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| 1 | Endoscopic diagnosis of sessile serrated adenoma/polyp with and without dysplasia/carcinoma显示文摘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 dysplasia/carcinoma and reduce the interval cancer rates. | Takashi Murakami Naoto Sakamoto Akihito Nagahara | 2018 | World Journal of Gastroenterology2018，24，29： | 25 |
| 2 | Clinicopathological features of alpha-fetoprotein producing early gastric cancer with enteroblastic differentiation显示文摘AIM To investigate clinicopathological features of early stage gastric cancer with enteroblastic differentiation(GCED).METHODS We retrospectively investigated data on 6 cases of early stage GCED and 186 cases of early stage conventional gastric cancer(CGC: well or moderately differentiated adenocarcinoma) who underwent endoscopic submucosal dissection or endoscopic mucosal resection from September 2011 to February 2015 in our hospital.GCED was defined as a tumor having a primitive intestine-like structure composed of cuboidal or columnar cells with clear cytoplasm and immunohistochemical positivity for either alpha-fetoprotein, Glypican 3 or SALL4. The following were compared between GCED and CGC: age, gender, location and size of tumor, macroscopic type, ulceration, depth of invasion, lymphatic and venous invasion, positive horizontal and vertical margin, curative resection rate.RESULTS Six cases(5 males, 1 female; mean age 75.7 years; 6 lesions) of early gastric cancer with a GCED component and 186 cases(139 males, 47 females; mean age 72.7 years; 209 lesions) of early stage CGC were investigated. Mean tumor diameters were similar but rates of submucosal invasion, lymphatic invasion, venous invasion, and non-curative resection were higher in GCED than CGC(66.6% vs 11.4%, 33.3% vs 2.3%, 66.6% vs 0.4%, 83.3% vs 11% respectively, P < 0.01). Deep submucosal invasion was not revealed endoscopically or by preoperative biopsy. Histologically, in GCED the superficial mucosal layer was covered with a CGC component. The GCED component tended to exist in the deeper part of the mucosa to the submucosa by lymphatic and/or venous invasion, without severe stromal reaction. In addition, Glypican 3 was the most sensitive marker for GCED(positivity, 83.3%), immunohistochemically.CONCLUSION Even in the early stage GCED has high malignant potential, and preoperative diagnosis is considered difficult. Endoscopists and pathologists should know the clinicopathological features of this highly malignant type of cancer. | Kohei Matsumoto Hiroya Ueyama Kenshi Matsumoto Yoichi Akazawa Hiroyuki Komori Tsutomu Takeda Takashi Murakami Daisuke Asaoka Mariko Hojo Natsumi Tomita Akihito Nagahara Yoshiaki Kajiyama Takashi Yao Sumio Watanabe | 2016 | World Journal of Gastroenterology2016，22，36： | 20 |
| 3 | Prognostic significance of the lymphocyte-to-monocyte ratio in patients with metastatic colorectal cancer显示文摘AIM:To evaluate the prognostic significance of the lymphocyte to monocyte ratio(LMR) in patients with unresectable metastatic colorectal cancer who received palliative chemotherapy.METHODS:A total of 104 patients with unresectable metastatic colorectal cancer who underwent palliative chemotherapy were enrolled. The LMR was calculated from blood samples by dividing the absolute lymphocyte count by the absolute monocyte count. Pretreatment LMR values were measured within one week before the initiation of chemotherapy,while posttreatment LMR values were measured eight weeks after the initiation of chemotherapy.RESULTS:The median pre-treatment LMR was 4.16(range:0.58-14.06). We set 3.38 as the cut-off level based on the receiver operating characteristic curve. Based on the cut-off level of 3.38,66 patients were classified into the high pre-treatment LMR group and 38 patients were classified into the low pretreatment LMR group. The low pre-treatment LMR group had a significantly worse overall survival rate(P = 0.0011). Moreover,patients who demonstrated low pre-treatment LMR and normalization after treatmentexhibited a better overall survival rate than the patients with low pre-treatment and post-treatment LMR values.CONCLUSION:The lymphocyte to monocyte ratio is a useful prognostic marker in patients with unresectable metastatic colorectal cancer who receive palliative chemotherapy. | Masatsune Shibutani Kiyoshi Maeda Hisashi Nagahara Hiroshi Ohtani Katsunobu Sakurai Sadaaki Yamazoe Kenjiro Kimura Takahiro Toyokawa Ryosuke Amano Hiroaki Tanaka Kazuya Muguruma Kosei Hirakawa | 2015 | World Journal of Gastroenterology2015，21，34： | 19 |
