71 results on '"Kasugai, K."'
Search Results
2. A case of the familial amyloid polyneuropathy diagnosed at the hematemesis
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Koguri T, Aihara M, Yoshida T, Kasugai K, Yamamoto Y, T Yokoi, Kamishima S, Nita M, Matsumura A, and Yamamoto M
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business.industry ,Amyloid polyneuropathy ,Medicine ,General Medicine ,business ,Bioinformatics - Abstract
症例は43歳,女性,長野県小川村の出身.平成8年1月30日,突然頻回の嘔吐発作後に吐血をきたし当科受診,上部消化管内視鏡検査にて吐血の原因はMallory-Weiss症候群と診断した.この時に施行した胃,十二指腸の生検組織からフミロイド沈着が確認され,さらに家族歴及び遺伝子解析にてI型家族性アミロイドポリニューロパシーと診断した.吐血を契機に行った内視鏡時の消化管生検が診断に有用であった家族性アミロイドポリニューロパシーを経験した.
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- 1998
3. Aesthetic Intelligence: The Role of Design in Ambient Intelligence.
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Röcker, C., Kasugai, K., Plewe, D., Kiriyama, T., Lugmayr, Artur, Röcker, C., Kasugai, K., Plewe, D., Kiriyama, T., and Lugmayr, Artur
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This paper illustrates the rationale behind the second international workshop on Aesthetic Intelligence. The workshop addresses the multiple facets of aesthetics in the design process of Ambient Intelligence technologies, especially in the fields of architecture, industrial and interface design as well as human-computer interaction.
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- 2012
4. Protective actions of E-cadherin expressed on rat cultured gastric epithelial cells against epithelial barrier dysfunctions induced by chemical hypoxia/reoxygenation
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Mizuno, M., Okayama, N., Kasugai, K., Yoshida, T., Miyata, M., Nitta, M., Joh, T., and Itoh, M.
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- 2001
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5. Crucial role of c-Jun NH2-terminal kinase 1 (JNK1) in cold restraint stress-induced gastric lesions in mice
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Kasugai, K., Watson, S.J., Flavell, R.A., Davis, R.J., and Todisco, A.
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- 2001
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6. Mitogenic activity due to epidermal growth factor in gastric juice of the rat
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Joh, T., Itoh, M., Kasugai, K., Seno, K., Okayama, N., Yokoyama, Y., and Takeuchi, T.
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- 1994
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7. Characterisation of colorectal cancer by hierarchical clustering analyses for five stroma-related markers.
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Ito S, Koshino A, Wang C, Otani T, Komura M, Ueki A, Kato S, Takahashi H, Ebi M, Ogasawara N, Tsuzuki T, Kasai K, Kasugai K, Takiguchi S, Takahashi S, and Inaguma S
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- Humans, Male, Female, Aged, Middle Aged, Cluster Analysis, Immunohistochemistry, Tumor Microenvironment, Prognosis, Membrane Glycoproteins analysis, Membrane Glycoproteins metabolism, Stromal Cells pathology, Stromal Cells metabolism, Decorin analysis, Decorin metabolism, Adult, Aged, 80 and over, Kaplan-Meier Estimate, Colorectal Neoplasms pathology, Colorectal Neoplasms mortality, Colorectal Neoplasms metabolism, Biomarkers, Tumor analysis, Cancer-Associated Fibroblasts pathology, Cancer-Associated Fibroblasts metabolism
- Abstract
Evidence for the tumour-supporting capacities of the tumour stroma has accumulated rapidly in colorectal cancer (CRC). Tumour stroma is composed of heterogeneous cells and components including cancer-associated fibroblasts (CAFs), small vessels, immune cells, and extracellular matrix proteins. The present study examined the characteristics of CAFs and collagen, major components of cancer stroma, by immunohistochemistry and Sirius red staining. The expression status of five independent CAF-related or stromal markers, decorin (DCN), fibroblast activation protein (FAP), podoplanin (PDPN), alpha-smooth muscle actin (ACTA2), and collagen, and their association with clinicopathological features and clinical outcomes were analysed. Patients with DCN-high tumours had a significantly worse 5-year survival rate (57.3% versus 79.0%; p = 0.044). Furthermore, hierarchical clustering analyses for these five markers identified three groups that showed specific characteristics: a solid group (cancer cell-rich, DCN
Low PDPNLow ); a PDPN-dominant group (DCNMid PDPNHigh ); and a DCN-dominant group (DCNHigh PDPNLow ), with a significant association with patient survival (p = 0.0085). Cox proportional hazards model identified the PDPN-dominant group (hazard ratio = 0.50, 95% CI = 0.26-0.96, p = 0.037) as a potential favourable factor compared with the DCN-dominant group. Of note, DCN-dominant tumours showed the most advanced pT stage and contained the lowest number of CD8+ and FOXP3+ immune cells. This study has revealed that immunohistochemistry and special staining of five stromal factors with hierarchical clustering analyses could be used for the prognostication of patients with CRC. Cancer stroma-targeting therapies may be candidate treatments for patients with CRC., (© 2024 The Author(s). The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)- Published
- 2024
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8. Factors Associated with Defecation Satisfaction among Japanese Adults with Chronic Constipation.
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Yamamoto S, Ohashi W, Yamaguchi Y, Igari H, Koshino A, Sugiyama T, Nagao K, Tamura Y, Izawa S, Mano M, Ebi M, Usami J, Hamano K, Izumi J, Wakita Y, Funaki Y, Ogasawara N, Sasanabe R, Sasaki M, Maekawa M, and Kasugai K
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Background: Constipation causes substantial morbidity worldwide. Methods: This survey assessed constipation-related factors in Japan using the Japanese version of the Irritable Bowel Syndrome Quality of Life (IBS-QOL-J) instrument. We also examined the relationship among laxative type, Bristol Stool Form Scale (BSFS) scores, and treatment cost. Finally, we examined differences in satisfaction scores according to laxative type, treatment type, treatment cost, and BSFS score. Results: IBS-QOL-J was higher among those taking salt and/or irritation laxatives. Those paying >JPY 5000 (USD 50.00) had the lowest IBS-QOL-J. IBS-QOL-J was significantly lower among those with a BSFS score of 1 or 2 (severe constipation). Conclusions: This study's findings suggest that a variety of factors, including treatment type and cost, are associated with defecation satisfaction. Those who had hard stools, used multiple laxatives, or spent more on treatment were less satisfied. Future strategies should target therapies that do not require multiple laxatives with lower treatment costs. Adequate defecation with a small number of appropriate laxatives at minimal cost appears to improve defecation satisfaction. It is desirable to identify appropriate laxatives and improve dietary habits and exercise routines. It is also necessary to stop blindly increasing laxative usage and properly diagnose constipation disorders such as anatomical abnormalities other than functional constipation.
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- 2024
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9. Simultaneous Expression of CD70 and POSTN in Cancer-Associated Fibroblasts Predicts Worse Survival of Colorectal Cancer Patients.
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Komura M, Wang C, Ito S, Kato S, Ueki A, Ebi M, Ogasawara N, Tsuzuki T, Kasai K, Kasugai K, Takiguchi S, Takahashi S, and Inaguma S
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- Humans, Fibroblasts metabolism, Immunohistochemistry, Cell Proliferation, Cell Adhesion Molecules metabolism, CD27 Ligand metabolism, Cancer-Associated Fibroblasts metabolism, Colorectal Neoplasms pathology
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Colorectal cancer (CRC) is one of the most common gastrointestinal cancers worldwide, with high morbidity and mortality rates. The evidence for the tumor-supporting capacities of cancer-associated fibroblasts (CAFs) that modulate cancer cell proliferation, invasion, metastasis, and tumor immunity, including in CRC, has been attracting attention. The present study examined the expression status of CD70 and POSTN in CRC and analyzed their association with clinicopathological features and clinical outcomes. In the present study, in total 15% (40/269) and 44% (119/269) of cases exhibited CD70 and POSTN expression on CAFs, respectively. Co-expression of CD70 and POSTN was detected in 8% (21/269) of patients. Fluorescent immunohistochemistry identified the co-expression of CD70 and POSTN with FAP and PDPN, respectively. ACTA2 was not co-expressed with CD70 or POSTN in CRC CAFs. CRC with CD70+/POSTN+ status in CAFs was significantly associated with distant organ metastasis ( p = 0.0020) or incomplete resection status ( p = 0.0011). CD70+/POSTN+ status tended to associate with advanced pT stage ( p = 0.032) or peritoneal metastasis ( p = 0.0059). Multivariate Cox hazards regression analysis identified CD70+/POSTN+ status in CAFs [hazard ratio (HR) = 3.78] as a potential independent risk factor. In vitro experiments revealed the activated phenotypes of colonic fibroblasts induced by CD70 and POSTN, while migration and invasion assays identified enhanced migration and invasion of CRC cells co-cultured with CD70- and POSTN-expressing colonic fibroblasts. On the basis of our observations, CD70 and POSTN immunohistochemistry can be used in the prognostication of CRC patients. CRC CAFs may be a promising target in the treatment of CRC patients.
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- 2024
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10. Background factors of idiopathic peptic ulcers and optimal treatment methods: a multicenter retrospective Japanese study.
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Nakajima N, Takeuchi T, Hokari R, Narimatsu K, Iijima K, Koizumi S, Kasugai K, Ebi M, Nagahara A, Takeda T, Tomita T, Shinzaki S, Mizukami K, Murakami K, Yagi N, Mukai R, Okumura T, Tanabe H, Tanaka K, Iwamoto J, Irisawa A, Fukushi K, Kataoka H, Nishie H, Fujiwara Y, Otani K, Handa O, Maruyama Y, Uraoka T, Hosaka H, Furuta T, Takagi T, Nakamura M, Nyumura Y, Hakoda A, Sugawara N, Iwatubo T, Ota K, Kawaguchi S, Higuchi K, and Nishikawa H
- Abstract
This study investigated the trends in idiopathic peptic ulcers, examined the characteristics of refractory idiopathic peptic ulcer, and identified the optimal treatment. The characteristics of 309 patients with idiopathic peptic ulcer were examined. We allocated idiopathic peptic ulcers that did not heal after 8 weeks' treatment (6 weeks for duodenal ulcers) to the refractory group and those that healed within this period to the healed group. The typical risk factors for idiopathic peptic ulcer (atherosclerosis-related underlying disease or liver cirrhosis complications) were absent in 46.6% of patients. Absence of gastric mucosal atrophy (refractory group: 51.4%, healed group: 28.4%; p = 0.016), and gastric fundic gland polyps (refractory group: 17.6%, healed group: 5.9%; p = 0.045) were significantly more common in the refractory group compared to the healed group. A history of H. pylori eradication (refractory group: 85.3%, healed group: 66.0%; p = 0.016), previous H. pylori infection (i.e., gastric mucosal atrophy or history of H. pylori eradication) (refractory group: 48.5%, healed group: 80.0%; p = 0.001), and potassium-competitive acid blocker treatment (refractory group: 28.6%, healed group, 64.1%; p = 0.001) were significantly more frequent in the healed group compared to the refractory group. Thus, acid hypersecretion may be a major factor underlying the refractoriness of idiopathic peptic ulcer., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2024 JCBN.)
