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Endoscopic Kyoto classification of Helicobacter pylori infection and gastric cancer risk diagnosis

World Journal of Gastroenterology 2020年第5期26卷 466-477页

作者： Osamu Toyoshima Toshihiro Nishizawa Kazuhiko Koike Department of Gastroenterology Toyoshima Endoscopy ClinicTokyo 157-0066Japan Department of Gastroenterology Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan Department of Gastroenterology and Hepatology International University of Health and WelfareMita HospitalTokyo 108-8329Japan

Recent advances in endoscopic technology allow detailed observation of the gastric mucosa.Today,endoscopy is used in the diagnosis of gastritis to determine the presence/absence of Helicobacter pylori(H.pylori)infection and evaluate gastric cancer risk.In 2013,the Japan Gastroenterological Endoscopy Society advocated the Kyoto classification,a new grading system for endoscopic gastritis.The Kyoto classification organized endoscopic findings related to H.pylori infection.The Kyoto classification score is the sum of scores for five endoscopic findings(atrophy,intestinal metaplasia,enlarged folds,nodularity,and diffuse redness with or without regular arrangement of collecting venules)and ranges from 0 to 8.Atrophy,intestinal metaplasia,enlarged folds,and nodularity contribute to gastric cancer risk.Diffuse redness and regular arrangement of collecting venules are related to H.pylori infection status.In subjects without a history of H.pylori eradication,the infection rates in those with Kyoto scores of 0,1,and≥2 were 1.5%,45%,and 82%,respectively.A Kyoto classification score of 0 indicates no H.pylori infection.A Kyoto classification score of 2 or more indicates H.pylori infection.Kyoto classification scores of patients with and without gastric cancer were 4.8 and 3.8,respectively.A Kyoto classification score of 4 or more might indicate gastric cancer risk.

关键词： Gastric cancer Helicobacter pylori Endoscopy Kyoto classification Atrophy Intestinal metaplasia Enlarged fold Nodularity Diffuse redness Regular arrangement of collecting venules

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Initial management for acute lower gastrointestinal bleeding

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World Journal of Gastroenterology 2019年第1期25卷 69-84页

作者： Tomonori Aoki Yoshihiro Hirata Atsuo Yamada Kazuhiko Koike Department of Gastroenterology Graduate School of Medicine the University of Tokyo Division of Advanced Genome Medicine the Institute of Medical Sciencethe University of Tokyo

Acute lower gastrointestinal bleeding(LGIB) is a common indication for hospital admission. Patients with LGIB often experience persistent or recurrent bleeding and require blood transfusions and interventions, such as colonoscopic,radiological, and surgical treatments. Appropriate decision-making is needed to initially manage acute LGIB, including emergency hospitalization, timing of colonoscopy, and medication use. In this literature review, we summarize the evidence for initial management of acute LGIB. Assessing various clinical factors,including comorbidities, medication use, presenting symptoms, vital signs, and laboratory data is useful for risk stratification of severe LGIB, and for discriminating upper gastrointestinal bleeding. Early timing of colonoscopy had the possibility of improving identification of the bleeding source, and the rate of endoscopic intervention, compared with elective colonoscopy. Contrast-enhanced computed tomography before colonoscopy may help identify stigmata of recent hemorrhage on colonoscopy, particularly in patients who can be examined immediately after the last hematochezia. How to deal with nonsteroidal antiinflammatory drugs(NSAIDs) and antithrombotic agents after hemostasis should be carefully considered because of the risk of rebleeding and thromboembolic events. In general, aspirin as primary prophylaxis for cardiovascular events and NSAIDs were suggested to be discontinued after LGIB. Managing acute LGIB based on this information would improve clinical outcomes. Further investigations are needed to distinguish patients with LGIB who require early colonoscopy and hemostatic intervention.

关键词： Lower gastrointestinal bleeding Predictive model Colonoscopy Computed tomography Medication

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Helicobacter pylori infection and liver diseases: Epidemiology and insights into pathogenesis

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World Journal of Gastroenterology 2018年第32期24卷 3617-3625页

作者： Kazuya Okushin Takeya Tsutsumi kazuhiko Ikeuchi Akira Kado Kenichiro Enooku Hidetaka Fujinaga Kyoji Moriya Hiroshi Yotsuyanagi Kazuhiko Koike Department of Gastroenterology Graduate School of Medicine The University of Tokyo Department of Infection Control and Prevention Graduate School of Medicine The University of Tokyo Division of Infectious Diseases Advanced Clinical Research Center Institute of Medical Science The University of Tokyo Department of Infectious Diseases The University of Tokyo