| 4 | Inflammation-based factors and prognosis in patients with colorectal cancer显示文摘Several parameters for predicting survival in patients with colorectal cancer have been identified, including the performance status, age, gender and tumor-nodemetastasis(TNM) stage. Although the TNM stage is important and useful for predicting the prognosis and determining the appropriate treatment, it is well known that the survival time varies widely, even in patients with the same stage of disease. Therefore, the identification of new parameters capable of more precisely predicting patient survival is needed to help select the optimal treatment, especially in patients in the advanced stage of disease. Although the TNM stage reflects the tumor characteristics, cancer progression and survival are not determined solely based on the local characteristics of the tumor, but also the host systemic immune/inflammatory response. Therefore, using a combination of parameters that reflect both tumor characteristics and the host systemic inflammatory status is thought to be important for accurately predicting patient survival. | Kiyoshi Maeda Masatusne Shibutani Hiroshi Otani Hisashi Nagahara Tetsuro Ikeya Yasuhito Iseki Hiroaki Tanaka Kazuya Muguruma Kosei Hirakawa | 2015 | World Journal of Gastrointestinal Oncology2015，7，8： | 12 |
| 5 | Factors associated with incomplete colonoscopy at a Japanese academic hospital显示文摘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. | Shigeo Koido Toshifumi Ohkusa Kosaburo Nakae Tetsuji Yokoyama Tomoyoshi Shibuya Naoto Sakamoto Kan Uchiyama Hiroshi Arakawa Taro Osada Akihito Nagahara Sumio Watanabe Hisao Tajiri | 2014 | World Journal of Gastroenterology2014，20，22： | 6 |
| 6 | A white opaque substance-positive gastric hyperplastic polyp with dysplasia显示文摘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. | Hiroya Ueyama Kenshi Matsumoto Akihito Nagahara Ryosuke Gushima Takuo Hayashi Takashi Yao Sumio Watanabe | 2013 | World Journal of Gastroenterology2013，19，26： | 4 |
| 7 | Seasonal variations in the onset of ulcerative colitis in Japan显示文摘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. | Shigeo Koido Toshifumi Ohkusa Hiroaki Saito Tetsuji Yokoyama Tomoyoshi Shibuya Naoto Sakamoto Kan Uchiyama Hiroshi Arakawa Taro Osada Akihito Nagahara Sumio Watanabe Hisao Tajiri | 2013 | World Journal of Gastroenterology2013，19，47： | 3 |
| 8 | Characteristic pathological findings and effects of ecabet sodium in rat reflux esophagitis显示文摘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. | Daisuke Asaoka Akihito Nagahara Masako Oguro Yuko Izumi Akihiko Kurosawa Taro Osada Masato Kawabe Mariko Hojo Michiro Otaka Sumio Watanabe | 2009 | World Journal of Gastroenterology2009，15，28： | 2 |
| 9 | Gastrointestinal stromal tumor of the stomach with a giant abscess penetrating the gastric lumen显示文摘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. | Taro Osada Akihito Nagahara Tomohiro Kodani Akihiro Namihisa Masato Kawabe Takashi Yoshizawa Toshifumi Ohkusa Sumio Watanabe | 2007 | World Journal of Gastroenterology2007，13，16： | 2 |
