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| 1 | Quality of ulcer healing in gastrointestinal tract:Its pathophysiology and clinical relevance显示文摘In this paper,we review the concept of quality of ulcer healing(QOUH) in the gastrointestinal tract and its role in the ulcer recurrence.In the past,peptic ulcer disease(PUD) has been a chronic disease with a cycle of repeated healing/remission and recurrence.The main etiological factor of PUD is Helicobacter pylori(H.pylori),which is also the cause of ulcer recurrence.However,H.pylori-negative ulcers are present in 12%-20% of patients;they also recur and are on occasion intractable.QOUH focuses on the fact that mucosal and submucosal structures within ulcer scars are incompletely regenerated.Within the scars of healed ulcers,regenerated tissue is immature and with distorted architecture,suggesting poor QOUH.The abnormalities in mucosal regeneration can be the basis for ulcer recurrence.Our studies have shown that persistence of macrophages in the regenerated area plays a key role in ulcer recurrence.Our studies in a rat model of ulcer recurrence have indicated that proinflammatory cytokines trigger activation of macrophages,which in turn produce increased amounts of cytokines and chemokines,which attract neutrophils to the regenerated area.Neutrophils release proteolytic enzymes that destroy the tissue,resulting in ulcer recurrence.Another important factor in poor QOUH can be deficiency of endogenous prostaglandins and a deficiency and/or an imbalance of endogenous growth factors.Topically active mucosal protective and antiulcer drugs promote high QOUH and reduce inflammatory cell infiltration in the ulcer scar.In addition to PUD,the concept of QOUH is likely applicable to inflammatory bowel diseases including Crohn's disease and ulcerative colitis. | Tetsuo Arakawa Toshio Watanabe Tetsuya Tanigawa Kazunari Tominaga Yasuhiro Fujiwara Kenichi Morimoto | 2012 | World Journal of Gastroenterology2012，18，35： | 16 |
| 2 | Clinical utility of the platelet-lymphocyte ratio as a predictor of postoperative complications after radical gastrectomy for clinical T2-4 gastric cancer显示文摘AIM To identify simple and sensitive markers for postoperative complications after gastrectomy, the predictive values were compared among candidate preoperative factors. METHODS Three-hundred and twelve patients with previously untreated clinical T2-4 gastric cancer who underwent a D2 standard gastrectomy(distal gastrectomy or total gastrectomy) were included in the analysis.Correlations between 21 parameters that can be determined by preoperative routine blood tests and clinically relevant postoperative complications(grade Ⅱ or higher according to the Clavien-Dindo classification) were evaluated. The optimal cutoff values and clinical significance of the selected markers were further evaluated by subgroup analyses according to age, body mass index, operative procedure and clinical disease stage.RESULTS Sixty-six patients(21.1%) experienced grade Ⅱ or higher postoperative complications. The plateletlymphocyte ratio(PLR, total lymphocyte count/platelet count × 100) exhibited the highest area under the curve value(0.639) for predicting postoperative complications among the 21 parameters, and the optimal cutoff value was determined to be 0.71(sensitivity = 70%, specificity = 56%). In the univariate analysis, the odds ratio of a low PLR for the occurrence of postoperative complications was 2.94(95%CI: 1.66-5.35, P < 0.001), and a multivariate binomial logistic analysis involving other potential