Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Tanaka Yoshimasa Last modified date:2024.06.27

Assistant Professor / Department of Hepatology and Pancreatology / Kyushu University Hospital


Papers
1. Y. Tanaka, Y. Motomura, K. Akahoshi, N. Nakama, T. Osoegawa, Y. Kashiwabara, T. Chaen, N. Higuchi, M. Kubokawa, K. Nishida, T. Yukaya, M. Oya, K. Nakamura, Capsule endoscopic detection of bleeding Meckels diverticulum, with capsule retention in the diverticulum, Endoscopy, 10.1055/s-0030-1255696, 42, SUPPL. 2, E199-E200, 2010.09.
2. AKAHOSHI KAZUYA, HONDA KUNIOMI, MOTOMURA YASUAKI, KUBOKAWA MASARU, OKAMOTO RISA, OSOEGAWA TAKASHI, NAKAMA NAOTAKA, KASHIWABARA YUMI, HIGUCHI NAOMI, TANAKA YOSHIMASA, OYA MASAFUMI, NAKAMURA KAZUHIKO, ENDOSCOPIC SUBMUCOSAL DISSECTION USING A GRASPING-TYPE SCISSORS FORCEPS FOR EARLY GASTRIC CANCERS AND ADENOMAS, Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 10.1111/j.1443-1661.2010.01037.x, 23, 1, 24-29, 2011.01.
3. Soichi Itaba, Kazuya Akahoshi, Yasuaki Motomura, Risa Iwao, Yoshimasa Tanaka, Keishi Komori, Takashi Osoegawa, Masaru Kubokawa, Terumasa Hisano, Hiroshi Matono, Masafumi Oya, Kazuhiko Nakamura, A case of rectal implantation cyst diagnosed by EUS and EUS-guided FNA, Journal of Japanese Society of Gastroenterology, 108, 12, 2030-2035, 2011.12, A 73-year-old woman was referred to our hospital complaining of bloody stool. She had undergone high anterior resection with the double stapling technique for a sigmoid colon cancer 2 years prior to this admission. Colonoscopy revealed a soft submucosal tumor, 4cm in size, on the anal side of the previous anastomosis in the rectum. EUS revealed a cystic lesion located in the third and fourth layers of the rectal wall. EUS-FNA was performed, and the content of the cystic lesion was transparent mucinous liquid. Histologically, the specimen revealed PAS and Alcian blue-positive mucinous material and a small number of inflammatory cells such as foamy macrophages. Therefore, this cystic lesion was diagnosed as a rectal implantation cyst..
4. Kazuhiko Nakamura, Tetsuhide Ito, Kazuhiro Kotoh, Eikichi Ihara, Haruei Ogino, Tsutomu Iwasa, Yoshimasa Tanaka, Yoichiro Iboshi, Ryoichi Takayanagi, Hepatopancreatobiliary manifestations of inflammatory bowel disease, Clinical Journal of Gastroenterology, 10.1007/s12328-011-0282-1, 5, 1, 1-8, 2012.02, Inflammatory bowel disease (IBD) is frequently associated with extraintestinal manifestations such as hepatopancreatobiliary manifestations (HPBMs), which include primary sclerosing cholangitis (PSC), pancreatitis, and cholelithiasis. PSC is correlated with IBD, particularly ulcerative colitis (UC); 70-80% of PSC patients in Western countries and 20-30% in Japan have comorbid UC. Therefore, patients diagnosed with PSC should be screened for UC by total colonoscopy. While symptoms of PSC-associated UC are usually milder than PSC-negative UC, these patients have a higher risk of colorectal cancer, particularly in the proximal colon. Therefore, regular colonoscopy surveillance is required regardless of UC symptoms. Administration of 5-aminosalicylic acid or ursodeoxycholic acid may prevent colorectal cancer and cholangiocarcinoma. While PSC is diagnosed by diffuse multifocal strictures on cholangiography, it must be carefully differentiated from immunoglobulin G4 (IgG4)-associated cholangitis, which shows a similar cholangiogram but requires different treatment. When PSC is suspected despite a normal cholangiogram, the patient may have small-duct PSC, which requires a liver biopsy. IBD patients have a high incidence of acute and chronic pancreatitis. Most cases are induced by cholelithiasis or medication, although some patients may have autoimmune pancreatitis (AIP), most commonly type 2 without elevation of serum IgG4. AIP should be accurately identified based on characteristic image findings, because AIP responds well to corticosteroids. Crohn's disease is frequently associated with gallstones, and several risk factors are indicated. HPBMs may influence the management of IBD, therefore, accurate diagnosis and an appropriate therapeutic strategy are important, as treatment depends upon the type of HPBM..
5. Y. Tanaka, K. Akahoshi, Y. Motomura, T. Osoegawa, T. Yukaya, E. Ihara, R. Iwao, K. Komori, N. Nakama, S. Itaba, M. Kubokawa, T. Hisano, K. Nakamura, Pretherapeutic evaluation of buried bumper syndrome by endoscopic ultrasonography, Endoscopy, 10.1055/s-0031-1291715, 44, SUPPL. 2, E162, 2012.05.
6. Yoshimasa Tanaka, Yasuaki Motomura, Kazuya Akahoshi, Risa Iwao, Keishi Komori, Naotaka Nakama, Takashi Osoegawa, Soichi Itaba, Masaru Kubokawa, Terumasa Hisano, Eikichi Ihara, Kazuhiko Nakamura, Ryoichi Takayanagi, Predictive factors for colonic diverticular rebleeding A retrospective analysis of the clinical and colonoscopic features of 111 patients, Gut and Liver, 10.5009/gnl.2012.6.3.334, 6, 3, 334-338, 2012.07, Background/Aims: Colonic diverticular bleeding can stop spontaneously or be stopped by endoscopic hemostasis. We analyzed the clinical and colonoscopic features of patients with colonic diverticular bleeding to establish the predictive factors for rebleeding. Methods: A total of 111 patients (median age, 72 years) with colonic diverticular bleeding in Aso Iizuka Hospital between April 2007 and July 2010 were enrolled. Age, sex, body mass index (BMI), comorbidity, medication, location of bleeding, colonoscopic findings and hemostatic methods were analyzed retrospectively from the hospital records. Results: The most common sites of bleeding were the ascending (39.6%) and sigmoid (29.7%) colon. Overt rebleeding occurred in 30 patients (27.0%). Spontaneous hemostasis was seen in 81 patients (73.0%), and endoscopic hemostatic treatment was performed in 30 patients. The BMI in the patients with colonic diverticular rebleeding was significantly higher than in patients without rebleeding. Colonoscopic findings of actively bleeding or nonbleeding visible vessels in the responsible diverticula were more frequent in the group with rebleeding. Conclusions: A higher BMI and colonoscopic findings of actively bleeding or nonbleeding visible vessels can be used as predictive factors for colonic diverticular rebleeding. Patients with such findings should be carefully followed up after hemostasis of the initial colonic diverticular bleeding..
