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1Pancreatic carcinoma coexisting with chronic pancreatitis versus tumor-forming pancreatitis:Diagnostic utility of the time-signal intensity curve from dynamic contrast-enhanced MR imaging显示文摘AIM: To evaluate the ability of the time-signal intensity curve (TIC) of the pancreas obtained from dynamic contrast-enhanced magnetic resonance imaging (MRI) for differentiation of focal pancreatic masses, especially pancreatic carcinoma coexisting with chronic pancreatitis and tumor-forming pancreatitis. METHODS: Forty-eight consecutive patients who underwent surgery for a focal pancreatic mass, including pancreatic ductal carcinoma (n = 33), tumor-forming pancreatitis (n = 8), and islet cell tumor (n = 7), were reviewed. Five pancreatic carcinomas coexisted with longstanding chronic pancreatitis. The pancreatic TICs were obtained from the pancreatic mass and the pancreatic parenchyma both proximal and distal to the mass lesion in each patient, prior to surgery, and were classified into 4 types according to the time to a peak: 25 s and 1, 2, and 3 min after the bolus injection of contrast material, namely, type-Ⅰ, Ⅱ, Ⅲ, and Ⅳ, respectively, and were then compared to the corresponding histological pancreatic conditions. RESULTS: Pancreatic carcinomas demonstrated type-Ⅲ (n = 13) or Ⅳ (n = 20) TIC. Tumor-forming pancreatitis showed type-Ⅱ (n = 5) or Ⅲ (n = 3) TIC. All islet cell tumors revealed type-Ⅰ. The type-Ⅳ TIC was only recognized in pancreatic carcinoma, and the TIC of carcinoma always depicted the slowest rise to a peak among the 3 pancreatic TICs measured in each patient, even in patients with chronic pancreatitis.CONCLUSION: Pancreatic TIC from dynamic MRI provides reliable information for distinguishing pancreatic carcinoma from other pancreatic masses, and may enable us to avoid unnecessary pancreatic surgery and delays in making a correct diagnosis of pancreatic carcinoma, especially, in patients with longstanding chronic pancreatitis.Yoshitsugu Tajima Tamotsu Kuroki Ryuji Tsutsumi Ichiro Isomoto Masataka Uetani Takashi Kanematsu 2007World Journal of Gastroenterology2007,13,6:28
2NAT2*6A, a haplotype of the N-acetyltransferase 2 gene, is an important biomarker for risk of anti-tuberculosis drug-induced hepatotoxicity in Japanese patients with tuberculosis显示文摘AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect, using multivariate logistic regression analysis.RESULTS: Statistical analysis revealed that the frequency of a variant haplotype, NAT2*6A , was signifi cantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity [P = 0.001, odds ratio (OR) = 3.535]. By contrast, the frequency of a wild-type (major) haplotype, 'NAT2*4', was signif icantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P < 0.001, OR = 0.265). There was no association between NAT2-haplotypes and skin rash or eosinophilia. CONCLUSION: The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2*4 and NAT2*6A, are useful new biomarkers for predicting anti- TB drug-induced hepatotoxicity.Norihide Higuchi Naoko Tahara Katsunori Yanagihara Kiyoyasu Fukushima Naofumi Suyama Yuichi Inoue Yoshitsugu Miyazaki Tsutomu Kobayashi Koh-ichiro Yoshiura Norio Niikawa, Chun-Yang Wen, Hajime Isomoto,Saburou Shikuwa, Katsuhisa Omagari, Yohei Mizuta, Shigeru Kohno, Kazuhiro Tsukamoto Norio Niikawa Chun-Yang Wen Hajime Isomoto Saburou Shikuwa Katsuhisa Omagari Yohei Mizuta Shigeru Kohno Kazuhiro Tsukamoto 2007World Journal of Gastroenterology2007,13,45:21
