研究者詳細 - 前田　啓子

A CASE OF INTRA-ABDOMINAL HAEMORRHAGE AFTER COLD SNARE POLYPECTOMY FOR COLORECTAL POLYPS

Ikegami S., Yamamura T., Nakamura M., Maeda K., Sawada T., Ishikawa E., Yamashita A., Kawamura T., Yokoi T., Kawashima H.

Gastroenterological Endoscopy 66 巻 ( 5 ) 頁： 1236 - 1241 2024年

記述言語：日本語出版者・発行元：Gastroenterological Endoscopy

A 51-year-old man underwent colonoscopy for endoscopic resection of polyps which were detected by CT colonography. Cold Snare Polypectomy (CSP) was performed for resection of an adenomatous polyp present in the splenic flexure. Two hours after the endoscopy, the patient experienced a sudden epigastric pain. Abdominal CT showed a mass-like thickening of the colon wall at the splenic flexure, leakage of contrast medium from the blood vessels in the wall, and hemorrhagic ascites in the abdominal cavity. The patient was diagnosed with intra-abdominal hemorrhage post a CSP procedure and underwent partial resection of the transverse colon through transverse colostomy. The surgical specimen showed a marked hematoma in the muscle layer below the site of CSP; however, no perforation was evident.

DOI： 10.11280/gee.66.1236

COLITIS CYSTICA PROFUNDA DIAGNOSED BY ESD

CiNii Research

Yamada K., Yamamura T., Nakamura M., Maeda K., Sawada T., Ishikawa E., Kajikawa G., Hasegawa I., Yokoi T., Kawashima H.

Gastroenterological Endoscopy 66 巻 ( 3 ) 頁： 279 - 285 2024年

記述言語：日本語出版者・発行元：Gastroenterological Endoscopy

A 46-year-old female patient presented to our hospital for close examination and treatment after a rectal mass was observed during a CS performed at another hospital. On repeat CS, we observed a 10-mm, submucosal, tumor-like mass in the lower rectum. EUS showed a 10-mm hypoechoic tumor located in the submucosa. We performed ESD because the boring biopsy specimens showed nonspecific pathologic findings. Pathological examination of the resected lesion confirmed the diagnosis of colitis cystica profunda.

DOI： 10.11280/gee.66.279

CiNii Research

Analysis of Neuropeptides in the Intestinal Mucus of Patients with Ulcerative Colitis Using RNA Sequencing. 査読有り国際誌

Nakamura M, Murate K, Maeda K, Yamamura T, Sawada T, Ishikawa E, Furukawa K, Hirose T, Uetsuki K, Iida T, Mizutani Y, Yamao K, Ishizu Y, Ishikawa T, Honda T, Kawashima H

Digestion 105 巻 ( 5 ) 頁： 400 - 410 2024年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Digestion

Introduction: Inflammation in ulcerative colitis (UC) originates in the colorectal mucosa. Transcriptome sequencing analysis of the colorectal mucosa allows the identification of potential neuropeptides related to local neurotransmission. The intestinal mucus lining the surface of the mucosa may harbor biomarkers of mucosal inflammation; however, this has not been sufficiently investigated, given the difficulty in obtaining human samples. We previously reported the feasibility of obtaining mucin samples for proteomic analysis by brushing during colonoscopy. Herein, we aimed to investigate the composition of the intestinal mucus and detect neuropeptides characteristic of UC. Methods: Mucus and mucosal samples were collected from patients with UC from the colorectum in areas showing remission or active UC using a brush catheter and biopsy forceps during colonoscopy. RNA sequencing findings of mucus samples of active and remission areas were compared. RNA and protein expression levels of significantly upregulated neuropeptides were analyzed. Results: Of the neuropeptides associated with UC, somatostatin (SST) was significantly elevated in areas of remission, according to RNA sequencing results of mucus and expression levels in mucus RNA and proteins. Conversely, SST expression in the mucosa was increased in the inflamed areas. Flow cytometry revealed that the fluorescence intensity of SST-positive cells in the remission zone was higher in the mucus than in the mucosa. Conclusion: SST expression in the mucus is considered to be an important factor associated with UC activity.

DOI： 10.1159/000540052

Real-World Effectiveness and Risk Factors for Discontinuation of Ustekinumab in Ulcerative Colitis.

