Escalating complexity of endoscopic retrograde cholangiopancreatography over the last decade with increasing reliance on advanced cannulation techniques

BACKGROUND At our academic tertiary care medical center, we have noted patients referred for endoscopic retrograde cholangiopancreatography(ERCP) who increasingly require advanced cannulation techniques. This trend is noted despite increased endoscopist experience and annual ERCP volume over the same period.AIM To evaluate this phenomenon of perceived escalation in complexity of cannulation at ERCP and assessed potential underlying factors.METHODS Demographic/clinical variables and records of ERCP patients at the beginning(2008), middle(2013) and end(2018) of the last decade were reviewed retrospectively. Cannulation approaches were classified as "standard" or "advanced" and duodenoscope position was labeled as "standard"(short position) or "non-standard"(e.g., long, semi-long).RESULTS Patients undergoing ERCP were older in 2018 compared to 2008(69.7 ± 15.2 years vs 55.1 ± 14.7, P < 0.05). Increased ampullary distortion and peri-ampullary diverticula were noted in 2018(P < 0.001). ERCPs were increasingly performed with a non-standard duodenoscope position, from 2.2%(2008) to 5.6%(2013) and 16.1%(2018)(P < 0.001). Utilization of more than one advanced cannulation technique for a given ERCP increased from 0.7%(2008) to 0.9%(2013) to 6.6%(2018)(P < 0.001). Primary mass size > 4 cm, pancreatic uncinate mass, and bilirubin > 10 mg/d L predicted use of advanced cannulation techniques(P < 0.03 for each).CONCLUSION Complexity of cannulation at ERCP has sharply increased over the past 5 years, with an increased proportion of elderly patients and those with malignancy requiring advanced cannulation approaches. These data suggest that complexity of cannulation at ERCP may be predicted based on patient/ampulla characteristics. This may inform selection of experienced, high-volume endoscopists to perform these complex procedures.

Sepsis during short bowel syndrome hospitalizations:Identifying trends,disparities,and clinical outcomes in the United States

BACKGROUND Short bowel syndrome(SBS)hospitalizations are often complicated with sepsis.There is a significant paucity of data on adult SBS hospitalizations in the United States and across the globe.AIM To assess trends and outcomes of SBS hospitalizations complicated by sepsis in the United States.METHODS The National Inpatient Sample was utilized to identify all adult SBS hospitalizations between 2005-2014.The study cohort was further divided based on the presence or absence of sepsis.Trends were identified,and hospitalization characteristics and clinical outcomes were compared.Predictors of mortality for SBS hospitalizations complicated with sepsis were assessed.RESULTS Of 247097 SBS hospitalizations,21.7%were complicated by sepsis.Septic SBS hospitalizations had a rising trend of hospitalizations from 20.8%in 2005 to 23.5%in 2014(P trend<0.0001).Compared to non-septic SBS hospitalizations,septic SBS hospitalizations had a higher proportion of males(32.8%vs 29.3%,P<0.0001),patients in the 35-49(45.9%vs 42.5%,P<0.0001)and 50-64(32.1%vs 31.1%,P<0.0001)age groups,and ethnic minorities,i.e.,Blacks(12.4%vs 11.3%,P<0.0001)and Hispanics(6.7%vs 5.5%,P<0.0001).Furthermore,septic SBS hospitalizations had a higher proportion of patients with intestinal transplantation(0.33%vs 0.22%,P<0.0001),inpatient mortality(8.5%vs 1.4%,P<0.0001),and mean length of stay(16.1 d vs 7.7 d,P<0.0001)compared to the non-sepsis cohort.A younger age,female gender,White race,and presence of comorbidities such as anemia and depression were identified to be independent predictors of inpatient mortality for septic SBS hospitalizations.CONCLUSION Septic SBS hospitalizations had a rising trend between 2005-2014 and were associated with higher inpatient mortality compared to non-septic SBS hospitalizations.

