Idiopathic inflammatory bowel disease(IBD) predominantly includes ulcerative colitis and Crohn's disease. The pathogenesis of IBD is complex and not completely understood. Micro RNAs belong to a class of noncoding...Idiopathic inflammatory bowel disease(IBD) predominantly includes ulcerative colitis and Crohn's disease. The pathogenesis of IBD is complex and not completely understood. Micro RNAs belong to a class of noncoding small RNAs that post-transcriptionally regulate gene expression. Unique micro RNA expression profiles have been explored in IBD. In this review,we focus on the unique micro RNA expression pattern in both tissue and peripheral blood from IBD patients and emphasize the potential diagnostic and therapeutic applications. The discovery of micro RNAs has contributed to our understanding of IBD pathogenesis and might lead to clinical advance in new therapeutics.展开更多
AIM To investigate the outcomes and recurrences of p T1 b esophageal adenocarcinoma(EAC) following endoscopic mucosal resection(EMR) and associated treatments.METHODS Patients undergoing EMR with pathologically confir...AIM To investigate the outcomes and recurrences of p T1 b esophageal adenocarcinoma(EAC) following endoscopic mucosal resection(EMR) and associated treatments.METHODS Patients undergoing EMR with pathologically confirmed T1 b EAC at two academic referral centers were retrospectively identified.Patients were divided into 4 groups based on treatment following EMR:Endoscopic therapy alone(group A),endoscopic therapy with either chemotherapy,radiation or both(group B),surgicalresection(group C) or no further treatment/lost to follow-up(<12 mo)(group D).Pathology specimens were reviewed by a central pathologist.Follow-up data was obtained from the academic centers,primary care physicians and/or referring physicians.Univariate analysis was performed to identify factors predicting recurrence of EAC.RESULTS Fifty-three patients with T1 b EAC underwent EMR,of which 32(60%) had adequate follow-up ≥ 12 mo(median 34 mo,range 12-103).There were 16 patients in group A,9 in group B,7 in group C and 21 in group D.Median follow-up in groups A to C was 34 mo(range 12-103).Recurrent EAC developed overall in 9 patients(28%) including 6(38%) in group A(median:21 mo,range:6-73),1(11%) in group B(median:30 mo,range:30-30) and 2(29%) in group C(median 21 mo,range:7-35.Six of 9 recurrences were local;of the 6 recurrences,5 were treated with endoscopy alone.No predictors of recurrence of EAC were identified.CONCLUSION Endoscopic therapy of T1 b EAC may be a reasonable strategy for a subset of patients including those either refusing or medically unfit for esophagectomy.展开更多
AIM To evaluate if any association existed between the extent of hepatic necrosis in initial liver biopsies and patient survival.METHODS Thirty-seven patients with fulminant liver failure, whose liver biopsy exhibited...AIM To evaluate if any association existed between the extent of hepatic necrosis in initial liver biopsies and patient survival.METHODS Thirty-seven patients with fulminant liver failure, whose liver biopsy exhibited substantial necrosis, were identified and included in the study. The histological and clinical data was then analyzed in order to assess the relationship between the extent of necrosis and patient survival, with and without liver transplantation. The patients were grouped based on the etiology of hepatic necrosis. Each of the etiology groups were then further stratified according to whether or not they had received a liver transplant post-index biopsy, and whether or not the patient survived.RESULTS The core tissue length ranged from 5 to 44 mm with an average of 23 mm. Causes of necrosis included 14 autoimmune hepatitis, 10 drug induced liver injury(DILI), 9 hepatitis virus infection, and 4 unknown origin. Among them, 11 showed submassive(26%-75% of the parenchymal volume) and 26 massive(76%-100%) necrosis. Transplant-free survival was worse in patients with a higher extent of necrosis(40%, 71.4% and 100% in groups with necrosis of 76%-100%, 51%-75%and 26%-50%, respectively). Additionally, transplantfree survival rates were 66.7%, 57.1%, and 25.0% in groups of autoimmune hepatitis, DILI, and viral hepatitis, respectively. Even after liver transplantation, the survival rate in patients as a result of viral hepatitis remained the lowest(80%, 100%, and 40% in groups of autoimmune hepatitis, DILI, and viral hepatitis, respectively).CONCLUSION Adequate liver biopsy with more than 75% necrosis is associated with significant transplant-free mortality that is critical in predicting survival.展开更多
