Requirement of a single high-risk feature as an indication for EUS for the diagnosis of asymptomatic pancreatic cysts.

BACKGROUND AND AIMS: Endoscopic ultrasound (EUS) is widely used to evaluate pancreatic cysts. Recent American Gastroenterological Association (AGA) guideline limits EUS for evaluation of cysts with at-least two high-risk features (size ≥ 3 cm, dilated main pancreatic duct or presence of a solid component). We have investigated the impact of this guideline on sensitivity of EUS for pancreatic cancer and the reduction of EUS procedures for pancreas cysts. METHODS: EUS procedures performed between 2004 and 2015 and related patient records were retrospectively reviewed to determine the presence or absence of high-risk features, and for the results of fine needle aspiration cytology. RESULTS: Two hundred ten patients (108 males) underwent EUS for diagnostic evaluation of pancreatic cysts. Four patients (1.9%), all with at-least one high-risk feature, were diagnosed with cytologically-proven pancreatic cancer. Only 2 patients with cancer had at-least two high-risk features that would have warranted EUS examination based on the new AGA guideline. The requirement for at-least two high-risk features would have decreased the number of EUS procedures by 91%, but reduced the sensitivity for pancreatic malignancy to 50%. If only one high-risk feature was required, EUS procedures would have been decreased by 67%, with a sensitivity of 100%. CONCLUSION: Limiting EUS to patients with pancreatic cysts with 2 or more high-risk features may substantially reduce the sensitivity for pancreatic malignancy. Performing EUS in patients with at least one high-risk feature may substantially decrease the need of invasive procedures without reducing sensitivity for detecting malignancy.

Endoscopic Diagnosis and Therapy in Gastroesophageal Variceal Bleeding.

Gastroesophageal variceal hemorrhage is a medical emergency with high morbidity and mortality. Endoscopic therapy is the mainstay of management of bleeding varices. It requires attention to technique and the appropriate choice of therapy for a given patient at a given point in time. Subjects must be monitored continuously after initiation of therapy for control of bleeding, and second-line definitive therapies must be introduced quickly if endoscopic and pharmacologic treatment fails.

Increased hepatic synthesis and dysregulation of cholesterol metabolism is associated with the severity of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular and liver-related mortality. NAFLD is characterized by both triglyceride and free cholesterol (FC) accumulation without a corresponding increment in cholesterol esters. The aim of this study was to evaluate the expression of cholesterol metabolic genes in NAFLD and relate these to disease phenotype. NAFLD was associated with increased SREBP-2 maturation, HMG CoA reductase (HMGCR) expression and decreased phosphorylation of HMGCR. Cholesterol synthesis was increased as measured by the circulating desmosterol:cholesterol ratio. miR-34a, a microRNA increased in NAFLD, inhibited sirtuin-1 with downstream dephosphorylation of AMP kinase and HMGCR. Cholesterol ester hydrolase was increased while ACAT-2 remained unchanged. LDL receptor expression was significantly decreased and similar in NAFLD subjects on or off statins. HMGCR expression was correlated with FC, histologic severity of NAFLD and LDL-cholesterol. These data demonstrate dysregulated cholesterol metabolism in NAFLD which may contribute to disease severity and cardiovascular risks.

Endoplasmic reticulum stress and the unfolded protein response.

The endoplasmic reticulum (ER) is the key cellular organelle involved in protein homoeostasis. The unfolded protein response (UPR) is a fundamental cellular process triggered by ER stress because of lack of ATP or primary ER dysfunction. The UPR is activated and dysregulated in non-alcoholic fatty liver disease (NAFLD). The UPR has been shown to be involved in both normal physiologic functions and the cellular response to a host of pathologic states. This article reviews the pathways by which the UPR unfolds and its potential role in the development and progression of NAFLD.

The impact of fat distribution on the severity of nonalcoholic fatty liver disease and metabolic syndrome.

UNLABELLED: The patterns of fat distribution and their relationship to severity of nonalcoholic fatty liver disease (NAFLD) are unknown. The objectives of this study were to define the fat distribution patterns and their relationship to histological severity and metabolic parameters in subjects with NAFLD. Anthropometric indices and total body fat were measured in 123 subjects. Fat distribution patterns were defined as: general, abdominal, limb, truncal, and dorsocervical lipohypertrophy (DCL) a novel finding in NAFLD. Eighty-one (66%) of the subjects were obese, and 94 (76%) had abdominal obesity. Thirty-five (28.5%) had DCL. Whereas body mass index (BMI) correlated best with the presence of diabetes (r = 0.22, P < 0.05), waist circumference (WC) correlated best with hypertension (r = 0.2, P < 0.05), hypertriglyceridemia (r = 0.37, P < 0.001), and insulin resistance (homeostasis model of assessment for insulin resistance [r = 0.68, P < 0.0001]). None of the patterns of fat distribution were significantly associated with severity of hepatic steatosis. Abdominal obesity (WC) correlated with inflammation (r = 0.2, P < 0.05) only. DCL correlated significantly with the severity of all histological parameters except steatosis. Whereas DCL was the single greatest contributor to the variability in severity of histological parameters, a model combining BMI, WC, and DCL showed the greatest contribution to the variability in severity of individual histological parameters. The addition of steatosis grade to the model significantly increased its contribution to the range of lobular inflammation. CONCLUSION: WC predicts metabolic risk profile with the most significance. However, DCL is most strongly associated with severity of steatohepatitis. WC and BMI added modestly to the contribution of DCL to severity of nonalcoholic steatohepatitis.

Carboxyhemoglobin levels in cirrhotic patients with and without hepatopulmonary syndrome.

BACKGROUND AND AIMS: Heme oxygenase (HO) catalyzes hemoglobin into bilirubin, iron, and carbon monoxide (CO), a known vasodilator. HO expression and CO production as measured by blood carboxyhemoglobin (COHb) levels increase in experimental hepatopulmonary syndrome (HPS) and contribute to vasodilatation. Whether CO contributes to HPS in humans is unknown. Our aim was to assess if arterial COHb levels are increased in cirrhotic patients with HPS relative to those without HPS. METHODS: We collected data prospectively in stable nonsmoking outpatients with cirrhosis. Demographic and clinical data and room-air arterial blood gases were collected and analyzed. HPS was diagnosed using established criteria. RESULTS: A total of 159 patients were studied. HPS was present in 27 (17%) patients. Mean age was 52 +/- 9 years, 54% were men, and hepatitis C and/or alcohol were the most common causes (53%). Fourteen percent were Child-Pugh class A, 53% were Child-Pugh class B, and 33% were Child-Pugh class C. Demographic and clinical features were similar between HPS and non-HPS patients except for the Child-Pugh score, which was lower in patients with HPS. Arterial Pa o 2 levels were lower and the alveolar-arterial oxygen gradient was higher in patients with HPS ( P < .001). COHb levels were increased in HPS relative to non-HPS ( P < .001) and correlated with Pa o 2 ( P < .001) and Aa po 2 ( P < .001) levels. CONCLUSIONS: COHb levels are increased in cirrhotic patients with HPS and correlate with gas exchange abnormalities. These results are consistent with findings in experimental HPS and suggest that CO may contribute to human HPS.