Acute pancreatitis(AP)is a leading cause of gastrointestinal-related hospitalizations in the United States,resulting in 300000 admissions per year with an estimated cost of over$2.6 billion annually.The severity of AP...Acute pancreatitis(AP)is a leading cause of gastrointestinal-related hospitalizations in the United States,resulting in 300000 admissions per year with an estimated cost of over$2.6 billion annually.The severity of AP is determined by the presence of pancreatic complications and end-organ damage.While moderate/severe pancreatitis can be associated with significant morbidity and mortality,the majority of patients have a mild presentation with an uncomplicated course and mortality rate of less than 2%.Despite favorable outcomes,the majority of mild AP patients are admitted,contributing to healthcare cost and burden.In this Editorial we review the performance of an emergency department(ED)pathway for patients with mild AP at a tertiary care center with the goal of reducing hospitalizations,resource utilization,and costs after several years of implementation of the pathway.We discuss the clinical course and outcomes of mild AP patients enrolled in the pathway who were successfully discharged from the ED compared to those who were admitted to the hospital,and identify predictors of successful ED discharge to select patients who can potentially be triaged to the pathway.We conclude that by implementing innovative clinical pathways which are established and reproducible,selected AP patients can be safely discharged from the ED,reducing hospitalizations and healthcare costs,without compromising clinical outcomes.We also identify a subset of patients most likely to succeed in this pathway.展开更多
Introduction:Sulfatase 2(SULF2),an endogenous extracellular sulfatase,can remove 6-O-sulfate groups of glucosamine residues from heparan sulfate(HS)chains to modulate the Wnt/β-catenin signaling pathway,which plays a...Introduction:Sulfatase 2(SULF2),an endogenous extracellular sulfatase,can remove 6-O-sulfate groups of glucosamine residues from heparan sulfate(HS)chains to modulate the Wnt/β-catenin signaling pathway,which plays an important role in both liver carcinogenesis and embryogenesis.Side population(SP)cells are widely identified as stem-like cancer cells and are closely related to carcinoma metastasis,recurrence,and poor patient prognosis.However,the roles of SULF2 in SP cells of hepatomas are unclear,and the underlying mechanism is undefined.Objectives:This study aimed to compare the heterogeneity between SP cells and non-side population(NSP)cells derived from three different liver cancer cell lines and to elucidate the involvement of the SULF2-Wnt/β-catenin axis in liver cancer stem cells(CSCs)and its impact on the processes of carcinogenesis and invasiveness.Methods:In this work,three different liver cancer SP cells(HepG2,Huh7,and PRC/PRL/5)were sorted by flow cytometry.We also examined the migration and invasion behaviors of SP and NSP cells.To determine if this high tumorigenic potential of SP cells is correlated to SULF2,qPCR,western blotting,and immunofluorescence analysis were conducted.We also performed nude mouse xenograft experiments for in vivo analysis.Results:The results from the in vitro colony formation assay showed that SP cells exhibited a 2-fold higher colony formation efficiency compared to their NSP counterparts.The SP cells exhibited significantly higher potentials in terms of their migratory capacity and invasive ability compared to NSP cells.We found that higher expression of SULF2 in SP cells was associated with greater capabilities for clonogenicity,migration,and invasion.It was also linked to higher activation of the Wnt/β-catenin signaling pathway via stimulation of key downstream factors,particularlyβ-catenin,c-Myc,and cyclin D1.Further,a positive correlation between the upregulated SULF2 expression and tumorigenesis in the in vivo nude mouse xenograft models was demonstrated,highlighting that the potential underlying mechanism was Wnt/β-catenin signaling pathway activation.Conclusion:Our findings show that variable SULF2 expression was associated with differential activation of the Wnt/β-catenin signaling pathway,which could lead to behavioral differences between SP and NSP cells and also among the SP cells of the three liver cancer cell lines assessed.It was reasonably concluded that the SULF2-Wnt/β-catenin axis could play an important role in the tumorigenicity of liver cancer stem cells.展开更多
Alcohol-associated hepatitis(AAH)is a severe form of liver disease caused by alcohol consumption.In the absence of confounding factors,clinical features and laboratory markers are sufficient to diagnose AAH,rule out a...Alcohol-associated hepatitis(AAH)is a severe form of liver disease caused by alcohol consumption.In the absence of confounding factors,clinical features and laboratory markers are sufficient to diagnose AAH,rule out alternative causes of liver injury and assess disease severity.Due to the elevated mortality of AAH,assessing the prognosis is a radical step in management.The Maddrey discriminant function(MDF)is the first established clinical prognostic score for AAH and was commonly used in the earliest AAH clinical trials.A MDF>32 indicates a poor prognosis and a potential benefit of initiating corticosteroids.The model for end stage liver disease(MELD)score has been studied for AAH prognostication and new evidence suggests MELD may predict mortality more accurately than MDF.The Lille score is usually combined to MDF or MELD score after corticosteroid initiation and offers the advantage of assessing response to treatment a 4-7 d into the course.Other commonly used scores include the Glasgow Alcoholic Hepatitis Score and the Age Bilirubin international normalized ratio Creatinine model.Clinical AAH correlate adequately with histologic severity scores and leave little indication for liver biopsy in assessing AAH prognosis.AAH presenting as acute on chronic liver failure(ACLF)is so far prognosticated with ACLF-specific scoring systems.New artificial intelligence-generated prognostic models have emerged and are being studied for use in AAH.Acute kidney injury(AKI)is one possible complication of AAH and is significantly associated with increased AAH mortality.Predicting AKI and alcohol relapse are important steps in the management of AAH.The aim of this review is to discuss the performance and limitations of different scoring models for AAH mortality,emphasize the most useful tools in prognostication and review predictors of recurrence.展开更多
BACKGROUND The strategy for preventing colorectal cancer is screening by colonoscopy,which offers a direct way for detection and removal of adenomatous polyps(APs).American College of Gastroenterology guidelines recom...BACKGROUND The strategy for preventing colorectal cancer is screening by colonoscopy,which offers a direct way for detection and removal of adenomatous polyps(APs).American College of Gastroenterology guidelines recommend that people aged≥45 years should undergo colonoscopy;however,how to deal with people aged≤45 years is still unknown.AIM To compare the prevalence of APs and high-grade neoplasia between the left and right colon in patients≤45 years.METHODS A retrospective observational study was conducted at a single tertiary III hospital in China.This study included patients aged 18-45 years with undergoing initial colonoscopy dissection and pathological diagnosis AP or high-grade neoplasia between February 2014 and January 2021.The number of APs in the entire colon while screening and post-polypectomy surveillance in following 1-3 years were evaluated.RESULTS A total of 3053 cases were included.The prevalence of APs in the left and right colon was 55.0%and 41.6%,respectively(OR 1.7,95%CI 1.6-2.4;P<0.05).For APs with high-grade neoplasia,the prevalence was 2.7%and 0.9%,respectively(OR 3.0,95%CI 2.0-4.6;P<0.05).Therefore,the prevalence of APs and high-grade neoplasia in the left colon was significantly higher than in the right colon in patients aged≤45 years.There were 327 patients who voluntarily participated in post-polypectomy surveillance in following 1-3 years,and APs were found in 216 cases(66.1%);170 cases had 1-3 polyps(52.0%)and 46 cases had>3 polyps(14.1%;OR 0.3,95%CI 0.1-0.6;P<0.05).CONCLUSION This study suggests that flexible sigmoidoscopy would be an optimal approach for initial screening in people aged≤45 years and would be a more cost-effective and safe strategy.展开更多
BACKGROUND Acute gallstone pancreatitis(AGP) is the most common cause of acute pancreatitis(AP) in the United States. Patients with AGP may also present with choledocholithiasis. In 2010, the American Society for Gast...BACKGROUND Acute gallstone pancreatitis(AGP) is the most common cause of acute pancreatitis(AP) in the United States. Patients with AGP may also present with choledocholithiasis. In 2010, the American Society for Gastrointestinal Endoscopy(ASGE) suggested a management algorithm based on probability for choledocholithiasis, recommending additional imaging for patients at intermediate risk and endoscopic retrograde cholangiopancreatography(ERCP) for patients at high risk of choledocholithiasis. In 2019, the ASGE guidelines were updated using more specific criteria to categorize individuals at high risk for choledocholithiasis. Neither ASGE guideline has been studied in AGP to determine the probability of having choledocholithiasis.AIM To determine compliance with ASGE guidelines, assess outcomes, and compare 2019 vs 2010 ASGE criteria for suspected choledocholithiasis in AGP.METHODS We conducted a retrospective cohort study of 882 patients admitted with AP to a single tertiary care center from 2008-2018. AP was diagnosed using revised Atlanta criteria and AGP was defined as the presence of gallstones on imaging or with cholestatic pattern of liver injury in the absence of another cause. Patients with chronic pancreatitis and pancreatic malignancy were excluded as were those who went directly to cholecystectomy prior to assessment for choledocholithiasis. Patients were assigned low, intermediate or high risk based on ASGE guidelines. Our primary outcomes of interest were the proportion of patients in the intermediate risk group undergoing magnetic resonance cholangiopancreatography(MRCP) first and the proportion of patients in the high risk group undergoing ERCP directly without preceding imaging. Secondary outcomes of interest included outcome differences based on if guidelines were not adhered to. We then evaluated