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- 2024
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11. Gastroesophageal Reflux Disease: Pathophysiology and New Treatment Trends.
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Kasugai K and Ogasawara N
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- Humans, Endoscopy, Europe, Proton Pump Inhibitors therapeutic use, Gastroesophageal Reflux drug therapy
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Gastroesophageal reflux disease (GERD) is caused by the reflux of gastric contents into the esophagus due to a decline in esophageal clearance and anti-reflux barrier mechanisms. Mucosal injury is caused by a combination of gastric juice directly damaging the esophageal mucosa and the immune and inflammatory mechanism in which inflammatory cytokines released from the esophageal mucosal epithelium cause neutrophil migration, triggering inflammation. Gastric secretion inhibitors are the first-line treatment for GERD, but they can be combined with prokinetic agents and Chinese herbal remedies. However, pharmacotherapy cannot improve anatomical problems or prevent physical causes of GERD, such as reflux of non-acidic contents. Therefore, surgery can be warranted, depending on the pathology. Intraluminal endoscopic therapy, which is both less invasive and more effective than surgery, was recently developed and applied in Europe and the United States. In Japan, intraluminal endoscopic therapies, such as anti-reflux mucosectomy, anti-reflux mucosal ablation, and endoscopic submucosal dissection, for GERD have been independently developed.
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- 2024
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12. A Vonoprazan, Clarithromycin, and Metronidazole Regimen as Helicobacter pylori Eradication Therapy for Patients with Penicillin Allergy in Light of Clarithromycin Resistance.
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Adachi K, Kato S, Koshino A, Nagao K, Sugiyama T, Yoshimine T, Yamaguchi Y, Izawa S, Ohashi W, Ebi M, Funaki Y, Ogasawara N, Sasaki M, and Kasugai K
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- Humans, Clarithromycin therapeutic use, Metronidazole therapeutic use, Anti-Bacterial Agents adverse effects, Retrospective Studies, Drug Therapy, Combination, Penicillins therapeutic use, Proton Pump Inhibitors adverse effects, Amoxicillin therapeutic use, Treatment Outcome, Helicobacter pylori, Helicobacter Infections drug therapy, Hypersensitivity drug therapy
- Abstract
Objective Vonoprazan (VPZ), clarithromycin (CAM), metronidazole (MNZ) and VPZ, MNZ, and sitafloxacin (STFX) regimen are all established Helicobacter pylori eradication therapies for patients with penicillin allergy in Japan. However, no study has assessed the efficacy of a VPZ, CAM, and MNZ (VCM) regimen in patients with clarithromycin resistance (CAM-R). We therefore assessed the efficacy of a VCM regimen for treating H. pylori infection in patients with CAM-R and penicillin allergy. Methods Fifty-three patients with penicillin allergy who received H. pylori eradication therapy were retrospectively analyzed. Eight patients received a 7-day proton-pump inhibitor, CAM, and MNZ (PCM) regimen; 35 patients [11 CAM-R, and 10 with clarithromycin sensitivity (CAM-S)] received 7-day VCM regimens; and 10 patients received 7-day VPZ, MNZ, and STFX (VMS) regimens. A
13 C-urea breath test was used to determine eradication. The efficacy of eradication was evaluated via both intention-to-treat (ITT) and per-protocol (PP) analyses. Results According to ITT and PP analyses, eradication rates (ERs) with PCM, VCM, and VMS therapies were 50.0% and 50.0%, 94.3% and 100%, and 90% and 90%, respectively. Treatment was successful in all patients with CAM-S. For patients with CAM-R, treatment was successful in 10 patients, and 1 patient discontinued treatment owing to an adverse event. According to ITT and PP analyses, ERs were 90.9% and 100% in CAM-R, and were 100% and 100% in CAM-S, respectively. Conclusion The VCM regimen for H. pylori eradication may be a viable candidate therapy for patients with penicillin allergy, regardless of CAM-R.- Published
- 2023
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13. Relationships between body mass index and constipation, gastroesophageal reflux disease, stool forms based on the Bristol Stool Form Scale, and education level: results from an internet survey in Japan.
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Ogasawara N, Kasugai K, Funaki Y, Ebi M, Izawa S, Tamura Y, Kato A, Yamaguchi Y, Adachi K, Sugiyama T, and Sasaki M
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Detailed evaluations of body mass index (BMI) and stool form based on the Bristol Stool Form Scale (BSFS) in individuals with constipation, gastroesophageal reflux disease (GERD), and concomitant constipation and GERD have not been performed in Japan. This study was an internet survey conducted to examine the relationships between BMI and constipation, GERD, stool forms based on the BSFS, and education level. This internet-based survey recruited participants from general public survey panels. 10,000 individuals meeting the eligibility criteria were enrolled. Questions included demographics, medical data, and assessments based on validated measures for constipation and GERD. BMI was significantly lower in males with versus without constipation. BMI was significantly higher with GERD both males and females. Mean BMI increased from the BSFS-1/2 group through the BSFS-3/4/5 to the BSFS-6/7 groups in both sexes. BMI was highest in individuals with a maximum education level of junior high school and second highest in individuals completing high school. This is the first real-world survey that closely examines the relationship between BMI and stool forms of individuals in Japan. When the BMI increased, stool forms varied from hard to watery in Japanese people. BMI was related with education level in Japan. (Trial registration: UMIN000039688)., Competing Interests: NO received expenses reimbursement related to this study from EA Pharma Co., Ltd. KK received expenses reimbursement related to this study from EA Pharma Co., Ltd.; research funding from EA Pharma Co., Ltd.; and scholarship donations from AstraZeneca and Daiichi Sankyo Co., Ltd., (Copyright © 2023 JCBN.)
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- 2023
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14. A case report of contrast-enhanced harmonic ultrasonography for the diagnosis of an esophageal duplication cyst.
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Adachi K, Tashiro T, Kato M, Ito T, Kato A, Takayama M, Kato S, Ono S, Yoshimine H, Koshino A, Nagao K, Kobayashi Y, Ebi M, Ogasawara N, Sasaki M, and Kasugai K
- Abstract
A 54-year-old man was referred to our hospital because of a suspected esophageal submucosal tumor on upper gastrointestinal radiography. Contrast-enhanced computed tomography showed a 52 mm homogeneous mass attached to the lower thoracic esophagus. Esophagogastroduodenoscopy revealed a 50 mm submucosal tumor in the lower esophagus, and endoscopic ultrasonography (EUS) showed a continuous hypoechoic lesion in the esophageal muscularis propria. Contrast-enhanced harmonic EUS revealed a non-echogenic area. T1 and T2 magnetic resonance imaging revealed a high-signal lesion. Based on imaging studies, an esophageal duplication cyst was diagnosed. Although asymptomatic, the patient underwent video-assisted thoracic surgery because of the possibility of rupture and the appearance of symptoms due to a future infection or enlargement, although this was not noted before. In our case, the esophageal duplication cyst appeared as a hypoechoic mass, requiring differentiation from submucosal tumor other than the cyst. Histologically, the cyst was covered by two layers of muscle covered by the chorioepithelial columnar epithelium. EUS fine-needle aspiration is effective in diagnosing submucosal tumor but also carries the risk of infection. Contrast-enhanced ultrasonography was used in this case to observe the interior and reach a preoperative diagnosis. Contrast-enhanced harmonic EUS appears to be effective in examining the interior of submucosal tumor lesions noninvasively., Competing Interests: None., (© 2023 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)
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- 2023
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15. Stromal POSTN Enhances Motility of Both Cancer and Stromal Cells and Predicts Poor Survival in Colorectal Cancer.
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Ueki A, Komura M, Koshino A, Wang C, Nagao K, Homochi M, Tsukada Y, Ebi M, Ogasawara N, Tsuzuki T, Kasai K, Kasugai K, Takahashi S, and Inaguma S
- Abstract
Evidence for the tumor-supporting capacities of cancer-associated fibroblasts (CAFs) has rapidly been accumulating. To uncover clinicopathological importance of periostin (POSTN) expression in colorectal cancer (CRC), the present study immunohistochemically examined its expression status. Furthermore, to reveal its mechanisms involved, molecular experiments were performed. In CRC tissues, 44% of the cases (119/269) exhibited POSTN expression in the CAFs. In contrast, CRC cells expressed POSTN at almost undetectable levels. Survival analyses identified that patients with POSTN-positive CRC had a significantly worse 5-year survival rate (63.2% vs. 81.2%; p = 0.011). Univariate analyses revealed that POSTN positivity was associated with peritoneal ( p = 0.0031) and distant organ metastasis ( p < 0.001). Furthermore, immunohistochemical analyses identified a significant association between POSTN and p53 complete loss status in CRC cells. Decorin and fibroblast activation protein expression in CAFs was also associated with POSTN. POSTN significantly enhanced the migration of both CRC cells and fibroblasts with FAK and AKT or STAT3 activation, and co-culture assays demonstrated the communication between CRC cells and fibroblasts, which enhanced STAT3 activation in fibroblasts. On the basis of our results, we speculated that stromal POSTN accelerated metastasis via stromal remodeling capacity and activated the migration of both tumor and stromal cells.
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- 2023
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16. Effectiveness of second-look endoscopy after gastric endoscopic submucosal dissection in patients taking antithrombotic agents: a multicenter propensity score matching analysis.