Both Helicobacter pylori(H. pylori) infection and liver diseases, including nonalcoholic fatty liver disease(NAFLD), viral hepatitis, and hepatocellular carcinoma(HCC), have high prevalences worldwide, and the relationship between H. pylori infection and liver disease has been discussed for many years. Although positive correlations between H. pylori and NAFLD have been identified in some clinical and experimental studies, nega-tive correlations have also been obtained in high-quality clinical studies. Associations between H. pylori and the pathogenesis of chronic viral hepatitis, mainly disease progression with fibrosis, have also been suggested in some clinical studies. Concerning HCC, a possible role for H. pylori in hepatocarcinogenesis has been identified since H. pylori genes have frequently been detected in resected HCC specimens. However, no study hasrevealed the direct involvement of H. pylori in promoting the development of HCC. Although findings regarding the correlations between H. pylori and liver disease pathogenesis have been accumulating, the existing data do not completely lead to an unequivocal conclusion. Further high-quality clinical and experimental analyses are necessary to evaluate the efficacy of H. pylori eradication in ameliorating the histopathological changes observed in each liver disease.

关键词： Helicobacter pylori Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Hepatitis C virus Hepatitis B virus Viral hepatitis Hepatocellular carcinoma

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Circulating RNAs as new biomarkers for detecting pancreatic cancer

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World Journal of Gastroenterology 2015年第28期21卷 8527-8540页

作者： Takahiro Kishikawa Motoyuki Otsuka Motoko Ohno Takeshi Yoshikawa Akemi Takata Kazuhiko Koike Department of Gastroenterology Graduate School of Medicine The University of Tokyo Japan Science and Technology Agency PRESTO

Pancreatic cancer remains difficult to treat and has a high mortality rate.It is difficult to diagnose early mainly due to the lack of screening imaging modalities and specific biomarkers.Consequently,it is important to develop biomarkers that enable the detection of early stage tumors.Emerging evidence is accumulating that tumor cells release substantial amounts of RNA into the bloodstream that strongly resist RNases in the blood and are present at sufficient levels for quantitative analyses.These circulating RNAs are upregulated in the serum and plasma of cancer patients,including those with pancreatic cancer,compared with healthy controls.The majority of RNA biomarker studies have assessed circulating microRNAs(miRs),which are often tissue-specific.There are few reports of the tumorspecific upregulation of other types of small noncoding RNAs(ncRNAs),such as small nucleolar RNAs and Piwi-interacting RNAs.Long ncRNAs(IncRNAs),such as HOTAIR and MALAT1,in the serum/plasma of pancreatic cancer patients have also been reported as diagnostic and prognostic markers.Among tissuederived RNAs,some miRs show increased expression even in pre-cancerous tissues,and their expression profiles may allow for the discrimination between a chronic inflammatory state and carcinoma.Additionally,some miRs and IncRNAs have been reported with significant alterations in expression according to disease progression,and they may thus represent potential candidate diagnostic or prognostic biomarkers that may be used to evaluate patients once detection methods in peripheral blood are well established.Furthermore,recent innovations in high-throughput sequencing techniques have enabled the discovery of unannotated tumor-associated ncRNAs and tumor-specific alternative splicing as novel and specific biomarkers of cancers.Although much work is required to clarify the release mechanism,origin of tumor-specific circulating RNAs,and selectivity of carrier complexes,and technical advances must also be achieved,such as creating a consensus normalizat

关键词： MicroRNA Non-coding RNA Pancreaticcancer Biomarkers Early detection

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Novel therapeutic approaches for hepatitis B virus covalently closed circular DNA

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World Journal of Gastroenterology 2015年第23期21卷 7084-7088页

作者： Motoko Ohno Motoyuki Otsuka Takahiro Kishikawa Takeshi Yoshikawa Akemi Takata Kazuhiko Koike Department of Gastroenterology Graduate School of Medicine the University of Tokyo

Hepatitis B virus(HBV) infection is a major global health problem. Although current therapies, such as the use of nucleos(t)ide analogs, inhibit HBV replication efficiently, they do not eliminate covalently closed circular DNA(ccc DNA), which persists in hepatocyte nuclei. As HBV ccc DNA is a viral transcription template, novel therapeutic approaches to directly target HBV ccc DNA are necessary to completely eradicate persistent HBV infections. HBV ccc DNA levels in HBV-infected human liver cells are extremely low; thus, more reliable and simple measurement methods are needed to correctly monitor their levels during therapeutic treatment. Although reverse transcription-polymerase chain reaction or Southern blot procedures are currently used in research studies, these methods are not completely reliable and are also time-consuming and labor-intensive. Genome editing technologies, such as zinc finger nucleases, transcription activator-like effector nucleases, and the clustered regularly interspaced short palindromic repeats/Cas9(CRISPR/Cas9) system, which are designed to target specific DNA sequences, represent highly promising potential therapeutic tools. In particular, the CRISPR/Cas9 system is an easily customizable sequencespecific nuclease with high flexibility and may be the most feasible approach to target HBV ccc DNA. Further research to develop easier, safer, and more effective protocols should be pursued.

