Faculty Profiles - NAKAMURA, Masanao

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

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

内視鏡を活用した小腸疾患のマネッジメント

中村正直

日本消化器内視鏡学会雑誌 Vol. 66 ( Supplement1 ) page： 684 - 685 2024

Deep learning-based lesion detection and severity grading of small-bowel Crohn’s disease ulcers on double-balloon endoscopy images 1）.

GASTROENTEROLOGICAL ENDOSCOPY Vol. 66 ( 9 ) page： 1813 - 1813 2024

DIAGNOSIS AND TREATMENT OF INTESTINAL LYMPHOMA

ISHIKAWA Eri, NAKAMURA Masanao, KAWASHIMA Hiroki

GASTROENTEROLOGICAL ENDOSCOPY Vol. 66 ( 11 ) page： 2533 - 2544 2024

Language：Japanese Publisher：Japan Gastroenterological Endoscopy Society

B-cell lymphomas, particularly diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), are the most common intestinal lymphomas. The histological type can be distinguished based on the site and endoscopic findings. DLBCL is often found in the ileocecum and is frequently classified as ulcerative or polypoid. Considering the risk of perforation during chemotherapy, surgical treatment can be considered in patients with intestinal DLBCL. FL is usually detected endoscopically as multiple white nodules in the second portion of the duodenum, and the watch-and-wait approach is mostly adequate because of the indolent clinical course of the condition. Mucosa-associated lymphoid tissue (MALT) lymphoma often involves the rectum, and its treatment is diverse, including endoscopic resection. Immunoproliferative small-intestinal disease (IPSID) is a subtype of gastrointestinal MALT lymphoma. Mantle cell lymphoma (MCL) is typically found as multiple lymphomatous polyposis and is classified as a low-grade B-cell lymphoma, including FL and MALT lymphoma. It is important to distinguish MCL from both FL and MALT lymphomas because the aggressive clinical course of the former necessitates different management strategies. Intestinal T-cell lymphomas have been partially renamed in the latest WHO 5th edition. If there is a case of iatrogenic immunodeficiency, the possibility of an Epstein-Barr virus-positive mucocutaneous ulcer needs to be considered as a diagnosis, and the condition is characterized by spontaneous remission after immunosuppression reduction or discontinuation.

DOI： 10.11280/gee.66.2533

Multicenter prospective registration study of efficacy and safety of capsule endoscopy in Crohn’s disease in Japan (SPREAD-J study)

今月の主題小腸画像診断のトピックス主題バルーン内視鏡:ダブルバルーン内視鏡を中心に-腫瘍性疾患と炎症性疾患に対する診断法の有用性と限界

中村正直, 山村健史, 前田啓子, 澤田つな騎, 石川恵里, 村手健太郎, 長谷川一成, 池上脩二, 山下彩子, 河村達哉, 大岩恵祐, 八田勇輔, 平松美緒, 廣瀬崇, 古川和宏, 川嶋啓揮

胃と腸 Vol. 58 ( 11 ) page： 1462 - 1469 2023.11

Sakurai T., Omori T., Tanaka H., Ito T., Ando K., Yamamura T., Nanjjo S., Osawa S., Takeda T., Watanabe K., Hiraga H., Yamamoto S., Ozeki K., Tanaka S., Tajiri H., Saruta M., Akutagawa T., Aoyama N., Iguchi T., Endo K., Esaki M., Ogata H., Oka S., Omiya N., Kagaya T., Kakimoto K., Kobayashi T., Sagami S., Sakuraba H., Shinzaki S., Sugimoto K., Takao M., Torisu T., Nakajima A., Nakamichi K., Nakamura M., Nakase H., Nishiyama R., Hayashi Y., Hayashida M., Hiraoka S., Fuijya M., Fukada N., Fukuda M., Mihara H., Yokoyama K., Yoshida Y., Wagatsuma K.

Journal of Gastroenterology Vol. 58 ( 10 ) page： 1003 - 1014 2023.10

Publisher：Journal of Gastroenterology

Background: Evidence of small-bowel capsule endoscopy (SBCE) for evaluating lesions in Crohn’s disease (CD) is lacking. We aimed to clarify the effectiveness and safety of SBCE in a large sample of patients with CD. Methods: This multicenter prospective registration study recorded the clinical information and SBCE results of patients with definitive CD (d-CD) or suspected CD (s-CD). The primary outcomes were the rates of successful assessment of disease activity using SBCE, definitive diagnosis of CD, and adverse events. Secondary outcomes were the assessment of SBCE findings in patients with d-CD and s-CD and factors affecting SBCE incompletion and retention; and tertiary outcomes included the association between clinical disease activity or blood examination, endoscopic disease activity, ileal CD, and the questionnaire assessment of patient acceptance of SBCE. Results: Of 544 patients analyzed, 541 underwent SBCE with 7 (1.3%) retention cases. Of 468 patients with d-CD, 97.6% could be evaluated for endoscopic activity. Of 76 patients with s-CD, 15.8% were diagnosed with ‘confirmed CD’. CD lesions were more frequently observed in the ileum and were only seen in the jejunum in 3.4% of the patients. Male sex and stenosis were risk factors for incomplete SBCE, and high C-reactive protein levels and stenosis were risk factors for capsule retention. In L1 (Montreal classification) patients, clinical remission was associated with endoscopic remission but showed low specificity and accuracy. The answers to the acceptability questionnaire showed the minimal invasiveness and tolerability of SBCE. Conclusion: SBCE is practical and safe in patients with CD.