3Prevention of esophageal strictures after endoscopic submucosal dissection显示文摘Endoscopic mucosal resection(EMR) and endoscopic submucosal dissection(ESD) have recently been accepted as less invasive methods for treating patients with early esophageal cancers such as squamous cell carcinoma and dysplasia of Barrett's esophagus.However,the large defects in the esophageal mucosa often cause severe esophageal strictures,which dramatically reduce the patient's quality of life.Although preventive endoscopic balloon dilatation can reduce dysphagia and the frequency of dilatation,other approaches are necessary to prevent esophageal strictures after ESD.This review describes several strategies for preventing esophageal strictures after ESD,with a particular focus on anti-inflammatory and tissue engineering approaches.The local injection of triamcinolone acetonide and other systemic steroid therapies are frequently used to prevent esophageal strictures after ESD.Tissue engineering approaches for preventing esophageal strictures have recently been applied in basic research studies.Scaffolds with temporary stents have been applied in five cases,and this technique has been shown to be safe and is anticipated to prevent esophageal strictures.Fabricated autologous oral mucosal epithelial cell sheets to cover the defective mucosa similarly to how commercially available skin products fabricated from epidermal cells are used for skin defects or in cases of intractable ulcers.Fabricated autologous oralmucosal-epithelial cell sheets have already been shown to be safe.Shinichiro Kobayashi Nobuo Kanai Takeshi Ohki Ryo Takagi Naoyuki Yamaguchi Hajime Isomoto Yoshiyuki Kasai Takahiro Hosoi Kazuhiko Nakao Susumu Eguchi Masakazu Yamamoto Masayuki Yamato Teruo Okano 2014World Journal of Gastroenterology2014,20,41:12
4High concentrations of human β-defensin 2 in gastric juice of patients with Helicobacter pylori infection显示文摘AIM: Human β-defensin (HBD)-1 and HBD-2 are endogenous antimicrobial peptides. Unlike HBD-1, the HBD-2 expression is augmented by Helicobacter pylori (H pylori). We sought to determine HBD-1 and HBD-2 concentrations in gastric juice duringH pylori infection.METHODS: HBD-1 and HBD-2 concentrations were measured by radioimmunoassay in plasma and gastric juice of 49 H pylori-infected and 33 uninfected subjects and before and after anti-H pyloritreatment in 13 patients with H pylori-associated gastritis. Interleukin (IL)-1β and IL-8 concentrations in gastric juice were measured by enzyme-linked immunosorbent assay (ELISA). Histological grades of gastritis were determined using two biopsy specimens taken from the antrum and corpus. Reverse phase high performance liquid chromatography (RP-HPLC)was used to identify HBD-2.RESULTS: HBD-2 concentrations in gastric juice, but not in plasma, were significantly higher in H pylori-positive than -negative subjects, albeit the post-treatment levels were unchanged. Immunoreactivity for HBD-2 was exclusively identified in H pylori-infected mucosa by RPHPLC. HBD-2 concentrations in gastric juice correlated with histological degree of neutrophil and mononuclear cell infiltration in the corpus. IL-1β levels correlated with those of IL-8, but not HBD-2. Plasma and gastric juice HBD-1concentrations were similar in H pylori-infected and uninfected subjects.CONCLUSION: Our results place the β-defensins, especially HBD-2, in the front line of innate immune defence.Moreover, HBD-2 may be involved in the pathogenesis of H pylori-associated gastritis, possibly through its function as immune and inflammatory mediator.Hajime Isomoto Hiroshi Mukae Hiroshi Ishimoto Yoshito Nishi Chun-Yang Wen Akihiro Wad Ken Ohnita Toshiya Hirayama Masamitsu Nakazato Shigeru Kohno 2005World Journal of Gastroenterology2005,11,31:10
