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联合血流介导的血管舒张和硝酸甘油诱导的血管舒张能更有效预测心血管事件

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中华高血压杂志 2016年第4期24卷 379-379页

作者：刘莉叶鹏 kajikawa M Maruhashi T Hida E Iwamoto Y Matsumoto T Iwamoto A Oda N kishimoto S Matsui S Hidaka T kihara Y chayama k Goto C Aibara Y Nakashima A Noma k Higashi Y

硝酸甘油诱导的血管舒张作为血流介导的血管舒张功能（flow-mediated vasodilation,FMD）的对照试验,用来区别内皮依赖性与非依赖性的血管舒张功能。近来,硝酸甘油诱导的血管舒张已被报道是动脉粥样硬化分级的有用标志物。该研究旨在评... 详细信息

硝酸甘油诱导的血管舒张作为血流介导的血管舒张功能（flow-mediated vasodilation,FMD）的对照试验,用来区别内皮依赖性与非依赖性的血管舒张功能。近来,硝酸甘油诱导的血管舒张已被报道是动脉粥样硬化分级的有用标志物。该研究旨在评估联合FMD与硝酸甘油诱导的血管舒张对未来心血管事件的预测价值。方法与结果：纳入研究对象402例,其中包括心血管病患者,测定FMD与硝酸甘油诱导的血管舒张。

关键词：血管舒张心血管事件心源性死亡心血管病患者血流介导内皮依赖性预测价值非依赖性急性心肌梗死特征曲线

Strategy for treatment of nonerosive reflux disease in Asia

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World Journal of Gastroenterology 2008年第20期14卷 3123-3128页

作者： Toru Hiyama Masaharu Yoshihara Shinji Tanaka ken Haruma kazuaki chayama Health Service Center Hiroshima University Department of Endoscopy Hiroshima University Hospital Division of Gastroenterology Department of Internal Medicine Kawasaki Medical School Department of Medicine and Molecular Science Division of Frontier Medical Science Programs for Biomedical Research Graduate School of Biomedical Sciences Hiroshima University

The paper is to review the clinical and pathophysiologic differences between of nonerosive reflux disease (NERD) and reflux esophagitis (RE), and to propose a treatment strategy for NERD, especially for patients in Asia. A Medline search was performed regarding the clinical and pathophysiologic differences between NERD and RE, and treatment of NERD and RE. The characteristics of NERD patients in Asia are as follows: (1) high proportion of female patients, (2) low frequency of hiatal hernia, (3) high frequency of H pylori infection, (4) severe glandular atrophy of the gastric mucosa, and (5) frequent resistance to proton pump inhibitor (PPI) therapy. In Asian NERD patients, exposure of the esophagus to acid is not increased, and esophageal motility is normal. These characteristics are similar to those of patients in Western countries. Our recommended first-choice treatment is administration of PPI in combination with a prokinetic agent. However, at present, because there is limited evidence regarding effective treatments for NERD, it is best to try several different treatment strategies to find the best treatment for each patient.

关键词： Nonerosive reflux disease Asia Treatment

Involvement of krüppel-like factor 6 (kLF6) mutation in the development of nonpolypoid colorectal carcinoma

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World Journal of Gastroenterology 2007年第29期13卷 3932-3938页

作者： Shinichi Mukai Toru Hiyama Shinji Tanaka Masaharu Yoshihara koji Arihiro kazuaki chayama Department of Medicine and Molecular Science Division of Frontier Medical Science Program for Biomedical Research Graduate School of Biomedical Sciences Hiroshima University Hiroshima Japan Health Service Center Hiroshima University Higashihiroshima Japan Department of Endoscopy Hiroshima University Hospital Hiroshima Japan Department of Anatomical Pathology Hiroshima University Hospital Hiroshima Japan