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Iwatsubo T, Takeuchi T, Hakoda A, Fujiwara Y, Nagami Y, Naito Y, Dohi O, Tatsuta T, Sawaya M, Jin X, Koike T, Sugimoto M, Murata M, Hamada K, Okada H, Kobara H, Chiyo T, Yoshida N, Tomatsuri N, Inaba T, Ishikawa S, Nagahara A, Ueyama H, Koizumi E, Iwakiri K, Mizukami K, Murakami K, Furuta T, Suzuki T, Ogasawara N, Kasugai K, Isomoto H, Kawaguchi K, Shibagaki K, Kataoka H, Shimura T, Suzuki H, Nishizawa T, and Higuchi K
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- Fibrinolytic Agents adverse effects, Gastric Mucosa surgery, Humans, Postoperative Hemorrhage epidemiology, Postoperative Hemorrhage etiology, Postoperative Hemorrhage prevention & control, Propensity Score, Prospective Studies, Retrospective Studies, Risk Factors, Endoscopic Mucosal Resection adverse effects, Stomach Neoplasms complications, Stomach Neoplasms surgery
- Abstract
Background: The risk of bleeding after gastric endoscopic submucosal dissection (ESD) in antithrombotic agent users has increased, and its management remains a problem. Second-look endoscopy (SLE) following gastric ESD in antithrombotic agent users may be effective in preventing delayed bleeding, but this requires elucidation. Therefore, this study aimed to investigate the efficacy of SLE in reducing bleeding after gastric ESD in patients receiving antithrombotic agents., Methods: This retrospective cohort study was conducted at 19 referral hospitals in Japan. A total of 1,245 patients who were receiving antithrombotic agents underwent gastric ESD between January 2013 and July 2018. The incidence of delayed bleeding was compared between SLE and non-SLE groups using propensity score matching analysis., Results: Overall, 858 patients (SLE group, 657 patients; non-SLE group, 201 patients) were analyzed. After matching, 198 pairs were created. Delayed bleeding occurred in 10 patients (5.1%) in the SLE group and 16 patients (8.1%) in the non-SLE group [odds ratio (OR) 0.605, 95% confidence interval (CI) 0.23-1.46, p = 0.310]. In the subgroup analysis, SLE reduced the incidence of delayed bleeding in patients receiving heparin bridging therapy (6.3% and 40.0%, respectively; p = 0.004). In the SLE group, prophylactic coagulation did not significantly reduce delayed bleeding compared to the no treatment group (14.6% and 8.6%, respectively; p = 0.140)., Conclusions: SLE was ineffective in reducing bleeding after gastric ESD in antithrombotic agent users, overall. A prospective comparative study is warranted to definitively evaluate the effectiveness of SLE in reducing bleeding in high-risk patients., (© 2022. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)
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- 2022
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17. Correction to: Effectiveness of second-look endoscopy after gastric endoscopic submucosal dissection in patients taking antithrombotic agents: a multicenter propensity score matching analysis.
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Iwatsubo T, Takeuchi T, Hakoda A, Fujiwara Y, Nagami Y, Naito Y, Dohi O, Tatsuta T, Sawaya M, Jin X, Koike T, Sugimoto M, Murata M, Hamada K, Okada H, Kobara H, Chiyo T, Yoshida N, Tomatsuri N, Inaba T, Ishikawa S, Nagahara A, Ueyama H, Koizumi E, Iwakiri K, Mizukami K, Murakami K, Furuta T, Suzuki T, Ogasawara N, Kasugai K, Isomoto H, Kawaguchi K, Shibagaki K, Kataoka H, Shimura T, Suzuki H, Nishizawa T, and Higuchi K
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- 2022
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18. A case report of olmesartan-associated sprue-like enteropathy: Diagnosis and healing confirmed by capsule endoscopy.
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Yamaguchi Y, Miwa T, Murakami R, Sugimura A, Yamamoto K, Sugiyama T, Tamura Y, Izawa S, Ebi M, Funaki Y, Ogasawara N, Sasaki M, and Kasugai K
- Abstract
Herein, we describe a case of olmesartan-related sprue-like enteropathy in which improvement in villous atrophy was confirmed by small-bowel capsule endoscopy (CE). We successfully treated a 66-year-old man with a chief complaint of loose diarrhea. The patient had persistent watery diarrhea 10 times a day and experienced a weight loss of 9 kg in 3 months. An abdominal computed tomography scan showed fluid retention in the small intestine. Blood test results revealed no inflammatory reaction. Esophagogastroduodenoscopy detected villous atrophy in the stomach and duodenum. Moreover, small-bowel CE showed villous atrophy in about two-thirds of the small intestine. Based on other examinations, hyperthyroidism, intestinal tuberculosis, intestinal amyloidosis, and intestinal malignant lymphoma were ruled out. Therefore, the patient was suspected of having an olmesartan-related sprue-like disease. Early after discontinuation of medication, diarrhea symptoms improved, and a repeat CE indicated improvements in small intestinal villous atrophy. Since the patient had been administered olmesartan for a long time and CE showed villous atrophy throughout the small bowel, we suspected him of having the olmesartan-associated sprue-like disease. The findings of gastric mucosa atrophy on esophagogastroduodenoscopy may lead to an early diagnosis of this disease. Olmesartan-related sprue-like enteropathy should be considered as a differential diagnosis in patients with chronic severe watery diarrhea., Competing Interests: None., (© 2022 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)
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- 2022
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19. Overlap Between Constipation and Gastroesophageal Reflux Disease in Japan: Results From an Internet Survey.
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Ogasawara N, Funaki Y, Kasugai K, Ebi M, Tamura Y, Izawa S, and Sasaki M
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Background/aims: Detailed evaluations of overlapping constipation and gastroesophageal reflux disease (GERD) have not been conducted in Japan. The REACTION-J2 study examined the overlap of these diseases in Japan., Methods: This internet-based survey recruited participants from general public survey panels. Questions included demographic and medical data and assessments based on validated measures for constipation and GERD. Associations between background factors affecting constipation/GERD overlap, disease measures, and treatment were also evaluated., Results: Among 10 000 survey responses received, functional constipation (Rome IV diagnostic criteria) was reported by 439 participants; chronic constipation (Japanese guidelines) by 3804 participants; and subjective constipation symptoms by 2563 participants. The number of participants with constipation/GERD overlap ranged from 73 to 1533 depending on the criteria used. Regardless of the definition used, all GERD groups had significantly higher odds of being constipated than non-GERD participants: the OR (95% CI) for all 9 combinations of definitions ranged between 1.56 (1.21, 2.01) and 2.67 (2.44, 2.92) (all P ≤ 0.001). Straining, hard stools, and sensations of incomplete evacuation and anorectal obstruction/blockage, according to chronic constipation criteria, were common. Participants with constipation/GERD overlap had poorer quality of life ( P < 0.001) and worse GERD symptom scores ( P < 0.001). The frequency of abnormal stools was highest ( P < 0.001) in the constipation/GERD overlap group. In the overlap group, 52.4% and 26.0% used gastric and constipation medication, respectively., Conclusion: Individuals with constipation/GERD overlap tend to have worsened symptoms and quality of life.
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- 2022
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20. An Ensemble-Based Deep Convolutional Neural Network for Computer-Aided Polyps Identification From Colonoscopy.
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Sharma P, Balabantaray BK, Bora K, Mallik S, Kasugai K, and Zhao Z
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Colorectal cancer (CRC) is the third leading cause of cancer death globally. Early detection and removal of precancerous polyps can significantly reduce the chance of CRC patient death. Currently, the polyp detection rate mainly depends on the skill and expertise of gastroenterologists. Over time, unidentified polyps can develop into cancer. Machine learning has recently emerged as a powerful method in assisting clinical diagnosis. Several classification models have been proposed to identify polyps, but their performance has not been comparable to an expert endoscopist yet. Here, we propose a multiple classifier consultation strategy to create an effective and powerful classifier for polyp identification. This strategy benefits from recent findings that different classification models can better learn and extract various information within the image. Therefore, our Ensemble classifier can derive a more consequential decision than each individual classifier. The extracted combined information inherits the ResNet's advantage of residual connection, while it also extracts objects when covered by occlusions through depth-wise separable convolution layer of the Xception model. Here, we applied our strategy to still frames extracted from a colonoscopy video. It outperformed other state-of-the-art techniques with a performance measure greater than 95% in each of the algorithm parameters. Our method will help researchers and gastroenterologists develop clinically applicable, computational-guided tools for colonoscopy screening. It may be extended to other clinical diagnoses that rely on image., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sharma, Balabantaray, Bora, Mallik, Kasugai and Zhao.)
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- 2022
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21. Small-Intestinal Metastasis from Lung Carcinoma.
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Ogasawara N, Ono S, Sugiyama T, Adachi K, Yamaguchi Y, Izawa S, Ebi M, Funaki Y, Sasaki M, and Kasugai K
- Abstract
A 62-year-old man was referred to our hospital because of abdominal pain. Computed tomography revealed an approximately 7-cm-diameter tumor in the left abdomen with metastatic lymph nodes, an approximately 1-cm-diameter round tumor in contact with the subclavian artery in the apical lobe of the right lung, and mediastinal lymph node enlargement in contact with the superior vena cava. Esophagogastroduodenoscopy and colonoscopy revealed no abnormalities. Double-balloon endoscopy revealed a whole circumferential ulcer in the jejunum approximately 20 cm from the ligament of Treitz. Biopsy analysis of an ulcer specimen revealed a poorly differentiated carcinoma. Immunohistochemical staining of the specimen showed that it was positive for thyroid transcription factor 1 and cytokeratin 7 and negative for cytokeratin 20, GATA-binding protein 3, caudal-type homeobox protein 2, and paired box 8. Positron emission tomography revealed positive findings in the small-intestinal tumor, nearby mesenteric lymph nodes, lymph nodes around the abdominal aorta, lung tumor, and mediastinal lymph node in the apical lobe of the right lung. Accordingly, the patient was diagnosed as having a lung carcinoma with small-intestinal metastasis (T1b, N3, M1c; cStage IVB). Pathological examination helped distinguish the primary small-intestinal tumor from the metastatic small-intestinal tumor and detect the tumor origin., Competing Interests: The authors declare no conflicts of interest pertaining to this manuscript., (Copyright © 2022 by S. Karger AG, Basel.)
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- 2022
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22. Gastric Plexiform Fibromyxoma Resected Using Nonexposed Endoscopic Wall-Inversion Surgery: A Case Report.
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Ebi M, Nagao K, Sugiyama T, Yamamoto K, Saito T, Kurahashi S, Yamaguchi Y, Adachi K, Tamura Y, Izawa S, Funaki Y, Ogasawara N, Sasaki M, Tsuzuki T, and Kasugai K
- Abstract
Gastric plexiform fibromyxoma is extremely rare. In our case, upper gastrointestinal endoscopy of a 41-year-old woman patient revealed a 1-cm submucosal tumor (SMT) in the greater curvature of the lower body of the stomach. On contrast-enhanced computed tomography, the tumor was hypervascular in the arterial phase with continuous enhancement in the post-venous phase. On endoscopic ultrasonography, it had a low echo pattern. The preoperative diagnosis was a gastric SMT with a rich vasculature; however because the biosy specimen did not contain tumor tissue, a malignant tumor could not be excluded. The patient underwent nonexposed endoscopic wall-inversion surgery (NEWS), and the tumor was completely resected. Immunohistochemical examination revealed that the tumor was positive for D2-40 and α-smooth muscle actin, but negative for c-kit, discovered on gastrointestinal stromal tumor-1, desmin, S100, Melan-A, signal transducer and activator of transcription 6, insulinoma-associated protein 1, CXCL13, ETS transcription factor, follicular dendritic cell, anaplastic lymphoma kinase, human melanoma black, h-caldesmon, and CD1a, 10, 21, 23, 31, 34, 68, and 163. Approximately, 1-2% of the tumor cell nuclei were Ki-67-positive. Finally, we diagnosed the tumor as a plexiform fibromyxoma. In conclusion, NEWS is an effective method for the treatment of SMTs with a diameter of <3 cm., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 by S. Karger AG, Basel.)