the diagnostic accuracy of 2019 in comparison to the 2010 ASGE criteria for patients with suspected choledocholithiasis. We performed the t test or Wilcoxon rank sum test, as appropriate, to analyze if there were outcome differences based on if guidelines were not adhered to. Kappa coefficients were calculated to measure the degree of agreement between pairs of variables.RESULTS In this cohort, we identified 235 patients with AGP of which 79 patients were excluded as they went directly to surgery for cholecystectomy without prior MRCP or ERCP. Of the remaining 156 patients, 79 patients were categorized as intermediate risk and 77 patients were high risk for choledocholithiasis according to the 2010 ASGE guidelines. Among 79 intermediate risk patients, 54(68%) underwent MRCP first whereas 25 patients(32%) went directly to ERCP. For the 54 patients with intermediate risk who had MRCP first, 36 patients had no choledocholithiasis while 18 patients had evidence of choledocholithiasis prompting ERCP. Of these patients, ERCP confirmed stone disease in 11 patients. Of the 25 intermediate risk patients who directly underwent ERCP, 18 patients had stone disease. One patient with a normal ERCP developed post ERCP pancreatitis. Patients undergoing MRCP in this group had a significantly longer length of stay(5.0 vs 4.0 d, P = 0.02). In the high risk group, 64 patients(83%) had ERCP without preceding imaging, of which, 53 patients had findings consistent with choledocholithiasis, of which 13 patients(17%) underwent MRCP before ERCP, all of which showed evidence of stone disease. Furthermore, all of these patients ultimately had an ERCP, of which 8 patients had evidence of stones and 5 had normal examination.RESULTS Our cohort also demonstrated that 58% of all 156 patients with AGP had confirmed choledocholithiasis(79% of the high risk group and 37% of the intermediate group when risk was assigned based on the 2010 ASGE guidelines). When the updated 2019 ASGE guidelines were applied instead of the original 2010 guidelines, there was moderate agreement between the 2010 and 2019 guidelines(kappa = 0.46, 95%CI: 0.34-0.58). Forty-two of 77 patients were still deemed to be high risk and 35 patients were downgraded to intermediate risk. Thirty-five patients who were originally assigned high risk were reclassified as intermediate risk. For these 35 patients, 26 patients had ERCP findings consistent with choledocholithiasis and 9 patients had a normal examination. Based on the 2019 criteria, 9/35 patients who were downgraded to intermediate risk had an unnecessary ERCP with normal findings(without a preceding MRCP).CONCLUSION Two-thirds in intermediate risk and 83% in high risk group followed ASGE guidelines for choledocholithiasis. One intermediate-group patient with normal ERCP had post-ERCP AP, highlighting the risk of unnecessary procedures.展开更多
BACKGROUND Gastrointestinal symptoms are prevalent in patients with cirrhosis.Cirrhotic patients have a known predilection to delayed gastric emptying compared to those without cirrhosis.However,the contributing facto...BACKGROUND Gastrointestinal symptoms are prevalent in patients with cirrhosis.Cirrhotic patients have a known predilection to delayed gastric emptying compared to those without cirrhosis.However,the contributing factors have not been fully elucidated.Retained gastric food on esophagogastroduodenoscopy(EGD)has been used as a surrogate marker for delayed gastric emptying with reasonably high specificity.Therefore,we hypothesize that the frequency of retained gastric food contents at EGD will be higher in a cirrhotic population compared to a control population without liver disease.Additionally,we hypothesize that increased frequency of gastric food contents will be associated with increased severity of cirrhosis.AIM To determine the relative frequency of delayed gastric emptying among cirrhotics as compared to non-cirrhotics and to identify associated factors.METHODSWe performed a retrospective case-control study of cirrhotic subjects whounderwent EGD at an academic medical center between 2000 and 2015. Threehundred sixty-four patients with confirmed cirrhosis, who underwent a total of1044 EGDs for the indication of esophageal variceal screening or surveillance,were identified. During the same period, 519 control patients without liverdisease, who underwent a total of 881 EGDs for the indication of anemia, wereidentified. The presence of retained food on EGD was used as a surrogate fordelayed gastric emptying. The relative frequency of delayed gastric emptyingamong cirrhotics was compared to non-cirrhotics. Characteristics of patients withand without retained food on EGD were compared using univariable andmultivariable logistic regression analysis to identify associated factors.RESULTSOverall, 40 (4.5%) patients had evidence of retained food on EGD. Cirrhotics weremore likely to have retained food on EGD than non-cirrhotics (9.1% vs 1.4%, P <0.001). Characteristics associated with retained food on univariable analysisincluded age less than 60 years (12.6% vs 5.2%, P = 0.015), opioid use (P = 0.004),Child-Pugh class C (24.1% Child-Pugh class C vs 6.4% Child-Pugh class A, P =0.007), and lower platelet count (P = 0.027). On multivariate logistic regressionanalysis, in addition to the presence of cirrhosis (adjusted OR = 5.83;95%CI: 2.32-14.7, P < 0.001), diabetes mellitus (types 1 and 2 combined) (OR = 2.34;95%CI:1.08-5.06, P = 0.031), opioid use (OR = 3.08;95%CI: 1.29-7.34, P = 0.011), andChild-Pugh class C (OR = 4.29;95%CI: 1.43-12.9, P = 0.01) were also associatedwith a higher likelihood of food retention on EGD.CONCLUSIONCirrhotics have a higher frequency of retained food at EGD than non-cirrhotics.Decompensated cirrhosis, defined by Child-Pugh class C, is associated with ahigher likelihood of delayed gastric emptying.展开更多
BACKGROUND The robust fibroinflammatory stroma characteristic of pancreatic ductal adenocarcinoma(PDA)impedes effective drug delivery.Pulsed focused ultrasound(pFUS)can disrupt this stroma and has improved survival in...BACKGROUND The robust fibroinflammatory stroma characteristic of pancreatic ductal adenocarcinoma(PDA)impedes effective drug delivery.Pulsed focused ultrasound(pFUS)can disrupt this stroma and has improved survival in an early clinical trial.Non-invasive methods to characterize pFUS treatment effects are desirable for advancement of this promising treatment modality in larger clinical trials.AIM To identify promising,non-invasive pre-clinical imaging methods to characterize acute pFUS treatment effects for in vivo models of PDA.METHODS We utilized quantitative magnetic resonance imaging methods at 14 tesla in three mouse models of PDA(subcutaneous,orthotopic and transgenic-KrasLSLG12D/+,Trp53LSL-R172H/+,Cre or“KPC”)to assess immediate tumor response to pFUS treatment(VIFU 2000 Alpinion Medical Systems;475 W peak electric power,1 ms pulse duration,1 Hz,duty cycle 0.1%)vs sham therapy,and correlated our results with histochemical data.These pFUS treatment parameters were previously shown to enhance tumor permeability to chemotherapeutics.T1 and T2 relaxation maps,high(126,180,234,340,549)vs low(7,47,81)b-value apparent diffusion coefficient(ADC)maps,magnetization transfer ratio(MTR)maps,and chemical exchange saturation transfer(CEST)maps for the amide proton spectrum(3.5 parts per million or“ppm”)and the glycosaminoglycan spectrum(0.5-1.5 ppm)were generated and analyzed pre-treatment,and immediately post-treatment,using ImageJ.Animals were sacrificed immediately following post-treatment imaging.The whole-tumor was selected as the region of interest for data analysis and subsequent statistical analysis.T-tests and Pearson correlation were used for statistical inference.RESULTS Mean high-b value ADC measurements increased significantly with pFUS treatment for all models.Mean glycosaminoglycan CEST and T2 measurements decreased significantly post-treatment for the KPC group.Mean MTR and amide CEST values increased significantly for the KPC group.Hyaluronic acid focal intensities in the treated regions were significantly lower following pFUS treatment for all animal models.The magnetic resonance imaging changes observed acutely following pFUS therapy likely reflect:(1)Sequelae of variable degrees of microcapillary hemorrhage(T1,MTR and amide CEST);(2)Lower PDA glycosaminoglycan content and associated water content(glycosaminoglycan CEST,T2 and hyaluronic acid focal intensity);and(3)Improved tumor diffusivity(ADC)post pFUS treatment.CONCLUSION T2,glycosaminoglycan CEST,and ADC maps may provide reliable quantitation of acute pFUS treatment effects for patients with PDA.展开更多
BACKGROUND The existence of genetic anticipation has been long disputed in inflammatory bowel disease(IBD)in the absence of the explanatory mechanism.AIM To determine whether it was predictive of genetic anticipation,...BACKGROUND The existence of genetic anticipation has been long disputed in inflammatory bowel disease(IBD)in the absence of the explanatory mechanism.AIM To determine whether it was predictive of genetic anticipation,we evaluated telomere length in IBD.We hypothesized that multiplex IBD families exhibit a genetic defect impacting telomere maintenance mechanisms.METHODS We studied three IBD families with multiple affected members in three successive generations.We determined telomere length(TL)in lymphocytes and granulocytes from peripheral blood of the affected members using flow cytometry and fluorescence in-situ hybridization(flow FISH).We also performed whole exome sequencing in the blood of all available family members and used PhenoDB to identify potential candidate gene variants with recessive or dominant modes of inheritance.RESULTS Out of twenty-four patients of European descent selected to participate in the study,eleven patients,eight parent-child pairs affected by IBD,were included in the genetic anticipation analysis.Median difference in age at diagnosis between two successive generations was 16.5 years,with earlier age at onset in the younger generations.In most of the affected members,the disease harbored similar gastrointestinal and extraintestinal involvement but was more aggressive among the younger generations.TL was not associated with earlier age at onset or more severe disease in members of successive generations affected by IBD.NOD2 gene mutations were present in the Crohn’s disease patients of one family.However,no gene variants were identified as potential candidates for inheritance.CONCLUSION Telomere shortening appears unlikely to be involved in mechanisms of possible genetic anticipation in IBD.Further studies using a larger sample size are required to confirm or refute our findings.展开更多