5Programmed cell death-1 inhibitor-related sclerosing cholangitis:A systematic review显示文摘BACKGROUND Programmed cell death-1(PD-1)inhibitor has been indicated for many types of malignancies.However,these inhibitors also cause immune-related adverse events.Hepatobiliary disorder is a phenotype of immune-related adverse event affecting 0%–4.5%of patients treated with PD-1 inhibitors.Recent studies have reported PD-1 inhibitor-related sclerosing cholangitis(SC);however,the associated clinical and pathological features are unclear.AIM To evaluate the clinical and pathological features of PD-1 inhibitor-related SC through a systematic review of the literature.METHODS The review,conducted using electronic databases in PubMed,was restricted to the period from January 2014 to September 2019 and focused on case reports/series on PD-1 inhibitor-related SC published in English.We scanned the references of the selected literature to identify any further relevant studies.Six cases previously studied by us,including three that have not yet been published,were included in this review.RESULTS Thirty-one PD-1 inhibitor-related SC cases were evaluated.Median age of patients was 67 years(range,43–89),with a male to female ratio of 21:10.The main disease requiring PD-1 inhibitor treatment was non-small cell lung cancer.Agents that caused PD-1 inhibitor-related SC were nivolumab(19 cases),pembrolizumab(10 cases),avelumab(1 case),and durvalumab(1 case).The median number of cycles until PD-1 inhibitor-related SC onset was 5.5(range,1–27).Abdominal pain or discomfort(35.5%,11/31)was the most frequent symptom.Blood serum tests identified liver dysfunction with a notable increase in biliary tract enzymes relative to hepatic enzymes,and a normal level of serum immunoglobulin G4.Biliary dilation without obstruction(76.9%,20/26),diffuse hypertrophy of the extrahepatic biliary tract(90.5%,19/21),and multiple strictures of the intrahepatic biliary tract(30.4%,7/23)were noted.In 11/23(47.8%)cases,pathological examination indicated that CD8+T cells were the dominant inflammatory cells in the bile duct or peribiliary tract.Although corticosteroids were mainly used for PD inhibitor-related SC treatment,the response rate was 11.5%(3/26).CONCLUSION Some clinical and pathological features of PD-1 inhibitor-related SC were revealed.To establish diagnostic criteria for PD-1 inhibitor-related SC,more cases need to be evaluated.Takumi Onoyama Yohei Takeda Taro Yamashita Wataru Hamamoto Yuri Sakamoto Hiroki Koda Soichiro Kawata Kazuya Matsumoto Hajime Isomoto 2020World Journal of Gastroenterology2020,26,3:7
6Association of polymorphic alleles of CTLA4 with inflammatory bowel disease in the Japanese显示文摘AIM: To examine an association between the cytotoxic T-lymphocyte antigen 4 (CTLA4) gene that plays a role in downregulation of T-cell activation and inflammatory bowel disease consisting of ulcerative colitis (UC) and Crohn's disease (CD) in the Japanese.METHODS: We studied 108 patients with UC, 79 patients with CD, and 200 sex-matched healthy controls, with respect to three single nucleotide polymorphisms (SNPs)in CTLA4, such as C-318T in the promoter region, A+49G in exon 1 and G+6230A in the 3' untranslated region (3'-UTR) by a PCR-restriction fragment length polymorphism method, and to an (AT)n repeat polymorphism in 3'-UTR by fragment analysis with fluorescence-labeling on denaturing sequence