Uchida G, Nakamura M, Yamamura T, Maeda K, Sawada T, Ishikawa E, Furukawa K, Iida T, Mizutani Y, Yamao K, Ishikawa T, Ishizu Y, Honda T, Ishigami M, Kawashima H

Inflammatory intestinal diseases 8 巻 ( 2 ) 頁： 60 - 68 2023年10月

記述言語：英語出版者・発行元：Inflammatory Intestinal Diseases

Introduction: Ustekinumab (UST) has been approved for the treatment of moderate-to-severe ulcerative colitis (UC). Real-world data showing the effectiveness and safety of UST are necessary to confirm the results of clinical trials for applicability in daily clinical practice. Although some studies have reported real-world evidence of UST, only few studies have confirmed its effectiveness in the real world. The aim of this study was to assess the short- and long-term effectiveness, durability, safety, and risk factors for discontinuation of UST in UC in clinical practice. Methods: This was a retrospective, single-center, observational study. From March 2020 to January 2023, all consecutive patients with active UC who were treated with UST at Nagoya University Hospital were included. The primary outcome was the clinical remission rate at weeks 2-8 and weeks 24-48. The secondary outcomes included clinical response, persistence of UST therapy, endoscopic changes during follow-up, risk factors for UST discontinuation, and occurrence of any adverse events. The clinical effectiveness was evaluated using the Lichtiger score. Results: A total of 31 patients were included in this study. The clinical remission rates were 9.7%, 29.0%, 54.8%, and 64.5% at weeks 2, 8, 24, and 48, respectively. Twelve (38.7%) patients discontinued UST during the follow-up period. The probability of continuing UST was 93.5%, 80.6%, 77%, and 70% at weeks 2, 8, 24, and 48, respectively. The major reason for discontinuation of UST was primary failure (75.0%). A high baseline C-reactive protein (CRP) level was a significant risk factor for the discontinuation of UST. No adverse events were observed in this study. Conclusion: UST is effective for patients with UC. High CRP levels were identified as a risk factor for UST discontinuation. The findings of this study would help clinicians to select appropriate treatment options for patients with UC by identifying the risk factors for treatment discontinuation.

DOI： 10.1159/000531497

Clinical characteristics of Dieulafoy's lesion in the small bowel diagnosed and treated by double-balloon endoscopy 査読有り国際誌

Nakamura, M; Yamamura, T; Maeda, K; Sawada, T; Ishikawa, E; Furukawa, K; Iida, T; Mizutani, Y; Yamao, K; Ishikawa, T; Honda, T; Ishigami, M; Kawashima, H

BMC GASTROENTEROLOGY 23 巻 ( 1 ) 頁： 290 - 290 2023年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BMC Gastroenterology

Background: Obscure gastrointestinal bleeding refers to bleeding for which the source cannot be ascertained even through balloon-assisted endoscopy. In certain instances, Dieulafoy’s lesion in the small bowel is presumed to be the underlying cause. Aim: This retrospective study aimed to elucidate the clinical characteristics of Dieulafoy’s lesion in the small bowel as diagnosed via double-balloon endoscopy while also exploring the feasibility of predicting bleeding from Dieulafoy’s lesion prior to endoscopy in cases of obscure gastrointestinal bleeding. Methods: A comprehensive analysis of our database was conducted, identifying 38 patients who received a diagnosis of Dieulafoy’s lesion and subsequently underwent treatment via double-balloon endoscopy. The clinical background, diagnosis, and treatment details of patients with Dieulafoy’s lesion were carefully examined. Results: The median age of the 38 patients was 72 years, and 50% of the patients were male. A total of 26 (68%) patients exhibited a high comorbidity index. The upper jejunum and lower ileum were the most frequently reported locations for the occurrence of Dieulafoy’s lesion in the small bowel. The detected Dieulafoy’s lesions exhibited active bleeding (n = 33) and an exposed vessel with plaque on the surface (n = 5). Rebleeding after endoscopic treatment occurred in 8 patients (21%, median period: 7 days, range: 1-366 days). We conducted an analysis to determine the definitive nature of the initial double-balloon endoscopy diagnosis. Multivariate analysis revealed that hematochezia of ≥ 2 episodes constituted the independent factor associated with ≥ 2 double-balloon endoscopy diagnoses. Additionally, we explored factors associated with rebleeding following endoscopic treatment. Although the number of hemoclips utilized displayed a likely association, multivariate analysis did not identify any independent factor associated with rebleeding. Conclusion: If a patient encounters multiple instances of hematochezia, promptly scheduling balloon-assisted endoscopy, equipped with optional instruments without delay is advised, after standard endoscopic evaluation with esophagogastroduodenoscopy and colonoscopy is unrevealing.

