Faculty Profiles - SAWADA Tsunaki

Papers - SAWADA Tsunaki

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CO<sub>2</sub> enterography in endoscopic retrograde cholangiography using double-balloon endoscopy: A randomized clinical trial

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

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY Vol. 38 ( 5 ) page： 761 - 767 2023.5

Language：English Publisher：Journal of Gastroenterology and Hepatology (Australia)

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

DOI： 10.1111/jgh.16112

Nationwide cohort study identifies clinical outcomes of angioectasia in patients with acute hematochezia

Kobayashi, M; Akiyama, S; Narasaka, T; Kobayashi, K; Yamauchi, A; Yamada, A; Omori, J; Ikeya, T; Aoyama, T; Tominaga, N; Sato, Y; Kishino, T; Ishii, N; Sawada, T; Murata, M; Takao, A; Mizukami, K; Kinjo, K; Fujimori, S; Uotani, T; Fujita, M; Sato, H; Suzuki, S; Hayasaka, J; Funabiki, T; Kinjo, Y; Mizuki, A; Kiyotoki, S; Mikami, T; Gushima, R; Fujii, H; Fuyuno, Y; Gunji, N; Toya, Y; Narimatsu, K; Manabe, N; Nagaike, K; Kinjo, T; Sumida, Y; Funakoshi, S; Kobayashi, K; Matsuhashi, T; Komaki, Y; Miki, K; Watanabe, K; Tsuchiya, K; Kaise, M; Nagata, N

JOURNAL OF GASTROENTEROLOGY Vol. 58 ( 4 ) page： 367 - 378 2023.4

Language：English Publisher：Journal of Gastroenterology

Background: While angioectasia is an important cause of acute hematochezia, relevant clinical features remain unclear. This study aims to reveal risk factors, clinical outcomes, and the effectiveness of therapeutic endoscopy for patients with acute hematochezia due to angioectasia. Methods: This retrospective cohort study was conducted at 49 Japanese hospitals between January 2010 and December 2019, enrolling patients hospitalized for acute hematochezia (CODE BLUE-J study). Baseline factors and clinical outcomes for angioectasia were analyzed. Results: Among 10,342 patients with acute hematochezia, 129 patients (1.2%) were diagnosed with angioectasia by colonoscopy. The following factors were significantly associated with angioectasia: chronic kidney disease, liver disease, female, body mass index < 25, and anticoagulant use. Patients with angioectasia were at a significant increased risk of blood transfusions compared to those without angioectasia (odds ratio [OR] 2.61; 95% confidence interval [CI] 1.69–4.02). Among patients with angioectasia, 36 patients (28%) experienced rebleeding during 1-year follow-up. The 1-year cumulative rebleeding rates were 37.0% in the endoscopic clipping group, 14.3% in the coagulation group, and 32.8% in the conservative management group. Compared to conservative management, coagulation therapy significantly reduced rebleeding risk (P = 0.038), while clipping did not (P = 0.81). Multivariate analysis showed coagulation therapy was an independent factor for reducing rebleeding risk (hazard ratio [HR] 0.40; 95% CI 0.16–0.96). Conclusions: Our data showed patients with angioectasia had a greater comorbidity burden and needed more blood transfusions in comparison with those without angioectasia. To reduce rebleeding risk, coagulation therapy can be superior for controlling hematochezia secondary to angioectasia.

DOI： 10.1007/s00535-022-01945-w

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

Accuracy of Serum Leucine-Rich Alpha-2 Glycoprotein in Evaluating Endoscopic Disease Activity in Crohn's Disease

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

INFLAMMATORY BOWEL DISEASES Vol. 29 ( 2 ) page： 245 - 253 2023.2

Language：English Publisher：Inflammatory bowel diseases

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

DOI： 10.1093/ibd/izac076

Timing of colonoscopy in acute lower GI bleeding: a multicenter retrospective cohort study

Shiratori, Y; Ishii, N; Aoki, T; Kobayashi, K; Yamauchi, A; Yamada, A; Omori, J; Aoyama, T; Tominaga, N; Sato, Y; Kishino, T; Sawada, T; Murata, M; Takao, A; Mizukami, K; Kinjo, K; Fujimori, S; Uotani, T; Fujita, M; Sato, H; Suzuki, S; Narasaka, T; Hayasaka, J; Funabiki, T; Kinjo, Y; Mizuki, A; Kiyotoki, S; Mikami, T; Gushima, R; Fujii, H; Fuyuno, Y; Gunji, N; Toya, Y; Narimatsu, K; Manabe, N; Nagaike, K; Kinjo, T; Sumida, Y; Funakoshi, S; Kobayashi, K; Matsuhashi, T; Komaki, Y; Miki, K; Watanabe, K; Yamamoto, K; Yoshimoto, T; Takasu, A; Ikeya, T; Omata, F; Fukuda, K; Kaise, M; Nagata, N