BACKGROUND Esophageal carcinoma presents as 2 types,esophageal adenocarcinoma(EAC)and esophageal squamous cell carcinoma(ESCC)with the frequency of both changing in the United States(US).AIM To investigate EAC/ESCC in...BACKGROUND Esophageal carcinoma presents as 2 types,esophageal adenocarcinoma(EAC)and esophageal squamous cell carcinoma(ESCC)with the frequency of both changing in the United States(US).AIM To investigate EAC/ESCC incidence time trends among the 3 main US racial groups and investigate trends in US EAC survival by ethnicity.METHODS Twenty-five years(1992-2016)of data from SEER 13 program was analyzed to compare incidence trends in EAC and ESCC between non-Hispanic whites(nHW),non-Hispanic Blacks(nHB)and Hispanics(Hisp)using SEERStat®.In addition,SEER 18 data,from 1975-2015,on EAC in the US was analyzed to evaluate racial disparities in incidence and survival using SEERStat®and Ederer II method.RESULTS In the 3 major US ethnic groups,age-adjusted incidence of ESCC has declined while EAC has continued to rise from 1992-2016.Of note,in Hisp,the EAC incidence rate increased while ESCC decreased from 1992 to 2016,resulting in EAC as the predominant esophageal cancer subtype in this group since 2011,joining nHW.Furthermore,although ESCC remains the predominant tumor in nHB,the difference between ESCC and EAC has narrowed dramatically over 25 years.EAC survival probabilities were worse in all minority groups compared to nHw.CONCLUSION Hisp have joined nHW as US ethnic groups more likely to have EAC than ESCC.Of note,EAC incidence in nHB is increasing at the highest rate nationally.Despite lower EAC incidence in all minority groups compared to nHW,these populations have decreased survival compared to nHW.展开更多
Various studies have shown the interplay between the intestinal microbiome,environmental factors,and genetic changes in colorectal cancer(CRC)development.In this review,we highlight the various gut and oral microbiota...Various studies have shown the interplay between the intestinal microbiome,environmental factors,and genetic changes in colorectal cancer(CRC)development.In this review,we highlight the various gut and oral microbiota associated with CRC and colorectal adenomas,and their proposed molecular mechanisms in relation to the processes of“the hallmarks of cancer”,and differences in microbial diversity and abundance between race/ethnicity.Patients with CRC showed increased levels of Bacteroides,Prevotella,Escherichia coli,enterotoxigenic Bacteroides fragilis,Streptococcus gallolyticus,Enterococcus faecalis,Fusobacterium nucleatum(F.nucleatum)and Clostridium difficile.Higher levels of Bacteroides have been found in African American(AA)compared to Caucasian American(CA)patients.Pro-inflammatory bacteria such as F.nucleatum and Enterobacter species were significantly higher in AAs.Also,AA patients have been shown to have decreased microbial diversity compared to CA patients.Some studies have shown that using microbiome profiles in conjunction with certain risk factors such as age,race and body mass index may help predict healthy colon vs one with adenomas or carcinomas.Periodontitis is one of the most common bacterial infections in humans and is more prevalent in Non-Hispanic-Blacks as compared to Non-Hispanic Whites.This condition causes increased systemic inflammation,immune dysregulation,gut microbiota dysbiosis and thereby possibly influencing colorectal carcinogenesis.Periodontal-associated bacteria such as Fusobacterium,Prevotella,Bacteroides and Porphyromonas have been found in CRC tissues and in feces of CRC patients.Therefore,a deeper understanding of the association between oral and gastrointestinal bacterial profile,in addition to identifying prevalent bacteria in patients with CRC and the differences observed in ethnicity/race,may play a pivotal role in predicting incidence,prognosis,and lead to the development of new treatments.展开更多
Background and Aims:Liver biopsy remains the gold stand-ard for staging of chronic liver disease following orthotopic liver transplantation.Noninvasive assessment of fibrosis with Fibro-test(FT)is well-studied in immu...Background and Aims:Liver biopsy remains the gold stand-ard for staging of chronic liver disease following orthotopic liver transplantation.Noninvasive assessment of fibrosis with Fibro-test(FT)is well-studied in immunocompetent populations with chronic hepatitis C virus infection.The aim of this study is to investigate the diagnostic value of FT in the assessment of hepatic fibrosis in the allografts of liver transplant recipients with evidence of recurrent hepatitis C.Methods:We retro-spectively compared liver biopsies and FT performed within a median of 1 month of each other in orthotopic liver transplan-tation recipients with recurrent hepatitis C.Results:The study population comprised 22 patients,most of them male(19/22),and with median age of 62 years.For all patients,there was at least a one-stage difference in fibrosis as assessed by liver biopsy compared to FT,while for the majority(16/22)there was at least a two-stage difference.The absence of correlation between the two modalities was statistically demonstrated(Mann-Whitney U test,p=0.01).In detecting significant fib-rosis(a METAVIR stage of F2 and above),an FT cut-off of 0.5 showed moderate sensitivity(77%)and negative predictive value(80%),but suboptimal specificity(61%)and positive predictive value(58%).Conclusions:In post-transplant pa-tients with recurrent hepatitis C,FT appears to be inaccurately assessing the degree of allograft fibrosis,therefore limiting its reliability as a staging tool.展开更多
Acute liver failure (ALF) is the rapid onset of severe liver dysfunction, defined by the presence of hepatic encephalop-athy and impaired synthetic function (international normal-ized ratio of≥1.5) in the absence of ...Acute liver failure (ALF) is the rapid onset of severe liver dysfunction, defined by the presence of hepatic encephalop-athy and impaired synthetic function (international normal-ized ratio of≥1.5) in the absence of underlying liver disease. The elevated international normalized ratio value in ALF is often misinterpreted as an increased hemorrhagic tendency, which can lead to inappropriate, prophylactic transfusions of blood products. However, global assessments of coagulop-athy via viscoelastic tests or thrombin generation assay suggest a reestablished hemostatic, or even hypercoagu-lable, status in patients with ALF. Although the current versions of global assays are not perfect, they can provide more nuanced insights into the hemostatic system in ALF than the conventional measures of coagulopathy.展开更多
Direct-acting antiviral (DAA) therapy is often well-tolerated, and adverse events from DAA therapy are uncommon. We report a case of a woman who underwent orthotopic liver transplant for chronic hepatitis C infection ...Direct-acting antiviral (DAA) therapy is often well-tolerated, and adverse events from DAA therapy are uncommon. We report a case of a woman who underwent orthotopic liver transplant for chronic hepatitis C infection and later devel-oped alloimmune hepatitis shortly after starting DAA therapy for recurrent hepatitis C infection. The patient developed acute alloimmune hepatitis approximately 2 weeks after starting treatment with sofosbuvir, velpatasvir, and voxilap-revir. This case report proposes a dysregulation of immune surveillance due to the DAA stimulation of host immunity and rapid elimination of hepatitis C viral load as a precipitating factor for the alloimmune process, leading to alloimmune hepatitis in a post-transplant patient who starts on DAA.展开更多
Background:Vibration controlled transient elastography(VCTE)and controlled attenuation parameter(CAP™)have shown reliable performance predicting fibrosis and steatosis in normal-to overweight patients but have not bee...Background:Vibration controlled transient elastography(VCTE)and controlled attenuation parameter(CAP™)have shown reliable performance predicting fibrosis and steatosis in normal-to overweight patients but have not been validated in severe to morbid obesity.This study aimed at determining the accuracy of VCTE,CAP™and the composite score FibroScan-AST(FAST)in patients with a body mass index(BMI)of≥35 kg/m^(2).Methods:Patients scheduled for bariatric-metabolic surgery underwent preoperative VCTE/CAP™measurement,and intraoperative liver biopsy.The feasibility and accuracy of VCTE,CAP™and the composite score FAST were retrospectively analysed to evaluate fibrosis,steatosis and active fibrotic non-alcoholic steatohepatitis[NASH+non-alcoholic fatty liver disease(NAFLD)activity score≥4+fibrosis grade≥2]using per protocol(PP)and intent to diagnose(ITD)calculation.Results:In total,170 patients(median BMI 44.4 kg/m²)were included in the study.Liver biopsy showed NASH,simple steatosis,and normal livers in 60.6%(n=103),28.8%(n=49),and 10.6%(n=18),respectively.VCTE and CAP™delivered reliable results in 90.6%(n=154/170)and 90.5%(n=134/148).The AUC(PP)of VCTE,CAP™,and FAST were 0.687(≥F2),0.786(≥F3),0.703(≥S2),0.738(S3),and 0.780(active fibrotic NASH).The AUC increased to 0.742(≥F2),0.842(≥F3),0.712(≥S2),0.780(S3),and 0.836(active fibrotic NASH)in patients below the median BMI of 44.4 kg/m².Conclusions:VCTE,CAP™and FAST show acceptable accuracy for the detection of fibrosis,steatosis and NASH in a real-life cohort of patients with obesity.Accuracy improves in patients with a BMI<44.4 kg/m^(2).展开更多
Introduction Over the past three decades,the field of gastroenterology(GI)has undergone tremendous transformation.Advances in research have led to a substantial growth in clinical knowledge across many GI conditions.A...Introduction Over the past three decades,the field of gastroenterology(GI)has undergone tremendous transformation.Advances in research have led to a substantial growth in clinical knowledge across many GI conditions.Additionally,over this time,the prevalence of patient complexity,including the number of co-morbidities,mental illness burden,socioeconomic factors,and multidisciplinary needs,have continued to increase.Thus,subspecialization within GI has been an adaptive response to keep pace with the rapid expansion of medical knowledge and evolving patient needs.展开更多