gels. Frequency of alleles and genotypes and their distribution were compared statistically between patients and controls and among subgroups of patients, using χ2 and Fisher exact tests.RESULTS: The frequency of 'A/A' genotype at the G+6230A SNP site was statistically lower in UC patients than in controls (3.7% vs 11.0%, P= 0.047, odds ratio (OR) = 0.311). Moreover, the frequency of'G/G' genotype at the A+49G SNP site was significantly higher in CD patients with fistula (48.6%) than those without it (26.2%)(P = 0.0388, OR=2.67).CONCLUSION: The results suggest that CTLA4 located at 2q33 is a determinant of UC and responsible for fistula formation in CD in the Japanese.Haruhisa Machida Kazuhiro Tsukamoto Chun-Yang Wen Yukiko Narumi Saburou Shikuwa Hajime Isomoto Fuminao Takeshima Yohei Mizuta Norio Niikawa Ikuo Murata Shigeru Kohno 2005World Journal of Gastroenterology2005,11,27:4
7Enlarged accessory spleen presenting stomach submucosal tumor显示文摘A 62-year-old man presented with upper abdominal discomfort underwent upper gastrointestinal endoscopy. Gastroscopy and endoscopic ultrasonography revealed a submucosal tumor (SMT) with homogenous echogenicity originated from extragastric organs. An abdominal contrast-enhanced computed tomography (CT) showed that the well-marginated ovoid mass, approximately 6 cm in diameter, enhanced homogenously to a similar degree as splenic parenchyma. 99mTechnetium sulfur colloid scintigraphy revealed the splenic nature of the mass. A diagnosis of accessory spleen mimicking gastric SMT was made. Subsequent follow-up was uneventful without performing splenectomy.Shunzen Chin Hajime Isomoto Yohei Mizuta Chun-Yang Wen Saburo Shikuwa Shigeru Kohno 2007World Journal of Gastroenterology2007,13,11:4
8Crohn's disease in Japanese is associated with a SNP-haplotype of N-acetyltransferase 2 gene显示文摘AIM: To investigate the frequency and distribution of N-acetyltransferase 2 (NAT2) and uridine 5′-diphosphate (UDP)-glucuronosyltransferase 1A7 (UGT1A7) genes in patients with ulcerative colitis (UC) and Crohn's disease (CD).METHODS: Frequencies and distributions of NAT2 and UGT1A7SNPs as well as their haplotypes were investigated in 95 patients with UC, 60 patients with CD, and 200gender-matched, unrelated, healthy, control volunteers by PCR-restriction fragment length polymorphism (RFLP),PCR-denaturing high-performance liquid chromatography (DHPLC), and direct DNA sequencing.RESULTS: Multiple logistic regression analysis revealed that the frequency of haplotype, NAT2*7B, significantly increased in CD patients, compared to that in controls (P= 0.0130, OR = 2.802, 95%CI = 1.243-6.316). However,there was no association between NAT2 haplotypes and UC, or between any UGT1A7haplotypes and inflammatory bowel disease (IBD).CONCLUSION: It is likely that the NAT2 gene is one of the determinants for CD in Japanese. Alternatively, a new CD determinant may exist in the 8p22 region, whereNAT2is located.Haruhisa Machida Kazuhiro Tsukamoto Chun-Yang Wen Saburou Shikuwa Hajime Isomoto Yohei Mizuta Fuminao Takeshima Kunihiko Murase Naomichi Matsumoto Ikuo Murata Shigeru Kohno Chen-Yang Wen 2005World Journal of Gastroenterology2005,11,31:3
