AIM:To elucidate the colonoscopic features of serrated lesions of the colorectum using magnifying colonoscopy.METHODS:Broad division of serrated lesions of the colorectum into hyperplastic polyps(HPs),traditional serr...AIM:To elucidate the colonoscopic features of serrated lesions of the colorectum using magnifying colonoscopy.METHODS:Broad division of serrated lesions of the colorectum into hyperplastic polyps(HPs),traditional serrated adenomas(TSAs),and sessile serrated adenomas/polyps(SSA/Ps) has been proposed on the basis of recent molecular biological studies.However,few reports have examined the colonoscopic features of these divisions,including magnified colonoscopic findings.This study examined 118 lesions excised in our hospital as suspected serrated lesions after magnified observation between January 2008 and September 2011.Patient characteristics(sex,age),conventional colonoscopic findings(location,size,morphology,color,mucin) and magnified colonoscopic findings(pit pattern diagnosis) were interpreted by five colonoscopists with experience in over 1000 colonoscopies,and were compared with histopathological diagnoses.The pit patterns were categorized according to Kudo's classification,but a more detailed investigation was also performed using the subclassification [type Ⅱ-Open(type Ⅱ-O),type Ⅱ-Long(type Ⅱ-L),or type Ⅳ-Serrated(type Ⅳ-S)] proposed by Kimura T and Yamano H.RESULTS:Lesions comprised 23 HPs(23/118:19.5%),39 TSAs(39/118:33.1%:with cancer in one case),50 SSA/Ps(50/118:42.4%:complicated with cancer in three cases),and six others(6/118:5.1%).We excluded six others,including three regular adenomas,one hamartoma,one inflammatory polyp,and one juvenile polyp for further analysis.Conventional colonoscopy showed that SSA/Ps were characterized as larger in diameter than TSAs and HPs(SSA/P vs HP,13.62 ± 8.62 mm vs 7.74 ± 3.24 mm,P < 0.001;SSA/Ps vs TSA,13.62 ± 8.62 mm vs 9.89 ± 5.73 mm,P < 0.01);common in the right side of the colon [HPs,30.4%(7/23):TSAs,20.5%(8/39):SSA/P,84.0%(42/50),P < 0.001];flat-elevated lesion [HPs,30.4%(7/23):TSAs,5.1%(2/39):SSA/Ps,90.0%(45/50),P < 0.001];normal-colored or pale imucosa [HPs,34.8%(8/23):TSAs,10.3%(4/39):SSA/Ps,80%(40/50),P < 0.001];and with large amounts of mucin [HPs,21.7%(5/23):TSAs,17.9%(7/39):SSA/Ps,72.0%(36/50),P < 0.001].In magnified colonoscopic findings,17 lesions showed either type Ⅱ pit pattern alone or partial type Ⅱ pit pattern as the basic architecture,with 14 HPs(14/17,70.0%) and 3 SSA/Ps.Magnified colonoscopy showed the type Ⅱ-O pit pattern as characteristic of SSA/Ps [sensitivity 83.7%(41/49),specificity 85.7%(54/63)].Cancer was also present in three lesions,in all of which a type Ⅵ pit pattern was also present within the same lesion.There were four HPs and four TSAs each.The type Ⅳ-S pit pattern was characteristic of TSAs [sensitivity 96.7%(30/31),specificity 89.9%(72/81)].Cancer was present in one lesion,in which a type Ⅵ pit pattern was also present within the same lesion.In our study,serrated lesions of the colorectum also possessed the features described in previous reports of conventional colonoscopic findings.The pit pattern diagnosis using magnifying colonoscopy,particularly magnified colonoscopic findings using subclassifications of surface architecture,reflected the pathological characteristics of SSA/Ps and TSAs,and will be useful for colonoscopic diagnosis.CONCLUSION:We suggest that this system could be a good diagnostic tool for SSA/Ps using magnifying colonoscopy.展开更多
Gastric cancer(GC)is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide.There is an increasing understanding of the roles that genetic and epigenetic alterations...Gastric cancer(GC)is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide.There is an increasing understanding of the roles that genetic and epigenetic alterations play in GCs.Recent studies using nextgeneration sequencing(NGS)have revealed a number of potential cancer-driving genes in GC.Whole-exome sequencing of GC has identified recurrent somatic mutations in the chromatin remodeling gene ARID1A and alterations in the cell adhesion gene FAT4,a member of the cadherin gene family.Mutations in chromatin remodeling genes(ARID1A,MLL3 and MLL)have been found in 47%of GCs.Whole-genome sequencing and whole-transcriptome