Background andAims:Hepatitis C Virus(HCV)is uniformly recurrent after liver transplant(LT)and recurrence is associated with an increased risk of mortality.Immunosuppressive medications increase the risk of chronic kid...Background andAims:Hepatitis C Virus(HCV)is uniformly recurrent after liver transplant(LT)and recurrence is associated with an increased risk of mortality.Immunosuppressive medications increase the risk of chronic kidney disease,and the presence of chronic kidney disease presents a challenge for HCV treatment in LT recipients.The aim of this study was to assess changes in glomerular filtration rates(GFRs)of LT recipients receiving HCV treatment.Methods:This is a retrospective study of LT patients who received HCV treatment between 2015 and 2016(n=60).The outcomes of interest were differences in serum creatinine levels and in GFR,measured at treatment initiation and at 24 weeks after treatment.The average age of the patients was 59 years-old,and 17%were cirrhotic and 67%were treatment-experienced.All patients received sofosbuvir/ledipasvir without ribavirin.Results:All patients achieved sustained virologic response at 12 weeks after treatment(SVR12).At baseline,55%of patients had GFR<60 mL/min per 1.73 m2.Among those patients,GFR did not change in 18%,33%had improved GFR,and 48%had worsened GFR.Up to 45%of the patients had a GFR>60 mL/min per 1.73 m2.Among those patients,GFR did not change in 81%,and 19%had worsened GFR.In the entire cohort,65%of patients had improved or stable GFR and 35%had worsened GFR.The average change in serum creatinine between baseline and 24 weeks was 0.10(p=0.18).Conclusions:This study showed improved or unchanged GFR in 65%and worsened GFR in 35%of LT recipients who achieved SVR12.Worsening of GFR was more frequently encountered in those with impaired renal function at baseline.Caution should be used when treating HCV in LT recipients,especially those with baseline status of renal impairment.展开更多
Liver transplantation remains the only curative therapy for end-stage liver disease and there is a well-established shortage of transplantable deceased donor organs to meet the growing demand of waitlisted patients.St...Liver transplantation remains the only curative therapy for end-stage liver disease and there is a well-established shortage of transplantable deceased donor organs to meet the growing demand of waitlisted patients.Steatotic liver grafts represent the most common type of so-called extended criteria donor(ECD)grafts aimed at ameliorating this disparity.However,steatotic grafts are associated with increased post-transplant complications and graft failure(1).Hepatic graft steatosis is strongly correlated with the high prevalence of non-alcoholic fatty liver disease(NAFLD)and metabolic(dysfunction)associated fatty liver disease(MAFLD)in the general population.NAFLD and MAFLD are related,but not equivalent,liver disorders that are linked with obesity and diabetes(2).Global prevalence of NAFLD is estimated at~25%and rising(3).Models predict that NAFLD prevalence will increase by 21%to affect 100.9 million persons worldwide by 2030(4).As more donors have NAFLD,the steatotic liver graft will continue to be a challenge for liver transplantation.But,promising efforts(e.g.,organ pump with defatting agents)are under way,aimed at expanding the donor pool in the coming years.Herein,we briefly summarize approaches for assessment of hepatic steatosis,describe recipient outcomes associated with the use of steatotic liver grafts,and highlight strategies that may be used to mitigate risk considering the ongoing NAFLD/MAFLD epidemic.展开更多
Introduction.Tumour cell implantation is a rare complication in patients with head and neck cancers,who have undergone percutaneous endoscopic gastrostomy(PEG)tube placement.It has not been reported in patients who un...Introduction.Tumour cell implantation is a rare complication in patients with head and neck cancers,who have undergone percutaneous endoscopic gastrostomy(PEG)tube placement.It has not been reported in patients who underwent a PEG insertion via the radiological or introducer technique.We describe a novel case presentation of metastatic disease in a patient who underwent PEG placement via the introducer(Russell)technique which,to the best of our knowledge,has not not previously been described.Case presentation.The patient was a 37-year-old Malay woman who developed metastatic squamous cell carcinoma deposits in her stomach and liver one month after a gastrostomy tube was removed following the completion of treatment for oropharyngeal carcinoma.Conclusion.Previous authors have advocated the use of alternative PEG insertion technique apart from the‘pull’technique to minimise the risk of tumour implantation from head and neck cancers.Our case report suggests that this risk is not totally eliminated when the PEG tube is inserted via the introducer technique.展开更多
Background and Aims:To evaluate the prevalence and significance of elevated cancer antigen-125(CA-125)levels in patients with cirrhosis being treated in a tertiary care liver center and its correlation with objective ...Background and Aims:To evaluate the prevalence and significance of elevated cancer antigen-125(CA-125)levels in patients with cirrhosis being treated in a tertiary care liver center and its correlation with objective markers of disease severity.Methods:We retrospectively reviewed medical records of 172 adult patients with cirrhosis(due to any etiology)after obtaining CA-125 serum analysis.Demographics,etiology of cirrhosis,model of end-stage liver disease(MELD)score,Child's Turcotte-Pugh classification,albumin bilirubin(ALBI)score,degree of ascites,presence of esophageal varices,serum CA-125 level and various other parameters were collected.Statistical analysis was performed using SPSS software and descriptive statistics.Results:Elevated CA-125 levels were noted in 147 patients(85%)of the study population.Higher MELD score was associated with higher CA-125 levels(p=0.001).Statistically significant correlation was observed between elevated CA-125 levels and degree of ascites(p<0.001),ALBI score(p<0.001)and Child's Turcotte-Pugh class(p<0.001).No correlation was observed with presence or absence of esophageal varices.Near-normal CA-125 levels were noted in patients with cirrhosis but undetectable ascites on ultrasound imaging.No differences were observed in mean values between male and female patients(p=0.207).Regression analysis confirmed that CA-125 levels had a better correlation with degree of ascites than MELD score or ALBI score.Conclusions:Elevated CA-125 levels were noted in 85%of patients with cirrhosis at our center.Our study establishes that the more advanced the degree of decompensation based on MELD score,Child's Turcotte-Pugh classification and ALBI score,the higher the elevation in CA-125.Absence of ascites was associated with normal CA-125 level,with a direct correlation between high levels and worsening ascites,but there was no statistically significant correlation with esophageal varices,indicating that elevated CA-125 levels could be related to mechanical stretch of the peritoneum rather than portal hypertension itself.Further multi-centered studies are required to confirm and validate these findings.展开更多
Bile acids modulate several gastrointestinal(GI)functions including electrolyte secretion and absorption,gastric emptying,and small intestinal and colonic motility.High concentrations of bile acids lead to diarrhea an...Bile acids modulate several gastrointestinal(GI)functions including electrolyte secretion and absorption,gastric emptying,and small intestinal and colonic motility.High concentrations of bile acids lead to diarrhea and are implicated in the development of esophageal,gastric and colonic cancer.Alterations in bile acid homeostasis are also implicated in the pathophysiology of irritable bowel syndrome(IBS)and inflammatory bowel disease(IBD).Our understanding of the mechanisms underlying these effects of bile acids on gut functions has been greatly enhanced by the discovery of bile acid receptors,including the nuclear receptors:farnesoid X receptor(FXR),vitamin D receptor(VDR),pregnane X receptor(PXR),and constitutive androstane receptor(CAR);and G protein-coupled receptors(GPCRs):Takeda G protein-coupled receptor 5(TGR5),sphingosine-1-phosphate receptor 2(S1PR2),and muscarinic acetylcholine receptor M3(M3R).For example,various studies provided evidence demonstrating the anti-inflammatory effects of FXR and TGR5 activation in models of intestinal inflammation.In addition,the activation of TGR5 in enteric neurons was recently shown to increase colonic motility,which may lead to bile acid-induced diarrhea(BAD).Interestingly,TGR5 induces the secretion of glucagon-like peptide-1(GLP-1)from L-cells to enhance insulin secretion and modulate glucose metabolism.Because of the importance of these receptors,agonists of TGR5 and intestine-specific FXR agonists are currently being tested as an option for the treatment of diabetes mellitus and primary bile acid diarrhea,respectively.This review summarizes current knowledge of the functional roles of bile acid receptors in the GI tract.展开更多
文摘Acute pancreatitis(AP)is a leading cause of gastrointestinal-related hospitalizations in the United States,resulting in 300000 admissions per year with an estimated cost of over$2.6 billion annually.The severity of AP is determined by the presence of pancreatic complications and end-organ damage.While moderate/severe pancreatitis can be associated with significant morbidity and mortality,the majority of patients have a mild presentation with an uncomplicated course and mortality rate of less than 2%.Despite favorable outcomes,the majority of mild AP patients are admitted,contributing to healthcare cost and burden.In this Editorial we review the performance of an emergency department(ED)pathway for patients with mild AP at a tertiary care center with the goal of reducing hospitalizations,resource utilization,and costs after several years of implementation of the pathway.We discuss the clinical course and outcomes of mild AP patients enrolled in the pathway who were successfully discharged from the ED compared to those who were admitted to the hospital,and identify predictors of successful ED discharge to select patients who can potentially be triaged to the pathway.We conclude that by implementing innovative clinical pathways which are established and reproducible,selected AP patients can be safely discharged from the ED,reducing hospitalizations and healthcare costs,without compromising clinical outcomes.We also identify a subset of patients most likely to succeed in this pathway.