9Constitutive androstane receptor agonist, TCPOBOP,attenuates steatohepatitis in the methionine choline-deficientdiet-fed mouse显示文摘AIM:To ascertain whether constitutive androstane receptor(CAR)activation by 1,4-bis-2-(3,5,-dichloropyridyloxy)benzene(TCPOBOP)modulates steatohepatitis in the methionine choline-deficient(MCD)diet-fed animal.METHODS:C57/BL6 wild-type mice were fed the MCD or standard diet for 2 wk and were treated with either the CAR agonist,TCPOBOP,or the CAR inverse agonist,androstanol.RESULTS:Expression of CYP2B10 and CYP3A11,known CAR target genes,increased 30-fold and 45-fold,respectively,in TCPOBOP-treated mice fed the MCD diet.TCPOBOP treatment reduced hepatic steatosis(44.6 ± 5.4% vs 30.4 ± 4.5%,P < 0.05)and serum triglyceride levels(48 ± 8 vs 20 ± 1 mg/dL,P < 0.05)in MCD diet-fed mice as compared with the standard diet-fed mice.This reduction in hepatic steatosis was accompanied by an increase in enzymes involved in fatty acid microsomal ω-oxidation and peroxisomal β-oxidation,namely CYP4A10,LPBE,and 3-ketoacyl-CoA thiolase.The reduction in steatosis was also accompanied by a reduction in liver cell apoptosis and inflammation.In contrast,androstanol was without effect on any of the above parameters.CONCLUSION:CAR activation stimulates induction of genes involved in fatty acid oxidation,and ameliorates hepatic steatosis,apoptosis and inflammation.Edwina S Baskin-Bey Akira Anan Hajime Isomoto Steven F Bronk Gregory J Gores 2007World Journal of Gastroenterology2007,13,42:3
10Role of the preoperative usefulness of the pathological diagnosis of pancreatic diseases显示文摘Pancreatic cancer is the fifth leading cause of cancer death and has the lowest survival rate of any solid cancer.Endoscopic ultrasound-guided fine-needle aspiration biopsy(EUS-FNA) is currently capable of providing a cytopathological diagnosis of pancreatic malignancies with a higher diagnostic power,with a sensitivity and specificity of 85%-89% and 98%-99%,compared to pancreatic juice cytology(PJC),whose sensitivity and specificity are only 33.3%-93% and 83.3%-100%.However,EUS-FNA is not effective in the cases of carcinoma in situ and minimally invasive carcinoma because both are undetectable by endoscopic ultrasonography,although PJC is able to detect them.As for the frequency of complications such as post endoscopic retrograde cholangiopancreatography pancreatitis,EUS-FNA is safer than PJC.To diagnose pancreatic cancer appropriately,it is necessary for us to master both procedures so that we can select the best methods of sampling tissues while considering the patient's safety and condition.Kazuya Matsumoto Yohei Takeda Takumi Onoyama Soichiro Kawata Hiroki Kurumi Masaru Ueki Norimasa Miura Hajime Isomoto 2016World Journal of Gastrointestinal Oncology2016,8,9:2
11Development of ulcerative colitis during the course of rheumatoid arthritis: Association with selective IgA deficiency显示文摘有风湿性关节炎(RA ) 的 29 年的历史的一个 56 岁的女人进入医院,抱怨高发烧,腹的疼痛和严重流血腹泻。结肠镜检查与从直肠延长到远侧的横向的冒号的自发的流血、弥漫的侵蚀和溃疡揭示了脆、水肿的粘膜。直肠的活体检视的组织病理学说的调查结果与 ulcerative (UC ) 兼容。作为有严重活跃左边的 UC 被诊断,她成功地被对待,静脉内的甲基氢化尼松由氢化尼松和 leukocytapheresis 列在后面。实验室测试揭示了低浆液和口水 IgA 层次,它可能在 UC 的发展起一个作用。到我们的知识,这是发生在 RA 的功课期间的 UC 的第一个盒子,由选择 IgA 缺乏伴随了。Yuki Asada Hajime Isomoto Saburo Shikuwa Chun Yang Wen Eiichiro Fukuda Masaru Miyazato, Kenta Okamoto Takashi Nakamura Hitoshi Nishiyama Yohei Mizuta Kiyoshi Migita Masahiro Ito Shigeru Kohno 2006World Journal of Gastroenterology2006,12,32:2
12Clinical characteristics of hepatocellular carcinoma in elderly patients显示文摘Takuya Honda Hisamitsu Miyaaki Tatsuki Ichikawa Naota Taura Satoshi Miuma Hidetaka Shibata Hajime Isomoto Fuminao Takeshima Kazuhiko Nakao 2011Oncology Letters2011,,5:2
13Management of complications associated with endoscopic submucosal dissection/ endoscopic mucosal resection for esophageal cancer显示文摘Hajime Isomoto Naoyuki Yamaguchi Hitomi Minami Kazuhiko Nakao 2013Digestive Endoscopy2013,,:2