BACKGROUND In order to improve risk stratification and clinical management of the pancreatic ductal adenocarcinoma(PDAC),the American Joint Committee on Cancer(AJCC)has published its eighth edition staging manual.Some...BACKGROUND In order to improve risk stratification and clinical management of the pancreatic ductal adenocarcinoma(PDAC),the American Joint Committee on Cancer(AJCC)has published its eighth edition staging manual.Some major changes have been introduced in the new staging system for both T and N categories.Given the rarity of resectable disease,distal pancreatic cancer is likely underrepresented in the published clinical studies,and how the impact of the staging system actually reflects on to clinical outcomes remain unclear.AIM To validate the AJCC 8th edition of TNM staging in distal PDAC.METHODS A retrospective cohort study was performed in seven academic medical centers in the United States.Clinicopathological prognostic factors associated with progression-free survival(PFS)and overall survival(OS)were evaluated through univariate and multivariate analyses.RESULTS Overall,454 patients were enrolled in the study,and were divided into 2 subgroups:Invasive intraductal papillary mucinous neoplasms(IPMN)(115 cases)and non-IPMN associated adenocarcinoma(339 cases).Compared to invasive IPMN,non-IPMN associated adenocarcinomas are more common in relatively younger patients,have larger tumor size,are more likely to have positive lymph nodes,and are associated with a higher tumor(T)stage and nodal(N)stage,lymphovascular invasion,perineural invasion,tumor recurrence,and a worse PFS and OS.The cohort was predominantly categorized as stage 3 per AJCC 7th edition staging manual,and it’s more evenly distributed based on 8th edition staging manual.T and N staging of both 7th and 8th edition sufficiently stratify PFS and OS in the entire cohort,although dividing into N1 and N2 according to the 8th edition does not show additional stratification.For PDAC arising in IPMN,T staging of the 7th edition and N1/N2 staging of the 8th edition appear to further stratify PFS and OS.For PDAC without an IPMN component,T staging from both versions fails to stratify PFS and OS.CONCLUSION The AJCC 8th edition TNM staging system provides even distribution for the T staging,however,it does not provide better risk stratification than previous staging system for distal pancreatic cancer.展开更多
The genetic basis underlying liver fibrosis remains largely unknown.We conducted a study to identify genetic alleles and underlying pathways associated with hepatic fibrogenesis and fibrosis at the genome-wide level i...The genetic basis underlying liver fibrosis remains largely unknown.We conducted a study to identify genetic alleles and underlying pathways associated with hepatic fibrogenesis and fibrosis at the genome-wide level in 121 human livers.By accepting a liberal significance level of P<1e-4,we identified 73 and 71 candidate loci respectively affecting the variability in alpha-smooth muscle actin(a-SMA)levels(fibrogenesis)and total collagen content(fibrosis).The top genetic loci associated with the two markers were BAZA1 and NOL10 for a-SMA expression and FAM46A for total collagen content(P<1e-6).We further investigated the relationship between the candidate loci and the nearby gene transcription levels(cis-expression quantitative trait loci)in the same liver samples.We found that 44 candidate loci for a-SMA expression and 44 for total collagen content were also associated with the transcription of the nearby genes(P<0.05).Pathway analyses of these genes indicated that macrophage migration inhibitory factor(MIF)related pathway is significantly associated with fibrogenesis and fibrosis,though different genes were enriched for each marker.The association between the single nucleotide polymorphisms,MIF and a-SMA showed that decreased MIF expression is correlated with increased a-SMA expression,suggesting that variations in MIF locus might affect the susceptibility of fibrogenesis through controlling MIF gene expression.In summary,our study identified candidate alleles and pathways underlying both fibrogenesis and fibrosis in human livers.Our bioinformatics analyses suggested MIF pathway as a strong candidate involved in liver fibrosis,thus further investigation for the role of the MIF pathway in liver fibrosis is warranted.The study was reviewed and approved by the Institutional Review Board(IRB)of Wayne State University(approval No.201842)on May 17,2018.展开更多
文摘Idiopathic inflammatory bowel disease(IBD) predominantly includes ulcerative colitis and Crohn's disease. The pathogenesis of IBD is complex and not completely understood. Micro RNAs belong to a class of noncoding small RNAs that post-transcriptionally regulate gene expression. Unique micro RNA expression profiles have been explored in IBD. In this review,we focus on the unique micro RNA expression pattern in both tissue and peripheral blood from IBD patients and emphasize the potential diagnostic and therapeutic applications. The discovery of micro RNAs has contributed to our understanding of IBD pathogenesis and might lead to clinical advance in new therapeutics.