7. Kazuhiko Nakamura, Kazuya Akahoshi, Toshiaki Ochiai, Keishi Komori, Kazuhiro Haraguchi, Munehiro Tanaka, Norimoto Nakamura, Yoshimasa Tanaka, Kana Kakigao, Haruei Ogino, Eikichi Ihara, Hirotada Akiho, Yasuaki Motomura, Teppei Kabemura, Naohiko Harada, Yoshiharu Chijiiwa, Tetsuhide Ito, Ryoichi Takayanagi, Characteristics of hemorrhagic peptic ulcers in patients receiving antithrombotic/nonsteroidal antiinflammatory drug therapy, Gut and Liver, 10.5009/gnl.2012.6.4.423, 6, 4, 423-426, 2012.10, Background/Aims: Antithrombotic/nonsteroidal antiinflammatory drug (NSAID) therapies increase the incidence of upper gastrointestinal bleeding. The features of hemorrhagic peptic ulcer disease in patients receiving antithrombotic/NSAID therapies were investigated. Methods: We investigated the medical records of 485 consecutive patients who underwent esophagogastroduodenoscopy and were diagnosed with hemorrhagic gastroduodenal ulcers. The patients treated with antithrombotic agents/NSAIDs were categorized as the antithrombotic therapy (AT) group (n=213). The patients who were not treated with antithrombotics/NSAIDs were categorized as the control (C) group (n=263). The clinical characteristics were compared between the groups. Results: The patients in the AT group were significantly older than those in the C group (p
8. Takashi Osoegawa, Yasuaki Motomura, Kazuya Akahoshi, Naomi Higuchi, Yoshimasa Tanaka, Terumasa Hisano, Souichi Itaba, Junya Gibo, Mariko Yamada, Masaru Kubokawa, Yorinobu Sumida, Hirotada Akiho, Eikichi Ihara, Kazuhiko Nakamura, Improved techniques for double-balloon-enteroscopy-assisted endoscopic retrograde cholangiopancreatography, World Journal of Gastroenterology, 10.3748/wjg.v18.i46.6843, 18, 46, 6843-6849, 2012.12, AIM: To investigate the clinical outcome of double balloon enteroscopy (DBE)-assisted endoscopic retrograde cholangiopancreatography (DB-ERCP) in patients with altered gastrointestinal anatomy. METHODS: Between September 2006 and April 2011, 47 procedures of DB-ERCP were performed in 28 patients with a Roux-en-Y total gastrectomy (n = 11), Billroth II gastrectomy (n = 15), or Roux-en-Y anastomosis with hepaticojejunostomy (n = 2). DB-ERCP was performed using a short-type DBE combined with several technical innovations such as using an endoscope attachment, marking by submucosal tattooing, selectively applying contrast medium, and CO2 insufflations. RESULTS: The papilla of Vater or hepaticojejunostomy site was reached in its entirety with a 96% success rate (45/47 procedures). There were no significant differences in the success rate of reaching the blind end with a DBE among Roux-en-Y total gastrectomy (96%), Billroth II reconstruction (94%), or pancreatoduodenectomy (100%), respectively (P = 0.91). The total successful rate of cannulation and contrast enhancement of the target bile duct in patients whom the blind end was reached with a DBE was 40/45 procedures (89%). Again, there were no significant differences in the success rate of cannulation and contrast enhancement of the target bile duct with a DBE among Roux-en-Y total gastrectomy (88%), Billroth II reconstruction (89%), or pancreatoduodenectomy (100%), respectively (P = 0.67). Treatment was achieved in all 40 procedures (100%) in patients whom the contrast enhancement of the bile duct was successful. Common endoscopic treatments were endoscopic biliary drainage (24 procedures) and extraction of stones (14 procedures). Biliary drainage was done by placement of plastic stents. Stones extraction was done by lithotomy with the mechanical lithotripter followed by extraction with a basket or by the balloon pull-through method. Endoscopic sphincterotomy was performed in 14 procedures with a needle precutting knife using a guidewire. The mean total duration of the procedure was 93.6 ± 6.8 min and the mean time required to reach the papilla was 30.5 ± 3.7 min. The mean time required to reach the papilla tended to be shorter in Billroth II reconstruction (20.9 ± 5.8 min) than that in Roux-en-Y total gastrectomy (37.1 ± 4.9 min) but there was no significant difference (P = 0.09). A major complication occurred in one patient (3.5%); perforation of the long limb in a patient with Billroth II anastomosis. CONCLUSION: Short-type DBE combined with several technical innovations enabled us to perform ERCP in most patients with altered gastrointestinal anatomy..
9. Yoshimasa Tanaka, Eikichi Ihara, Katsuya Hirano, Mayumi Hirano, Kazuhiko Nakamura, Hirotada Akiho, Ryoichi Takayanagi, Trypsin Induced BiPhasic Contraction and Relaxation in the Porcine Lower Esophageal Sphincter, GASTROENTEROLOGY, 144, 5, S857-S857, 2013.05, 0.
10. Kazumasa Muta, Eikichi Ihara, Xiaopeng Bai, Yoshimasa Tanaka, Kazuhiko Nakamura, Hirotada Akiho, Ryoichi Takayanagi, Acotiamide, a Novel Prokinetic Drug, Reduces Both Esophageal Body Contractility and the Tone of the Lower Esophageal Sphincter, GASTROENTEROLOGY, 146, 5, S683-S683, 2014.05.
11. Xiaopeng Bai, Yoshimasa Tanaka, Eikichi Ihara, Katsuya Hirano, Mayumi Hirano, Kazuhiko Nakamura, Hirotada Akiho, Ryoichi Takayanagi, Different Contractile and Relaxant Effects of Trypsin in Phasic Smooth Muscles of the Esophageal Body and the Tonic Lower Esophageal Sphincter, GASTROENTEROLOGY, 146, 5, S862-S862, 2014.05.
12. Yoshimasa Tanaka, Eikichi Ihara, Katsuya Hirano, Shunsuke Takahashi, Mayumi Hirano, Kazuhiko Nakamura, Hirotada Akiho, Yoshinao Oda, Ryoichi Takayanagi, Trypsin-induced biphasic regulation of tone in the porcine lower esophageal sphincter, European Journal of Pharmacology, 10.1016/j.ejphar.2015.02.008, 752, 97-105, 2015.04, The lower esophageal sphincter (LES) plays an important role in coordinated esophageal motility. The present study aimed to elucidate how trypsin affects LES contractility. Porcine LES circular smooth muscle strips were prepared. Contractile responses to trypsin were assessed. Trypsin (300 nM) induced a transient contraction. At concentrations of 1 μM or higher, trypsin induced biphasic responses, consisting of a transient contraction followed by a transient relaxation. Pretreatment with either 1 μM tetrodotoxin or carbenoxolone had no effect on these responses. In contrast, trypsin-induced responses were completely blocked by pretreatment with the serine protease inhibitor. Pretreatment with 10 μM FSLLRY-NH2, a PAR2 antagonist, significantly inhibited trypsin-induced biphasic responses. Trypsin (1 μM)-induced contractions were partially inhibited by pretreatment with 10 μM Y-27632. In addition, trypsin (10 μM)-induced relaxation was partially inhibited by pretreatment with 10 μM Y-27632, 10 μM PD98059 or 10 μM SB203580. Trypsin-induced relaxation was abolished by increasing the extracellular K+ concentration to 40 mM, but not by pretreatment with l-arginine methyl ester. Furthermore, trypsin-induced relaxation was partially inhibited by pretreatment with 10 μM glibenclamide or 1 μM 4-aminopyridine. Trypsin causes biphasic regulation of LES tone by directly acting on smooth muscle. Rho-associated protein kinase (ROK) is involved in trypsin-induced contraction, whereas ROK, ERK1/2, p38MAPK, and membrane hyperpolarization are involved in relaxation. The regulation of LES tone by trypsin may play a role in esophageal motility..
