CA 19-9 levels in patients with acute pancreatitis due to gallstone and metabolic/toxic reasons

SUMMARY OBJECTIVE Acute pancreatitis (AP) is an important clinical event with an increased frequency due to increased life expectancy, obesity, and alcohol use. There are some data about the elevation of carbohydrate antigen (CA) 19-9 levels in benign and malignant pancreaticobiliary events in the literature, but in AP they are limited. The aim of this study was to evaluate the CA 19-9 level in patients with AP and determine its relationship according to the cause. METHODS Between 2010-2018, 173 patients evaluated with CA 19-9 levels as well as by standard laboratory tests were included in the study. CA 1 9-9 levels and laboratory findings were compared in patients with pancreatitis due to gallstone (group 1) and metabolic/toxic reasons such as hyperlipidemia, alcohol, or drug use (group 2). RESULTS There were 114 (66%) patients in the group 1 and 59 (34%) patients in the group 2. The majority of patients with high CA 19-9 level were in group 1 (92.1% vs 6.8%). CA 19-9 level, as well as amylase, lipase, AST, ALT and bilirubin levels were found to be statistically higher in patients with AP due to gallstone compared to patients with metabolic/toxic AP. CONCLUSIONS Patients with AP due to gallstone, were found to have a high level of CA 19-9 at admission. Early stage CA 19-9 levels may contribute to standard laboratory tests in the etiology of the disease in patients diagnosed with AP.

RESUMO OBJETIVO A pancreatite aguda (PA) é um evento clínico importante e cada vez mais frequente devido ao aumento da expectativa de vida, obesidade e do consumo de álcool. Existem alguns dados na literatura sobre a elevação dos níveis do antígeno carboidrato (CA) 19-9 em eventos pancreato-biliares benignos e malignos, mas eles são limitados em relação à PA. O objetivo deste estudo foi avaliar o nível de CA 19-9 em pacientes com PA e determinar sua relação com a causa da doença. PACIENTES E MÉTODOS Entre 2010 e 2018, 173 pacientes submetidos a uma avaliação dos níveis de CA 19-9, bem como testes laboratoriais padrão, foram incluídos no estudo. Os níveis de CA 19-9 e os achados laboratoriais foram comparados em pacientes com pancreatite devido a cálculos biliares (grupo 1) e razões metabólicas/tóxicas, como hiperlipidemia, álcool, ou uso de drogas (grupo 2). RESULTADOS Um total de 114 (66%) pacientes foi incluído no grupo 1 e 59 (34%) no grupo 2. A maioria dos pacientes com alto nível de CA 19-9 estavam no grupo 1 (92,1% versus 6,8%). O CA 19-9, bem como os níveis de amilase, lipase, AST, ALT e bilirrubina foram estatisticamente mais altos em pacientes com PA devido a cálculos biliares em comparação àqueles com PA devido a alterações metabólicas/tóxicas. CONCLUSÃO Pacientes com PA devido a cálculos biliares apresentaram um alto nível de CA 19-9 no momento da internação. O nível de CA 19-9 na fase inicial pode contribuir para testes laboratoriais padrão na etiologia da doença em pacientes com diagnóstico de PA.

Efecto de una dieta alta en grasas en el proceso de formación de cálculos biliares de colesterol / Effect of a high-fat diet on cholesterol gallstone formation

Background: It is known that some nutrients play an important role in the development of cholelithiasis. Cholesterol is carried by micelles and vesicles in the bile. During the first stage of gallstone formation, cholesterol crystals derive from thermodynamically unstable vesicles. Aim: To determine the effect of a high fat diet on blood lipids and bile composition, and its implication in the formation of gallstones. Material and Methods: Two groups of 15 BALB/c mice each, coming from the same litter, were treated with a control or with a high-fat diet (64% fat and 0.14% cholesterol). After two months, the animals were sacrificed, blood and bile samples were obtained. Serum glucose and the corresponding lipid profiles were measured. In bile samples, cholesterol and phospholipid levels were analyzed, and cholesterol transporters (vesicles and micelles) were separated by gel filtration chromatography. Results: Treated animals showed an 87% increase in serum total cholesterol (p < 0.01), a 97% increase in HDL-cholesterol (p < 0.05) and a 140% increase in LDL-cholesterol (p < 0.05). No changes in serum triglycerides or glucose were observed. In bile, a 13% increase in biliary cholesterol (p < 0.05) was observed but no change in biliary phospholipids. Also, an increase in biliary vesicular transporters and an increase of cholesterol/phospholipid ratio in vesicular transporters were observed. Conclusions: A high fat diet may contribute to the formation of gallstones in our experimental model.