AIM： To examine kruppel-like factor 6 （kLF6） mutations in nonpolypoid-type tumors and alterations of k-ras, p53, and B-raf in relation between mutation and morphologic type, particularly nonpolypoid-type colorectal carcinomas. METHODS： Fifty-five early nonpolypoid colorectal carcinomas were analyzed. Loss of heterozygosity （LOH） of kLF6 and p53 was determined by microsatellite assay. Mutations of kLF6, k-ras, and B-raf were examined by polymerase chain reaction-single-strand conformation polymorphism followed by direct sequencing. In LOH- positive and/or mutation-positive tumors, multiple （4-7） samples in each tumor were microdissected and examined for genetic alterations, p53 expression was evaluated by immunohistochemistry. RESULTS： LOH of kLF6 and p53 was found in 14 of 29 （48.3%） and 14 of 31 （45.2%） tumors, respectively. In tO of the 14 （71.4%） kLF6 LOH-positive tumors and 9 of the 14 （64.3%） p53 LOH-positive tumors, LOH was found in all of the microdissected samples. In 1 of the tO （10.0%） kLF6 LOH-positive tumors, a single missense mutation was identified. k-ras and B-raf mutations were found in 5 of 55 （9.1%） and 6 of 55 （10.9%） tumors, respectively. However, these mutations were detected only in subsets of microdissected tumor samples. CONCLUSION： These data suggest that kLF6 and p53 mutations are involved in the development of nonpolypoid colorectal carcinoma, whereas k-ras and B-raf mutations are not.

关键词： Nonpolypoid colorectal carcinoma kLF6 p53 k-ras B-raf

Causal role of Helicobacter pylori infection and eradication therapy in gastric carcinogenesis

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World Journal of Gastroenterology 2006年第1期12卷 10-16页

作者： Masanori Ito Shinji Tanaka Tomoari kamada ken Haruma kazuaki chayama Department of Medicine and Molecular Science Hiroshima UniversityHiroshimaJapan Department of Endoscopy Hiroshima University HospitalHiroshimaJapan Gastroenterology Unit Department of Internal MedicineKawasaki Medical SchoolKurashikiJapan

Many epidemiological reports indicate that Helicobacter pylori （H pylori） infection plays an important role in gastric carcinogenesis. Several genetic and epigenetic alterations contribute to the initiation, promotion, and progression of the cancer cells in a multi-step manner. H pylori is known to induce chronic inflammation in the gastric mucosa. Its products, including superoxides, participate in the DNA damage followed by initiation, and the inflammation-derived cytokines and growth factors contribute to the promotion of gastric carcinogenesis. By eradicating H pylori, gastric inflammation can be cured; the therapy diminishes the levels not only of inflammatory cell infiltration, but also atrophy/ intestinal metaplasia in part. A randomized controlled trial revealed that the eradication therapy diminished the gastric cancer prevalence in cases without precancerous conditions. In addition, recent epidemiological studies from Japanese groups demonstrated that the development of gastric cancer, especially of the intestinal type, was decreased by successful eradication therapy, although these were designed in a non- randomized manner. However, it should be mentioned that endoscopic detection is the only way to evaluate the degree of gastric carcinogenesis. We have reported that the endoscopic and histological morphologies could be modified by eradication therapy and it might contribute to the prevalence of gastric cancer development. Considering the biological nature of cancer cell proliferation, it is considered that a sufficiently long-term follow-up would be essential to discuss the anticancer effect of eradication therapy.

关键词： H pylori Eradication Gastritis Gastric neoplasm, Endoscopy

Patients with early recurrence of hepatocellular carcinoma have poor prognosis

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Hepatobiliary & Pancreatic Diseases International 2017年第3期16卷 279-288页

作者： Tomoki kobayashi Hiroshi Aikata Tsuyoshi kobayashi Hideki Ohdan koji Arihiro kazuaki chayama Department of Gastroenterology and Metabolism Hiroshima University Hospital Hiroshima Japan Department of Anatomical Pathology Hiroshima University Hospital Hiroshima Japan Department of Gastroenterological and Transplant Surgery Applied Life Sciences Institute of Biomedical and Health Sciences Hiroshima University Hiroshima Japan Liver Research Project Center Hiroshima University Hiroshima Japan