risk factors identified a low PLR as an independent risk factor for postoperative complications(OR = 3.32, 95%CI: 1.82-6.25, P < 0.001). In subgroups classified according to age, body mass index, operative procedure and clinical disease stage, the low PLR group exhibited an increased incidence of postoperative complications. CONCLUSION The preoperative PLR is a simple and useful predictor of complications after curative gastrectomy in patients with clinical T2-4 gastric cancer. | Kenichi Inaoka Mitsuro Kanda Hiroaki Uda Yuri Tanaka Chie Tanaka Daisuke Kobayashi Hideki Takami Naoki Iwata Masamichi Hayashi Yukiko Niwa Suguru Yamada Tsutomu Fujii Hiroyuki Sugimoto Kenta Murotani Michitaka Fujiwara Yasuhiro Kodera | 2017 | World Journal of Gastroenterology2017，23，14： | 13 |
| 3 | Visualizing the hepatic vascular architecture using superb microvascular imaging in patients with hepatitis C virus: A novel technique显示文摘AIM: To identify the hepatic vascular architecture of patients with hepatitis C virus(HCV) using superb microvascular imaging(SMI) and investigate the use of SMI in the evaluation of liver fibrosis.METHODS: SMI was performed in 100 HCV patients. SMI images were classified into five types according to the vascular pattern, and these patterns were compared with the fibrosis stage. Moreover, the images were analyzed to examine vascularity by integrating the number of SMI signals in the region of interest ROI [number of vascular trees(VT)]. The number of VT, fibrosis stage, serum parameters of liver function, and CD34 expression were investigated.RESULTS: There was a significant difference between SMI distribution pattern and fibrosis stage(P < 0.001). The mean VT values in each of the fibrosis stages were as follows: 26.69 ± 7.08 in F0, 27.72 ± 9.32 in F1, 36.74 ± 9.23 in F2, 37.36 ± 5.32 in F3, and 58.14 ± 14.08 in F4. The VT showed excellent diagnostic ability for F4 [area under the receiver operator characteristic(AUROC): 0.911]. The VT was significantly correlated with the CD34 labeling index(r = 0.617, P < 0.0001).CONCLUSION: SMI permitted the detailed delineation of the vascular architecture in chronic liver disease. SMI appears to be a reliable tool for noninvasively detecting significant fibrosis or cirrhosis in HCV patients. | Hidekatsu Kuroda Tamami Abe Keisuke Kakisaka Yudai Fujiwara Yuichi Yoshida Akio Miyasaka Kazuyuki Ishida Hideaki Ishida Tamotsu Sugai Yasuhiro Takikawa | 2016 | World Journal of Gastroenterology2016，22，26： | 12 |
| 4 | Chemotherapy as a component of multimodal therapy for gastric carcinoma显示文摘局部地先进的胃的癌症的预后仍然保持差,并且几多,包含外科,化疗,和放射的形式策略在临床的试用被测试了。独自与外科在治疗上测试手术后的辅助化疗的利益的阶段 III 试用几乎没在幸存上揭示很少影响,与在西方的国家的一些小试用的例外。从探索手术后的 chemoradiation 的美国的大试用是在这个范畴的第一主要成功。从日本试用的结果建议有口头的 fluoropyrimidines 的中等化疗可能对更少进展(T2 阶段) 是有效的癌症,尽管另一确定的试用被需要证明这,指。调查者最近转到 neoadjuvant 化疗,并且一些有希望的结果从阶段 II trials using 被报导了活跃的药联合。在 2005,测试在前和手术后的化疗的大阶段 III 试用为将切除证明了它的幸存利益有能力的胃的癌症。因为病理学的完全的反应的率被认为影响这策略的治疗结果,进一步增加病理学的完全的反应的发生的 neoadjuvant chemoradiation 能是突破,并且分阶段执行测试这策略的 III 研究在不久的将来可以被保证。 | Yasuhiro Kodera Michitaka Fujiwara Masahiko Koike Akimasa Nakao | 2006 | World Journal of Gastroenterology2006，12，13： | 12 |