[Evaluation of relationship between serum cholesterol and triglyceride level and gallstone incidence]

Cholecystectomy is one of the most common operations in the field of general surgery. It has higher cost in operations with complication and in these cases mortality and morbidity will increase. The main goal of this research is the study and compare of cholesterol and triglyceride serum level in gallstone group and control group. The role of Serum total cholesterol and triglyceride level in the etiology of gallstone disease was assessed in a case control study in Emam Reza hospital. Study include 37 cases [15 males and 22 females] with surgically or ultrasonographicaly confirmed cholecystolithiasis and 35 cases [16 males and 19 females] as control outpatient and hospital admitted patient without debilitating disease [such as umbilical and inguinal Hernia] over age of forty. Mean age in stone group was 54 years and in control group was 57 years. Serum cholesterol and triglyceride concentration in gallstone patient was 193 mg/dl and 135.9 mg/dl respectively were compared with control series with cholesterol and triglyceride levels 176 mg/dl and 121.8 mg/dl respectively [p=0.258 for cholesterol and p=0.368 for triglyceride]. Gallstone patient had higher serum cholesterol and triglyceride level than control group but these differences were not statistically significant

New Insights into the Roles of Megalin/LRP2 and the Regulation of its Functional Expression

Since the discovery of the low-density lipoprotein receptor (LDLR) and its association with familial hypercholesterolemia in the early 1980s, a family of structurally related proteins has been discovered that has apolipoprotein E as a common ligand, and the broad functions of its members have been described. LRP2, or megalin, is a member of the LDLR family and was initially called gp330. Megalin is an endocytic receptor expressed on the apical surface of several epithelial cells that internalizes a variety of ligands including nutrients, hormones and their carrier proteins, signaling molecules, morphogens, and extracellular matrix proteins. Once internalized, these ligands are directed to the lysosomal degradation pathway or transported by transcytosis from one side of the cell to the opposite membrane. The availability of megalin at the cell surface is controlled by several regulatory mechanisms, including the phosphorylation of its cytoplasmic domain by GSK3, the proteolysis of the extracellular domain at the cell surface (shedding), the subsequent intramembrane proteolysis of the transmembrane domain by the gamma-secretase complex, and exosome secretion. Based on the important roles of its ligands and its tissue expression pattern, megalin has been recognized as an important component of many pathological conditions, including diabetic nephropathy, Lowe syndrome, Dent disease, Alzheimer's disease (AD) and gallstone disease. In addition, the expression of megalin and some of its ligands in the central and peripheral nervous system suggests a role for this receptor in neural regeneration processes. Despite its obvious importance, the regulation of megalin expression is poorly understood. In this review, we describe the functions of megalin and its association with certain pathological conditions as well as the current understanding of the mechanisms that underlie the control of megalin expression.

Epithelial-Mesenchymal Transitions of Bile Duct Epithelial Cells in Primary Hepatolithiasis

The purpose of this study was to explore the role of epithelial-mesenchymal transition in the pathogenesis of hepatolithiasis. Thirty-one patients with primary hepatolithiasis were enrolled in this study. Expressions of E-cadherin, alpha-catenin, alpha-SMA, vimentin, S100A4, TGF-beta1 and P-smad2/3 in hepatolithiasis bile duct epithelial cells were examined by immunohistochemistry staining. The results showed that the expressions of the epithelial markers E-cadherin and alpha-catenin were frequently lost in hepatolithiasis (32.3% and 25.9% of cases, respectively), while the mesenchymal markers vimentin, alpha-SMA and S100A4 were found to be present in hepatolithiasis (35.5%, 29.0%, and 32.3% of cases, respectively). The increased mesenchymal marker expression was correlated with decreased epithelial marker expression. The expressions of TGF-beta1 and P-smad2/3 in hepatolithiasis were correlated with the expression of S100A4. These data indicate that TGF-beta1-mediated epithelial-mesenchymal transition might be involved in the formation of hepatolithiasis.

Tissue plasminogen activator and plasminogen activator inhibitor-1 in human choledochal bile

Fibrinolytic properties have been detected in animal and human gallbladder (GB) bile. Plasminogen activator inhibitor-1 (PAI-1) has been reported in greater concentration in GB stone bile and may be a nucleating factor in the pathogenesis of GB stone formation. It is unknown whether or not human choledochal bile has similar properties, which could have a role in choledocholithiasis. The aims of this study were to determine the presence of fibrinolytic properties of human choledochal bile and to compare those properties among normal, acalculous, and calculous-infected choledochal bile. Tissue plasminogen activator (t-PA) and PAI-1 of choledochal bile were measured by enzyme linked immunosorbent assay in patients with cholangitis due to acalculous bile duct obstructions (n = 9), choledocholithiasis with cholangitis (n = 20), and normal bile (n = 7). The t-PA concentration of choledochal bile was no different among the three groups (acalculous-infected bile, median 4.61 ng/ml, and calculous-infected bile, 4.61 ng/ml, versus normal bile, 7.33 ng/ml). PAI-1 was detected in choledochal bile in significantly greater concentrations in patients with acalculous cholangitis due to bile duct obstructions and choledocholithiasis with cholangitis (acalculous-infected bile, median 0.36 ng/ml, and calculous-infected bile, 0.1 ng/ml, versus normal bile, 0.02 ng/ml, p < 0.05), but the bile concentration of PAI-1 was no different between the acalculous and calculous-infected choledochal bile. Human choledochal bile possesses t-PA and PAI-1. PAI-1 was present in greater concentrations in both acalculous and calculous-infected choledochal bile. Increased levels of PAI-1 may be an epiphenomenon of cholangitis rather than a factor in the pathogenesis of choledocholithiasis.