Faculty Profiles - MAEDA Keiko

Artificial intelligence-based diagnostic imaging system with virtual enteroscopy and virtual unfolded views to evaluate small bowel lesions in Crohn's disease. Reviewed International journal

Kazuhiro Furukawa, Masahiro Oda, Osamu Watanabe, Masanao Nakamura, Takeshi Yamamura, Keiko Maeda, Kensaku Mori, Hiroki Kawashima

Revista espanola de enfermedades digestivas 2024.3

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

Since even subtle mucosal changes may be depicted using virtual endoscopy created by the three-dimensional reconstruction of MDCT images, we developed a novel diagnostic imaging system that integrates and displays virtual enteroscopy, curved planar reconstruction, and a virtual unfolded view, the width of which changes with increases/decreases in the inner luminal diameter. The system is also equipped with artificial intelligence that superimposes and displays depressed areas, generates an automatic small bowel centerline that connects fragmented small bowel regions, and performs electronic cleansing. We retrospectively evaluated the diagnostic performance of this system for small bowel lesions in Crohn's disease, which were divided into two groups: endoscopically-observable and endoscopically-unobservable. Lesion detection rates for stenoses, longitudinal ulcers with a cobblestone appearance, and scars were excellent in both groups. This system, when used in combination with endoscopy, shows slight mucosal changes in areas in which an endoscope cannot reach due to strictures, thereby extending the range of observation of the small bowel. This system is a useful diagnostic modality that has the capacity to assess mucosal healing and provide extraluminal information.

DOI： 10.17235/reed.2024.10405/2024

Reply: Interleukin-18 Inhibition in Inflammatory Bowel Diseases: A Delicate Balance.

Maeda K, Kawashima H

Inflammatory bowel diseases 2024.3

Risk factors for rebleeding in gastroduodenal ulcers. International journal

Nobuhito Ito, Kohei Funasaka, Toshihisa Fujiyoshi, Kazuki Nishida, Yusuke Satta, Kazuhiro Furukawa, Naomi Kakushima, Satoshi Furune, Eri Ishikawa, Yasuyuki Mizutani, Tsunaki Sawada, Keiko Maeda, Takuya Ishikawa, Takeshi Yamamura, Eizaburo Ohno, Masanao Nakamura, Ryoji Miyahara, Yoji Sasaki, Jun-Ichi Haruta, Mitsuhiro Fujishiro, Hiroki Kawashima

Irish journal of medical science Vol. 193 ( 1 ) page： 173 - 179 2024.2

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

BACKGROUND: Rebleeding after hemostasis of the gastroduodenal ulcer (GDU) is one of the indicators associated with death among GDU patients. However, there are few studies on risk score that contribute to rebleeding after endoscopic hemostasis of bleeding peptic ulcers. AIMS: The aim of this study was to identify factors associated with rebleeding, including patient factors, after endoscopic hemostasis of bleeding gastroduodenal ulcers and to stratify the risk of rebleeding. METHODS: We retrospectively enrolled 587 consecutive patients who were treated for Forrest Ia to IIa bleeding gastroduodenal ulcers with endoscopic hemostasis at three institutions. Risk factors associated with rebleeding were assessed using univariate and multivariate logistic regression analyses. The Rebleeding Nagoya University (Rebleeding-N) scoring system was developed based on the extracted factors. The Rebleeding-N score was internally validated using bootstrap resampling methods. RESULTS: Sixty-four patients (11%) had rebleeding after hemostasis of gastroduodenal ulcers. Multivariate logistic regression analysis revealed four independent rebleeding risk factors: blood transfusion, albumin <2.5, duodenal ulcer, and diameter of the exposed vessel ≧2 mm. Patients with 4 risk factors in the Rebleeding-N score had a 54% rebleeding rate, and patients with 3 risk factors had 44% and 25% rebleeding rates. In the internal validation, the mean area under the curve of the Rebleeding-N score was 0.830 (95% CI = 0.786-0.870). CONCLUSIONS: Rebleeding after clip hemostasis of bleeding gastroduodenal ulcers was associated with blood transfusion, albumin <2.5, diameter of the exposed vessel ≧2 mm, and duodenal ulcer. The Rebleeding-N score was able to stratify the risk of rebleeding.

DOI： 10.1007/s11845-023-03450-2

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

IKEGAMI Shuji, YAMAMURA Takeshi, NAKAMURA Masanao, MAEDA Keiko, SAWADA Tsunaki, ISHIKAWA Eri, YAMASHITA Ayako, KAWAMURA Tatsuya, YOKOI Takio, KAWASHIMA Hiroki

GASTROENTEROLOGICAL ENDOSCOPY Vol. 66 ( 5 ) page： 1236 - 1241 2024

Language：Japanese Publisher：Japan Gastroenterological Endoscopy Society

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

OLITIS CYSTICA PROFUNDA DIAGNOSED BY ESD

YAMADA Kentaro, YAMAMURA Takeshi, NAKAMURA Masanao, MAEDA Keiko, SAWADA Tsunaki, ISHIKAWA Eri, KAJIKAWA Go, HASEGAWA Issei, YOKOI Takio, KAWASHIMA Hiroki

GASTROENTEROLOGICAL ENDOSCOPY Vol. 66 ( 3 ) page： 279 - 285 2024

Language：Japanese Publisher：Japan Gastroenterological Endoscopy Society

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

Analysis of Neuropeptides in the Intestinal Mucus of Patients with Ulcerative Colitis Using RNA Sequencing. Reviewed International journal

Masanao Nakamura, Kentaro Murate, Keiko Maeda, Takeshi Yamamura, Tsunaki Sawada, Eri Ishikawa, Kazuhiro Furukawa, Takashi Hirose, Kota Uetsuki, Tadashi Iida, Yasuyuki Mizutani, Kentaro Yamao, Yoji Ishizu, Takuya Ishikawa, Takashi Honda, Hiroki Kawashima

Digestion Vol. 105 ( 5 ) page： 400 - 410 2024

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

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 Vol. 8 ( 2 ) page： 60 - 68 2023.10

Language：English Publisher：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. Reviewed International journal

Masanao Nakamura, Takeshi Yamamura, Keiko Maeda, Tsunaki Sawada, Eri Ishikawa, Kazuhiro Furukawa, Tadashi Iida, Yasuyuki Mizutani, Kentaro Yamao, Takuya Ishikawa, Takashi Honda, Masatoshi Ishigami, Hiroki Kawashima

BMC gastroenterology Vol. 23 ( 1 ) page： 290 - 290 2023.8

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

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 Vol. 4 ( 2 ) 2023.6

Efficacy of 1-kestose supplementation in patients with mild to moderate ulcerative colitis: A randomised, double-blind, placebo-controlled pilot study. Reviewed International journal

Shuji Ikegami, Masanao Nakamura, Takashi Honda, Takeshi Yamamura, Keiko Maeda, Tsunaki Sawada, Eri Ishikawa, Kenta Yamamoto, Satoshi Furune, Takuya Ishikawa, Kazuhiro Furukawa, Eizaburo Ohno, Masatoshi Ishigami, Fumie Kinoshita, Yoshihiro Kadota, Takumi Tochio, Yoshiharu Shimomura, Yoshiki Hirooka, Hiroki Kawashima

Alimentary pharmacology & therapeutics Vol. 57 ( 11 ) page： 1249 - 1257 2023.6

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

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 Vol. 97 ( 6 ) page： AB1211 - AB1212 2023.6

CO2 enterography in endoscopic retrograde cholangiography using double-balloon endoscopy: A randomized clinical trial. Reviewed International journal

Kentaro Murate, Masanao Nakamura, Takeshi Yamamura, Keiko Maeda, Tsunaki Sawada, Eri Ishikawa, Yuichi Kida, Masaya Esaki, Motonobu Hamazaki, Tadashi Iida, Yasuyuki Mizutani, Kentaro Yamao, Takuya Ishikawa, Kazuhiro Furukawa, Eizaburo Ohno, Takashi Honda, Masatoshi Ishigami, Fumie Kinoshita, Masahiko Ando, Hiroki Kawashima

Journal of gastroenterology and hepatology Vol. 38 ( 5 ) page： 761 - 767 2023.5

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

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 Vol. 20 ( 2 ) page： 325 - 332 2023.4

Language：English Publisher：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. International journal

Hisanori Muto, Takashi Honda, Taku Tanaka, Shinya Yokoyama, Kenta Yamamoto, Takanori Ito, Norihiro Imai, Yoji Ishizu, Keiko Maeda, Tetsuya Ishikawa, Shungo Adachi, Chikara Sato, Noriko M Tsuji, Masatoshi Ishigami, Mitsuhiro Fujishiro, Hiroki Kawashima

Nutrients Vol. 15 ( 6 ) 2023.3

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

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. Reviewed International journal

Tatsuya Kawamura, Takeshi Yamamura, Masanao Nakamura, Keiko Maeda, Tsunaki Sawada, Eri Ishikawa, Tadashi Iida, Yasuyuki Mizutani, Takuya Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Eizaburo Ohno, Takashi Honda, Hiroki Kawashima, Masatoshi Ishigami

Inflammatory bowel diseases Vol. 29 ( 2 ) page： 245 - 253 2023.2

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

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 Yuichi, SAWADA Tsunaki, ISHIKAWA Eri, SAKAKIBARA Ayako, YAMAMURA Takeshi, MAEDA Keiko, ESAKI Masaya, HAMAZAKI Motonobu, MURATE Kentaro, NAKAMURA Masanao

GASTROENTEROLOGICAL ENDOSCOPY Vol. 65 ( 7 ) page： 1232 - 1238 2023

Language：Japanese Publisher：Japan Gastroenterological Endoscopy Society

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

Diagnostic Performance of Endocytoscopy for Esophageal Eosinophilia. Reviewed International journal

Emiko Hida, Koichi Muroi, Naomi Kakushima, Satoshi Furune, Eri Ishikawa, Yasuyuki Mizutani, Tsunaki Sawada, Maeda Keiko, Takeshi Yamamura, Takuya Ishikawa, Kazuhiro Furukawa, Eizaburo Ohno, Masanao Nakamura, Kazuki Nishida, Mitsuhiro Fujishiro, Hiroki Kawashima

Digestion Vol. 104 ( 3 ) page： 202 - 211 2023

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

INTRODUCTION: Eosinophils in the esophageal epithelium are unevenly distributed in eosinophilic esophagitis (EoE). Esophageal eosinophilia (EE) may be observable by endocytoscopy (EC). This study aimed to evaluate the diagnostic performance of EC for the diagnosis of EE. METHODS: A total of 33 EoE patients underwent EC with methylene blue staining from March 2020 to April 2021. A total of 194 EC images with corresponding biopsies were obtained. Three findings of EC, increased squamous cells (item I), increased inflammatory cells (item II), and cells with bilobed nuclei (item III), were established. These findings were reviewed by two endoscopists to diagnose EE. Another four endoscopists reviewed the images for interobserver agreement. RESULTS: When all three items were met by EC, the sensitivity and the accuracy for the diagnosis of EE were 88% and 76%, respectively. The integrated diagnostic odds ratios (ORs) for the diagnosis of EE of the four endoscopists were significant (OR: 3.98, 95% CI: 2.94-5.40, p < 0.001). The results were similar when only item III was met. Interobserver agreement was good for item III to diagnose EE (kappa value = 0.653). DISCUSSION/CONCLUSION: The diagnostic performance of EC for EE is acceptable and has good interobserver agreement. It may be useful for targeted biopsy in EoE patients.