关键词： Hepatitis B virus Covalently closed circularHBV DNA Genome editing

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Endoscopic submucosal dissection for superficial esophageal neoplasms

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World Journal of Gastrointestinal Endoscopy 2012年第5期4卷 162-166页

作者： Satoshi Ono Mitsuhiro Fujishiro Kazuhiko Koike Center for Epidemiology and Preventive Medicine Graduate School of MedicineUniversity of Tokyo7-3-1HongoBunkyoTokyo 113-8655Japan Department of Endoscopy and Endoscopic Surgery Graduate School of MedicineUniversity of Tokyo7-3-1HongoBunkyoTokyo 113-8655Japan Department of Gastroenterology Graduate School of MedicineUniversity of Tokyo7-3-1HongoBunkyoTokyo 113-8655Japan

Endoscopic submucosal dissection(ESD) is currently accepted as the major treatment modality for superficial neoplasms in the gastrointestinal tract including the esophagus.An important advantage of ESD is its effectiveness in resecting lesions regardless of their size and severity of fibrosis.Based on excellent outcomes for esophageal neoplasms with a small likelihood of lymph node metastasis,the number of ESD candidates has increased.On the other hand,ESD still requires highly skilled endoscopists due to technical difficulties.To avoid unnecessary complications including perforation and postoperative stricture,the indications for ESD require careful consideration and a full understanding of this modality.This article,in the highlight topic series,provides detailed information on the indication,procedure,outcome,complications and their prevention in ESD of superficial esophageal neoplasms.

关键词： Complications Endoscopic submucosal dissection Esophageal neoplasm Indication Outcome Squamous cell carcinoma

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Diagnostic and therapeutic application of noncoding RNAs for hepatocellular carcinoma

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World Journal of Hepatology 2015年第1期7卷 1-6页

作者： Chikako Shibata Motoyuki Otsuka Takahiro Kishikawa Motoko Ohno Takeshi Yoshikawa Akemi Takata Kazuhiko Koike Department of Gastroenterology Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan Japan Science and Technology Agency PRESTOKawaguchiSaitama 332-0012Japan

Micro RNAs(mi RNAs) are small,noncoding RNA molecules that regulate gene expression posttranscriptionally,targeting thousands of messenger RNAs. Long noncoding RNAs(lnc RNAs),another class of noncoding RNAs,have been determined to be also involved in transcription regulation and translation of target genes. Since deregulated expression levels or functions of miR NAs and lncR NAs in hepatocellular carcinoma(HCC) are frequently observed,clinical use of noncoding RNAs for novel diagnostic and therapeutic applications in the management of HCCs is highly and emergently e xpe c t e d. H e r e,we s ummar iz e r e c e nt f indings regarding deregulated mi RNAs and lnc RNAs for their potential clinical use as diagnostic and prognostic biomarkers of HCC. Specifically,we emphasize the deregulated expression levels of such noncoding RNAs in patients' sera as noninvasive biomarkers,a field that requires urgent improvement in the clinical surveillance of HCC. Since nucleotide-based strategies are being applied to clinical therapeutics,we further summarize clinical and preclinical trials using oligonucleotides involving the use of miR NAs and small interfering RNAs against HCC as novel therapeutics. Finally,we discuss current open questions,which must be clarified in the near future for realistic clinical applications of these new strategies.

关键词： MicroRNA Long noncoding RNA Hepatocellularcarcinoma Clinical trials Biomarker

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Anchor-wire technique for multiple plastic biliary stents to prevent stent dislocation

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World Journal of Gastroenterology 2011年第28期17卷 3366-3368页

作者： Tsuyoshi Hamada Yousuke Nakai Saburo Matsubara Hiroyuki Isayama Akiko Narita Kazuhiro Watanabe Yukihiro koike Shigeo Matsukawa Tateo Kawase Kazuhiko Koike Department of Gastroenterology Kanto Central Hospital Department of Gastroenterology Graduate School of MedicineThe University of Tokyo

