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Endoscopic diagnosis of sessile serrated adenoma/polyp with and without dysplasia/carcinoma

World Journal of Gastroenterology 2018年第29期24卷 3250-3259页

作者： Takashi Murakami Naoto Sakamoto akihito nagahara Department of Gastroenterology Juntendo University School of Medicine

Sessile serrated adenoma/polyps(SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in colorectal carcinomas with BRAF mutations, methylation for DNA repair genes, a Cp G island methylator phenotype, and high levels of microsatellite instability. Some of these lesions can rapidly become dysplastic or invasive carcinomas that exhibit high lymphatic invasion and lymph node metastasis potentials. Detecting serrated lesions, including SSA/Ps with and without dysplasia/carcinoma, is critical, but SSA/Ps can be difficult to detect, are inconsistently identified by endoscopists and pathologists, and are often incompletely resected. Therefore, SSA/Ps are considered to be major contributors to "interval cancers". If colonoscopists can identify the specific endoscopic characteristics of SSA/Ps, their detection and the effectiveness of colonoscopy may improve. Here, the endoscopic features of SSA/Ps with and without dysplasia/carcinoma, including the characteristics determined using magnifying endoscopy, are reviewed in the context of previous reports. Endoscopically, these subtle polyps are like hyperplastic polyps, because they are slightly elevated and pale. Unlike hyperplastic polyps, SSA/Ps are usually larger than 5 mm, frequently covered by a thin layer called the ‘‘mucus cap'', and are more commonly located in the proximal colon. Magnifying narrow-band imaging findings, which include dark spots inside the crypts and varicose microvascular vessels, in addition to the type II-open pit patterns detected using magnifying chromoendoscopy, effectively differentiate SSA/Ps from hyperplastic polyps. The lesions' endoscopic characteristics, which include their(semi)pedunculated morphologies, double elevations, central depressions, and reddishness, and the use of magnifying endoscopy, might help to detect dysplasia/carcinoma within SSA/Ps. Greater awareness may promote further research into improving the detection, identification, and complete resection rates of SSA/Ps with and without dysplasi

关键词： Sessile serrated adenoma/polyp Invasive carcinoma arising from sessile serrated adenoma/polyp Serrated neoplasia pathway Endoscopic diagnosis Sessile serrated adenoma/polyp with cytological dysplasia

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Corticotropin-releasing factor secretion from dendritic cells stimulated by commensal bacteria

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World Journal of Gastroenterology 2011年第35期17卷 4017-4022页

作者： Mariko Hojo Toshifumi Ohkusa Harumi Tomeoku Shigeo Koido Daisuke Asaoka akihito nagahara Sumio Watanabe Department of Gastroenterology Juntendo University School of MedicineTokyo 113-8421Japan Department of Gastroenterology and Hepatology The Jikei University Kashiwa HospitalChiba 277-8567Japan

AIM:To study the production and secretion of corticotropin-releasing factor (CRF) by dendritic cells and the influence of commensal bacteria.METHODS:JAWSⅡ cells (ATCC CRL-11904),a mouse dendritic cell line,were seeded into 24-well culture plates and grown for 3 d.Commensal bacterial strains of Clostridium clostrodiiforme (JCM1291),Bacteroides vulgatus (B.vulgatus) (JCM5856),Escherichia coli (JCM1649),or Fusobacterium varium (F.varium) (ATCC8501) were added to the cells except for the control well,and incubated for 2 h.After incubation,we performed enzyme-linked immunosorbent assay for the cultured medium and reverse transcription polymerase chain reaction for the dendritic cells,and compared these values with controls.RESULTS:The level of CRF secretion by control dendritic cells was 40.4±6.2 pg/mL.The CRF levels for cells incubated with F.varium and B.vulgatus were significantly higher than that of the control (P<0.0001).CRF mRNA was present in the control sample without bacteria,and CRF mRNA levels in all samples treated with bacteria were above that of the control sample.F.varium caused the greatest increase in CRF mRNA expression.CONCLUSION:Our results suggest that dendritic cells produce CRF,a process augmented by commensal bacteria.