sequencing analyses have also discovered novel alterations in GC.Recent studies of cancer epigenetics have revealed widespread alterations in genes involved in the epigenetic machinery,such as DNA methylation,histone modifications,nucleosome positioning,noncoding RNAs and microRNAs.Recent advances in molecular research on GC have resulted in the introduction of new diagnostic and therapeutic strategies into clinical settings.The antihuman epidermal growth receptor 2(HER2)antibody trastuzumab has led to an era of personalized therapy in GC.In addition,ramucirumab,a monoclonal antibody targeting vascular endothelial growth factor receptor(VEGFR)-2,is the first biological treatment that showed survival benefits as a single-agent therapy in patients with advanced GC who progressed after firstline chemotherapy.Using NGS to systematically identify gene alterations in GC is a promising approach with remarkable potential for investigating the pathogenesis of GC and identifying novel therapeutic targets,as well as useful biomarkers.In this review,we will summarize the recent advances in the understanding of the molecular pathogenesis of GC,focusing on the potential use of these genetic and epigenetic alterations as diagnostic biomarkers and novel therapeutic targets.展开更多
Antiplatelet therapy is the standard of care for the secondary prevention of acute coronary syndrome and ischemic stroke, especially after coronary intervention. However, this therapy is associated with bleeding compl...Antiplatelet therapy is the standard of care for the secondary prevention of acute coronary syndrome and ischemic stroke, especially after coronary intervention. However, this therapy is associated with bleeding complications such as gastrointestinal bleeding, which is one of the most common life-threatening complications. Early endoscopy is recommended for most patients with acute upper gastrointestinal bleeding. After successful endoscopic hemostasis, immediate resumption of antiplatelet therapy with proton-pump inhibitors(PPIs) is recommended to prevent further ischemic events. PPI prophylaxis during antiplatelet therapy reduces the risk of upper gastrointestinal bleeding. The potential negative metabolic interaction between PPIs and clopidogrel is still unclear.展开更多
基金Supported by The Japanese Foundation for Research and Promotion of Endoscopy (JFE),in partThe Japanese Society of Gastroenterology (JSGE),to Watanabe Y+1 种基金The Princess Takamatsu Cancer Research FundA Generous Gift from both the JFE and the JSGE
文摘AIM:To elucidate the colonoscopic features of serrated lesions of the colorectum using magnifying colonoscopy.METHODS:Broad division of serrated lesions of the colorectum into hyperplastic polyps(HPs),traditional serrated adenomas(TSAs),and sessile serrated adenomas/polyps(SSA/Ps) has been proposed on the basis of recent molecular biological studies.However,few reports have examined the colonoscopic features of these divisions,including magnified colonoscopic findings.This study examined 118 lesions excised in our hospital as suspected serrated lesions after magnified observation between January 2008 and September 2011.Patient characteristics(sex,age),conventional colonoscopic findings(location,size,morphology,color,mucin) and magnified colonoscopic findings(pit pattern diagnosis) were interpreted by five colonoscopists with experience in over 1000 colonoscopies,and were compared with histopathological diagnoses.The pit patterns were categorized according to Kudo's classification,but a more detailed investigation was also performed using the subclassification [type Ⅱ-Open(type Ⅱ-O),type Ⅱ-Long(type Ⅱ-L),or type Ⅳ-Serrated(type Ⅳ-S)] proposed by Kimura T and Yamano H.RESULTS:Lesions comprised 23 HPs(23/118:19.5%),39 TSAs(39/118:33.1%:with cancer in one case),50 SSA/Ps(50/118:42.4%:complicated with cancer in three cases),and six others(6/118:5.1%).We excluded six others,including three regular adenomas,one hamartoma,one inflammatory polyp,and one juvenile polyp for further analysis.Conventional colonoscopy showed that SSA/Ps were characterized as larger in diameter than TSAs and HPs(SSA/P vs HP,13.62 ± 8.62 mm vs 7.74 ± 3.24 mm,P < 0.001;SSA/Ps vs TSA,13.62 ± 8.62 mm vs 9.89 ± 5.73 mm,P < 0.01);common in the right side of the colon [HPs,30.4%(7/23):TSAs,20.5%(8/39):SSA/P,84.0%(42/50),P < 0.001];flat-elevated lesion [HPs,30.4%(7/23):TSAs,5.1%(2/39):SSA/Ps,90.0%(45/50),P < 0.001];normal-colored or pale imucosa [HPs,34.8%(8/23):TSAs,10.3%(4/39):SSA/Ps,80%(40/50),P < 0.001];and with large amounts of mucin [HPs,21.7%(5/23):TSAs,17.9%(7/39):SSA/Ps,72.0%(36/50),P < 0.001].In magnified colonoscopic findings,17 lesions showed either type Ⅱ pit pattern alone or partial type Ⅱ pit pattern as the basic architecture,with 14 HPs(14/17,70.0%) and 3 SSA/Ps.Magnified colonoscopy showed the type Ⅱ-O pit pattern as characteristic of SSA/Ps [sensitivity 83.7%(41/49),specificity 85.7%(54/63)].Cancer was also present in three lesions,in all of which a type Ⅵ pit pattern was also present within the same lesion.There were four HPs and four TSAs each.The type Ⅳ-S pit pattern was characteristic of TSAs [sensitivity 96.7%(30/31),specificity 89.9%(72/81)].Cancer was present in one lesion,in which a type Ⅵ pit pattern was also present within the same lesion.In our study,serrated lesions of the colorectum also possessed the features described in previous reports of conventional colonoscopic findings.The pit pattern diagnosis using magnifying colonoscopy,particularly magnified colonoscopic findings using subclassifications of surface architecture,reflected the pathological characteristics of SSA/Ps and TSAs,and will be useful for colonoscopic diagnosis.CONCLUSION:We suggest that this system could be a good diagnostic tool for SSA/Ps using magnifying colonoscopy.
基金Supported by Grants-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science and Technology of Japan
文摘Gastric cancer(GC)is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide.There is an increasing understanding of the roles that genetic and epigenetic alterations play in GCs.Recent studies using nextgeneration sequencing(NGS)have revealed a number of potential cancer-driving genes in GC.Whole-exome sequencing of GC has identified recurrent somatic mutations in the chromatin remodeling gene ARID1A and alterations in the cell adhesion gene FAT4,a member of the cadherin gene family.Mutations in chromatin remodeling genes(ARID1A,MLL3 and MLL)have been found in 47%of GCs.Whole-genome sequencing and whole-transcriptome sequencing analyses have also discovered novel alterations in GC.Recent studies of cancer epigenetics have revealed widespread alterations in genes involved in the epigenetic machinery,such as DNA methylation,histone modifications,nucleosome positioning,noncoding RNAs and microRNAs.Recent advances in molecular research on GC have resulted in the introduction of new diagnostic and therapeutic strategies into clinical settings.The antihuman epidermal growth receptor 2(HER2)antibody trastuzumab has led to an era of personalized therapy in GC.In addition,ramucirumab,a monoclonal antibody targeting vascular endothelial growth factor receptor(VEGFR)-2,is the first biological treatment that showed survival benefits as a single-agent therapy in patients with advanced GC who progressed after firstline chemotherapy.Using NGS to systematically identify gene alterations in GC is a promising approach with remarkable potential for investigating the pathogenesis of GC and identifying novel therapeutic targets,as well as useful biomarkers.In this review,we will summarize the recent advances in the understanding of the molecular pathogenesis of GC,focusing on the potential use of these genetic and epigenetic alterations as diagnostic biomarkers and novel therapeutic targets.
文摘Antiplatelet therapy is the standard of care for the secondary prevention of acute coronary syndrome and ischemic stroke, especially after coronary intervention. However, this therapy is associated with bleeding complications such as gastrointestinal bleeding, which is one of the most common life-threatening complications. Early endoscopy is recommended for most patients with acute upper gastrointestinal bleeding. After successful endoscopic hemostasis, immediate resumption of antiplatelet therapy with proton-pump inhibitors(PPIs) is recommended to prevent further ischemic events. PPI prophylaxis during antiplatelet therapy reduces the risk of upper gastrointestinal bleeding. The potential negative metabolic interaction between PPIs and clopidogrel is still unclear.