DOI： 10.1159/000528174

Factors related to delayed adverse events of endoscopic submucosal dissection in the duodenum. Reviewed International journal

Tatsuya Kawamura, Takashi Hirose, Naomi Kakushima, Kazuhiro Furukawa, Satoshi Furune, Eri Ishikawa, Tsunaki Sawada, Keiko Maeda, Takeshi Yamamura, Takuya Ishikawa, Eizaburo Ohno, Masanao Nakamura, Takashi Honda, Masatoshi Ishigami, Hiroki Kawashima, Mitsuhiro Fujishiro

Digestive diseases (Basel, Switzerland) Vol. 41 ( 1 ) page： 80 - 88 2023

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

INTRODUCTION: Endoscopic submucosal dissection for duodenal neoplasms (D-ESD) is considered a technically demanding procedure regarding the high risk of delayed adverse events. Data regarding optimal managements of ulcers after D-ESD are lacking. METHODS: A retrospective analysis was performed on consecutive 145 cases of D-ESD for superficial non-ampullary duodenal epithelial tumors at a single referral center. Factors related to delayed adverse events and the healing process of ulcers after D-ESD were analyzed. RESULTS: Complete ulcer suture after D-ESD was performed in 128 cases (88%). Two delayed perforation occurred among cases with incomplete suture. Delayed bleeding occurred in 8 cases (6%) within three weeks. The ulcer closure rate at second-look endoscopy was significantly low among cases with delayed bleeding (12.5% vs 75%, P=0.001). The bleeding rate before second-look endoscopy was significantly high among patients who did not have complete ulcer closure after D-ESD (0.8% vs 12%, P=0.036). The ratio of lesions located in the 2nd oral-Vater was significantly low among ulcers re-opened at second-look endoscopy (38% vs 14%, P=0.044). Proton-pump inhibitors (PPI) were administered for a median of seven weeks (range 1-8 weeks). At three weeks, active ulcer stages were observed in a few cases, and healing or scarring was observed in most cases. CONCLUSIONS: Complete ulcer suture was related to decreased risk of delayed adverse events after D-ESD. From the bleeding period and healing process of D-ESD ulcers, the minimum required length of PPI may be three weeks after D-ESD.

DOI： 10.1159/000522362

Network Analysis of Gut Microbiota Including Fusobacterium and Oral Origin Bacteria and Their Distribution on Tumor Surface, Normal Mucosa, and in Feces in Patients with Colorectal Cancer

特集消化管内視鏡治療のリスク克服に向けて 1.待機的内視鏡治療に潜むリスクとそのマネジメント(6)大腸EMR/ESD

山村健史, 中村正直, 前田啓子, 澤田つな騎, 石川恵里, 古川和宏, 川嶋啓揮

臨床消化器内科 Vol. 38 ( 1 ) page： 42 - 47 2022.12

Ohashi, A; Yamamura, T; Nakamura, M; Maeda, K; Sawada, T; Ishikawa, E; Yamamoto, K; Ishikawa, T; Kakushima, N; Furukawa, K; Ohno, E; Honda, T; Kawashima, H; Ishigami, M; Fujishiro, M

DIGESTION Vol. 103 ( 6 ) page： 451 - 461 2022.12

Language：English Publisher：Digestion

Introduction: Fusobacterium and several bacteria are reported to be associated with colorectal cancer (CRC). However, their relationship and whether they cause CRC or are just adapted to the cancerous environment is not known. We approached this subject by investigating the correlation and distribution of the bacteria throughout the colon in patients with CRC and elucidated the relationship between microbiota and CRC. Methods: Twenty-five patients with CRC who underwent colonoscopy for endoscopic submucosal dissection or surgery were prospectively enrolled. Fecal samples were taken before bowel preparation, and mucosal samples were collected from three sites (tumor surface, tumor-adjacent mucosa, and cecum) during colonoscopy using a cytology brush. The microbiota was identified and analyzed by sequencing of the 16S rRNA gene of the V3-V4 region. We evaluated the correlation between the bacteria based on network analysis and the distribution of Fusobacterium in the colon. Results: A network consisting of many bacteria was found in all sites; especially, oral origin bacteria including Fusobacterium formed a positively correlated network on tumor surface. Streptococcus showed a significantly higher relative abundance on tumor surface than in feces. The relative abundance of Fusobacterium had significant positive correlations between tumor surface and feces, tumor-adjacent mucosa, and cecum. Conclusion: In patients with CRC, many bacteria were correlated with each other, and Fusobacterium and oral origin bacteria formed a positively correlated network on tumor surface. Fusobacterium was equally distributed on tumor surface and throughout the lumen and mucus in the colon. In the colon where Fusobacterium is widely distributed, Fusobacterium would adhere to the tumor surface and be correlated with oral origin bacteria to make a microenvironment that is favorable for CRC.

DOI： 10.1159/000527170

The effects of ustekinumab on small intestinal lesions and stenotic lesions

Wada Hirotaka, Murate Kentaro, Nakamura Masanao, Furukawa Kazuhiro, Kakushima Naomi, Yamamura Takeshi, Maeda Keiko, Sawada Tsunaki, Ishikawa Eri, Ishikawa Takuya, Ohno Eizaburo, Honda Takashi, Kawashima Hiroki, Nakayama Goro, Hattori Norifumi, Umeda Shinichi, Ishigami Masatoshi

NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 84 ( 4 ) page： 825 - 838 2022.11

Language：English Publisher：Nagoya Journal of Medical Science

Crohn’s disease patients suffer from symptoms originating from small bowel lesions, including strictures. As many of these patients also have a potential risk of surgery, it is important to consider various therapeutic strategies for small bowel lesions. We retrospectively analyzed the therapeutic effects of ustekinumab, interleukin-12 and -23 blocker, for small intestinal lesions and intestinal stenosis in order to contribute to the optimal management of Crohn’s disease. Patients who underwent total colonoscopy or small bowel endoscopy before and after the introduction of ustekinumab were enrolled in this study. The colonoscopy findings were evaluated by the simple endoscopic score for Crohn’s disease, and small bowel endoscopy findings were evaluated using the modified simple endoscopic score for Crohn’s disease. Endoscopic scores were compared before and after the introduction of ustekinumab and between the responders and non-responders to ustekinumab. Responders were defined as those whose Crohn’s disease activity index score at 24 weeks fell below 150 points, or those whose score decreased by more than 100 points from the pre-induction level. A total of 50 patients were enrolled in the study, and the number of responders was 35. Pre-induction simple endoscopic scores were lower for responders, but no significant difference was observed in the modified simple endoscopic scores. The total decrease in the endoscopic score was significantly higher in the responders for both the small and large intestine. Use of ustekinumab as a first-line treatment for patients with small bowel lesions or stricture-prone lesions may be a new treatment consideration in the future.

DOI： 10.18999/nagjms.84.4.825

Analysis of immunologic comorbidities in ulcerative colitis patients: a tool to prevent exacerbations in ulcerative colitis cases. Reviewed

Miguel Ricardo Rodríguez Meza, Masanao Nakamura, Takeshi Yamamura, Keiko Maeda, Tsunaki Sawada, Eri Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Tadashi Iida, Yasuyuki Mizutani, Takuya Ishikawa, Eizaburo Ohno, Takashi Honda, Hiroki Kawashima, Masatoshi Ishigami

Nagoya journal of medical science Vol. 84 ( 4 ) page： 733 - 745 2022.11

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

There have been previous studies, especially in Western countries and even in some areas in Asia, about extra-intestinal manifestations (EIMs) and its link with the outcome of inflammatory bowel disease (IBD), which includes Crohn's disease (CD), and ulcerative colitis (UC). This link is crucial when discussing a patient's prognosis and important when dealing with UC management. The aim of this study was to clarify the most common comorbidities associated with UC, emphasizing immunologic comorbidities in Japan. This study was a retrospective analysis performed at Nagoya University Hospital. The data collection started in March, 2019, and continued for two years. We retrieved the medical records of 105 patients with UC diagnosis, from which the data of 176 EIMs were extracted and analyzed. Results showed that EIMs with UC in the active phase accounted for 43.7% of total EIMs. Twenty-six patients with immune-mediated inflammatory disease frequently had an active phase (odds ratio [OR] 3.84, 99% CI, 1.44-10.27). Comorbidities showing an active manifestation of symptoms and UC in the active phase were significantly correlated in patients with immunological comorbidities, such as peripheral arthritis (r = 0.97, p < 0.01) and rheumatoid arthritis (RA) (r = 0.99, p < 0.01), as well as in patients with primary sclerosis cholangitis (PSC) (r = 0.98, p < 0.01). In conclusion, this analysis suggests the importance of having full comprehension of how immunological comorbidities affect the natural development of UC, which is of vital importance to prevent further UC complications and properly adjust the management of the disease.