13. Kazumasa Muta, Eikichi Ihara, Keita Fukaura, Xiaopeng Bai, Yoshimasa Tanaka, Kazuhiko Nakamura, Toshiaki Ochiai, Osamu Tsuchida, Hirotada Akiho, Ryoichi Takayanagi, Acotiamide Has the Potential to Become a Promising Treatment for Patients With Esophagogastric Junction Outflow Obstruction, GASTROENTEROLOGY, 148, 4, S803-S803, 2015.04.
14. Yoshimasa Tanaka, Eikichi Ihara, Kazumasa Muta, Keita Fukaura, Koji Mukai, Xiaopeng Bai, Kazuhiko Nakamura, Hirotada Akiho, Ryoichi Takayanagi, Clinical Characteristics Associated With Function of Esophageal Motility: A Retrospective Analysis of 97 Patients, GASTROENTEROLOGY, 148, 4, S818-S818, 2015.04.
15. Xiaopeng Bai, Eikichi Ihara, Yoshimasa Tanaka, Katsuya Hirano, Mayumi Hirano, Hirotada Akiho, Kazuhiko Nakamura, Ryoichi Takayanagi, Endogenous H2S Contributes to Myogenic Tone Generation in Lower Esophageal Sphincter: Possible Involvement of Na+/CA(2+) Exchanger, GASTROENTEROLOGY, 148, 4, S78-S78, 2015.04.
16. Keita Fukaura, Eikichi Ihara, Kazumasa Muta, Yoshimasa Tanaka, Xiaopeng Bai, Kazuhiko Nakamura, Ryoichi Takayanagi, The Cytokine Expression Patterns of Esophageal Mucosa Are Associated With Esophageal Motility Function in Human, GASTROENTEROLOGY, 148, 4, S882-S882, 2015.04.
17. Xiaopeng Bai, Eikichi Ihara, Yoshimasa Tanaka, Katsuya Hirano, Mayumi Hirano, Kazuhiko Nakamura, Involvement of Different Subtypes of Receptor in Prostaglandin E2-Induced Motile Function in Lower Esophageal Sphincter and Esophageal Body Smooth Muscle, GASTROENTEROLOGY, 150, 4, S458-S458, 2016.04, 0.
18. Kazumasa Muta, Eikichi Ihara, Keita Fukaura, Xiaopeng Bai, Yoshimasa Tanaka, Osamu Tsuchida, Toshiaki Ochiai, Tsutomu Iwasa, Akira Aso, Kazuhiko Nakamura, Mechanisms of Acotiamide-Sensitive Impaired Lower Esophageal Sphincter Accommodation in Patients With Esophagogastric Junction Outflow Obstruction, GASTROENTEROLOGY, 10.1016/S0016-5085(16)31612-2, 150, 4, S468-S468, 2016.04.
19. Eikichi Ihara, Keita Fukaura, Kazumasa Muta, Yoshimasa Tanaka, Xiaopeng Bai, Tsutomu Iwasa, Akira Aso, Hirotada Akiho, Kazuhiko Nakamura, Protease-Activated Receptor Expression in the Esophagus Is Associated With Esophageal Mucosal Integrity and Esophageal Motility Function, GASTROENTEROLOGY, 10.1016/S0016-5085(16)30272-4, 150, 4, S43-S44, 2016.04, 0.
20. Xiaopeng Bai, Eikichi Ihara, Yoshimasa Tanaka, Katsuya Hirano, Mayumi Hirano, Hirotada Akiho, Kazuhiko Nakamura, Trypsin Induced a Transient Contraction via a PAR2/TRPV1/Neurokinin Receptors Pathway in Circular Smooth Muscle of Porcine Esophageal Body, GASTROENTEROLOGY, 150, 4, S458-S458, 2016.04, 0.
21. Yoshimasa Tanaka, Eikichi Ihara, Kazuhiko Nakamura, Kazumasa Muta, Keita Fukaura, Koji Mukai, Xiaopeng Bai, Ryoichi Takayanagi, Clinical characteristics associated with esophageal motility function, Journal of Gastroenterology and Hepatology (Australia), 10.1111/jgh.13262, 31, 6, 1133-1140, 2016.06, Background and Aim:: Esophageal motility disorders (EMDs) affect coordinated esophageal contractility. Recent developments in high-resolution manometry have improved diagnosis of EMDs; however, the etiology of EMDs remains to be determined. This study aimed to determine which clinical characteristics are associated with esophageal motility. Methods:: From May 2013 to July 2014, 97 patients (54 women, 43 men; age, 16-89years) with suspected EMDs were assessed by high-resolution manometry in Kyushu University Hospital. Esophageal motility was evaluated by measuring the distal contractile integral (DCI), basal lower esophageal sphincter pressure, and integrated relaxation pressure (IRP). Data on age, gender, body mass index (BMI), Brinkman Index, and blood tests were retrospectively collected and analyzed. Results:: Fifty patients were diagnosed as normal, nine with achalasia, twelve with esophagogastric junction outflow obstruction, four with distal esophageal spasm, one with jackhammer esophagus, six with absent peristalsis, ten with frequent failed peristalsis, and five with weak peristalsis. The median DCI was 1229.0mmHg-s-cm, the median basal lower esophageal sphincter pressure was 25.3mmHg, and the median IRP was 9.6mmHg. Patients with major motility disorders were excluded from analysis. By multivariate regression analysis, BMI (P=0.029) and total cholesterol (P=0.023) were negatively associated with DCI, while BMI (P=0.007) was negatively associated with IRP and glucose (P=0.044) was positively associated with IRP. Conclusions:: Both BMI and total cholesterol could be highly predictive factors for esophageal body contractility, while BMI and glucose could be predictive factors for lower esophageal sphincter contractile function..
22. Eikichi Ihara, Kazumasa Muta, Keita Fukaura, Yoshimasa Tanaka, Xiaopeng Bai, Akira Aso, Tsutomu Iwasa, Kazuhiko Nakamura, New Approach to Diagnosis and Treatment of Esophageal Motility Disorders by High-Resolution manometry, Fukuoka igaku zasshi = Hukuoka acta medica, 107, 7, 121-130, 2016.07, Esophageal motility disorders (EMD) is characterized by impaired coordinated esophageal motility function with symptoms including dysphasia, heartburn or noncardiac chest pain. Since EMDs is functional disorders, it is usually difficult to make a diagnosis by conventional examinations including endoscopy and esophagography. Recently developed high-resolution manometry allows us to evaluate esophageal motility function precisely and to make a differential diagnosis of EMDs, together with Chicago Classification (CC) version 3.0 (CC ver3.0). In this article, we reviewed diagnosis of EMDs based on CC ver3.0 and current treatment strategy for EMDs..
23. Xiaopeng Bai, Eikichi Ihara, Yoshimasa Tanaka, Katsuya Hirano, Mayumi Hirano, Kazuhiko Nakamura, Endogenous H2S maintains myogenic tone in lower esophageal sphincter: A possible target for treatment of lower esophageal sphincter dysfunction, JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 31, 11-11, 2016.11.