关键词：促肾上腺皮质激素释放因子树突状细胞共生细菌细胞分泌慢性肾功能衰竭逆转录聚合酶链反应酶联免疫吸附试验 mRNA水平

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Characteristic pathological findings and effects of ecabet sodium in rat reflux esophagitis

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World Journal of Gastroenterology 2009年第28期15卷 3480-3485页

作者： Daisuke Asaoka akihito nagahara Masako Oguro Yuko Izumi Akihiko Kurosawa Taro Osada Masato Kawabe Mariko Hojo Michiro Otaka Sumio Watanabe Department of Gastroenterology Juntendo University School of Medicine

AIM:To explore the pathological flndings in the entire esophagus in rats with reflux esophagitis, and the effects of ecabet sodium(ES).METHODS:A rat model of chronic acid reflux esophagitis was used.In the treatment group, ES was administered after surgery(n = 16).No drug was administered postoperatively to the esophagitis group(n = 9).Shamoperated rats were used as a control group(n = 5).Rats were sacriflced on day 7 after the operation.The epithelial thickness and leukocyte inflltration were examined in the upper, middle and lower areas of the esophagus.The survival rate, incidence of esophageal ulcer, and mean surface area and number of esophageal ulcers were determined in the esophagitis and ES groups.Esophageal histology was assessed in all three groups.RESULTS:Leukocyte infiltration in the esophagitis group was 26.3 ± 22.0 in the middle esophagus and 8.2 ± 4.9 in the upper esophagus, which was signiflcantly greater than that in the controls(1.3 ± 1.1 and 1.4 ± 1.0, respectively)(P < 0.05).The thickness of the epithelium in the esophagitis group was 210.8 ± 47.7 μm in the lower esophagus and 204.2 ± 60.1 μm in the middle esophagus, which was significantlygreater than that in the controls(26.0 ± 5.5 and 21.0 ± 6.5 μm, respectively)(P < 0.05).The mean number of ulcers per animal in the ES group in the entire esophagus was 5.4 ± 2.5, which was signiflcantly less than that in the esophagitis group(9.0 ± 3.5)(P < 0.05).The epithelial thickness in the ES group was 97.5 ± 32.2 μm in the lower esophagus, which was decreased compared with that in the esophagitis group(210.8 ± 47.7 μm)(P < 0.05).CONCLUSION:Mucosal inflammation extended to the upper esophagus close to the hypopharynx.Our study suggested that ES may have a useful defensive role in reflux esophagitis.

关键词：特征和食管大鼠病理钠

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Gastrointestinal stromal tumor of the stomach with a giant abscess penetrating the gastric lumen

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World Journal of Gastroenterology 2007年第16期13卷 2385-2387页

作者： Taro Osada akihito nagahara Tomohiro Kodani Akihiro Namihisa Masato Kawabe Takashi Yoshizawa Toshifumi Ohkusa Sumio Watanabe Sumio Watanabe Department of Gastroenterology Juntendo University School of Medicine 2-1-1 Hongo Bunkyo-ku Tokyo 113-8421 Japan

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. In large GISTs, cystic degeneration, necrosis and focal hemorrhage that occur inside the tumor can result in gastrointestinal bleeding. We describe a case of a 74-year old male with GIST of the stomach accompanied with a giant abscess that penetrated the gastric lumen. The patient experienced undiagnosed fever for two months prior to hospitalization. Gastrointestinal endoscopy, X-ray series and computed tomography of the patient’s abdomen revealed a gastric submucosal tumor in the fornix, with a fistula to the gastric lumen that was inundated with a great deal of pus. The mass was diagnosed as a GIST from biopsy specimens. The patient was treated by endoscopic drainage of the abscess and intravenous administration of antibiotics. Eventually, a partial gastrectomy was performed. He was also administered Imanitib mesylate as adjuvant therapy. He was followed up for 2 years and no metastasis or recurrence was recognized at the follow- up examinations. This is the first report of a patient with clearly diagnosed GIST with endoscopic evidence of an abscess penetrating into the gastric lumen.