DOI： 10.18999/nagjms.84.4.733

Fecal microbiota transplantation in the treatment of irritable bowel syndrome: a single-center prospective study in Japan. Reviewed International journal

Motonobu Hamazaki, Tsunaki Sawada, Takeshi Yamamura, Keiko Maeda, Yasuyuki Mizutani, Eri Ishikawa, Satoshi Furune, Kenta Yamamoto, Takuya Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Eizaburo Ohno, Takashi Honda, Hiroki Kawashima, Masatoshi Ishigami, Masanao Nakamura, Mitsuhiro Fujishiro

BMC gastroenterology Vol. 22 ( 1 ) page： 342 - 342 2022.7

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

BACKGROUND: Fecal microbiota transplantation (FMT) is a potential treatment for irritable bowel syndrome (IBS), but its efficacy in Japanese IBS patients is unknown. This study aimed to evaluate the efficacy, side effects, and microbiome changes following FMT in Japanese IBS patients. METHODS: Seventeen Japanese patients with refractory IBS received FMT (4 donors) under colonoscopy. Responders were defined by an improvement in the IBS severity index (IBS-SI) of 50 points or more after 12 weeks. We evaluated the IBS-SI and Bristol Stool Form Scale (BSFS) and compared the diversity and microbiome before and 12 weeks after FMT. For the microbiome, we analyzed the V3-V4 region of the 16S rRNA gene. RESULTS: IBS-SI decreased an average of 115.58 points after 12 weeks, and 10 patients (58.8%) were considered responders. Eight patients with diarrhea (66.7%) and three patients with constipation (60.0%) showed improvement in the BSFS. Two patients complained of mild abdominal pain, but there were no cases with severe side-effects. α-diversity was increased only in the responder group (p = 0.017). Patients who closely paralleled the donor microbiome had a higher rate of IBS-SI improvement. The relative abundance of Neisseria and Akkermansia increased and Desulfovibrio and Delftia were decreased in the responder group after FMT. CONCLUSIONS: Following FMT, about 60% of Japanese patients with IBS showed improvement in both the IBS-SI and BSFS, without severe side effects. Increased α-diversity and similarity to the donor microbiome after FMT may be associated with better treatment effects. TRIAL REGISTRATION: This study was registered in the University Hospital Medical Information Network Clinical Trial Registration (UMIN000026363). Registered 31 May 2017, https://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000026363 . The study was registered prospectively.

DOI： 10.1186/s12876-022-02408-5

Effects of steroid use for stenosis prevention after endoscopic submucosal dissection for cervical esophageal cancer. Reviewed

Koichi Muroi, Naomi Kakushima, Kazuhiro Furukawa, Satoshi Furune, Nobuhito Ito, Takashi Hirose, Eri Ishikawa, Yasuyuki Mizutani, Tsunaki Sawada, Keiko Maeda, Takeshi Yamamura, Takuya Ishikawa, Eizaburo Ohno, Masanao Nakamura, Hiroki Kawashima, Kohei Funasaka, Ryoji Miyahara, Mitsuhiro Fujishiro

International journal of clinical oncology Vol. 27 ( 5 ) page： 940 - 947 2022.5

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

BACKGROUND AND AIM: Esophageal stenosis is a serious complication after endoscopic submucosal dissection (ESD) for thoracic esophageal cancer (TEC), and steroid has been applied for stenosis prevention. However, the rate of stenosis and effect of steroid for ESD of cervical esophageal cancer (CEC) remain unknown. The aim was to clarify the rate and managements of post-ESD stenosis for CEC. METHODS: A total of 325 lesions with 272 patients who underwent ESD for esophageal cancers were enrolled and were divided to the CEC group (43 lesions) or the TEC group (282 lesions). Patient characteristics, clinicopathological features, procedure-related outcomes of esophageal ESD, stenosis rate and clinical outcome of steroid use cases were evaluated. RESULTS: More patients in the CEC group received preventive steroid treatment compared to the TEC group (37.2% vs 14.5%, P = 0.001). The rate of post-ESD stenosis tended to be higher in the CEC group (11.6%) than in the TEC group (6.7%). For cases of 3/4 ≤ of circumference, local injection with oral steroid had lower stenosis rate than local injection only in both groups (CEC 40% vs 100%, TEC 30.7% vs 56.3%). More sessions and longer duration of dilation were needed to release the stenosis in the CEC group (20 times vs. 5 times, P = 0.015; 196 days vs. 55 days, P = 0.043). CONCLUSION: The post-ESD stenosis rate of CEC tended to be higher than that of TEC. More intensive preventive measures for post-ESD stenosis may be needed for CEC than TEC.

DOI： 10.1007/s10147-022-02139-3

Gelsolin as a Potential Biomarker for Endoscopic Activity and Mucosal Healing in Ulcerative Colitis. Reviewed International journal

Keiko Maeda, Masanao Nakamura, Takeshi Yamamura, Tsunaki Sawada, Eri Ishikawa, Akina Oishi, Shuji Ikegami, Naomi Kakushima, Kazuhiro Furukawa, Tadashi Iida, Yasuyuki Mizutani, Takuya Ishikawa, Eizaburo Ohno, Takashi Honda, Masatoshi Ishigami, Hiroki Kawashima

Biomedicines Vol. 10 ( 4 ) 2022.4

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

The therapeutic goal in ulcerative colitis is mucosal healing, which requires improved non-invasive biomarkers to evaluate disease activity. Gelsolin is associated with several autoimmune diseases, and here, we aimed to analyze its usefulness as a serological biomarker for clinical and endoscopic activities in ulcerative colitis. Patients with ulcerative colitis (n = 138) who had undergone blood tests and colonoscopy were included. Serum gelsolin was measured using enzyme-linked immunosorbent assay, and correlation between the gelsolin level and clinical and endoscopic activities was examined. The serum gelsolin level in patients with ulcerative colitis was significantly lower than that in healthy subjects, and it decreased in proportion to increasing Mayo score and Mayo endoscopic subscore. The area under the curve for correlation between clinical and endoscopic remission and serum gelsolin level was higher than that for C-reactive protein. Furthermore, in C-reactive protein-negative patients, the serum gelsolin level was lower in the active phase than in remission. Our findings indicate that the serum gelsolin level correlates with clinical and endoscopic activities in ulcerative colitis, has a higher sensitivity and specificity than C-reactive protein, and can detect mucosal healing, suggesting that gelsolin can be used as a biomarker for ulcerative colitis.

DOI： 10.3390/biomedicines10040872

Diagnostic performance of endoscopic classifications for neoplastic lesions in patients with ulcerative colitis: A retrospective case-control study. Reviewed International journal

Yuichi Kida, Takeshi Yamamura, Keiko Maeda, Tsunaki Sawada, Eri Ishikawa, Yasuyuki Mizutani, Naomi Kakushima, Kazuhiro Furukawa, Takuya Ishikawa, Eizaburo Ohno, Hiroki Kawashima, Masanao Nakamura, Masatoshi Ishigami, Mitsuhiro Fujishiro

World journal of gastroenterology Vol. 28 ( 10 ) page： 1055 - 1066 2022.3

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

BACKGROUND: It is unclear whether the Japan Narrow-Band Imaging Expert Team (JNET) classification and pit pattern classification are applicable for diagnosing neoplastic lesions in patients with ulcerative colitis (UC). AIM: To clarify the diagnostic performance of these classifications for neoplastic lesions in patients with UC. METHODS: This study was conducted as a single-center, retrospective case-control study. Twenty-one lesions in 19 patients with UC-associated neoplasms (UCAN) and 23 lesions in 22 UC patients with sporadic neoplasms (SN), evaluated by magnifying image-enhanced endoscopy, were retrospectively and separately assessed by six endoscopists (three experts, three non-experts), using the JNET and pit pattern classifications. The results were compared with the pathological diagnoses to evaluate the diagnostic performance. Inter- and intra-observer agreements were calculated. RESULTS: In this study, JNET type 2A and pit pattern type III/IV were used as indicators of low-grade dysplasia, JNET type 2B and pit pattern type VI low irregularity were used as indicators of high-grade dysplasia to shallow submucosal invasive carcinoma, JNET type 3 and pit pattern type VI high irregularity/VN were used as indicators of deep submucosal invasive carcinoma. In the UCAN group, JNET type 2A and pit pattern type III/IV had a low positive predictive value (PPV; 50.0% and 40.0%, respectively); however, they had a high negative predictive value (NPV; 94.7% and 100%, respectively). Conversely, in the SN group, JNET type 2A and pit pattern type III/IV had a high PPV (100% for both) but a low NPV (63.6% and 77.8%, respectively). In both groups, JNET type 3 and pit pattern type VI-high irregularity/VN showed high specificity. The inter-observer agreement of JNET classification and pit pattern classification for UCAN among experts were 0.401 and 0.364, in the same manner for SN, 0.666 and 0.597, respectively. The intra-observer agreements of JNET classification and pit pattern classification for UCAN among experts were 0.387, 0.454, for SN, 0.803 and 0.567, respectively. CONCLUSION: The accuracy of endoscopic diagnosis using both classifications was lower for UCAN than for SN. Endoscopic diagnosis of UCAN tended to be underestimated compared with the pathological results.