BACkGROUND： Early recurrence （ER） after hepatic resection （HR） is a poor prognostic factor for patients with hepatocellular carcinoma （HCC）. This study aimed to identify the clinico- pathological features, outcomes, and risk factors for ER after HR for small HCC in order to clarify the reasons why ER is a worse recurrence pattern. METHODS： We retrospectively examined 130 patients who underwent HR for small HCC （___30 mm）. Recurrence was clas- sifted into ER （〈2 years） and late recurrence （LR）（_〉2 years）. The clinicopathological features, outcomes, and risk factors for ER were analyzed by multivariate analysis. RESULTS： ER was observed in 39 patients （30.0%）. The sur- vival rate of the ER group was significantly lower than that of the LR group （P〈0.005）, and ER was an independent prognos- tic factor for poor survival （P=0.0001）. The ER group had a significantly higher frequency （P=0.0039） and shorter interval （P=0.027） of development to carcinoma beyond the Milan criteria （DBMC） compared with the LR group, and ER was an independent risk factor for DBMC （P〈0.0001）. Multi-nodularity, non-simple nodular type, and microvascular invasion were independent predictors for ER （P=0.012, 0.010, and 0.019, respectively）.CONCLUSIONS： ER was a highly malignant recurrence pattern associated with DBMC and subsequent poor survival after HR for small HCC. Multi-nodularity, non-simple nodular type, and microvascular invasion predict ER, and taking these factors into consideration may be useful for the decision of the treatment strategy for small HCC after HR.

关键词： early recurrence small hepatocellular carcinoma risk factors beyond the Milan criteria

Medical malpractice litigation related to gastrointestinal endoscopy in Japan:A two-decade review of civil court cases

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World Journal of Gastroenterology 2006年第42期12卷 6857-6860页

作者： Toru Hiyama Shinji Tanaka Masaharu Yoshihara Tatsuma Fukuhara Shinichi Mukai kazuaki chayama Health Service Center Hiroshima University Higashihiroshima Department of Endoscopy Hiroshima University Hospital Hiroshima Department of Medicine and Molecular Science Division of Frontier Medical Science Programs for Biomedical Research Graduate School of Biomedical Sciences Hiroshima University Hiroshima Japan

AIM: To examine the allegations in malpractice litigations related to gastrointestinal endoscopy in Japan. METHODS: A retrospective review of cases tried in the civil court system during the 21-year period from 1985 to 2005, identified in a computerized legal database, was undertaken. RESULTS: Eighteen malpractice litigations and a total of 30 allegations were identified. Of the 18 (44%) malpractice litigations, 8 (44%) were related to eso- phagogastroduodenoscopy, 4 (22%) to colonoscopy, 4 (22%) to endoscopic sphincterotomy, and 2 (11%) to endoscopic retrograde cholangiopancreatography. Seventeen (94%) cases pertained to complications, and the remaining (6%) case pertained to misdiagnosis. In 10 cases, the patient died of the complications. Allegations were categorized as: (1) performance error during the endoscopic procedure (n = 12, 40%); (2) lack of informed consent (n = 9, 30%); (3) performance error during the treatment after the endoscopic procedure (n = 4, 13%); (4) premedication error (n = 3, 10%); (5) diagnostic error (n = 1, 3%); and (6) indication error for the endoscopic procedure (n = 1, 3%). CONCLUSION: These data may aid in the design of risk prevention strategies to be used by gastrointestinal endoscopists.

关键词： Gastrointestinal endoscopy Malpractice Litigation Risk management

Outcome of patients who have undergone total enteroscopy for obscure gastrointestinal bleeding

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World Journal of Gastroenterology 2012年第7期18卷 666-672页

作者： Takayoshi Shishido Shiro Oka Shinji Tanaka Hiroki Imagawa Yoshito Takemura Shigeto Yoshida kazuaki chayama Department of Gastroenterology Hiroshima UniversityHiroshima 734-8551Japan Department of Endoscopy Hiroshima University HospitalHiroshima 734-8551Japan

AIM： To assess the diagnostic success and outcome among patients with obscure gastrointestinal bleeding who underwent total enteroscopy with double-balloon endoscopy.