24. Bai Xiaopeng, Yoshimasa Tanaka, Eikichi Ihara, Katsuya Hirano, Kayoko Nakano, Mayumi Hirano, Yoshinao Oda, Kazuhiko Nakamura, Trypsin induces biphasic muscle contraction and relaxation via transient receptor potential vanilloid 1 and neurokinin receptors 1/2 in porcine esophageal body, European Journal of Pharmacology, 10.1016/j.ejphar.2017.01.004, 797, 65-74, 2017.01, Duodenal reflux of fluids containing trypsin relates to refractory gastroesophageal reflux disease (GERD). Esophageal peristalsis and clearance are important factors in GERD pathogenesis. However, the function of trypsin in esophageal body contractility is not fully understood. In this study, effects of trypsin on circular smooth muscle (CSM) and longitudinal smooth muscle (LSM) of the porcine esophageal body were examined. Trypsin elicited a concentration dependent biphasic response, a major contraction and a subsequent relaxation only in CSM. In CSM, contraction occurred at trypsin concentrations of 100 nM and relaxation at 1 μM. A proteinase-activated receptor (PAR)2 activating peptide, SLIGKV-NH2(1 mM), induced a monophasic contraction. Those responses were unaffected by tetrodotoxin though abolished by the gap junction uncouplers carbenoxolone and octanol. They were also partially inhibited by a transient receptor potential vanilloid type 1 (TRPV1) antagonist and abolished by combination of neurokinin receptor 1 (NK1) and NK2antagonists, but not by an NK3antagonist, suggesting a PAR2-TRPV1-substance P pathway in sensory neurons. Substance P (100 nM), an agonist for various NK receptors (NK1, NK2and NK3) with differing affinities, induced significant contraction in CSM, but not in LSM. The contraction was also blocked by the combination of NK1and NK2antagonists, but not by the NK3antagonist. Moreover, substance P-induced contractions were unaffected by the TRPV1 antagonist, but inhibited by a gap junction uncoupler. In conclusion, trypsin induced a biphasic response only in CSM and this was mediated by PAR2, TRPV1 and NK1/2. Gap junctions were indispensable in this tachykinin-induced response..
25. Xiaopeng Bai, Eikichi Ihara, Katsuya Hirano, Yoshimasa Tanaka, Kayoko Nakano, Satomi Kita, Takahiro Iwamoto, Haruei Ogino, Mayumi Hirano, Yoshinao Oda, Kazuhiko Nakamura, Yoshihiro Ogawa, Endogenous Hydrogen Sulfide Contributes to Tone Generation in Porcine Lower Esophageal Sphincter Via Na+/Ca2+ Exchanger, CMGH, 10.1016/j.jcmgh.2017.11.004, 5, 3, 209-221, 2018.03, Background and Aims: Hydrogen sulfide (H2S) is a major physiologic gastrotransmitter. Its role in the regulation of the lower esophageal sphincter (LES) function remains unknown. The present study addresses this question. Methods: Isometric contraction was monitored in circular smooth muscle strips of porcine LES. Changes in cytosolic Ca2+ concentration ([Ca2+]i) and force were simultaneously monitored in fura-2-loaded strips with front-surface fluorometry. The contribution of endogenous H2S to LES contractility was investigated by examining the effects of inhibitors of H2S-generating enzymes, including cystathionine-β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase, on the LES function. Results: Porcine LES strips myogenically maintained a tetrodotoxin-resistant basal tone. Application of AOA (cystathionine-β-synthase inhibitor) or L-aspartic acid (L-Asp; 3-mercaptopyruvate sulfurtransferase inhibitor) but not DL-PAG (cystathionine-γ-lyase inhibitor), decreased this basal tone. The relaxant effects of AOA and L-Asp were additive. Maximum relaxation was obtained by combination of 1 mM AOA and 3 mM L-Asp. Immunohistochemical analyses revealed that cystathionine-β-synthase and 3-mercaptopyruvate sulfurtransferase, but not cystathionine-γ-lyase, were expressed in porcine LES. AOA+L-Asp–induced relaxation was accompanied by a decrease in [Ca2+]i and inversely correlated with the extracellular Na+ concentration ([Na+]o) (25-137.4 mM), indicating involvement of an Na+/Ca2+ exchanger. The reduction in the basal [Ca2+]i level by AOA was significantly augmented in the antral smooth muscle sheets of Na+/Ca2+ exchanger transgenic mice compared with wild-type mice. Conclusions: Endogenous H2S regulates the LES myogenic tone by maintaining the basal [Ca2+]i via Na+/Ca2+ exchanger. H2S-generating enzymes may be a potential therapeutic target for esophageal motility disorders, such as achalasia..
26. Yasuyo Hayashi, Mitsuru Esaki, Taizo Hosokawa, Yoshimasa Tanaka, Haruei Ogino, Takahiro Mizutani, Eikichi Ihara, Hirotada Akiho, COMPARISON BETWEEN CLUTCH CUTTER AND OTHER DEVICES IN THE TECHNICAL OUTCOMES IN ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY GASTRIC CANCER, GASTROINTESTINAL ENDOSCOPY, 87, 6, AB266-AB266, 2018.06.
27. Yasuyo Hayashi, Mitsuru Esaki, Sho Suzuki, Eikichi Ihara, Azusa Yokoyama, Seiichiro Sakisaka, Taizo Hosokawa, Yoshimasa Tanaka, Takahiro Mizutani, Shinichi Tsuruta, Aya Iwao, Shun Yamakawa, Akira Irie, Yosuke Minoda, Yoshitaka Hata, Haruei Ogino, Hirotada Akiho, Yoshihiro Ogawa, Clutch Cutter knife efficacy in endoscopic submucosal dissection for early gastric neoplasms, World Journal of Gastrointestinal Oncology, 10.4251/wjgo.v10.i12.487, 10, 12, 487-495, 2018.12, AIM To compare the outcomes of endoscopic submucosal dissection (ESD) for gastric neoplasms using Clutch Cutter (ESD-C) or other knives (ESD-O). METHODS This was a single-center retrospective study. Gastric neoplasms treated by ESD between April 2016 and October 2017 at Kitakyushu Municipal Medical Center were reviewed. Multivariate analyses and propensity score matching were used to reduce biases. Covariates included factors that might affect outcomes of ESD, including age, sex, underlying disease, anti-thrombotic drugs use, tumor location, tumor position, tumor size, tumor depth, tumor morphology, tumor histology, ulcer (scar), and operator skill. The treatment outcomes were compared among two groups. The primary outcome was ESD procedure time. Secondary outcomes were en bloc, complete, and curative resection rates, and adverse events rates including perforation and delayed bleeding. RESULTS A total of 155 patients were included in this study; 44 pairs were created by propensity score matching. Background characteristics were quite similar among two groups after matching. Procedure time was significantly shorter for ESD-C (median; 49 min) than for ESD-O (median; 88.5 min) (P