DOI： 10.3748/wjg.v28.i10.1055

Artificial intelligence-based diagnosis of upper gastrointestinal subepithelial lesions on endoscopic ultrasonography images. Reviewed

Keiko Hirai, Takamichi Kuwahara, Kazuhiro Furukawa, Naomi Kakushima, Satoshi Furune, Hideko Yamamoto, Takahiro Marukawa, Hiromitsu Asai, Kenichi Matsui, Yoji Sasaki, Daisuke Sakai, Koji Yamada, Takahiro Nishikawa, Daijuro Hayashi, Tomohiko Obayashi, Takuma Komiyama, Eri Ishikawa, Tsunaki Sawada, Keiko Maeda, Takeshi Yamamura, Takuya Ishikawa, Eizaburo Ohno, Masanao Nakamura, Hiroki Kawashima, Masatoshi Ishigami, Mitsuhiro Fujishiro

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association Vol. 25 ( 2 ) page： 382 - 391 2022.3

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

BACKGROUND: Endoscopic ultrasonography (EUS) is useful for the differential diagnosis of subepithelial lesions (SELs); however, not all of them are easy to distinguish. Gastrointestinal stromal tumors (GISTs) are the commonest SELs, are considered potentially malignant, and differentiating them from benign SELs is important. Artificial intelligence (AI) using deep learning has developed remarkably in the medical field. This study aimed to investigate the efficacy of an AI system for classifying SELs on EUS images. METHODS: EUS images of pathologically confirmed upper gastrointestinal SELs (GIST, leiomyoma, schwannoma, neuroendocrine tumor [NET], and ectopic pancreas) were collected from 12 hospitals. These images were divided into development and test datasets in the ratio of 4:1 using random sampling; the development dataset was divided into training and validation datasets. The same test dataset was diagnosed by two experts and two non-experts. RESULTS: A total of 16,110 images were collected from 631 cases for the development and test datasets. The accuracy of the AI system for the five-category classification (GIST, leiomyoma, schwannoma, NET, and ectopic pancreas) was 86.1%, which was significantly higher than that of all endoscopists. The sensitivity, specificity, and accuracy of the AI system for differentiating GISTs from non-GISTs were 98.8%, 67.6%, and 89.3%, respectively. Its sensitivity and accuracy were significantly higher than those of all the endoscopists. CONCLUSION: The AI system, classifying SELs, showed higher diagnostic performance than that of the experts and may assist in improving the diagnosis of SELs in clinical practice.

DOI： 10.1007/s10120-021-01261-x

Fecal incontinence and oral regurgitation during duodenal endoscopic submucosal dissection using the water pressure method. Reviewed International journal

Yoshihisa Takada, Takashi Hirose, Kazuki Nishida, Naomi Kakushima, Kazuhiro Furukawa, Satoshi Furune, Eri Ishikawa, Tsunaki Sawada, Keiko Maeda, Takeshi Yamamura, Takuya Ishikawa, Eizaburo Ohno, Masanao Nakamura, Takashi Honda, Masatoshi Ishigami, Hiroki Kawashima, Mitsuhiro Fujishiro

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society Vol. 34 ( 3 ) page： 526 - 534 2022.3

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

OBJECTIVES: Endoscopic submucosal dissection (ESD) in the duodenum is challenging. The water pressure method (WP-ESD) has been developed with a decreased rate of perforation. However, details of perioperative adverse events of WP-ESD are unknown. The purpose of this study was to clarify the frequency and related factors of fecal incontinence and oral regurgitation during WP-ESD. METHODS: A chart-based retrospective analysis was performed on 43 patients who underwent duodenal WP-ESD. The saline volume given into the body was calculated in all cases. All adverse events during WP-ESD until 6 weeks were extracted, and factors related to intraoperative fecal incontinence or oral regurgitation were analyzed. The frequency of fecal incontinence and oral regurgitation was also compared to those of 83 conventional ESD cases. RESULTS: In WP-ESD, intraoperative fecal incontinence occurred in 12 (28%), oral regurgitation in six (14%), and aspiration pneumonia in one patient. For fecal incontinence, the infusion speed (saline volume divided by resection time) around 17 mL/min was a significant factor in multivariable analysis. For oral regurgitation, only tumor size was a significant factor in univariate analysis (P = 0.027). Significant difference was observed in the frequency of fecal incontinence between WP-ESD and conventional ESD (28% vs. 0%, P < 0.001), but no difference was observed in oral regurgitation or aspiration pneumonia. CONCLUSIONS: Intraoperative fecal incontinence is a unique adverse event of WP-ESD related to the infusion speed. WP-ESD did not pose a risk for oral regurgitation, but we should be aware of the risk in large tumor cases.

DOI： 10.1111/den.14070

今月の主題炎症性腸疾患の粘膜治癒を再考する主題 Crohn病における小腸粘膜治癒評価の意義-小腸カプセル内視鏡の立場から

中村正直, 山村健史, 前田啓子, 澤田つな騎, 石川恵里, 角嶋直美, 古川和宏, 飯田忠, 水谷泰之, 石川卓哉, 大野栄三郎, 川嶋啓揮, 藤城光弘

胃と腸 Vol. 57 ( 2 ) page： 183 - 189 2022.2

Depletion of the apical endosome in response to viruses and bacterial toxins provides cell-autonomous host defense at mucosal surfaces. Reviewed International journal

Keiko Maeda, Nicholas C Zachos, Megan H Orzalli, Stefanie S Schmieder, Denis Chang, Katlynn Bugda Gwilt, Michele Doucet, Nicholas W Baetz, Sun Lee, Sue E Crawford, Mary K Estes, Jonathan C Kagan, Jerrold R Turner, Wayne I Lencer

Cell host & microbe Vol. 30 ( 2 ) page： 216 - + 2022.2

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

Polarized epithelial cells form an essential barrier against infection at mucosal surfaces. Many pathogens breach this barrier to cause disease, often by co-opting cellular endocytosis mechanisms to enter the cell through the lumenal (apical) cell surface. We recently discovered that the loss of the cell polarity gene PARD6B selectively diminishes apical endosome function. Here, we find that in response to the entry of certain viruses and bacterial toxins into the epithelial cells via the apical membrane, PARD6B and aPKC, two components of the PARD6B-aPKC-Cdc42 apical polarity complex, undergo rapid proteasome-dependent degradation. The perturbation of apical membrane glycosphingolipids by toxin- or virus-binding initiates degradation of PARD6B. The loss of PARD6B causes the depletion of apical endosome function and renders the cell resistant to further infection from the lumenal cell surface, thus enabling a form of cell-autonomous host defense.

DOI： 10.1016/j.chom.2021.12.011

Initial experience of tofacitinib for treating refractory moderate-to-severe ulcerative colitis. Reviewed

Masanao Nakamura, Takeshi Yamamura, Keiko Maeda, Tsunaki Sawada, Yasuyuki Mizutani, Eri Ishikawa, Takuya Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Eizaburo Ohno, Hiroki Kawashima, Takashi Honda, Masatoshi Ishigami, Mitsuhiro Fujishiro

Nagoya journal of medical science Vol. 84 ( 1 ) page： 169 - 179 2022.2

Language：English

Ulcerative colitis (UC) is an incurable, chronic inflammatory disease of the large bowel whose etiology and pathogenesis have not yet been comprehensively explained. Tofacitinib is a small molecule Janus kinase inhibitor that was introduced for treating refractory UC. We aimed to examine the efficacy and safety of tofacitinib for the treatment of 18 patients with UC. Continuous treatment rates were 50, 38, and 33% at 8, 24, and 52 weeks, respectively. Overall, 83.3% of these patients showed tumor necrosis factor (TNF) antibody failure status. When the effective status was defined as a Lichtiger index (LI) that decreased by 3 points or more or was less than 4 points and remission status was defined as an LI less than 4 points, the effective and remission rates (%) at 2, 8, and 16 weeks were 55.5 (10/18) and 22.2 (4/18), 38.8 (7/18) and 33.3 (6/18), and 38.8 (7/18) and 38.8 (7/18), respectively. Background characteristics of 2-week responders and non-responders were compared. C-reactive protein level in responders was significantly lower than that in non-responders, and the hemoglobin level in responders was significantly higher than that in non-responders. This study provides preliminary results of the effectiveness of tofacitinib even for TNF antibody and tacrolimus failure patients.

DOI： 10.18999/nagjms.84.1.169

Evaluation of ulcerative colitis activity using transabdominal ultrasound shear wave elastography. Reviewed International journal

Kenta Yamada, Takuya Ishikawa, Hiroki Kawashima, Eizaburo Ohno, Tadashi Iida, Eri Ishikawa, Yasuyuki Mizutani, Tsunaki Sawada, Keiko Maeda, Takeshi Yamamura, Naomi Kakushima, Kazuhiro Furukawa, Masanao Nakamura, Masatoshi Ishigami, Mitsuhiro Fujishiro

Quantitative imaging in medicine and surgery Vol. 12 ( 1 ) page： 618 - 626 2022.1

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

BACKGROUND: Transabdominal ultrasound (US) has been reported to be effective in the evaluation of ulcerative colitis (UC). US can measure shear wave elastography (SWE) and shear wave dispersion (SWD), which may be correlated with inflammation and necrosis. We aimed to investigate the relationship between UC activity and SWE and SWD. METHODS: Patients with UC who underwent US within 2 days before or after a colonoscopy between April 2019 and March 2020 were included. SWE and SWD were measured in the sigmoid colon; the correlations of SWE and SWD with the Lichtiger index and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) were investigated. We also compared SWE and SWD between patients with mucosal healing and those in the active phase according to the UCEIS. RESULTS: Twenty-six UC patients were enrolled. The median Lichtiger index, UCEIS, SWE values, and SWD values were 8 [interquartile range (IQR), 5.3-10.8], 4 (IQR, 3.3-5), 1.69 (IQR, 1.49-2.16) m/s, and 11.9 (IQR, 10.9-13.3) (m/s)/kHz, respectively. The Lichtiger index and UCEIS were negatively correlated with the SWE values (rs=-0.404 and rs=-0.506) but not with the SWD values (rs=0.004 and rs=0.002). The SWE values differed significantly between the mucosal healing and active phase groups [2.40 (IQR, 2.18-3.38) vs. 1.62 (IQR, 1.44-1.95) m/s, P=0.007], whereas the SWD values did not [13.1 (IQR, 7.05-21.6) vs. 11.9 (IQR, 11.1-13.2) (m/s)/kHz, P=0.918]. CONCLUSIONS: SWE may be useful for the evaluation of UC activity and could be a noninvasive method of assessing disease severity.