基金supported by the Shenzhen Science and Technology Innovation Commission Fundamental Research Key Projects(Nos.JCYJ20180508153013853,JCYJ20180508152130899)the Shenzhen Science and Technology Innovation Fund(No.JCYJ20150331142757381)the National Natural Science Foundation of China(Nos.81641051,81872368).
文摘Introduction:Sulfatase 2(SULF2),an endogenous extracellular sulfatase,can remove 6-O-sulfate groups of glucosamine residues from heparan sulfate(HS)chains to modulate the Wnt/β-catenin signaling pathway,which plays an important role in both liver carcinogenesis and embryogenesis.Side population(SP)cells are widely identified as stem-like cancer cells and are closely related to carcinoma metastasis,recurrence,and poor patient prognosis.However,the roles of SULF2 in SP cells of hepatomas are unclear,and the underlying mechanism is undefined.Objectives:This study aimed to compare the heterogeneity between SP cells and non-side population(NSP)cells derived from three different liver cancer cell lines and to elucidate the involvement of the SULF2-Wnt/β-catenin axis in liver cancer stem cells(CSCs)and its impact on the processes of carcinogenesis and invasiveness.Methods:In this work,three different liver cancer SP cells(HepG2,Huh7,and PRC/PRL/5)were sorted by flow cytometry.We also examined the migration and invasion behaviors of SP and NSP cells.To determine if this high tumorigenic potential of SP cells is correlated to SULF2,qPCR,western blotting,and immunofluorescence analysis were conducted.We also performed nude mouse xenograft experiments for in vivo analysis.Results:The results from the in vitro colony formation assay showed that SP cells exhibited a 2-fold higher colony formation efficiency compared to their NSP counterparts.The SP cells exhibited significantly higher potentials in terms of their migratory capacity and invasive ability compared to NSP cells.We found that higher expression of SULF2 in SP cells was associated with greater capabilities for clonogenicity,migration,and invasion.It was also linked to higher activation of the Wnt/β-catenin signaling pathway via stimulation of key downstream factors,particularlyβ-catenin,c-Myc,and cyclin D1.Further,a positive correlation between the upregulated SULF2 expression and tumorigenesis in the in vivo nude mouse xenograft models was demonstrated,highlighting that the potential underlying mechanism was Wnt/β-catenin signaling pathway activation.Conclusion:Our findings show that variable SULF2 expression was associated with differential activation of the Wnt/β-catenin signaling pathway,which could lead to behavioral differences between SP and NSP cells and also among the SP cells of the three liver cancer cell lines assessed.It was reasonably concluded that the SULF2-Wnt/β-catenin axis could play an important role in the tumorigenicity of liver cancer stem cells.
文摘Alcohol-associated hepatitis(AAH)is a severe form of liver disease caused by alcohol consumption.In the absence of confounding factors,clinical features and laboratory markers are sufficient to diagnose AAH,rule out alternative causes of liver injury and assess disease severity.Due to the elevated mortality of AAH,assessing the prognosis is a radical step in management.The Maddrey discriminant function(MDF)is the first established clinical prognostic score for AAH and was commonly used in the earliest AAH clinical trials.A MDF>32 indicates a poor prognosis and a potential benefit of initiating corticosteroids.The model for end stage liver disease(MELD)score has been studied for AAH prognostication and new evidence suggests MELD may predict mortality more accurately than MDF.The Lille score is usually combined to MDF or MELD score after corticosteroid initiation and offers the advantage of assessing response to treatment a 4-7 d into the course.Other commonly used scores include the Glasgow Alcoholic Hepatitis Score and the Age Bilirubin international normalized ratio Creatinine model.Clinical AAH correlate adequately with histologic severity scores and leave little indication for liver biopsy in assessing AAH prognosis.AAH presenting as acute on chronic liver failure(ACLF)is so far prognosticated with ACLF-specific scoring systems.New artificial intelligence-generated prognostic models have emerged and are being studied for use in AAH.Acute kidney injury(AKI)is one possible complication of AAH and is significantly associated with increased AAH mortality.Predicting AKI and alcohol relapse are important steps in the management of AAH.The aim of this review is to discuss the performance and limitations of different scoring models for AAH mortality,emphasize the most useful tools in prognostication and review predictors of recurrence.
基金Supported by Shenzhen Science and Technology Innovation Commission Key Program of Fundamental Research,China,No.JCYJ20210324120200001Shenzhen Science and Technology Program of Shenzhen Clinical Research Center for Digestive Diseases,China,No.20220822182953001.
文摘BACKGROUND The strategy for preventing colorectal cancer is screening by colonoscopy,which offers a direct way for detection and removal of adenomatous polyps(APs).American College of Gastroenterology guidelines recommend that people aged≥45 years should undergo colonoscopy;however,how to deal with people aged≤45 years is still unknown.AIM To compare the prevalence of APs and high-grade neoplasia between the left and right colon in patients≤45 years.METHODS A retrospective observational study was conducted at a single tertiary III hospital in China.This study included patients aged 18-45 years with undergoing initial colonoscopy dissection and pathological diagnosis AP or high-grade neoplasia between February 2014 and January 2021.The number of APs in the entire colon while screening and post-polypectomy surveillance in following 1-3 years were evaluated.RESULTS A total of 3053 cases were included.The prevalence of APs in the left and right colon was 55.0%and 41.6%,respectively(OR 1.7,95%CI 1.6-2.4;P<0.05).For APs with high-grade neoplasia,the prevalence was 2.7%and 0.9%,respectively(OR 3.0,95%CI 2.0-4.6;P<0.05).Therefore,the prevalence of APs and high-grade neoplasia in the left colon was significantly higher than in the right colon in patients aged≤45 years.There were 327 patients who voluntarily participated in post-polypectomy surveillance in following 1-3 years,and APs were found in 216 cases(66.1%);170 cases had 1-3 polyps(52.0%)and 46 cases had>3 polyps(14.1%;OR 0.3,95%CI 0.1-0.6;P<0.05).CONCLUSION This study suggests that flexible sigmoidoscopy would be an optimal approach for initial screening in people aged≤45 years and would be a more cost-effective and safe strategy.