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- 2022
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23. The Complete Loss of p53 Expression Uniquely Predicts Worse Prognosis in Colorectal Cancer.
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Nagao K, Koshino A, Sugimura-Nagata A, Nagano A, Komura M, Ueki A, Ebi M, Ogasawara N, Tsuzuki T, Kasai K, Takahashi S, Kasugai K, and Inaguma S
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- Activated-Leukocyte Cell Adhesion Molecule metabolism, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, DNA Mismatch Repair, Female, Humans, Immunohistochemistry, Tumor Suppressor Protein p53 genetics, Colorectal Neoplasms pathology, Tumor Suppressor Protein p53 metabolism
- Abstract
p53 immunohistochemistry is considered an accurate surrogate marker reflecting the underlying TP53 mutation status and has utility in tumor diagnostics. In the present study, 269 primary CRCs were immunohistochemically evaluated for p53 expression to assess its utility in diagnostic pathology and prognostication. p53 expression was wild-type in 59 cases (23%), overexpressed in 143 cases (55%), completely lost in 50 cases (19%), and cytoplasmic in 10 cases (4%). p53 immunoreactivity was associated with tumor size (p = 0.0056), mucus production (p = 0.0015), and mismatch repair (MMR) system status (p < 0.0001). Furthermore, among CRCs with wild-type p53 expression, a significantly higher number of cases had decreased CDX2 than those with p53 overexpression (p = 0.012) or complete p53 loss (p = 0.043). In contrast, among CRCs with p53 overexpression, there were significantly fewer ALCAM-positive cases than p53 wild-type cases (p = 0.0045). However, no significant association was detected between p53 immunoreactivity and the “stem-like” immunophenotype defined by CDX2 downregulation and ALCAM-positivity. Multivariate Cox hazards regression analysis identified tubular-forming histology (hazard ratio [HR] = 0.17, p < 0.0001), younger age (HR = 0.52, p = 0.021), and female sex (HR = 0.55, p = 0.046) as potential favorable factors. The analysis also revealed complete p53 loss (HR = 2.16, p = 0.0087), incomplete resection (HR = 2.65, p = 0.0068), and peritoneal metastasis (HR = 5.32, p < 0.0001) as potential independent risk factors for patients with CRC. The sub-cohort survival analyses classified according to chemotherapy after surgery revealed that CRC patients with wild-type p53 expression tended to have better survival than those with overexpression or complete loss after chemotherapy. Thus, immunohistochemistry for p53 could be used for the prognostication and chemotherapy target selection of patients with CRC.
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- 2022
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24. Background factors involved in the epidemiology of functional constipation in the Japanese population: a cross-sectional study.
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Yamamoto S, Ohashi W, Yamaguchi Y, Inamoto S, Koshino A, Sugiyama T, Nagao K, Tamura Y, Izawa S, Ebi M, Usami J, Hamano K, Izumi J, Wakita Y, Funaki Y, Ogasawara N, Sasaki M, Maekawa M, and Kasugai K
- Abstract
Background: Functional constipation (FC), a functional bowel disorder with symptoms of constipation, has considerable impact on quality of life. As data regarding its prevalence and epidemiology are lacking, this study aimed to evaluate the prevalence, population composition, lifestyle, quality of life, and clinical characteristics of these individuals by comparing people with and without FC. These parameters were also compared among individuals with strong and weak awareness of constipation., Methods: An internet survey was conducted among 10,000 individuals aged 20-69 years from the general Japanese population; they were registered with an internet survey company. The following data were obtained: age, sex, educational history, occupation, residence, history of other diseases, lifestyle (including smoking/drinking habits using the Japanese Health Practice Index, medication use, symptoms of constipation according to the Rome III criteria, stool types according to the Bristol stool scale, and use of laxatives, including the place of purchase and cost per month or acceptable cost per month. The 8-item Short Form Health Survey Questionnaire was also used; FC was diagnosed based on Rome III criteria. All respondents were classified according to their awareness of constipation (i.e. strong or weak), and their characteristic features were compared., Results: The data of 3000 respondents were evaluated; 262 (8.7%) had FC, which was common among older adults, women, and homemakers. FC was associated with changes in the frequency of bowel movement, sensation of incomplete or scanty evacuation, and the use of manual maneuvers; these are consequential clinical symptoms of FC. These individuals frequently skipped breakfast, had insufficient sleep, had more severe constipation, and had purchased laxatives in pharmacies or online more often than those without FC. A strong awareness of constipation was significantly more prevalent among women and homemakers. A history of anemia and cardiovascular disease was significantly more frequent in the strong awareness group, whereas a history of hypertension was more frequent in the weak awareness group., Conclusions: Appropriate and comprehensive management should be provided for FC, based on the understanding of its characteristic features and considering the symptoms and lifestyle., (© 2022. The Author(s).)
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- 2022
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25. SPATA18 Expression Predicts Favorable Clinical Outcome in Colorectal Cancer.
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Sugimura-Nagata A, Koshino A, Nagao K, Nagano A, Komura M, Ueki A, Ebi M, Ogasawara N, Tsuzuki T, Kasai K, Takahashi S, Kasugai K, and Inaguma S
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- Aged, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Humans, Immunohistochemistry, Lymphatic Metastasis, Male, Mutation, Colorectal Neoplasms pathology, Mitochondrial Proteins metabolism, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism
- Abstract
Dysregulation of mitochondrial quality control has been reported to be associated with cancer and degenerative diseases. SPATA18 (spermatogenesis-associated 18, also known as Mieap) encodes a p53-inducible protein that can induce lysosome-like organelles within mitochondria that eliminate oxidized mitochondrial proteins and has tumor suppressor functions in mitochondrial quality control. In the present study, 268 primary colorectal cancers (CRCs) were evaluated immunohistochemically for SPATA18 expression to assess its predictive utility and its association with cellular proliferation activity. Furthermore, the association with p53 immunoreactivity, a surrogate marker for TP53 mutation, was analyzed. Non-neoplastic colonic mucosa showed cytoplasmic SPATA18 expression. Seventy-two percent of the lesions (193/268) displayed high SPATA18 expression in the cytoplasm of CRC cells. Univariate analyses revealed significant associations between SPATA18 expression and tumor size (p < 0.0001), histological differentiation (p = 0.0017), and lymph node metastasis (p = 0.00039). The log-rank test revealed that patients with SPATA18-high CRCs had significantly better survival than SPATA18-low patients (p < 0.0001). Multivariate Cox hazards regression analysis identified tubular-forming histology (hazard ratio [HR] = 0.25), age < 70 years (HR = 0.50), and SPATA18-high (HR = 0.55) as potential favorable factors. Lymph node metastasis (HR = 1.98) and peritoneal metastasis (HR = 5.45) were cited as potential independent risk factors. Cellular proliferation activity was significantly higher in SPATA18-high tumors. However, no significant correlation was detected between SPATA18 expression and p53 immunoreactivity or KRAS/BRAF mutation status. On the basis of our observations, SPATA18 immunohistochemistry can be used in the prognostication of CRC patients.
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- 2022
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26. PBK Enhances Cellular Proliferation With Histone H3 Phosphorylation and Suppresses Migration and Invasion With CDH1 Stabilization in Colorectal Cancer.
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Koshino A, Nagano A, Ota A, Hyodo T, Ueki A, Komura M, Sugimura-Nagata A, Ebi M, Ogasawara N, Kasai K, Hosokawa Y, Kasugai K, Takahashi S, and Inaguma S
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Colorectal cancer (CRC) is one of the most frequent gastrointestinal malignancies with high morbidity and mortality rates. Several biological markers for the prognostication of patient outcome of CRCs are available. Recently, our group identified two favorable factors for the survival of CRC patients: PDZ-binding kinase (PBK) and phospho-histone H3 (PHH3). Both showed a significant inverse association to pT stage. The aim of this study was to uncover the mechanism through which these cellular proliferation-associated protein expressions lead to favorable clinical outcome in CRC patients. We first confirmed co-expression of PBK and PHH3 in CRC cells. Further investigation showed that aberrantly expressed PBK up-regulated the cellular proliferation of CRC cells with accumulation of PHH3. The PBK inhibitor OTS514 suppressed cellular proliferation of CRC cells through down-regulation of PHH3 and induction of apoptosis. In vitro studies revealed that PBK suppressed the migration and invasion of CRC cells with suppression of Wnt/β-catenin signaling and CDH1 stabilization. Exogeneous PBK up-regulated the phosphorylated CDH1 at S840, S846, and S847 residues in cultured cells. Recombinant PBK directly phosphorylated HH3; however, it failed to phosphorylate CDH1 directly in vitro . The present study demonstrated the association of two markers PBK and PHH3 in CRC. We further identified one of the potential mechanisms by which higher expression of these cellular proliferation-associated proteins leads to the better survival of CRC patients, which likely involves PBK-mediated suppression of the migration and invasion of CRC cells. Our findings suggest that PBK-targeting therapeutics may be useful for the treatment of CRC patients with PBK-expressing tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Koshino, Nagano, Ota, Hyodo, Ueki, Komura, Sugimura-Nagata, Ebi, Ogasawara, Kasai, Hosokawa, Kasugai, Takahashi and Inaguma.)
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- 2022
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27. Internet Survey of Japanese Patients With Chronic Constipation: Focus on Correlations Between Sleep Quality, Symptom Severity, and Quality of Life.