Pre-operative total parenteral nutrition improves post-operative outcomes in a subset of Crohn’s disease patients undergoing major abdominal surgery

Background:Despitemajor advances in themedicalmanagement of Crohn’s disease(CD),a significant proportion of patients will require surgery within 5 years of diagnosis.Malnutrition is an independent risk factor for adverse post-operative outcomes following gastrointestinal surgery.Data on the value of pre-operative total parenteral nutrition(TPN)in CD patients aremixed and there is a paucity of data in the biologic era.We aimed to define the role of pre-operative TPN in this population.Methods:This was a retrospective cohort study conducted at a tertiary referral center.CD patients who underwent major abdominal surgery were identified.Patients receiving pre-operative TPN were compared to controls.We compared the incidence of 30-day infectious and non-infectious post-operative complications between the two groups.Results:A total of 144 CD patients who underwent major abdominal surgery between March 2007 and March 2017 were included.Fifty-five patients who received pre-operative TPN were compared to 89 controls.Twenty-one(14.6%)patients developed infectious complications(18.2%in TPN group vs 12.3%in non-TPN group,P=0.34)and 23(15.9%)developed noninfectious complications(14.5%in TPN group vs 16.9%in non-TPN group,P=0.71).In a multivariate analysis,controlling for differences in baseline disease severity and malnutrition between groups,patients receiving pre-operative TPN for60 days had significantly lower odds of developing non-infectious complications(odds ratio 0.07,95%confidence interval:0.01–0.80,P=0.03).Weight loss of>10%in the past 6 months was a significant predictor of post-operative complications.Conclusions:In a subset of malnourished CD patients,TPN is safe and allows comparable operative outcomes to controls.Pre-operative TPN for60 days reduced post-operative non-infectious complications without associated increase in infectious complications.

Cytomegalovirus infection after liver transplantation

Human cytomegalovirus(CMV)represents the most common opportunistic infection in liver transplant recipients.CMV infections in post liver transplant patients cause significant morbidity and mortality,directly affecting posttransplant outcomes.This review will provide the framework for the surveillance,diagnosis,prophylaxis and treatment of CMV in the liver transplant population.

Fecal cytolysin does not predict disease severity in acutely decompensated cirrhosis and acute-on-chronic liver failure

Background:Cirrhosis with acute decompensation(AD)and acute-on-chronic liver failure(ACLF)are characterized by high morbidity and mortality.Cytolysin,a toxin from Enterococcus faecalis(E.faecalis),is associated with mortality in alcohol-associated hepatitis(AH).It is unclear whether cytolysin also contributes to disease severity in AD and ACLF.Methods:We studied the role of fecal cytolysin in 78 cirrhotic patients with AD/ACLF.Bacterial DNA from fecal samples was extracted and real-time quantitative polymerase chain reaction(PCR)was performed.The association between fecal cytolysin and liver disease severity in cirrhosis with AD or ACLF was analyzed.Results:Fecal cytolysin and E.faecalis abundance did not predict chronic liver failure(CLIF-C)AD and ACLF scores.Presence of fecal cytolysin was not associated with other liver disease markers,including Fibrosis-4(FIB-4)index,‘Age,serum Bilirubin,INR,and serum Creatinine(ABIC)’score,Child-Pugh score,model for end-stage liver disease(MELD)nor MELD-Na scores in AD or ACLF patients.Conclusions:Fecal cytolysin does not predict disease severity in AD and ACLF patients.The predictive value of fecal cytolysin positivity for mortality appears to be restricted to AH.

Evidence-based endoscopic management of Barrett’s esophagus

Barrett’s esophagus(BE)develops as a consequence of chronic esophageal acid exposure,and is the major risk factor for esophageal adenocarcinoma(EAC).The practices of endoscopic screening for—and surveillance of—BE,while widespread,have failed to reduce the incidence of EAC.The majority of EACs are diagnosed in patients without a known history of BE,and current diagnostic tools are lacking in their ability to stratify patients with BE into those at low risk and those at high risk for progression to malignancy.Nonetheless,advances in endoscopic imaging and mucosal therapeutics have provided unprecedented opportunities for intervention for BE,and have vastly altered the approach to management of BE-associated mucosal neoplasia.

The β-catenin/YAP signaling axis is a key regulator of melanoma-associated fibroblasts