DOI： 10.21037/qims-21-403

Preliminary Comparison of Endoscopic Brush and Net Catheters as the Sampling Tool to Analyze the Intestinal Mucus in the Rectum with Ulcerative Colitis Patients. International journal

Masanao Nakamura, Keiko Maeda, Kenta Yamamoto, Takeshi Yamamura, Tsunaki Sawada, Eri Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Tadashi Iida, Yasuyuki Mizutani, Takuya Ishikawa, Eizaburo Ohno, Takashi Honda, Masatoshi Ishigami, Hiroki Kawashima

Digestion Vol. 103 ( 3 ) page： 232 - 243 2022

Language：English

BACKGROUND: The pathophysiology of ulcerative colitis (UC) remains unclear, but early lesions on the colorectal mucosal surface may play an important role in its etiology. Intestinal mucus samples, including inner and outer layers, are collected by net or brush catheters, but the quality of the samples obtained by each method has not been fully investigated. OBJECTIVE: The purpose of this study was to compare the microbiome and protein content of intestinal mucus collected by net and brush catheters during colonoscopy. METHODS: Intestinal mucus samples from the lower rectum of 4 patients with UC were collected using a net catheter, a brush catheter, and intestinal fluid suction. Microbiome and protein content were analyzed using 16S rRNA gene sequencing and mass spectrometry. RESULTS: The patients demonstrated significant differences in microbiome alpha diversity (p < 0.05), but this difference was not observed between the sampling methods. Net catheter samples demonstrated higher total protein concentrations than brush catheter samples. The brush catheter group had more Lachnospira, a butyrate-producing bacterium, when compared to the net group. The brush catheter group also had more oral bacteria of Staphylococcus and Dialister in those with active phase when compared to the net group. CONCLUSIONS: Brush catheters are more likely to collect the intestinal mucus inner layer, whereas net catheters are more likely to collect larger samples that include the outer mucus layer, as well as the intestinal fluid. Two sampling methods with different types of collection of the mucosa may lead to different results among patients with mucosal vulnerabilities.

DOI： 10.1159/000521929

小腸Dieulafoy病変（矢野-山本分類Type 2a）の診断と治療についての臨床的検討

中村正直, 山村健史, 前田啓子, 澤田つな騎, 石川恵里, 川嶋啓揮

日本小腸学会学術集会プログラム・抄録集 Vol. 6 ( 0 ) page： 65 - 65 2022

Language：Japanese Publisher：日本小腸学会

【背景】小腸Dieulafoy病変は、内視鏡観察時に自然止血されている可能性があるため確定診断と治療が遅れる傾向を有する。一方では、Dieulafoy病変の臨床的特徴を把握しておくことによって診断のタイミングや治療戦略を事前に検討できるかもしれない。本研究の目的は、当院で経験された同病変の臨床的特徴を後方視的に調査し、その最適な診断と治療につき検討することであった。【対象・方法】対象は当院において2003年6月から2022年7月の間に小腸出血が疑われダブルバルーン内視鏡（以下DBE）を施行し、Dieulafoy病変と診断、内視鏡治療を受けた36例であった。本研究におけるDieulafoy病変の定義は、粘膜面の変化は露出血管部のみとし、付着する血栓を認める場合と露出血管からの噴出性かそれに準じる活動性出血を認める場合とした。臨床的背景、治療方法などを検討した。【結果】男性/女性は19/17例、平均年齢は71±10歳であった。33例でなんらかの基礎疾患を有していた。抗血栓薬の使用を19例で認め、ワーファリン10例、バイアスピリン7例（重複あり）の順で多かった。累計の出血エピソードは中央値で2回（1-18回）であった。最低血中ヘモグロビン値は5.9±1.7g/dl、赤血球輸血は2例以外の全例で行われていた。症状発現からDBEまでは中央値18日（2-63日）であった。DBE時の所見について、病変部位は深部十二指腸、上部空腸、中部空腸、下部空腸、中部回腸、下部回腸で各々3、18、8、2、2,6例で認められた（重複あり）。治療はクリッピング34例、APC凝固2例であった。偶発症は再出血10例（27.7％）、急性膵炎1例であった。【結語】小腸Dieulafoy病変は診断に苦慮し、治療までに時間と輸血処置などを多く要していた。本病変が疑われた際には早めの内視鏡検査が検討される。

DOI： 10.32264/shocho.6.0_65

Immunoproliferative Small Intestinal Disease Diagnosed by Double-balloon Endoscopy with Biopsy Sampling. Reviewed

Miguel Ricardo Rodríguez Meza, Masanao Nakamura, Takeshi Yamamura, Keiko Maeda, Tsunaki Sawada, Eri Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Eizaburo Ohno, Takashi Honda, Hiroki Kawashima, Masatoshi Ishigami

Internal medicine (Tokyo, Japan) Vol. 61 ( 17 ) page： 2593 - 2599 2022

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

We herein report an 80-year-old man diagnosed with immunoproliferative small intestine disease (IPSID) via small bowel endoscopy with a biopsy. He developed persistent diarrhea and subsequently presented with hypoproteinemia and moderate anemia. Transanal double-balloon endoscopy showed prominent villous edema in the middle and lower ileum, while a histological examination showed high lymphocyte/plasma cell infiltration in the mucosal layer. Furthermore, an immunostaining analysis showed that CD3 and CD20 were partially positive, while CD138 was diffusely positive. Immunoglobulin A positivity was also observed. He was diagnosed with IPSID and received a nutritional agent and minocycline. After three months, the patients' symptoms improved.

DOI： 10.2169/internalmedicine.8847-21

Real-world local recurrence rate after cold polypectomy in colorectal polyps less than 10 mm using propensity score matching. International journal

Masashi Saito, Takeshi Yamamura, Masanao Nakamura, Keiko Maeda, Tsunaki Sawada, Eri Ishikawa, Yasuyuki Mizutani, Takuya Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Eizaburo Ohno, Hiroki Kawashima, Masatoshi Ishigami, Mitsuhiro Fujishiro

World journal of gastroenterology Vol. 27 ( 47 ) page： 8182 - 8193 2021.12

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

BACKGROUND: Cold polypectomy (CP) is a simple and safe procedure for polyps less than 10 mm in size; however, there is concern about local recurrence following CP because of unidentified margins of excised specimens and the lack of tumor suppression effect by coagulation. Some clinical trials have evaluated local persistent recurrence; their results suggest that a higher rate of local recurrence has not been documented so far. There were few reports that observed the course over long periods of time after CP in clinical practice. AIM: To evaluate the presence of local recurrence following CP and hot polypectomy (HP) using propensity score matching. METHODS: We analyzed 275 patients who underwent polypectomy for non-pedunculated colorectal polyps less than 10 mm (959 Lesions) between October 2016 and 2017 and underwent follow-up endoscopy subsequently. We divided them into the CP group (706 Lesions), wherein CP was performed, and the HP group (253 Lesions), wherein HP was performed. Using propensity score matching, we extracted 215 Lesions in each group and evaluated the local recurrence and content of CP in the real clinic and adverse events using medical records. RESULTS: After propensity score matching, there were no significant differences in the patients' and their endoscopic background (age, use of antithrombotics, indications, size, morphology, location of polyps, and polypectomy device) between the groups. The mean duration between colorectal polypectomy and the next follow-up colonoscopy was 17.5 ± 7.1 (range, 6-39) mo in the CP group and 15.7 ± 6.0 (range, 6-35) mo in the HP group, which was significantly longer in the CP group (P = 0.005). The local recurrence rate was 0.93% in the CP group and 0.93% in the HP group, without a significant difference (P = 0.688). Additionally, no differences were observed in the macroscopic en bloc resection rate, histopathological complete resection rate, and pathological results between the groups. Adverse events did not occur in either group. CONCLUSION: Local recurrence after CP was equivalent to that following HP in clinical practice. CP is useful and safe in the treatment of non-pedunculated polyps of less than 10 mm.

DOI： 10.3748/wjg.v27.i47.8182

特集 Cold polypectomyの課題 4.症例からみえた課題(1)小腸ポリープに対するcold polypectomy

山村健史, 中村正直, 前田啓子, 澤田つな騎, 石川恵里, 角嶋直美, 古川和宏, 川嶋啓揮

臨床消化器内科 Vol. 37 ( 1 ) page： 93 - 96 2021.12

Clinical characteristics of gastrointestinal immune-related adverse events of immune checkpoint inhibitors and their association with survival. Reviewed International journal

Kentaro Yamada, Tsunaki Sawada, Masanao Nakamura, Takeshi Yamamura, Keiko Maeda, Eri Ishikawa, Tadashi Iida, Yasuyuki Mizutani, Naomi Kakushima, Takuya Ishikawa, Kazuhiro Furukawa, Eizaburo Ohno, Takashi Honda, Hiroki Kawashima, Masatoshi Ishigami, Satoshi Furune, Tetsunari Hase, Kenji Yokota, Osamu Maeda, Naozumi Hashimoto, Masashi Akiyama, Yuichi Ando, Mitsuhiro Fujishiro

World journal of gastroenterology Vol. 27 ( 41 ) page： 7190 - 7206 2021.11

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

BACKGROUND: Despite the popularity of immune checkpoint inhibitors (ICIs) in the treatment of advanced cancer, patients often develop gastrointestinal (GI) and non-GI immune-related adverse events (irAEs). The clinical characteristics and survival outcomes of GI-irAEs have not been fully elucidated in previous reports. This necessitates the evaluation of the impact of GI-irAEs on patients receiving ICI treatment. AIM: To evaluate the clinical characteristics of GI-irAEs and their impact on survival in patients treated with ICIs. METHODS: In this single-center, retrospective, observational study, we reviewed the records of 661 patients who received ICIs for various cancers at Nagoya University Hospital from September 2014 to August 2020. We analyzed the clinical characteristics of patients who received ICI treatment. We also evaluated the correlation between GI-irAE development and prognosis in non-small cell lung cancer (LC) and malignant melanoma (MM). Kaplan-Meier analysis was used to compare the median overall survival (OS). Multivariate Cox proportional hazards models were used to identify prognostic factors. A P value < 0.05 was considered statistically significant. RESULTS: GI-irAEs occurred in 34 of 605 patients (5.6%) treated with an anti-programmed cell death-1/programmed death-ligand 1 (anti-PD-1/PD-L1) antibody alone and in nine of 56 patients (16.1%) treated with an anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody alone or a combination of anti-PD-1 and anti-CTLA-4 antibodies. The cumulative incidence and median daily diarrhea frequency were significantly higher in patients receiving anti-CTLA-4 antibodies (P < 0.05). In 130 patients with MM, OS was significantly prolonged in the group that continued ICI treatment despite the development of GI-irAEs compared to the group that did not experience GI-irAEs (P = 0.035). In contrast, in 209 patients with non-small cell LC, there was no significant difference in OS between the groups. The multivariate analyses showed that a performance status of 2-3 (hazard ratio: 2.406; 95% confidence interval: 1.125-5.147; P = 0.024) was an independent predictive factor for OS in patients with MM. CONCLUSION: Patients receiving anti-CTLA-4 antibodies develop GI-irAEs more frequently and with higher severity than those receiving anti-PD-1/PD-L1 antibodies. Continuing ICI treatment in patients with MM with GI-irAEs have better OS.