DOI： 10.1007/s00535-023-02017-3

Impact of elobixibat on liver tumors, microbiome, and bile acid levels in a mouse model of nonalcoholic steatohepatitis

Sugiyama Yoshiaki, Yamamoto Kenta, Honda Takashi, Kato Asuka, Muto Hisanori, Yokoyama Shinya, Ito Takanori, Imai Norihiro, Ishizu Yoji, Nakamura Masanao, Asano Tomomi, Enomoto Atsushi, Zaitsu Kei, Ishigami Masatoshi, Fujishiro Mitsuhiro, Kawashima Hiroki

HEPATOLOGY INTERNATIONAL 2023.9

Language：English Publisher：Hepatology International

Background: Elevated bile acid levels have been associated with liver tumors in fatty liver. Ileal bile acid transporter inhibitors may inhibit bile acid absorption in the distal ileum and increase bile acid levels in the colon, potentially decreasing the serum and hepatic bile acid levels. This study aimed to investigate the impact of these factors on liver tumor. Methods: C57BL/6J mice received a one-time intraperitoneal injection of 25-mg/kg diethylnitrosamine. They were fed a choline-deficient high-fat diet for 20 weeks starting from 8 weeks of age, with or without elobixibat (EA Pharma, Tokyo, Japan). Results: Both groups showed liver fat accumulation and fibrosis, with no significant differences between the two groups. However, mice with elobixibat showed fewer liver tumors. The total serum bile acid levels, including free, tauro-conjugated, glyco-conjugated, and tauro-α/β-muricholic acids in the liver, were noticeably reduced following elobixibat treatment. The proportion of gram-positive bacteria in feces was significantly lower in the group treated with elobixibat (5.4%) than in the group without elobixibat (33.7%). Conclusion: Elobixibat suppressed tumor growth by inhibiting bile acid reabsorption, and decreasing total bile acid and primary bile acid levels in the serum and liver. Additionally, the presence of bile acids in the colon may have led to a significant reduction in the proportion of gram-positive bacteria, potentially resulting in decreased secondary bile acid synthesis.

DOI： 10.1007/s12072-023-10581-2

Clinical characteristics of Dieulafoy's lesion in the small bowel diagnosed and treated by double-balloon endoscopy

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

BMC GASTROENTEROLOGY Vol. 23 ( 1 ) page： 290 2023.8

Language：English Publisher：BMC Gastroenterology

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

DOI： 10.1186/s12876-023-02913-1

Trajectory analyses to identify persistently low responders to COVID-19 vaccination in patients with inflammatory bowel disease: a prospective multicentre controlled study, J-COMBAT

Watanabe Kenji, Nojima Masanori, Nakase Hiroshi, Sato Toshiyuki, Matsuura Minoru, Aoyama Nobuo, Kobayashi Taku, Sakuraba Hirotake, Nishishita Masakazu, Yokoyama Kaoru, Esaki Motohiro, Hirai Fumihito, Nagahori Masakazu, Nanjo Sohachi, Omori Teppei, Tanida Satoshi, Yokoyama Yoshihiro, Moriya Kei, Maemoto Atsuo, Handa Osamu, Ohmiya Naoki, Tsuchiya Kiichiro, Shinzaki Shinichiro, Kato Shingo, Uraoka Toshio, Tanaka Hiroki, Takatsu Noritaka, Nishida Atsushi, Umeno Junji, Nakamura Masanao, Mishima Yoshiyuki, Fujiya Mikihiro, Tsuchida Kenji, Hiraoka Sakiko, Okabe Makoto, Toyonaga Takahiko, Matsuoka Katsuyoshi, Andoh Akira, Hirota Yoshio, Hisamatsu Tadakazu, J COMBAT Study Grp