关键词： Double-balloon endoscopy Small bowel Obscure gastrointestinal bleeding Total enteroscopy Outcome

Clinical significance of type V_I pit pattern subclassification in determining the depth of invasion of colorectal neoplasms

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World Journal of Gastroenterology 2008年第2期14卷 211-217页

作者： Hiroyuki kanao Shinji Tanaka Shiro Oka Iwao kaneko Shigeto Yoshida koji Arihiro Masaharu Yoshihara kazuaki chayama Department of Medicine and Molecular Science Hiroshima University Graduate School of Biomedical Science Hiroshima Japan Department of Endoscopy Hiroshima University Hospital Hiroshima Japan Department of Pathology Hiroshima University Hospital Hiroshima Japan Health Service Center Hiroshima University Hiroshima Japan

AIM: To clarify whether subclassification of the type VI pit pattern on the basis of magnifying colonoscopy findings is useful in determining the type and depth of invasion of colorectal ***: We retrospectively analyzed 272 colorectal neoplasms (117 dysplasias and 155 submucosal invasive carcinomas; 228 patients) with a type V pit pattern [type VI, n = 202; type VN, n = 70 (kudo and Tsuruta classification system)]. We divided lesions with a type VI pit pattern into two subclasses, mildly irregular lesions and severely irregular lesions, according to the prominent and detailed magnifying colonoscopy findings. We examined the relation between these two subclasses and histology/invasion ***: One hundred and four lesions (51.5%) were judged to be mildly irregular, and 98 lesions (48.5%) were judged to be severely irregular. Ninety-seven (93.3%) mildly irregular lesions showed dysplasias or submucosal invasion of less than 1000 μm (SM < 1000 μm). Fifty-five (56.1%) severely irregular lesions showed submucosal invasion equal to or deeper than 1000 μm (SM ≥ 1000 μm). Mild irregularity was found significantly more often in dysplasias or lesions with SM < 1000 μm than in lesions with SM ≥ 1000 μm (P < 0.01).CONCLUSION: Subclassification of the type VI pit pattern is useful for identifying dysplasias or lesions with SM < 1000 μm.

关键词： Colorectal neoplasm Magnification Type VI pit pattern Depth of invasion

Selective decrease in colonic CD56^+ T and CD161^+ T cells in the inflamed mucosa of patients with ulcerative colitis

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World Journal of Gastroenterology 2007年第45期13卷 5995-6002页

作者： Masaru Shimamoto Yoshitaka Ueno Shinji Tanaka Toshiko Onitake Rie Hanaoka kyoko Yoshioka Tsuyoshi Hatakeyama kazuaki chayama Department of Medicine and Molecular Science Hiroshima University Hiroshima 734-8551Japan Department of Endoscopy Hiroshima University Hospital Hiroshima Japan

AIM： To investigate the role of local colonic mucosal Nk receptor-positive T （NkR＋ T） cells in the regulation of intestinal inflammation, we analyzed the population and function of these cells in ulcerative colitis （UC）. METHODS： Colonic mucosal tissues were obtained from colonoscopic biopsies of the descending colon from 96 patients with UC （51 endoscopically uninflamed, 45 inflamed） and 18 normal controls. Endoscopic appearance and histologic score at the biopsied site were determined by MaLts＇ classification. A single cell suspension was prepared from each biopsy by collagenase digestion. Two NkR^＋ T cell subsets, CD56^＋（CD56^＋CD3^＋） T cells and CD161＋（CD161^＋CD3^＋） T cells, were detected by flow cytometric analysis. Intracellular cytokine analysis for anti-inflammatory cytokine interleukin-10 （IL-10） was performed by in vitro stimulation with phorbol-myristateacetate （PMA） and ionomycin. RESULTS： CD56^＋ T cells and CD161^＋ T cells are present in the normal human colon and account for 6.7% and 21.3% of all mononuclear cells, respectively. The populations of both CD56＋ T cells and CD161^＋ T cells were decreased significantly in the inflamed mucosa of UC. In contrast, the frequency of conventional T cells （CD56 CD3^＋ cells and CD161CD3^＋ cells） was similar among the patient and control groups. The populations of NkR^＋ T cells were correlated inversely with the severity of inflammation, which was classified according to the endoscopic and histologic Marts＇ criteria. Interestingly, approximately 4% of mucosal NkR＋ T cells expressing IL-10 were detected by in vitro stimulation with PMA and ***： Selective reduction in the population of colonic mucosal NkR＋T cells may contribute to the development of intestinal inflammation in UC.

关键词： Natural killer T cells Ulcerative colitis Interleukin-10