文摘AIM To investigate the outcomes and recurrences of p T1 b esophageal adenocarcinoma(EAC) following endoscopic mucosal resection(EMR) and associated treatments.METHODS Patients undergoing EMR with pathologically confirmed T1 b EAC at two academic referral centers were retrospectively identified.Patients were divided into 4 groups based on treatment following EMR:Endoscopic therapy alone(group A),endoscopic therapy with either chemotherapy,radiation or both(group B),surgicalresection(group C) or no further treatment/lost to follow-up(<12 mo)(group D).Pathology specimens were reviewed by a central pathologist.Follow-up data was obtained from the academic centers,primary care physicians and/or referring physicians.Univariate analysis was performed to identify factors predicting recurrence of EAC.RESULTS Fifty-three patients with T1 b EAC underwent EMR,of which 32(60%) had adequate follow-up ≥ 12 mo(median 34 mo,range 12-103).There were 16 patients in group A,9 in group B,7 in group C and 21 in group D.Median follow-up in groups A to C was 34 mo(range 12-103).Recurrent EAC developed overall in 9 patients(28%) including 6(38%) in group A(median:21 mo,range:6-73),1(11%) in group B(median:30 mo,range:30-30) and 2(29%) in group C(median 21 mo,range:7-35.Six of 9 recurrences were local;of the 6 recurrences,5 were treated with endoscopy alone.No predictors of recurrence of EAC were identified.CONCLUSION Endoscopic therapy of T1 b EAC may be a reasonable strategy for a subset of patients including those either refusing or medically unfit for esophagectomy.
文摘AIM To evaluate if any association existed between the extent of hepatic necrosis in initial liver biopsies and patient survival.METHODS Thirty-seven patients with fulminant liver failure, whose liver biopsy exhibited substantial necrosis, were identified and included in the study. The histological and clinical data was then analyzed in order to assess the relationship between the extent of necrosis and patient survival, with and without liver transplantation. The patients were grouped based on the etiology of hepatic necrosis. Each of the etiology groups were then further stratified according to whether or not they had received a liver transplant post-index biopsy, and whether or not the patient survived.RESULTS The core tissue length ranged from 5 to 44 mm with an average of 23 mm. Causes of necrosis included 14 autoimmune hepatitis, 10 drug induced liver injury(DILI), 9 hepatitis virus infection, and 4 unknown origin. Among them, 11 showed submassive(26%-75% of the parenchymal volume) and 26 massive(76%-100%) necrosis. Transplant-free survival was worse in patients with a higher extent of necrosis(40%, 71.4% and 100% in groups with necrosis of 76%-100%, 51%-75%and 26%-50%, respectively). Additionally, transplantfree survival rates were 66.7%, 57.1%, and 25.0% in groups of autoimmune hepatitis, DILI, and viral hepatitis, respectively. Even after liver transplantation, the survival rate in patients as a result of viral hepatitis remained the lowest(80%, 100%, and 40% in groups of autoimmune hepatitis, DILI, and viral hepatitis, respectively).CONCLUSION Adequate liver biopsy with more than 75% necrosis is associated with significant transplant-free mortality that is critical in predicting survival.