DOI： 10.3748/wjg.v27.i41.7190

Endocytoscopy Is Useful for the Diagnosis of Superficial Nonampullary Duodenal Epithelial Tumors. Reviewed International journal

Takashi Hirose, Naomi Kakushima, Kazuhiro Furukawa, Satoshi Furune, Eri Ishikawa, Tsunaki Sawada, Keiko Maeda, Takeshi Yamamura, Takuya Ishikawa, Eizaburo Ohno, Masanao Nakamura, Kazuki Nishida, Takio Yokoi, Hiroki Kawashima, Mitsuhiro Fujishiro

Digestion Vol. 102 ( 6 ) page： 895 - 902 2021.11

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

INTRODUCTION: Endoscopic criteria for the diagnosis of superficial nonampullary duodenal epithelial tumors (SNADETs) are lacking. The aim of this study was to explore the usefulness of endocytoscopy (ECS) in the duodenum. METHODS: A total of 77 ECS images stained by methylene blue and 58 images with double staining of methylene blue and crystal violet were obtained from 20 patients. Images were classified into 3 grades based on nuclear and villi atypia: EC A, B, and C. Diagnostic performance of ECS classification to predict histology and interobserver agreement was evaluated. The performance was compared between staining methods and ×520 or ×936 zoom. RESULTS: With methylene blue staining, high rates of accuracy, sensitivity, specificity, and positive predictive value (PPV) over 90% were achieved for tumor and nontumor diagnosis as assessed by EC A versus EC B. High rates of accuracy, sensitivity, PPV, and negative predictive value over 90% were achieved for the differentiation between the diagnosis of the Vienna category 3 and 4/5 as assessed by EC B versus C. The accuracy rate of interpreting ECS images with ×936 zoom among 10 endoscopists was 82%, and the interobserver agreement rate was 0.803 (Kendall's coefficient of concordance). In the ×936 zoom group, methylene blue staining was significantly associated with higher accuracy rate (odds ratio 1.76 [1.06-2.92], p value 0.0297). No benefit was observed by double staining. CONCLUSIONS: ECS diagnosis with methylene blue provides a high accuracy rate and good interobserver agreement to predict histology of SNADETs.

DOI： 10.1159/000516512

Detection of Colorectal Neoplasms Using Linked Color Imaging: A Prospective, Randomized, Tandem Colonoscopy Trial. Reviewed International journal

Issei Hasegawa, Takeshi Yamamura, Hiroto Suzuki, Keiko Maeda, Tsunaki Sawada, Yasuyuki Mizutani, Eri Ishikawa, Takuya Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Eizaburo Ohno, Hiroki Kawashima, Masanao Nakamura, Mitsuhiro Fujishiro

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Vol. 19 ( 8 ) page： 1708 - + 2021.8

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

BACKGROUND AND AIMS: A higher adenoma detection rate (ADR) has been shown to be related to a lower incidence and mortality of colorectal cancer. We analyzed the efficacy of linked color imaging (LCI) by assessing the detection, miss, and visibility of various featured adenomas as compared with white light imaging (WLI). METHODS: This was a prospective, randomized, tandem trial. The participants were randomly assigned to 2 groups: first observation by LCI, then second observation by WLI (LCI group); or both observations by WLI (WLI group). Suspected neoplastic lesions were resected after magnifying image-enhanced endoscopy. The primary outcome was to compare the ADR during the first observation. Secondary outcomes included evaluation of adenoma miss rate (AMR) and visibility score. RESULTS: A total of 780 patients were randomized, 700 of whom were included in the final analysis. The ADR was 69.6% and 63.2% in the LCI and WLI groups, respectively, with no significant difference. However, LCI improved the average ADR in low-detectors compared with high-detectors (76.0% vs 55.1%; P < .001). Total AMR was 20.6% in the LCI group, which was significantly lower than that in the WLI group (31.1%) (P < .001). AMR in the LCI group was significantly lower, especially for diminutive adenomas (23.4% vs 35.1%; P < .001) and nonpolypoid lesions (25.6% vs 37.9%; P < .001) compared with the WLI group. CONCLUSION: Although both methods provided a similar ADR, LCI had a lower AMR than WLI. LCI could benefit endoscopists with lower ADR, an observation that warrants additional study. (UMIN Clinical Trials Registry, Number: UMIN000026359).

DOI： 10.1016/j.cgh.2021.04.004

Difference of efficacy for small bowel lesion in Crohn

Sawada, T; Nakamura, M; Yamamura, T; Maeda, K; Ishikawa, E; Fujishiro, M

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY Vol. 36 page： 116 - 116 2021.8

An evaluation of resectability among endoscopic treatment methods for rectal neuroendocrine tumors <10 mm. Reviewed International journal

Kazuhiro Toriyama, Takeshi Yamamura, Masanao Nakamura, Keiko Maeda, Tsunaki Sawada, Yasuyuki Mizutani, Eri Ishikawa, Kazuhiro Furukawa, Takuya Ishikawa, Eizaburo Ohno, Hiroki Kawashima, Mitsuhiro Fujishiro

Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology Vol. 22 ( 2 ) page： 104 - 110 2021.6

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

BACKGROUND AND STUDY AIMS: With respect to rectal neuroendocrine tumor (NET) resection, it remains unclear which of the following methods is the most effective: conventional endoscopic mucosal resection (cEMR), EMR using a fitted cap (EMR-C), EMR with a ligation band device (EMR-L), or endoscopic submucosal dissection (ESD). Thus, in this study, we aim to retrospectively evaluate the most effective endoscopic resection for rectal NETs < 10 mm. PATIENTS AND METHODS: In total, 61 consecutive patients with primary rectal NETs < 10 mm in diameter were included in this study; they were then divided into three groups: those with cEMR; those with modified EMR (mEMR) involving EMR-C and EMR-L; and those with ESD. The primary endpoint was to evaluate the difference in the complete en bloc resection rate. The secondary endpoint was to investigate differences in procedure time and complications. RESULTS: Among the three groups, a significant difference was found in procedure time (cEMR vs ESD, P < .01; mEMR vs ESD, P < .01), en bloc resection rate (cEMR vs mEMR, P = .015), tumor size (mEMR vs ESD, P < .01), percentage of tumor diameter ≥ 5 mm (mEMR vs ESD, P < .01), and complete en bloc resection rate (cEMR vs mEMR, P = .014). Meanwhile, no significant difference was noted in terms of complication rate among the three groups. CONCLUSION: The mEMR was the most suitable resection method for rectal NETs < 10 mm with respect to the risks and benefits from procedure-related factors, such as complete en bloc resection rate, procedure time, and complication rate.

DOI： 10.1016/j.ajg.2021.05.007

Diagnostic yield of colon capsule endoscopy for Crohn's disease lesions in the whole gastrointestinal tract

Yamada Keisaku, Nakamura Masanao, Yamamura Takeshi, Maeda Keiko, Sawada Tsunaki, Mizutani Yasuyuki, Ishikawa Eri, Ishikawa Takuya, Kakushima Naomi, Furukawa Kazuhiro, Ohno Eizaburo, Kawashima Hiroki, Honda Takashi, Ishigami Masatoshi, Fujishiro Mitsuhiro

BMC GASTROENTEROLOGY Vol. 21 ( 1 ) 2021.2

Ustekinumab is effective against small bowel lesions in Crohn's disease: two case reports

Murate Kentaro, Nakamura Masanao, Yamamura Takeshi, Maeda Keiko, Sawada Tsunaki, Mizutani Yasuyuki, Ishikawa Eri, Kakushima Naomi, Furukawa Kazuhiro, Ohno Eizaburo, Honda Takashi, Kawashima Hiroki, Ishigami Masatoshi, Fujishiro Mitsuhiro

CLINICAL JOURNAL OF GASTROENTEROLOGY Vol. 14 ( 1 ) page： 129 - 135 2021.2

Gastrointestinal tract metastasis of lung cancer: The PD-L1 expression and correlated clinicopathological variables

Ishikawa Eri, Nakaguro Masato, Nakamura Masanao, Yamamura Takeshi, Sawada Tsunaki, Mizutani Yasuyuki, Maeda Keiko, Furukawa Kazuhiro, Shimoyama Yoshie, Kawashima Hiroki, Fujishiro Mitsuhiro

PATHOLOGY INTERNATIONAL Vol. 71 ( 1 ) page： 33 - 41 2021.1

The microbiome can predict mucosal healing in small intestine in patients with Crohn's disease

Hattori Shun, Nakamura Masanao, Yamamura Takeshi, Maeda Keiko, Sawada Tsunaki, Mizutani Yasuyuki, Yamamoto Kenta, Ishikawa Takuya, Furukawa Kazuhiro, Ohno Eizaburo, Honda Takashi, Kawashima Hiroki, Ishigami Masatoshi, Hirooka Yoshiki, Fujishiro Mitsuhiro

JOURNAL OF GASTROENTEROLOGY Vol. 55 ( 12 ) page： 1138 - 1149 2020.12

Endoscopic Ultrasound Elastography as a Novel Diagnostic Method for the Assessment of Hardness and Depth of Invasion in Colorectal Neoplasms

Esaki Masaya, Yamamura Takeshi, Nakamura Masanao, Maeda Keiko, Sawada Tsunaki, Mizutani Yasuyuki, Ishikawa Eri, Suzuki Hiroto, Kuno Takeshi, Yamada Kentaro, Hasegawa Issei, Ishikawa Takuya, Kakushima Naomi, Furukawa Kazuhiro, Ohno Eizaburo, Kawashima Hiroki, Hirooka Yoshiki, Fujishiro Mitsuhiro

DIGESTION 2020.11

Accuracy of carbon dioxide insufflation for endoscopic retrograde cholangiopancreatography using double-balloon endoscopy