JOURNAL OF GASTROENTEROLOGY Vol. 58 ( 10 ) page： 1015 - 1029 2023.8

Language：English Publisher：Journal of Gastroenterology

Background: The degree of immune response to COVID-19 vaccination in inflammatory bowel disease (IBD) patients based on actual changes in anti-SARS-CoV-2 antibody titres over time is unknown. Methods: Data were prospectively acquired at four predetermined time points before and after two vaccine doses in a multicentre observational controlled study. The primary outcome was humoral immune response and vaccination safety in IBD patients. We performed trajectory analysis to identify the degree of immune response and associated factors in IBD patients compared with controls. Results: Overall, 645 IBD patients and 199 control participants were analysed. At 3 months after the second vaccination, the seronegative proportions were 20.3% (combination of anti-tumour necrosis factor [TNF]α and thiopurine) and 70.0% (triple combination including steroids), despite that 80.0% receiving the triple combination therapy were seropositive at 4 weeks after the second vaccination. Trajectory analyses indicated three degrees of change in immune response over time in IBD patients: high (57.7%), medium (35.6%), and persistently low (6.7%). In the control group, there was only one degree, which corresponded with IBD high responders. Older age, combined anti-TNFα and thiopurine (odds ratio [OR], 37.68; 95% confidence interval [CI], 5.64–251.54), steroids (OR, 21.47; 95%CI, 5.47–84.26), and tofacitinib (OR, 10.66; 95%CI, 1.49–76.31) were factors associated with persistently low response. Allergy history (OR, 0.17; 95%CI, 0.04–0.68) was a negatively associated factor. Adverse reactions after the second vaccination were significantly fewer in IBD than controls (31.0% vs 59.8%; p < 0.001). Conclusions: Most IBD patients showed a sufficient immune response to COVID-19 vaccination regardless of clinical factors. Assessment of changes over time is essential to optimize COVID-19 vaccination, especially in persistently low responders. Graphical abstract: [Figure not available: see fulltext.].

DOI： 10.1007/s00535-023-02029-z

Letter: 1-kestose, the smallest fructooligosaccharide component, protection for mild to moderate ulcerative colitis patients-authors' reply.

Ikegami S, Nakamura M, Honda T, Kawashima H

Alimentary pharmacology & therapeutics Vol. 57 ( 11 ) page： 1351 - 1352 2023.6

ENDOSCOPIC TREATMENT OF DUODENAL NEUROENDOCRINE TUMORS

Furukawa Kazuhiro, Furune Satoshi, Ishikawa Eri, Sawada Tsunaki, Maeda Keiko, Yamamura Takeshi, Ishikawa Takuya, Nakamura Masanao, Kawashima Hiroki

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

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

Muroi Koichi, Kakushima Naomi, Furukawa Kazuhiro, Furune Satoshi, Ito Nobuhito, Hirose Takashi, Hida Emiko, Suzuki Tomohiko, Suzuki Takahiro, Hirai Keiko, Shibata Hiroyuki, Ishikawa Eri, Sawada Tsunaki, Maeda Keiko, Yamamura Takeshi, Ohno Eizaburo, Nakamura Masanao, Fujishiro Mitsuhiro, Kawashima Hiroki

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

Anxiety and behavioral changes in Japanese patients with inflammatory bowel disease due to COVID-19 pandemic: a national survey.

Hiroshi Nakase, Kohei Wagatsuma, Masanori Nojima, Takayuki Matsumoto, Minoru Matsuura, Hideki Iijima, Katsuyoshi Matsuoka, Naoki Ohmiya, Shunji Ishihara, Fumihito Hirai, Ken Takeuchi, Satoshi Tamura, Fukunori Kinjo, Nobuhiro Ueno, Makoto Naganuma, Kenji Watanabe, Rintaro Moroi, Nobuaki Nishimata, Satoshi Motoya, Koichi Kurahara, Sakuma Takahashi, Atsuo Maemoto, Hirotake Sakuraba, Masayuki Saruta, Keiichi Tominaga, Takashi Hisabe, Hiroki Tanaka, Shuji Terai, Sakiko Hiraoka, Hironobu Takedomi, Kazuyuki Narimatsu, Katsuya Endo, Masanao Nakamura, Tadakazu Hisamatsu