文摘BACKGROUND In order to improve risk stratification and clinical management of the pancreatic ductal adenocarcinoma(PDAC),the American Joint Committee on Cancer(AJCC)has published its eighth edition staging manual.Some major changes have been introduced in the new staging system for both T and N categories.Given the rarity of resectable disease,distal pancreatic cancer is likely underrepresented in the published clinical studies,and how the impact of the staging system actually reflects on to clinical outcomes remain unclear.AIM To validate the AJCC 8th edition of TNM staging in distal PDAC.METHODS A retrospective cohort study was performed in seven academic medical centers in the United States.Clinicopathological prognostic factors associated with progression-free survival(PFS)and overall survival(OS)were evaluated through univariate and multivariate analyses.RESULTS Overall,454 patients were enrolled in the study,and were divided into 2 subgroups:Invasive intraductal papillary mucinous neoplasms(IPMN)(115 cases)and non-IPMN associated adenocarcinoma(339 cases).Compared to invasive IPMN,non-IPMN associated adenocarcinomas are more common in relatively younger patients,have larger tumor size,are more likely to have positive lymph nodes,and are associated with a higher tumor(T)stage and nodal(N)stage,lymphovascular invasion,perineural invasion,tumor recurrence,and a worse PFS and OS.The cohort was predominantly categorized as stage 3 per AJCC 7th edition staging manual,and it’s more evenly distributed based on 8th edition staging manual.T and N staging of both 7th and 8th edition sufficiently stratify PFS and OS in the entire cohort,although dividing into N1 and N2 according to the 8th edition does not show additional stratification.For PDAC arising in IPMN,T staging of the 7th edition and N1/N2 staging of the 8th edition appear to further stratify PFS and OS.For PDAC without an IPMN component,T staging from both versions fails to stratify PFS and OS.CONCLUSION The AJCC 8th edition TNM staging system provides even distribution for the T staging,however,it does not provide better risk stratification than previous staging system for distal pancreatic cancer.
基金supported in part by a NIH grant,No.R01 DK106540(to WL).
文摘The genetic basis underlying liver fibrosis remains largely unknown.We conducted a study to identify genetic alleles and underlying pathways associated with hepatic fibrogenesis and fibrosis at the genome-wide level in 121 human livers.By accepting a liberal significance level of P<1e-4,we identified 73 and 71 candidate loci respectively affecting the variability in alpha-smooth muscle actin(a-SMA)levels(fibrogenesis)and total collagen content(fibrosis).The top genetic loci associated with the two markers were BAZA1 and NOL10 for a-SMA expression and FAM46A for total collagen content(P<1e-6).We further investigated the relationship between the candidate loci and the nearby gene transcription levels(cis-expression quantitative trait loci)in the same liver samples.We found that 44 candidate loci for a-SMA expression and 44 for total collagen content were also associated with the transcription of the nearby genes(P<0.05).Pathway analyses of these genes indicated that macrophage migration inhibitory factor(MIF)related pathway is significantly associated with fibrogenesis and fibrosis,though different genes were enriched for each marker.The association between the single nucleotide polymorphisms,MIF and a-SMA showed that decreased MIF expression is correlated with increased a-SMA expression,suggesting that variations in MIF locus might affect the susceptibility of fibrogenesis through controlling MIF gene expression.In summary,our study identified candidate alleles and pathways underlying both fibrogenesis and fibrosis in human livers.Our bioinformatics analyses suggested MIF pathway as a strong candidate involved in liver fibrosis,thus further investigation for the role of the MIF pathway in liver fibrosis is warranted.The study was reviewed and approved by the Institutional Review Board(IRB)of Wayne State University(approval No.201842)on May 17,2018.