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Yamamoto S, Kawamura Y, Yamamoto K, Yamaguchi Y, Tamura Y, Izawa S, Nakagawa H, Wakita Y, Hijikata Y, Ebi M, Funaki Y, Ohashi W, Ogasawara N, Sasaki M, Maekawa M, and Kasugai K
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Background/aims: Chronic constipation and lifestyle factors can affect sleep quality. We evaluated the relationship between chronic constipation and sleep in the Japanese population., Methods: This cross-sectional internet-based survey included 3000 subjects with constipation, classified according to sleep status (good/poor). Primary endpoints were Bristol stool form scale (BSFS) score and correlations between sleep disorder criteria of the Pittsburgh Sleep Quality Index (PSQI) and sleep status (good/poor sleep). Secondary endpoints included correlations between quality of life (QOL) and mood, medical, lifestyle, and sleep factors., Results: The proportion of participants with BSFS category 4 (normal stool) was significantly higher in the good sleep group ( P < 0.001). Sleep disturbance ( P < 0.05), sleep quality, and duration, use of hypnotic medication, and daytime dysfunction of PSQI (all P < 0.001) significantly correlated with poor sleep. In the poor sleep group, QOL was significantly worse and anxiety and depression levels were significantly higher (all P < 0.001) compared with the good sleep group. Anemia and smoking (both P < 0.05), recent body weight increases, and poor eating habits (all P < 0.001) were significantly higher in the poor sleep group. Male sex, onset associated with change in frequency of stools, sensation of incomplete evacuation for at least 25% of defecations, and manual maneuvers to facilitate at least 25% of defecations correlated with poor sleep., Conclusions: Subjects with constipation and poor sleep experienced severe symptoms and had poor QOL. These data support the need for a multifocal treatment approach, including lifestyle advice and pharmacotherapy.
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- 2021
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28. Expression and Prognostic Significance of CD47-SIRPA Macrophage Checkpoint Molecules in Colorectal Cancer.
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Sugimura-Nagata A, Koshino A, Inoue S, Matsuo-Nagano A, Komura M, Riku M, Ito H, Inoko A, Murakami H, Ebi M, Ogasawara N, Tsuzuki T, Takahashi S, Kasugai K, Kasai K, and Inaguma S
- Subjects
- Aged, Aged, 80 and over, Antigens, CD metabolism, Antigens, Differentiation, Myelomonocytic metabolism, Biomarkers, Tumor metabolism, Colorectal Neoplasms metabolism, Colorectal Neoplasms surgery, Female, Humans, Intestinal Mucosa metabolism, Intestinal Mucosa pathology, Macrophages metabolism, Macrophages pathology, Male, Middle Aged, Prognosis, Receptors, Cell Surface metabolism, Survival Analysis, Antigens, Differentiation metabolism, CD47 Antigen metabolism, Colorectal Neoplasms mortality, Colorectal Neoplasms pathology, Receptors, Immunologic metabolism
- Abstract
Despite the confirmed anti-cancer effects of T-cell immune checkpoint inhibitors, in colorectal cancer (CRC) they are only effective in a small subset of patients with microsatellite-unstable tumors. Thus, therapeutics targeting other types of CRCs or tumors refractory to T-cell checkpoint inhibitors are desired. The binding of aberrantly expressed CD47 on tumor cells to signal regulatory protein-alpha (SIRPA) on macrophages allows tumor cells to evade immune destruction. Based on these observations, drugs targeting the macrophage checkpoint have been developed with the expectation of anti-cancer effects against T-cell immune checkpoint inhibitor-refractory tumors. In the present study, 269 primary CRCs were evaluated immunohistochemically for CD47, SIRPA, CD68, and CD163 expression to assess their predictive utility and the applicability of CD47-SIRPA axis-modulating drugs. Thirty-five percent of the lesions (95/269) displayed CD47 expression on the cytomembrane of CRC cells. CRCs contained various numbers of tumor-associated immune cells (TAIs) with SIRPA, CD68, or CD163 expression. The log-rank test revealed that patients with CD47-positive CRCs had significantly worse survival than CD47-negative patients. Multivariate Cox hazards regression analysis identified tubular-forming histology (hazard ratio (R) = 0.23), age < 70 years (HR = 0.48), and high SIRPA-positive TAI counts (HR = 0.55) as potential favorable factors. High tumor CD47 expression (HR = 1.75), lymph node metastasis (HR = 2.26), and peritoneal metastasis (HR = 5.80) were cited as potential independent risk factors. Based on our observations, CD47-SIRPA pathway-modulating therapies may be effective in patients with CRC.
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- 2021
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29. Rapidly Progressing Aseptic Abscesses in a Patient with Ulcerative Colitis.
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Yamaguchi Y, Nakagawa M, Nakagawa S, Nagao K, Inoue S, Sugiyama T, Izawa S, Hijikata Y, Ebi M, Funaki Y, Ogasawara N, Sasaki M, and Kasugai K
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- Gastrointestinal Agents therapeutic use, Humans, Infliximab therapeutic use, Japan, Male, Middle Aged, Treatment Outcome, Colitis drug therapy, Colitis, Ulcerative complications, Colitis, Ulcerative diagnosis, Colitis, Ulcerative therapy, Inflammatory Bowel Diseases drug therapy
- Abstract
Aseptic abscesses (AAs) are extraintestinal manifestations of inflammatory bowel disease (IBD). IBD-associated AAs are rare in Japan. We treated a 45-year-old man with ulcerative colitis (UC)-associated AAs. During remission, multiple progressive abscesses were detected in the spleen; he underwent splenectomy because an infectious disease was suspected. Although his condition improved temporarily after splenectomy, a large liver abscess was noted, and a diagnosis of UC-associated AAs was made. Granulocytapheresis (GCAP) and infliximab (IFX) administration resolved the abscess. This is the first reported case of UC-associated AAs in a Japanese patient treated by splenectomy, GCAP, and IFX.
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- 2021
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30. Computational learning of features for automated colonic polyp classification.
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Bora K, Bhuyan MK, Kasugai K, Mallik S, and Zhao Z
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- Colonic Polyps pathology, Databases, Factual, Humans, Colonic Polyps classification, Support Vector Machine
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Shape, texture, and color are critical features for assessing the degree of dysplasia in colonic polyps. A comprehensive analysis of these features is presented in this paper. Shape features are extracted using generic Fourier descriptor. The nonsubsampled contourlet transform is used as texture and color feature descriptor, with different combinations of filters. Analysis of variance (ANOVA) is applied to measure statistical significance of the contribution of different descriptors between two colonic polyps: non-neoplastic and neoplastic. Final descriptors selected after ANOVA are optimized using the fuzzy entropy-based feature ranking algorithm. Finally, classification is performed using Least Square Support Vector Machine and Multi-layer Perceptron with five-fold cross-validation to avoid overfitting. Evaluation of our analytical approach using two datasets suggested that the feature descriptors could efficiently designate a colonic polyp, which subsequently can help the early detection of colorectal carcinoma. Based on the comparison with four deep learning models, we demonstrate that the proposed approach out-performs the existing feature-based methods of colonic polyp identification.
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- 2021
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31. The association among enterobacterial flora, dietary factors, and prognosis in patients with ulcerative colitis.
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Sugiyama T, Sasaki M, Nakagawa S, Inoue S, Adachi K, Yoshimine T, Yamaguchi Y, Tamura Y, Izawa S, Hijikata Y, Ebi M, Mizuno M, Yamamoto S, Funaki Y, Ogasawara N, Goto C, and Kasugai K
- Abstract
The role of enterobacterial flora in the onset and progression of inflammatory bowel diseases is a topic of considerable interest. Here, we assessed the association among enterobacterial flora, dietary factors, and ulcerative colitis (UC) progression. Forty-six patients with UC who were diagnosed as being in remission were enrolled. We collected each patient's stool sample one or two days before diagnostic colonoscopy. After colonoscopy, we observed the patients for one year and then retrospectively divided them into two groups: remission ( n = 39) and relapse ( n = 7) groups, depending on whether the relapse occurred during the follow-up period, and analyzed the relationship among patient characteristics, dietary factors, enterobacterial flora, and UC relapse. Overall, there were no significant differences in bacterial community populations between the remission and relapse groups, except that the order Lactobacillales was detected at a significantly higher rate in the relapse than in the remission group (100% vs 71.4%, p <0.05). Vitamin C intake was significantly higher in the remission than in the relapse group ( p <0.05). Although there were no obvious differences in enterobacterial flora between the remission and relapse groups, there was a relationship among enterobacterial flora, diet, and UC progression. Given that the enterobacterial flora was only analyzed at the initiation of the study, we conclude that in future analyses, enterobacterial flora should be sampled at numerous time points to examine its role in UC progression. Further long-term longitudinal studies examining enterobacterial flora, dietary factors, and UC progression are also required., Competing Interests: KK received lecture fees from Daiichi Sankyo Co., Ltd., Astra Zeneca Co., Ltd., EA Pharma Co., Ltd., Mylan Co., Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., and Takeda Pharmaceutical Co., Ltd. KK received research grants from Astellas Co., Ltd., Daiichi Sankyo Co., Ltd., EA Pharma Co., Ltd., Mitsubishi Tanabe Pharma Co., Ltd., and Takeda Pharmaceutical Co., Ltd. The other authors have no conflicts of interest to declare., (Copyright © 2020 JCBNCopyright © 2020 JCBN.)
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- 2020
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32. Randomised trial of acid inhibition by vonoprazan 10/20 mg once daily vs rabeprazole 10/20 mg twice daily in healthy Japanese volunteers (SAMURAI pH study).
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Takeuchi T, Furuta T, Fujiwara Y, Sugimoto M, Kasugai K, Kusano M, Okada H, Suzuki T, Higuchi T, Kagami T, Uotani T, Yamade M, Sawada A, Tanaka F, Harada S, Ota K, Kojima Y, Murata M, Tamura Y, Funaki Y, Kawamura O, Okamoto Y, Fujimoto K, and Higuchi K
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- Adolescent, Adult, Antacids adverse effects, Cross-Over Studies, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Gastric Juice metabolism, Healthy Volunteers, Humans, Hydrogen-Ion Concentration, Japan, Male, Polymorphism, Genetic, Proton Pump Inhibitors adverse effects, Pyrroles adverse effects, Rabeprazole adverse effects, Sulfonamides adverse effects, Young Adult, Antacids administration & dosage, Gastric Acid metabolism, Gastric Juice drug effects, Proton Pump Inhibitors administration & dosage, Pyrroles administration & dosage, Rabeprazole administration & dosage, Sulfonamides administration & dosage
- Abstract
Background: Vonoprazan (V), a potassium-competitive acid blocker, has a more durable acid-inhibitory effect as compared with standard-dose proton pump inhibitors (PPIs) but has not been compared with 2-4 times higher daily PPI doses administered in two divided doses., Aims: To evaluate the acid-inhibitory effect of V 10/20 mg once-daily (OD; V10/V20) vs rabeprazole (R) 10/20 mg twice-daily (BID; R20/R40) in healthy Japanese volunteers., Methods: This multicentre, randomised, open-label, two-period, crossover study compared V10 or V20 vs R20, or V20 vs R40 using three cohorts of 10 healthy Japanese adults. Within each cohort, subjects were randomised to receive V or R for 7 days and, following a washout period ≥7 days, the other treatment for 7 days. On day 6 of each period, 24-hours multichannel gastric impedance-pH monitoring was performed. Percent times pH ≥ 3, ≥4 and ≥5 (pH 3, 4 and 5 holding time ratios [HTRs]) in 24 hours were evaluated as primary pharmacodynamic endpoints., Results: Acid-inhibitory effect (24-hours pH 3 HTR) of V20 was greater than those of R20 (91.0% vs 65.3%; P = .0049) and R40 (98.5% vs 85.9%; P = .0073). Similar results were obtained for 24-hours pH 4 and 5 HTRs. V20 also achieved greater nocturnal pH 4 (91.5% vs 73.2%; P = .0319) and 5 HTRs (78.8% vs 62.2%; P = .0325) as compared with R40. One subject (20%) developed diarrhoea while receiving R40 which was considered treatment-related., Conclusions: Compared with 2-4 times the standard daily dose of R, V20 exerts a more potent and durable acid-inhibitory effect. Trial identifier: UMIN000022198 (www.umin.ac.jp/ctr/index.htm)., (© 2020 John Wiley & Sons Ltd.)