GASTROINTESTINAL ENDOSCOPY Vol. 97 ( 1 ) page： 89 - + 2023.1

Language：English Publisher：Gastrointestinal Endoscopy

Background and Aims: We aimed to determine the optimal timing of colonoscopy and factors that benefit patients who undergo early colonoscopy for acute lower GI bleeding. Methods: We identified 10,342 patients with acute hematochezia (CODE BLUE-J study) admitted to 49 hospitals in Japan. Of these, 6270 patients who underwent a colonoscopy within 120 hours were included in this study. The inverse probability of treatment weighting method was used to adjust for baseline characteristics among early (≤24 hours, n = 4133), elective (24-48 hours, n = 1137), and late (48-120 hours, n = 1000) colonoscopy. The average treatment effect was evaluated for outcomes. The primary outcome was 30-day rebleeding rate. Results: The early group had a significantly higher rate of stigmata of recent hemorrhage (SRH) identification and a shorter length of stay than the elective and late groups. However, the 30-day rebleeding rate was significantly higher in the early group than in the elective and late groups. Interventional radiology (IVR) or surgery requirement and 30-day mortality did not significantly differ among groups. The interaction with heterogeneity of effects was observed between early and late colonoscopy and shock index (shock index <1, odds ratio [OR], 2.097; shock index ≥1, OR, 1.095; P for interaction = .038) and performance status (0-2, OR, 2.481; ≥3, OR, .458; P for interaction = .022) for 30-day rebleeding. Early colonoscopy had a significantly lower IVR or surgery requirement in the shock index ≥1 cohort (OR, .267; 95% confidence interval, .099-.721) compared with late colonoscopy. Conclusions: Early colonoscopy increased the rate of SRH identification and shortened the length of stay but involved an increased risk of rebleeding and did not improve mortality and IVR or surgery requirement. Early colonoscopy particularly benefited patients with a shock index ≥1 or performance status ≥3 at presentation.

DOI： 10.1016/j.gie.2022.07.025

MODIFIED N SCORE IS HELPFUL FOR IDENTIFYING PATIENTS WHO NEED ENDOSCOPIC INTERVENTION AMONG THOSE WITH BLACK STOOLS WITHOUT HEMATEMESIS

ITO Nobuhito, FUNASAKA Kohei, FUJIYOSHI Toshihisa, FURUKAWA Kazuhiro, KAKUSHIMA Naomi, FURUNE Satoshi, ISHIKAWA Eri, MIZUTANI Yasuyuki, SAWADA Tsunaki, MAEDA Keiko, ISHIKAWA Takuya, YAMAMURA Takeshi, OHNO Eizaburo, NAKAMURA Masanao, KAWASHIMA Hiroki, MIYAHARA Ryoji, HIROOKA Yoshiki, HARUTA Jun-Ichi, FUJISHIRO Mitsuhiro

GASTROENTEROLOGICAL ENDOSCOPY Vol. 65 ( 6 ) page： 1165 - 1174 2023

Language：Japanese Publisher：Japan Gastroenterological Endoscopy Society

<p>Objectives: Although black stools are one of the signs of upper gastrointestinal bleeding, not all patients without hematemesis need endoscopic intervention. There is no apparent indicator to select who needs treatment thus far. The aim of this study was to establish a novel score that predicts the need for endoscopic intervention in patients with black stools without hematemesis.</p><p>Methods: We retrospectively enrolled 721 consecutive patients with black stools without hematemesis who underwent emergency endoscopy from two facilities. In the development stage (from January 2016 to December 2018), risk factors that predict the need for endoscopic intervention were determined from the data of 422 patients by multivariate logistic regression analysis, and a novel scoring system, named the modified Nagoya University score (modified N score), was developed. In the validation stage (from January 2019 to September 2020), we evaluated the diagnostic value of the modified N score for 299 patients.</p><p>Results: Multivariate logistic regression analysis revealed four predictive factors for endoscopic intervention: syncope, the blood urea nitrogen (BUN) level, and the BUN/creatinine ratio as positive indicators and anticoagulant drug use as a negative indicator. In the validation stage, the area under the curve of the modified N score was 0.731, and the modified N score showed a sensitivity of 82.0% and a specificity of 58.8%.</p><p>Conclusions: Our modified N score, which consists of only four factors, can identify patients who need endoscopic intervention among those with black stools without hematemesis.</p>