关键词：胃肠道间质瘤脓肿穿孔胃穿孔引流治疗

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A white opaque substance-positive gastric hyperplastic polyp with dysplasia

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World Journal of Gastroenterology 2013年第26期19卷 4262-4266页

作者： Hiroya Ueyama Kenshi Matsumoto akihito nagahara Ryosuke Gushima Takuo Hayashi Takashi Yao Sumio Watanabe Department of Gastroenterology Juntendo University School of Medicine Department of Human Pathology Juntendo University School of Medicine

The endoscopic findings of gastric hyperplastic polyps (HPs) with dysplasia have not been well-defined, and the clinical significance of these lesions, including their malignant potential, is unclear. In this report, we describe a case of a white opaque substance (WOS)positive gastric HP with dysplasia. A 76-year-old woman was referred to our hospital for endoscopic resection of a gastric HP. Upper endoscopy revealed a 25-mm whitish and reddish polypoid lesion on the greater curvature in the lower third of the stomach. The whitish part was diagnosed as a WOS using conventional and magnifying endoscopy with narrow band imaging. An examination of the biopsy specimen indicated that the lesion was a typical gastric HP. However, because of its color and the presence of a WOS, we suspected that this lesion was an atypical gastric HP. Therefore, we performed a polypectomy. Histopathologically, diffuse lowto high-grade dysplasia was found on the surface of the polyp. We performed immunohistochemical staining using a monoclonal antibody specific for adipophilin as a marker of lipid droplets (LDs). LDs were detected in approximately all of the neoplastic cells, especially in the surface epithelium of the intervening apical parts and were located in the subnuclear cytoplasm of the neoplastic cells. According to endoscopic and histopathological findings, the WOS-positive epithelium indicated dysplasia of the gastrointestinal phenotype, which could absorb lipids. The presence of a WOS in a gastric HP may be considered an endoscopic finding that is predictive of the neoplastic transformation of a gastric HP. We suggest that a WOS-positive gastric HP should be resected endoscopically to investigate its neoplastic transformation.

关键词： Gastric hyperplastic polyp with dysplasia White opaque substance Adipophilin Lipid droplet Narrow band imaging

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Symptoms of Gastro-Esophageal Reflux Disease: A Comparative Study between Elderly and Younger Patients in Japan

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Health 2014年第14期6卷 1700-1705页

作者： Mariko Hojo akihito nagahara Daisuke Asaoka Hiroya Ueyama Yuji Shimada Kenshi Matsumoto Sumio Watanabe Department of Gastroenterology School of Medicine Juntendo University Tokyo Japan

The difference in gastro-esophageal reflux disease (GERD) symptoms between elderly and younger GERD patients has not been fully studied. Our aim was to examine if there was any difference in the degree of GERD symptoms between elderly and younger patients with reflux esophagitis. Patients who were diagnosed by endoscopic examination as having reflux esophagitis and who answered the questionnaire on the frequency scale for the symptoms of GERD (FSSG) were included. Elderly and younger adult patients were defined as patients aged 65 and over or less than 65, respectively. 596 subjects were included. 184 subjects (mean 71.1 years;114 males) were classified into the Elderly group, and 412 subjects (mean 51.2 years;307 males) into the Younger group. The mean FSSG score of the Elderly and Younger groups was 6.7 and 8.4, respectively (p = 0.0024). Among those with severe esophagitis, the mean FSSG score of the Elderly and Younger groups was 8.5 and 8.7, respectively (p = 0.58). Although elderly patients tended to have less degree of GERD symptoms than younger patients, these findings suggest that there may be no significant age-related difference in complaints of GERD symptoms among severe reflux esophagitis patients.