28. Shohei Hamada, Eikichi Ihara, Hiroko Ikeda, Kazumasa Muta, Haruei Ogino, Takatoshi Chinen, Yoshimasa Tanaka, Yoshihiro Ogawa, Clinical Characterization of Vonoprazan-Refractory Gastroesophageal Reflux Disease, Digestion, 10.1159/000503340, 2019.01, Introduction: The newly developed vonoprazan (a potassium-competitive acid blocker) has a greater ability to suppress gastric acid production than convention proton pump inhibitors (PPIs). The objective of the present study was to determine how vonoprazan influences the pathogenesis of refractory gastroesophageal reflux disease (GERD) in clinical practice. Methods: Between March 2013 and November 2018, a total of 73 refractory GERD patients (34 in the conventional PPI group versus 39 in the vonoprazan group) were enrolled in this retrospective study. We then compared the underlying disease conditions between the 2 groups, examined by high-resolution manometry and multichannel intraluminal impedance/pH (MII-pH) monitoring. Results: There was a significant difference in the proportion of underlying disease conditions, including erosive esophagitis, non-erosive reflux disease, reflux hypersensitivity, functional heartburn and oesophageal motility disorder (EMD), between the conventional PPI (6, 14, 23, 40 and 17% respectively) and vonoprazan groups (0, 0, 10, 49, and 41% respectively; p
29. Shohei Hamada, Eikichi Ihara, Hiroko Ikeda, Kazumasa Muta, Haruei Ogino, Takatoshi Chinen, Yoshimasa Tanaka, Yoshihiro Ogawa, Clinical Characterization of Vonoprazan-Refractory Gastroesophageal Reflux Disease, Digestion, 10.1159/000503340, 102, 2, 197-204, 102:197-204., 2019.01, Introduction: The newly developed vonoprazan (a potassium-competitive acid blocker) has a greater ability to suppress gastric acid production than convention proton pump inhibitors (PPIs). The objective of the present study was to determine how vonoprazan influences the pathogenesis of refractory gastroesophageal reflux disease (GERD) in clinical practice. Methods: Between March 2013 and November 2018, a total of 73 refractory GERD patients (34 in the conventional PPI group versus 39 in the vonoprazan group) were enrolled in this retrospective study. We then compared the underlying disease conditions between the 2 groups, examined by high-resolution manometry and multichannel intraluminal impedance/pH (MII-pH) monitoring. Results: There was a significant difference in the proportion of underlying disease conditions, including erosive esophagitis, non-erosive reflux disease, reflux hypersensitivity, functional heartburn and oesophageal motility disorder (EMD), between the conventional PPI (6, 14, 23, 40 and 17% respectively) and vonoprazan groups (0, 0, 10, 49, and 41% respectively; p
30. Xiaopeng Bai, Eikichi Ihara, Yoshihihro Otsuka, Shinichi Tsuruta, Katsuya Hirano, Yoshimasa Tanaka, Haruei Ogino, Mayumi Hirano, Takatoshi Chinen, Hirotada Akiho, Kazuhiko Nakamura, Yoshinao Oda, Yoshihiro Ogawa, Involvement of different receptor subtypes in prostaglandin E2-induced contraction and relaxation in the lower esophageal sphincter and esophageal body, European Journal of Pharmacology, 10.1016/j.ejphar.2019.172405, 857, 2019.08, Prostaglandin E2 (PGE2) plays a role in the pathogenesis of gastro-esophageal reflux disease (GERD). There are 4 subtypes of PGE2, PGE2 receptor 1, 2, 3 and 4 (EP 1–4). In GERD patents, PGE2, EP2 and EP4 are upregulated. However, the effects of PGE2 on esophageal motility remain elusive. We examined how PGE2 regulates motility in the porcine circular smooth muscle of the lower esophageal sphincter (LES), and the circular and longitudinal smooth muscle of the esophagus body in organ bath. PGE2 induced tonic relaxation in the LES and circular smooth muscle, but transient contraction in longitudinal smooth muscle. The relaxation of the LES and circular smooth muscle was similar in pattern and mechanism, but was much larger in the LES. The relaxation was completely blocked by a voltage-gated K+ channel blocker or 40 mM K+ depolarization, indicating the involvement of K+ channel. Longitudinal smooth muscle contraction was completely blocked by an L-type Ca2+ channel blocker, showing the contribution of Ca2+ movement. The involvement of the EP receptor in motility was examined with selective receptor agonists and antagonists. Activation of EP2 and EP4 caused relaxation in the LES and circular smooth muscle. Compatible with PGE2, EP2 and EP4 agonists caused more significant relaxation in the LES than in circular smooth muscle. EP1 contributed to the longitudinal smooth muscle contraction. The different effects of PGE2 in the LES, circular and longitudinal smooth muscle contributes to esophageal motility, their impairment might increase the amount and frequency of esophageal reflux..
31. Okuno H, Ogino H, Ihara E, Nishioka K, Tanaka Y, Chinen T, Kohjima M, Oono T, Tanaka M, Goya T, Fujimori N, Iboshi Y, Gotoda T, Ogawa Y, Discriminant equation using mucosally expressed cytokines and transcription factor for making definite diagnosis of inflammatory bowel disease unclassified, BMC GASTROENTEROLOGY, 10.1186/s12876-021-01656-1, 21, 1, 73-73, Feb 16;21:73., 2021.02, BACKGROUND: The pathological conditions of UC and CD involved in inflammatory bowel disease-unclassified (IBD-U), UC with primary sclerosing cholangitis (PSC-UC), and UC with autoimmune pancreatitis type 2 (AIP-UC) remain unclear. Therefore, it is difficult to decide the appropriate treatments for these subtypes of UC. Our aim was to examine whether the discriminant equation using the mucosally expressed mediators designed as our previous study for IBD, could characterize IBD-U, PSC-UC, or AIP-UC. METHODS: A total of 56 patients including UC (n = 24), CD (n = 15), IBD-U (n = 10), PSC-UC (n = 4), and AIP-UC (n = 3), along with 9 control patients were enrolled in this study. Mucosally expressed inflammatory mediators related to Th1, Th2, Th17, and Treg were measured using quantitative PCR in endoscopic biopsies from the inflamed intestines of the patients. The IBD-U, PSC-UC or AIP-UC were characterized using discriminant analysis and principle component analysis. RESULTS: Through discriminant analyses, combinations of 3 to 7 inflammatory mediators were used to discriminate between UC and CD. Moreover, the identified 3 markers could diagnose patients with IBD-U as UC or CD with high accuracy. The distribution graph of inflammatory mediators using the principal component analysis revealed that PSC-UC and AIP-UC exhibited CD-like and UC-like features, respectively. CONCLUSIONS: The discriminant equation using mucosally expressed mediators of IL-13, IL-21 and T-bet can be used as a universal diagnostic tool not only for IBD-U but also to assess pathological conditions in PSC-UC and AIP-UC..
32. Ogino H, Fukaura K, Iboshi Y, Nagamatsu Y, Okuno H, Nishioka K, Nishihara Y, Tanaka Y, Chinen T, Ihara E, Ogawa Y., Role of the IL-23-T-bet/GATA3 Axis for the Pathogenesis of Ulcerative Colitis., Inflammation. 2021 Apr;44(2):592-603., 10.1007/s10753-020-01358-y, 44, 2, 592-603, 2021.04.