DOI： 10.1186/s12876-023-02913-1

Protocol for measuring transcytosis and recycling of IgG in intestinal epithelial Caco-2 cells and primary human intestinal organoids

Maeda, K; Gwilt, KB; Schmieder, SS; Zachos, NC; Lencer, WI

STAR PROTOCOLS 4 巻 ( 2 ) 2023年6月

Efficacy of 1-kestose supplementation in patients with mild to moderate ulcerative colitis: A randomised, double-blind, placebo-controlled pilot study 査読有り国際誌

Ikegami, S; Nakamura, M; Honda, T; Yamamura, T; Maeda, K; Sawada, T; Ishikawa, E; Yamamoto, K; Furune, S; Ishikawa, T; Furukawa, K; Ohno, E; Ishigami, M; Kinoshita, F; Kadota, Y; Tochio, T; Shimomura, Y; Hirooka, Y; Kawashima, H

ALIMENTARY PHARMACOLOGY & THERAPEUTICS 57 巻 ( 11 ) 頁： 1249 - 1257 2023年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Alimentary Pharmacology and Therapeutics

Background: Ulcerative colitis involves an excessive immune response to intestinal bacteria. Whether administering prebiotic 1-kestose is effective for active ulcerative colitis remains controversial. Aims: This randomised, double-blind, placebo-controlled pilot trial investigated the efficacy of 1-kestose against active ulcerative colitis. Methods: Forty patients with mild to moderate active ulcerative colitis were randomly treated with 1-kestose (N = 20) or placebo (maltose, N = 20) orally for 8 weeks in addition to the standard treatment. The Lichtiger clinical activity index and Ulcerative Colitis Endoscopic Index of Severity were determined. Faecal samples were analysed to evaluate the gut microbiome and metabolites. Results: The clinical activity index at week 8 was significantly lower in the 1-kestose group than in the placebo group (3.8 ± 2.7 vs. 5.6 ± 2.1, p = 0.026). Clinical remission and response rates were higher in the 1-kestose group than in the placebo group (remission: 55% vs. 20%, p = 0.048; response: 60% vs. 25%, p = 0.054). The Ulcerative Colitis Endoscopic Index of Severity at week 8 was not significantly different (2.8 ± 1.6 vs. 3.5 ± 1.6, p = 0.145). Faecal analysis showed significantly reduced alpha-diversity in the 1-kestose group, with a decreased relative abundance of several bacteria, including Ruminococcus gnavus group. The short-chain fatty acid levels were not significantly different between the groups. The incidence of adverse events was comparable between the groups. Discussion: Oral 1-kestose is well tolerated and provides clinical improvement for patients with mild to moderate ulcerative colitis through modulation of the gut microbiome.

DOI： 10.1111/apt.17387

ENDOSCOPIC TREATMENT OF DUODENAL NEUROENDOCRINE TUMORS

Furukawa, K; Furune, S; Ishikawa, E; Sawada, T; Maeda, K; Yamamura, T; Ishikawa, T; Nakamura, M; Kawashima, H

GASTROINTESTINAL ENDOSCOPY 97 巻 ( 6 ) 頁： AB1211 - AB1212 2023年6月

CO<sub>2</sub> enterography in endoscopic retrograde cholangiography using double-balloon endoscopy: A randomized clinical trial 査読有り国際誌

Murate, K; Nakamura, M; Yamamura, T; Maeda, K; Sawada, T; Ishikawa, E; Kida, Y; Esaki, M; Hamazaki, M; Iida, T; Mizutani, Y; Yamao, K; Ishikawa, T; Furukawa, K; Ohno, E; Honda, T; Ishigami, M; Kinoshita, F; Ando, M; Kawashima, H

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 38 巻 ( 5 ) 頁： 761 - 767 2023年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Gastroenterology and Hepatology (Australia)