DOI： 10.11280/gee.65.1165

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

<p>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.</p>

DOI： 10.11280/gee.65.1232

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

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, H; Murate, K; Nakamura, M; Furukawa, K; Kakushima, N; Yamamura, T; Maeda, K; Sawada, T; Ishikawa, E; Ishikawa, T; Ohno, E; Honda, T; Kawashima, H; Nakayama, G; Hattori, N; Umeda, S; Ishigami, M

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

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

NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 84 ( 4 ) page： 733 - 745 2022.11

Language：English Publisher：Nagoya Journal of Medical Science

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

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

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

Internal Medicine Vol. 61 ( 17 ) page： 2593 - 2599 2022.9

Language：English Publisher：The Japanese Society of Internal Medicine

<p>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 Cluster of differentiation (CD) 3 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. </p>

DOI： 10.2169/internalmedicine.8847-21

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

Meza MRR, Nakamura M, Yamamura T, Maeda K, Sawada T, Ishikawa E, Kakushima N, Furukawa K, Ohno E, Honda T, Kawashima H, Ishigami M

Internal medicine (Tokyo, Japan) Vol. 61 ( 17 ) page： 2593 - 2599 2022.9

Modified N score is helpful for identifying patients who need endoscopic intervention among those with black stools without hematemesis

Ito, N; Funasaka, K; Fujiyoshi, T; Furukawa, K; Kakushima, N; Furune, S; Ishikawa, E; Mizutani, Y; Sawada, T; Maeda, K; Ishikawa, T; Yamamura, T; Ohno, E; Nakamura, M; Kawashima, H; Miyahara, R; Hirooka, Y; Haruta, JI; Fujishiro, M

DIGESTIVE ENDOSCOPY Vol. 34 ( 6 ) page： 1157 - 1165 2022.9

Language：English Publisher：Digestive Endoscopy

Objectives: Although black stools are one of the signs of upper gastrointestinal bleeding, not all patients without hematemesis need endoscopic intervention. There is no apparent indicator to select who needs treatment thus far. The aim of this study was to establish a novel score that predicts the need for endoscopic intervention in patients with black stools without hematemesis. Methods: We retrospectively enrolled 721 consecutive patients with black stools without hematemesis who underwent emergency endoscopy from two facilities. In the development stage (from January 2016 to December 2018), risk factors that predict the need for endoscopic intervention were determined from the data of 422 patients by multivariate logistic regression analysis, and a novel scoring system, named the modified Nagoya University score (modified N score), was developed. In the validation stage (from January 2019 to September 2020), we evaluated the diagnostic value of the modified N score for 299 patients. Results: Multivariate logistic regression analysis revealed four predictive factors for endoscopic intervention: syncope, the blood urea nitrogen (BUN) level, and the BUN/creatinine ratio as positive indicators and anticoagulant drug use as a negative indicator. In the validation stage, the area under the curve of the modified N score was 0.731, and the modified N score showed a sensitivity of 82.0% and a specificity of 58.8%. Conclusions: Our modified N score, which consists of only four factors, can identify patients who need endoscopic intervention among those with black stools without hematemesis.

DOI： 10.1111/den.14323

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

Hamazaki, M; Sawada, T; Yamamura, T; Maeda, K; Mizutani, Y; Ishikawa, E; Furune, S; Yamamoto, K; Ishikawa, T; Kakushima, N; Furukawa, K; Ohno, E; Honda, T; Kawashima, H; Ishigami, M; Nakamura, M; Fujishiro, M

BMC GASTROENTEROLOGY Vol. 22 ( 1 ) page： 342 2022.7

Language：English Publisher：BMC Gastroenterology

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

Gelsolin as a Potential Biomarker for Endoscopic Activity and Mucosal Healing in Ulcerative Colitis

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

BIOMEDICINES Vol. 10 ( 4 ) 2022.4

Language：English Publisher：Biomedicines

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

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

WORLD JOURNAL OF GASTROENTEROLOGY Vol. 28 ( 10 ) page： 1055 - 1066 2022.3

Language：English Publisher：World Journal of Gastroenterology

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 highgrade 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 interobserver 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

Hirai, K; Kuwahara, T; Furukawa, K; Kakushima, N; Furune, S; Yamamoto, H; Marukawa, T; Asai, H; Matsui, K; Sasaki, Y; Sakai, D; Yamada, K; Nishikawa, T; Hayashi, D; Obayashi, T; Komiyama, T; Ishikawa, E; Sawada, T; Maeda, K; Yamamura, T; Ishikawa, T; Ohno, E; Nakamura, M; Kawashima, H; Ishigami, M; Fujishiro, M

GASTRIC CANCER Vol. 25 ( 2 ) page： 382 - 391 2022.3

Language：English Publisher：Gastric Cancer

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

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

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

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

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 2022.2

Language：Japanese Publisher：International Journal of Clinical Oncology

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

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