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- 2020
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33. Markedly Effective Steroid Treatment of Three Patients with Allergy-related Jackhammer Esophagus.
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Funaki Y, Ogasawara N, Kawamura Y, Yoshimine T, Tamura Y, Izawa S, Tsuyuki T, Ebi M, Sasaki M, and Kasugai K
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- Adult, Biopsy, Endosonography, Eosinophilic Esophagitis complications, Esophageal Motility Disorders complications, Female, Humans, Immunoglobulin E blood, Male, Manometry, Middle Aged, Treatment Outcome, Esophageal Motility Disorders drug therapy
- Abstract
We experienced marked efficacy with steroid treatment of three patients with jackhammer esophagus (JHE). An esophageal biopsy revealed eosinophilic esophagitis (EoE) in two patients. One of the patients without EoE had eosinophilia and an increased serum immunoglobulin E level, and endoscopic ultrasonography revealed thickening of the esophageal muscularis propria. Esophageal manometry was used to diagnose all cases of JHE. Treatment consisted of steroid administration, which improved the symptoms and resolved the esophageal muscularis propria thickening in all patients. The esophageal manometry findings also normalized following treatment. Allergic diseases, including EoE, were assumed to have caused JHE.
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- 2020
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34. Diffuse mesothelin expression leads to worse prognosis through enhanced cellular proliferation in colorectal cancer.
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Inoue S, Tsunoda T, Riku M, Ito H, Inoko A, Murakami H, Ebi M, Ogasawara N, Pastan I, Kasugai K, Kasai K, Ikeda H, and Inaguma S
- Abstract
Mesothelin (MSLN) is a glycophosphatidylinositol (GPI)-linked cell surface protein that is highly expressed in several types of malignant tumor, including malignant pleural mesothelioma, ovarian cancer and pancreatic adenocarcinoma. Recently, a comprehensive immunohistochemical study using MN-1 monoclonal antibody identified a significant number of colorectal tumors in which MSLN was expressed. However, the clinicopathological profiles and survival of patients with MSLN-positive colorectal cancer have not been fully analyzed. In the current study, the expression of MSLN in 270 primary and 44 metastatic colorectal tumors was immunohistochemically analyzed to determine the clinical usefulness of MSLN immunohistochemistry and to identify potential candidates for future anti-MSLN therapy. In vitro experiments using colon cancer cell lines were performed to investigate the biological significance of MSLN expression in tumors. The results of univariate analyses identified a significant correlation between MSLN expression and females (P=0.0042). Furthermore, an inverse correlation between MSLN expression and solid/sheet-like proliferation (P=0.014) was also revealed. Additionally, overall survival was significantly shorter in patients with diffuse luminal/membranous expression of MSLN (P=0.018). Multivariable Cox hazards regression analysis revealed diffuse MSLN expression (hazard ratio, 2.26; 95% confidence interval, 1.04-4.91; P=0.039) as a potential risk factor. When comparing primary CRCs and the metastasis of each, a weakly positive correlation was identified for MSLN positivity (% positive cells; R=0.484; P<0.0001). The in vitro experiments revealed a positive role for MSLN in colon cancer cell proliferation. Thus, MSLN immunohistochemistry may be useful in the prognostication of patients with CRC. The results demonstrated that significant numbers of patients with MSLN-positive CRC exhibiting metastasis could be targeted by anti-MSLN therapies., (Copyright: © Inoue et al.)
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- 2020
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35. Vonoprazan-Based Triple-Therapy Could Improve Efficacy of the Tailored Therapy of Helicobacter pylori Infection.
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Shinmura T, Adachi K, Yamaguchi Y, Izawa S, Hijikata Y, Ebi M, Funaki Y, Ogasawara N, Sasaki M, and Kasugai K
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- Aged, Amoxicillin therapeutic use, Anti-Bacterial Agents therapeutic use, Breath Tests methods, Clarithromycin therapeutic use, Drug Resistance, Bacterial, Drug Therapy, Combination, Female, Humans, Male, Microbial Sensitivity Tests methods, Middle Aged, Retrospective Studies, Treatment Outcome, Helicobacter Infections drug therapy, Helicobacter pylori drug effects, Proton Pump Inhibitors therapeutic use, Pyrroles therapeutic use, Sulfonamides therapeutic use
- Abstract
Background and Aims: The prevalence of clarithromycin resistant bacteria is increasing, and the effectiveness of Helicobacter pylori (H. pylori) triple therapy is gradually decreasing in Japan. Vonoprazan, a potassiumcompetitive acid blocker, has been reported for its effectiveness in eradicating H. pylori. We aimed to evaluate the efficacy of tailored vonoprazan-based triple therapy in patients with H. pylori. This study is the first to compare the efficacy of vonoprazan-based tailored triple therapy to that of vonoprazan-based conventional therapy., Method: This retrospective cohort study evaluated the treatment efficacy in 920 patients. Of these, 541 received conventional and 379 received tailored therapy. Successful eradication was confirmed by a negative 13C-urea breath test 6-8 weeks following completion of H. pylori eradication therapy, and the data were evaluated using the Chi-square test, or Fisher's exact test, as appropriate., Results: The eradication rate of tailored therapy was 90% and 96.3% by intent-to-treat analysis and per protocol analysis, respectively, which was significantly higher than the 85% and 90.2% found for conventional therapy (p < 0.05 and p < 0.001, respectively). Amoxicillin- or clarithromycin-resistant bacteria did not affect treatment outcomes. By univariate and multivariate analysis, both amoxicillin- and clarithromycin-resistant bacteria and conventional therapy were detected as risk factors for eradication failure (odds ratio = 6.267, 95% CI [1.056-119.924], p < 0.05, and odd ratio =3.113, 95% confidence interval [1.688-6.160], p < 0.001, by multivariate analysis)., Conclusion: Vonoprazan-based triple therapy could be a more effective treatment for H. pylori infection than conventional therapy when combined with a therapy regimen tailored according to bacterial antibiotic susceptibility.
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- 2019
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36. Endoscopic Resection of a Pedunculated Cavernous Hemangioma of the Sigmoid Colon: A Case Report.
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Ogasawara N, Suzuki M, Adachi K, Yamaguchi Y, Yamamoto S, Hijikata Y, Ebi M, Funaki Y, Sasaki M, and Kasugai K
- Abstract
Hemangiomas are common benign tumors that usually occur on the head and neck in children. However, colonic hemangiomas are rare in clinical practice. Approximately 80% of colonic hemangiomas are of the cavernous type, and morphologically, ≥80% of colonic hemangiomas are sessile and semi-pedunculated. Notably, pedunculated colonic hemangiomas are rare. A 69-year-old woman presented with hematochezia and underwent colonoscopy, which revealed a soft pedunculated submucosal tumor (SMT) measuring 1.5 cm in diameter, in the sigmoid colon. The surface of the SMT resembled the surrounding normal colonic mucosa with regard to color and appearance, with multiple red patches. Narrow-band imaging revealed a few telangiectasias on the surface of the SMT. The lesion could not be definitively diagnosed based on endoscopic findings. Therefore, for more accurate diagnosis, the SMT was removed by snare polypectomy with electrocautery after clipping the basal portion of the tumor stalk for prophylactic hemostasis. Histopathological examination of the specimen revealed a cavernous hemangioma with a negative resection margin. We report a case of a pedunculated cavernous hemangioma of the sigmoid colon removed by snare polypectomy with electrocautery after clipping the basal portion of the tumor stalk for prophylactic hemostasis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 by S. Karger AG, Basel.)
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- 2019
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37. Esophageal Leiomyosarcoma Diagnosed by Endoscopic Ultrasound-guided Fine-needle Aspiration Biopsy and Cured with Surgical Resection.
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Ebi M, Sakamoto K, Inoue S, Ozeki T, Kimura M, Kondo R, Sugiyama T, Yamamoto K, Adachi K, Yoshimine T, Yamaguchi Y, Tamura Y, Izawa S, Hijikata Y, Funaki Y, Ogasawara N, Sasaki M, and Kasugai K
- Subjects
- Aged, 80 and over, Endoscopic Ultrasound-Guided Fine Needle Aspiration, Esophageal Neoplasms diagnosis, Esophageal Neoplasms surgery, Esophagoscopy, Humans, Leiomyosarcoma diagnosis, Leiomyosarcoma surgery, Male, Esophageal Neoplasms pathology, Leiomyosarcoma pathology
- Abstract
Esophageal leiomyosarcomas are rare. We herein present the case of an 82-year-old patient who underwent upper gastrointestinal endoscopy, which revealed a submucosal tumor of 30 mm in diameter that was in contact with the esophagus. Endoscopic ultrasound-guided fine needle aspiration biopsy was performed and the histopathological findings indicated esophageal leiomyosarcoma. Surgical resection was performed. On histopathological examination, the tumor was found to consist of spindle cells with deep chromatin nuclei. The tumor was finally diagnosed as esophageal leiomyosarcoma. We were able to diagnose early-stage esophageal leiomyosarcoma using endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA). EUS-FNA is mostly recommended as a diagnostic tool for esophageal submucosal tumors.
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- 2019
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38. Gut microbiota disorders cause type 2 diabetes mellitus and homeostatic disturbances in gut-related metabolism in Japanese subjects.