Background and Aim: Double-balloon endoscopic retrograde cholangiography (DBERC) is a valuable procedure for patients with altered gastrointestinal anatomy. Nonetheless, it is time-consuming and burdensome for both patients and endoscopists, partly because route selection in the reconstructed bowel with complicating loop is challenging. Carbon dioxide insufflation enterography is reportedly useful for route selection in the blind loop. This prospective randomized clinical trial investigated the usefulness of carbon dioxide insufflation enterography for route selection by comparing it with conventional observation. Methods: Patients scheduled to undergo DBERC were consecutively registered. They were divided into carbon dioxide insufflation enterography and conventional groups via randomization according to stratification factors, type of reconstruction methods, and experience with DBERC. The primary endpoint was the correct rate of initial route selection. The secondary endpoints were the insertion time, examination time, amount of anesthesia drugs, and complications. Results: The correct rate of route selection was significantly higher in the carbon dioxide insufflation enterography group (23/25, 92%) than in the visual method (15/25, 60%) (P = 0.018). The insertion time was significantly shorter in the carbon dioxide insufflation enterography group than in the visual group (10.8 ± 11.1 min vs 29.8 ± 15.7 min; P < 0.001). No significant differences in complications were noted between the two groups. The amounts of sedatives and analgesics used were significantly lower in the carbon dioxide insufflation enterography group (P < 0.001 and P < 0.001, respectively). Conclusions: Carbon dioxide insufflation enterography can reduce the burden of DBERC on patients and endoscopists by shortening the examination time and reducing the amount of medication.

DOI： 10.1111/jgh.16112

Novel endoscopic approaches using the endocytoscopy for the target biopsy in esophageal eosinophilia

Muroi, K; Kakushima, N; Furukawa, K; Furune, S; Ito, N; Hirose, T; Hida, E; Suzuki, T; Suzuki, T; Hirai, K; Shibata, H; Ishikawa, E; Sawada, T; Maeda, K; Yamamura, T; Ohno, E; Nakamura, M; Fujishiro, M; Kawashima, H

ESOPHAGUS 20 巻 ( 2 ) 頁： 325 - 332 2023年4月

記述言語：英語出版者・発行元：Esophagus

Background and aims: Multiple biopsies are recommended for the diagnosis of eosinophilic esophagitis (EoE) because inflammatory changes are frequently patchy. Reports on EoE using endocytoscopy (ECS) are limited. This present study aimed to assess if diagnostic yield improves by adding ECS on conventional white light imaging (WLI) in patients with esophageal eosinophilia (EE). Methods: A total of 284 biopsy specimens from 71 patients with a known diagnosis of EE were enrolled and divided into the WLI group (156 specimens) or the ECS group (128 specimens). Four biopsies from 5 and 10 cm proximal to the esophagogastric junction were taken from each patient. In the ECS group, the biopsy was performed where bilobed nuclei were observed. The biopsy sensitivity for EE, eosinophil count of a single specimen and the biopsy sensitivity of each endoscopic finding were evaluated between both groups. Results: The sensitivity of a single biopsy specimen was higher in the ECS group than that of the WLI group (62.5 vs. 41.7%, P < 0.001). In addition, the median eosinophil count in the ECS group was significantly higher [19 vs. 6.5/high-power field (HPF), P < 0.001]. For each endoscopic finding, ECS-based biopsy had higher sensitivity than that of WLI in the diagnosis of edema (33.1 vs. 11.3%, P = 0.007) and linear furrows (75.8 vs. 52%, P = 0.005). Conclusion: This study showed that adding ECS to WLI improved the biopsy sensitivity and eosinophil detection in patients with EE.

DOI： 10.1007/s10388-022-00963-0

Proteomic Analysis Reveals Changes in Tight Junctions in the Small Intestinal Epithelium of Mice Fed a High-Fat Diet 国際誌

Muto, H; Honda, T; Tanaka, T; Yokoyama, S; Yamamoto, K; Ito, T; Imai, N; Ishizu, Y; Maeda, K; Ishikawa, T; Adachi, S; Sato, C; Tsuji, NM; Ishigami, M; Fujishiro, M; Kawashima, H

NUTRIENTS 15 巻 ( 6 ) 2023年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nutrients

The impact of a high-fat diet (HFD) on intestinal permeability has been well established. When bacteria and their metabolites from the intestinal tract flow into the portal vein, inflammation in the liver is triggered. However, the exact mechanism behind the development of a leaky gut caused by an HFD is unclear. In this study, we investigated the mechanism underlying the leaky gut related to an HFD. C57BL/6J mice were fed an HFD or control diet for 24 weeks, and their small intestine epithelial cells (IECs) were analyzed using deep quantitative proteomics. A significant increase in fat accumulation in the liver and a trend toward increased intestinal permeability were observed in the HFD group compared to the control group. Proteomics analysis of the upper small intestine epithelial cells identified 3684 proteins, of which 1032 were differentially expressed proteins (DEPs). Functional analysis of DEPs showed significant enrichment of proteins related to endocytosis, protein transport, and tight junctions (TJ). Expression of Cldn7 was inversely correlated with intestinal barrier function and strongly correlated with that of Epcam. This study will make important foundational contributions by providing a comprehensive depiction of protein expression in IECs affected by HFD, including an indication that the Epcam/Cldn7 complex plays a role in leaky gut.