| 5 | Molecular diagnosis and therapy for occult peritoneal metastasis in gastric cancer patients显示文摘To apply an individualized oncological approach to gastric cancer patients,the accurate diagnosis of disease entities is required.Peritoneal metastasis is the most frequent mode of metastasis in gastric cancer,and the tumor-node-metastasis classification includes cytological detection of intraperitoneal cancer cells as part of the staging process,denoting metastatic disease.The accuracy of cytological diagnosis leaves room for improvement;therefore,highly sensitive molecular diagnostics,such as an enzyme immunoassay,reverse transcription polymerase chain reaction,and virusguided imaging,have been developed to detect minute cancer cells in the peritoneal cavity.Molecular targeting therapy has also been spun off from basic research in the past decade.Although conventional cytologyis still the mainstay,novel approaches could serve as practical complementary diagnostics to cytology in near future. | Shunsuke Kagawa Kunitoshi Shigeyasu Michihiro Ishida Megumi Watanabe Hiroshi Tazawa Takeshi Nagasaka Yasuhiro Shirakawa Toshiyoshi Fujiwara | 2014 | World Journal of Gastroenterology2014，20，47： | 11 |
| 6 | Change in arterial tumor perfusion is an early biomarker of lenvatinib efficacy in patients with unresectable hepatocellular carcinoma显示文摘BACKGROUND Lenvatinib is one of the first-line tyrosine kinase inhibitors used for unresectable hepatocellular carcinoma(HCC). In the present study, we evaluated the potential of early changes in the time-intensity curve(TIC) of arterial phase on contrastenhanced ultrasound(CEUS) as early imaging biomarkers of lenvatinib efficacy.AIM To evaluate the potential of the early changes in the TIC of CEUS as early imaging biomarkers of lenvatinib efficacy in patients with unresectable HCC.METHODS We analyzed 20 consecutive patients with unresectable HCC treated with lenvatinib from March to November 2018. Tumor response at 8 wk was assessed by computed tomography using the modified Response Evaluation Criteria in Solid Tumors(m RECIST). CEUS was performed at baseline before treatment(Day 0) and on day 7(Day 7), and the images were analyzed in the arterial phase for 20 seconds after the contrast agent arrived at the target tumor. Three perfusion parameters were extracted from the TICs: the slope of wash-in(Slope),time to peak(TTP) intensity, and the total area under the curve(AUC) during wash-in. The rate of change in the TIC parameters between Day 0 and Day 7 was compared between treatment responders and non-responders based on m RECIST.RESULTS The rate of change for all TIC parameters showed significant differences between the responders(n = 9) and non-responders(n = 11)(Slope, P = 0.025; TTP, P =0.004; and AUC, P = 0.0003). The area under the receiver operating curve values for slope, TTP, and AUC for the prediction of responders were 0.805, 0.869, and0.939, respectively.CONCLUSION CEUS may be useful for the early prediction of tumor response to lenvatinib therapy in patients with unresectable HCC. | Hidekatsu Kuorda Tamami Abe Yudai Fujiwara Takuya Okamoto Miki Yonezawa Hiroki Sato Kei Endo Takayoshi Oikawa Kei Sawara Yasuhiro Takikawa | 2019 | World Journal of Gastroenterology2019，25，19： | 8 |
| 7 | Prognostic significance of perioperative tumor marker levels in stage Ⅱ/Ⅲ gastric cancer显示文摘AIM To evaluate the prognostic significance of perioperative carcinoembryonic antigen(CEA) and carbohydrate antigen 19-9(CA19-9) levels in stage Ⅱ/Ⅲ gastric cancer.METHODS From a multi-institutional retrospective database compiled by integrating clinical data from nine institutions, data of 998 patients who underwent curative resection for stage Ⅱ/Ⅲ gastric cancer between 2010 and 2014 were retrieved and analyzed. The prognostic impact of the preoperative and postoperative levels and chronological changes in CEA, CA19-9 and their combination were evaluated. To test whether postoperative adjuvant chemotherapy alters