β-catenin is a multifunctional protein that plays crucial roles in embryonic development,physiological homeostasis,and a wide variety of human cancers.Previously,we showed that in vivo targeted ablation ofβ-catenin in melanoma-associated fibroblasts after melanoma formation significantly suppressed tumor growth.However,when the expression ofβ-catenin was ablated in melanoma-associated fibroblasts before tumor initiation,melanoma development was surprisingly accelerated.How stromalβ-catenin deficiency leads to opposite biological effects in melanoma progression is not completely understood.Here,we report thatβ-catenin is indispensable for the activation of primary human stromal fibroblasts and the mediation of fibroblast-melanoma cell interactions.Using coimmunoprecipitation and proximity ligation assays,we identified Yes-associated protein(YAP)as an importantβ-catenin-interacting partner in stromal fibroblasts.YAP is highly expressed in the nuclei of cancer-associated fibroblasts(CAFs)in both human and murine melanomas.Mechanistic investigation revealed that YAP nuclear translocation is significantly modulated by Wnt/β-catenin activity in fibroblasts.Blocking Wnt/β-catenin signaling in stromal fibroblasts inhibited YAP nuclear translocation.In the absence of YAP,the ability of stromal fibroblasts to remodel the extracellular matrix(ECM)was inhibited,which is consistent with the phenotype observed in cells withβ-catenin deficiency.Further studies showed that the expression of ECM proteins and enzymes required for remodeling the ECM was suppressed in stromal fibroblasts after YAP ablation.Collectively,our data provide a new paradigm in which theβ-catenin-YAP signaling axis regulates the activation and tumor-promoting function of stromal fibroblasts.

Environmental toxicant-induced maladaptive mitochondrial changes:A potential unifying mechanism in fatty liver disease?

Occupational and environmental exposures to industrial chemicals are well known to cause hepatotoxicity and liver injury.However,despite extensive evidence showing that exposure can lead to disease,current research approaches and regulatory policies fail to address the possibility that subtle changes caused by low level exposure to chemicals may also enhance preexisting conditions.In recent years,the conceptual understanding of the contribution of environmental chemicals to liver disease has progressed significantly.Mitochondria are often target of toxicity of environmental toxicants resulting in multisystem disorders involving different cells,tissues,and organs.Here,we review persistent maladaptive changes to mitochondria in response to environmental toxicant exposure as a mechanism of hepatotoxicity.With better understanding of the mechanism(s) and risk factors that mediate the initiation and progression of toxicant-induced liver disease,rational targeted therapy can be developed to better predict risk,as well as to treat or prevent this disease.

Erythroid Lineage Cells in the Liver:Novel Immune Regulators and Beyond

The lineage of the erythroid cell has been revisited in recent years. Instead of being classified as simply inert oxygen carriers, emerging evidence has shown that they are a tightly regulated in immune potent population with potential devel-opmental plasticity for lineage crossing. Erythroid cells have been reported to exert immune regulatory function through secreted cytokines, or cell-cell contact, depending on the conditions of the microenvironment and disease models. In this review, we explain the natural history of erythroid cells in the liver through a developmental lens, as it offers perspec-tives into newly recognized roles of this lineage in liver biology. Here, we review the known immune roles of erythroid cells and discuss the mechanisms in the context of disease models and stages. Then, we explore the capability of erythroid lineage as a cell source for regenerative medicine. We propose that the versatile lineage of erythroid cells provides an underappreciated and potentially promising area for basic and translational research in the field of liver disease.

Proteomics and metabolic phenotyping define principal roles for the aryl hydrocarbon receptor in mouse liver

Dioxin-like molecules have been associated with endocrine disruption and liver disease.To better understand aryl hydrocarbon receptor(AHR)biology,metabolic phenotyping and liver proteomics were performed in mice following ligand-activation or whole-body genetic ablation of this receptor.Male wild type(WT)and Ahr^(-/-) mice(Taconic)were fed a control diet and exposed to 3,3',4,4',5-pentachlorobiphenyl(PCB126)(61 nmol/kg by gavage)or vehicle for two weeks.PCB126 increased expression of canonical AHR targets(Cyp1 a1 and Cyp1 a2)in WT but not Ahr^(-/-).Knockouts had increased adiposity with decreased glucose tolerance;smaller livers with increased steatosis and perilipin-2;and paradoxically decreased blood lipids.PCB126 was associated with increased hepatic triglycerides in Ahr^(-/-).The liver proteome was impacted more so by Ahr^(-/-) genotype than ligandactivation,but top gene ontology(GO)processes were similar.The PCB126-associated liver proteome was Ahr-dependent.Ahr principally regulated liver metabolism(e.g.,lipids,xenobiotics,organic acids)and bioenergetics,but it also impacted liver endocrine response(e.g.,the insulin receptor)and function,including the production of steroids,hepatokines,and pheromone binding proteins.These effects could have been indirectly mediated by interacting transcription factors or microRNAs.The biologic roles of the AHR and its ligands warrant more research in liver metabolic health and disease.