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Adachi K, Sugiyama T, Yamaguchi Y, Tamura Y, Izawa S, Hijikata Y, Ebi M, Funaki Y, Ogasawara N, Goto C, Sasaki M, and Kasugai K
- Abstract
Few studies have investigated the host-microbe metabolic axis in people with type 2 diabetes mellitus (T2DM). This study aimed to determine and compare the nutrient intakes and metabolic markers and to elucidate the relationships among these factors in Japanese T2DM patients and control individuals. Fifty-nine Japanese T2DM patients and 59 matched healthy control individuals participated in this study. We examined the differences regarding the participants' dietary habits, microbiota, and fecal short-chain fatty acids, and analyzed the relationships between the gut microbiota and blood metabolic markers in the T2DM patients and the control subjects. The T2DM patients consumed more carbohydrates, and had lower fecal propionate and butyrate concentrations, larger fecal populations of Bifidobacterium spp. and bacteria of the order Lactobacillales , and smaller fecal Bacteroides spp. populations than the control individuals. In the T2DM patients, the level of Bifidobacterium spp. correlated negatively with the carbohydrate intake and the level of bacteria of the order Lactobacillales correlated negatively with the protein intake. T2DM patients have gut dysbiosis that may contribute to disease onset and influence its prognosis. Furthermore, homeostatic disturbances in the gut-related metabolism may underlie the pathogenesis of T2DM., Competing Interests: K. Kasugai received research grants and lectures fees from AstraZenekca Co., Ltd., EA Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., and Takeda Pharmaceutical Co., Ltd. M. Sasaki received grants for joint research from Amano Enzyme I.
- Published
- 2019
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39. A Small Bowel Ulcer due to Clopidogrel with Cytomegalovirus Enteritis Diagnosed by Capsule and Double-Balloon Endoscopy.
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Ebi M, Inoue S, Sugiyama T, Yamamoto K, Adachi K, Yoshimine T, Yamaguchi Y, Tamura Y, Izawa S, Hijikata Y, Funaki Y, Ogasawara N, Sasaki M, and Kasugai K
- Abstract
We report the first case of small bowel ulcers due to clopidogrel in a 74-year-old man. He presented with diarrhea and melena after having been taking low-dose aspirin (LDA) and clopidogrel. There was no evidence of bleeding in the stomach, duodenum, or colon. Capsule endoscopy showed multiple ulcers and erosions in the small intestine. Double-balloon endoscopy revealed multiple ulcers throughout the ileum. Examination of the biopsy specimen showed cytomegalovirus infection. His LDA was discontinued and he was prescribed ganciclovir. However, the small bowel ulcers were aggravated. Therefore, clopidogrel was discontinued. The small bowel ulcers subsequently healed completely, forming scars.
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- 2018
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40. Risk Factors for Delayed Ulcer Healing after Endoscopic Submucosal Dissection of Gastric Neoplasms.
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Shimozato A, Sasaki M, Ogasawara N, Funaki Y, Ebi M, Tamura Y, Izawa S, Hijikata Y, Yamaguchi Y, and Kasugai K
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- Adenocarcinoma pathology, Adenoma pathology, Adenoma surgery, Aged, Female, Follow-Up Studies, Humans, Male, Proton Pump Inhibitors therapeutic use, ROC Curve, Retrospective Studies, Risk Factors, Stomach Neoplasms pathology, Stomach Ulcer drug therapy, Stomach Ulcer pathology, Stomach Ulcer physiopathology, Time Factors, Adenocarcinoma surgery, Endoscopic Mucosal Resection adverse effects, Stomach Neoplasms surgery, Stomach Ulcer etiology, Wound Healing physiology
- Abstract
Background and Aims: With improved technology, the size of artificial ulcers after endoscopic submucosal dissection (ESD) has increased. The aim of our study was to examine the risk factors for delayed gastric ulcer healing after ESD, including the possible benefit of potassium-competitive acid blocker (P-CAB) treatment., Methods: The primary outcome was the rate of healing of the artificial ulcers induced by ESD at 8 weeks post intervention. Design - retrospective case series. Setting - Aichi Medical University Hospital. Patients - patients who underwent ESD for gastric neoplasm, between April 2015 and March 2017. Intervention - ESD, with a follow-up endoscopic examination at 8 weeks post-ESD. Univariate and multivariate analyses were used to identify the independent risk factors for delayed healing., Results: Of the 73 gastric neoplasms included in the analysis, delayed ulcer healing was identified in 21.9%. Dyslipidemia (p=0.04), ESD procedure time (p=0.003) and artificial ulcer size (p<0.001) were identified as risk factors for delayed healing, with location in the lower third of the stomach [Odds ratio (OR) 6.76; p=0.016] and artificial ulcer size (OR, 1.18; p=0.024) retained as independent risk factors. A cut-off ulcer size of 854 mm2 was predictive of delayed healing, with a sensitivity of 29.8% and specificity of 87.5%. For large ulcers, the rate of healing of 70% with vonoprazan was higher than the rate of 47.6% with proton pump inhibitors (PPIs), although this difference was not significant., Conclusion: For artificial ulcers after ESD with a resection diameter >35 mm, it might be desirable to use PPIs for >8 weeks or P-CAB.
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- 2017
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41. Transglucosidase improves the bowel movements in type 2 diabetes mellitus patients: A preliminary randomized double-blind, placebo-controlled study.
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Shimozato A, Sasaki M, Ogasawara N, Funaki Y, Ebi M, Goto C, Koikeda S, Joh T, and Kasugai K
- Abstract
Background: Recent studies have highlighted the relationship between gut microbiota and bowel movements., Objective: We aimed to evaluate transglucosidase treatment efficacy for bowel movements in patients with type 2 diabetes mellitus and to clarify the relationship between bowel movements, dietary habits, gut microbiota and fecal short-chain fatty acids., Methods: In this randomized double-blind, placebo-controlled study, 66 patients received placebo or transglucosidase (300 or 900 mg/day) orally, for 12 weeks. Fecal bacterial communities and short-chain fatty acids were analyzed before and after the treatment., Results: Transglucosidase treatment significantly ( p < 0.05) affected fecal microbiota ( Prevotella spp., Bacteroides spp., Bifidobacterium spp., and Clostridium subcluster XIVa) and fecal short-chain fatty acid (acetate, valerate, succinate and lactate) content. Clostridium cluster IV, Clostridium subcluster XIVa, Clostridium cluster XVIII and fecal pH increased significantly and order Lactobacillales decreased in patients with bowel movement disorder compared with controls. Transglucosidase treatment significantly improved bowel movements compared with placebo treatment (46.2%, 95% confidence interval: 19.2-74.9% vs . 0%, 95% confidence interval: 0-33.6%, p < 0.05). This effect was not observed in patients without bowel movement disorder., Conclusion: Patients with bowel movement disorder suffer from gut dysbiosis. Transglucosidase treatment alleviates bowel movement disorder symptoms in type 2 diabetes mellitus patients by increasing fecal acetate level.
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- 2017
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42. Successful Endoscopic Submucosal Dissection of a Large Terminal Ileal Lipoma.
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Noda H, Ogasawara N, Tamura Y, Kondo Y, Izawa S, Ebi M, Funaki Y, Sasaki M, and Kasugai K
- Abstract
A 78-year-old woman who had recurrent right lower abdominal pain for about 1 year underwent computed tomography (CT) because of a follow-up observation 1 year after right breast cancer surgery. CT revealed a tumor in the colon. The patient was referred to our hospital for detailed examinations. An abdominal CT showed a low-density tumor of approximately 30 mm in the ascending colon, and the CT density inside the tumor was same as that of fatty tissues. A subsequent colonoscopy showed a submucosal tumor (SMT) in the proximal ascending colon developing from the terminal ileum. A colonoscopic ultrasonography revealed that the SMT was a high-echoic mass mainly localized in the submucosal layer. Based on the findings from CT, colonoscopy, and colonoscopic ultrasonography, the SMT was diagnosed as a pedunculated lipoma originating from the terminal ileum and treated with endoscopic submucosal dissection (ESD) because of recurrent abdominal pain. The 40-mm tumor was resected en bloc without complications. ESD may be more appropriate than polypectomy and surgery for removal of small intestinal tumors, because ESD allows direct visualization of the cutting line and exactly dissects the submucosal layers without damaging the muscular layers. ESD is a potentially useful treatment to remove intestinal lipomas.
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- 2016
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43. The Influence of Snare Size on the Utility and Safety of Cold Snare Polypectomy for the Removal of Colonic Polyps in Japanese Patients.
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Noda H, Ogasawara N, Sugiyama T, Yoshimine T, Tamura Y, Izawa S, Kondo Y, Ebi M, Funaki Y, Sasaki M, and Kasugai K
- Abstract
Background: Cold snare polypectomy (CSP) has been recently reported to be useful for the removal of small colonic polyps. However, the relationship between the histologically complete resection rate and snare size used during CSP has not been reported. Our aim was to assess the utility of CSP., Methods: We analyzed the histologically complete resection rates and the frequency of complications for 175 colon polyps removed by CSP. Moreover, we examined the histologically complete resection rate associated with different snare sizes used during CSP., Results: There was no significant difference in the histologically complete resection rate between endoscopic mucosal resection (EMR) (60.9%) and CSP (53.1%). There were also no significant differences in the frequency of complications including perforation and postoperative bleeding between EMR (perforation: none; postoperative bleeding: two patients) and CSP (perforation: none; postoperative bleeding: none). Histological examination revealed that the complete resection rate of CSP using a short snare (61.6%) was significantly higher than that of CSP using a long snare (44.9%; P < 0.05). There were no significant differences in the frequency of complications between CSP using the short snare and that using the long snare., Conclusions: CSP is a safe, useful method for the removal of colonic polyps. CSP using the short snare improved the histologically complete resection rates compared to the long snare. Future studies to further assess the utility of CSP are required.
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- 2016
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44. A Novel Potassium-Competitive Acid Blocker Improves the Efficacy of Clarithromycin-containing 7-day Triple Therapy against Helicobacter pylori.
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Noda H, Noguchi S, Yoshimine T, Goji S, Adachi K, Tamura Y, Izawa S, Ebi M, Yamamoto S, Ogasawara N, Funaki Y, Sasaki M, and Kasugai K
- Subjects
- Aged, Amoxicillin adverse effects, Anti-Bacterial Agents adverse effects, Clarithromycin adverse effects, Drug Administration Schedule, Drug Resistance, Bacterial drug effects, Female, Helicobacter Infections diagnosis, Helicobacter Infections microbiology, Helicobacter pylori pathogenicity, Humans, Japan, Male, Middle Aged, Prospective Studies, Proton Pump Inhibitors adverse effects, Pyrroles adverse effects, Remission Induction, Retrospective Studies, Sulfonamides adverse effects, Time Factors, Treatment Outcome, Amoxicillin administration & dosage, Anti-Bacterial Agents administration & dosage, Clarithromycin administration & dosage, Helicobacter Infections drug therapy, Helicobacter pylori drug effects, Proton Pump Inhibitors administration & dosage, Pyrroles administration & dosage, Sulfonamides administration & dosage
- Abstract
Background and Aims: In Japan, 7-day triple therapy for Helicobacter pylori including clarithromycin (CAM) was approved in 2000. However, antibiotic resistance subsequently reduced this rate to an unacceptable level (70%). Vonoprazan, an orally bioavailable potassium-competitive acid blocker (P-CAB), was approved in Japan in 2014. This could improve eradication rates by increasing the intragastric pH, thus increasing bacterial antibiotic susceptibility. This study compared the efficacy of 7-day triple therapies that included CAM and vonoprazan or proton pump inhibitor (PPI)., Methods: We prospectively analyzed H. pylori eradication rates in 146 patients receiving 7-day triple therapy containing P-CAB (April 2015 to September 2015), and in a retrospective cohort of 1,305 patients who received 7-day triple therapy containing a PPI (April 2011 to September 2015)., Results: H. pylori was eradicated in a significantly higher number of P-CAB-treated patients (89.7% [131/146]) than PPI-treated patients (73.9% [965/1305]; p < 0.05). The eradication rates in P-CAB-treated CAM-sensitive and CAM-resistant bacteria were 100% (44/44) and 87.5% (28/32), respectively, which were significantly higher than the corresponding rates in PPI-treated patients (88.0% [22/25] and 53.8% [7/13], p < 0.05)., Conclusion: P-CAB improved the efficacy of CAM-containing 7-day triple therapy and would be a valuable first-line treatment for H. pylori infection.