In endoscopic placement of multiple plastic biliary stents (PBSs),we sometimes experience proximal dislocation of the first PBS at the time of subsequent PBS insertion.We describe the case of a 79-year-old male with obstructive jaundice caused by cholangiocarcinoma who needed to receive multiple PBS placements for management of cholangitis.Although proximal dislocation of the first PBS was observed,we prevented the dislocation via our technique of using guidewire inserted from the distal end of the first PBS to the side hole as the anchor-wire.We could complete this technique only by inserting guidewire through the side hole of the first PBS during the process of releasing the first PBS and pulling out the guidewire and the inner sheath.It did not matter whether the anchor-wire went towards the third portion of the duodenum or the duodenal bulb.Here we introduce this "anchor-wire technique",which is useful for the prevention of PBS proximal dislocation in placing multiple PBSs.

关键词：技术支架错位胆道塑料锚 PBS 十二指肠

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Inflammation and de-differentiation in pancreatic carcinogenesis

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World Journal of Clinical Cases 2018年第15期6卷 882-891页

作者： Takahiro Seimiya Motoyuki Otsuka Takuma Iwata Eri Tanaka Tatsunori Suzuki Kazuma Sekiba Mari Yamagami Rei Ishibashi Kazuhiko Koike Department of Gastroenterology Graduate School of Medicine The University of Tokyo

Pancreatic cancer is a malignancy with an extremely poor prognosis. Chronic pancreatitis is a well-known risk factor for pancreatic cancer. Inflammation is thought to influence carcinogenesis through DNA damage and activation of intracellular signaling pathways. Many transcription factors and signaling pathways co-operate to determine and maintain cell identity at each phase of pancreatic organogenesis and cell differentiation. Recent studies have shown that carcinogenesis is promoted through the suppression of transcription factors related to differentiation. Pancreatitis also demonstrates transcriptional changes, suggesting that multifactorial epigenetic changes lead to impaired differentiation. Taken together, these factors may constitute an important framework for pancreatic carcinogenesis. In this review, we discuss the role of inflammation and de-differentiation in the development of pancreatic cancer, as well as the future of novel therapeutic applications.

关键词： Pancreatitis Inflammation Organogenesis Differentiation Transcription factor Pancreatic cancer

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Impact of fecal occult blood on obscure gastrointestinal bleeding:Observational study

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World Journal of Gastroenterology 2015年第1期21卷 326-332页

作者： Yuka Kobayashi Hirotsugu Watabe Atsuo Yamada Hirobumi Suzuki Yoshihiro Hirata Yutaka Yamaji Haruhiko Yoshida Kazuhiko Koike Department of Gastroenterology Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan

AIM: To elucidate the association between small bowel diseases(SBDs) and positive fecal occult blood test(FOBT) in patients with obscure gastrointestinal bleeding(OGIB).METHODS: Between February 2008 and August 2013, 202 patients with OGIB who performed both capsule endoscopy(CE) and FOBT were enrolled(mean age; 63.6 ± 14.0 years, 118 males, 96 previous overt bleeding, 106 with occult bleeding). All patients underwent immunochemical FOBTs twice prior to CE. Three experienced endoscopists independently reviewed CE videos. All reviews and consensus meeting were conducted without any information on FOBT results. The prevalence of SBDs was compared between patients with positive and negative FOBT.RESULTS: CE revealed SBDs in 72 patients(36%). FOBT was positive in 100 patients(50%) and negative in 102(50%). The prevalence of SBDs was significantly higher in patients with positive FOBT than those with negative FOBT(46% vs 25%, P = 0.002). In particular, among patients with occult OGIB, the prevalence of SBDs was higher in positive FOBT group than negative FOBT group(45% vs 18%, P = 0.002). On the other hand, among patients with previous overt OGIB, there was no significant difference in the prevalence of SBDs between positive and negative FOBT group(47% vs 33%, P = 0.18). In disease specific analysis among patients with occult OGIB, the prevalence of ulcer and tumor were higher in positive FOBT group than negative FOBT group. In multivariate analysis, only positive FOBT was a predictive factors of SBDs in patients with OGIB(OR = 2.5, 95%CI: 1.4-4.6, P = 0.003). Furthermore, the trend was evidentam on g patients with occult OGIB who underwent FOBT on the same day or a day before CE. The prevalence of SBDs in positive vs negative FOBT group were 54% vs 13% in patients with occult OGIB who underwent FOBT on the same day or the day before CE(P = 0.001), while there was no significant difference between positive and negative FOBT group in those who underwent FOBT two or more days before CE(43% vs 25%, P = 0.20).CONCLUSION:

关键词： Capsule endoscopy Fecal occult blood test Obscure

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