关键词： Gastro-Esophageal Reflux Disease Reflux Esophagitis Los Angeles Classification Elderly FSSG Questionnaire

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Quit smoking improves gastroesophageal reflux symptoms and quality of life

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Health 2011年第11期3卷 677-683页

作者： Kou Nakajima akihito nagahara Akihiko Kurosawa Kuniaki Seyama Daisuke Asaoka Taro Osada Mariko Hojo Sumio Watanabe 不详

Background: Smoking is considered to be risk factors of gastroesophageal reflux disease (GERD). The present study aimed to reveal whether quit smoking improves GERD symptoms and QOL of patients. Methods: In this prospective study, 33 patients who participated in a 12-week quit smoking program filled out the Frequency Scale for the Symptoms of GERD (FSSG) questionnaire, and SF8 QOL questionnaire. Patients filled out the questionnaires at baseline and during the program at 2 weeks, 4 weeks, 8 weeks and 12 weeks. In the FSSG, the responses were scored and the reflux score (RS), dysmotility score (DS) and total score (TS) were calculated. Results: There were 22 males and 11 females. Their mean age was 54.8 ± 13.0 (mean ± SD) yr, BMI was 22.9 ± 4.0, and duration of smoking was 33.5 ± 12.5 years. Ten patients belonged to GERD subgroup (baselineFSSGscore ≥ 8). All patients were successful at quit smoking. Scores of TS/RS/DS are 8.6 ± 1.8 (mean ± SE)/4.2 ± 0.9/4.5 ± 0.9 at baseline, 4.7 ± 1.6**/2.5 ± 0.9**/2.3 ± 0.7** at 2 w, 5.7 ± 1.3**/2.6 ± 0.6*/3.0 ± 0.7* at 4 w, 4.5 ± 1.4*/2.2 ± 0.8*/2.3 ± 0.8* at 8 w and 3.7 ± 1.2**/1.7 ± 0.6**/2.0 ± 0.7** at 12 w, respectively (**p < 0.01, *p < 0.05 vs. baseline). Among GERD subgroup, Scores of TS/RS/DS are 18.0 ± 2.9/8.9 ± 1.6/9.1 ± 1.5 at baseline, 8.8 ± 3.0/5.1 ± 1.7/3.7 ± 1.6 at 2 w, 10.8 ± 2.9/5.4 ± 1.6/5.4 ± 1.5 at 4 w, 7.6 ± 2.9*/4.1 ± 1.6/3.5 ± 1.5* at 8 w and 7.1 ± 2.9*/3.2 ± 1.6*/3.9 ± 1.5* at 12w, respectively. Regarding QOL, physical component score has significantly improved at 2, 4, 8 and 12 w and mental component score at 4w, respectively. Conclusions: Quit smoking significantly improved not only GERD symptoms but also QOL, indicating that quit smoking might be an option in the treatment strategy of GERD symptoms.

关键词： Quit Smoking FSSG GERD SF8

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Malignant lymphoma in the ileum diagnosed by double-balloon enteroscopy

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World Journal of Gastroenterology 2007年第24期13卷 3388-3391页

作者： Kazuko Beppu Taro Osada akihito nagahara Naoto Sakamoto Tomoyoshi Shibuya Masato Kawabe Takeshi Terai Toshifumi Ohkusa Tatsuo Ogihara Nobuhiro Sato Toshiki Kamano Yasuo Hayashida Sumio Watanabe Department of Gastroenterology Juntendo University School of Medicine 2-1-1 Hongo Bunkyo-ku Tokyo 113-8421 Japan Department of Coloproctological Surgery Juntendo University School of Medicine dicine 2-1-1 Hongo Bunkyo-ku Tokyo 113-8421 Japan Department of General Medicine Juntendo University School of Medicine 2-1-1 Hongo Bunkyo-ku Tokyo 113-8421 Japan

A 73-year old man presented with abdominal pain. A tumor with central ulceration was observed in the ileum using double-balloon enteroscopy. Histological findings of the biopsy specimens were consistent with malignant lymphoma. Double-balloon enteroscopy confirmed the diagnosis of a malignant lymphoma tumor which was surgically resected. The patient is still in complete remission now.