文摘BACKGROUND Acute gallstone pancreatitis(AGP) is the most common cause of acute pancreatitis(AP) in the United States. Patients with AGP may also present with choledocholithiasis. In 2010, the American Society for Gastrointestinal Endoscopy(ASGE) suggested a management algorithm based on probability for choledocholithiasis, recommending additional imaging for patients at intermediate risk and endoscopic retrograde cholangiopancreatography(ERCP) for patients at high risk of choledocholithiasis. In 2019, the ASGE guidelines were updated using more specific criteria to categorize individuals at high risk for choledocholithiasis. Neither ASGE guideline has been studied in AGP to determine the probability of having choledocholithiasis.AIM To determine compliance with ASGE guidelines, assess outcomes, and compare 2019 vs 2010 ASGE criteria for suspected choledocholithiasis in AGP.METHODS We conducted a retrospective cohort study of 882 patients admitted with AP to a single tertiary care center from 2008-2018. AP was diagnosed using revised Atlanta criteria and AGP was defined as the presence of gallstones on imaging or with cholestatic pattern of liver injury in the absence of another cause. Patients with chronic pancreatitis and pancreatic malignancy were excluded as were those who went directly to cholecystectomy prior to assessment for choledocholithiasis. Patients were assigned low, intermediate or high risk based on ASGE guidelines. Our primary outcomes of interest were the proportion of patients in the intermediate risk group undergoing magnetic resonance cholangiopancreatography(MRCP) first and the proportion of patients in the high risk group undergoing ERCP directly without preceding imaging. Secondary outcomes of interest included outcome differences based on if guidelines were not adhered to. We then evaluated the diagnostic accuracy of 2019 in comparison to the 2010 ASGE criteria for patients with suspected choledocholithiasis. We performed the t test or Wilcoxon rank sum test, as appropriate, to analyze if there were outcome differences based on if guidelines were not adhered to. Kappa coefficients were calculated to measure the degree of agreement between pairs of variables.RESULTS In this cohort, we identified 235 patients with AGP of which 79 patients were excluded as they went directly to surgery for cholecystectomy without prior MRCP or ERCP. Of the remaining 156 patients, 79 patients were categorized as intermediate risk and 77 patients were high risk for choledocholithiasis according to the 2010 ASGE guidelines. Among 79 intermediate risk patients, 54(68%) underwent MRCP first whereas 25 patients(32%) went directly to ERCP. For the 54 patients with intermediate risk who had MRCP first, 36 patients had no choledocholithiasis while 18 patients had evidence of choledocholithiasis prompting ERCP. Of these patients, ERCP confirmed stone disease in 11 patients. Of the 25 intermediate risk patients who directly underwent ERCP, 18 patients had stone disease. One patient with a normal ERCP developed post ERCP pancreatitis. Patients undergoing MRCP in this group had a significantly longer length of stay(5.0 vs 4.0 d, P = 0.02). In the high risk group, 64 patients(83%) had ERCP without preceding imaging, of which, 53 patients had findings consistent with choledocholithiasis, of which 13 patients(17%) underwent MRCP before ERCP, all of which showed evidence of stone disease. Furthermore, all of these patients ultimately had an ERCP, of which 8 patients had evidence of stones and 5 had normal examination.RESULTS Our cohort also demonstrated that 58% of all 156 patients with AGP had confirmed choledocholithiasis(79% of the high risk group and 37% of the intermediate group when risk was assigned based on the 2010 ASGE guidelines). When the updated 2019 ASGE guidelines were applied instead of the original 2010 guidelines, there was moderate agreement between the 2010 and 2019 guidelines(kappa = 0.46, 95%CI: 0.34-0.58). Forty-two of 77 patients were still deemed to be high risk and 35 patients were downgraded to intermediate risk. Thirty-five patients who were originally assigned high risk were reclassified as intermediate risk. For these 35 patients, 26 patients had ERCP findings consistent with choledocholithiasis and 9 patients had a normal examination. Based on the 2019 criteria, 9/35 patients who were downgraded to intermediate risk had an unnecessary ERCP with normal findings(without a preceding MRCP).CONCLUSION Two-thirds in intermediate risk and 83% in high risk group followed ASGE guidelines for choledocholithiasis. One intermediate-group patient with normal ERCP had post-ERCP AP, highlighting the risk of unnecessary procedures.
基金Supported by Clinical and Translational Science Center,No.CTSC Grant UL1 TR002384
文摘BACKGROUND Gastrointestinal symptoms are prevalent in patients with cirrhosis.Cirrhotic patients have a known predilection to delayed gastric emptying compared to those without cirrhosis.However,the contributing factors have not been fully elucidated.Retained gastric food on esophagogastroduodenoscopy(EGD)has been used as a surrogate marker for delayed gastric emptying with reasonably high specificity.Therefore,we hypothesize that the frequency of retained gastric food contents at EGD will be higher in a cirrhotic population compared to a control population without liver disease.Additionally,we hypothesize that increased frequency of gastric food contents will be associated with increased severity of cirrhosis.AIM To determine the relative frequency of delayed gastric emptying among cirrhotics as compared to non-cirrhotics and to identify associated factors.METHODSWe performed a retrospective case-control study of cirrhotic subjects whounderwent EGD at an academic medical center between 2000 and 2015. Threehundred sixty-four patients with confirmed cirrhosis, who underwent a total of1044 EGDs for the indication of esophageal variceal screening or surveillance,were identified. During the same period, 519 control patients without liverdisease, who underwent a total of 881 EGDs for the indication of anemia, wereidentified. The presence of retained food on EGD was used as a surrogate fordelayed gastric emptying. The relative frequency of delayed gastric emptyingamong cirrhotics was compared to non-cirrhotics. Characteristics of patients withand without retained food on EGD were compared using univariable andmultivariable logistic regression analysis to identify associated factors.RESULTSOverall, 40 (4.5%) patients had evidence of retained food on EGD. Cirrhotics weremore likely to have retained food on EGD than non-cirrhotics (9.1% vs 1.4%, P <0.001). Characteristics associated with retained food on univariable analysisincluded age less than 60 years (12.6% vs 5.2%, P = 0.015), opioid use (P = 0.004),Child-Pugh class C (24.1% Child-Pugh class C vs 6.4% Child-Pugh class A, P =0.007), and lower platelet count (P = 0.027). On multivariate logistic regressionanalysis, in addition to the presence of cirrhosis (adjusted OR = 5.83;95%CI: 2.32-14.7, P < 0.001), diabetes mellitus (types 1 and 2 combined) (OR = 2.34;95%CI:1.08-5.06, P = 0.031), opioid use (OR = 3.08;95%CI: 1.29-7.34, P = 0.011), andChild-Pugh class C (OR = 4.29;95%CI: 1.43-12.9, P = 0.01) were also associatedwith a higher likelihood of food retention on EGD.CONCLUSIONCirrhotics have a higher frequency of retained food at EGD than non-cirrhotics.Decompensated cirrhosis, defined by Child-Pugh class C, is associated with ahigher likelihood of delayed gastric emptying.
基金Supported by National Institutes of Health,National Cancer Institute,No.R01 CA188654 and No.R01CA154451
文摘BACKGROUND The robust fibroinflammatory stroma characteristic of pancreatic ductal adenocarcinoma(PDA)impedes effective drug delivery.Pulsed focused ultrasound(pFUS)can disrupt this stroma and has improved survival in an early clinical trial.Non-invasive methods to characterize pFUS treatment effects are desirable for advancement of this promising treatment modality in larger clinical trials.AIM To identify promising,non-invasive pre-clinical imaging methods to characterize acute pFUS treatment effects for in vivo models of PDA.METHODS We utilized quantitative magnetic resonance imaging methods at 14 tesla in three mouse models of PDA(subcutaneous,orthotopic and transgenic-KrasLSLG12D/+,Trp53LSL-R172H/+,Cre or“KPC”)to assess immediate tumor response to pFUS treatment(VIFU 2000 Alpinion Medical Systems;475 W peak electric power,1 ms pulse duration,1 Hz,duty cycle 0.1%)vs sham therapy,and correlated our results with histochemical data.These pFUS treatment parameters were previously shown to enhance tumor permeability to chemotherapeutics.T1 and T2 relaxation maps,high(126,180,234,340,549)vs low(7,47,81)b-value apparent diffusion coefficient(ADC)maps,magnetization transfer ratio(MTR)maps,and chemical exchange saturation transfer(CEST)maps for the amide proton spectrum(3.5 parts per million or“ppm”)and the glycosaminoglycan spectrum(0.5-1.5 ppm)were generated and analyzed pre-treatment,and immediately post-treatment,using ImageJ.Animals were sacrificed immediately following post-treatment imaging.The whole-tumor was selected as the region of interest for data analysis and subsequent statistical analysis.T-tests and Pearson correlation were used for statistical inference.RESULTS Mean high-b value ADC measurements increased significantly with pFUS treatment for all models.Mean glycosaminoglycan CEST and T2 measurements decreased significantly post-treatment for the KPC group.Mean MTR and amide CEST values increased significantly for the KPC group.Hyaluronic acid focal intensities in the treated regions were significantly lower following pFUS treatment for all animal models.The magnetic resonance imaging changes observed acutely following pFUS therapy likely reflect:(1)Sequelae of variable degrees of microcapillary hemorrhage(T1,MTR and amide CEST);(2)Lower PDA glycosaminoglycan content and associated water content(glycosaminoglycan CEST,T2 and hyaluronic acid focal intensity);and(3)Improved tumor diffusivity(ADC)post pFUS treatment.CONCLUSION T2,glycosaminoglycan CEST,and ADC maps may provide reliable quantitation of acute pFUS treatment effects for patients with PDA.