the prognostic impact of perioperative CEA and CA19-9 levels, the hazard ratios for mortality were compared between patients who underwent surgery alone and patients who underwent surgery followed by adjuvant chemotherapy.RESULTS The prognostic impact of postoperative CEA and CA19-9 was superior to that of the preoperative levels. Multivariable analysis identified high postoperative CEA and CA19-9 levels as independent prognostic factors for overall survival.Disease-free survival rates clearly decreased in a stepwise manner in association with postoperative CEA and CA19-9 levels, and patients with high levels of both markers showed significantly poorer prognosis than other patient groups. When we analyzed perioperative changes in serum CEA and CA19-9 levels, patients with high levels before and after surgery had the worst disease-free survival rates among all patient groups. Patients with normalized CEA levels after surgery had a significantly lower disease-free survival rate than those with normal perioperative levels, whereas patients with normalized CA19-9 levels after surgery had equivalent survival to those with normal perioperative levels. The prognostic impact of high CEA levels was observably smaller in patients who underwent adjuvant chemotherapy than in patients who underwent surgery alone, whereas that of high CA19-9 was greater in patients who underwent adjuvant chemotherapy. High postoperative CEA levels were significantly associated with an increased prevalence of liver, lung and bone recurrences, and high postoperative CA19-9 levels were significantly associated with increased frequencies of lymph node and liver recurrences.CONCLUSION The evaluation of serum CEA and CA 19-9 levels both before and after surgery provides useful information for precise risk stratification after curative gastrectomy. | Yasuhito Suenaga Mitsuro Kanda Seiji Ito Yoshinari Mochizuki Hitoshi Teramoto Kiyoshi Ishigure Toshifumi Murai Takahiro Asada Akiharu Ishiyama Hidenobu Matsushita Chie Tanaka Daisuke Kobayashi Michitaka Fujiwara Kenta Murotani Yasuhiro Kodera | 2019 | World Journal of Gastrointestinal Oncology2019，11，1： | 7 |
| 8 | Glutamine depletion induces murine neonatal melena with increased apoptosis of the intestinal epithelium显示文摘AIM:To investigate the possible biological outcome and effect of glutamine depletion in neonatal mice and rodent intestinal epithelial cells.METHODS:We developed three kinds of artificial milk with different amounts of glutamine;Complete amino acid milk (CAM),which is based on maternal mouse milk,glutamine-depleted milk (GDM),and glutaminerich milk (GRM).GRM contains three-fold more glutamine than CAM.Eighty-seven newborn mice were divided into three groups and were fed with either of CAM,GDM,or GRM via a recently improved nipple-bottle system for seven days.After the feeding period,the mice were subjected to macroscopic and microscopic observations by immunohistochemistry for 5-bromo-2'deoxyuridine (BrdU) and Ki-67 as markers of cell proliferation,and for cleaved-caspase-3 as a marker of apoptosis.Moreover,IEC6 rat intestinal epithelial cells were cultured in different concentrations of glutamine and were subject to a 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)2H-5-tetrazolio]-1,3-benzene disulfonate cell proliferation assay,flow cytometry,and western blotting to examine the biological effect of glutamine on cell growth and apoptosis.RESULTS:During the feeding period,we found colonic hemorrhage in six of 28 GDM-fed mice (21.4%),but not in the GRM-fed mice,with no differences