33. Muta K, Ihara E, Hamada S, Ikeda H, Wada M, Hata Y, Bai X, Nishihara Y, Tanaka Y, Ogino H, Ogawa Y, Physiological and pathological roles of the accommodation response in lower esophageal sphincter relaxation during wet swallows., Scientific reports, 10.1038/s41598-021-87052-x, 11, 1, 7898-7898, Apr 12;11:7898., 2021.04, The preparatory accommodation response of lower esophageal sphincter (LES) before swallowing is one of the mechanisms involved in LES relaxation during wet swallows, however, the physiological and/or pathological roles of LES accommodation remain to be determined in humans. To address this problem, we conducted a prospective observational study of 38 patients with normal high-resolution manometry (HRM) and 23 patients with idiopathic esophagogastric junction outflow obstruction (EGJOO) to assess dry and wet swallows. The LES accommodation measurement was proposed for practical use in evaluating the LES accommodation response. Although swallow-induced LES relaxation was observed in both dry and wet swallows, LES accommodation (6.4, 3.1-11.1 mmHg) was only observed in wet swallows. The extent of LES accommodation was impaired in idiopathic EGJOO (0.6, - 0.6-6 mmHg), and the LES accommodation measurement of patients with idiopathic EGJOO (36.8, 29.5-44.3 mmHg) was significantly higher in comparison to those with normal HRM (23.8, 18-28.6 mmHg). Successful LES relaxation in wet swallowing can be achieved by LES accommodation in combination with swallow-induced LES relaxation. Impaired LES accommodation is characteristic of idiopathic EGJOO. In addition to the IRP value, the LES accommodation measurement may be useful for evaluating the LES relaxation function in clinical practice..
34. Eikichi Ihara, Shohei Hamada, Kazumasa Muta, Masafumi Wada, Yoshitaka Hata, Hiroko Ikeda, Yoshimasa Tanaka, Haruei Ogino, Takatoshi Chinen, Yoshihiro Ogawa, USEFULNESS OF ONIGIRI ESOPHAGOGRAPHY COMBINED WITH AN OBSTRUCTION LEVEL CLASSIFICATION SYSTEM IN SCREENING ESOPHAGEAL MOTILITY DISORDERS, GASTROENTEROLOGY, 160, 6, S648-S649, 2021.05.
35. Nishihara Y, Ogino H, Tanaka M, Ihara E, Fukaura K, Nishioka K, Chinen T, Tanaka Y, Nakayama J, Kang D, Ogawa Y., Mucosa-associated gut microbiota reflects clinical course of ulcerative colitis, SCIENTIFIC REPORTS, 10.1038/s41598-021-92870-0, 11, 1, 13743-13743, Jul 2;11:13743., 2021.07, This longitudinal study was designed to elucidate whether gut microbiota is associated with relapse and treatment response in ulcerative colitis (UC) patients. Fifty-one patients with UC were enrolled between 2012 and 2017, and followed up through 2020. Colon mucosal biopsy were obtained at enrollment, and 16S ribosomal RNA sequencing was performed using extracted RNA. Of the 51 patients, 24 were in remission and 27 had active UC at enrollment. Of the 24 patients in remission, 17 maintained remission and 7 developed relapse during follow-up. The 7 patients with relapse showed lower diversity, with a lower proportion of Clostridiales (p = 0.0043), and a higher proportion of Bacteroides (p = 0.047) at enrollment than those without relapse. The 27 patients with active UC were classified into response (n = 6), refractory (n = 13), and non-response (n = 8) groups according to their treatment response in 6 months. The refractory and non-response groups showed lower diversity with a lower proportion of Prevotella (p = 0.048 and 0.043) at enrollment than the response group. This study is the first demonstration that reduced diversity and particular microbes are associated with the later clinical course of relapse events and treatment response in UC..
36. Hamada S, Ihara E, Muta K, Wada M, Hata Y, Ikeda H, Tanaka Y, Ogino H, Chinen T, Ogawa Y., Onigiri esophagography as a screening test for esophageal motility disorders., Journal of neurogastroenterology and motility, 10.5056/jnm20138, 28, 1, 43-52, In press., 2021.07, Background/Aims: No screening test for esophageal motility disorder (EMD) has been established, the objective of this study is to examine the potential usefulness of our newly developed "Onigiri esophagography" combined with an obstruction level (OL) classification system in screening for EMD. Methods: A total of 102 patients with suspected EMDs who underwent both high-resolution manometry (HRM) and Onigiri esophagography between April 2017 and January 2019 were examined. The EMD diagnosis was performed based on the Chicago classification version 3.0 by HRM. Onigiri esophagography was performed using a liquid medium (barium sulfate) followed by a solid medium, which consisted of an Onigiri (a Japanese rice ball) with barium powder. The extent of medium obstruction was assessed by the OL classification, which was defined in a stepwise fashion from OL0 (no obstruction) to OL4 (severe obstruction). Results: The patients with OL0 (32.3%), OL1 (50.0%), OL2 (88.0%), OL3 (100.0%), and OL4 (100.0%) were diagnosed EMDs by HRM. The area under the curve, as determined by a receiver operating characteristic analysis, for the OL classification was 0.86. Using the cutoff value of OL1, the sensitivity and specificity were 87.3% and 61.3%, respectively, while using a cutoff value of OL2, the sensitivity and specificity were 73.2% and 90.3%, respectively. Conclusion: In conclusion, Onigiri esophagography combined with the OL classification system can be used as a screening test for EMDs with a cutoff value of OL1..
37. Kei Nishioka, Haruei Ogino, Takatoshi Chinen, Eikichi Ihara, Yoshimasa Tanaka, Kazuhiko Nakamura, Yoshihiro Ogawa, Mucosal IL23A expression predicts the response to Ustekinumab in inflammatory bowel disease., Journal of gastroenterology, 10.1007/s00535-021-01819-7, 2021.08, BACKGROUND: Biologics against tumor necrosis factor-α (TNF) and the p40 subunit of interleukin (IL)-12 and IL-23 are increasingly used in inflammatory bowel disease (IBD) treatment. However, information on response prediction to these agents is limited. Thus, we aimed to identify factors for IBD treatment response prediction. METHODS: We conducted a retrospective study in 33 IBD subjects for anti-TNF and a prospective study of 23 IBD and 11 non-IBD subjects for ustekinumab (UST). Mucosal biopsy specimens were obtained before treatment with biologics. The expression of 18 immune-related genes encoding representative cytokines and transcription factors was analyzed by quantitative polymerase chain reaction. RESULTS: There was no difference between the treatment-resistant and -sensitive groups with regard to clinical characteristics. A higher expression of oncostatin M (OSM) and its receptor OSMR in the intestinal mucosa was most strongly associated with anti-TNF resistance, whereas lower IL23A expression was most strongly associated with UST resistance. In addition to the absolute expression levels of genes, concordant or discordant expression patterns of particular gene sets were associated with treatment sensitivity and resistance. CONCLUSIONS: The association of anti-TNF resistance and mucosal OSM and OSMR expression was consistent with the results of a previous study in a European cohort. Our observation that IBD subjects with higher mucosal IL23A expression were more likely to achieve remission by UST has not been previously reported. The response to biologics may thus be predicted in IBD patients through the analysis of mucosal gene expression levels and patterns..