| 10 | Pretreatment AKR1B10 expression predicts the risk of hepatocellular carcinoma development after hepatitis C virus eradication显示文摘AIM To clarify the association between aldo-keto reductase family 1 member B10(AKR1B10) expression and hepatocarcinogenesis after hepatitis C virus eradication.METHODS In this study,we enrolled 303 chronic hepatitis C patients who had achieved sustained virological response(SVR) through interferon-based antiviral therapy. Pretreatment AKR1B10 expression in the liver was immunohistochemically assessed and quantified as a percentage of positive staining area by using image-analysis software. A multivariate Cox analysis was used to estimate the hazard ratios(HRs) of AKR1B10 expression for hepatocellular carcinoma(HCC) development after achieving SVR. The cumulative incidences of HCC development were evaluated using Kaplan-Meier analysis and the log-rank test.RESULTS Of the 303 chronic hepatitis C patients,153(50.5%) showed scarce hepatic AKR1B10 expression,quantified as 0%,which was similar to the expression in control normal liver tissues. However,the remaining 150 patients(49.5%) exhibited various degrees of AKR1B10 expression in the liver,with a maximal AKR1B10 expression of 73%. During the median follow-up time of 3.6 years(range 1.0-10.0 years),8/303 patients developed HCC. Multivariate analysis revealed that only high AKR1B10 expression(≥ 8%) was an independent risk factor for HCC development(HR = 15.4,95%CI: 1. 8- 1 3 2. 5,P = 0. 0 1 2). T h e 5- y e a r c u m u l a t i v e incidences of HCC development were 13.7% and 0.5% in patients with high and low AKR1B10 expression,respectively(P < 0.001). During the follow-up period after viral eradication,patients expressing high levels of AKR1B10 expressed markedly higher levels of alanine aminotransferase and α-fetoprotein than did patients exhibiting low AKR1B10 expression.CONCLUSION Chronic hepatitis C patients expressing high levels of hepatic AKR1B10 had an increased risk of HCC development even after SVR. | Ayato Murata Takuya Genda Takafumi Ichida Nozomi Amano Sho Sato Hironori Tsuzura Shunsuke Sato Yutaka Narita Yoshio Kanemitsu Yuji Shimada Katsuharu Hirano Katsuyori Iijima Ryo Wada Akihito Nagahara Sumio Watanabe | 2016 | World Journal of Gastroenterology2016，22，33： | 2 |
| 11 | Phase I clinical trial of peptide vaccination with URLC10 and VEGFR1epitope peptides in patients with advanced gastric cancer显示文摘 | Yoshie Higashihara Junko Kato Akihito Nagahara Kentaro Izumi Masae Konishi Tomohiro Kodani Nobuko Serizawa Taro Osada Sumio Watanabe | 2014 | International Journal of Oncology2014，，： | 2 |
| 12 | Baseline gastric mucosal atrophy is a risk factor associated with the development of gastric cancer after Helicobacter pylori eradication therapy in patients with peptic ulcer diseases显示文摘 | Susumu Take Motowo Mizuno Kuniharu Ishiki Yasuhiro Nagahara Tomowo Yoshida Kenji Yokota Keiji Oguma | 2007 | Journal of Gastroenterology2007，，17： | 2 |
| 13 | Camera array calibration for light field acquisition显示文摘 | Yichao XU Kazuki MAENO Hajime NAGAHARA Rin-ichiro TANIGUCHI | 2015 | Frontiers of Computer Science2015，9，5： | 2 |
| 14 | The epidermal growth factor receptor gene sequence is highly conserved in primary gastric cancers显示文摘 | Mimori K Nagahara H Sudo T | 2006 | J Surg Oncol2006，93，1： | 1 |
| 15 | FHIT is up-regulated by inflammatory stimuli and inhibits prostaglandin E2-mediated cancer progression显示文摘 | Mimori K Ishii H Nagahara H | 2006 | Cancer Res2006，66，5： | 1 |
| 16 | Potential of adenovirus‐mediated REIC / Dkk ‐3 gene therapy for use in the treatment of pancreatic cancer显示文摘 | Daisuke Uchida Hidenori Shiraha Hironari Kato Teruya Nagahara Masaya Iwamuro Junro Kataoka Shigeru Horiguchi Masami Watanabe Akinobu Takaki Kazuhiro Nouso Yasutomo Nasu Takahito Yagi Hiromi Kumon Kazuhide Yamamoto | 2014 | J Gastroenterol Hepatol2014，，5： | 1 |
| 17 | Transduction of full-length TAT fusion proteins into mammalian cells: TAT-p27Kipl induces cell migration 显示文摘 | Vocero Akbani AM Snyder EL | 1998 | Nat Med1998，4，12： | 1 |
| 18 | Simulation of space weathering of planet-forming materials : Nanosecond pulse laser irradiation and proton implantation on olivine and pyrnxene samples 显示文摘 | Yamada M Sasaki S Nagahara H | 1999 | Earth Planets Space1999，，： | 1 |
| 19 | Transduction of full-length TAT fusion proteins into mammalian cells: TAT-p27Kipl induces cell migration显示文摘 | Nagahara H Vocero-Akbani AM Snyder EL | 1998 | Nature Med1998，4，： | 1 |
| 20 | Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models ofAlzheimer' s disease 显示文摘 | Nagahara AH Merrill DA Coppola G | 2009 | Nat Med2009，，： | 1 |
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