Faculty Profiles - MAEDA Keiko

Papers - MAEDA Keiko

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

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

<p>【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。</p><p>【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。</p><p>【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。</p><p>【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。</p>

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

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