14Novel serine/threonine kinase 11 gene mutations in PeutzJeghers syndrome patients and endoscopic management显示文摘AIM:To explore mutations in serine/threonine kinase 11(STK11) gene in Peutz-Jeghers syndrome(PJS) with gastrointestinal(GI) hamartomatous polyps.METHODS:Six Japanese PJS patients in 3 families were enrolled in this study.Each of the cases had hamartomatous polyposis in the gastrointestinal tract,including the small intestine,along with mucocutaneous hyperpigmentation.Narrow-band imaging(NBI)-magnification endoscopy was employed to detect microvascular and microsurface irregularities in the GI lesions.NBI magnification findings could be classified into three groups(type A,type B,or type C).Endoscopic polypectomy was performed using double-balloon enteroscopy or colonoscopy.Genomic DNA was extracted from a whole blood sample from each subject.All of the coding exons of STK11 gene,its boundary regions,and the promoter region containing the polymorphic regions were amplified by polymerase chain reaction,and direct sequencing was performed to assess the germline mutations.RESULTS:NBI-magnification endoscopic observation could detect the abnormalities in microvessels and microsurface structures of GI polyps.Overall,we found 5 cases of type A and one case without the examination for the gastric polyps,while there were 4 cases of type B and 2 case of type A for the colorectal polyps.Seventy-nine small-bowel and 115 colorectal polyps over 27 sessions for each were resected endoscopically without significant complications.The only delayed complication included the occurrence of bleeding in a case,and this was successfully managed with hemoclips.Resected polyps contained no malignant components.Based on mutation analysis,all 3 cases in Family I exhibited the +658C>T nonsense mutation in exon 5,which resulted in the production of a truncated protein(Q220X).In Family II,a case had-252C>A and-193C>A in the promoter region.In Family III,a case was found to have the +1062C>G(F342L) mutation in exon 8.CONCLUSION:We found two novel mutations of STK11 in association with PJS.Endoscopic polypectomy of GI polyps in PJS patients appears to be useful to prevent emergency laparotomies and reduce the cancer risk.Hiroyuki Yajima Hajime Isomoto Hiroaki Nishioka Naoyuki Yamaguchi Ken Ohnita Tatsuki Ichikawa Fuminao Takeshima Saburo Shikuwa Masahiro Ito Kazuhiko Nakao Kazuhiro Tsukamoto Shigeru Kohno 2013World Journal of Gastrointestinal Endoscopy2013,5,3:2
15Interleukin 6 upregulates myeloid cell leukemia-1 expression through a STAT3 pathway in cholangiocarcinoma cells显示文摘Isomoto H Kobayashi S Werneburg NW 2005Hepatology2005,42,6:1
16Distal spread of rectal cancer and optimal distal margin of resection for sphincter-preserving surgery显示文摘Shirouzu K Isomoto H Kakegawa T 1995Cancer1995,76,3:1
17SUR2 subtyope (A and B)-dependent differential activation of the cloned ATP-sensitive K^+ channels by pinacidil and nicorandil 显示文摘Shindo T Yamada M Isomoto S 1998Br J Pharmacol1998,1245,:1
18Helicobacter and gastric malignancies显示文摘Ferreira AC Isomoto H Moriyama M 2008Helicobacter2008,,:1
19High-dose rabe- prazole-amoxieillin versus rabeprazoleamoxicillin-metron- idazole as second-line treatment after failure of the Japanese standard regimen for Helicobacter pylori infection显示文摘Isomoto H Inoue K Furusu H 2003Allmerit Pharmacol Ther2003,18,1:1
20Expres- sion of nuclear factor-kappaB in helicobacter pylori-infected gastric mucosa detected with southwestern histochemistry 显示文摘ISOMOTO H MIYAZAKI M MIZUTA Y 2000ScandJ Gastroenterol2000,35,3:1
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