and CDKN2A (with classification of negative/low and high). Microsatellite instability (MSI) was also examined. RESULTS: 5q AI and methylation of the SFRP1 and SALL4 genes were common molecular events in both LST-Gs and LST-NGs. Neither MSI nor mutations in BRAF ware observed in the LSTs. TP53 mutations were rarely found in LSTs. The frequencies of KRAS and APC mutations and the methylation levels of ZFP64, RASSF2A, and HPP1 genes were significantly higher in LST-Gs than in LST-NGs. Protruding adenomas showed alterations common to LST-Gs. Negative/low methylation status was common among the three types of tumors. CONCLUSION: Combined genetic and epigenetic data suggested that the molecular mechanisms of tumorigenesis were different between LST-Gs and LST-NGs.. |
| 33. |
Yosuke Toya, Masaki Endo, Shotaro Nakamura, Risaburo Akasaka, Takashi Kosaka, Shunichi Yanai, Keisuke Kawasaki, Keisuke Koeda, Tamotsu Sugai, Takayuki Matsumoto, Clinical outcomes of non-curative endoscopic submucosal dissection with negative resected margins for gastric cancer., Gastrointestinal endoscopy, 10.1016/j.gie.2016.11.018, 85, 6, 1218-1224, 2017.06, BACKGROUND AND AIMS: There has been little information about the long-term outcomes of patients with early gastric cancer (EGC) treated by non-curative endoscopic submucosal dissection (ESD) with negative resected margins (R0 resection). We aimed to compare the clinical outcomes of non-curative ESD with R0 resection between patients who underwent additional gastrectomy and those who did not. METHODS: Among EGC patients treated by ESD from 2002 to 2010, 66 patients were treated by non-curative ESD with R0 resection. Patients received either additional gastrectomy (group A, n = 45) or were followed up without gastrectomy (group B, n = 21). The clinicopathologic findings and the subsequent clinical course were compared between the 2 groups. RESULTS: Patients in group A were younger than those in group B (68.0 vs 71.0 years, P = .006). The follow-up period was longer in group A than in group B (7.8 vs 5.9 years, P = .011). The percentage of patients who died of any cause was not statistically lower in group A than in group B (13.3% vs 33.3%, P = .06). Although the overall survival rate was higher in group A than in group B (93.3% vs 76.2%, P = .028), disease-specific survival rates did not differ between the 2 groups (97.8% vs 100%, P = .495). A Cox proportional hazards model showed that gastrectomy was not an independent factor associated with overall survival. CONCLUSIONS: Careful follow-up may be an alternative strategy to gastrectomy for a subgroup of patients treated by non-curative ESD with R0 resection.. |
| 34. |
Tamotsu Sugai, Ryo Sugimoto, Wataru Habano, Masaki Endoh, Makoto Eizuka, Koudai Tsuchida, Eiichiro Yamamoto, Keisuke Kawasaki, Syunichi Yanai, Takayuki Matsumoto, Hiromu Suzuki, Genetic differences stratified by PCR-based microsatellite analysis in gastric intramucosal neoplasia., Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 10.1007/s10120-016-0616-2, 20, 2, 286-296, 2017.03, BACKGROUND: Although genetic alterations in patients with advanced gastric cancer have been extensively studied, those in patients with intramucosal neoplasia (IMN) are still poorly understood. METHODS: We evaluated genetic differences in 158 IMNs, including 51 low-grade dysplasias, 58 high-grade dysplasias (HGDs), 30 intramucosal cancers (IMCs), and 19 mixed tumors (composed of IMC and HGD within the same tumor), using PCR-based microsatellite analysis [allelic imbalance (AI) and microsatellite instability (MSI)]. We classified the DNA methylation status as a hypermethylated epigenome, a moderately methylated epigenome, or a hypomethylated epigenome. In addition, p53 overexpression, β-catenin nuclear localization, and mucin expression were also examined. RESULTS: From cluster analysis, the IMNs examined were categorized into four subgroups as follows. Tumors in subgroup 1 were characterized by MSI-high status, a hypermethylated epigenome, and loss or reduction of expression of MLH-1. Tumors in subgroup 2 showed a mixed pattern consisting of AI and MSI. In contrast, tumors in subgroup 3, which showed accumulation of multiple AIs, were closely associated with HGD, IMC, or mixed tumor and exhibited nuclear expression of β-catenin. Tumors in subgroup 4, which were generally low-grade dysplasias, exhibited a low frequency of AIs and no MSI. Although the mucin phenotype was not correlated with any subgroup, expression of mucin was associated with some subgroups. Overexpression of p53 was common in all subgroups. CONCLUSION: The approach described herein was useful for studying genetic differences in IMNs. In addition, we suggest that stratification of genetic differences may help to identify genetic molecular profiles in IMNs.. |