基金The authors thank Professor Mary Armanios for assistance with telomere analysis. Theauthors would like to dedicate this paper in memoriam to Dr. Theodore M. Bayless, agreat mentor and a believer in genetic anticipation in inflammatory bowel disease.
文摘BACKGROUND The existence of genetic anticipation has been long disputed in inflammatory bowel disease(IBD)in the absence of the explanatory mechanism.AIM To determine whether it was predictive of genetic anticipation,we evaluated telomere length in IBD.We hypothesized that multiplex IBD families exhibit a genetic defect impacting telomere maintenance mechanisms.METHODS We studied three IBD families with multiple affected members in three successive generations.We determined telomere length(TL)in lymphocytes and granulocytes from peripheral blood of the affected members using flow cytometry and fluorescence in-situ hybridization(flow FISH).We also performed whole exome sequencing in the blood of all available family members and used PhenoDB to identify potential candidate gene variants with recessive or dominant modes of inheritance.RESULTS Out of twenty-four patients of European descent selected to participate in the study,eleven patients,eight parent-child pairs affected by IBD,were included in the genetic anticipation analysis.Median difference in age at diagnosis between two successive generations was 16.5 years,with earlier age at onset in the younger generations.In most of the affected members,the disease harbored similar gastrointestinal and extraintestinal involvement but was more aggressive among the younger generations.TL was not associated with earlier age at onset or more severe disease in members of successive generations affected by IBD.NOD2 gene mutations were present in the Crohn’s disease patients of one family.However,no gene variants were identified as potential candidates for inheritance.CONCLUSION Telomere shortening appears unlikely to be involved in mechanisms of possible genetic anticipation in IBD.Further studies using a larger sample size are required to confirm or refute our findings.
文摘BACKGROUND Esophageal carcinoma presents as 2 types,esophageal adenocarcinoma(EAC)and esophageal squamous cell carcinoma(ESCC)with the frequency of both changing in the United States(US).AIM To investigate EAC/ESCC incidence time trends among the 3 main US racial groups and investigate trends in US EAC survival by ethnicity.METHODS Twenty-five years(1992-2016)of data from SEER 13 program was analyzed to compare incidence trends in EAC and ESCC between non-Hispanic whites(nHW),non-Hispanic Blacks(nHB)and Hispanics(Hisp)using SEERStat®.In addition,SEER 18 data,from 1975-2015,on EAC in the US was analyzed to evaluate racial disparities in incidence and survival using SEERStat®and Ederer II method.RESULTS In the 3 major US ethnic groups,age-adjusted incidence of ESCC has declined while EAC has continued to rise from 1992-2016.Of note,in Hisp,the EAC incidence rate increased while ESCC decreased from 1992 to 2016,resulting in EAC as the predominant esophageal cancer subtype in this group since 2011,joining nHW.Furthermore,although ESCC remains the predominant tumor in nHB,the difference between ESCC and EAC has narrowed dramatically over 25 years.EAC survival probabilities were worse in all minority groups compared to nHw.CONCLUSION Hisp have joined nHW as US ethnic groups more likely to have EAC than ESCC.Of note,EAC incidence in nHB is increasing at the highest rate nationally.Despite lower EAC incidence in all minority groups compared to nHW,these populations have decreased survival compared to nHW.
文摘Various studies have shown the interplay between the intestinal microbiome,environmental factors,and genetic changes in colorectal cancer(CRC)development.In this review,we highlight the various gut and oral microbiota associated with CRC and colorectal adenomas,and their proposed molecular mechanisms in relation to the processes of“the hallmarks of cancer”,and differences in microbial diversity and abundance between race/ethnicity.Patients with CRC showed increased levels of Bacteroides,Prevotella,Escherichia coli,enterotoxigenic Bacteroides fragilis,Streptococcus gallolyticus,Enterococcus faecalis,Fusobacterium nucleatum(F.nucleatum)and Clostridium difficile.Higher levels of Bacteroides have been found in African American(AA)compared to Caucasian American(CA)patients.Pro-inflammatory bacteria such as F.nucleatum and Enterobacter species were significantly higher in AAs.Also,AA patients have been shown to have decreased microbial diversity compared to CA patients.Some studies have shown that using microbiome profiles in conjunction with certain risk factors such as age,race and body mass index may help predict healthy colon vs one with adenomas or carcinomas.Periodontitis is one of the most common bacterial infections in humans and is more prevalent in Non-Hispanic-Blacks as compared to Non-Hispanic Whites.This condition causes increased systemic inflammation,immune dysregulation,gut microbiota dysbiosis and thereby possibly influencing colorectal carcinogenesis.Periodontal-associated bacteria such as Fusobacterium,Prevotella,Bacteroides and Porphyromonas have been found in CRC tissues and in feces of CRC patients.Therefore,a deeper understanding of the association between oral and gastrointestinal bacterial profile,in addition to identifying prevalent bacteria in patients with CRC and the differences observed in ethnicity/race,may play a pivotal role in predicting incidence,prognosis,and lead to the development of new treatments.
文摘Background and Aims:Liver biopsy remains the gold stand-ard for staging of chronic liver disease following orthotopic liver transplantation.Noninvasive assessment of fibrosis with Fibro-test(FT)is well-studied in immunocompetent populations with chronic hepatitis C virus infection.The aim of this study is to investigate the diagnostic value of FT in the assessment of hepatic fibrosis in the allografts of liver transplant recipients with evidence of recurrent hepatitis C.Methods:We retro-spectively compared liver biopsies and FT performed within a median of 1 month of each other in orthotopic liver transplan-tation recipients with recurrent hepatitis C.Results:The study population comprised 22 patients,most of them male(19/22),and with median age of 62 years.For all patients,there was at least a one-stage difference in fibrosis as assessed by liver biopsy compared to FT,while for the majority(16/22)there was at least a two-stage difference.The absence of correlation between the two modalities was statistically demonstrated(Mann-Whitney U test,p=0.01).In detecting significant fib-rosis(a METAVIR stage of F2 and above),an FT cut-off of 0.5 showed moderate sensitivity(77%)and negative predictive value(80%),but suboptimal specificity(61%)and positive predictive value(58%).Conclusions:In post-transplant pa-tients with recurrent hepatitis C,FT appears to be inaccurately assessing the degree of allograft fibrosis,therefore limiting its reliability as a staging tool.
基金This work was supported by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under award number K23AA028297(to PHC)and Johns Hopkins University Clinician Scientist Award(to PHC).
文摘Acute liver failure (ALF) is the rapid onset of severe liver dysfunction, defined by the presence of hepatic encephalop-athy and impaired synthetic function (international normal-ized ratio of≥1.5) in the absence of underlying liver disease. The elevated international normalized ratio value in ALF is often misinterpreted as an increased hemorrhagic tendency, which can lead to inappropriate, prophylactic transfusions of blood products. However, global assessments of coagulop-athy via viscoelastic tests or thrombin generation assay suggest a reestablished hemostatic, or even hypercoagu-lable, status in patients with ALF. Although the current versions of global assays are not perfect, they can provide more nuanced insights into the hemostatic system in ALF than the conventional measures of coagulopathy.
文摘Direct-acting antiviral (DAA) therapy is often well-tolerated, and adverse events from DAA therapy are uncommon. We report a case of a woman who underwent orthotopic liver transplant for chronic hepatitis C infection and later devel-oped alloimmune hepatitis shortly after starting DAA therapy for recurrent hepatitis C infection. The patient developed acute alloimmune hepatitis approximately 2 weeks after starting treatment with sofosbuvir, velpatasvir, and voxilap-revir. This case report proposes a dysregulation of immune surveillance due to the DAA stimulation of host immunity and rapid elimination of hepatitis C viral load as a precipitating factor for the alloimmune process, leading to alloimmune hepatitis in a post-transplant patient who starts on DAA.
文摘Background:Vibration controlled transient elastography(VCTE)and controlled attenuation parameter(CAP™)have shown reliable performance predicting fibrosis and steatosis in normal-to overweight patients but have not been validated in severe to morbid obesity.This study aimed at determining the accuracy of VCTE,CAP™and the composite score FibroScan-AST(FAST)in patients with a body mass index(BMI)of≥35 kg/m^(2).Methods:Patients scheduled for bariatric-metabolic surgery underwent preoperative VCTE/CAP™measurement,and intraoperative liver biopsy.The feasibility and accuracy of VCTE,CAP™and the composite score FAST were retrospectively analysed to evaluate fibrosis,steatosis and active fibrotic non-alcoholic steatohepatitis[NASH+non-alcoholic fatty liver disease(NAFLD)activity score≥4+fibrosis grade≥2]using per protocol(PP)and intent to diagnose(ITD)calculation.Results:In total,170 patients(median BMI 44.4 kg/m²)were included in the study.Liver biopsy showed NASH,simple steatosis,and normal livers in 60.6%(n=103),28.8%(n=49),and 10.6%(n=18),respectively.VCTE and CAP™delivered reliable results in 90.6%(n=154/170)and 90.5%(n=134/148).The AUC(PP)of VCTE,CAP™,and FAST were 0.687(≥F2),0.786(≥F3),0.703(≥S2),0.738(S3),and 0.780(active fibrotic NASH).The AUC increased to 0.742(≥F2),0.842(≥F3),0.712(≥S2),0.780(S3),and 0.836(active fibrotic NASH)in patients below the median BMI of 44.4 kg/m².Conclusions:VCTE,CAP™and FAST show acceptable accuracy for the detection of fibrosis,steatosis and NASH in a real-life cohort of patients with obesity.Accuracy improves in patients with a BMI<44.4 kg/m^(2).