in body weight gain between each group.Microscopic examination showed destruction of microvilli and the disappearance of glycocalyx of the intestinal wall in the colon epithelial tissues taken from GDM-fed mice.Intake of GDM reduced BrdU incorporation (the average percentage of BrdU-positive staining;GRM:13.8%,CAM:10.7%,GDM:1.14%,GRM vs GDM:P < 0.001,CAM vs GDM:P < 0.001) and Ki-67 labeling index (the average percentage of Ki67-positive staining;GRM:24.5%,CAM:22.4% GDM:19.4%,GRM vs GDM:P=0.001,CAM vs GDM:P =0.049),suggesting that glutamine depletion inhibited cell proliferation of intestinal epithelial cells.Glutamine deprivation further caused the deformation of the nuclear membrane and the plasma membrane,accompanied by chromatin degeneration and an absence of fat droplets from the colonic epithelia,indicating that the cells underwent apoptosis.Moreover,immunohistochemical analysis revealed the appearance of cleaved caspase-3 in colonic epithelial cells of GDM-fed mice.Finally,when IEC6 rat intestinal epithelial cells were cultured without glutamine,cell proliferation was significantly suppressed after 24 h (relative cell growth;4 mmol/L:100.0% ± 36.1%,0 mmol/L:25.3% ± 25.0%,P < 0.05),with severe cellular damage.The cells underwent apoptosis,accompanied by increased cell population in sub-G0 phase (4 mmol/L:1.68%,0.4 mmol/L:1.35%,0 mmol/L:5.21%),where dying cells are supposed to accumulate.CONCLUSION:Glutamine is an important alimentary component for the maintenance of intestinal mucosa.Glutamine deprivation can cause instability of the intestinal epithelial alignment by increased apoptosis. | Takayuki Motoki Yoshio Naomoto Junji Hoshiba Yasuhiro Shirakawa Tomoki Yamatsuji Junji Matsuoka Munenori Takaoka Yasuko Tomono Yasuhiro Fujiwara Hiroshi Tsuchita Mehmet Gunduz Hitoshi Nagatsuka Noriaki Tanaka Toshiyoshi Fujiwara | 2011 | World Journal of Gastroenterology2011，17，6： | 4 |
| 9 | Prognostic Significance of Intraperitoneal Cancer Cells in Gastric Carcinoma: Analysis of Real Time Reverse Transcriptase-Polymerase Chain Reaction after 5 Years of Followup显示文摘 | Yasuhiro Kodera Hayao Nakanishi Seiji Ito Yoshinari Mochizuki Norifumi Ohashi Yoshitaka Yamamura Michitaka Fujiwara Masahiko Koike Masae Tatematsu Akimasa Nakao | 2006 | Journal of the American College of Surgeons2006，，： | 3 |
| 10 | B?cell translocation gene 1 serves as a novel prognostic indicator ofhepatocellular carcinoma显示文摘 | Mitsuro Kanda Hiroyuki Sugimoto Shuji Nomoto Hisaharu Oya Soki Hibino Dai Shimizu Hideki Takami Ryoji Hashimoto Yukiyasu Okamura Suguru Yamada Tsutomu Fujii Goro Nakayama Masahiko Koike Michitaka Fujiwara Yasuhiro Kodera | 2015 | International Journal of Oncology2015，，2： | 3 |
| 11 | A prospective, single-blind trial comparing wireless capsule endoscopy and double-balloon enteroscopy in patients with obscure gastrointestinal bleeding显示文摘 | Natsuhiko Kameda Kazuhide Higuchi Masatsugu Shiba Hirohisa Machida Hirotoshi Okazaki Hirokazu Yamagami Tetsuya Tanigawa Kenji Watanabe Toshio Watanabe Kazunari Tominaga Yasuhiro Fujiwara Nobuhide Oshitani Tetsuo Arakawa | 2008 | Journal of Gastroenterology2008，，6： | 2 |