DOI： 10.3390/nu15061473

Accuracy of Serum Leucine-Rich Alpha-2 Glycoprotein in Evaluating Endoscopic Disease Activity in Crohn's Disease 査読有り国際誌

Kawamura, T; Yamamura, T; Nakamura, M; Maeda, K; Sawada, T; Ishikawa, E; Iida, T; Mizutani, Y; Ishikawa, T; Kakushima, N; Furukawa, K; Ohno, E; Honda, T; Kawashima, H; Ishigami, M

INFLAMMATORY BOWEL DISEASES 29 巻 ( 2 ) 頁： 245 - 253 2023年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Inflammatory Bowel Diseases

Background: Mucosal healing, confirmed by endoscopic evaluation, is the long-term goal of treatment for Crohn’s disease (CD). Leucine-rich alpha-2 glycoprotein (LRG) is a new serum biomarker correlated with disease activity in inflammatory bowel disease. However, studies evaluating its relationship with CD, particularly in the context of small intestinal lesions, are scarce.The aim of this study was to investigate the accuracy of LRG in assessing endoscopic activity, especially remission, in patients with CD. Methods: Between July 2020 and March 2021, 72 patients with CD who underwent LRG testing and double-balloon endoscopy at the same time were included. Endoscopic activity was evaluated using the applied Simple Endoscopic Score for Crohn’s disease, including small intestine lesions.The relationship of LRG with clinical symptoms and endoscopic activity was assessed, and its predictive accuracy was evaluated. Results: Leucine-rich alpha-2 glycoprotein showed a significant positive correlation with endoscopic activity (r = 0.619, P < .001), even in patients with active lesions in the small intestine (r = 0.626, P < .001). Multivariate logistic regression revealed that LRG was the only factor associated with endoscopic remission. An LRG cutoff value of 8.9 μg/mL had a sensitivity of 93.3%; specificity of 83.3%; positive predictive value of 96.6%; negative predictive value of 71.4%; accuracy of 91.7%; and area under the curve of 0.904 for the prediction of endoscopic remission. Conclusions: Leucine-rich alpha-2 glycoprotein can be used in assessing endoscopic activity and is a reliable marker of endoscopic remission in CD patients. It can be an intermediate target in the treatment of CD.

DOI： 10.1093/ibd/izac076

SMALL INTESTINAL GANGLIONEUROMATOSIS IN A PATIENT WITH NEUROFIBROMATOSIS TYPE 1: A CASE REPORT

Kida Y., Sawada T., Ishikawa E., Sakakibara A., Yamamura T., Maeda K., Esaki M., Hamazaki M., Murate K., Nakamura M.

Gastroenterological Endoscopy 65 巻 ( 7 ) 頁： 1232 - 1238 2023年

記述言語：日本語出版者・発行元：Gastroenterological Endoscopy

A 50-year-old woman with neurofibromatosis type 1 who hospitalized for chronic diarrhea was transferred to our hospital for evaluation of small intestinal dilatation and thickening. Transoral double-balloon enteroscopy revealed jejunal dilatation and suppressed peristalsis; however, mucosal inflammation, such as ulcers or erosions were not detected. Transanal double-balloon enteroscopy detected the intestinal stenosis with inflammatory polyps and a longitudinal ulcer. Histopathological evaluation of duodenal, jejunal, and ileal specimens by biopsy revealed ganglion cells and Schwannian cells; therefore, the patient was diagnosed with ganglioneuromatosis with neurofibromatosis type 1. Small intestinal dilatation was associated with suppressed peristalsis caused by ganglioneuromatosis and was diagnosed as secondary chronic intestinal pseudo-obstruction. Abdominal distention persisted despite conservative therapy. However, she remained asymptomatic, and oral intake remained unaffected. Ganglioneuromatosis is rare; however, clinicians should be mindful that ganglioneuromatosis is an abdominal complication associated with systemic disease such as neurofibromatosis type 1 and multiple endocrine neoplasia type 2B.

DOI： 10.11280/gee.65.1232