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- 2016
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45. Thread-Traction with a Sheath of Polypectomy Snare Facilitates Endoscopic Submucosal Dissection of Early Gastric Cancers.
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Noda H, Ogasawara N, Koshino A, Fukuta S, Nagoya T, Hoshino H, Nagao K, Sugiyama T, Kondo Y, Ito Y, Izawa S, Ebi M, Funaki Y, Sasaki M, and Kasugai K
- Abstract
Although the thread-traction (TT) method has been found useful during endoscopic submucosal dissection (ESD) for early gastric cancers, the movement of the thread interferes with the movement of the endoscope, and the lesion can only be pulled to the mouth side. We have developed the novel TT method using a sheath of polypectomy snare (TTSPS). The TTSPS method enables free and independent movement of the thread and the endoscope and allows pulling the lesion towards the anal as well as oral side. The median dissection times, numbers of instances of arterial bleeding, and numbers of local injections into the submucosal layer were significantly lower for ESD with TTSPS than for conventional ESD. Countertraction ESD using the TTSPS method is straightforward, safe, easy, noninvasive, and cost effective, and it uses instruments readily available in most hospitals to enhance visualization of cutting lines. Therefore, the TTSPS method can be universally applied in conventional ESD.
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- 2016
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46. Helicobacter suis-Infected Nodular Gastritis and a Review of Diagnostic Sensitivity for Helicobacter heilmannii-Like Organisms.
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Goji S, Tamura Y, Sasaki M, Nakamura M, Matsui H, Murayama SY, Ebi M, Ogasawara N, Funaki Y, and Kasugai K
- Abstract
Helicobacter heilmannii-like organisms (HHLOs) are associated with mucosa-associated lymphoid tissue lymphoma and peptic ulcer. However, the sensitivity of diagnostic tests for HHLOs, such as rapid urease test (RUT), urea breath test (UBT) and blood antibody, is not high. Tightly coiled spiral microorganisms were found in the gastric mucosal biopsy specimen of a 48-year-old asymptomatic woman. Her findings were positive for RUT and UBT, but negative for blood antibody and stool antigen against H. pylori. A 7-day course of esomeprazole, amoxicillin and clarithromycin was administered, resulting in the successful eradication of the HHLOs. Analysis of the 16S rRNA and urease genes suggested a diagnosis of the HHLO H. suis. The sensitivity results of RUT, UBT, culture, blood antibody, immunohistochemistry and stool antigen were 40.0, 14.8, 0, 23.1, 40.0 and 0%, respectively. We report asymptomatic nodular gastritis due to an HHLO. Histological techniques, most likely with smears, are expected to be the most effective method for diagnosing infections by HHLOs, and genetic diagnosis by polymerase chain reaction can be very useful to identify the species of HHLOs.
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- 2015
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47. Pathophysiology of functional heartburn based on Rome III criteria in Japanese patients.
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Tamura Y, Funaki Y, Izawa S, Iida A, Yamaguchi Y, Adachi K, Ogasawara N, Sasaki M, Kaneko H, and Kasugai K
- Subjects
- Adult, Aged, Aged, 80 and over, Diagnosis, Differential, Esophageal pH Monitoring, Female, Gastroesophageal Reflux drug therapy, Gastroesophageal Reflux ethnology, Heartburn drug therapy, Heartburn ethnology, Humans, Japan epidemiology, Male, Manometry, Middle Aged, Predictive Value of Tests, Pressure, Prospective Studies, Proton Pump Inhibitors therapeutic use, Surveys and Questionnaires, Asian People, Esophagus physiopathology, Gastroesophageal Reflux diagnosis, Gastroesophageal Reflux physiopathology, Heartburn diagnosis, Heartburn physiopathology
- Abstract
Aim: To investigate the pathophysiology of functional heartburn (FH) in Japanese patients., Methods: A total of 111 patients with proton pump inhibitor (PPI)-refractory non-erosive gastroesophageal reflux disease underwent intraesophageal pressure testing and 24-h multichannel intraluminal impedance-pH (24MII-pH) testing. The patients also completed several questionnaires while they were receiving the PPI treatment, including the questionnaire for the diagnosis of reflux disease (QUEST), the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), the gastrointestinal symptoms rating scale (GSRS), SF-36, and the Cornell Medical Index (CMI). The subjects were classified into FH and endoscopy-negative reflux disease (ENRD) groups based on the Rome III criteria., Results: Thirty-three patients with esophageal motility disorder were excluded from this study, while 22 patients with abnormal esophageal acid exposure time (pH-POS) and 34 with hypersensitive esophagus (HE) were included in the ENRD group. The FH group included 22 patients with no reflux involvement. Sex, age, and body mass index did not differ significantly between the groups. The mean SF-36 values were < 50 (normal) for all scales in these groups, with no significant differences. The GSRS scores in these groups were not different and showed overlap with other gastrointestinal symptoms. The QUEST and the FSSG scores did not differ significantly between the groups. Neuroticism was diagnosed using the CMI questionnaire in 17 of the 78 included subjects within the pH-POS (n = 4), HE (n = 8), and FH (n = 5) groups, with no significant differences., Conclusion: Clinical characteristics of the FH and PPI-refractory ENRD groups were similar. Therefore, esophageal function should be examined via manometry and 24MII-pH testing to differentiate between them.
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- 2015
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48. Prolonged Survival in a Case of Chemotherapy-Sensitive Gastric Cancer That Produced Alpha-Fetoprotein and Protein Induced by Vitamin K Antagonist-II.
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Ogasawara N, Takahashi E, Matsumoto T, Amaike M, Nohara M, Nagao K, Ebi M, Funaki Y, Sasaki M, and Kasugai K
- Abstract
The number of reported cases of alpha-fetoprotein (AFP)-producing gastric cancer has gradually increased, with a reported prevalence of 1.3-1.5% of all gastric cancer cases. However, reports of gastric cancer accompanied by elevated serum levels of both AFP and protein induced by vitamin K antagonist-II (PIVKA-II) are rare. The prognosis of AFP- and PIVKA-II-producing gastric cancer has been reported to be very poor because the tumor cells were considered to have a high malignant potential and the cancer progressed rapidly. We described a case of gastric cancer producing AFP and PIVKA-II in which chemotherapy was effective and resulted in prolonged survival, and these two tumor markers were useful for monitoring the treatment response. Routine health screening using upper abdominal ultrasonography revealed hepatic tumors in an apparently healthy 65-year-old man. Whole-body computed tomography (CT) revealed multiple hepatic tumors, and an esophagogastroduodenoscopy (EGD) revealed a Bormann type 3 tumor in the lower stomach. A biopsy specimen confirmed that the tumor was immunohistochemically positive for AFP, PIVKA-II, and human epidermal growth factor receptor 2. After chemotherapy, the gastric tumor appeared as a small elevated lesion on EGD, and CT revealed a remarkable reduction in the size of the metastatic liver tumors. The patient is still alive, 35 months after the initial chemotherapy.
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- 2015
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49. Recovering 3D Shape with Absolute Size from Endoscope Images Using RBF Neural Network.
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Tsuda S, Iwahori Y, Bhuyan MK, Woodham RJ, and Kasugai K
- Abstract
Medical diagnosis judges the status of polyp from the size and the 3D shape of the polyp from its medical endoscope image. However the medical doctor judges the status empirically from the endoscope image and more accurate 3D shape recovery from its 2D image has been demanded to support this judgment. As a method to recover 3D shape with high speed, VBW (Vogel-Breuß-Weickert) model is proposed to recover 3D shape under the condition of point light source illumination and perspective projection. However, VBW model recovers the relative shape but there is a problem that the shape cannot be recovered with the exact size. Here, shape modification is introduced to recover the exact shape with modification from that with VBW model. RBF-NN is introduced for the mapping between input and output. Input is given as the output of gradient parameters of VBW model for the generated sphere. Output is given as the true gradient parameters of true values of the generated sphere. Learning mapping with NN can modify the gradient and the depth can be recovered according to the modified gradient parameters. Performance of the proposed approach is confirmed via computer simulation and real experiment.
- Published
- 2015
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50. A Patient with Vigorous Achalasia and Rapid Enlargement of an Epiphrenic Esophageal Diverticulum.
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Tamura Y, Funaki Y, Adachi K, Noda H, Izawa S, Iida A, Ogasawara N, Miyaji M, Sasaki M, and Kasugai K
- Subjects
- Diverticulum, Esophageal surgery, Esophageal Achalasia diagnosis, Fundoplication methods, Heartburn etiology, Humans, Male, Middle Aged, Proton Pump Inhibitors therapeutic use, Treatment Outcome, Diverticulum, Esophageal diagnosis, Esophageal Achalasia surgery, Heartburn surgery, Laparoscopy methods
- Abstract
A 47-year-old man was found to have a 3-cm epiphrenic esophageal diverticulum on an upper gastrointestinal (UGI) barium study. He developed the symptoms of heartburn approximately 12 months later. UGI endoscopy indicated non-erosive gastroesophageal reflux disease (NERD) and an epiphrenic esophageal diverticulum. A proton pump inhibitor (PPI) did not relieve the symptoms. An UGI barium study at that time showed that the epiphrenic esophageal diverticulum had enlarged to 7 cm, and esophageal manometry showed findings of achalasia and diffuse esophageal spasm (DES), thus vigorous achalasia was diagnosed. Resection of the epiphrenic esophageal diverticulum, myotomy, and fundoplication (the Heller-Dor procedure) were successfully performed and no postoperative symptoms were encountered.
- Published
- 2015
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