Niwa Yoshiki, Nakamura Masanao, Kawashima Hiroki, Yamamura Takeshi, Maeda Keiko, Sawada Tsunaki, Mizutani Yasuyuki, Ishikawa Eri, Ishikawa Takuya, Kakushima Naomi, Furukawa Kazuhiro, Ohno Eizaburo, Honda Takashi, Ishigami Masatoshi, Fujishiro Mitsuhiro

WORLD JOURNAL OF GASTROENTEROLOGY Vol. 26 ( 42 ) page： 6669 - 6678 2020.11

Endoscopic Activity and Serum TNF-alpha Level at Baseline Are Associated With Clinical Response to Ustekinumab in Crohn's Disease Patients

Murate Kentaro, Maeda Keiko, Nakamura Masanao, Sugiyama Daisuke, Wada Hirotaka, Yamamura Takeshi, Sawada Tsunaki, Mizutani Yasuyuki, Ishikawa Takuya, Furukawa Kazuhiro, Ohno Eizaburo, Honda Takashi, Kawashima Hiroki, Miyahara Ryoji, Ishigami Masatoshi, Nishikawa Hiroyoshi, Fujishiro Mitsuhiro

INFLAMMATORY BOWEL DISEASES Vol. 26 ( 11 ) page： 1669 - 1681 2020.11

Mutation analysis of gastrointestinal stromal tumors using RNA obtained via endoscopic ultrasound-guided fine-needle aspiration

Funasaka Kohei, Miyahara Ryoji, Furukawa Kazuhiro, Sawada Tsunaki, Maeda Keiko, Yamamura Takeshi, Ishikawa Takuya, Ohno Eizaburo, Nakamura Masanao, Kawashima Hiroki, Hirooka Yoshiki, Ohmiya Naoki, Fujishiro Mitsuhiro

TRANSLATIONAL ONCOLOGY Vol. 13 ( 11 ) 2020.11

New modality for the quantitative evaluation of tissue elasticity using a forward-viewing radial-array echoendoscope for colorectal neoplasms

Esaki Masaya, Yamamura Takeshi, Nakamura Masanao, Maeda Keiko, Sawada Tsunaki, Mizutani Yasuyuki, Ishikawa Eri, Furukawa Kazuhiro, Kawashima Hiroki, Hirooka Yoshiki, Fujishiro Mitsuhiro

INTERNATIONAL JOURNAL OF COLORECTAL DISEASE 2020.10

A forward-viewing radial-array echoendoscope is useful for diagnosing the depth of colorectal neoplasia invasion

Kuno Takeshi, Yamamura Takeshi, Nakamura Masanao, Maeda Keiko, Sawada Tsunaki, Mizutani Yasuyuki, Esaki Masaya, Ishikawa Takuya, Furukawa Kazuhiro, Ohno Eizaburo, Kawashima Hiroki, Fujishiro Mitsuhiro

SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES 2020.9

診断に苦慮した広範囲胆管癌の1例

芳川昌功, 川嶋啓揮, 大野栄三郎, 石川卓哉, 小屋敏也, 田中浩敬, 酒井大輔, 飯田忠, 西尾亮, 鈴木博貴, 植月康太, 八鹿潤, 山田健太, 澤田つな騎, 前田啓子, 山村健史, 古川和宏, 舩坂好平, 中村正直, 宮原良二, 廣岡芳樹

肝胆膵治療研究会誌 Vol. 16 ( 1 ) page： 93 - 93 2020.9

表在型食道扁平上皮癌におけるLinked Color Imagingで観察される色情報と深達度および血管径との相関に関する検討

小林健一, 宮原良二, 舩坂好平, 古川和宏, 澤田つな騎, 前田啓子, 山村健史, 石川卓也, 大野栄三郎, 中村正直, 川嶋啓揮, 中黒匡人, 奥村結希, 廣岡芳樹, 藤城光弘

Gastroenterological Endoscopy Vol. 62 ( 9 ) page： 1624 - 1633 2020.9

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

【背景】食道扁平上皮癌の治療方針決定に正確な深達度診断が重要であるが,MM/SM1の正診率は低く解決すべき課題となっている.本研究の目的はLED光源を用いたLCIにおける食道表在癌に対する色と深達度の関連性について検討することである.【方法】表在型食道癌と診断された病変に対し白色光につづいてLCIで観察を行った.色合いの評価についてはCIE-L*a*b*空間を用いて色値を算出し,深達度ごとの癌部と非癌部の色差を算出した.血管径およびintrapapillary capillary loopの分岐角を病理的に算出し,色合いとの相関を検討した.【結果】48症例52病変が登録された.深達度別の正常と病変部の色差において,MM/SM1以深群ではEP/LPM群に比べて有意に色差が大きかった(P=0.025).血管径はb*値と弱い正の相関を認めた(相関係数=0.302,P=0.033).【結論】LED光源を用いたLCI観察は,表在型食道癌における深達度診断の向上に有用である可能性があるが,その有用性を示すのにはさらなる検討が必要である.(著者抄録)

特集クローン病小腸狭窄病変に対する内視鏡的バルーン拡張術─基本からピットフォールまで Ⅱ.クローン病小腸狭窄病変に対するバルーン拡張術(4)クローン病におけるバルーン拡張術のコツ　a.ダブルバルーン内視鏡の立場から

中村正直, 山村健史, 前田啓子, 澤田つな騎, 水谷泰之, 石川恵里, 古川和宏, 角嶋　直美, 藤城光弘

INTESTINE Vol. 24 ( 3 ) page： 197 - 202 2020.8

特集分子標的時代のIBD 診療 -IBD の寛解導入,寛解維持の実践 3.IBD 治療における寛解導入と寛解維持に関するトピック(5)UC 関連腫瘍の早期診断と治療

山村健史, 中村正直, 前田啓子, 澤田つな騎, 石川恵里, 喜田裕一, 古川和宏, 川嶋啓揮, 藤城光弘

臨床消化器内科 Vol. 35 ( 10 ) page： 1267 - 1273 2020.8

Subjective Symptoms in Patients with Eosinophilic Esophagitis Are Related to Esophageal Wall Thickness and Esophageal Body Pressure.

Muroi K, Kakushima N, Furukawa K, Ishikawa E, Sawada T, Ishikawa T, Maeda K, Yamamura T, Ohno E, Nakamura M, Kawashima H, Funasaka K, Miyahara R, Fujishiro M

Digestive diseases and sciences 2020.8

Filtrated Adipose Tissue-Derived Mesenchymal Stem Cell Lysate Ameliorates Experimental Acute Colitis in Mice.

Nishikawa T, Maeda K, Nakamura M, Yamamura T, Sawada T, Mizutani Y, Ito T, Ishikawa T, Furukawa K, Ohno E, Miyahara R, Kawashima H, Honda T, Ishigami M, Yamamoto T, Matsumoto S, Hotta Y, Fujishiro M

Digestive diseases and sciences 2020.6

Clinical Factors Associated with Missing Colorectal Polyp on Colon Capsule Endoscopy

Yamada Keisaku, Nakamura Masanao, Yamamura Takeshi, Maeda Keiko, Sawada Tsunaki, Mizutani Yasuyuki, Ishikawa Takuya, Furukawa Kazuhiro, Ohno Eizaburo, Miyahara Ryoji, Kawashima Hiroki, Hotta Naoki, Hirooka Yoshiki

DIGESTION Vol. 101 ( 3 ) page： 316-322 2020.5

Double-balloon endoscopic retrograde cholangiopancreatography for patients who underwent liver operation: A retrospective study.

Nishio R, Kawashima H, Nakamura M, Ohno E, Ishikawa T, Yamamura T, Maeda K, Sawada T, Tanaka H, Sakai D, Miyahara R, Ishigami M, Hirooka Y, Fujishiro M

World journal of gastroenterology Vol. 26 ( 10 ) page： 1056 - 1066 2020.3

Usefulness of Endoscopic Ultrasound Elastography Combined With the Strain Ratio in the Estimation of Treatment Effect in Autoimmune Pancreatitis.

Ishikawa T, Kawashima H, Ohno E, Tanaka H, Maeda K, Sawada T, Yamamura T, Furukawa K, Nakamura M, Miyahara R, Ishigami M, Fujishiro M

Pancreas Vol. 49 ( 2 ) page： E21 - E22 2020.2

Color information from linked color imaging is associated with invasion depth and vascular diameter in superficial esophageal squamous cell carcinoma

Kobayashi Kenichi, Miyahara Ryoji, Funasaka Kohei, Furukawa Kazuhiro, Sawada Tsunaki, Maeda Keiko, Yamamura Takeshi, Ishikawa Takuya, Ohno Eizaburo, Nakamura Masanao, Kawashima Hiroki, Nakaguro Masato, Okumura Yuki, Hirooka Yoshiki, Fujishiro Mitsuhiro

DIGESTIVE ENDOSCOPY Vol. 32 ( 1 ) page： 65 - 73 2020.1

A Case of Refractory Ulcerative Colitis Improved by Scheduled Combination Therapy of Vedolizumab and Granulocyte and Monocyte Adsorptive Apheresis.

Nakamura M, Yamamura T, Maeda K, Sawada T, Mizutani Y, Ishikawa E, Ohashi A, Kajikawa G, Furukawa K, Ohno E, Honda T, Kawashima H, Ishigami M, Fujishiro M

Internal medicine (Tokyo, Japan) Vol. 59 ( 23 ) page： 3009 - 3014 2020

Comparison of high-resolution manometry in patients complaining of dysphagia among patients with or without diabetes mellitus

Muroi K.

Digestion 2020

A Prospective Study of Factors Associated with Abdominal Pain in Patients during Unsedated Colonoscopy Using a Magnifying Endoscope.