文摘Introduction Over the past three decades,the field of gastroenterology(GI)has undergone tremendous transformation.Advances in research have led to a substantial growth in clinical knowledge across many GI conditions.Additionally,over this time,the prevalence of patient complexity,including the number of co-morbidities,mental illness burden,socioeconomic factors,and multidisciplinary needs,have continued to increase.Thus,subspecialization within GI has been an adaptive response to keep pace with the rapid expansion of medical knowledge and evolving patient needs.
文摘Background andAims:Hepatitis C Virus(HCV)is uniformly recurrent after liver transplant(LT)and recurrence is associated with an increased risk of mortality.Immunosuppressive medications increase the risk of chronic kidney disease,and the presence of chronic kidney disease presents a challenge for HCV treatment in LT recipients.The aim of this study was to assess changes in glomerular filtration rates(GFRs)of LT recipients receiving HCV treatment.Methods:This is a retrospective study of LT patients who received HCV treatment between 2015 and 2016(n=60).The outcomes of interest were differences in serum creatinine levels and in GFR,measured at treatment initiation and at 24 weeks after treatment.The average age of the patients was 59 years-old,and 17%were cirrhotic and 67%were treatment-experienced.All patients received sofosbuvir/ledipasvir without ribavirin.Results:All patients achieved sustained virologic response at 12 weeks after treatment(SVR12).At baseline,55%of patients had GFR<60 mL/min per 1.73 m2.Among those patients,GFR did not change in 18%,33%had improved GFR,and 48%had worsened GFR.Up to 45%of the patients had a GFR>60 mL/min per 1.73 m2.Among those patients,GFR did not change in 81%,and 19%had worsened GFR.In the entire cohort,65%of patients had improved or stable GFR and 35%had worsened GFR.The average change in serum creatinine between baseline and 24 weeks was 0.10(p=0.18).Conclusions:This study showed improved or unchanged GFR in 65%and worsened GFR in 35%of LT recipients who achieved SVR12.Worsening of GFR was more frequently encountered in those with impaired renal function at baseline.Caution should be used when treating HCV in LT recipients,especially those with baseline status of renal impairment.
基金the National Heart,Lung,and Blood Institute(K23 HL136891 to LBV).
文摘Liver transplantation remains the only curative therapy for end-stage liver disease and there is a well-established shortage of transplantable deceased donor organs to meet the growing demand of waitlisted patients.Steatotic liver grafts represent the most common type of so-called extended criteria donor(ECD)grafts aimed at ameliorating this disparity.However,steatotic grafts are associated with increased post-transplant complications and graft failure(1).Hepatic graft steatosis is strongly correlated with the high prevalence of non-alcoholic fatty liver disease(NAFLD)and metabolic(dysfunction)associated fatty liver disease(MAFLD)in the general population.NAFLD and MAFLD are related,but not equivalent,liver disorders that are linked with obesity and diabetes(2).Global prevalence of NAFLD is estimated at~25%and rising(3).Models predict that NAFLD prevalence will increase by 21%to affect 100.9 million persons worldwide by 2030(4).As more donors have NAFLD,the steatotic liver graft will continue to be a challenge for liver transplantation.But,promising efforts(e.g.,organ pump with defatting agents)are under way,aimed at expanding the donor pool in the coming years.Herein,we briefly summarize approaches for assessment of hepatic steatosis,describe recipient outcomes associated with the use of steatotic liver grafts,and highlight strategies that may be used to mitigate risk considering the ongoing NAFLD/MAFLD epidemic.
文摘Introduction.Tumour cell implantation is a rare complication in patients with head and neck cancers,who have undergone percutaneous endoscopic gastrostomy(PEG)tube placement.It has not been reported in patients who underwent a PEG insertion via the radiological or introducer technique.We describe a novel case presentation of metastatic disease in a patient who underwent PEG placement via the introducer(Russell)technique which,to the best of our knowledge,has not not previously been described.Case presentation.The patient was a 37-year-old Malay woman who developed metastatic squamous cell carcinoma deposits in her stomach and liver one month after a gastrostomy tube was removed following the completion of treatment for oropharyngeal carcinoma.Conclusion.Previous authors have advocated the use of alternative PEG insertion technique apart from the‘pull’technique to minimise the risk of tumour implantation from head and neck cancers.Our case report suggests that this risk is not totally eliminated when the PEG tube is inserted via the introducer technique.
文摘Background and Aims:To evaluate the prevalence and significance of elevated cancer antigen-125(CA-125)levels in patients with cirrhosis being treated in a tertiary care liver center and its correlation with objective markers of disease severity.Methods:We retrospectively reviewed medical records of 172 adult patients with cirrhosis(due to any etiology)after obtaining CA-125 serum analysis.Demographics,etiology of cirrhosis,model of end-stage liver disease(MELD)score,Child's Turcotte-Pugh classification,albumin bilirubin(ALBI)score,degree of ascites,presence of esophageal varices,serum CA-125 level and various other parameters were collected.Statistical analysis was performed using SPSS software and descriptive statistics.Results:Elevated CA-125 levels were noted in 147 patients(85%)of the study population.Higher MELD score was associated with higher CA-125 levels(p=0.001).Statistically significant correlation was observed between elevated CA-125 levels and degree of ascites(p<0.001),ALBI score(p<0.001)and Child's Turcotte-Pugh class(p<0.001).No correlation was observed with presence or absence of esophageal varices.Near-normal CA-125 levels were noted in patients with cirrhosis but undetectable ascites on ultrasound imaging.No differences were observed in mean values between male and female patients(p=0.207).Regression analysis confirmed that CA-125 levels had a better correlation with degree of ascites than MELD score or ALBI score.Conclusions:Elevated CA-125 levels were noted in 85%of patients with cirrhosis at our center.Our study establishes that the more advanced the degree of decompensation based on MELD score,Child's Turcotte-Pugh classification and ALBI score,the higher the elevation in CA-125.Absence of ascites was associated with normal CA-125 level,with a direct correlation between high levels and worsening ascites,but there was no statistically significant correlation with esophageal varices,indicating that elevated CA-125 levels could be related to mechanical stretch of the peritoneum rather than portal hypertension itself.Further multi-centered studies are required to confirm and validate these findings.
基金The work in the authors'laboratories was supported by merit review grants from the Department of Veterans Affairs,United States(VA):BX000152(W.A.Alrefai)and BX002011(P.K.Dudeja)F30 grant DK117535(A.L.Ticho)and R01 grants:DK109709(W.A.Alrefai),DK54016(P.K.Dudeja),DK81858(P.K.Dudeja),DK92441(P.K.Dudeja),DK98170(R.K.Gill),from the USA National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health,United States.
文摘Bile acids modulate several gastrointestinal(GI)functions including electrolyte secretion and absorption,gastric emptying,and small intestinal and colonic motility.High concentrations of bile acids lead to diarrhea and are implicated in the development of esophageal,gastric and colonic cancer.Alterations in bile acid homeostasis are also implicated in the pathophysiology of irritable bowel syndrome(IBS)and inflammatory bowel disease(IBD).Our understanding of the mechanisms underlying these effects of bile acids on gut functions has been greatly enhanced by the discovery of bile acid receptors,including the nuclear receptors:farnesoid X receptor(FXR),vitamin D receptor(VDR),pregnane X receptor(PXR),and constitutive androstane receptor(CAR);and G protein-coupled receptors(GPCRs):Takeda G protein-coupled receptor 5(TGR5),sphingosine-1-phosphate receptor 2(S1PR2),and muscarinic acetylcholine receptor M3(M3R).For example,various studies provided evidence demonstrating the anti-inflammatory effects of FXR and TGR5 activation in models of intestinal inflammation.In addition,the activation of TGR5 in enteric neurons was recently shown to increase colonic motility,which may lead to bile acid-induced diarrhea(BAD).Interestingly,TGR5 induces the secretion of glucagon-like peptide-1(GLP-1)from L-cells to enhance insulin secretion and modulate glucose metabolism.Because of the importance of these receptors,agonists of TGR5 and intestine-specific FXR agonists are currently being tested as an option for the treatment of diabetes mellitus and primary bile acid diarrhea,respectively.This review summarizes current knowledge of the functional roles of bile acid receptors in the GI tract.