Journal of gastroenterology Vol. 58 ( 3 ) page： 205 - 216 2023.3

Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Gastroenterology

BACKGROUND: Given the increasing health concerns for patients with inflammatory bowel disease (IBD), amidst the COVID-19 pandemic, we investigated the impact of the pandemic on the anxiety and behavioral changes in Japanese patients with IBD. METHODS: We analyzed 3032 questionnaires from patients with IBD, aged 16 years or older visiting 30 hospitals and 1 clinic between March 2020 and June 2021. The primary outcome was the score of the anxiety experienced by patients with IBD during the pandemic. RESULTS: Participants reported a median age of 44 years; 43.3% of the patients were women. Moreover, 60.6% and 39.4% were diagnosed with ulcerative colitis and Crohn's disease, respectively, with a median disease duration of 10 years. Participants indicated an average of disease-related anxiety score of 5.1 ± 2.5 on a ten-point scale, with a tendency to increase, 1 month after the number of infected persons per population increased. The top three causes for anxiety were the risk of contracting COVID-19 during hospital visits, SARS-CoV-2 infection due to IBD, and infection by IBD medication. Factors associated with anxiety were gender (women), being a homemaker, hospital visit timings, mode of transportation (train), use of immunosuppressive drugs, and nutritional therapy. Most patients continued attending their scheduled hospital visits, taking their medications, experienced the need for a family doctor, and sought guidance and information regarding COVID-19 from primary doctors, television, and Internet news. CONCLUSIONS: Patients with IBD experienced moderate disease-related anxiety due to the pandemic and should be proactively informed about infectious diseases to relieve their anxiety.

DOI： 10.1007/s00535-022-01949-6

CO2 enterography in endoscopic retrograde cholangiography using double-balloon endoscopy: A randomized clinical trial. 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 2023.1

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

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 2023.1

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

Differences in the Intestinal Microbiome Associated with Diarrhea during Lenvatinib Treatment for Hepatocellular Carcinoma

Inukai Yosuke, Yamamoto Kenta, Honda Takashi, Ito Takanori, Imai Norihiro, Ishizu Yoji, Nakamura Masanao, Kawashima Hiroki, Ishigami Masatoshi

DIGESTIVE DISEASES Vol. 41 ( 1 ) page： 138 - 147 2023.1

Language：English Publisher：Digestive Diseases

Introduction: Lenvatinib has been widely used for the treatment of advanced hepatocellular carcinoma (HCC). Some adverse events, including diarrhea, have been reported for lenvatinib. Diarrhea may be associated with the changes in the intestinal microbiome; however, the underlying mechanism has not been elucidated. Aim: In this study, we aimed to investigate the relationship between the intestinal microbiome and diarrhea caused by lenvatinib via analysis of fecal samples collected before treatment. Methods: A total of 21 patients with advanced HCC who were treated with lenvatinib were enrolled. Fecal samples were collected from patients. The patients were divided into diarrhea (n = 8) and nondiarrhea groups (n = 12). We compared the characteristics of patients, incidence of adverse events, composition of the intestinal microbiome, and enrichment of functional pathways between both groups using QIIME2 and PICRUSt2. Results: The median age of the two groups was 73 years. The nondiarrhea group comprised a relatively higher number of male patients than the diarrhea group; however, there were no significant differences in patient characteristics between both groups. The proportion of the microbiome was similar, and alpha and beta diversities were not significantly different between both groups. The relative abundance of order Bacteroidales, including Parabacteroides and Prevotella, was higher in the diarrhea group than in the nondiarrhea group. PICRUSt2 analysis showed some metabolic pathways, including butanoate (butyrate) metabolism, were enriched in the nondiarrhea group when compared with those in the diarrhea group. Conclusion: Differences in the intestinal microbiomes and their functions may influence the incidence of diarrhea during lenvatinib treatment.

DOI： 10.1159/000524298

Current status of transanal total mesorectal excision for rectal cancer and the expanding indications of the transanal approach for extended pelvic surgeries. International journal

Kay Uehara, Atsushi Ogura, Yuki Murata, Masanori Sando, Toshiki Mukai, Toshisada Aiba, Takeshi Yamamura, Masanao Nakamura

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society Vol. 35 ( 2 ) page： 243 - 254 2023.1

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

Transanal total mesorectal excision (taTME) has been rapidly accepted as a promising surgical approach to the distal rectum. The benefits include ease of access to the bottom of the deep pelvis linearly over a short distance in order to easily visualize the important anatomy. Furthermore, the distal resection margins can be secured under direct vision. Additionally, a two-team approach combining taTME with a transabdominal approach could decrease the operative time and conversion rate. Although taTME was expected to become more rapidly popularized worldwide, enthusiasm for it has stalled due to unfamiliar intraoperative complications, a lack of oncologic evidence from randomized trials, and the widespread use of robotic surgery. While international registries have reported favorable short- and medium-term outcomes from taTME, a Norwegian national study reported a high local recurrence rate of 9.5%. The characteristics of the recurrences included rapid, multifocal growth in the pelvis, which was quite different from recurrences following traditional transabdominal TME; thus, the Norwegian Colorectal Cancer Group reached a consensus for a temporary moratorium on the performance of taTME. To ensure acceptable baseline quality and patient safety, taTME should be performed by well-trained colorectal surgeons. Although the appropriate indications for taTME remain controversial, the transanal approach is extremely important as a means of goal setting in difficult TME cases and as an aid to the transabdominal approach in various types of extended pelvic surgeries. The benefits in transanal lateral lymph node dissection and pelvic exenteration are presented herein.

DOI： 10.1111/den.14464