| 12 | Successful treatment of giant rectal varices by modified percutaneous transhepatic obliteration with sclerosant:Report of a case显示文摘We present a female patient with continuous melena, diagnosed with rectal variceal bleeding. She had a history of esophageal varices, which were treated with endoscopic therapy. Five years after the treatment of esophageal varices, continuous melena occurred. Since colonoscopy showed that the melena was caused by giant rectal varices, we thought that they were not suitable to receive endoscopic treatment. We chose the modified percutaneous transhepatic obliteration with sclerosant, which is one of the interventional radiology techniques but a new clinical procedure for rectal varices. After the patient received this therapy, her condition of rectal varices was markedly improved. | Hirotoshi Okazaki Kazuhide Higuchi Masatsugu Shiba Shirou Nakamura Tomoko Wada Kazuki Yamamori Ai Machida Kaori Kadouchi Akihiro Tamori Kazunari Tominaga Toshio Watanabe Yasuhiro Fujiwara Kenji Nakamura Tetsuo Arakawa | 2006 | World Journal of Gastroenterology2006，12，33： | 2 |
| 13 | Small Bowel Injury by Low-Dose Enteric-Coated Aspirin and Treatment With Misoprostol: A Pilot Study显示文摘 | Toshio Watanabe Satoshi Sugimori Natsuhiko Kameda Hirohisa Machida Hirotoshi Okazaki Tetsuya Tanigawa Kenji Watanabe Kazunari Tominaga Yasuhiro Fujiwara Nobuhide Oshitani Kazuhide Higuchi Tetsuo Arakawa | 2008 | Clinical Gastroenterology and Hepatology2008，，11： | 2 |
| 14 | Phase I and pharmacokinetic study of nab-paclitaxel, nanoparticle albumin-bound paclitaxel, administered weekly to Japanese patients with solid tumors and metastatic breast cancer显示文摘 | Masashi Ando Kan Yonemori Noriyuki Katsumata Chikako Shimizu Taizo Hirata Harukaze Yamamoto Kenji Hashimoto Mayu Yunokawa Kenji Tamura Yasuhiro Fujiwara | 2012 | Cancer Chemotherapy and Pharmacology2012，，2： | 2 |
| 15 | Longterm Outcomes of Early-Stage Gastric Carcinoma Patients Treated with Laparoscopy-Assisted Surgery显示文摘 | Michitaka Fujiwara Yasuhiro Kodera Kazunari Misawa Mizunobu Kinoshita Takashi Kinoshita Shinichi Miura Norifumi Ohashi Goro Nakayama Masahiko Koike Akimasa Nakao | 2008 | Journal of the American College of Surgeons2008，，1： | 2 |
| 16 | Free jejunal graft for hypopharyngeal and esophageal reconstruction显示文摘 | Yasuhiro Shirakawa Yoshio Naomoto Kazuhiro Noma Ryoko Ono Tetsuji Nobuhisa Masahiko Kobayashi Toshiya Fujiwara Hirofumi Noguchi Takaomi Ohkawa Tomoki Yamatsuji Minoru Haisa Junji Matsuoka Mehmet Gunduz Noriaki Tanaka | 2004 | Langenbeck’s Archives of Surgery2004，，5： | 1 |
| 17 | Postoperative adjuvant chemotherapy with S-1 alters recurrence patterns and prognostic factors among patients with stage II/III gastric cancer: A propensity score matching analysis显示文摘 | Mitsuro Kanda Kenta Murotani Daisuke Kobayashi Chie Tanaka Suguru Yamada Tsutomu Fujii Goro Nakayama Hiroyuki Sugimoto Masahiko Koike Michitaka Fujiwara Yasuhiro Kodera | 2015 | Surgery2015，，6： | 1 |
| 18 | Translational implication of Kallmann syndrome-1 gene expression inhepatocellular carcinoma显示文摘 | Yuri Tanaka Mitsuro Kanda Hiroyuki Sugimoto Dai Shimizu Satoshi Sueoka Hideki Takami Kazuhiro Ezaka Ryoji Hashimoto Yukiyasu Okamura Naoki Iwata Chie Tanaka Suguru Yamada Tsutomu Fujii Goro Nakayama Masahiko Koike Shuji Nomoto Michitaka Fujiwara Yasuhiro | 2015 | International Journal of Oncology2015，，6： | 1 |
| 19 | Clinical significance of expression and epigenetic profiling of TUSC1 in gastric cancer显示文摘 | Mitsuro Kanda Dai Shimizu Shuji Nomoto Soki Hibino Hisaharu Oya Hideki Takami Daisuke Kobayashi Suguru Yamada Yoshikuni Inokawa Chie Tanaka Tsutomu Fujii Hiroyuki Sugimoto Masahiko Koike Michitaka Fujiwara Yasuhiro Kodera | 2014 | J. Surg. Oncol2014，，2： | 1 |
| 20 | Evaluation of back-side flaws of the bottom plates of an oil-storage tank by the RFECT 显示文摘 | Naoya Kasai Yasuhiro Fujiwara Kazuyoshi Sekine | 2008 | NDT&E international2008，41，5： | 1 |
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