| 35. |
Kawasaki K, Kurahara K, Oshiro Y, Yanai S, Kobayashi H, Nakamura S, Fuchigami T, Sugai T, Matsumoto T, Clinicopathologic features of inverted serrated lesions of the large bowel, Digestion, 2016.06. |
| 36. |
Kei A Sato, Tsuyoshi Hachiya, Takeshi Iwaya, Kohei Kume, Teppei Matsuo, Keisuke Kawasaki, Yukito Abiko, Risaburo Akasaka, Takayuki Matsumoto, Koki Otsuka, Satoshi S Nishizuka, Individualized Mutation Detection in Circulating Tumor DNA for Monitoring Colorectal Tumor Burden Using a Cancer-Associated Gene Sequencing Panel., PloS one, 10.1371/journal.pone.0146275, 11, 1, e0146275, 2016.01, BACKGROUND: Circulating tumor DNA (ctDNA) carries information on tumor burden. However, the mutation spectrum is different among tumors. This study was designed to examine the utility of ctDNA for monitoring tumor burden based on an individual mutation profile. METHODOLOGY: DNA was extracted from a total of 176 samples, including pre- and post-operational plasma, primary tumors, and peripheral blood mononuclear cells (PBMC), from 44 individuals with colorectal tumor who underwent curative resection of colorectal tumors, as well as nine healthy individuals. Using a panel of 50 cancer-associated genes, tumor-unique mutations were identified by comparing the single nucleotide variants (SNVs) from tumors and PBMCs with an Ion PGM sequencer. A group of the tumor-unique mutations from individual tumors were designated as individual marker mutations (MMs) to trace tumor burden by ctDNA using droplet digital PCR (ddPCR). From these experiments, three major objectives were assessed: (a) Tumor-unique mutations; (b) mutation spectrum of a tumor; and (c) changes in allele frequency of the MMs in ctDNA after curative resection of the tumor. RESULTS: A total of 128 gene point mutations were identified in 27 colorectal tumors. Twenty-six genes were mutated in at least 1 sample, while 14 genes were found to be mutated in only 1 sample, respectively. An average of 2.7 genes were mutated per tumor. Subsequently, 24 MMs were selected from SNVs for tumor burden monitoring. Among the MMs found by ddPCR with > 0.1% variant allele frequency in plasma DNA, 100% (8 out of 8) exhibited a decrease in post-operation ctDNA, whereas none of the 16 MMs found by ddPCR with |
| 37. |
Kawasaki K, Kurahara K, Yanai S, Oshiro Y, Eizuka M, Uesugi N, Ishida K, Nakamura S, Fuchigami T, Sugai T, Matsumoto T, Significance of a white opaque substance under magnifying narrow-band imaging colonoscopy for the diagnosis of colorectal epithelial neoplasms., Gastrointest Endosc, 2015.12. |
| 38. |
Kawasaki K, Kurahara K, Yanai S, Kochi S, Fuchigami T, Matsumoto T., Low-Dose Aspirin and Non-steroidal Anti-inflammatory Drugs Increase the Risk of Bleeding in Patients with Gastroduodenal Ulcer, Dig Dis Sci, 2015.04. |
| 39. |
Tomohiro Nagasue, Shotaro Nakamura, Shuji Kochi, Koichi Kurahara, Hiroki Yaita, Keisuke Kawasaki, Tadahiko Fuchigami, Time trends of the impact of Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs on peptic ulcer bleeding in Japanese patients., Digestion, 10.1159/000368810, 91, 1, 37-41, 2015.01, BACKGROUND/AIMS: Helicobacter pylori infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) are the main causes of peptic ulcers. The purpose of the present study was to elucidate the time trends of the impact of H. pylori infection and use of NSAIDs and/or antithrombotic agents on peptic ulcer bleeding (PUB) in Japanese patients. METHODS: We retrospectively reviewed 719 patients who had received endoscopic hemostasis for PUB between 2002 and 2013. Subjects were divided into either the first-half group (2002-2007, n = 363) or the second-half group (2008-2013, n = 356). The clinical characteristics of the patients, including the prevalence of H. pylori infection and use of NSAIDs and antithrombotic agents, were compared between the two groups. RESULTS: Compared to the first-half group, patients in the second-half group were characterized by older age (proportion of the patients above 60 years old, 63.9 vs. 76.7%, p = 0.0002), less frequent H. pylori infection (71.6 vs. 57.9%, p |
| 40. |
Yanai S, Nakamura S, Takeshita M, Fujita K, Hirahashi M, Kawasaki K, Kurahara K, Sakai Y, Matsumoto T. , Translocation t(14;18)/IGH-BCL2 in gastrointestinal follicular lymphoma: correlation with clinicopathologic features in 48 patients. , Cancer, 2011.06. |