38. Otsuka Y, Bai X, Tanaka Y, Ihara E, Chinen T, Ogino H, Ogawa Y., Involvement of interstitial cells of Cajal in nicotinic acetylcholine receptor-induced relaxation of the porcine lower esophageal sphincter., European journal of pharmacology, 10.1016/j.ejphar.2021.174491, 910, 174491-174491, Nov 5;910:174491., 2021.09, The interstitial cells of Cajal (ICCs) play an important role in coordinated gastrointestinal motility. The present study aimed to elucidate whether or how ICCs are involved in the lower esophageal sphincter (LES) relaxation induced by stimulation of the nicotinic acetylcholine receptor. The application of 1,1-dimethyl-4-phenyl-piperazinium (DMPP; a nicotinic acetylcholine receptor agonist) induced a transient relaxation in the circular smooth muscle of the porcine LES. DMPP-induced relaxation was abolished by not only 1 μM tetrodotoxin but also the inhibition of ICC activity by pretreatment with 100 μM carbenoxolone (a gap junction inhibitor), pretreatment with 100 μM CaCCinh-A01 (an anoctamin-1 blocker acting as a calcium-activated chloride channel inhibitor), and pretreatment with Cl--free solution. However, pretreatment with 100 μM Nω-nitro-L-arginine methyl ester had little effect on DMPP-induced relaxation. Furthermore, DMPP-induced relaxation was inhibited by pretreatment with 1 mM suramin, a purinergic P2 receptor antagonist, but not by 1 μM VIP (6-28), a vasoactive intestinal peptide (VIP) receptor antagonist. Stimulation of the purinergic P2 receptor with adenosine triphosphate (ATP) induced relaxation, which was abolished by the inhibition of ICC activity by pretreatment with CaCCinh-A01. In conclusion, membrane hyperpolarization of the ICCs via the activation of anoctamin-1 plays a central role in DMPP-induced relaxation. ATP may be a neurotransmitter for inhibitory enteric neurons, which stimulate the ICCs. The ICCs act as the interface of neurotransmission of nicotinic acetylcholine receptor in order to induce LES relaxation..
39. 牟田 和正, 伊原 栄吉, 池田 浩子, 和田 将史, 水流 大尭, 畑 佳孝, 白 暁鵬, 田中 義将, 荻野 治栄, 小川 佳宏, 嚥下時におけるLES accommodationの生理的・病理的役割(Physiological and pathological roles of the LES accommodation during swallowing), 日本食道学会学術集会プログラム・抄録集, 75回, 76-76, 2021.09.
40. Ihara E, Ogino H, Muta K, Hamada S, Wada M, Hata Y, Ikeda H, Bai X, Minoda Y, Esaki M, Tanaka Y, Chinen T, Ogawa Y., The treatment effects of acotiamide in esophagogastric outflow obstruction: a prospective longitudinal observational study, ESOPHAGUS, 10.1007/s10388-021-00887-1, 19, 2, 332-342, In press., 2021.10, OBJECTIVES: We have found that an altered lower esophageal sphincter (LES) accommodation response is an underlying cause of esophagogastric junction outflow obstruction (EGJOO). The objective of this study was to examine the treatment effect of acotiamide, a prokinetic agent which improves impaired gastric accommodation in functional dyspepsia, in patients with EGJOO. METHODS: A prospective observational longitudinal study was conducted between October 2014 and March 2020. Acotiamide (100 mg, 3 times a day) was administered to 25 patients with EGJOO for 4 weeks. High-resolution manometry (HRM) was performed just before and after 4 weeks of treatment. RESULTS: As the primary outcome, the extent of integrated relaxation pressure (IRP) after treatment (14.6, 12.1-22.0 mmHg) was significantly lower than that before treatment (19.4, 17.1-27.4 mmHg). The extent of LES accommodation index after treatment (32.7, 21.0-40.0 mmHg) was also significantly lower than that before treatment (39.3, 31.2-50.2 mmHg). Acotiamide normalized the IRP (
41. Yoko Igarashi-Hisayoshi, Eikichi Ihara, Xiaopeng Bai, Chika Higashi, Hiroko Ikeda, Yoshimasa Tanaka, Mayumi Hirano, Haruei Ogino, Takatoshi Chinen, Yasushi Taguchi, Yoshihiro Ogawa, Determination of Region-Specific Roles of the M3 Muscarinic Acetylcholine Receptor in Gastrointestinal Motility., Digestive diseases and sciences, 10.1007/s10620-022-07637-y, 68, 2, 439-450, 2022.08, BACKGROUND: The specific role of the M3 muscarinic acetylcholine receptor in gastrointestinal motility under physiological conditions is unclear, due to a lack of subtype-selective compounds. AIMS: The objective of this study was to determine the region-specific role of the M3 receptor in gastrointestinal motility. METHODS: We developed a novel positive allosteric modulator (PAM) for the M3 receptor, PAM-369. The effects of PAM-369 on the carbachol-induced contractile response of porcine esophageal smooth muscle and mouse colonic smooth muscle (ex vivo) and on the transit in mouse small intestine and rat colon (in vivo) were examined. RESULTS: PAM-369 selectively potentiated the M3 receptor under the stimulation of its orthosteric ligands without agonistic or antagonistic activity. Half-maximal effective concentrations of PAM activity for human, mouse, and rat M3 receptors were 0.253, 0.345, and 0.127 μM, respectively. PAM-369 enhanced carbachol-induced contraction in porcine esophageal smooth muscle and mouse colonic smooth muscle without causing any contractile responses by itself. The oral administration of 30 mg/kg PAM-369 increased the small intestinal transit in both normal motility and loperamide-induced intestinal dysmotility mice but had no effects on the colonic transit, although the M3 receptor mRNA expression is higher in the colon than in the small intestine. CONCLUSIONS: This study provided the first direct evidence that the M3 receptor has different region-specific roles in the motility function between the small intestine and colon in physiological and pathophysiological contexts. Selective PAMs designed for targeted subtypes of muscarinic receptors are useful for elucidating the subtype-specific function..
42. Yoshitaka Hata, Eikichi Ihara, Masafumi Wada, Hirotaka Tsuru, Kazumasa Muta, Yosuke Minoda, Xiaopeng Bai, Mitsuru Esaki, Yoshimasa Tanaka, Takatoshi Chinen, Haruei Ogino, Ryuichi Sakamoto, Yoshihiro Ogawa, Improved esophagography screening for esophageal motility disorders using wave appearance and supra-junctional ballooning., Journal of gastroenterology, 10.1007/s00535-022-01913-4, 57, 11, 838-847, 2022.08, BACKGROUND: High-resolution manometry (HRM) is the gold standard for diagnosing esophageal motility disorders (EMDs); however, it requires specialized equipment. The development of more accessible screening examinations is expected. We evaluated the utility of barium esophagography (BE) screening using two novel findings to diagnose EMDs. METHODS: Between January 2013 and October 2020, 244 patients with suspected EMDs who underwent both HRM and BE were analyzed. The EMD diagnosis was based on HRM findings using Chicago Classification version 3.0. BE was performed using sequential esophagography with barium sulfate. Three conventional BE findings (air-fluid level, rosary-bead/corkscrew appearance, and absent/weak peristalsis) and two novel BE findings (wave appearance and supra-junctional ballooning) were used for diagnosis. RESULTS: The sensitivity and specificity of BE screening using the two novel findings and conventional findings to diagnose EMDs were 79.4% and 88%, respectively [area under the receiver-operating characteristic curve (AUC) = 0.837]. Without these novel findings, they were 63.9% and 96%, respectively (AUC = 0.800), respectively. Achalasia was highly correlated with the air-fluid level (88.7%). Absent contractility was highly correlated with absent/weak peristalsis (85.7%). Relatively high correlations were observed between distal esophageal spasm and rosary-bead/corkscrew appearance (60%), and between achalasia and wave appearance (59.7%). The intra-observer reproducibility and inter-observer agreement for individual BE findings were 84.4% and 75%, respectively. Wave appearance was associated with higher integrated relaxation pressure (IRP) and shorter distal latency. Supra-junctional ballooning was associated with higher IRP. CONCLUSIONS: BE screening using two additional novel findings to diagnose EMDs could be useful in general practice..