关键词：淋巴瘤诊断治疗方法症状

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Factors associated with incomplete colonoscopy at a Japanese academic hospital

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World Journal of Gastroenterology 2014年第22期20卷 6961-6967页

作者： Shigeo Koido Toshifumi Ohkusa Kosaburo Nakae Tetsuji Yokoyama Tomoyoshi Shibuya Naoto Sakamoto Kan Uchiyama Hiroshi Arakawa Taro Osada akihito nagahara Sumio Watanabe Hisao Tajiri Division of Gastroenterology and Hepatology Department of Internal MedicineThe Jikei University School of MedicineChiba 277-8567Japan Department of Gastroenterology Juntendo University School of MedicineTokyo 113-8421Japan Department of Technology Assessment and Biostatistics National Institute of Public HealthSaitama 351-0197Japan

AIM:To evaluate significant risk factors for incomplete colonoscopy at a Japanese academic hospital.METHODS:A total of 11812 consecutive Japanese people were identified who underwent a colonoscopy at an academic hospital.A multiple logistic regression model was used to evaluate retrospectively the significant risk factors for incomplete colonoscopy.RESULTS:The cecal intubation rate was 95.0%.By univariate analysis,age,female sex,poor bowel cleansing,and a history of abdominal or pelvic surgery were significant risk factors for incomplete colonoscopy(P<0.001).Moreover,age-and sex-adjusted analysis showed that significant risk factors for incomplete colonoscopy were female sex(OR=1.38,95%CI:1.17-1.64,P=0.0002),age≥60 years old(OR=1.44,95%CI:1.22-1.71,P<0.0001),a history of prior abdominal or pelvic surgery(OR=1.55,95%CI:1.28-1.86,P<0.0001),poor bowel cleansing(OR=4.64,95%CI:3.69-5.84,P<0.0001),and inflammatory bowel disease(IBD)(OR=1.48,95%CI:1.13-1.95,P=0.0048).In Japanese men,by age-adjusted analysis,IBD(OR=1.69,95%CI:1.18-2.43,P=0.005)was an independent risk factor for incomplete colonoscopy.CONCLUSION:Several characteristics in the Japanese population were identified that could predict technical difficulty with colonoscopy.

关键词： Colonoscopy Incomplete Intubation rates Japanese a

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Seasonal variations in the onset of ulcerative colitis in Japan

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World Journal of Gastroenterology 2013年第47期19卷 9063-9068页

作者： Shigeo Koido Toshifumi Ohkusa Hiroaki Saito Tetsuji Yokoyama Tomoyoshi Shibuya Naoto Sakamoto Kan Uchiyama Hiroshi Arakawa Taro Osada akihito nagahara Sumio Watanabe Hisao Tajiri Division of Gastroenterology and Hepatology Department of Internal Medicinethe Jikei University School of MedicineChiba 277-8567Japan Department of Gastroenterology Juntendo University School of MedicineTokyo 113-8421Japan Department of Health Promotion National Institute of Public HealthSaitama 351-0197Japan

AIM:To investigate seasonal variations in the onset and relapse of ulcerative colitis(UC)in Japanese patients.METHODS:Between 1994 and 2006,198 Japanese patients diagnosed with UC according to conventional criteria in an academic hospital were enrolled for onset evaluation.Among 265 Japanese patients with UC who were observed for more than 12 mo,165 patients relapsed(239 times)and were enrolled for relapse evaluation.The patients’symptoms were recorded each month for 12 consecutive years.RESULTS:There was monthly seasonality in symptom onset during October and March for UC.The onset of symptoms in UC patients frequently occurred during the winter.Variation in UC onset was observed according to both month(P=0.015)and season(P=0.048).Relapse commonly occurred in October,and variations in relapse were not significant either in month(P=0.52)or season(P=0.12).Upper respiratory inflammation was the main factor responsible for relapse.CONCLUSION:Our results suggest that environmental factors associated with winter and spring seasonality may be responsible for triggering the clinical onset of UC in Japan.

关键词： Japanese population Onset Relapse Seasonal variations Ulcerative colitis

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