Suzuki H, Nakamura M, Yamamura T, Maeda K, Sawada T, Mizutani Y, Ishikawa T, Furukawa K, Ohno E, Honda T, Kawashima H, Ishigami M, Fujishiro M

Internal medicine (Tokyo, Japan) Vol. 59 ( 15 ) page： 1795 - 1801 2020

単発性小腸Peutz-Jeghers型ポリープに関する臨床的検討

鳥山和浩, 中村正直, 山村健史, 前田啓子, 澤田つな騎, 水谷泰之, 石川恵里, 梶川豪, 村手健太郎, 喜田裕一, 江崎正哉, 濱崎元伸, 角嶋直美, 古川和宏, 藤城光弘

日本小腸学会学術集会プログラム・抄録集 Vol. 4 ( 0 ) page： 39 - 39 2020

Language：Japanese Publisher：日本小腸学会

【背景】Peutz-Jeghers症候群（PJS）は食道を除く全消化管において上皮の過形成と粘膜筋板のポリープ内への樹枝状増生を特徴とする過誤腫性ポリポーシスと皮膚、粘膜の色素斑を特徴とする常染色体優性遺伝性疾患である。一方、家族歴や皮膚、粘膜の色素沈着を伴わない単発性のPeutz-Jeghers型ポリープ（PJP）を認めることがあるが、その臨床的特徴に関する報告は少ないのが現状である。【目的】単発性小腸PJPにおける臨床的特徴を明らかにする。【対象】2007年4月から2020年5月までに当院で内視鏡治療を施行し、病理組織学的にPJPと診断された単発性小腸PJP16症例。【結果】レトロスペクティブにカルテ、内視鏡画像をレビューした。性別は男性10例、女性6例、診断時年齢中央値（範囲）は61（18-82）歳。診断契機は貧血7例、黒色便5例、腹痛1例、イレウス症状1例、他疾患精査時の偶発的発見が2例。原発部位は空腸14例、回腸2例で、腫瘍径中央値（範囲）は25（4-35）mm。切除したPJP全病変で病変内に悪性腫瘍の併存は認めなかった。癌の既往歴を有したのは6例（前立腺癌2例、舌癌1例、大腸癌1例、胃癌1例、子宮体癌1例）。観察期間中央値（範囲）は4.6（0.1-53.7）ヶ月で再発並びに関連死は認めなかった。【考察】単発性小腸PJPにおいては診断時の年齢が高く、発見契機としては出血関連症状が多く、病変部位は空腸に多い特徴があった。【結語】当院で経験した単発性小腸PJPの臨床的特徴を検討した。今後更なる症例の蓄積が必要である。

DOI： 10.32264/shocho.4.0_39

Objective evaluation of the therapeutic effect of ustekinumab on Crohn's disease

Specific members of gut microbiota predict mucosal healing in Crohn's disease

Hattori S., Nakamura M., Yamamura T., Maeda K., Sawada T., Mizutani Y., Yamamoto K., Pu L. Zorron Cheng Tao, Honda T., Ishikawa T., Furukawa K., Ohno E., Miyahara R., Kawashima H., Fujishiro M.

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY Vol. 34 page： 152 - 152 2019.9

Yamamura, T; Nakamura, M; Murate, K; Maeda, K; Sawada, T; Mizutani, Y; Nishikawa, T; Hattori, S; Yamamoto, K; Pu, LZCT; Ishikawa, T; Furukawa, K; Ohno, E; Miyahara, R; Kawashima, H; Fujishiro, M

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY Vol. 34 page： 145 - 145 2019.9

Roles of the mesenchymal stromal/stem cell marker meflin in cardiac tissue repair and the development of diastolic dysfunction

Hara A.

Circulation Research Vol. 125 ( 4 ) page： 414 - 430 2019.8

USEFULNESS OF THE FORWARD-VIEWING RADIAL-ARRAY ECHOENDOSCOPE IN THE DIAGNOSIS OF INVASION DEPTH OF COLORECTAL NEOPLASIA Reviewed International journal

Kuno Takeshi, Yamamura Takeshi, Nakamura Masanao, Maeda Keiko, Sawada Tsunaki, Mizutani Yasuyuki, Suzuki Hiroto, Esaki Masaya, Ishikawa Takuya, Furukawa Kazuhiro, Ohno Eizaburo, Kawashima Hiroki, Miyahara Ryoji, Hirooka Yoshiki

GASTROINTESTINAL ENDOSCOPY Vol. 89 ( 6 ) page： AB324 - AB324 2019.6

ダブルバルーン小腸内視鏡を用いた硬化療法にて治療効果を得た小腸多発血管腫の1例

山田啓策, 山村健史, 中村正直, 澤田つな騎, 水谷泰之, 前田啓子, 古川和宏, 宮原良二, 横井太紀雄, 廣岡芳樹

Gastroenterological Endoscopy Vol. 61 ( 6 ) page： 1231 - 1236 2019.6

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

70歳代男性。1ヵ月間持続する黒色便にて当科紹介となった。上下部消化管内視鏡検査では、明らかな出血源を認めなかった。小腸出血を疑いカプセル内視鏡検査を施行したところ、全小腸にわたり多発する隆起性病変を認めた。ダブルバルーン小腸内視鏡検査を行いジャンボバイオプシー目的の内視鏡的粘膜切除術(Endoscopic mucosal resection:EMR)にて海綿状血管腫と診断した。後日多発する血管腫に対してpolidocanol(Aethoxysklerol)による硬化療法を行った。4日後の内視鏡観察では、血管腫は縮小を認め、以後黒色便も消失した。小腸に多発する血管腫に対して内視鏡的硬化療法が有用であった1例を経験したので報告する。(著者抄録)

CLINICAL SIGNIFICANCE OF THE PATENCY OF GASTROINTESTINAL TRACT IN CROHN'S DISEASE EVALUATED BY PATENCY CAPSULE

Nakamura, M; Yamamura, T; Maeda, K; Sawada, T; Mizutani, Y; Kuno, T; Yamada, K; Ishikawa, T; Furukawa, K; Ohno, E; Miyahara, R; Kawashima, H; Hirooka, Y

GASTROINTESTINAL ENDOSCOPY Vol. 89 ( 6 ) page： AB333 - AB333 2019.6

Yamada, K; Nakamura, M; Yamamura, T; Maeda, K; Sawada, T; Mizutani, Y; Niwa, Y; Ishikawa, E; Otsuka, H; Suzuki, H; Ishikawa, T; Furukawa, K; Ohno, E; Miyahara, R; Kawashima, H; Hotta, N; Pu, LZCT; Hirooka, Y

GASTROINTESTINAL ENDOSCOPY Vol. 89 ( 6 ) page： AB155 - AB155 2019.6

今月の主題知っておきたい小腸疾患主題小腸の非腫瘍性疾患-小腸リンパ管拡張症

中村正直, 山村健史, 前田啓子, 澤田つな騎, 水谷泰之, 丹羽慶樹, 石川恵里, 大塚裕之, 鈴木悠土, 西川貴広, 石田哲也, 久野剛史, 服部峻, 山田啓策, 廣岡芳樹, 藤城光弘

胃と腸 Vol. 54 ( 4 ) page： 532 - 536 2019.4

Utility of linked color imaging for endoscopic diagnosis of early gastric cancer

Fujiyoshi Toshihisa, Miyahara Ryoji, Funasaka Kohei, Furukawa Kazuhiro, Sawada Tsunaki, Maeda Keiko, Yamamura Takeshi, Ishikawa Takuya, Ohno Eizaburo, Nakamura Masanao, Kawashima Hiroki, Nakaguro Masato, Nakatochi Masahiro, Hirooka Yoshiki

WORLD JOURNAL OF GASTROENTEROLOGY Vol. 25 ( 10 ) page： 1248-1258 2019.3

A case of multiple hemangiomas of the small intestine treated by sclerotherapy using double-balloon enteroscopy

Yamada K.

Gastroenterological Endoscopy Vol. 61 ( 6 ) page： 1231 - 1236 2019

Lewis Score on Capsule Endoscopy as a Predictor of the Risk for Crohn's Disease-Related Emergency Hospitalization and Clinical Relapse in Patients with Small Bowel Crohn's Disease

Nishikawa Takahiro, Nakamura Masanao, Yamamura Takeshi, Maeda Keiko, Sawada Tsunaki, Mizutani Yasuyuki, Ishikawa Takuya, Furukawa Kazuhiro, Ohno Eizaburo, Miyahara Ryoji, Kawashima Hiroki, Hirooka Yoshiki

GASTROENTEROLOGY RESEARCH AND PRACTICE Vol. 2019 page： 4274257 2019

腸リンパ管拡張症の診断と治療

中村正直, 山村健史, 前田啓子, 澤田つな騎, 水谷泰之, 藤城光弘

日本小腸学会学術集会プログラム・抄録集 Vol. 3 ( 0 ) page： 34_2 - 34_2 2019

Language：Japanese Publisher：日本小腸学会

【背景・目的】　小腸内視鏡診断の進歩により腸リンパ管拡張症（Intestinal lymphangiectasia：IL）を含む蛋白漏出性腸症の小腸精査が可能になった。本研究の目的はILの臨床経過を後ろ向きに評価し、その特徴を明らかにしたうえでより良い治療法を模索することであった。【対象と方法】　対象は2003年6月から2019年6月までにILと診断された17例（男性9例、女性8例、発症年齢は中央値37歳、0-75歳）であった。ILの診断は蛋白漏出性腸症と診断され且つ内視鏡下生検もしくは剖検にて病理学的に腸リンパ管拡張を認めたもので、他疾患が否定的であったものとした。白色絨毛、散布性白点を有する白色絨毛群（WV）と、異常なしもしくは軽度絨毛腫大、ケルクリング襞腫大を認める非白色絨毛群（NWV）に分けて臨床成績を比較検討した。【結果】　WV、NWVは10例、7例であった。平均血清アルブミン値（g/dl）はWV：NWV = 2.0：1.2でNWVにおいて有意に低かった（P = 0.0061）。平均α1アンチトリプシンクリアランスはWV：NWV = 132：284（P = 0.0509）であった。ステロイド治療への反応はWV：NWV = 2/7：6/6 例でみられた。平均観察期間48箇月において1例のILが影響した死亡例を経験したが、重篤な真菌感染症によるものであった。【結論】　NWV群は蛋白漏出は多いがステロイドへの反応がWV群よりも良好であった。治療のゴールドスタンダードは存在せず可能な可能で効果があるものを続けることが現状であった。

DOI： 10.32264/shocho.3.0_34_2