43. Yosuke Minoda, Eikichi Ihara, Nao Fujimori, Shuzaburo Nagatomo, Mitsuru Esaki, Yoshitaka Hata, Xiaopeng Bai, Yoshimasa Tanaka, Haruei Ogino, Takatoshi Chinen, Qingjiang Hu, Eiji Oki, Hidetaka Yamamoto, Yoshihiro Ogawa, Efficacy of ultrasound endoscopy with artificial intelligence for the differential diagnosis of non-gastric gastrointestinal stromal tumors., Scientific reports, 10.1038/s41598-022-20863-8, 12, 1, 16640-16640, 2022.10, Gastrointestinal stromal tumors (GISTs) are common subepithelial lesions (SELs) and require treatment considering their malignant potential. We recently developed an endoscopic ultrasound-based artificial intelligence (EUS-AI) system to differentiate GISTs from non-GISTs in gastric SELs, which were used to train the system. We assessed whether the EUS-AI system designed for diagnosing gastric GISTs could be applied to non-gastric GISTs. Between January 2015 and January 2021, 52 patients with non-gastric SELs (esophagus, n = 15; duodenum, n = 26; colon, n = 11) were enrolled. The ability of EUS-AI to differentiate GISTs from non-GISTs in non-gastric SELs was examined. The accuracy, sensitivity, and specificity of EUS-AI for discriminating GISTs from non-GISTs in non-gastric SELs were 94.4%, 100%, and 86.1%, respectively, with an area under the curve of 0.98 based on the cutoff value set using the Youden index. In the subanalysis, the accuracy, sensitivity, and specificity of EUS-AI were highest in the esophagus (100%, 100%, 100%; duodenum, 96.2%, 100%, 0%; colon, 90.9%, 100%, 0%); the cutoff values were determined using the Youden index or the value determined using stomach cases. The diagnostic accuracy of EUS-AI increased as lesion size increased, regardless of lesion location. EUS-AI based on gastric SELs had good diagnostic ability for non-gastric GISTs..
44. Yosuke Minoda, Mitsuru Esaki, Eikichi Ihara, Shuzaburo Nagatomo, Kei Nishioka, Nao Fujimori, Haruei Ogino, Xiaopeng Bai, Yoshimasa Tanaka, Takatoshi Chinen, Qingjiang Hu, Mitsuhiko Ota, Shinya Umekita, Hidetaka Yamamoto, Yoshihiro Ogawa, Auxiliary diagnosis of subepithelial lesions by impedance measurement during endoscopic ultrasound guided fine-needle biopsy., Gastrointestinal endoscopy, 10.1016/j.gie.2022.11.022, 97, 5, 977-984, 2022.11, INTRODUCTION: Endoscopic ultrasound guided fine-needle aspiration/biopsy (EUS-FNA/B) is the gold standard for diagnosing subepithelial lesions (SELs); however, its diagnostic ability for SELs
45. Masafumi Wada, Yosuke Minoda, Eikichi Ihara, Hirotaka Tsuru, Yoshitaka Hata, Shuzaburo Nagatomo, Mitsuru Esaki, Xiaopeng Bai, Yoshimasa Tanaka, Takatoshi Chinen, Haruei Ogino, Yoshihiro Ogawa, Development of a new endoscopy system to visualize bilirubin for the diagnosis of duodenogastroesophageal reflux., Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 10.1111/den.14749, 2023.12, OBJECTIVES: Reflux hypersensitivity (RH) is a form of refractory gastroesophageal reflux disease in which duodenogastroesophageal reflux (DGER) plays a role. This study aimed to determine the usefulness of an endoscopy system equipped with image-enhanced technology for evaluating DGER and RH. METHODS: The image enhancement mode for detecting bilirubin and calculated values were defined as the Bil mode and Bil value, respectively. First, the visibility of the Bil mode was validated for a bilirubin solution and bile concentrations ranging from 0.01% to 100% (0.002-20 mg/dL). Second, visibility scores of the Bil mode, when applied to the porcine esophagus sprayed with a bilirubin solution, were compared to those of the blue laser imaging (BLI) and white light imaging (WLI) modes. Third, a clinical study was conducted to determine the correlations between esophageal Bil values and the number of nonacid reflux events (NNRE) during multichannel intraluminal impedance-pH monitoring as well as the utility of esophageal Bil values for the differential diagnosis of RH. RESULTS: Bilirubin solution and bile concentrations higher than 1% were visualized in red using the Bil mode. The visibility score was significantly higher with the Bil mode than with the BLI and WLI modes for 1% to 6% bilirubin solutions (P 
46. Hiroko Ikeda, Eikichi Ihara, Kosuke Takeya, Koji Mukai, Manabu Onimaru, Kenoki Ouchida, Yoshitaka Hata, Xiaopeng Bai, Yoshimasa Tanaka, Taisuke Sasaki, Fumiyo Saito, Masumi Eto, Jiro Nakayama, Yoshinao Oda, Masafumi Nakamura, Haruhiro Inoue, Yoshihiro Ogawa, The interplay between alterations in esophageal microbiota associated with Th17 immune response and impaired LC20 phosphorylation in achalasia., Journal of gastroenterology, 10.1007/s00535-024-02088-w, 2024.03, BACKGROUND: Achalasia is an esophageal motility disorder with an unknown etiology. We aimed to determine the pathogenesis of achalasia by studying alterations in esophageal smooth muscle contraction and the associated inflammatory response, and evaluate the role of esophageal microbiota in achalasia development. METHODS: We analyzed esophageal mucosa and lower esophageal sphincter (LES) samples, obtained from patients with type II achalasia who underwent peroral endoscopic myotomy. Esophageal conditioned media obtained from patients were transferred into the mouse esophagus to determine whether the esophageal intraluminal environment is associated with achalasia. RESULTS: Approximately 30% of 20-kDa myosin light chains (LC20) was phosphorylated in LES from the control group under resting and stimulated conditions, whereas less than 10% of LC20 phosphorylation was detected in achalasia under all conditions. The hypophosphorylation of LC20 in achalasia was associated with the downregulation of the myosin phosphatase-inhibitor protein CPI-17. Th17-related cytokines, including IL-17A, IL-17F, IL-22, and IL-23A, were significantly upregulated in achalasia. α-Diversity index of esophageal microbiota and the proportion of several microbes, including Actinomyces and Dialister, increased in achalasia. Actinomyces levels positively correlated with IL-23A levels, whereas Dialister levels were positively associated with IL-17A, IL-17F, and IL-22 levels. Esophageal IL-17F levels increased in mice after oral administration of the conditioned media. CONCLUSIONS: In LES of patients with achalasia, hypophosphorylation of LC20, a possible cause of impaired contractility, was associated with CPI-17 downregulation and an increased Th17-related immune response. The esophageal intraluminal environment, represented by the esophageal microbiota, could be associated with the development and exacerbation of achalasia..